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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The treatment of rheumatoid arthritis &#40;RA&#41; changed dramatically with the appearance of biological drugs more than 15 years ago&#46; The release of the first anti-TNF agents&#44; including infliximab &#40;chimeric&#41;&#44; adalimumab &#40;humanized&#41; and etanercept &#40;soluble receptor&#41; represented a paradigm shift in the treatment of a chronic inflammatory disease that had few treatment options and&#44; for many&#44; a poor prognosis&#46; Soon after&#44; the appearance of new therapeutic medications such as tocilizumab &#40;inhibitor of IL-6&#41;&#44; rituximab &#40;anti-CD20&#41;&#44; abatacept &#40;T cell co-stimulation blocker&#41;&#44; along with new subcutaneous anti-TNF drugs &#40;golimumab and certolizumab pegol&#41;&#44; has completed the arsenal of commonly used biologic disease-modifying anti-rheumatic drugs &#40;b-DMARDs&#41;&#46; Parallel to the appearance of those therapies&#44; we have improved the management of older drugs such as methotrexate&#44; with optimization of the dose or improving bioavailability with the subcutaneous route of administration&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Based on recent publications&#44; the treatment of RA may be headed for yet another shift in paradigm&#46; After years of experience with b-DMARDs and the availability of extensive records such as Biobadaser&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">1</span></a> we have reassuring safety data&#46; In addition&#44; we have studies comparing the effectiveness of different anti-TNF agents as the first b-DMARDs in large populations of na&#239;ve patients&#44; with no noticeable differences between them in usual clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a> Not only have new and more effective drugs been developed but the entire approach to treatment has been revolutionized by the adoption of treat-to-target &#40;T2T&#41; strategies&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a> Since then&#44; multiple trials have been released to propose variations of this approach&#46; Aligned to the T2T strategy&#44; the recent <span class="elsevierStyleItalic">Stratege</span> study recommends initial MTX treatment optimization before initiation of a biologic agent and emphasizes the importance of treat-to-target strategy&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> And a recent meta-analysis of different randomized controlled trials evaluated 13 studies out of 44&#44;651 citations to compare cycling strategies between different anti TNF agents &#40;including adalimumab&#44; etanercept&#44; certolizumab&#44; golimumab&#44; and infliximab&#41; with swapping strategies &#40;including tocilizumab&#44; abatacept&#44; rituximab&#44; and tofacitinib&#41; and found that cycling to a different anti-TNF drug after an initial anti-TNF failure can be effective and should be considered before switching to a different targeted therapy&#46; These data suggest that many patients who fail a specific agent will not fail anti-TNF drugs as a class&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> For those who are treated with biologic agents other than an anti-TNF&#44; monotherapy may be just as effective as combination with a conventional&#44; synthetic DMARD&#58; at the 2016 American College of Rheumatology meeting&#44; Gottenberg et al&#46; presented long-term registry data from 4498 patients with RA demonstrating that in a real world setting&#44; monotherapy with abatacept&#44; rituximab or tocilizumab was not associated with lower long term retention than combination with synthetic DMARDs&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">One of the biggest complaints about research in RA in recent years has been the lack of head to head studies between biological therapies&#46; At last&#44; the results of such studies are beginning to appear&#58; the Ample study compared abatacept with adalimumab<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">7</span></a> and&#44; recently&#44; the results of a new trial comparing certolizumab and adalimumab was released&#46; The EXXELERATE study is the first trial to directly compare two anti-TNF agents and confirms similar early and long-term efficacy of both certolizumab and adalimumab in combination with MTX&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Considering that cost is a major impediment to the treatment of patients with RA who warrant biologic therapy&#44; the development of biosimilars represents an important advance&#46; Several studies of therapeutic bioequivalence have demonstrated equal safety and efficacy for biosimilars as compared with the original molecule&#46; A study comparing etanercept &#40;ETN&#41; with a biosimilar &#40;SB4&#41; version confirmed that long-term efficacy &#40;as assessed by DAS28&#44; SDAI&#44; CDAI&#44; and HAQ-DI&#41; and safety were comparable between both agents during the trial&#44; as well as during the extension period&#46; In addition&#44; efficacy was sustained after switching from etanercept to SB4&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">What should we expect from the future of RA treatment&#63; Since 