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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Psoriatic arthritis &#40;PsA&#41; is a heterogeneous disease due its diverse musculo-skeletal phenotypes &#40;peripheral arthritis&#44; axial disease&#44; enthesitis&#44; dactylitis&#41;&#44; and its extra-articular manifestations&#44; in particular the skin and nails&#44; as well as other organs &#40;ileitis&#44; inflammatory bowel disease&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">1&#44;2</span></a> Although skin psoriasis and PsA share certain pathophysiological processes like angiogenesis and increased proinflammatory cytokine expression&#44; there are differences such as the unequal efficacy of certain drugs for the skin and the joints&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The conventional synthetic disease-modifying antirheumatic drugs &#40;cDMARDs&#41; were first tried on rheumatoid arthritis &#40;RA&#41;&#44; and in general there is limited evidence for their efficacy in PsA&#46;<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">5&#44;6</span></a> On the other hand&#44; the inclusion of the biological therapies&#44; TNF-alpha inhibitors&#44; has fundamentally improved management of this disease&#46; Nevertheless&#44; there are a great many patients with PsA for whom these therapies are contraindicated&#44; lose their efficacy or have side effects&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Fortunately&#44; PsA has gone from a disease whose treatment was derived from that of RA&#44; to become a priority disease for the research and development of new therapeutic targets&#46; The modulating biological therapies that target IL23&#47;IL17 &#40;ustekinumab&#44; secukinumab&#41;&#44; and targeted synthetic disease-modifying antirheumatic drugs &#40;tDMARDS&#41; &#40;apremilast&#41; are now a reality for our patients&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">7</span></a> Although they have all demonstrated efficacy and safety in treating PsA&#44; due to the lack of clinical trials where they have been directly compared &#40;head-to-head studies&#41;&#44; and recorded clinical experience&#44; there are no clear recommendations as to the order&#44; stage or domain of the disease when the different available drugs should be given&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In the management of PsA it is also very important to define the treatment objective properly&#44; and to use certain treatment strategies &#40;tight control&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">For all the above reasons&#44; recommendations are required based on the most recent evidence&#44; and on expert opinion on PsA treatment&#46; EULAR<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">9</span></a> and GRAPPA<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">10</span></a> have recently revised their 2011 and 2009 recommendations&#44; respectively&#46; In this paper we present the updated recommendations of the Spanish Society of Rheumatology &#40;SER&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">11</span></a> which seek to help rheumatologists to optimise the therapeutic management of PsA&#46; This document not only gathers the principal aspects of control and treatment with biological drugs but also covers important aspects in the management of PsA such as early diagnosis&#44; therapeutic objectives&#44; the use of synthetic DMARDs&#44; comorbidities&#44; and treatment optimisation&#46; However&#44; the recommendations focus chiefly on therapeutic strategies using synthetic and biological DMARDs&#46; Under no circumstances do these recommendations claim to be a strict protocol for the management and treatment of the disease&#44; but rather to serve as a basis to increase the quality of care of patients with PsA&#44; and help therapeutic decision-making&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">We used a qualitative synthesis of the scientific evidence and consensus techniques in this project &#40;&#8220;reasoned judgement&#8221; and &#8220;modified Delphi technique&#8221;&#41;&#44; agreed by experts based on their clinical experience&#44; and the scientific evidence&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Phases of the Process</span><p id="par0035" class="elsevierStylePara elsevierViewall">A series of steps were followed in preparing the recommendations document as described below&#58;</p><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Creation of the working group&#46;</span> The paper was started by setting up a panel of experts selected through an open call to all SER members&#46; The Committee for Practice Guidelines &#40;CPG&#41; and SER Recommendations evaluated the curricula of the applicants according to objective criteria of their contribution to knowledge on PsA&#44; principally by participation in journal publications of impact over the past 5 years&#46; The panel of experts comprised 8 rheumatologists&#44; members of SER&#46; The clinical and methodological aspects were managed by one of these rheumatologists as the principal investigator &#40;PI&#41;&#44; and by a methodology specialist&#44; SER Investigation Unit &#40;IU&#41; technician&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Identification of the key areas for updating the previous consensus&#46;</span> All the members of the working team participated to structure the document&#44; and establish the content and key aspects&#46; The recommendations from the previous Consensus and the last version of the 2015 ESPOGUIA<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">12</span></a> were chosen for updating&#46; First&#44; the clinical questions were identified that might most impact the use of biological therapy for PsA&#46; Then the content and results that did not have to answer the formulation of the research question were established&#46; The methodology to follow in the process of preparing the recommendations was also defined&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Literature search&#46;</span> The clinical questions were reformulated in 7 questions in PICO format&#46; A search strategy was designed to answer the questions&#44; and the scientific evidence from studies published up to February 2016 was reviewed&#46; The databases used were&#58; PubMed &#40;MEDLINE&#41;&#44; EMBASE&#44; and Cochrane Library &#40;Wiley Online&#41;&#46; The process was completed with a manual search of references&#44; posters and conference summaries that the reviewers and experts considered of interest&#46; The literature search strategies&#44; from the 7 systematic reviews &#40;SR&#41;&#44; can be found in the supplementary material that is detailed in a methodological annex on the SER website&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Analysis and synthesis of the scientific evidence&#46;</span> Various rheumatologists&#44; from the SER working group of evidence reviewers&#44; were in charge of systematically reviewing the available scientific evidence&#46; After a critical reading of the full text of the studies chosen for each review&#44; they prepared an abstract using a standardised form including tables and text to describe the methodology&#44; results and quality of each study&#46; The reasons for excluding the articles that were not included in the selection were detailed&#46; The overall level of scientific evidence was assessed using the modified levels of evidence of the Oxford Centre for Evidence-based Medicine &#40;CEBM&#41; &#40;<a id="intr0010" class="elsevierStyleInterRef" href="http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009">http&#58;&#47;&#47;www&#46;cebm&#46;net&#47;oxford-centre-evidence-based-medicine-levels-evidence-march-2009</a>&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Formulation of the recommendations&#46;</span> When the critical reading had been completed&#44; the PI and the expert panel went on to formulate specific scientific evidence-based recommendations&#46; This formulation was based on &#8220;formal assessment&#8221; or &#8220;reasoned judgement&#8221;&#44; summarising the evidence beforehand for each of the clinical questions&#46; The quality&#44; quantity and consistency of the scientific evidence were considered&#44; commonality of the results&#44; their applicability and clinical impact&#46; Two consensus rounds were used to formulate the recommendations&#59; first&#44; in an in-person meeting&#44; with the &#8220;reasoned judgement&#8221; consensus system&#44; all the experts drafted and discussed the recommendations and they were discussed in the presence of the methodologist&#59; then&#44; using a Delphi questionnaire&#44; the level of agreement of the experts was agreed scoring each of the recommendations using a Likert scale from 1 to 5 &#40;1&#58; completely disagree&#59; 2&#58; moderately disagree&#59; 3&#58; neither agree nor disagree&#59; 4&#58; moderately agree&#59; 5&#58; completely agree&#41;&#46; A high level of agreement was defined for drafting when more than 75&#37; panellists awarded &#8805;4 on the Likert scale&#46; The level of evidence and grading of the strength of recommendations were based on the modified Oxford system 2009&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Public exposure&#46;</span> The draft of this SER Recommendations document underwent a process of public exposure by partner members of SER and of different interest groups &#40;pharmaceutical industry&#44; other scientific societies&#44; and patient associations&#41;&#44; to determine their assessment and scientific argument for the methodology and the recommendations&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Structure</span><p id="par0070" class="elsevierStylePara elsevierViewall">The document gathers all the recommendations&#44; formulated and subdivided into two sections&#58; general principles and specific recommendations&#46; A therapeutic algorithm was created based on the recommendations&#44; which presents the treatment approach after diagnosis of PsA in summarised form&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">A total of 17 recommendations were formulated on the treatment and use of biological therapies for PsA &#40;<a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">General Recommendations</span><p id="par0080" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 1&#46;</span> PsA is a chronic inflammatory musculoskeletal disease whose diagnosis&#44; treatment and evolutionary control should be managed by rheumatologists&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8226;</span></span><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 2&#46;</span> The clinical presentation of PsA is very heterogeneous&#44; and it has some associated comorbidities that occasionally require multidisciplinary management&#46; Coordinated management with the dermatologist is important&#44; especially for patients with moderate-severe psoriasis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 3&#46;</span> The therapeutic objective of PsA is to control inflammation and preserve the patients&#8217; functional capacity&#44; achieving clinical remission or minimal&#47;low disease activity according to the different validated indices&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8226;</span></span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 4<span class="elsevierStyleBold">&#46;</span></span> Establishing a therapeutic objective and strict clinical monitoring are crucial to achieve optimal control of clinical activity&#44; and an appropriate therapeutic response&#46; Once the therapeutic objective has been achieved&#44; quarterly follow-up seems reasonable&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8226;</span></span><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 5<span class="elsevierStyleBold">&#46;</span></span> The cardiovascular risk profile must be taken into account on assessment and during the therapeutic management of these patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 6<span class="elsevierStyleBold">&#46;</span></span> The most appropriate therapeutic decision will depend on the judgement of the specialist&#44; and will be agreed with the patient&#46; This decision will be taken based principally on the scientific evidence&#44; and the features of the patient and their disease&#46;</p></li></ul></p><p id="par0115" class="elsevierStylePara elsevierViewall">The clinical presentation of PsA is very heterogeneous and includes articular and extra-articular manifestations&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">1&#44;4</span></a> As the specialists with the best knowledge and experience in the clinical and therapeutic management of this disease&#44; rheumatologists should be in charge of diagnosis and treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">9&#44;13&#44;14</span></a> However&#44; due to the diversity of its clinical expression and associate comorbidities&#44; multidisciplinary management of these patients is important&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">15&#8211;17</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The clinical objective when treating patients with PsA is not as well defined as that of RA&#46;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">18&#8211;22</span></a> Irrespective of the activity index used to monitor clinical activity&#44; the priority should be to control inflammation as soon as possible&#44; and improve the functional capacity and quality of life of patients with PsA&#46;<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">23&#8211;25</span></a> Clinical remission can be difficult to achieve&#44; especially in long-term PsA&#46;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">26&#8211;28</span></a> In this subgroup it can be sufficient to obtain minimal&#47;low disease activity&#8212;to achieve 5 of the 7 criteria proposed&#44; from musculoskeletal and skin manifestations to assessment of the patient him or herself&#46;<a class="elsevierStyleCrossRefs" href="#bib0635"><span class="elsevierStyleSup">24&#44;29&#44;30</span></a> Although there is no consensus on the best tool to monitor clinical activity&#44; the use is recommended of validated and quantifiable indices that cover parameters of inflammatory activity &#40;joint involvement &#91;peripheral and&#47;or axial&#93;&#44; dactylitis&#44; enthesitis and acute phase reagents&#41;&#44; and more subjective parameters that impact the patients&#8217; function and quality of life &#40;pain&#44; fatigue&#44; overall assessment of the patient&#44; functional capacity and quality of life&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0625"><span class="elsevierStyleSup">22&#44;23&#44;31&#8211;34</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">A recent clinical trial has shown better outcomes after strict monitoring &#40;<span class="elsevierStyleItalic">tight control</span>&#44; every 4 weeks&#41; compared to routine clinical practice &#40;every 12 weeks&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">35</span></a> Although&#44; at present&#44; the best monitoring interval for patients is not clear&#44; it seems reasonable to perform stricter control &#40;every 4 weeks&#41; after the disease has been diagnosed or whenever the response to a treatment needs to be assessed&#46; When the therapeutic objective has been achieved&#44; quarterly monitoring is sufficient&#46;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">9&#44;35</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Several guidelines are currently available for the management of PsA patients that constitute essential tools for the therapeutic approach to these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">9&#44;36</span></a> In clinical practice&#44; however&#44; it is recommended that the comorbidities associated with the disease should be considered when making therapeutic decisions&#44; as well as the patient&#39;s opinion&#44; explaining the risk&#47;benefit of each&#44; because this can encourage better treatment adherence and compliance&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Approaching cardiovascular risk in patients with chronic inflammatory diseases is important&#44; since there is a known connection between inflammation&#44; endothelial dysfunction and increased atherogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">37</span></a> An increase in cardiovascular risk factors &#40;hypertension&#44; diabetes&#44; dyslipidaemia&#44; etc&#46;&#41; has been observed in patients with PsA associated with the role of inflammation&#44; resulting in a greater prevalence of cardiovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">38</span></a> Obesity prevention is another significant aspect that we need to stress&#44; since as well as being a cardiovascular risk factor it can also be associated with a poorer response to immunosuppressive treatments&#44; and greater difficulty in achieving a status of minimal disease activity&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">39</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">We infer from a systematic review of this field&#44; that the epidemiological data are insufficient to reach definitive conclusions on the effects of biological drugs and cDMARDs on cardiovascular events in patients with PsA&#46; However TNFi and methotrexate &#40;MTX&#41;&#44; acting as inflammation inhibitors&#44; can have cardioprotective effects&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">40</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Furthermore&#44; the specialist&#39;s therapeutic decision should be the most cost-effective possible with the greatest clinical benefit for the patient&#44; without constituting an added burden for the national health system&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Specific Recommendations</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Early Intervention</span><p id="par0150" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8226;</span></span><p id="par0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 7&#46;</span> Early intervention with cDMARDs is recommended for patients with PsA&#44; principally those with poor baseline prognostic factors&#44; in order to improve the signs and symptoms&#44; functional capacity&#44; and quality of life &#40;LE&#58; 4&#44; GR&#58; D&#41;&#46;</p></li></ul></p><p id="par0160" class="elsevierStylePara elsevierViewall">Although the scientific evidence is sparse and controversial in this field&#44; six studies were found that answered this question indirectly&#46; Long duration of the disease&#44;<a class="elsevierStyleCrossRefs" href="#bib0720"><span class="elsevierStyleSup">41&#44;42</span></a> and delayed diagnosis of early PsA<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">43</span></a> are major factors influencing progression of structural joint damage&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Various studies have assessed functional capacity in early and established PsA&#46;<a class="elsevierStyleCrossRefs" href="#bib0690"><span class="elsevierStyleSup">35&#44;43&#44;44</span></a> It has been observed that delayed diagnosis&#44; smoking&#44; advanced age&#44; being female&#44; and a history of TNF-I treatments are associated with poorer functional capacity&#46;<a class="elsevierStyleCrossRefs" href="#bib0720"><span class="elsevierStyleSup">41&#44;43</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">It was found in the Swedish Early PsA Registry that a shorter duration of symptoms&#44; a low baseline HAQ&#44; and axial disease in males were independent predictive factors of minimal disease activity&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">44</span></a> The authors suggest that early diagnosis in patients with polyarticular involvement can be important to start specific treatment more