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

Mark C. Genovese, Kenneth Kalunian, Jacques Eric Gottenberg, Neelufar Mozaffarian, Beatrix Bartok, Franziska Matzkies, Jie Gao, Ying Guo, Chantal Tasset, John S. Sundy, Kurt De Vlam, David Walker, Tsutomu Takeuchi

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)315-325
Number of pages11
JournalJAMA - Journal of the American Medical Association
Volume322
Issue number4
DOIs
Publication statusPublished - 2019 Jul 23

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Antirheumatic Agents
Rheumatoid Arthritis
Randomized Controlled Trials
Placebos
Drug Therapy
Nasopharyngitis
C-Reactive Protein
Joints
Gastrointestinal Tuberculosis
Retinal Vein Occlusion
Opportunistic Infections
Herpes Zoster
Therapeutics
Health Surveys
Respiratory Tract Infections
Signs and Symptoms
Fatigue
Headache
Chronic Disease
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / Genovese, Mark C.; Kalunian, Kenneth; Gottenberg, Jacques Eric; Mozaffarian, Neelufar; Bartok, Beatrix; Matzkies, Franziska; Gao, Jie; Guo, Ying; Tasset, Chantal; Sundy, John S.; De Vlam, Kurt; Walker, David; Takeuchi, Tsutomu.

In: JAMA - Journal of the American Medical Association, Vol. 322, No. 4, 23.07.2019, p. 315-325.

Research output: Contribution to journalArticle

Genovese, Mark C. ; Kalunian, Kenneth ; Gottenberg, Jacques Eric ; Mozaffarian, Neelufar ; Bartok, Beatrix ; Matzkies, Franziska ; Gao, Jie ; Guo, Ying ; Tasset, Chantal ; Sundy, John S. ; De Vlam, Kurt ; Walker, David ; Takeuchi, Tsutomu. / 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. In: JAMA - Journal of the American Medical Association. 2019 ; Vol. 322, No. 4. pp. 315-325.
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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.",
author = "Genovese, {Mark C.} and Kenneth Kalunian and Gottenberg, {Jacques Eric} and Neelufar Mozaffarian and Beatrix Bartok and Franziska Matzkies and Jie Gao and Ying Guo and Chantal Tasset and Sundy, {John S.} and {De Vlam}, Kurt and David Walker and Tsutomu Takeuchi",
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TY - JOUR

T1 - Effect of Filgotinib vs Placebo on Clinical Response in Patients with Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy

T2 - The FINCH 2 Randomized Clinical Trial

AU - Genovese, Mark C.

AU - Kalunian, Kenneth

AU - Gottenberg, Jacques Eric

AU - Mozaffarian, Neelufar

AU - Bartok, Beatrix

AU - Matzkies, Franziska

AU - Gao, Jie

AU - Guo, Ying

AU - Tasset, Chantal

AU - Sundy, John S.

AU - De Vlam, Kurt

AU - Walker, David

AU - Takeuchi, Tsutomu

PY - 2019/7/23

Y1 - 2019/7/23

N2 - 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.

AB - 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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