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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">Inflammatory joint diseases&#44; such as rheumatoid arthritis &#40;RA&#41;&#44; axial spondyloarthritis &#40;SpA&#41; and psoriatic arthritis &#40;PsA&#41;&#44; are characterised by chronic inflammation&#44; joint destruction&#44; and functional disability&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Conventional synthetic disease-modifying drugs &#40;csDMARD&#41; are the mainstay of treatment for these patients&#46; However&#44; approximately one third of patients do not respond to them and require targeted synthetic &#40;tsDMARD&#41; or biological &#40;bDMARD&#41; disease modifying drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> These drugs have been shown to control inflammatory activity and improve physical function and quality of life in these patients over the long term&#46; A significant proportion of patients treated with a bDMARD do not respond to initial treatment or efficacy is lost over time&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and treatment is discontinued in more than 10&#37; due to side effects&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Despite their advantages&#44; the high cost of these treatments limits their use&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Therefore&#44; the biosimilar &#40;BS&#41; agents&#44; because of their lower cost&#44; are making biological therapies prompter and more accessible to a greater number of patients due to their greater efficiency&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">According to the European Medicines Agency &#40;EMA&#41;&#44; a BS is a biological drug that contains a version of the active substance of an already authorised original biological product &#40;the reference drug&#41;&#46; It must demonstrate similarity to the reference drug in terms of quality characteristics&#44; biological activity&#44; safety&#44; and efficacy&#44; following a full comparability exercise&#46; A BS is not like a generic drug that has a simpler structure and is identical to its reference drug&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Enbrel&#174; &#40;etanercept&#41; is an anti-TNF agent approved for use in adult patients with moderate to severe active and&#47;or progressive RA&#44; active and progressive&#44; severe axial PsA&#44; in young people with juvenile idiopathic arthritis&#44; including polyarticular&#44; extended oligoarticular&#44; PsA and enthesitis-related arthritis&#44; and severe plaque psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Several etanercept BS have been evaluated in clinical trials &#40;CTs&#41;&#44; as cheaper alternatives to the reference product&#46; Reducing the cost of treatment is the main attraction for the BS that are entering the global market&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Biogen&#39;s Benepali&#174; &#40;SB4&#41; was the first etanercept BS approved for use in January 2016&#46; Several studies have been published in the lead-up to its approval and marketing&#46; A phase III parallel-group&#44; randomised&#44; double-blind&#44; trial in 596 patients with moderate-severe RA previously treated with methotrexate showed equal efficacy to Enbrel&#44; with a similar ACR20 response at week 24 in both groups &#40;78&#46;1&#37; with Benepali vs&#46; 80&#46;3&#37; with Enbrel&#41; and with a comparable incidence of adverse events&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> In this regard&#44; a phase I trial in a Korean population &#40;n&#8239;&#61;&#8239;138&#41; demonstrated an equivalent safety&#44; pharmacokinetic and tolerability profile between Benepali and Enbrel&#46; However&#44; Benepali had a lower immunogenicity profile than Enbrel&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">However&#44; other than these CTs&#44; to date there have been no studies conducted under clinical practice conditions to confirm these results&#46; Therefore&#44; our aim was to evaluate the effectiveness&#44; safety&#44; and costs of the Benepali BS in patients with chronic inflammatory arthritis&#44; and compare with the reference drug&#44; under routine clinical practice conditions&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design and scope</span><p id="par0030" class="elsevierStylePara elsevierViewall">A retrospective observational study based on a case series of patients with RA&#44; axial SpA and PsA treated with Benepali or Enbrel&#46; A cost-minimisation pharmacoeconomic analysis was also carried out&#46; The study was conducted at IBIMA by the Rheumatology Department of the Hospital Regional Universitario de M&#225;laga &#40;HRUM&#41;&#44; Spain&#46; The protocol for the research project was approved by a provincial ethics committee of Malaga in which the work was performed&#44; and it conforms to the provisions of the Declaration of Helsinki&#46; The study was approved by the hospital&#39;s clinical research ethics committee &#40;CEIC&#41;&#46; Informed consent was obtained from all individual participants included in the study&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients</span><p id="par0035" class="elsevierStylePara elsevierViewall">All patients were included consecutively who had started treatment with the BS &#40;from March 2017 to August 2018&#41; or their original drug &#40;from February 2015 to August 2018&#41; and had received at least one dose of treatment&#46; Selection criteria were age &#8805;18 years&#44; RA according to American College of Rheumatology&#47;European League Against Rheumatism 2010 criteria&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> or axial SpA according to ASAS&#47;EULAR 2010 criteria&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> or PsA according to CASPAR 2006 criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Patients with any other inflammatory or rheumatic disease&#44; except secondary Sj&#246;gren&#39;s syndrome&#44; were