2014&#44; a new oral therapy&#44; tofacintinib&#44; a Janus kinase &#40;JAK1&#44; JAK3&#41; inhibitor&#44; has been available in the US though it is not yet available in Europe&#46; At the recent meeting of the ACR&#44; several studies presented data about this new agent&#46; We have learned that a lack of early change in disease activity score in patients treated with tofacitinib&#44; predicts a low likelihood of achieving low disease activity at month 6&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">10</span></a> Recent open-label&#44; long-term extension studies have released valuable data regarding the safety and efficacy of tofacitinib over 8 years&#44; including the risk of major adverse cardiovascular events &#40;MACE&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">11</span></a> In the pooled analyses of tofacitinib-treated patients&#44; increases in HDL-cholesterol appeared to offset the increases in total and LDL cholesterol&#44; so that MACE risk was actually reduced&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Interest is growing in the promise of combining biologic therapies&#46; Tumor necrosis factor &#40;TNF&#41; and interleukin 17 &#40;IL-17&#41; appear to independently contribute to the pathophysiology of rheumatoid arthritis &#40;RA&#41;&#44; synergistically inducing inflammatory mediators leading to joint destruction&#46; In a mouse model of RA&#44; dual neutralization of TNF and IL-17 conferred superior joint protection compared with inhibition of either target individually&#46; A recent abstract presented at the 2016 ACR meeting showed the usefulness of ABT-122&#44; a drug that inhibits both TNF and IL-17&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">13</span></a> The authors found that dual cytokine inhibition of TNF-&#945; and IL-17 demonstrated good tolerability and maintenance of benefit in the open label extension period when continued for up to 36 weeks in patients with RA receiving background methotrexate&#46; This included those switching from ADA to ABT-122&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Recent studies of a new oral JAK1&#47;JAK2 inhibitor&#44; baricitinib&#44; have reported positive efficacy and safety data among elderly patients with moderate to severe rheumatoid arthritis&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">14</span></a> A recent trial from Taylor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a> found similar results among RA patients switching from adalimumab to baricitinib in a phase 3 trial&#46; A systematic review and meta-analysis presented by Zamora et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a> suggests that baricitinib alone or combined with methotrexate was more effective than methotrexate alone at 12&#8211;24 weeks&#46; Moreover&#44; baricitinib had similar effects as adalimumab&#44; but slightly higher rates of severe adverse reactions&#46; Thus&#44; baricitinib could become an additional therapeutic option to treat patients with moderate to severe disease with an inadequate response to other agents&#46; Some concerns have been recently raised regarding the incidence of herpes zoster and unfavorable lipid changes among baricitinib-treated patients&#46; Integrated analyses have shown that treatment with baricitinib was associated with an increased risk of herpes zoster compared with placebo&#44; with an overall rate of 3&#46;3&#47;100 patient-years&#46; Rates appeared to diminish with prolonged exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a> Secondly&#44; in a trial from McInnes et al&#46;&#44; baricitinib was associated with increased LDL-C&#44; HDL-C&#44; and TG levels&#44; with a stable LDL-C&#47;HDL-C ratio&#46; In patients initiating statin therapy during the study&#44; the elevation in total cholesterol&#44; LDL-C&#44; and TG decreased to pretreatment levels&#44; while HDL-C remained elevated with statin therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Besides tofacitinib and baricitinib&#44; other new targeted therapies were presented at the recent ACR meeting that may soon be available&#46; Olokizumab&#44; an interleukin-6 &#40;IL-6&#41;-targeting monoclonal antibody<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">19</span></a> and sirukumab&#44; another anti-IL-6 monoclonal antibody have shown promising results in reducing joint inflammation and fatigue as well as other signs and symptoms of RA&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">20&#44;21</span></a> Sarilumab &#40;150 or 200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks subcutaneously&#41; has also shown promising clinical outcome results after 3 years of treatment and&#44; in addition&#44; pooled safety and efficacy data have been recently presented for elderly patients with RA&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">22&#44;23</span></a> A new selective JAK1 inhibitor&#44; filgotinib&#44; is another treatment that could become a viable option for RA therapy in the future&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">24</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Presentations at the most recent ACR and EULAR meetings suggest that a number of new drugs and targets may change and advance our approach