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Is filgotinib more effective than placebo in active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drug therapy?
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%).
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.
Patients with active rheumatoid arthritis (RA) despite treatment with biologic disease-modifying antirheumatic drug (bDMARD) therapy need treatment options.
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.
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.
Among 448 patients who were treated (mean [SD] age, 56  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.
ClinicalTrials.gov Identifier: NCT02873936
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Corresponding Author: Mark C. Genovese, MD, Division of Immunology and Rheumatology, Stanford University School of Medicine, 1000 Welch Rd, Ste 203, Palo Alto, CA 94304 (firstname.lastname@example.org).
Accepted for Publication: June 6, 2019.
Correction: This article was corrected online on February 4, 2020, to fix demographic data reported in Table 1 and disease characteristic data reported in eTable 2 in Supplement 3.
Author Contributions: Dr Genovese had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Genovese, Mozaffarian, Matzkies, Tasset, Sundy, Takeuchi.
Acquisition, analysis, or interpretation of data: Genovese, Kalunian, Gottenberg, Mozaffarian, Bartok, Matzkies, Gao, Guo, Tasset, Sundy, de Vlam, Walker.
Drafting of the manuscript: Genovese, Bartok, Matzkies, Sundy, Walker.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Matzkies, Gao, Guo.
Obtained funding: Genovese, Matzkies.
Administrative, technical, or material support: Genovese, Kalunian, Matzkies, Sundy.
Supervision: Genovese, Gottenberg, Mozaffarian, Bartok, Matzkies, Sundy, de Vlam, Takeuchi.
Conflict of Interest Disclosures: Dr Genovese reported receiving grants and personal fees from Gilead and grants from Galapagos during the conduct of the study and grants and personal fees from Lilly, AbbVie, Pfizer, Astellas, Vertex, Sanofi, EMD Serono, and Genentech/Roche and personal fees from Incyte outside the submitted work. Dr Kalunian reported receiving grants from Gilead during the conduct of the study. Dr Gottenberg reported receiving personal fees from AbbVie, Pfizer, UCB, Eli Lilly, and Sanofi-Genzyme; grants and personal fees from Bristol-Myers Squibb; and nonfinancial support from Roche outside the submitted work. Drs Mozaffarian, Bartok, Matzkies, Gao, Guo, and Sundy are employees and stockholders of Gilead Sciences. Dr Tasset is an employee and stockholder of Galapagos NV. Dr Walker reported serving on advisory boards and speaking at meetings for Eli Lilly, Pfizer, Novartis, and Gilead. Dr Takeuchi reported receiving grants and personal fees from AbbVie, Astellas Pharma Inc, Chugai Pharmaceutical Co Ltd, Daiichi Sankyo Co, Eisai Co Ltd, Mitsubishi Tanabe Pharma Co, Nipponkayaku Co Ltd, Pfizer Japan Inc, and Takeda Pharmaceutical Co Ltd; personal fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly Japan, GlaxoSmithKline, Janssen Pharmaceutical, Novartis Pharma, AYUMI Pharmaceutical Corporation, Sanofi, Teijin Pharma Ltd, Taiho Pharmaceutical Co Ltd, Taisho Pharmaceutical Co Ltd, and UCB Japan Co Ltd; and grants from Asahikasei Pharma Corp during the conduct of the study. No other disclosures were reported.
Funding/Support: This study was supported by Gilead Sciences Inc.
Role of the Funder/Sponsor: The trial was designed by Gilead Sciences Inc in collaboration with academic advisors; Gilead had an oversight role in the conduct of the study and collection, analysis, and interpretation of the data; and Gilead employee authors were involved in the preparation, review, and approval of the manuscript and the decision to submit the manuscript for publication. Gilead did not have the right to veto publication or to control the decision regarding to which journal the article was submitted.
Additional Contributions: We thank all of the patients, their families, and the FINCH investigators/site staff. Assistance with manuscript preparation, development of tables and figures, and process support was provided by Beth Sesler, PhD, CMPP, at Impact Communications and funded by Gilead Sciences Inc.
Data Sharing Statement: See Supplement 4.
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