excluded&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Protocol</span><p id="par0040" class="elsevierStylePara elsevierViewall">All patients who met the inclusion criteria and none of the exclusion criteria were recruited&#46; All patients were prospectively followed up in a specific biological therapy unit &#40;BTU&#41; according to a pre-established protocol of systematic data collection&#46; This protocol includes&#44; among other variables&#44; data on disease activity&#44; physical function&#44; and adverse effects&#46; The BTU reviews patients treated with biological therapies every 3 months in general and specific consultations &#40;for subcutaneous biologicals&#41; alternately&#46; Benepali or Enbrel were prescribed according to each physician&#8217;s judgement&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Variables and definition</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Effectiveness</span><p id="par0045" class="elsevierStylePara elsevierViewall">The primary efficacy endpoint of the BS or its original was drug retention &#40;survival&#41; time&#44; measured as the time from initiation to discontinuation of treatment or loss to follow-up or study end date at 52 weeks&#46; Secondary outcome variables of effectiveness included the effectiveness of the BS and its original measured as the proportion of patients achieving low disease activity or remission at 52 weeks&#44; based on DAS28&#44; BASDAI and ASDAS&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Safety</span><p id="par0050" class="elsevierStylePara elsevierViewall">Safety was assessed by calculating the incidence rates of adverse effects between 2015 and 2018&#46; This was done by dividing the total number of adverse effects by the total follow-up time of all patients in years &#40;number of events&#47;patient-year&#41;&#46; Adverse events were classified as mild-moderate&#44; severe&#44; and serious&#44; with mild-moderate being understood as signs or symptoms that are easily tolerated&#44; could interfere with usual activities&#44; and require medical intervention or treatment&#59; severe as disabling and incapacitating for usual activities and requiring medical intervention or therapy&#59; and serious as life-threatening&#44; requiring&#44; or prolonging hospitalisation&#44; causing congenital anomaly or causing significant persistent disability&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Economic study</span><p id="par0055" class="elsevierStylePara elsevierViewall">The costs of each treatment were calculated by patient-week cost&#44; considering the procurement price of the drug&#44; corresponding to the latest tender of the provincial purchasing platform&#46; The costs of administering the drug in the hospital were not considered&#46; This resulted in a price of &#8364;5&#44;540 per year of treatment with the BS and &#8364;7&#44;306 per year of treatment with the original drug&#46; To analyse the costs overall&#44; the total cost of treatment was calculated by the sum of the partial costs for each patient throughout the study&#46; For the BS patients&#44; in addition&#44; a calculation was made of the cost that would have been incurred by each patient if they had been treated with the original drug&#46; The official price of each drug was calculated based on the laboratory&#39;s sale price &#40;LSP&#41;&#58; &#8364;106&#46;55 per 50&#8239;mg injection of the BS&#44; and &#8364;140&#46;5 of Enbrel&#44; which corresponded to the weekly cost of treatment per patient&#46; Total cost&#58; the result of multiplying the weekly cost by the patient-week total&#46; Actual total cost&#58; final cost in Euros of the treatment administered to the patients included in the study&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Other variables</span><p id="par0060" class="elsevierStylePara elsevierViewall">Age &#40;years&#41;&#44; sex&#44; duration of symptoms&#44; date of starting the BS&#47;original and date of event and date of discontinuation of treatment were included for all patients&#46; Disease Activity Score 28 joints &#40;DAS28&#41; with erythrocyte sedimentation rate &#40;DAS28-ESR&#41; &#40;continuous&#44; range 0&#8211;9&#41; &#40;&#60;2&#46;6 points&#58; remission&#44; &#8804;3&#46;2&#58; low disease activity&#41;&#44; Clinical Disease Activity Index &#40;CDAI&#59; continuous&#44; range 0&#8211;76&#41; and Simplified Disease Activity Index &#40;SDAI&#59; continuous&#44; range 0&#8211;86&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Ankylosing Spondylitis Disease Activity Score &#40;ASDAS&#59; continuous&#59; &#60;1&#46;3 low disease activity&#44; 1&#46;3&#8211;2&#46;1 moderate activity&#44; 2&#46;1&#8211;3&#46;5 high activity&#44; &#62;3&#46;5 very high activity&#41;&#44; Bath Ankylosing Spondylitis Disease Activity Index &#40;BASDAI&#59; continuous&#44; range 0&#8211;10&#59; &#60;4 low activity or remission&#41;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> as appropriate&#44; collected at baseline visit and 1-year visit&#46; Physical function&#58; Health Assessment Questionnaire &#40;HAQ&#41; Spanish version &#40;continuous&#44; range 0&#8211;3&#41;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and Bath Ankylosing Spondylitis Functional Index &#40;BASFI&#59; continuous&#44; range 0&#8211;10&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The presence of radiological erosions &#40;categorical&#44; yes&#47;no&#41; and laboratory variables were also collected&#58; rheumatoid factor&#44; measured in U&#47;mL&#44; was considered elevated if &#62;20&#8239;U&#47;mL&#59; presence of ACPA&#44; measured in U&#47;mL&#44; was considered positive if &#62;10&#8239;U&#47;mL&#59; and HLA-B27 positive or not&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Statistical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">We performed a descriptive analysis&#46; Qualitative variables were expressed as absolute number and percentage and quantitative variables as mean and standard deviation &#40;SD&#41; or median and interquartile