promptly&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">44</span></a> Therefore&#44; although there are few studies that cover this subject&#44; we can consider the polyarticular forms with raised inflammatory reactants&#44; delayed diagnosis and therapy&#44; dactylitis&#44; the presence of baseline erosions&#44; and smoking to be factors of poor prognosis&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The TICOPA study demonstrated that early therapeutic intervention&#44; and tight clinical follow-up &#40;every 4 weeks&#41; achieved better clinical responses &#40;assessed by ACR and MDA&#41; than the routine clinical practice &#40;every 12 weeks&#41; in a cohort of early PsA&#44; although they found no differences in radiographic progression at 48 weeks&#44;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">35</span></a> largely due to the poor overall progression of both cohorts&#46; On the other hand&#44; an open study performed on 35 patients with PsA observed that a delay of 3 months in starting treatment with MTX had no relevant clinical impact&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">45</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Peripheral Arthritis</span><p id="par0180" class="elsevierStylePara elsevierViewall">Nonsteroidal anti-inflammatory drugs &#40;NSAIDs&#41; and oral corticosteroids&#44; used at the minimum necessary dose for the shortest possible time&#44; can be useful as symptomatic treatment for peripheral PsA&#44; without causing a delay in initiating disease-modifying treatment for patients for whom it is indicated&#46; Local therapy in the form of corticosteroid injections is particularly recommended for enthesitis and dactylitis&#44; and is also useful for peripheral mono- or oligoarticular arthritis&#46; Ultrasound guidance can be useful for these procedures&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Synthetic Disease-modifying Anti-rheumatic Drugs &#40;DMARDs&#41;</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conventional Synthetic Disease-modifying Anti-rheumatic Drugs &#40;cDMARDs&#41;</span><p id="par0185" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 8&#46;</span> The cDMARDs &#40;MTX&#44; leflunomide&#44; sulfasalazine&#41; are recommended as first-line treatment for active peripheral PsA &#40;LE&#58; 2b&#44; GR&#58; <span class="elsevierStyleSmallCaps">C</span>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 9&#46;</span> MTX is recommended as first choice&#44; due to its effects on arthritis and psoriasis &#40;LE&#58; 4&#44; GR&#58; D&#41;&#46;</p></li></ul></p><p id="par0200" class="elsevierStylePara elsevierViewall">The cDMARDs are recommended as the first therapeutic option for patients with peripheral PsA&#46; MTX is the treatment of choice and leflunomide and sulfasalazine are other valid options&#46; Clinical trials of MTX&#44; due to different methodological circumstances&#44; have not provided conclusive data on its efficacy for PsA&#46;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">46</span></a> However&#44; extensive experience in routine clinical practice&#44; and data from observational studies and registries suggest that MTX is effective for PsA&#46; In the Norwegian registry&#44; survival for MTX at 2 years was 65&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">47</span></a> and in the TICOPA<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">35</span></a> study&#44; 22&#37; of the patients on MTX as monotherapy achieved minimal disease activity&#46; As yet&#44; there is insufficient evidence for the role played by the cDMARDs in inhibiting structural damage&#44; although MTX at high doses might have some effect&#46;<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">49</span></a> For all these reasons&#44; MTX is recommended as the first therapeutic option based on broad clinical experience&#44; its efficacy in areas such as the skin&#44;<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">50</span></a> its low cost and universal access&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Targeted Synthetic Disease-modifying Antirheumatic Drugs &#40;tDMARDS&#41;</span><p id="par0205" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0210" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 10&#46;</span> Apremilast is recommended for the treatment of peripheral arthritis&#44; after cDMARD failure or intolerance&#44; when it is considered more appropriate than biological therapy due to the patient&#39;s profile &#40;LE&#58; 2b&#44; GR&#58; C&#41;&#46;</p></li></ul></p><p id="par0215" class="elsevierStylePara elsevierViewall">Apremilast is a small molecule that inhibits phosphodiesterase 4 &#40;PDE 4&#41;&#46; PDE4 inhibition causes an increase in intracellular levels of cyclic adenosine monophosphate &#40;cAMP&#41;&#44; modulating inflammatory cytokine expression&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">51</span></a> The efficacy data on apremilast for peripheral arthritis&#44; based on the results of clinical trials&#44; seem to be inferior to biological therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0775"><span class="elsevierStyleSup">52&#8211;54</span></a> The lack of data on radiographic progression&#44; lack of experience in its use&#44; and the lack of comparative studies with cDMARDs or biological agents&#44; are currently giving rise to some doubt as to its place in the peripheral PsA therapeutic algorithm&#46; However&#44; its good safety profile supports is use in patients for whom other therapeutic options are not suitable&#44; due to comorbidities or a history of severe infections&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">55</span></a> In addition&#44; it can promote weight loss &#40;between 5&#37;-10&#37;&#41;&#44; which is of interest for PsA patients who are overweight or obese&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Biological Therapies &#40;TNFi&#44; Anti-IL12&#47;23&#44; Anti-IL17&#41;</span><p id="par0220" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0225" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 11&#46;</span> Biological therapy is recommended for peripheral PsA patients refractory to at least one cDMARDs &#40;LE&#58; 1b&#44; GR&#58; A&#41;&#46;</p></li></ul></p><p id="par0230" class="elsevierStylePara elsevierViewall">Biological therapy would be indicated for patients with peripheral PsA where DMARDs have proved ineffective&#44; or been discontinued due to intolerance&#46; Various clinical trials have demonstrated that the TNFi agents are effective in all the domains of PsA&#46; They have also been demonstrated to have a significant effect on structural damage inhibition&#46;<a class="elsevierStyleCrossRefs" href="#bib0755"><span class="elsevierStyleSup">48&#44;56&#8211;58</span></a> We also now have 2 new agents with a different mechanism of action&#44; ustekinumab &#40;i-IL12&#47;23&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0810"><span class="elsevierStyleSup">59&#8211;61</span></a> and secukinumab &#40;i-IL17&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0825"><span class="elsevierStyleSup">62&#44;63</span></a> which have been recently shown to be effective in controlling the manifestations of PsA and in radiographic damage inhibition&#46; Therefore&#44; they are equally valid options for PsA patients and when there has been an inadequate response to DMARDs&#44; especially for cases with severe skin involvement&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Despite the lack of clinical trials that directly compare the diverse molecules available&#44; the differences between them do not appear significant&#46; They are all good treatment options in the event of synthetic DMARD failure&#46; However&#44; based on years of experience in clinical practice and that reflected in the different international registries&#44; the panel of experts suggest the TNF inhibitors as the first option&#46; The other drugs are equally valid options&#44; however&#44; and therefore the physician&#39;s judgement must prevail&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the biological therapies with their current indication for the treatment of PsA in our country&#46;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0245" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 12&#46;</span> Biological therapy is recommended&#44; in monotherapy and in combination with cDMARDs&#44; for all the peripheral manifestations of PsA&#46; Combining the therapy with MTX can increase the survival of the monoclonal&#44; especially the chimeric&#44; TNFi drugs &#40;LE&#58; 2b&#44; GR&#58; C&#41;&#46;</p></li></ul></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0250" class="elsevierStylePara elsevierViewall">Although the usefulness of biological therapy in combination with DMARDs has been demonstrated&#44; and is specifically recommended by SER&#44;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">64</span></a> there is more controversy surrounding its use for PsA&#46; There are no direct comparisons of efficacy and safety between the combined treatment of MTX and biological therapy&#44; and biological therapy in monotherapy for PsA&#46; The data from clinical trials show no significant differences in terms of efficacy &#40;ACR responses&#41; or safety outcomes between patients on combined treatment and patients with biological treatment in monotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0790"><span class="elsevierStyleSup">55&#44;57&#44;63&#8211;76</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Therefore&#44; no valid conclusions can be drawn of efficacy or safety for each biological drug combined with MTX compared with biological therapy in monotherapy&#46; In general&#44; the combination with MTX showed no significant clinical improvement&#46;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">65</span></a> However&#44; in some registries&#44; combined therapy with MTX provides greater survival of the drug&#44; especially in monoclonal antibodies&#44; and particularly with infliximab&#44; therefore it could be considered for use in this circumstance&#46;<a class="elsevierStyleCrossRefs" href="#bib0900"><span class="elsevierStyleSup">77&#8211;80</span></a><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8226;</span><p id="par0260" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 13&#46;</span> In patients with peripheral PsA&#44; and after failure of a TNFi&#44; a change to another biological therapy is recommended&#44; either another TNFi or a drug with a different mechanism of action&#44; such as i-IL12&#47;23 or i-IL17 or a tDMARD &#40;apremilast&#41; &#40;LE&#58; 1b&#44; 2b&#59; GR&#58; B&#41;&#46;</p></li></ul></p><p id="par0265" class="elsevierStylePara elsevierViewall">The data from clinical trials indicate that response to a second TNFi agent is good&#44; although inferior in general to that achieved in patients with no previous exposure to these drugs&#46; The registries show a slight reduction in the survival of the second biological agent compared to the first&#44; and clearly poorer survival for the third&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">There are no studies that compare the usefulness of a second TNFi compared to a change of therapeutic target &#40;IL12&#47;23 or IL17&#41;&#44; and therefore both therapeutic options are currently equally valid&#46; In the studies on ustekinumab and those on secukinumab&#44; as with the TNFi drugs&#44; it has been demonstrated that the response to these drugs in patients with no previous exposure to biological agents is better if compared to the response obtained in patients where a TNFi has already failed&#46; Therefore&#44; the expected efficacy will always be better the earlier we use the biological drug&#44; irrespective of which&#46;<a class="elsevierStyleCrossRefs" href="#bib0830"><span class="elsevierStyleSup">63&#44;81&#8211;90</span></a> Apremilast has also shown better ACR20 responses in patients with no previous exposure to biological therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">53</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows an algorithm for the management of peripheral arthritis&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Enthesitis</span><p id="par0280" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8226;</span></span><p id="par0285" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 14&#46;</span> Biological therapy or tDMARDS &#40;apremilast&#41; are recommended for patients with PsA and enthesitis refractory to NSAIDs and local treatment &#40;LE&#58; 2b&#44; GR&#58; C&#41;&#46;</p></li></ul></p><p id="par0290" class="elsevierStylePara elsevierViewall">A NSAID&#44; physiotherapy and local peri-enthesis corticosteriod injections are recommended first for the forms of PsA with predominantly enthesitis involvement&#44; although to date there are no randomised and placebo-controlled studies to vouch for their efficacy&#46; There is no evidence to support the use of tDMARDS for enthesitis&#46; However&#44; tDMARDS can be considered for patients with PsA and enthesitis as long as there is associated peripheral arthritis&#46; If a good response is not achieved despite the aforementioned treatment&#44; the appropriate option would be biological therapy or apremilast&#46;<a class="elsevierStyleCrossRef" href="#bib0970"><span class="elsevierStyleSup">91</span></a> The TNFi drugs<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">92</span></a> and subsequently ustekinumab&#44;<a class="elsevierStyleCrossRefs" href="#bib0810"><span class="elsevierStyleSup">59&#44;60</span></a> secukinumab&#44;<a class="elsevierStyleCrossRefs" href="#bib0830"><span class="elsevierStyleSup">63&#44;82</span></a> and apremilast<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">54</span></a> have proven efficacy in the treatment of enthesitis&#44; but there is no data to show the clear superiority of one drug over the rest&#46; For this reason&#44; they would all be good treatment options for patients refractory to NSAIDs and&#47;or local treatment&#46; However&#44; based on years of experience in clinical practice and the international registries&#44; the panel of experts suggest the TNFi as the first option&#59; the other drugs are equally valid options&#44; and therefore the final decision must be that of the physician&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows an algorithm for the management of enthesitis&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Dactylitis</span><p id="par0300" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0305" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 15&#46;</span> Biological treatment or tDMARDS &#40;apremilast&#41; are recommended for patients with PsA and dactylitis refractory to NSAIDs and local corticosteroid injections &#40;LE&#58; 2b&#44; GR&#58; C&#41;&#46;</p></li></ul></p><p id="par0310" class="elsevierStylePara elsevierViewall">For the forms of PsA with dactylitis the first recommendation is NSAIDs and local corticosteroid injections&#44; although at present we do not have randomised and placebo-controlled studies to vouch for their efficacy&#46; The cDMARDs could be considered for patients with PsA and dactylitis as long as there is associated peripheral arthritis&#46; The cDMARDs have an effect size that is generally small for pure dactylitis&#46;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">92</span></a> The data for the TNFi drugs&#44;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">92</span></a> ustekinumab&#44;<a class="elsevierStyleCrossRefs" href="#bib0810"><span class="elsevierStyleSup">59&#44;60</span></a> secukinumab&#44;<a class="elsevierStyleCrossRefs" href="#bib0830"><span class="elsevierStyleSup">63&#44;82</span></a> and apremilast<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">54</span></a> is favourable for dactylitis&#58; none of the molecules have been demonstrated as superior over the rest&#46; These drugs are a therapeutic option for patients for whom local measures have failed&#46; However&#44; based on our years of experience in clinical practice&#44; and the experience reflected in the different international registries&#44; the panel of experts suggest the TNFi as the first option&#46; The other drugs are equally valid options and therefore the judgement of the physician should prevail&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> shows an algorithm for the management of dactylitis&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Axial Involvement</span><p id="par0320" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0325" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 16&#46;</span> Biological therapy &#40;TNFi or IL17i&#41; is recommended for patients with predominantly axial forms of PsA refractory to NSAIDs&#44; &#40;LE&#58; 4&#44; GR&#58; D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8226;</span><p id="par0330" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 17&#46;</span> The cDMARDs are not recommended for axial forms of PsA &#40;LE&#58; 2b&#44; GR&#58; C&#41;&#46;</p></li></ul></p><p id="par0335" class="elsevierStylePara elsevierViewall">In the absence of specific studies on PsA with predominant axial involvement&#44; the general recommendations apply for axial spondyloarthritis &#40;axial SpA&#41;&#44; which include&#44; in addition to physical exercise&#44; at least 2 NSAIDs at maximum dose for a period of 4 weeks each&#46;<a class="elsevierStyleCrossRef" href="#bib0980"><span class="elsevierStyleSup">93</span></a> Biological treatment can be started for the patients for whom these measures prove ineffective&#46; The use of cDMARDs is not justified because of the lack of evidence as to their efficacy at axial level&#46; There is currently insufficient scientific evidence to indicate the use of apremilast for patients with axial SpA&#46; A phase II&#44; single-centre&#44; double-blind&#44; placebo-controlled pilot study assessed the efficacy of apremilast 30<span class="elsevierStyleHsp" style=""></span>mg compared to a placebo over 12 weeks&#44; in 36 patients with active ankylosing spondylitis&#46;<a class="elsevierStyleCrossRef" href="#bib0985"><span class="elsevierStyleSup">94</span></a> Although there were differences in favour of the patient treated with apremilast&#44; they were not statistically significant&#44; including the change in BASDAI at week 12 that was the main aim of the study&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">Given the lack of comparative studies&#44; the first biological agent should be a TNFi&#44; in line with routine clinical practice&#46; However&#44; recently published data on secukinumab in ankylosing spondylitis are equally optimal&#44;<a class="elsevierStyleCrossRef" href="#bib0990"><span class="elsevierStyleSup">95</span></a> although at present there is no indication for this drug in the non-radiographic form&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">A recent publication on ustekinumab<a class="elsevierStyleCrossRef" href="#bib0995"><span class="elsevierStyleSup">96</span></a> of a post hoc analysis of its 2 clinical trials in PsA demonstrated a significant improvement in BASDAI and ASDAS-CRP at week 24 in the subgroup of patients with psoriatic arthritis&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">At present we do not have any trials that demonstrate a significant effect of the biological therapies on structural damage in axial PsA&#44; although there are data that show a potential slowing down effect of spinal radiographic progression associated with biological therapy on axial SpA&#46;<a class="elsevierStyleCrossRefs" href="#bib1000"><span class="elsevierStyleSup">97&#44;98</span></a></p><p id="par0355" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a> shows an algorithm for the management of axial disease&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Discussion</span><p