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      Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial

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          Abstract

          Objectives

          To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure.

          Methods

          This 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24.

          Results

          The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was −1.0 and −0.94 with FIL200+MTX and FIL100+MTX, respectively, versus −0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments.

          Conclusions

          FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.

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          Most cited references 21

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          2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

          The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis." In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1). This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct "rheumatoid arthritis."
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            Rheumatoid arthritis.

            Rheumatoid arthritis is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. Early diagnosis is key to optimal therapeutic success, particularly in patients with well-characterised risk factors for poor outcomes such as high disease activity, presence of autoantibodies, and early joint damage. Treatment algorithms involve measuring disease activity with composite indices, applying a treatment-to-target strategy, and use of conventional, biological, and newz non-biological disease-modifying antirheumatic drugs. After the treatment target of stringent remission (or at least low disease activity) is maintained, dose reduction should be attempted. Although the prospects for most patients are now favourable, many still do not respond to current therapies. Accordingly, new therapies are urgently required. In this Seminar, we describe current insights into genetics and aetiology, pathophysiology, epidemiology, assessment, therapeutic agents, and treatment strategies together with unmet needs of patients with rheumatoid arthritis.
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              EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update

              To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.
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                Author and article information

                Journal
                Ann Rheum Dis
                Ann Rheum Dis
                annrheumdis
                ard
                Annals of the Rheumatic Diseases
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0003-4967
                1468-2060
                June 2021
                15 January 2021
                : 80
                : 6
                : 727-738
                Affiliations
                [1 ] departmentDepartment of Development and Regeneration, Skeletal Biology and Engineering Research Center , KU Leuven , Leuven, Flanders, Belgium
                [2 ] departmentDivision of Rheumatology , University Hospitals KU Leuven , Leuven, Flanders, Belgium
                [3 ] departmentGeisel School of Medicine at Dartmouth , Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire, USA
                [4 ] departmentDepartment of Rheumatology , Leiden University Medical Center , Leiden, The Netherlands
                [5 ] Timaru Medical Specialists Limited , Timaru, New Zealand
                [6 ] University of Southern California Keck School of Medicine , Los Angeles, California, USA
                [7 ] departmentDivision of Rheumatology, Department of Medicine , UMass Memorial Medical Center , Worcester, Massachusetts, USA
                [8 ] departmentDivision of Rheumatology, Department of Medicine , University of Massachusetts Medical School , Worcester, Massachusetts, USA
                [9 ] Centre for Rheumatic Diseases , Pune, India
                [10 ] Gilead Sciences , Foster City, California, USA
                [11 ] Galapagos NV , Mechelen, Belgium
                [12 ] departmentDepartment of Medicine , Duke University Medical Center , Durham, North Carolina, USA
                [13 ] Ichnos Sciences , New York, New York, USA
                [14 ] Cosme Argerich Hospital , Buenos Aires, Argentina
                [15 ] Investigaciones Reumatologicas y Osteologicas SRL IRO , Buenos Aires, Argentina
                [16 ] departmentDepartment of Rheumatology & Clinical Immunology , Amsterdam University Medical Center , Amsterdam, The Netherlands
                [17 ] departmentDepartment of Rheumatology , Zuyderland Hospital , Heerlen, The Netherlands
                [18 ] departmentDepartment of Rheumatology, Endocrinology and Nephrology , Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Sapporo, Japan
                [19 ] departmentDepartment of Rheumatology and Clinical Immunology , Charité University Hospital , Berlin, Germany
                [20 ] Free University and Humboldt University , Berlin, Germany
                Author notes
                [Correspondence to ] Dr René Westhovens, Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, 3000 Leuven, Flanders, Belgium; rene.westhovens@ 123456uzleuven.be
                Article
                annrheumdis-2020-219213
                10.1136/annrheumdis-2020-219213
                8142453
                33452004
                © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                Product
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100005564, Gilead Sciences;
                Award ID: N/A
                Categories
                Rheumatoid Arthritis
                1506
                2311
                2502
                Custom metadata
                unlocked

                Immunology

                arthritis, rheumatoid, therapeutics, antirheumatic agents

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