range &#40;IQR&#41;&#44; according to their distribution&#46; Normality adjustment of continuous variables was confirmed with the Kolgomorov&#8211;Smirnov test&#46; The Student&#8217;s t-test for independent samples or Mann-Whitney test was used in cases of non-normality between mean DAS28-ESR&#44; HAQ&#44; CRP&#44; ESR&#44; BASDAI and BASFI between baseline and 52 weeks&#46; The survival time of Benepali and Enbrel was analysed using Kaplan Meier curves&#46; Survival likelihoods and their 95&#37; confidence interval were calculated&#46; For all analyses&#44; a value of <span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;&#46;05 was considered significant&#46; All data were analysed using R2&#46;4&#46;0 statistical software&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">Between January 2015 and August 2018 &#40;inclusive&#41; 138 patients with different rheumatic diseases started treatment with etanercept&#58; 85 &#40;61&#46;5&#37;&#41; patients with RA&#44; 29 &#40;21&#46;0&#37;&#41; with axial SpA and 24 &#40;17&#46;3&#37;&#41; with PsA&#46; Of these&#44; 79 &#40;57&#46;2&#37;&#41; received the BS &#40;43 &#91;54&#46;4&#37;&#93; RA&#44; 20 &#91;25&#46;3&#37;&#93; AS and 16 &#91;20&#46;2&#37;&#93; PsA&#41; and 59 &#40;42&#46;7&#37;&#41; the original drug &#40;42 &#91;71&#46;2&#37;&#93; RA&#44; 9 &#91;15&#46;2&#37;&#93; AS and 8 &#91;13&#46;5&#37;&#93; PsA&#41;&#46;</p><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Patient characteristics</span><p id="par0075" class="elsevierStylePara elsevierViewall">The main characteristics of the patients in both treatment groups are described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The majority were women around 52 years of age with long-standing disease&#46; Patients on the original drug tended to have a longer disease duration and more were smokers than those on the BS&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Twenty-three patients &#40;39&#37;&#41; with the original drug had previously had another biological therapy&#44; compared to 14 patients &#40;17&#46;7&#37;&#41; of those treated with the BS &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;005&#41;&#44; which was mostly another anti-TNF&#44; in 16 patients &#40;27&#46;1&#37;&#41; in the original group versus 12 &#40;15&#46;2&#37;&#41; patients in the BS group&#46; Most patients were concomitantly taking a DMARD&#44; mainly methotrexate&#58; 32 &#40;54&#46;1&#37;&#41; with the original drug and 38 &#40;48&#46;8&#37;&#41; with the BS&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;521&#46; Only 21&#37; of patients in both groups started treatment in monotherapy &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;680&#41;&#46; Twenty-two patients &#40;37&#46;5&#37;&#41; on the original drug and 28 &#40;35&#46;4&#37;&#41; on the BS &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;823&#41; were taking low-dose corticosteroids at baseline &#40;mean &#91;SD&#93; prednisone treated with the original of 3&#46;7 &#91;5&#46;9&#93; vs&#46; 4&#46;4 &#91;7&#46;5&#93; with the BS&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;579&#41;&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Effectiveness of the biosimilar vs&#46; the original drug</span><p id="par0085" class="elsevierStylePara elsevierViewall">No differences were observed in treatment retention &#40;median &#91;95&#37; confidence interval&#44; 95&#37; CI&#93; 12&#46;0 months &#91;10&#46;2&#8211;12&#46;0&#93; for the BS and 12&#46;0 months &#91;12&#46;0-12&#46;0&#93; for the original drug&#59; logrank test <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;225&#41;&#46; Neither were there differences between diagnoses or in corticosteroid consumption&#46; After the 52 weeks&#44; 9 patients &#40;13&#46;2&#37;&#41; with the BS and 7 &#40;13&#46;5&#37;&#41; with the original drug &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;971&#41; continued to take corticosteroids at low doses &#40;mean &#91;SD&#93; prednisone equivalent dose with the BS 11&#46;8&#8239;mg&#47;day<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> vs&#46; 10&#8239;mg&#47;day<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;7</span></a> with the original&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;341&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Fifty-five patients &#40;70&#37;&#41; in the BS group and 48 patients &#40;81&#46;4&#37;&#41; treated with the original drug &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;117&#41; continued treatment at 52 weeks&#46; The reason for discontinuation was mostly primary failure in 15&#47;24 &#40;62&#46;5&#37;&#41; with the BS and 5&#47;11 &#40;45&#46;5&#37;&#41; with the original &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;039&#41;&#46; Eight &#40;33&#46;3&#37;&#41; patients discontinued treatment due to adverse effects in the BS group versus 5 &#40;45&#46;5&#37;&#41; in the original group&#46; One patient &#40;4&#46;2&#37;&#41; with a desire for pregnancy and good disease control discontinued treatment in the BS group&#46; One patient in each group discontinued treatment due to loss of efficacy&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#44; both treatment groups obtained similar improvements after 52 weeks of treatment in terms of inflammatory activity&#44; physical function&#44; and acute phase reactants &#40;CRP and ESR&#41;&#44; except the patients with SpA and PsA&#44; who&#44; in general&#44; obtained better results with the BS&#44; as can be seen from the BASDAI and ASDAS scores&#46; There was significant improvement and no differences in either group in SDAI&#44; CDAI&#44; NAJ&#44; NIJ&#44; VAS&#44; physician and patient VAS and HAQ&#46; The proportion of patients achieving remission or low disease activity at week 52 was 40 patients &#40;50&#46;6&#37;&#41; with the BS and 31 patients &#40;52&#46;5&#37;&#41; with the original &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;659&#41;&#46; After one year of treatment&#44; the