id="par0360" class="elsevierStylePara elsevierViewall">This new SER Recommendations document seeks to serve as a guideline for treatment using the synthetic DMARDs and biological therapy for practitioners caring for PsA patients&#46; These recommendations&#44; based on the best available scientific evidence and on the clinical experience of experts in PsA&#44; are also based on the recommendations of the previous Consensus and the latest version of ESPOGUIA 2015&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">12</span></a></p><p id="par0365" class="elsevierStylePara elsevierViewall">PsA is one of the most heterogeneous forms of chronic arthritis from a clinical perspective&#44; and therefore the different therapeutic approaches and the different methods for assessing results for this entity currently pose a challenge to all clinicians in charge of diagnosing and treating this population&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">8</span></a> Although in recent years new drugs have been incorporated with different mechanisms of action&#44; and different treatment modalities have been tested &#40;T2T strategies&#41;&#44; the overall management of PsA patients remains a challenge&#46; Therefore&#44; the primary aim of this recommendations document is to provide clinicians with the best available evidence &#40;and failing this&#44; the best opinion agreed by the panel members&#41; for the rational and well-founded use of the various treatment options using synthetic and biological DMARDs for PsA&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">The valid contributions of the previous PsA consensus document have been kept&#44; therefore that stated in that document about cDMARDs remains in this document&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">11</span></a> Unlike the previous consensus document on the use of biological agents for PsA&#44; this document provides a series of hierarchical principles for managing the disease&#44; the best evidence has been reviewed on the new molecules that have appeared and have been approved since the previous consensus&#44; and an algorithm is provided for the management of PsA&#46; With all of this&#44; the group of experts expects the management of PsA to be guided by best evidence&#44; reducing as much as is possible the variability of this complex medical process&#46;</p><p id="par0375" class="elsevierStylePara elsevierViewall">The EULAR and GRAPPA recommendations for the management of PsA have been published recently&#46;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">9&#44;10</span></a> Our document&#44; although some aspects contained in those recommendations may overlap&#44; has been adapted as much as possible to the care reality of patients with PsA in Spain&#44; and this could be key in generalising the recommendations contained herein&#46;</p><p id="par0380" class="elsevierStylePara elsevierViewall">Our document does not cover aspects relating to the skin and nail involvement of psoriasis&#44; unlike the GRAPPA recommendations&#44; since we consider that the management of these processes falls to the dermatologist&#44; and the Spanish Academy of Dermatology and Venereology &#40;AEDV&#41; regularly publishes consensus documents similar to ours&#44; but obviously focussing on the management of those two aspects&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">99</span></a></p><p id="par0385" class="elsevierStylePara elsevierViewall">In recent years&#44; new therapies have been added to the therapeutic arsenal against PsA due to their mechanism of action&#46; This document has included this new evidence&#44; especially with regard to IL12&#47;23 and IL17 pathway inhibition &#40;ustekinumab and secukinumab&#44; respectively&#41;&#46; In this respect&#44; we decided to place the TNFi inhibitors&#44; IL12&#47;23-i and IL17-i&#44; at the same level&#44; which is also expressed in the therapeutic algorithm&#46; This is based on the fact that&#44; despite the absence of clinical trials that directly compare the efficacy of the diverse molecules available&#44; the differences between them to not appear to be significant&#46; In the section on new drugs&#44; we have also included a new tDMARD&#44; the PDE-4 inhibitor &#40;apremilast&#41;&#46; Only clinical experience will clarify the doubts as to its place in the therapeutic algorithm of PsA&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">7</span></a> The recommendations for these new PsA drugs are based on the best available evidence&#44; but should be evaluated circumspectly because they are recently approved drugs&#46; Therefore&#44; the medium to long-term effectiveness and safety are still unknown from a real world evidence &#40;RWE&#41; or daily practice perspective&#46;</p><p id="par0390" class="elsevierStylePara elsevierViewall">PsA and psoriasis are disorders with a large group of associated comorbidities&#44; which has led some experts to propose the concept of psoriatic disease to better capture the systemic nature of both entities&#46;<a class="elsevierStyleCrossRef" href="#bib1015"><span class="elsevierStyleSup">100</span></a> Cardiovascular comorbidity is perhaps the most relevant&#46; This is why we have included specific recommendations in this regard in this document&#44; although we recognise that this domain of the disease is in an active phase of evolution&#44; and more evidence is needed to support the potential benefits of the synthetic and biological DMARDs in the reduction of cardiovascular risk&#46;</p><p id="par0395" class="elsevierStylePara elsevierViewall">The optimisation of biological therapies is an aspect highlighted in the recent literature&#46; No specific recommendation is made in this document in this regard&#44; since there are no consistent published data&#44; but we do mention the need to assess this type of strategy individually&#46; The optimisation of the biological therapies has been incorporated into the routine for managing these patients in our country&#44; there being safety&#44; effectiveness&#44; cost and care equity reasons to support this type of approach&#46; The SER and the Spanish Society of Hospital Pharmacies have recently published a positioning document for optimising biological therapy in different rheumatological diseases&#44; including PsA&#46;<a class="elsevierStyleCrossRef" href="#bib1020"><span class="elsevierStyleSup">101</span></a> Even so&#44; this aspect is principally aimed at the TNFi&#44; since&#44; given the very recent incorporation of other non-TNFi&#44; it is not possible to make an extrapolation to the optimisation of these new agents&#46;</p><p id="par0400" class="elsevierStylePara elsevierViewall">At present&#44; only one trial has been published on T2T approach for PsA &#40;the TICOPA study&#41;&#44; which seems to indicate that this management method might achieve better results in skin and joint outcomes compared to standard management&#44; although at the cost of more adverse events&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">35</span></a> We believe that more information is still required on this type of approach to the disease before making a positive recommendation&#46; Furthermore&#44; although the evidence for early intervention with DMARDs in PsA is not supported by very solid evidence&#44; it is obvious that early diagnosis of the disease&#44; recognition of the adverse prognosis or poor outcome factors&#44; and the consequent establishment of early drug intervention should set the bases for better management of the disease in all its domains&#44; and ultimately&#44; a general improvement in outcomes for PsA&#46;<a class="elsevierStyleCrossRef" href="#bib1025"><span class="elsevierStyleSup">102</span></a></p><p id="par0405" class="elsevierStylePara elsevierViewall">These recommendations do not mention anything to do with the use of biosimilars in PsA either&#46; A biosimilar is a biological drug that contains a version of the active substance of an already authorised original biological product &#40;reference drug&#41;&#46; With regard to its original product&#44; a biosimilar must demonstrate high similarity in terms of quality&#44; biological activity&#44; safety and efficacy&#44; aspects that should be contrasted by the appropriate randomised clinical trials&#46; At present&#44; the safe use of these products in our country is guaranteed thanks to the regulatory framework in terms of quality&#44; preclinical and clinical criteria established by regulatory authorities such as the EMA&#46; The interchangeability and therapeutic substitution of these drugs should not be automatic or based on purely economic criteria&#44; since the benefit to the patient must always prevail in our decisions&#46; Therefore&#44; the panel of experts making these recommendations concur with what has already been expressed by the SER in their positioning document&#46;<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">103</span></a></p><p id="par0410" class="elsevierStylePara elsevierViewall">In sum&#44; this new recommendation document combines the best available evidence&#44; incorporating the evidence on the new molecules and new PsA treatment approaches&#44; together with the vision of rheumatologists who are experts in this disease&#46; The essence of this manuscript lies in collecting all the aspects that help the clinician to make a reasoned therapeutic decision for a case of PsA&#46; This means that&#44; when choosing a particular drug&#44; the decision should include aspects of the disease itself &#40;clinical phenotype&#44; severity&#44; poor prognosis factors&#41; together with other aspects of each molecule &#40;evidence&#44; experience&#44; efficacy&#44; safety&#44; optimisation&#41;&#46; In some cases&#44; financial costs might be an aspect to be taken into account&#44; especially when differences cannot be established based on scientific evidence&#44; without implying an absolute limitation of medical judgement&#44; which is the basis of the final decision&#46;</p><p id="par0415" class="elsevierStylePara elsevierViewall">It will soon be necessary to review and update the recommendations contained in this document&#44; since new molecules and new treatment methods are on the short-term horizon&#44; and we will probably have better evidence on aspects such as the therapeutic role of current and future treatments on cardiovascular risk&#44; the use of biosimilars&#44; and the optimisation of the current and future biological therapies&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Research Agenda</span><p id="par0420" class="elsevierStylePara elsevierViewall">Although these recommendations should help towards a better approach to PsA&#44; the expert panel acknowledges that many aspects are still to be covered in a future research agenda&#46; Some of these aspects include&#58;<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8226;</span><p id="par0425" class="elsevierStylePara elsevierViewall">Assessing from a RWE perspective the true effectiveness and safety of the new molecules approved for PsA&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8226;</span><p id="par0430" class="elsevierStylePara elsevierViewall">Studying whether there is a particular PsA phenotype that would accommodate the initial use of biological therapy without the prior need for synthetic DMARDs&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">&#8226;</span><p id="par0435" class="elsevierStylePara elsevierViewall">An analysis of the therapeutic role of combining new synthetic DMARDs &#40;apremilast&#41; with biological therapy or conventional synthetic DMARDs&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8226;</span><p id="par0440" class="elsevierStylePara elsevierViewall">Assessing pharmacogenomic biomarkers of therapeutic response&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8226;</span><p id="par0445" class="elsevierStylePara elsevierViewall">An in-depth examination of the therapeutic effects of the current and future molecules on the reduction of cardiovascular risk in this population&#46;</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">&#8226;</span><p id="par0450" class="elsevierStylePara elsevierViewall">A search for evidence to support the early therapeutic use of the current and future DMARDs on the different domains of psoriatic disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">&#8226;</span><p id="par0455" class="elsevierStylePara elsevierViewall">An in-depth study of the therapeutic niche for the new molecules in the PsA treatment algorithms&#46;</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">&#8226;</span><p id="par0460" class="elsevierStylePara elsevierViewall">Improving the optimisation strategies for the biological therapies for PsA&#46;</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">&#8226;</span><p id="par0465" class="elsevierStylePara elsevierViewall">Extending the evidence to solidly recommend the T2T strategies&#46;</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">&#8226;</span><p id="par0470" class="elsevierStylePara elsevierViewall">An analysis of the effect of biological therapies on the inhibition of radiographic progression in forms of axial PsA&#46;</p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">&#8226;</span><p id="par0475" class="elsevierStylePara elsevierViewall">An evaluation of the role of the biosimilars in the management of PsA&#46;</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">&#8226;</span><p id="par0480" class="elsevierStylePara elsevierViewall">Developing pathophysiological studies on the different phenotypes of the disease to discover which cells and molecules predominate in each&#44; in order to improve our therapeutic strategy&#46;</p></li></ul></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Ethical Disclosures</span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Protection of human and animal subjects</span><p id="par0485" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Confidentiality of data</span><p id="par0490" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Right to privacy and informed consent</span><p id="par0495" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Funding</span><p id="par0500" class="elsevierStylePara elsevierViewall">Spanish Rheumatology Foundation&#46;</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Conflicts of Interest</span><p id="par0505" class="elsevierStylePara elsevierViewall">Chamaida Plasencia Rodr&#237;guez received a grant with no restrictions from Pfizer&#59; fees as a speaker for Pfizer&#46;</p><p id="par0510" class="elsevierStylePara elsevierViewall">Juan Carlos Torre Alonso received funding from MSD&#44; Abbvie&#44; Pfizer&#44; Celgene&#44; Janssen for attending courses&#47;conferences&#59; and has received fees as a speaker and consultant for MSD&#44; Abbvie&#44; Pfizer&#44; UCB&#44; Celgene and Novartis&#46;</p><p id="par0515" class="elsevierStylePara elsevierViewall">Juan D Ca&#241;ete Crespillo has received funding from Novartis&#44; Janssen and Celgene for attending meetings&#44; conferences and courses&#59; fees from Abbvie&#44; Janssen and Celgene for speaking&#59; and has received funding from Abbvie&#44; Celgene&#44; Boehringer&#44; Janssen and Novartis for consultancy to pharmaceutical companies and other technologies&#46;</p><p id="par0520" class="elsevierStylePara elsevierViewall">Ruben Queiro Silva has received funding from Abbvie&#44; Celgene&#44; Pfizer&#44; MSD&#44; Janssen and UCB for attending meetings&#44; conferences&#44; courses and for speaking&#59; funding from Janssen and Celgene for taking part in a research study&#59; and has received financial help from Novartis&#44; Abbvie&#44; UCB&#44; Celgene and Pfizer for consultancy to pharmaceutical companies and other technologies&#46;</p><p id="par0525" class="elsevierStylePara elsevierViewall">Mireia Moreno Mart&#237;nez-Losa has received funding from Abbvie&#44; Pfizer&#44; MSD&#44; Janssen&#44; Celgene&#44; MSD&#44; Roche and UCB for attending meetings&#44; conferences&#44; courses and for speaking&#59; and has received financial help from Janssen for consultancy to pharmaceutical companies or other technologies&#46;</p><p id="par0530" class="elsevierStylePara elsevierViewall">Raquel Almod&#243;var Gonz&#225;lez has received funding from Abbvie&#44; Pfizer&#44; MSD&#44; Roche for attending meetings&#44; conferences and courses&#59; fees from Abbvie&#44; Celgene&#44; Novartis&#44; Pfizer&#44; Roche&#44; UCB for speaking&#59; and has received funding from Abbvie&#44; Jansen&#44; MSD&#44; Novartis&#44; Pfizer&#44; Roche for undertaking educational programmes and courses&#46; And has received financial help from Abbvie&#44; Celgene&#44; Janssen&#44; MSD&#44; Pfizer&#44; UCB for consultancy to pharmaceutical companies and other technologies&#46;</p><p id="par0535" class="elsevierStylePara elsevierViewall">Carlos Montilla Morales has received funding from Abbvie&#44; MSD and Janssen for attending meetings&#44; conferences&#44; courses and for speaking&#46; He has received financial help from Janssen for consultancy&#46;</p><p id="par0540" class="elsevierStylePara elsevierViewall">Julio Ram&#237;rez Garc&#237;a has received funding from MSD&#44; Abbvie&#44; Pfizer&#44; Bristol&#44; UCB&#44; Novartis&#44; Janssen&#44; Celgene and Roche for scientific talks and for attending meetings&#44; conferences and training courses&#46;</p><p id="par0545" class="elsevierStylePara elsevierViewall">Petra D&#237;az del Campo Fontecha has no conflict of interests to declare&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The main purpose of this recommendation statement is to provide clinicians with the best available evidence and the best opinion agreed upon by the panellists for a rational use of synthetic disease modifying antirheumatic drugs &#40;DMARDs&#41; and biologicals in psoriatic arthritis &#40;PsA&#41; patients&#46; The present document also focuses on important aspects in the management of PsA&#44; such as early diagnosis&#44; therapeutic objectives&#44; comorbidities and optimisation of treatment&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The recommendations were agreed by consensus by a panel of 8 expert rheumatologists&#44; previously selected by the Spanish Society of Rheumatology &#40;SER&#41; through an open call&#46; The phases of the work were&#58; identification of key areas for updating the previous consensus&#44; analysis and synthesis of scientific evidence &#40;modified Oxford system&#44; Centre for Evidence-based Medicine&#44; 2009&#41; and formulation of recommendations based on this evidence and by consensus techniques&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Seventeen recommendations were issued for the treatment of PsA patients&#46; Six of them were of general nature&#44; ranging from the early diagnosis and treatment to the importance of assessing comorbidities&#46; The other 11 were focused on the indications for DMARDs and biological therapy in the distinct clinical forms of the disease&#46; Likewise&#44; the situation of failure of the first biological is addressed and treatment algorithms and a table with the different biological therapies are also included&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We present the update of SER recommendations for the treatment of PsA with DMARDs and biologics&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La primera finalidad de este documento de recomendaciones es proporcionar al cl&#237;nico la mejor evidencia disponible y&#44; en su defecto&#44; la mejor opini&#243;n consensuada por los panelistas para un uso racional y fundado de las diversas opciones de tratamiento con f&#225;rmacos antirreum&#225;ticos modificadores de la enfermedad &#40;FAME&#41; sint&#233;ticos y biol&#243;gicos en artropat&#237;a psori&#225;sica &#40;APs&#41;&#46; El presente documento tambi&#233;n incide sobre aspectos importantes en el manejo de la APs&#44; como el diagn&#243;stico precoz&#44; los objetivos terap&#233;uticos&#44; las comorbilidades y la optimizaci&#243;n del tratamiento&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Las recomendaciones se consensuaron a trav&#233;s de un panel de 8 reumat&#243;logos expertos&#44; previamente seleccionados por la Sociedad Espa&#241;ola de Reumatolog&#237;a &#40;SER&#41; mediante una convocatoria abierta&#46; Las fases del trabajo fueron&#58; identificaci&#243;n de las &#225;reas claves para la actualizaci&#243;n del consenso anterior&#44; an&#225;lisis y s&#237;ntesis de la evidencia cient&#237;fica &#40;sistema modificado de Oxford&#44; CEBM&#44; 2009&#41; y formulaci&#243;n de recomendaciones a partir de esta evidencia y de t&#233;cnicas de consenso&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se emiten un total de 17 recomendaciones para el tratamiento de los pacientes con APs&#46; Seis de ellas de car&#225;cter general&#44; que abarcan desde la transcendencia del diagn&#243;stico y tratamiento precoz hasta la importancia de las comorbilidades&#46; El resto&#44; las 11 espec&#237;ficas&#44; se centran en las indicaciones de los FAME y la terapia biol&#243;gica en las diferentes formas cl&#237;nicas de la enfermedad&#46; As&#237; mismo&#44; se abordan las situaciones de fracaso a un primer biol&#243;gico y se incluyen los algoritmos de tratamientos y una tabla con las diferentes terapias biol&#243;gicas&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se presenta la actualizaci&#243;n de las recomendaciones de la SER para el tratamiento de la APs con FAME y terapia biol&#243;gica&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Torre Alonso JC&#44; D&#237;az del Campo Fontecha P&#44; Almod&#243;var R&#44; Ca&#241;ete JD&#44; Montilla Morales C&#44; Moreno M&#44; et al&#46; Recomendaciones de la Sociedad Espa&#241;ola de Reumatolog&#237;a sobre el tratamiento y uso de terapias sist&#233;micas biol&#243;gicas y no biol&#243;gicas en artritis psori&#225;sica&#46; Reumatol Clin&#46; 2018&#59;14&#58;254&#8211;268&#46;</p>"