to RA&#46; Complementing treatments targeting TNF&#44; IL-6&#44; CTL4&#47;CD28 co-stimulation blocker&#44; or B-cells&#44; our patients with RA may soon benefit from the development of new molecules directed against G-CSF&#44; JAK kinase or even monoclonal antibodies directed against 2 or more targets&#46; Recently&#44; Kalden<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">25</span></a> reviewed older biologic agents &#40;now considered &#8220;classic&#8221;&#41;&#44; as well as new small molecules&#44; combination therapies &#40;such as kinase inhibitors and b-DMARDs&#41;&#44; and b-DMARDs directed against interleukin-17 or complement component 5&#46; Finally&#44; a proteasome inhibitor such as bortezomib&#44; has also been proposed as a potential antirheumatic agent&#59; proteasomes degrade proteins in mammalian cells and are established targets of anticancer drugs&#44; such as multiple myeloma&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">26</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Keeping up with new and emerging therapeutic strategies will require frequent updates by clinicians and researchers&#46; However&#44; in the near-run&#44; one of the biggest changes we are likely to see is the growing presence of biosimilars&#46; 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        "texto" => "<p id="par0055" class="elsevierStylePara elsevierViewall">H&#232;ctor Corominas is currently a member of the visiting faculty in the Rheumatology Division and Lupus Center of the Beth Israel Deaconess Medical Center&#44; Harvard Medical School&#44; partially supported thanks to a grant from the <span class="elsevierStyleGrantSponsor" id="gs1">Sociedad Espa&#241;ola de Reumatolog&#237;a &#40;SER&#41;</span> and <span class="elsevierStyleGrantSponsor" id="gs2">Societat Catalana de Reumatologia &#40;SCR&#41;</span>&#46;</p>"
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Editorial
What lies in the near future for the treatment of rheumatoid arthritis?
¿Qué pasará en un futuro próximo para el tratamiento de la artritis reumatoide?
Hèctor Corominasa,b,
Corresponding author
, Robert H. Shmerlinga
a Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
b Servei de Reumatologia, Hospital Moisès Broggi, Sant Joan Despí, Barcelona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The treatment of rheumatoid arthritis &#40;RA&#41; changed dramatically with the appearance of biological drugs more than 15 years ago&#46; The release of the first anti-TNF agents&#44; including infliximab &#40;chimeric&#41;&#44; adalimumab &#40;humanized&#41; and etanercept &#40;soluble receptor&#41; represented a paradigm shift in the treatment of a chronic inflammatory disease that had few treatment options and&#44; for many&#44; a poor prognosis&#46; Soon after&#44; the appearance of new therapeutic medications such as tocilizumab &#40;inhibitor of IL-6&#41;&#44; rituximab &#40;anti-CD20&#41;&#44; abatacept &#40;T cell co-stimulation blocker&#41;&#44; along with new subcutaneous anti-TNF drugs &#40;golimumab and certolizumab pegol&#41;&#44; has completed the arsenal of commonly used biologic disease-modifying anti-rheumatic drugs &#40;b-DMARDs&#41;&#46; Parallel to the appearance of those therapies&#44; we have improved the management of older drugs such as methotrexate&#44; with optimization of the dose or improving bioavailability with the subcutaneous route of administration&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Based on recent publications&#44; the treatment of RA may be headed for yet another shift in paradigm&#46; After years of experience with b-DMARDs and the availability of extensive records such as Biobadaser&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">1</span></a> we have reassuring safety data&#46; In addition&#44; we have studies comparing the effectiveness of different anti-TNF agents as the first b-DMARDs in large populations of na&#239;ve patients&#44; with no noticeable differences between them in usual clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a> Not only have new and more effective drugs been developed but the entire approach to treatment has been revolutionized by the adoption of treat-to-target &#40;T2T&#41; strategies&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a> Since then&#44; multiple trials have been released to propose variations of this approach&#46; Aligned to the T2T strategy&#44; the recent <span class="elsevierStyleItalic">Stratege</span> study recommends initial MTX treatment optimization before initiation of a biologic agent and emphasizes the importance of treat-to-target strategy&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> And a recent meta-analysis of different randomized controlled trials evaluated 13 studies out of 44&#44;651 citations to compare cycling strategies between different anti TNF agents &#40;including adalimumab&#44; etanercept&#44; certolizumab&#44; golimumab&#44; and infliximab&#41; with swapping strategies &#40;including tocilizumab&#44; abatacept&#44; rituximab&#44; and tofacitinib&#41; and found that cycling to a different anti-TNF drug after an initial anti-TNF failure can be effective and should be considered before switching to a different targeted