drug dose was optimised in 8 patients &#40;10&#46;4&#37;&#41; treated with the BS and in 2 patients &#40;3&#46;4&#37;&#41; treated with the original &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;121&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Adverse effects</span><p id="par0100" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#44; there was no difference between the two treatments in the total number of adverse effects &#40;&#46;43 events&#47;patient-year &#91;95&#37; CI&#58; &#46;27&#8211;&#46;58&#93; with the BS versus &#46;53 &#91;95&#37; CI&#58; &#46;33&#8211;&#46;73&#93; with the original&#41;&#46; The most frequent adverse effects were mild-moderate &#40;rate &#46;41 &#91;95&#37; CI&#58; &#46;26&#8211;&#46;57&#93; BS vs&#46; &#46;49 &#91;95&#37; CI&#58; &#46;3&#8211;&#46;68&#93; original&#41;&#59; most were infections &#40;bronchitis&#44; colds&#44; urine infections&#44; herpes simplex&#44; shingles&#41;&#46; One patient &#40;1&#46;3&#37;&#41; with the BS developed paradoxical psoriasis&#46; Injection site skin reactions were more frequent with the original &#40;1 &#91;1&#46;3&#37;&#93; with the BS vs&#46; 9 &#91;15&#46;3&#37;&#93; with the original&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;001&#41;&#44; while headaches were more frequent with the BS &#40;9 &#91;11&#46;4&#37;&#93; vs&#46; 0 with the original&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;007&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Eight patients &#40;10&#46;1&#37;&#41; discontinued the BS due to non-serious adverse effects &#40;2 disabling headaches&#44; 1 increased baseline dyspnoea&#44; 1 gastritis&#44; 3 patients with recurrent infections and 1 neutropenia&#41;&#46; Five patients &#40;8&#46;5&#37;&#41; with the original discontinued the drug also due to adverse effects &#40;1 pneumonia&#44; 3 patients with skin reactions and 1 adenocarcinoma of the ovary&#41;&#46; Three patients discontinued the drug due to a serious adverse effect &#40;rate &#46;04 &#91;95&#37; CI&#58; &#46;0&#8211;&#46;09&#93; BS vs&#46; &#46;04 &#91;95&#37; CI&#58; &#46;01&#8211;&#46;09&#93; original&#41;&#58; one patient treated with the BS suffered severe neutropenia&#44; another patient due to pneumonia and the third due to undifferentiated gynaecological adenocarcinoma&#44; both treated with the original&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Costs of the biosimilar</span><p id="par0110" class="elsevierStylePara elsevierViewall">The cost of the BS during the follow-up period was &#8364;5&#44;540 patient-year&#44; compared to &#8364;7&#44;306 patient-year for the original&#46; The real total cost of treatment for all BS patients followed for 3&#44;523&#46;32 weeks was &#8364;375&#44;409&#46;75&#44; while the total cost using the original drug would have been &#8364;493&#44;793&#46;3&#46; This resulted in a net saving for the centre during follow-up of &#8364;118&#44;383&#46;55 &#40;&#8364;1&#44;747&#46;2&#47;patient-year&#41;&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">The economic impact of the different rheumatic diseases is largely due to the costs of treatment&#46; Therefore&#44; the choice of each drug should not only depend on its efficacy&#44; but also its efficiency and safety&#46; We conducted a study to evaluate the efficacy&#44; safety&#44; and cost of the Benepali BS in a group of patients with different rheumatic diseases&#44; based on our clinical practice&#46; To date&#44; no study had been conducted in clinical practice to compare efficacy between the BS and reference drugs&#46; Nor has the survival of the BS in inflammatory rheumatic diseases been analysed&#46; In our study&#44; all patients showed significant improvement in disease activity and physical function parameters assessed at 52 weeks of treatment with Benepali or Enbrel&#46; Furthermore&#44; in both groups&#44; half of the patients achieved a state of remission-low disease activity by DAS28 and BASDAI&#46; In addition&#44; we found no significant differences between the two treatment groups in the improvement observed in patients after 52 weeks&#46; At 12 months we only observed differences between both groups in higher median CRP in patients treated with Benepali&#44; but despite significant differences&#44; the CRP value was lower than 5&#8239;mg&#47;l in both groups&#46; Neither could these results be explained by higher corticosteroid use in the Enbrel patients&#44; as the mean dose used in both groups was similar&#46; We observed a higher BASFI score in patients treated with Enbrel&#44; which may be explained by the longer disease course of these patients&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The comparability in efficacy that we observed is similar to that described in other CTs&#46; The study by Chadwick et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> shows the clinical efficacy of etanercept for RA evaluated in several randomised controlled trials &#40;RCTs&#41; and extension studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> It also evaluates the efficacy of different BS such as Benepali or Erelzi&#46; In a phase III RCT conducted in 596 patients randomised to Benepali or Enbrel&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> a significant improvement in DAS28 at week 24 was observed in both groups of patients&#46; About 50&#37; of patients in this study achieved low disease activity or remission status at week 24 according to DAS28&#46; Furthermore&#44; no significant differences were observed between the two treatments in the improvement measured by DAS28 or in other activity variables such as ACR20&#44; ACR50&#44; or physical function by HAQ&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Similarly&#44; another phase III RCT<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> compared the efficacy and safety of Benepali and Enbrel at week 52 in patients with RA&#46; In this study they observed that 41&#37; of patients with Enbrel achieved low disease