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          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Axial disease treatment algorithm&#46;</p> <p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">NSAIDs&#58; Non-steroidal anti-inflammatory drugs&#59; TNFi&#58; tumour necrosis factor inhibitor&#59; IL17i&#58; interleukin inhibitor 17&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">GA&#58; grade of agreement&#59; GR&#58; grade of recommendation&#59; SER&#58; Spanish Rheumatology Society&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">General recommendations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GA<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 1</span>&#46; PsA is a chronic inflammatory musculoskeletal disease whose diagnosis&#44; treatment and evolutionary control should be managed by rheumatologists&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 2</span>&#46; The clinical presentation of PsA is very heterogeneous and it has some associated comorbidities that occasionally require multidisciplinary management&#46; Coordinated management with the dermatologist is important&#44; especially for patients with moderate-severe psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 3&#46;</span> The therapeutic objective of PsA is to control inflammation and preserve the patients&#8217; functional capacity&#44; achieving clinical remission or minimal&#47;low disease activity according to the different validated indices&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 4&#46;</span> Establishing a therapeutic objective and strict clinical monitoring are crucial to achieve optimal control of clinical activity and an appropriate therapeutic response&#46; Once the therapeutic objective has been achieved&#44; quarterly follow-up seems reasonable&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 5&#46;</span> The cardiovascular risk profile must be taken into account on assessment and during the therapeutic management of these patients&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 6</span>&#46; The most appropriate therapeutic decision will depend on the judgement of the specialist and will be agreed with the patient&#46; This decision will be taken based principally on the scientific evidence and the features of the patient and their disease&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1853014.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">SER Recommendations on the Treatment and Use of Biological Therapies for Psoriatic Arthritis&#46; General Recommendations&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">NSAIDs&#58; Non-steroidal anti-inflammatory drugs&#59; DMARDs&#58; disease-modifying antirheumatic drugs&#59; cDMARDs&#58; conventional synthetic DMARDs&#59; tDMARDs&#58; targeted DMARDs&#59; GA&#58; grade of agreement&#59; GR&#58; grade of recommendation&#59; IL12i&#44; IL23i or IL17i&#58; interleukin inhibitor 12&#44; 23 or 17&#59; PDE4i&#58; TNFi&#58; tumour necrosis factor inhibitors&#59; LE&#58; level of evidence&#59; SER&#58; Spanish Society of Rheumatology&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Specific recommendations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GA<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 7&#46;</span> Early intervention with cDMARDs is recommended for patients with PsA&#44; principally those with poor baseline prognostic factors&#44; in order to improve the signs and symptoms&#44; functional capacity and quality of life&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 8</span>&#46; The cDMARDs &#40;MTX&#44; leflunomide&#44; sulfasalazine&#41; are recommended as first-line treatment for active peripheral PsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 9</span>&#46; MTX is recommended as first choice&#44; due to its effects on arthritis and psoriasis &#40;LE&#58; 4&#44; GR&#58; D&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 10&#46;</span> Apremilast is recommended for the treatment of peripheral arthritis&#44; after cDMARD failure or intolerance&#44; when it is considered more appropriate than biological therapy due to the patient&#39;s profile&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 11</span>&#46; Biological therapy is recommended for peripheral PsA patients refractory to at least one cDMARD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 12&#46;</span> Biological therapy is recommended&#44; in monotherapy and in combination with cDMARDs&#44; for all the peripheral manifestations of PsA&#46; Combining the therapy with MTX can increase the survival of the monoclonal&#44; especially the chimeric&#44; TNFi drugs&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 13&#46;</span> In patients with peripheral PsA&#44; and after failure of a TNFi&#44; a change to another biological therapy is recommended&#44; either another TNFi or a drug with a different mechanism of action&#44; such as i-IL12&#47;23 or i-IL17 or a tDMARD &#40;apremilast&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1b&#44; 2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 14&#46;</span> Biological therapy or tDMARDS &#40;apremilast&#41; are recommended for patients with PsA and enthesitis refractory to NSAID and local treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 15&#46;</span> Biological treatment or tDMARDS &#40;apremilast&#41; are recommended for patients with PsA and dactylitis refractory to NSAIDs and local corticosteroid injections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 16&#46;</span> Biological therapy &#40;TNFi or IL17i&#41; is recommended for patients with predominantly axial forms of PsA refractory to NSAIDs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 17&#46;</span> The cDMARDs are not recommended for axial forms of PsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1853016.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">SER Recommendations on the Treatment and Use of Biological Therapies in Psoriatic Arthritis&#46; Specific Recommendations&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">The data in this table were obtained from the data sheet of the Spanish Agency of Medicines and Medical Devices &#40;AEMPS&#41;&#46;</p><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">ILD&#58; interstitial lung disease&#59; DMARDs&#58; disease-modifying antirheumatic drugs&#59; AHT&#58; arterial hypertension&#59; HF&#58; heart failure&#59; CHF&#58; congestive heart failure&#59; i&#46;v&#46;&#58; intravenous&#59; SLE&#58; systemic lupus erythematosus&#59; MTX&#58; methotrexate&#59; NYHA&#58; New York Heart Association&#59; TBC&#58; tuberculosis&#59; TNF&#58; tumour necrosis factor&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Biological therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Active ingredient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dosage and administration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Indications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Contraindications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse events<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TNFi alpha&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Adalimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose&#58; 40<span class="elsevierStyleHsp" style=""></span>mg<br>-Route&#58; subcutaneous<br>-Frequency&#58; every 2 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active and progressive psoriatic arthritis in adults when the response to previous therapy with DMARDs has been insufficient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Hypersensitivity to the active ingredient or excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; reaction at the injection site &#40;pain&#44; redness&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Active TBC&#44; serious infections such as sepsis and opportunistic infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; headache&#44; respiratory&#44; urinary infection&#44; herpes&#44; diarrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Moderate to severe HF &#40;NYHA classes <span class="elsevierStyleSmallCaps">III&#47;IV</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; SLE&#44; TBC&#44; arrhythmia&#44; sepsis&#44; cytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; CHF&#44; multiple sclerosis&#44; lymphoma&#44; solid malignant tumour&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Certolizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose&#58; 200<span class="elsevierStyleHsp" style=""></span>mg or 400<span class="elsevierStyleHsp" style=""></span>mg<br>-Route&#58; subcutaneous<br>-Frequency&#58; initially &#40;400<span class="elsevierStyleHsp" style=""></span>mg at weeks 0&#44; 2 and 4&#41;&#44; maintenance &#40;200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks or 400<span class="elsevierStyleHsp" style=""></span>mg every 4 weeks&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active psoriatic arthritis in adults&#44; when the previous response to treatment with DMARDs has been inadequate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">-</span> Hypersensitivity to the active ingredient or excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Active TBC&#44; serious infections such as sepsis and opportunistic infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; bacterial and viral infections&#44; leukopenias&#44; headache&#44; AHT&#44; nausea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Moderate to severe HF &#40;NYHA classes <span class="elsevierStyleSmallCaps">III&#47;IV</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; sepsis&#44; TBC&#44; fungal infections&#44; lymphatic system neoplasms&#44; solid tumours&#44; non-melanoma skin cancers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; polycytopenia&#44; splenomegaly&#44; melanoma&#44; pericarditis&#44; ILD&#44; pneumonitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Etanercept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose&#58; 25 or 50<span class="elsevierStyleHsp" style=""></span>mg<br>-Route&#58; subcutaneous<br>-Frequency&#58; 25<span class="elsevierStyleHsp" style=""></span>mg twice per week &#40;interval of 72&#8211;96<span class="elsevierStyleHsp" style=""></span>h&#41;&#59; 50<span class="elsevierStyleHsp" style=""></span>mg once a week&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active psoriatic arthritis in adults&#44; when previous response to treatment with DMARDs has been inadequate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Hypersensitivity to the active ingredient or excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; reaction at the injection site&#44; respiratory&#44; urinary&#44; skin infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Sepsis or risk of sepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; allergy&#44; autoantibodies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Active infections &#40;including chronic or localised&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; serious infections&#44; thrombocytopenia&#44; psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; pancytopenia&#44; TBC&#44; SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Golimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose&#58; 50<span class="elsevierStyleHsp" style=""></span>mg<br>-Dose&#58; 100<span class="elsevierStyleHsp" style=""></span>mg in patients with psoriatic arthritis&#44; with a body weight of more than 100<span class="elsevierStyleHsp" style=""></span>kg who have not achieved an appropriate clinical response after 3 or 4 doses&#44; the dose of golimumab can be increased to 100<span class="elsevierStyleHsp" style=""></span>mg administered once a month<br>-Route&#58; subcutaneous<br>-Frequency&#58; once a month&#44; the same day every month&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Alone&#44; or in combination with MTX&#44; indicated for the treatment of active and progressive psoriatic arthritis in adults&#44; when the response to previous treatment with DMARDs has been inadequate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Hypersensitivity to the active ingredient or excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; upper respiratory tract infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Active TBC&#44; serious infections such as sepsis and opportunistic infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; cellulitis&#44; herpes&#44; bronchitis&#44; sinusitis&#44; AHT&#44; superficial fungal infections&#44; anaemia&#44; antibodies&#44; allergic reaction&#44; depression&#44; insomnia&#44; headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Moderate or severe HF &#40;NYHA classes <span class="elsevierStyleSmallCaps">III&#47;IV</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; TBC&#44; CHF&#44; sepsis&#44; neoplasms&#44; &#8593; glucose&#44; lipids&#44; thrombosis&#44; arrhythmia&#44; eye conditions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; hepatitis B reactivation&#44; lymphoma&#44; pancytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Infliximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose &#40;according to body weight&#41;&#58; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg<br>-Route&#58; i&#46;v&#46; infusion over 2<span class="elsevierStyleHsp" style=""></span>h<br>-Frequency&#58; after the first dose&#44; another at 2 and at 6 weeks&#46; Then 1 every 6&#8211;8 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active psoriatic arthritis in adults&#44; when previous response to treatment with DMARDs has been inadequate<br>Should be given in combination with MTX or used in monotherapy in the event of contraindication or intolerance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Hypersensitivity to the active ingredient&#44; excipients or other murine proteins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; injection reaction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Active TBC&#44; serious infections such as septicaemia&#44; abscesses and opportunistic infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; headache&#44; respiratory infection&#44; herpes&#44; diarrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Moderate to severe HF &#40;NYHA classes <span class="elsevierStyleSmallCaps">III</span>&#47;<span class="elsevierStyleSmallCaps">IV</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; SLE&#44; TBC&#44; sepsis&#44; cytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; CHF&#44; multiple sclerosis&#44; lymphoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">i-IL17A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Secukinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose&#58; 150<span class="elsevierStyleHsp" style=""></span>mg<br>-Dose refractory to previous biological therapy&#58; 300<span class="elsevierStyleHsp" style=""></span>mg<br>-Route&#58; subcutaneous<br>-Frequency&#58; initially at week 0&#44; 1&#44; 2 and 3&#46; Then monthly maintenance&#44; starting in week 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active psoriatic arthritis in adult patients who have shown inadequate response to treatment with DMARDs<br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Severe hypersensitivity to the active ingredient or one of its excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; upper respiratory tract infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Clinically relevant active infections &#40;e&#46;g&#46;&#44; active TBC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; oral herpes&#44; rhinorrhoea&#44; diarrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; urticaria&#44; conjunctivitis&#44; neutropenia&#44; oral candidiasis&#44; athlete&#39;s foot&#44; otitis externa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; anaphylactic reactions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">i-IL12&#47;23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Initial dose of 45<span class="elsevierStyleHsp" style=""></span>mg administered subcutaneously followed by a second dose of 45<span class="elsevierStyleHsp" style=""></span>mg 4 weeks later and then every 12 weeks<br>-As an alternative a dose of 90<span class="elsevierStyleHsp" style=""></span>mg can be given to patients who weigh over 100<span class="elsevierStyleHsp" style=""></span>kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active psoriatic arthritis in adult patients who have shown inadequate response to treatment with DMARDs<br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">- Severe hypersensitivity to the active ingredient or one of its excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; nasopharyngitis and headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Clinically relevant active infections &#40;e&#46;g&#46;&#44; active TBC&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; viral respiratory tract infections&#44; mycotic infection&#44; depression&#44; pustular psoriasis&#44; injection site reactions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; anaphylactic reactions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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Special Article
Recommendations of the Spanish Society of Rheumatology on Treatment and Use of Systemic Biological and Non-biological Therapies in Psoriatic Arthritis
Recomendaciones de la Sociedad Española de Reumatología sobre el tratamiento y uso de terapias sistémicas biológicas y no biológicas en artritis psoriásica
Juan Carlos Torre Alonsoa, Petra Díaz del Campo Fontechab, Raquel Almodóvarc, Juan D. Cañeted, Carlos Montilla Moralese, Mireia Morenof, Chamaida Plasencia-Rodríguezg, Julio Ramírez Garcíah, Rubén Queiroi,
Corresponding author
rubenque7@yahoo.es

Corresponding author.
