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Original Investigation
July 23/30, 2019

Effect of Filgotinib vs Placebo on Clinical Response in Patients With Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy: The FINCH 2 Randomized Clinical Trial

Author Affiliations
  • 1Division of Immunology and Rheumatology, Stanford University, Stanford, California
  • 2Division of Rheumatology, Allergy, and Immunology, University of California, San Diego, La Jolla
  • 3Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France
  • 4Gilead Sciences Inc, Foster City, California
  • 5Galapagos NV, Mechelen, Belgium
  • 6Department of Rheumatology, Universitair Ziekenhuis Leuven, Leuven, Belgium
  • 7Northumbria Healthcare, North Shields, United Kingdom
  • 8Division of Rheumatology, Keio University School of Medicine, Tokyo, Japan
JAMA. 2019;322(4):315-325. doi:10.1001/jama.2019.9055
Key Points

Question  Is filgotinib more effective than placebo in active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drug therapy?

Findings  In this randomized clinical trial of 448 patients with active rheumatoid arthritis who had an inadequate response or intolerance to 1 or more biologic disease-modifying antirheumatic drugs, clinical response as measured by American College of Rheumatology 20% response was achieved at week 12 by significantly greater proportions of patients treated with filgotinib, 200 mg (66.0%) or 100 mg (57.5%), compared with placebo (31.1%).

Meaning  A greater proportion of patients who received filgotinib, compared with those who received placebo, achieved clinical response at 12 weeks, but further research is needed to assess longer-term efficacy and safety.

Abstract

Importance  Patients with active rheumatoid arthritis (RA) despite treatment with biologic disease-modifying antirheumatic drug (bDMARD) therapy need treatment options.

Objective  To evaluate the effects of filgotinib vs placebo on the signs and symptoms of RA in a treatment-refractory population.

Design, Setting, and Participants  A 24-week, randomized, placebo-controlled, multinational phase 3 trial conducted from July 2016 to June 2018 at 114 sites internationally, randomizing 449 adult patients (and treating 448) with moderately to severely active RA and inadequate response/intolerance to 1 or more prior bDMARDs.

Interventions  Filgotinib, 200 mg (n = 148); filgotinib, 100 mg (n = 153); or placebo (n = 148) once daily; patients continued concomitant stable conventional synthetic DMARDs (csDMARDs).

Main Outcomes and Measures  The primary end point was the proportion of patients who achieved 20% improvement in the American College of Rheumatology criteria (ACR20) at week 12. Secondary outcomes included week 12 assessments of low disease activity (disease activity score in 28 joints–C-reactive protein [DAS28-CRP] ≤3.2) and change in Health Assessment Questionnaire–Disability Index, 36-Item Short-Form Health Survey Physical Component, and Functional Assessment of Chronic Illness Therapy–Fatigue scores, as well as week 24 assessment of remission (DAS28-CRP <2.6) and adverse events.

Results  Among 448 patients who were treated (mean [SD] age, 56 [12] years; 360 women [80.4%]; mean [SD] DAS28-CRP score, 5.9 [0.96]; 105 [23.4%] with ≥3 prior bDMARDs), 381 (85%) completed the study. At week 12, more patients receiving filgotinib, 200 mg (66.0%) or 100 mg (57.5%), achieved ACR20 response (placebo, 31.1%; difference vs placebo: 34.9% [95% CI, 23.5%-46.3%] and 26.4% [95% CI, 15.0%-37.9%], respectively; both P < .001), including among patients with prior exposure to 3 or more bDMARDs (70.3%, 58.8%, and 17.6%, respectively; difference vs placebo: 52.6% [95% CI, 30.3%-75.0%] for filgotinib, 200 mg, and 41.2% [95% CI, 17.3%-65.0%] for filgotinib, 100 mg; both P < .001). The most common adverse events were nasopharyngitis (10.2%) for filgotinib, 200 mg; headache, nasopharyngitis, and upper respiratory infection (5.9% each) for filgotinib, 100 mg; and RA (6.1%) for placebo. Four uncomplicated herpes zoster cases and 1 retinal vein occlusion were reported with filgotinib; there were no opportunistic infections, active tuberculosis, malignancies, gastrointestinal perforations, or deaths.

Conclusions and Relevance  Among patients with active RA who had an inadequate response or intolerance to 1 or more bDMARDs, filgotinib, 100 mg daily or 200 mg daily, compared with placebo resulted in a significantly greater proportion achieving a clinical response at week 12. However, further research is needed to assess longer-term efficacy and safety.

Trial Registration  ClinicalTrials.gov Identifier: NCT02873936

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