activity-remission at 52 weeks versus 35&#37; with Benepali&#44; showing no significant differences either group&#46; Furthermore&#44; at 52 weeks&#44; a significant improvement was also observed in all activity and physical function parameters measured in both groups of patients&#46; However&#44; we were not able to compare these data with other studies in routine clinical practice because so far&#44; we only have the results from CTs on the effectiveness of these drugs and the different reference biologicals&#46; Therefore&#44; more data are needed in real clinical practice to corroborate this benefit&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">There are many factors that influence a drug&#8217;s retention time&#44; including the availability of treatment alternatives&#44; effectiveness&#44; drug toxicity&#44; disease severity and adherence to treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Longer treatment retention time usually translates into greater effectiveness and safety of treatment&#46; There are currently no survival studies in rheumatology with BS&#44; but there are studies with its reference drug&#46; Zink et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> conducted a survival study of different anti-TNFs in RA&#44; in which they observed that after one year of treatment 70&#37; of patients continued with Enbrel&#46; In other studies&#44; such as that by Khraishi et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> this figure was 66&#37;&#46; In our study&#44; these data are similar to the above&#44; and after one year of follow-up 81&#37; of patients were still on Enbrel and 72&#37; were still on Benepali&#46; In these data we can see that both treatment groups are similar in survival&#44; with a slightly higher percentage with Enbrel&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">As mentioned above&#44; drug safety is a fundamental factor in influencing this survival&#46; The use of BS has been the subject of debate in recent years and they have been used in clinical practice with caution&#44; mainly due to a lack of knowledge of their possible adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> In this regard&#44; adverse effects were somewhat more frequent in the Enbrel group than in the Benepali group &#40;46&#37; vs&#46; 36&#37;&#41;&#44; than mild-moderate adverse effects&#46; However&#44; drug discontinuation was higher with Benepali than with Enbrel &#40;30&#46;4&#37; vs&#46; 18&#46;6&#37;&#41; due to inefficacy rather than adverse effects&#46; This higher drug discontinuation rate may be the reason why the survival we observed with Benepali was somewhat lower than with Enbrel&#46; In this regard&#44; although both drugs showed efficacy&#44; it is known that a significant proportion do not respond to initial treatment or efficacy is lost over time&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In the phase III RCT by Emery et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> the percentage of adverse events in the Benepali group was 58&#37; compared to 60&#37; with Enbrel during the study up to week 52&#46; Also&#44; in the phase III CT<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> the incidence of treatment emergent adverse events was comparable between the two groups &#40;55&#46;2&#37; vs&#46; 58&#46;2&#37;&#41;&#46; In our data&#44; the safety profile of Benepali was comparable to that of Enbrel and similar to those observed in these and other etanercept studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;29</span></a> They are also consistent in that most adverse effects are mild-moderate&#46; The most frequently described adverse effects are always respiratory infections&#44; liver profile disturbances and injection site reactions&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#8211;32</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">In our study we show that&#44; considering the cost-effectiveness of Benepali&#44; the use of this BS is as effective as the reference drug&#44; but more cost-effective&#44; representing a great saving for the hospital&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">One of the most important aspects of this study is the progress that is being made with the new incorporation of these treatments&#44; with similar efficacy to their reference drugs&#44; resulting in a reduction in hospital costs&#46; According to our data&#44; the savings from treatment in the Benepali group compared to Enbrel is &#8364;1&#44;747&#46;2&#47;patient-year&#46; A study by Kowalik et al&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> describes the introduction of BS as a measure to reduce direct and indirect costs in RA&#46; Moreover&#44; not only do they show savings in the prescription of the BS drug but also&#44; after marketing&#44; a reduction in the price of the original drug&#46; In general&#44; biological drugs are associated with high cost&#44; which restricts their use and leads to inequality in different countries&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> Since BS are a lower-cost alternative to reference drugs&#44; the current inequality in healthcare provision could be gradually diminishing&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> In fact&#44; budget impact analyses following the introduction of BS&#44; such as infliximab&#44; in different European countries have shown that switching to BS therapy results in significant cost savings and increased access to these therapies&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Our study has some limitations&#44; primarily its retrospective design&#46; Although the design is technically retrospective&#44; it is in fact mostly prospective&#44; as all variables analysed were collected prospectively and systematically&#44; based on a previously designed protocol&#46; This explains the absence of data loss and the very consistent results&#46; A second limitation would be the small number of patients&#44; which would influence