a Unidad de Reumatología, Hospital Monte Naranco y Universidad de Oviedo, Oviedo, Spain
b Unidad de Investigación, Sociedad Española de Reumatología, Madrid, Spain
c Unidad de Reumatología, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain
d Unidad de Artritis, Servicio de Reumatología, Hospital Clínic, Barcelona, Spain
e Servicio de Reumatología, Hospital Clínico Universitario de Salamanca, Salamanca, Spain
f Servicio de Reumatología, Parc Taulí Hospital Universitari, Sabadell, Barcelona, Spain
g Servicio de Reumatología, Hospital Universitario La Paz, IdiPaz, Madrid, Spain
h Unidad de Artritis, Servicio de Reumatología, IDIBAPS y Hospital Clínic, Barcelona, Spain
i Sección de Reumatología, Hospital Universitario Central de Asturias, Oviedo, Spain
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respectively&#46; In this paper we present the updated recommendations of the Spanish Society of Rheumatology &#40;SER&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">11</span></a> which seek to help rheumatologists to optimise the therapeutic management of PsA&#46; This document not only gathers the principal aspects of control and treatment with biological drugs but also covers important aspects in the management of PsA such as early diagnosis&#44; therapeutic objectives&#44; the use of synthetic DMARDs&#44; comorbidities&#44; and treatment optimisation&#46; However&#44; the recommendations focus chiefly on therapeutic strategies using synthetic and biological DMARDs&#46; Under no circumstances do these recommendations claim to be a strict protocol for the management and treatment of the disease&#44; but rather to serve as a basis to increase the quality of care of patients with PsA&#44; and help therapeutic decision-making&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">We used a qualitative synthesis of the scientific evidence and consensus techniques in this project &#40;&#8220;reasoned judgement&#8221; and &#8220;modified Delphi technique&#8221;&#41;&#44; agreed by experts based on their clinical experience&#44; and the scientific evidence&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Phases of the Process</span><p id="par0035" class="elsevierStylePara elsevierViewall">A series of steps were followed in preparing the recommendations document as described below&#58;</p><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Creation of the working group&#46;</span> The paper was started by setting up a panel of experts selected through an open call to all SER members&#46; The Committee for Practice Guidelines &#40;CPG&#41; and SER Recommendations evaluated the curricula of the applicants according to objective criteria of their contribution to knowledge on PsA&#44; principally by participation in journal publications of impact over the past 5 years&#46; The panel of experts comprised 8 rheumatologists&#44; members of SER&#46; The clinical and methodological aspects were managed by one of these rheumatologists as the principal investigator &#40;PI&#41;&#44; and by a methodology specialist&#44; SER Investigation Unit &#40;IU&#41; technician&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Identification of the key areas for updating the previous consensus&#46;</span> All the members of the working team participated to structure the document&#44; and establish the content and key aspects&#46; The recommendations from the previous Consensus and the last version of the 2015 ESPOGUIA<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">12</span></a> were chosen for updating&#46; First&#44; the clinical questions were identified that might most impact the use of biological therapy for PsA&#46; Then the content and results that did not have to answer the formulation of the research question were established&#46; The methodology to follow in the process of preparing the recommendations was also defined&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Literature search&#46;</span> The clinical questions were reformulated in 7 questions in PICO format&#46; A search strategy was designed to answer the questions&#44; and the scientific evidence from studies published up to February 2016 was reviewed&#46; The databases used were&#58; PubMed &#40;MEDLINE&#41;&#44; EMBASE&#44; and Cochrane Library &#40;Wiley Online&#41;&#46; The process was completed with a manual search of references&#44; posters and conference summaries that the reviewers and experts considered of interest&#46; The literature search strategies&#44; from the 7 systematic reviews &#40;SR&#41;&#44; can be found in the supplementary material that is detailed in a methodological annex on the SER website&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Analysis and synthesis of the scientific evidence&#46;</span> Various rheumatologists&#44; from the SER working group of evidence reviewers&#44; were in charge of systematically reviewing the available scientific evidence&#46; After a critical reading of the full text of the studies chosen for each review&#44; they prepared an abstract using a standardised form including tables and text to describe the methodology&#44; results and quality of each study&#46; The reasons for excluding the articles that were not included in the selection were detailed&#46; The overall level of scientific evidence was assessed using the modified levels of evidence of the Oxford Centre for Evidence-based Medicine &#40;CEBM&#41; &#40;<a id="intr0010" class="elsevierStyleInterRef" href="http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009">http&#58;&#47;&#47;www&#46;cebm&#46;net&#47;oxford-centre-evidence-based-medicine-levels-evidence-march-2009</a>&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Formulation of the recommendations&#46;</span> When the critical reading had been completed&#44; the PI and the expert panel went on to formulate specific scientific evidence-based recommendations&#46; This formulation was based on &#8220;formal assessment&#8221; or &#8220;reasoned judgement&#8221;&#44; summarising the evidence beforehand for each of the clinical questions&#46; The quality&#44; quantity and consistency of the scientific evidence were considered&#44; commonality of the results&#44; their applicability and clinical impact&#46; Two consensus rounds were used to formulate the recommendations&#59; first&#44; in an in-person meeting&#44; with the &#8220;reasoned judgement&#8221; consensus system&#44; all the experts drafted and discussed the recommendations and they were discussed in the presence of the methodologist&#59; then&#44; using a Delphi questionnaire&#44; the level of agreement of the experts was agreed scoring each of the recommendations using a Likert scale from 1 to 5 &#40;1&#58; completely disagree&#59; 2&#58; moderately disagree&#59; 3&#58; neither agree nor disagree&#59; 4&#58; moderately agree&#59; 5&#58; completely agree&#41;&#46; A high level of agreement was defined for drafting when more than 75&#37; panellists awarded &#8805;4 on the Likert scale&#46; The level of evidence and grading of the strength of recommendations were based on the modified Oxford system 2009&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Public exposure&#46;</span> The draft of this SER Recommendations document underwent a process of public exposure by partner members of SER and of different interest groups &#40;pharmaceutical industry&#44; other scientific societies&#44; and patient associations&#41;&#44; to determine their assessment and scientific argument for the methodology and the recommendations&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Structure</span><p id="par0070" class="elsevierStylePara elsevierViewall">The document gathers all the recommendations&#44; formulated and subdivided into two sections&#58; general principles and specific recommendations&#46; A therapeutic algorithm was created based on the recommendations&#44; which presents the treatment approach after diagnosis of PsA in summarised form&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">A total of 17 recommendations were formulated on the treatment and use of biological therapies for PsA &#40;<a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">General Recommendations</span><p id="par0080" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 1&#46;</span> PsA is a chronic inflammatory musculoskeletal disease whose diagnosis&#44; treatment and evolutionary control should be managed by rheumatologists&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8226;</span></span><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 2&#46;</span> The clinical presentation of PsA is very heterogeneous&#44; and it has some associated comorbidities that occasionally require multidisciplinary management&#46; Coordinated management with the dermatologist is important&#44; especially for patients with moderate-severe psoriasis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 3&#46;</span> The therapeutic objective of PsA is to control inflammation and preserve the patients&#8217; functional capacity&#44; achieving clinical remission or minimal&#47;low disease activity according to the different validated indices&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8226;</span></span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 4<span class="elsevierStyleBold">&#46;</span></span> Establishing a therapeutic objective and strict clinical monitoring are crucial to achieve optimal control of clinical activity&#44; and an appropriate therapeutic response&#46; Once the therapeutic objective has been achieved&#44; quarterly follow-up seems reasonable&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8226;</span></span><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 5<span class="elsevierStyleBold">&#46;</span></span> The cardiovascular risk profile must be taken into account on assessment and during the therapeutic management of these patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 6<span class="elsevierStyleBold">&#46;</span></span> The most appropriate therapeutic decision will depend on the judgement of the specialist&#44; and will be agreed with the patient&#46; This decision will be taken based principally on the scientific evidence&#44; and the features of the patient and their disease&#46;</p></li></ul></p><p id="par0115" class="elsevierStylePara elsevierViewall">The clinical presentation of PsA is very heterogeneous and includes articular and extra-articular manifestations&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">1&#44;4</span></a> As the specialists with the best knowledge and experience in the clinical and therapeutic management of this disease&#44; rheumatologists should be in charge of diagnosis and treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">9&#44;13&#44;14</span></a> However&#44; due to the diversity of its clinical expression and associate comorbidities&#44; multidisciplinary management of these patients is important&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">15&#8211;17</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The clinical objective when treating patients with PsA is not as well defined as that of RA&#46;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">18&#8211;22</span></a> Irrespective of the activity index used to monitor clinical activity&#44; the priority should be to control inflammation as soon as possible&#44; and improve the functional capacity and quality of life of patients with PsA&#46;<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">23&#8211;25</span></a> Clinical remission can be difficult to achieve&#44; especially in long-term PsA&#46;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">26&#8211;28</span></a> In this subgroup it can be sufficient to obtain minimal&#47;low disease activity&#8212;to achieve 5 of the 7 criteria proposed&#44; from musculoskeletal and skin manifestations to assessment of the patient him or herself&#46;<a class="elsevierStyleCrossRefs" href="#bib0635"><span class="elsevierStyleSup">24&#44;29&#44;30</span></a> Although there is no consensus on the best tool to monitor clinical activity&#44; the use is recommended of validated and quantifiable indices that cover parameters of inflammatory activity &#40;joint involvement &#91;peripheral and&#47;or axial&#93;&#44; dactylitis&#44; enthesitis and acute phase reagents&#41;&#44; and more subjective parameters that impact the patients&#8217; function and quality of life &#40;pain&#44; fatigue&#44; overall assessment of the patient&#44; functional capacity and quality of life&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0625"><span class="elsevierStyleSup">22&#44;23&#44;31&#8211;34</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">A recent clinical trial has shown better outcomes after strict monitoring &#40;<span class="elsevierStyleItalic">tight control</span>&#44; every 4 weeks&#41; compared to routine clinical practice &#40;every 12 weeks&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">35</span></a> Although&#44; at present&#44; the best monitoring interval for patients is not clear&#44; it seems reasonable to perform stricter control &#40;every 4 weeks&#41; after the disease has been diagnosed or whenever the response to a treatment needs to be assessed&#46; When the therapeutic objective has been achieved&#44; quarterly monitoring is sufficient&#46;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">9&#44;35</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Several guidelines are currently available for the management of PsA patients that constitute essential tools for the therapeutic approach to these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">9&#44;36</span></a> In clinical practice&#44; however&#44; it is recommended that the comorbidities associated with the disease should be considered when making therapeutic decisions&#44; as well as the patient&#39;s opinion&#44; explaining the risk&#47;benefit of each&#44; because this can encourage better treatment adherence and compliance&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Approaching cardiovascular risk in patients with chronic inflammatory diseases is important&#44; since there is a known connection between inflammation&#44; endothelial dysfunction and increased atherogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">37</span></a> An increase in cardiovascular risk factors &#40;hypertension&#44; diabetes&#44; dyslipidaemia&#44; etc&#46;&#41; has been observed in patients with PsA associated with the role of inflammation&#44; resulting in a greater prevalence of cardiovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">38</span></a> Obesity prevention is another significant aspect that we need to stress&#44; since as well as being a cardiovascular risk factor it can also be associated with a poorer response to immunosuppressive treatments&#44; and greater difficulty in achieving a status of minimal disease activity&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">39</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">We infer from a systematic review of this field&#44; that the epidemiological data are insufficient to reach definitive conclusions on the effects of biological drugs and cDMARDs on cardiovascular events in patients with PsA&#46; However TNFi and methotrexate &#40;MTX&#41;&#44; acting as inflammation inhibitors&#44; can have cardioprotective effects&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">40</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Furthermore&#44; the specialist&#39;s therapeutic decision should be the most cost-effective possible with the greatest clinical benefit for the patient&#44; without constituting an added burden for the national health system&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Specific Recommendations</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Early Intervention</span><p id="par0150" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8226;</span></span><p id="par0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 7&#46;</span> Early intervention with cDMARDs is recommended for patients with PsA&#44; principally those with poor baseline prognostic factors&#44; in order to improve the signs and symptoms&#44; functional capacity&#44; and quality of life &#40;LE&#58; 4&#44; GR&#58; D&#41;&#46;</p></li></ul></p><p id="par0160" class="elsevierStylePara elsevierViewall">Although the scientific evidence is sparse and controversial in this field&#44; six studies were found that answered this question indirectly&#46; Long duration of the disease&#44;<a class="elsevierStyleCrossRefs" href="#bib0720"><span class="elsevierStyleSup">41&#44;42</span></a> and delayed diagnosis of early PsA<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">43</span></a> are major factors influencing progression of structural joint damage&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Various studies have assessed functional capacity in early and established PsA&#46;<a class="elsevierStyleCrossRefs" href="#bib0690"><span class="elsevierStyleSup">35&#44;43&#44;44</span></a> It has been observed that delayed diagnosis&#44; smoking&#44; advanced age&#44; being female&#44; and a history of TNF-I treatments are associated with poorer functional capacity&#46;<a class="elsevierStyleCrossRefs" href="#bib0720"><span class="elsevierStyleSup">41&#44;43</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">It was found in the Swedish Early PsA Registry that a shorter duration of symptoms&#44; a low baseline HAQ&#44; and axial disease in males were independent predictive factors of minimal disease activity&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">44</span></a> The authors suggest that early diagnosis in patients with polyarticular involvement can be important to start specific treatment more promptly&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">44</span></a> Therefore&#44; although there are few studies that cover this subject&#44; we can consider the polyarticular forms with raised inflammatory reactants&#44; delayed diagnosis and therapy&#44; dactylitis&#44; the presence of baseline erosions&#44; and smoking to be factors of poor prognosis&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The TICOPA study demonstrated that early therapeutic intervention&#44; and tight clinical follow-up &#40;every 4 weeks&#41; achieved better clinical responses &#40;assessed by ACR and MDA&#41; than the routine clinical practice &#40;every 12 weeks&#41; in a cohort of early PsA&#44; although they found no differences in radiographic progression at 48 weeks&#44;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">35</span></a> largely due to the poor overall progression of both cohorts&#46; On the other hand&#44; an open study performed on 35 patients with PsA observed that a delay of 3 months in starting treatment with MTX had no relevant clinical impact&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">45</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Peripheral Arthritis</span><p id="par0180" class="elsevierStylePara elsevierViewall">Nonsteroidal anti-inflammatory drugs &#40;NSAIDs&#41; and oral corticosteroids&#44; used at the minimum necessary dose for the shortest possible time&#44; can be useful as symptomatic treatment for peripheral PsA&#44; without causing a delay in