therapy&#46; These data suggest that many patients who fail a specific agent will not fail anti-TNF drugs as a class&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> For those who are treated with biologic agents other than an anti-TNF&#44; monotherapy may be just as effective as combination with a conventional&#44; synthetic DMARD&#58; at the 2016 American College of Rheumatology meeting&#44; Gottenberg et al&#46; presented long-term registry data from 4498 patients with RA demonstrating that in a real world setting&#44; monotherapy with abatacept&#44; rituximab or tocilizumab was not associated with lower long term retention than combination with synthetic DMARDs&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">One of the biggest complaints about research in RA in recent years has been the lack of head to head studies between biological therapies&#46; At last&#44; the results of such studies are beginning to appear&#58; the Ample study compared abatacept with adalimumab<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">7</span></a> and&#44; recently&#44; the results of a new trial comparing certolizumab and adalimumab was released&#46; The EXXELERATE study is the first trial to directly compare two anti-TNF agents and confirms similar early and long-term efficacy of both certolizumab and adalimumab in combination with MTX&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Considering that cost is a major impediment to the treatment of patients with RA who warrant biologic therapy&#44; the development of biosimilars represents an important advance&#46; Several studies of therapeutic bioequivalence have demonstrated equal safety and efficacy for biosimilars as compared with the original molecule&#46; A study comparing etanercept &#40;ETN&#41; with a biosimilar &#40;SB4&#41; version confirmed that long-term efficacy &#40;as assessed by DAS28&#44; SDAI&#44; CDAI&#44; and HAQ-DI&#41; and safety were comparable between both agents during the trial&#44; as well as during the extension period&#46; In addition&#44; efficacy was sustained after switching from etanercept to SB4&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">What should we expect from the future of RA treatment&#63; Since 2014&#44; a new oral therapy&#44; tofacintinib&#44; a Janus kinase &#40;JAK1&#44; JAK3&#41; inhibitor&#44; has been available in the US though it is not yet available in Europe&#46; At the recent meeting of the ACR&#44; several studies presented data about this new agent&#46; We have learned that a lack of early change in disease activity score in patients treated with tofacitinib&#44; predicts a low likelihood of achieving low disease activity at month 6&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">10</span></a> Recent open-label&#44; long-term extension studies have released valuable data regarding the safety and efficacy of tofacitinib over 8 years&#44; including the risk of major adverse cardiovascular events &#40;MACE&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">11</span></a> In the pooled analyses of tofacitinib-treated patients&#44; increases in HDL-cholesterol appeared to offset the increases in total and LDL cholesterol&#44; so that MACE risk was actually reduced&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Interest is growing in the promise of combining biologic therapies&#46; Tumor necrosis factor &#40;TNF&#41; and interleukin 17 &#40;IL-17&#41; appear to independently contribute to the pathophysiology of rheumatoid arthritis &#40;RA&#41;&#44; synergistically inducing inflammatory mediators leading to joint destruction&#46; In a mouse model of RA&#44; dual neutralization of TNF and IL-17 conferred superior joint protection compared with inhibition of either target individually&#46; A recent abstract presented at the 2016 ACR meeting showed the usefulness of ABT-122&#44; a drug that inhibits both TNF and IL-17&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">13</span></a> The authors found that dual cytokine inhibition of TNF-&#945; and IL-17 demonstrated good tolerability and maintenance of benefit in the open label extension period when continued for up to 36 weeks in patients with RA receiving background methotrexate&#46; This included those switching from ADA to ABT-122&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Recent studies of a new oral JAK1&#47;JAK2 inhibitor&#44; baricitinib&#44; have reported positive efficacy and safety data among elderly patients with moderate to severe rheumatoid arthritis&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">14</span></a> A recent trial from Taylor et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a> found similar results among RA patients switching from adalimumab to baricitinib in a phase 3 trial&#46; A systematic review and meta-analysis presented by Zamora et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a> suggests that baricitinib alone or combined with methotrexate was more effective than methotrexate alone at 12&#8211;24 weeks&#46; Moreover&#44; baricitinib had similar effects as adalimumab&#44; but slightly higher rates of severe adverse reactions&#46; Thus&#44; baricitinib could become an additional therapeutic option to treat patients with moderate to severe