the statistical power&#46; However&#44; all the patients are from routine clinical practice&#44; and despite being a heterogeneous sample because we include different diseases in the study &#40;unlike the RCTs mentioned&#44; which only include RA&#41;&#44; we found differences in the main variables in the use of the BS&#46; Finally&#44; there are limitations due to different follow-up times for each patient and disease course&#46; The choice of treatment with Enbrel or Benepali&#44; fell to each physician according to the characteristics of the patient and&#44; obviously&#44; taking cost into consideration&#46; Therefore&#44; since Benepali&#8217;s marketing&#44; there has been increased prescription of Benepali compared to Enbrel&#44; therefore more patients can be treated at the same price&#46; The recent marketing of Benepali and increase in its prescription explain why&#44; in our study&#44; the percentage of patients who had previously received other biological drugs was higher with Enbrel than with Benepali &#40;39&#37; vs&#46; 17&#37;&#44; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;005&#41;&#44; as well as the longer disease course in the patients with Enbrel&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In conclusion&#44; these results demonstrate the effectiveness of Benepali in safely controlling the signs and symptoms of patients with inflammatory joint diseases&#44; comparable to Enbrel in clinical practice&#46; These results are comparable to those of the CTs&#46; In addition&#44; this disease control is maintained at a lower cost&#46; Benepali represents a reduction in hospital costs that should be considered&#46; These benefits are homogeneous&#44; according to our study&#44; in the different rheumatic diseases that we have included here&#59; however&#44; further studies with a larger number of patients and the inclusion in clinical practice of other already marketed BS are necessary to consolidate these results&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Funding</span><p id="par0155" class="elsevierStylePara elsevierViewall">Research grants from the Spanish Rheumatology Foundation &#40;FER&#41;&#46; We received no other financial support or other benefits from commercial sources&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflict of interests</span><p id="par0160" class="elsevierStylePara elsevierViewall">Marta Rojas-Gim&#233;nez&#58; talks for MSD&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Natalia Mena-V&#225;zquez&#58; talks for MSD&#44; UCB and Roche&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Carmen Mar&#237;a Romero-Barco&#58; talks&#47;presentations for AbbVie&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Sara Manrique-Arija&#58; talks&#47;presentations for AbbVie&#44; Pfizer&#44; and MSD&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Inmaculada Ure&#241;a-Garnica has no conflict of interest to declare&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Gisela Diaz-Cordov&#233;s&#58; talks&#47;presentations for AbbVie&#44; Pfizer&#44; and MSD&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Francisco Gabriel Jim&#233;nez-N&#250;&#241;ez&#58; talks&#47;presentations for AbbVie&#44; Pfizer&#44; and MSD&#46;</p></span></span>"
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          "titulo" => "Introduction"
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              "titulo" => "Effectiveness of the biosimilar vs&#46; the original drug"
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    "fechaRecibido" => "2020-02-04"
    "fechaAceptado" => "2020-06-29"
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            0 => "Rheumatic disease"
            1 => "Disease-modifying anti-rheumatic drugs"
            2 => "Biologic therapy"
            3 => "Pharmacoeconomics"
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          "palabras" => array:4 [
            0 => "Enfermedades reum&#225;ticas"
            1 => "F&#225;rmacos modificadores de la enfermedad"
            2 => "Terapia biol&#243;gica"
            3 => "An&#225;lisis farmacoecon&#243;mico"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">To assess the effectiveness&#44; safety and cost of Etanercept biosimilar in patients with rheumatoid arthritis &#40;RA&#41;&#44; spondyloarthritis &#40;SpA&#41; and psoriatic arthritis &#40;PsA&#41; compared to the standard drug in real clinical practice&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Retrospective observational study&#46; Case series of 138 patients with RA&#44; SpA or PsA treated with at least one dose of Benepali&#174; &#40;n&#8239;&#61;&#8239;79&#41; or Enbrel&#174; &#40;n&#8239;&#61;&#8239;59&#41;&#46; Drug retention time was the primary efficacy endpoint compared to the biosimilar and the original&#46; The proportion of patients achieving low disease activity or remission after 52&#8239;weeks was used as the secondary outcome&#46; Safety was assessed by means of the adverse effects incidence rate&#46; A cost minimization analysis was performed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">No differences were observed regarding treatment retention time between drugs &#40;median &#91;95&#37; confidence interval&#44; 95&#37;&#8239;CI&#93; at 12&#46;0&#8239;months &#91;10&#46;2&#8211;12&#46;0&#93; for the biosimilar and 12&#46;0&#8239;months &#91;12&#46;0&#8211;12&#46;0&#93; for the original&#41;&#46; Similar improvements&#44; in terms of inflammatory activity and physical function&#44; were obtained after 52&#8239;weeks except for patients with SpA and PsA who&#44; in general&#44; experienced improvements of BASDAI and ASDAS with the original compared with the biosimilar&#46; No significant differences were observed in the total number of adverse effects &#40;&#46;43 events&#47;patient-years versus the biosimilar and &#46;53 versus the original&#41;&#46; Using the biosimilar in place of the original drug resulted in a net savings of 