initiating disease-modifying treatment for patients for whom it is indicated&#46; Local therapy in the form of corticosteroid injections is particularly recommended for enthesitis and dactylitis&#44; and is also useful for peripheral mono- or oligoarticular arthritis&#46; Ultrasound guidance can be useful for these procedures&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Synthetic Disease-modifying Anti-rheumatic Drugs &#40;DMARDs&#41;</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conventional Synthetic Disease-modifying Anti-rheumatic Drugs &#40;cDMARDs&#41;</span><p id="par0185" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 8&#46;</span> The cDMARDs &#40;MTX&#44; leflunomide&#44; sulfasalazine&#41; are recommended as first-line treatment for active peripheral PsA &#40;LE&#58; 2b&#44; GR&#58; <span class="elsevierStyleSmallCaps">C</span>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 9&#46;</span> MTX is recommended as first choice&#44; due to its effects on arthritis and psoriasis &#40;LE&#58; 4&#44; GR&#58; D&#41;&#46;</p></li></ul></p><p id="par0200" class="elsevierStylePara elsevierViewall">The cDMARDs are recommended as the first therapeutic option for patients with peripheral PsA&#46; MTX is the treatment of choice and leflunomide and sulfasalazine are other valid options&#46; Clinical trials of MTX&#44; due to different methodological circumstances&#44; have not provided conclusive data on its efficacy for PsA&#46;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">46</span></a> However&#44; extensive experience in routine clinical practice&#44; and data from observational studies and registries suggest that MTX is effective for PsA&#46; In the Norwegian registry&#44; survival for MTX at 2 years was 65&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">47</span></a> and in the TICOPA<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">35</span></a> study&#44; 22&#37; of the patients on MTX as monotherapy achieved minimal disease activity&#46; As yet&#44; there is insufficient evidence for the role played by the cDMARDs in inhibiting structural damage&#44; although MTX at high doses might have some effect&#46;<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">49</span></a> For all these reasons&#44; MTX is recommended as the first therapeutic option based on broad clinical experience&#44; its efficacy in areas such as the skin&#44;<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">50</span></a> its low cost and universal access&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Targeted Synthetic Disease-modifying Antirheumatic Drugs &#40;tDMARDS&#41;</span><p id="par0205" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0210" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 10&#46;</span> Apremilast is recommended for the treatment of peripheral arthritis&#44; after cDMARD failure or intolerance&#44; when it is considered more appropriate than biological therapy due to the patient&#39;s profile &#40;LE&#58; 2b&#44; GR&#58; C&#41;&#46;</p></li></ul></p><p id="par0215" class="elsevierStylePara elsevierViewall">Apremilast is a small molecule that inhibits phosphodiesterase 4 &#40;PDE 4&#41;&#46; PDE4 inhibition causes an increase in intracellular levels of cyclic adenosine monophosphate &#40;cAMP&#41;&#44; modulating inflammatory cytokine expression&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">51</span></a> The efficacy data on apremilast for peripheral arthritis&#44; based on the results of clinical trials&#44; seem to be inferior to biological therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0775"><span class="elsevierStyleSup">52&#8211;54</span></a> The lack of data on radiographic progression&#44; lack of experience in its use&#44; and the lack of comparative studies with cDMARDs or biological agents&#44; are currently giving rise to some doubt as to its place in the peripheral PsA therapeutic algorithm&#46; However&#44; its good safety profile supports is use in patients for whom other therapeutic options are not suitable&#44; due to comorbidities or a history of severe infections&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">55</span></a> In addition&#44; it can promote weight loss &#40;between 5&#37;-10&#37;&#41;&#44; which is of interest for PsA patients who are overweight or obese&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Biological Therapies &#40;TNFi&#44; Anti-IL12&#47;23&#44; Anti-IL17&#41;</span><p id="par0220" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0225" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 11&#46;</span> Biological therapy is recommended for peripheral PsA patients refractory to at least one cDMARDs &#40;LE&#58; 1b&#44; GR&#58; A&#41;&#46;</p></li></ul></p><p id="par0230" class="elsevierStylePara elsevierViewall">Biological therapy would be indicated for patients with peripheral PsA where DMARDs have proved ineffective&#44; or been discontinued due to intolerance&#46; Various clinical trials have demonstrated that the TNFi agents are effective in all the domains of PsA&#46; They have also been demonstrated to have a significant effect on structural damage inhibition&#46;<a class="elsevierStyleCrossRefs" href="#bib0755"><span class="elsevierStyleSup">48&#44;56&#8211;58</span></a> We also now have 2 new agents with a different mechanism of action&#44; ustekinumab &#40;i-IL12&#47;23&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0810"><span class="elsevierStyleSup">59&#8211;61</span></a> and secukinumab &#40;i-IL17&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0825"><span class="elsevierStyleSup">62&#44;63</span></a> which have been recently shown to be effective in controlling the manifestations of PsA and in radiographic damage inhibition&#46; Therefore&#44; they are equally valid options for PsA patients and when there has been an inadequate response to DMARDs&#44; especially for cases with severe skin involvement&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Despite the lack of clinical trials that directly compare the diverse molecules available&#44; the differences between them do not appear significant&#46; They are all good treatment options in the event of synthetic DMARD failure&#46; However&#44; based on years of experience in clinical practice and that reflected in the different international registries&#44; the panel of experts suggest the TNF inhibitors as the first option&#46; The other drugs are equally valid options&#44; however&#44; and therefore the physician&#39;s judgement must prevail&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the biological therapies with their current indication for the treatment of PsA in our country&#46;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0245" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 12&#46;</span> Biological therapy is recommended&#44; in monotherapy and in combination with cDMARDs&#44; for all the peripheral manifestations of PsA&#46; Combining the therapy with MTX can increase the survival of the monoclonal&#44; especially the chimeric&#44; TNFi drugs &#40;LE&#58; 2b&#44; GR&#58; C&#41;&#46;</p></li></ul></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0250" class="elsevierStylePara elsevierViewall">Although the usefulness of biological therapy in combination with DMARDs has been demonstrated&#44; and is specifically recommended by SER&#44;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">64</span></a> there is more controversy surrounding its use for PsA&#46; There are no direct comparisons of efficacy and safety between the combined treatment of MTX and biological therapy&#44; and biological therapy in monotherapy for PsA&#46; The data from clinical trials show no significant differences in terms of efficacy &#40;ACR responses&#41; or safety outcomes between patients on combined treatment and patients with biological treatment in monotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0790"><span class="elsevierStyleSup">55&#44;57&#44;63&#8211;76</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Therefore&#44; no valid conclusions can be drawn of efficacy or safety for each biological drug combined with MTX compared with biological therapy in monotherapy&#46; In general&#44; the combination with MTX showed no significant clinical improvement&#46;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">65</span></a> However&#44; in some registries&#44; combined therapy with MTX provides greater survival of the drug&#44; especially in monoclonal antibodies&#44; and particularly with infliximab&#44; therefore it could be considered for use in this circumstance&#46;<a class="elsevierStyleCrossRefs" href="#bib0900"><span class="elsevierStyleSup">77&#8211;80</span></a><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8226;</span><p id="par0260" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 13&#46;</span> In patients with peripheral PsA&#44; and after failure of a TNFi&#44; a change to another biological therapy is recommended&#44; either another TNFi or a drug with a different mechanism of action&#44; such as i-IL12&#47;23 or i-IL17 or a tDMARD &#40;apremilast&#41; &#40;LE&#58; 1b&#44; 2b&#59; GR&#58; B&#41;&#46;</p></li></ul></p><p id="par0265" class="elsevierStylePara elsevierViewall">The data from clinical trials indicate that response to a second TNFi agent is good&#44; although inferior in general to that achieved in patients with no previous exposure to these drugs&#46; The registries show a slight reduction in the survival of the second biological agent compared to the first&#44; and clearly poorer survival for the third&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">There are no studies that compare the usefulness of a second TNFi compared to a change of therapeutic target &#40;IL12&#47;23 or IL17&#41;&#44; and therefore both therapeutic options are currently equally valid&#46; In the studies on ustekinumab and those on secukinumab&#44; as with the TNFi drugs&#44; it has been demonstrated that the response to these drugs in patients with no previous exposure to biological agents is better if compared to the response obtained in patients where a TNFi has already failed&#46; Therefore&#44; the expected efficacy will always be better the earlier we use the biological drug&#44; irrespective of which&#46;<a class="elsevierStyleCrossRefs" href="#bib0830"><span class="elsevierStyleSup">63&#44;81&#8211;90</span></a> Apremilast has also shown better ACR20 responses in patients with no previous exposure to biological therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">53</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows an algorithm for the management of peripheral arthritis&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Enthesitis</span><p id="par0280" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8226;</span></span><p id="par0285" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 14&#46;</span> Biological therapy or tDMARDS &#40;apremilast&#41; are recommended for patients with PsA and enthesitis refractory to NSAIDs and local treatment &#40;LE&#58; 2b&#44; GR&#58; C&#41;&#46;</p></li></ul></p><p id="par0290" class="elsevierStylePara elsevierViewall">A NSAID&#44; physiotherapy and local peri-enthesis corticosteriod injections are recommended first for the forms of PsA with predominantly enthesitis involvement&#44; although to date there are no randomised and placebo-controlled studies to vouch for their efficacy&#46; There is no evidence to support the use of tDMARDS for enthesitis&#46; However&#44; tDMARDS can be considered for patients with PsA and enthesitis as long as there is associated peripheral arthritis&#46; If a good response is not achieved despite the aforementioned treatment&#44; the appropriate option would be biological therapy or apremilast&#46;<a class="elsevierStyleCrossRef" href="#bib0970"><span class="elsevierStyleSup">91</span></a> The TNFi drugs<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">92</span></a> and subsequently ustekinumab&#44;<a class="elsevierStyleCrossRefs" href="#bib0810"><span class="elsevierStyleSup">59&#44;60</span></a> secukinumab&#44;<a class="elsevierStyleCrossRefs" href="#bib0830"><span class="elsevierStyleSup">63&#44;82</span></a> and apremilast<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">54</span></a> have proven efficacy in the treatment of enthesitis&#44; but there is no data to show the clear superiority of one drug over the rest&#46; For this reason&#44; they would all be good treatment options for patients refractory to NSAIDs and&#47;or local treatment&#46; However&#44; based on years of experience in clinical practice and the international registries&#44; the panel of experts suggest the TNFi as the first option&#59; the other drugs are equally valid options&#44; and therefore the final decision must be that of the physician&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows an algorithm for the management of enthesitis&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Dactylitis</span><p id="par0300" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0305" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 15&#46;</span> Biological treatment or tDMARDS &#40;apremilast&#41; are recommended for patients with PsA and dactylitis refractory to NSAIDs and local corticosteroid injections &#40;LE&#58; 2b&#44; GR&#58; C&#41;&#46;</p></li></ul></p><p id="par0310" class="elsevierStylePara elsevierViewall">For the forms of PsA with dactylitis the first recommendation is NSAIDs and local corticosteroid injections&#44; although at present we do not have randomised and placebo-controlled studies to vouch for their efficacy&#46; The cDMARDs could be considered for patients with PsA and dactylitis as long as there is associated peripheral arthritis&#46; The cDMARDs have an effect size that is generally small for pure dactylitis&#46;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">92</span></a> The data for the TNFi drugs&#44;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">92</span></a> ustekinumab&#44;<a class="elsevierStyleCrossRefs" href="#bib0810"><span class="elsevierStyleSup">59&#44;60</span></a> secukinumab&#44;<a class="elsevierStyleCrossRefs" href="#bib0830"><span class="elsevierStyleSup">63&#44;82</span></a> and apremilast<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">54</span></a> is favourable for dactylitis&#58; none of the molecules have been demonstrated as superior over the rest&#46; These drugs are a therapeutic option for patients for whom local measures have failed&#46; However&#44; based on our years of experience in clinical practice&#44; and the experience reflected in the different international registries&#44; the panel of experts suggest the TNFi as the first option&#46; The other drugs are equally valid options and therefore the judgement of the physician should prevail&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> shows an algorithm for the management of dactylitis&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Axial Involvement</span><p id="par0320" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0325" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 16&#46;</span> Biological therapy &#40;TNFi or IL17i&#41; is recommended for patients with predominantly axial forms of PsA refractory to NSAIDs&#44; &#40;LE&#58; 4&#44; GR&#58; D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8226;</span><p id="par0330" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Recommendation 17&#46;</span> The cDMARDs are not recommended for axial forms of PsA &#40;LE&#58; 2b&#44; GR&#58; C&#41;&#46;</p></li></ul></p><p id="par0335" class="elsevierStylePara elsevierViewall">In the absence of specific studies on PsA with predominant axial involvement&#44; the general recommendations apply for axial spondyloarthritis &#40;axial SpA&#41;&#44; which include&#44; in addition to physical exercise&#44; at least 2 NSAIDs at maximum dose for a period of 4 weeks each&#46;<a class="elsevierStyleCrossRef" href="#bib0980"><span class="elsevierStyleSup">93</span></a> Biological treatment can be started for the patients for whom these measures prove ineffective&#46; The use of cDMARDs is not justified because of the lack of evidence as to their efficacy at axial level&#46; There is currently insufficient scientific evidence to indicate the use of apremilast for patients with axial SpA&#46; A phase II&#44; single-centre&#44; double-blind&#44; placebo-controlled pilot study assessed the efficacy of apremilast 30<span class="elsevierStyleHsp" style=""></span>mg compared to a placebo over 12 weeks&#44; in 36 patients with active ankylosing spondylitis&#46;<a class="elsevierStyleCrossRef" href="#bib0985"><span class="elsevierStyleSup">94</span></a> Although there were differences in favour of the patient treated with apremilast&#44; they were not statistically significant&#44; including the change in BASDAI at week 12 that was the main aim of the study&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">Given the lack of comparative studies&#44; the first biological agent should be a TNFi&#44; in line with routine clinical practice&#46; However&#44; recently published data on secukinumab in ankylosing spondylitis are equally optimal&#44;<a class="elsevierStyleCrossRef" href="#bib0990"><span class="elsevierStyleSup">95</span></a> although at present there is no indication for this drug in the non-radiographic form&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">A recent publication on ustekinumab<a class="elsevierStyleCrossRef" href="#bib0995"><span class="elsevierStyleSup">96</span></a> of a post hoc analysis of its 2 clinical trials in PsA demonstrated a significant improvement in BASDAI and ASDAS-CRP at week 24 in the subgroup of patients with psoriatic arthritis&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">At present we do not have any trials that demonstrate a significant effect of the biological therapies on structural damage in axial PsA&#44; although there are data that show a potential slowing down effect of spinal radiographic progression associated with biological therapy on axial SpA&#46;<a class="elsevierStyleCrossRefs" href="#bib1000"><span class="elsevierStyleSup">97&#44;98</span></a></p><p id="par0355" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a> shows an algorithm for the management of axial disease&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Discussion</span><p id="par0360" class="elsevierStylePara elsevierViewall">This new SER Recommendations document seeks to serve as a guideline for treatment using the synthetic DMARDs and biological therapy for practitioners caring for PsA patients&#46; These recommendations&#44; based on the best available scientific evidence and on the clinical experience of experts in PsA&#44; are also based on the recommendations of the previous Consensus and the latest version of ESPOGUIA 2015&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">12</span></a></p><p id="par0365" class="elsevierStylePara elsevierViewall">PsA is one of the most heterogeneous forms of chronic arthritis from a clinical perspective&#44; and therefore the different therapeutic approaches and the different methods for assessing results for this entity currently pose a challenge to all clinicians in charge of diagnosing