disease with an inadequate response to other agents&#46; Some concerns have been recently raised regarding the incidence of herpes zoster and unfavorable lipid changes among baricitinib-treated patients&#46; Integrated analyses have shown that treatment with baricitinib was associated with an increased risk of herpes zoster compared with placebo&#44; with an overall rate of 3&#46;3&#47;100 patient-years&#46; Rates appeared to diminish with prolonged exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a> Secondly&#44; in a trial from McInnes et al&#46;&#44; baricitinib was associated with increased LDL-C&#44; HDL-C&#44; and TG levels&#44; with a stable LDL-C&#47;HDL-C ratio&#46; In patients initiating statin therapy during the study&#44; the elevation in total cholesterol&#44; LDL-C&#44; and TG decreased to pretreatment levels&#44; while HDL-C remained elevated with statin therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Besides tofacitinib and baricitinib&#44; other new targeted therapies were presented at the recent ACR meeting that may soon be available&#46; Olokizumab&#44; an interleukin-6 &#40;IL-6&#41;-targeting monoclonal antibody<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">19</span></a> and sirukumab&#44; another anti-IL-6 monoclonal antibody have shown promising results in reducing joint inflammation and fatigue as well as other signs and symptoms of RA&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">20&#44;21</span></a> Sarilumab &#40;150 or 200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks subcutaneously&#41; has also shown promising clinical outcome results after 3 years of treatment and&#44; in addition&#44; pooled safety and efficacy data have been recently presented for elderly patients with RA&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">22&#44;23</span></a> A new selective JAK1 inhibitor&#44; filgotinib&#44; is another treatment that could become a viable option for RA therapy in the future&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">24</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Presentations at the most recent ACR and EULAR meetings suggest that a number of new drugs and targets may change and advance our approach to RA&#46; Complementing treatments targeting TNF&#44; IL-6&#44; CTL4&#47;CD28 co-stimulation blocker&#44; or B-cells&#44; our patients with RA may soon benefit from the development of new molecules directed against G-CSF&#44; JAK kinase or even monoclonal antibodies directed against 2 or more targets&#46; Recently&#44; Kalden<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">25</span></a> reviewed older biologic agents &#40;now considered &#8220;classic&#8221;&#41;&#44; as well as new small molecules&#44; combination therapies &#40;such as kinase inhibitors and b-DMARDs&#41;&#44; and b-DMARDs directed against interleukin-17 or complement component 5&#46; Finally&#44; a proteasome inhibitor such as bortezomib&#44; has also been proposed as a potential antirheumatic agent&#59; proteasomes degrade proteins in mammalian cells and are established targets of anticancer drugs&#44; such as multiple myeloma&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">26</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Keeping up with new and emerging therapeutic strategies will require frequent updates by clinicians and researchers&#46; However&#44; in the near-run&#44; one of the biggest changes we are likely to see is the growing presence of biosimilars&#46; Additional research&#44; clinical experience and time will reveal their importance and usefulness&#46;</p></span>"
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                        0 => array:2 [
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                      "titulo" => "Lack of early change in disease activity score predicts the likelihood of achieving low disease activity at month 6&#58; tofacitinib monotherapy versus methotrexate in methotrexate-naive patients with rheumatoid arthritis"
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                        0 => array:2 [
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                0 => array:3 [
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                      "autores" => array:1 [
                        0 => array:2 [
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                  "host" => array:1 [
                    0 => array:1 [
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                0 => array:3 [
                  "comentario" => "&#91;abstract&#93;"
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                      "titulo" => "Major adverse cardiovascular events&#58; risk factors in patients with RA treated with tofacitinib"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                      "titulo" => "Dual cytokine inhibition with ABT-122 a Tnf- and IL-17-targeted dual variable domain immunoglobulin &#40;DVD-Ig&#8482;&#41;&#58; results from a 24-week open-label extension study in patients with rheumatoid arthritis"
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Article information
ISSN: 21735743
Original language: English
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