118&#44;383&#46;55&#8239;&#8364; &#40;1&#44;747&#46;20&#8239;&#8364;&#47;patient-years&#41; for the hospital&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The biosimilar Benepali is as effective and safe as the original and much more cost-effective&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Evaluar la efectividad&#44; la seguridad y los costes de etanercept biosimilar &#40;BS&#41; en pacientes con artritis reumatoide &#40;AR&#41;&#44; espondiloartritis &#40;EspA&#41; y artritis psori&#225;sica &#40;APs&#41; y en comparaci&#243;n con su original&#44; en condiciones de pr&#225;ctica cl&#237;nica habitual&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional retrospectivo&#46; Se incluyeron 138 pacientes con AR&#44; EspA o APs tratados con al menos una dosis de Benepali&#174; &#40;n&#8239;&#61;&#8239;79&#41; o Enbrel&#174; &#40;n&#8239;&#61;&#8239;59&#41;&#46; Como desenlace principal de efectividad del BS o de su original se us&#243; el tiempo de retenci&#243;n del f&#225;rmaco&#46; Como desenlace secundario de efectividad se midi&#243; la proporci&#243;n de pacientes que alcanzaban baja actividad o remisi&#243;n a las 52&#8239;semanas&#46; La seguridad fue evaluada mediante tasas de incidencia de efectos adversos&#46; Se hizo un an&#225;lisis de minimizaci&#243;n de costes&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">No se observaron diferencias en cuanto a retenci&#243;n del tratamiento &#40;mediana &#91;intervalo de confianza del 95&#37;&#44; IC&#8239;95&#37;&#93; de 12&#44;0&#8239;meses &#91;10&#44;2&#8211;12&#44;0&#93; para BS y 12&#44;0 meses &#91;12&#44;0&#8211;12&#44;0&#93; para el original&#41;&#46; Se obtuvieron mejor&#237;as similares despu&#233;s de 52&#8239;semanas en actividad inflamatoria y funci&#243;n f&#237;sica&#44; excepto en los pacientes con EspA y APs&#44; que en general obtuvieron mejores valores de BASDAI y ASDAS con el BS&#46; No se registraron diferencias en el n&#250;mero total de efectos adversos &#40;0&#44;43 eventos&#47;pacientes-a&#241;o con BS frente a 0&#44;53 con original&#41;&#46; El uso del BS&#44; en lugar de su original&#44; supuso un ahorro neto para el centro de 118&#46;383&#44;55&#8239;&#8364; &#40;1&#46;747&#44;2&#8364;&#47;pacientes-a&#241;o&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">El uso del BS parece tan eficaz y seguro como su original y mucho m&#225;s coste-efectivo&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Rojas-Gim&#233;nez M&#44; Mena-V&#225;zquez N&#44; Romero-Barco CM&#44; Manrique-Arija S&#44; Ure&#241;a-Garnica I&#44; Diaz-Cordov&#233;s G&#44; et al&#46; Efectividad&#44; seguridad y an&#225;lisis econ&#243;mico de Benepali en pr&#225;ctica cl&#237;nica&#46; Reumatol Clin&#46; 2021&#59;17&#58;588&#8211;594&#46;</p>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">ACPA&#58; Anti-citrullinated Protein Antibodies&#59; IQR&#58; Interquartile Range&#59; RF&#58; Rheumatoid Factor&#59; SD&#58; Standard Deviation&#59; TNF&#58; Tumour Necrosis Factor&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Age in years&#44; mean &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#46;8 &#40;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&#46;5 &#40;13&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;604&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Females&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;64&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47 &#40;59&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;572&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Caucasian&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57 &#40;96&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77 &#40;97&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;766&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Smokers&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;28&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;098&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Disease course in years&#44; median &#40;IQR&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;8 &#40;9&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;7&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;064&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Diagnosis</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Rheumatoid arthritis&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42 &#40;71&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43 &#40;54&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;132&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>RF positive&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;85&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;79&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;421&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ACPA positive&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35 &#40;83&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;86&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;728&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Erosions&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;39&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;331&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Spondyloarthritis&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;15&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;25&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HLAB27 positive&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;44&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Erosions&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;10&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;629&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Radiographic sacroiliitis&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;77&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;891&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Uveitis&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;557&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Psoriatic