and treating this population&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">8</span></a> Although in recent years new drugs have been incorporated with different mechanisms of action&#44; and different treatment modalities have been tested &#40;T2T strategies&#41;&#44; the overall management of PsA patients remains a challenge&#46; Therefore&#44; the primary aim of this recommendations document is to provide clinicians with the best available evidence &#40;and failing this&#44; the best opinion agreed by the panel members&#41; for the rational and well-founded use of the various treatment options using synthetic and biological DMARDs for PsA&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">The valid contributions of the previous PsA consensus document have been kept&#44; therefore that stated in that document about cDMARDs remains in this document&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">11</span></a> Unlike the previous consensus document on the use of biological agents for PsA&#44; this document provides a series of hierarchical principles for managing the disease&#44; the best evidence has been reviewed on the new molecules that have appeared and have been approved since the previous consensus&#44; and an algorithm is provided for the management of PsA&#46; With all of this&#44; the group of experts expects the management of PsA to be guided by best evidence&#44; reducing as much as is possible the variability of this complex medical process&#46;</p><p id="par0375" class="elsevierStylePara elsevierViewall">The EULAR and GRAPPA recommendations for the management of PsA have been published recently&#46;<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">9&#44;10</span></a> Our document&#44; although some aspects contained in those recommendations may overlap&#44; has been adapted as much as possible to the care reality of patients with PsA in Spain&#44; and this could be key in generalising the recommendations contained herein&#46;</p><p id="par0380" class="elsevierStylePara elsevierViewall">Our document does not cover aspects relating to the skin and nail involvement of psoriasis&#44; unlike the GRAPPA recommendations&#44; since we consider that the management of these processes falls to the dermatologist&#44; and the Spanish Academy of Dermatology and Venereology &#40;AEDV&#41; regularly publishes consensus documents similar to ours&#44; but obviously focussing on the management of those two aspects&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">99</span></a></p><p id="par0385" class="elsevierStylePara elsevierViewall">In recent years&#44; new therapies have been added to the therapeutic arsenal against PsA due to their mechanism of action&#46; This document has included this new evidence&#44; especially with regard to IL12&#47;23 and IL17 pathway inhibition &#40;ustekinumab and secukinumab&#44; respectively&#41;&#46; In this respect&#44; we decided to place the TNFi inhibitors&#44; IL12&#47;23-i and IL17-i&#44; at the same level&#44; which is also expressed in the therapeutic algorithm&#46; This is based on the fact that&#44; despite the absence of clinical trials that directly compare the efficacy of the diverse molecules available&#44; the differences between them to not appear to be significant&#46; In the section on new drugs&#44; we have also included a new tDMARD&#44; the PDE-4 inhibitor &#40;apremilast&#41;&#46; Only clinical experience will clarify the doubts as to its place in the therapeutic algorithm of PsA&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">7</span></a> The recommendations for these new PsA drugs are based on the best available evidence&#44; but should be evaluated circumspectly because they are recently approved drugs&#46; Therefore&#44; the medium to long-term effectiveness and safety are still unknown from a real world evidence &#40;RWE&#41; or daily practice perspective&#46;</p><p id="par0390" class="elsevierStylePara elsevierViewall">PsA and psoriasis are disorders with a large group of associated comorbidities&#44; which has led some experts to propose the concept of psoriatic disease to better capture the systemic nature of both entities&#46;<a class="elsevierStyleCrossRef" href="#bib1015"><span class="elsevierStyleSup">100</span></a> Cardiovascular comorbidity is perhaps the most relevant&#46; This is why we have included specific recommendations in this regard in this document&#44; although we recognise that this domain of the disease is in an active phase of evolution&#44; and more evidence is needed to support the potential benefits of the synthetic and biological DMARDs in the reduction of cardiovascular risk&#46;</p><p id="par0395" class="elsevierStylePara elsevierViewall">The optimisation of biological therapies is an aspect highlighted in the recent literature&#46; No specific recommendation is made in this document in this regard&#44; since there are no consistent published data&#44; but we do mention the need to assess this type of strategy individually&#46; The optimisation of the biological therapies has been incorporated into the routine for managing these patients in our country&#44; there being safety&#44; effectiveness&#44; cost and care equity reasons to support this type of approach&#46; The SER and the Spanish Society of Hospital Pharmacies have recently published a positioning document for optimising biological therapy in different rheumatological diseases&#44; including PsA&#46;<a class="elsevierStyleCrossRef" href="#bib1020"><span class="elsevierStyleSup">101</span></a> Even so&#44; this aspect is principally aimed at the TNFi&#44; since&#44; given the very recent incorporation of other non-TNFi&#44; it is not possible to make an extrapolation to the optimisation of these new agents&#46;</p><p id="par0400" class="elsevierStylePara elsevierViewall">At present&#44; only one trial has been published on T2T approach for PsA &#40;the TICOPA study&#41;&#44; which seems to indicate that this management method might achieve better results in skin and joint outcomes compared to standard management&#44; although at the cost of more adverse events&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">35</span></a> We believe that more information is still required on this type of approach to the disease before making a positive recommendation&#46; Furthermore&#44; although the evidence for early intervention with DMARDs in PsA is not supported by very solid evidence&#44; it is obvious that early diagnosis of the disease&#44; recognition of the adverse prognosis or poor outcome factors&#44; and the consequent establishment of early drug intervention should set the bases for better management of the disease in all its domains&#44; and ultimately&#44; a general improvement in outcomes for PsA&#46;<a class="elsevierStyleCrossRef" href="#bib1025"><span class="elsevierStyleSup">102</span></a></p><p id="par0405" class="elsevierStylePara elsevierViewall">These recommendations do not mention anything to do with the use of biosimilars in PsA either&#46; A biosimilar is a biological drug that contains a version of the active substance of an already authorised original biological product &#40;reference drug&#41;&#46; With regard to its original product&#44; a biosimilar must demonstrate high similarity in terms of quality&#44; biological activity&#44; safety and efficacy&#44; aspects that should be contrasted by the appropriate randomised clinical trials&#46; At present&#44; the safe use of these products in our country is guaranteed thanks to the regulatory framework in terms of quality&#44; preclinical and clinical criteria established by regulatory authorities such as the EMA&#46; The interchangeability and therapeutic substitution of these drugs should not be automatic or based on purely economic criteria&#44; since the benefit to the patient must always prevail in our decisions&#46; Therefore&#44; the panel of experts making these recommendations concur with what has already been expressed by the SER in their positioning document&#46;<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">103</span></a></p><p id="par0410" class="elsevierStylePara elsevierViewall">In sum&#44; this new recommendation document combines the best available evidence&#44; incorporating the evidence on the new molecules and new PsA treatment approaches&#44; together with the vision of rheumatologists who are experts in this disease&#46; The essence of this manuscript lies in collecting all the aspects that help the clinician to make a reasoned therapeutic decision for a case of PsA&#46; This means that&#44; when choosing a particular drug&#44; the decision should include aspects of the disease itself &#40;clinical phenotype&#44; severity&#44; poor prognosis factors&#41; together with other aspects of each molecule &#40;evidence&#44; experience&#44; efficacy&#44; safety&#44; optimisation&#41;&#46; In some cases&#44; financial costs might be an aspect to be taken into account&#44; especially when differences cannot be established based on scientific evidence&#44; without implying an absolute limitation of medical judgement&#44; which is the basis of the final decision&#46;</p><p id="par0415" class="elsevierStylePara elsevierViewall">It will soon be necessary to review and update the recommendations contained in this document&#44; since new molecules and new treatment methods are on the short-term horizon&#44; and we will probably have better evidence on aspects such as the therapeutic role of current and future treatments on cardiovascular risk&#44; the use of biosimilars&#44; and the optimisation of the current and future biological therapies&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Research Agenda</span><p id="par0420" class="elsevierStylePara elsevierViewall">Although these recommendations should help towards a better approach to PsA&#44; the expert panel acknowledges that many aspects are still to be covered in a future research agenda&#46; Some of these aspects include&#58;<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8226;</span><p id="par0425" class="elsevierStylePara elsevierViewall">Assessing from a RWE perspective the true effectiveness and safety of the new molecules approved for PsA&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8226;</span><p id="par0430" class="elsevierStylePara elsevierViewall">Studying whether there is a particular PsA phenotype that would accommodate the initial use of biological therapy without the prior need for synthetic DMARDs&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">&#8226;</span><p id="par0435" class="elsevierStylePara elsevierViewall">An analysis of the therapeutic role of combining new synthetic DMARDs &#40;apremilast&#41; with biological therapy or conventional synthetic DMARDs&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8226;</span><p id="par0440" class="elsevierStylePara elsevierViewall">Assessing pharmacogenomic biomarkers of therapeutic response&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8226;</span><p id="par0445" class="elsevierStylePara elsevierViewall">An in-depth examination of the therapeutic effects of the current and future molecules on the reduction of cardiovascular risk in this population&#46;</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">&#8226;</span><p id="par0450" class="elsevierStylePara elsevierViewall">A search for evidence to support the early therapeutic use of the current and future DMARDs on the different domains of psoriatic disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">&#8226;</span><p id="par0455" class="elsevierStylePara elsevierViewall">An in-depth study of the therapeutic niche for the new molecules in the PsA treatment algorithms&#46;</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">&#8226;</span><p id="par0460" class="elsevierStylePara elsevierViewall">Improving the optimisation strategies for the biological therapies for PsA&#46;</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">&#8226;</span><p id="par0465" class="elsevierStylePara elsevierViewall">Extending the evidence to solidly recommend the T2T strategies&#46;</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">&#8226;</span><p id="par0470" class="elsevierStylePara elsevierViewall">An analysis of the effect of biological therapies on the inhibition of radiographic progression in forms of axial PsA&#46;</p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">&#8226;</span><p id="par0475" class="elsevierStylePara elsevierViewall">An evaluation of the role of the biosimilars in the management of PsA&#46;</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">&#8226;</span><p id="par0480" class="elsevierStylePara elsevierViewall">Developing pathophysiological studies on the different phenotypes of the disease to discover which cells and molecules predominate in each&#44; in order to improve our therapeutic strategy&#46;</p></li></ul></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Ethical Disclosures</span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Protection of human and animal subjects</span><p id="par0485" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Confidentiality of data</span><p id="par0490" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Right to privacy and informed consent</span><p id="par0495" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Funding</span><p id="par0500" class="elsevierStylePara elsevierViewall">Spanish Rheumatology Foundation&#46;</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Conflicts of Interest</span><p id="par0505" class="elsevierStylePara elsevierViewall">Chamaida Plasencia Rodr&#237;guez received a grant with no restrictions from Pfizer&#59; fees as a speaker for Pfizer&#46;</p><p id="par0510" class="elsevierStylePara elsevierViewall">Juan Carlos Torre Alonso received funding from MSD&#44; Abbvie&#44; Pfizer&#44; Celgene&#44; Janssen for attending courses&#47;conferences&#59; and has received fees as a speaker and consultant for MSD&#44; Abbvie&#44; Pfizer&#44; UCB&#44; Celgene and Novartis&#46;</p><p id="par0515" class="elsevierStylePara elsevierViewall">Juan D Ca&#241;ete Crespillo has received funding from Novartis&#44; Janssen and Celgene for attending meetings&#44; conferences and courses&#59; fees from Abbvie&#44; Janssen and Celgene for speaking&#59; and has received funding from Abbvie&#44; Celgene&#44; Boehringer&#44; Janssen and Novartis for consultancy to pharmaceutical companies and other technologies&#46;</p><p id="par0520" class="elsevierStylePara elsevierViewall">Ruben Queiro Silva has received funding from Abbvie&#44; Celgene&#44; Pfizer&#44; MSD&#44; Janssen and UCB for attending meetings&#44; conferences&#44; courses and for speaking&#59; funding from Janssen and Celgene for taking part in a research study&#59; and has received financial help from Novartis&#44; Abbvie&#44; UCB&#44; Celgene and Pfizer for consultancy to pharmaceutical companies and other technologies&#46;</p><p id="par0525" class="elsevierStylePara elsevierViewall">Mireia Moreno Mart&#237;nez-Losa has received funding from Abbvie&#44; Pfizer&#44; MSD&#44; Janssen&#44; Celgene&#44; MSD&#44; Roche and UCB for attending meetings&#44; conferences&#44; courses and for speaking&#59; and has received financial help from Janssen for consultancy to pharmaceutical companies or other technologies&#46;</p><p id="par0530" class="elsevierStylePara elsevierViewall">Raquel Almod&#243;var Gonz&#225;lez has received funding from Abbvie&#44; Pfizer&#44; MSD&#44; Roche for attending meetings&#44; conferences and courses&#59; fees from Abbvie&#44; Celgene&#44; Novartis&#44; Pfizer&#44; Roche&#44; UCB for speaking&#59; and has received funding from Abbvie&#44; Jansen&#44; MSD&#44; Novartis&#44; Pfizer&#44; Roche for undertaking educational programmes and courses&#46; And has received financial help from Abbvie&#44; Celgene&#44; Janssen&#44; MSD&#44; Pfizer&#44; UCB for consultancy to pharmaceutical companies and other technologies&#46;</p><p id="par0535" class="elsevierStylePara elsevierViewall">Carlos Montilla Morales has received funding from Abbvie&#44; MSD and Janssen for attending meetings&#44; conferences&#44; courses and for speaking&#46; He has received financial help from Janssen for consultancy&#46;</p><p id="par0540" class="elsevierStylePara elsevierViewall">Julio Ram&#237;rez Garc&#237;a has received funding from MSD&#44; Abbvie&#44; Pfizer&#44; Bristol&#44; UCB&#44; Novartis&#44; Janssen&#44; Celgene and Roche for scientific talks and for attending meetings&#44; conferences and training courses&#46;</p><p id="par0545" class="elsevierStylePara elsevierViewall">Petra D&#237;az del Campo Fontecha has no conflict of interests to declare&#46;</p></span></span>"
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    "fechaRecibido" => "2017-07-22"
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            0 => "Psoriatic arthritis"
            1 => "Treatment of psoriatic arthritis"
            2 => "Recommendations"
            3 => "Disease modifying antirheumatic drugs &#40;DMARDs&#41;"
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            0 => "Artritis psori&#225;sica"
            1 => "Tratamiento artritis psori&#225;sica"
            2 => "Recomendaciones"