arthritis&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;13&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;20&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HLAB27 positive&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;18&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;190&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Erosions&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6 &#40;37&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#46;204&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Radiographic sacroiliitis&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Uveitis&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;6&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Previous biological treatment&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;17&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anti TNF&#945;&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;27&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;15&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tocilizumab&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;2&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tofacitinib&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1 &#40;1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Abatacept&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;3&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Original&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12&#46;0 &#91;12&#46;0-12&#46;0&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">DAS28&#44; mean &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#46;7 &#40;1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;9 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Original&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;6 &#40;1&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Original&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;26&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BASDAI&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;7 &#40;1&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;9 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Original&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;7 &#40;1&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;046&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BASFI&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;7 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;9 &#40;2&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Original&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;5 &#40;2&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;2 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;296&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ASDAS&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;3 &#40;0&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;058&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Original&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;3 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;4 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Remission-low disease activity&#44; n &#40;&#37;&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;659&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40 &#40;50&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Original&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;52&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">BS &#40;n&#8239;&#61;&#8239;79&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Original &#40;n&#8239;&#61;&#8239;59&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Total patients with adverse effects&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;39&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;45&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;377&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Total patients with mild-moderate adverse effects&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;35&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;42&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;347&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Infections&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;22&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;28&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;420&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Injection site reactions&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;15&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Other&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;11&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Total patients with severe adverse effects&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Total patients with serious adverse effects&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;3&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;428&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Discontinuation of treatment&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;30&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;18&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">15 &#40;17&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Loss of efficacy&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;1&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">11 &#40;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "A phase III randomised&#44; double-blind&#44; parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Emery"
                            1 => "J&#46; Vencovsk&#253;"
                            2 => "A&#46; Sylwestrzak"
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                    0 => array:2 [
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                      "titulo" => "The 2010 ACR&#47;EULAR classification criteria for rheumatoid arthritis in the Heinola inception cohort--diagnoses confirmed by long-term follow-up"
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