            3 => "F&#225;rmacos antirreum&#225;ticos modificadores de la enfermedad &#40;FAME&#41; sint&#233;ticos"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The main purpose of this recommendation statement is to provide clinicians with the best available evidence and the best opinion agreed upon by the panellists for a rational use of synthetic disease modifying antirheumatic drugs &#40;DMARDs&#41; and biologicals in psoriatic arthritis &#40;PsA&#41; patients&#46; The present document also focuses on important aspects in the management of PsA&#44; such as early diagnosis&#44; therapeutic objectives&#44; comorbidities and optimisation of treatment&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The recommendations were agreed by consensus by a panel of 8 expert rheumatologists&#44; previously selected by the Spanish Society of Rheumatology &#40;SER&#41; through an open call&#46; The phases of the work were&#58; identification of key areas for updating the previous consensus&#44; analysis and synthesis of scientific evidence &#40;modified Oxford system&#44; Centre for Evidence-based Medicine&#44; 2009&#41; and formulation of recommendations based on this evidence and by consensus techniques&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Seventeen recommendations were issued for the treatment of PsA patients&#46; Six of them were of general nature&#44; ranging from the early diagnosis and treatment to the importance of assessing comorbidities&#46; The other 11 were focused on the indications for DMARDs and biological therapy in the distinct clinical forms of the disease&#46; Likewise&#44; the situation of failure of the first biological is addressed and treatment algorithms and a table with the different biological therapies are also included&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We present the update of SER recommendations for the treatment of PsA with DMARDs and biologics&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La primera finalidad de este documento de recomendaciones es proporcionar al cl&#237;nico la mejor evidencia disponible y&#44; en su defecto&#44; la mejor opini&#243;n consensuada por los panelistas para un uso racional y fundado de las diversas opciones de tratamiento con f&#225;rmacos antirreum&#225;ticos modificadores de la enfermedad &#40;FAME&#41; sint&#233;ticos y biol&#243;gicos en artropat&#237;a psori&#225;sica &#40;APs&#41;&#46; El presente documento tambi&#233;n incide sobre aspectos importantes en el manejo de la APs&#44; como el diagn&#243;stico precoz&#44; los objetivos terap&#233;uticos&#44; las comorbilidades y la optimizaci&#243;n del tratamiento&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Las recomendaciones se consensuaron a trav&#233;s de un panel de 8 reumat&#243;logos expertos&#44; previamente seleccionados por la Sociedad Espa&#241;ola de Reumatolog&#237;a &#40;SER&#41; mediante una convocatoria abierta&#46; Las fases del trabajo fueron&#58; identificaci&#243;n de las &#225;reas claves para la actualizaci&#243;n del consenso anterior&#44; an&#225;lisis y s&#237;ntesis de la evidencia cient&#237;fica &#40;sistema modificado de Oxford&#44; CEBM&#44; 2009&#41; y formulaci&#243;n de recomendaciones a partir de esta evidencia y de t&#233;cnicas de consenso&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se emiten un total de 17 recomendaciones para el tratamiento de los pacientes con APs&#46; Seis de ellas de car&#225;cter general&#44; que abarcan desde la transcendencia del diagn&#243;stico y tratamiento precoz hasta la importancia de las comorbilidades&#46; El resto&#44; las 11 espec&#237;ficas&#44; se centran en las indicaciones de los FAME y la terapia biol&#243;gica en las diferentes formas cl&#237;nicas de la enfermedad&#46; As&#237; mismo&#44; se abordan las situaciones de fracaso a un primer biol&#243;gico y se incluyen los algoritmos de tratamientos y una tabla con las diferentes terapias biol&#243;gicas&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se presenta la actualizaci&#243;n de las recomendaciones de la SER para el tratamiento de la APs con FAME y terapia biol&#243;gica&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Torre Alonso JC&#44; D&#237;az del Campo Fontecha P&#44; Almod&#243;var R&#44; Ca&#241;ete JD&#44; Montilla Morales C&#44; Moreno M&#44; et al&#46; Recomendaciones de la Sociedad Espa&#241;ola de Reumatolog&#237;a sobre el tratamiento y uso de terapias sist&#233;micas biol&#243;gicas y no biol&#243;gicas en artritis psori&#225;sica&#46; Reumatol Clin&#46; 2018&#59;14&#58;254&#8211;268&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">General recommendations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GA<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 1</span>&#46; PsA is a chronic inflammatory musculoskeletal disease whose diagnosis&#44; treatment and evolutionary control should be managed by rheumatologists&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 2</span>&#46; The clinical presentation of PsA is very heterogeneous and it has some associated comorbidities that occasionally require multidisciplinary management&#46; Coordinated management with the dermatologist is important&#44; especially for patients with moderate-severe psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 3&#46;</span> The therapeutic objective of PsA is to control inflammation and preserve the patients&#8217; functional capacity&#44; achieving clinical remission or minimal&#47;low disease activity according to the different validated indices&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 4&#46;</span> Establishing a therapeutic objective and strict clinical monitoring are crucial to achieve optimal control of clinical activity and an appropriate therapeutic response&#46; Once the therapeutic objective has been achieved&#44; quarterly follow-up seems reasonable&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 5&#46;</span> The cardiovascular risk profile must be taken into account on assessment and during the therapeutic management of these patients&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 6</span>&#46; The most appropriate therapeutic decision will depend on the judgement of the specialist and will be agreed with the patient&#46; This decision will be taken based principally on the scientific evidence and the features of the patient and their disease&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">SER Recommendations on the Treatment and Use of Biological Therapies for Psoriatic Arthritis&#46; General Recommendations&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
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            "identificador" => "at2"
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">NSAIDs&#58; Non-steroidal anti-inflammatory drugs&#59; DMARDs&#58; disease-modifying antirheumatic drugs&#59; cDMARDs&#58; conventional synthetic DMARDs&#59; tDMARDs&#58; targeted DMARDs&#59; GA&#58; grade of agreement&#59; GR&#58; grade of recommendation&#59; IL12i&#44; IL23i or IL17i&#58; interleukin inhibitor 12&#44; 23 or 17&#59; PDE4i&#58; TNFi&#58; tumour necrosis factor inhibitors&#59; LE&#58; level of evidence&#59; SER&#58; Spanish Society of Rheumatology&#46;</p>"
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Specific recommendations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GA<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 7&#46;</span> Early intervention with cDMARDs is recommended for patients with PsA&#44; principally those with poor baseline prognostic factors&#44; in order to improve the signs and symptoms&#44; functional capacity and quality of life&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 8</span>&#46; The cDMARDs &#40;MTX&#44; leflunomide&#44; sulfasalazine&#41; are recommended as first-line treatment for active peripheral PsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 9</span>&#46; MTX is recommended as first choice&#44; due to its effects on arthritis and psoriasis &#40;LE&#58; 4&#44; GR&#58; D&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 10&#46;</span> Apremilast is recommended for the treatment of peripheral arthritis&#44; after cDMARD failure or intolerance&#44; when it is considered more appropriate than biological therapy due to the patient&#39;s profile&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 11</span>&#46; Biological therapy is recommended for peripheral PsA patients refractory to at least one cDMARD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 12&#46;</span> Biological therapy is recommended&#44; in monotherapy and in combination with cDMARDs&#44; for all the peripheral manifestations of PsA&#46; Combining the therapy with MTX can increase the survival of the monoclonal&#44; especially the chimeric&#44; TNFi drugs&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 13&#46;</span> In patients with peripheral PsA&#44; and after failure of a TNFi&#44; a change to another biological therapy is recommended&#44; either another TNFi or a drug with a different mechanism of action&#44; such as i-IL12&#47;23 or i-IL17 or a tDMARD &#40;apremilast&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1b&#44; 2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 14&#46;</span> Biological therapy or tDMARDS &#40;apremilast&#41; are recommended for patients with PsA and enthesitis refractory to NSAID and local treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 15&#46;</span> Biological treatment or tDMARDS &#40;apremilast&#41; are recommended for patients with PsA and dactylitis refractory to NSAIDs and local corticosteroid injections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 16&#46;</span> Biological therapy &#40;TNFi or IL17i&#41; is recommended for patients with predominantly axial forms of PsA refractory to NSAIDs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recommendation 17&#46;</span> The cDMARDs are not recommended for axial forms of PsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">SER Recommendations on the Treatment and Use of Biological Therapies in Psoriatic Arthritis&#46; Specific Recommendations&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">The data in this table were obtained from the data sheet of the Spanish Agency of Medicines and Medical Devices &#40;AEMPS&#41;&#46;</p><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">ILD&#58; interstitial lung disease&#59; DMARDs&#58; disease-modifying antirheumatic drugs&#59; AHT&#58; arterial hypertension&#59; HF&#58; heart failure&#59; CHF&#58; congestive heart failure&#59; i&#46;v&#46;&#58; intravenous&#59; SLE&#58; systemic lupus erythematosus&#59; MTX&#58; methotrexate&#59; NYHA&#58; New York Heart Association&#59; TBC&#58; tuberculosis&#59; TNF&#58; tumour necrosis factor&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Biological therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Active ingredient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dosage and administration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Indications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Contraindications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse events<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TNFi alpha&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Adalimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose&#58; 40<span class="elsevierStyleHsp" style=""></span>mg<br>-Route&#58; subcutaneous<br>-Frequency&#58; every 2 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active and progressive psoriatic arthritis in adults when the response to previous therapy with DMARDs has been insufficient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Hypersensitivity to the active ingredient or excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; reaction at the injection site &#40;pain&#44; redness&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Active TBC&#44; serious infections such as sepsis and opportunistic infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; headache&#44; respiratory&#44; urinary infection&#44; herpes&#44; diarrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Moderate to severe HF &#40;NYHA classes <span class="elsevierStyleSmallCaps">III&#47;IV</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; SLE&#44; TBC&#44; arrhythmia&#44; sepsis&#44; cytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; CHF&#44; multiple sclerosis&#44; lymphoma&#44; solid malignant tumour&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Certolizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose&#58; 200<span class="elsevierStyleHsp" style=""></span>mg or 400<span class="elsevierStyleHsp" style=""></span>mg<br>-Route&#58; subcutaneous<br>-Frequency&#58; initially &#40;400<span class="elsevierStyleHsp" style=""></span>mg at weeks 0&#44; 2 and 4&#41;&#44; maintenance &#40;200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks or 400<span class="elsevierStyleHsp" style=""></span>mg every 4 weeks&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active psoriatic arthritis in adults&#44; when the previous response to treatment with DMARDs has been inadequate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">-</span> Hypersensitivity to the active ingredient or excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Active TBC&#44; serious infections such as sepsis and opportunistic infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; bacterial and viral infections&#44; leukopenias&#44; headache&#44; AHT&#44; nausea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Moderate to severe HF &#40;NYHA classes <span class="elsevierStyleSmallCaps">III&#47;IV</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; sepsis&#44; TBC&#44; fungal infections&#44; lymphatic system neoplasms&#44; solid tumours&#44; non-melanoma skin cancers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; polycytopenia&#44; splenomegaly&#44; melanoma&#44; pericarditis&#44; ILD&#44; pneumonitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Etanercept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose&#58; 25 or 50<span class="elsevierStyleHsp" style=""></span>mg<br>-Route&#58; subcutaneous<br>-Frequency&#58; 25<span class="elsevierStyleHsp" style=""></span>mg twice per week &#40;interval of 72&#8211;96<span class="elsevierStyleHsp" style=""></span>h&#41;&#59; 50<span class="elsevierStyleHsp" style=""></span>mg once a week&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active psoriatic arthritis in adults&#44; when previous response to treatment with DMARDs has been inadequate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Hypersensitivity to the active ingredient or excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; reaction at the injection site&#44; respiratory&#44; urinary&#44; skin infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Sepsis or risk of sepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; allergy&#44; autoantibodies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Active infections &#40;including chronic or localised&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; serious infections&#44; thrombocytopenia&#44; psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; pancytopenia&#44; TBC&#44; SLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Golimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose&#58; 50<span class="elsevierStyleHsp" style=""></span>mg<br>-Dose&#58; 100<span class="elsevierStyleHsp" style=""></span>mg in patients with psoriatic arthritis&#44; with a body weight of more than 100<span class="elsevierStyleHsp" style=""></span>kg who have not achieved an appropriate clinical response after 3 or 4 doses&#44; the dose of golimumab can be increased to 100<span class="elsevierStyleHsp" style=""></span>mg administered once a month<br>-Route&#58; subcutaneous<br>-Frequency&#58; once a month&#44; the same day every month&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Alone&#44; or in combination with MTX&#44; indicated for the treatment of active and progressive psoriatic arthritis in adults&#44; when the response to previous treatment with DMARDs has been inadequate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Hypersensitivity to the active ingredient or excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; upper respiratory tract infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Active TBC&#44; serious infections such as sepsis and opportunistic infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; cellulitis&#44; herpes&#44; bronchitis&#44; sinusitis&#44; AHT&#44; superficial fungal infections&#44; anaemia&#44; antibodies&#44; allergic reaction&#44; depression&#44; insomnia&#44; headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Moderate or severe HF &#40;NYHA classes <span class="elsevierStyleSmallCaps">III&#47;IV</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; TBC&#44; CHF&#44; sepsis&#44; neoplasms&#44; &#8593; glucose&#44; lipids&#44; thrombosis&#44; arrhythmia&#44; eye conditions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; hepatitis B reactivation&#44; lymphoma&#44; pancytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Infliximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose &#40;according to body weight&#41;&#58; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg<br>-Route&#58; i&#46;v&#46; infusion over 2<span class="elsevierStyleHsp" style=""></span>h<br>-Frequency&#58; after the first dose&#44; another at 2 and at 6 weeks&#46; Then 1 every 6&#8211;8 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active psoriatic arthritis in adults&#44; when previous response to treatment with DMARDs has been inadequate<br>Should be given in combination with MTX or used in monotherapy in the event of contraindication or intolerance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Hypersensitivity to the active ingredient&#44; excipients or other murine proteins&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; injection reaction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Active TBC&#44; serious infections such as septicaemia&#44; abscesses and opportunistic infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; headache&#44; respiratory infection&#44; herpes&#44; diarrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Moderate to severe HF &#40;NYHA classes <span class="elsevierStyleSmallCaps">III</span>&#47;<span class="elsevierStyleSmallCaps">IV</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; SLE&#44; TBC&#44; sepsis&#44; cytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; CHF&#44; multiple sclerosis&#44; lymphoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">i-IL17A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Secukinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Dose&#58; 150<span class="elsevierStyleHsp" style=""></span>mg<br>-Dose refractory to previous biological therapy&#58; 300<span class="elsevierStyleHsp" style=""></span>mg<br>-Route&#58; subcutaneous<br>-Frequency&#58; initially at week 0&#44; 1&#44; 2 and 3&#46; Then monthly maintenance&#44; starting in week 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active psoriatic arthritis in adult patients who have shown inadequate response to treatment with DMARDs<br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Severe hypersensitivity to the active ingredient or one of its excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; upper respiratory tract infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Clinically relevant active infections &#40;e&#46;g&#46;&#44; active TBC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; oral herpes&#44; rhinorrhoea&#44; diarrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; urticaria&#44; conjunctivitis&#44; neutropenia&#44; oral candidiasis&#44; athlete&#39;s foot&#44; otitis externa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Rare&#58; anaphylactic reactions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">i-IL12&#47;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Initial dose of 45<span class="elsevierStyleHsp" style=""></span>mg administered subcutaneously followed by a second dose of 45<span class="elsevierStyleHsp" style=""></span>mg 4 weeks later and then every 12 weeks<br>-As an alternative a dose of 90<span class="elsevierStyleHsp" style=""></span>mg can be given to patients who weigh over 100<span class="elsevierStyleHsp" style=""></span>kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Active psoriatic arthritis in adult patients who have shown inadequate response to treatment with DMARDs<br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">- Severe hypersensitivity to the active ingredient or one of its excipients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Very common&#58; nasopharyngitis and headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Clinically relevant active infections &#40;e&#46;g&#46;&#44; active TBC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Common&#58; myalgias&#44; back pain&#44; tiredness&#44; diarrhoea&#44; dizziness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-Not very common&#58; viral respiratory tract infections&#44; mycotic infection&#44; depression&#44; pustular psoriasis&#44; injection site reactions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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