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  1. Bernard Combe1,
  2. Alan Kivitz2,
  3. Yoshiya Tanaka3,
  4. Désirée van der Heijde4,
  5. Franziska Matzkies5,
  6. Beatrix Bartok5,
  7. Lei Ye5,
  8. Ying Guo5,
  9. Chantal Tasset6,
  10. John Sundy5,
  11. Neelufar Mozaffarian5,
  12. Robert B.M. Landewé7,
  13. Sang-Cheol Bae8,
  14. Edward C. Keystone9,10,
  15. Peter Nash11
  1. 1CHU Montpellier, Montpellier University, Montpellier, France
  2. 2Altoona Center for Clinical Research, Duncansville, United States of America
  3. 3University of Occupational and Environmental Health Japan, Kitakyushu, Japan
  4. 4Leiden University Medical Center, Leiden, Netherlands
  5. 5Gilead Sciences, Inc., Foster City, United States of America
  6. 6Galapagos NV, Mechelen, Belgium
  7. 7Amsterdam University Medical Center, Amsterdam, Netherlands
  8. 8Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Rep. of (South Korea)
  9. 9Mount Sinai Hospital, Toronto, Canada
  10. 10University of Toronto, Toronto, Canada
  11. 11University of Queensland, St. Lucia, Australia


Background Filgotinib (FIL) is an orally administered, potent and selective inhibitor of Janus kinase 1 (JAK1) that has shown good efficacy and was well tolerated for treatment of rheumatoid arthritis (RA).

Objectives To evaluate efficacy and safety of FIL treatment in patients with RA who have had an inadequate response to methotrexate (MTX).

Methods This phase 3, double-blind, active- and placebo (PBO)-controlled study randomized patients with active RA (3:3:2:3) to FIL 200 mg, FIL 100 mg, active comparator (adalimumab [ADA] 40mg every 2 weeks), or PBO daily for up to 52 weeks; results through week 24 are presented. Patients were also receiving MTX for ≥12 weeks with a stable dose of MTX for ≥4 weeks before initiation of study drug. Primary efficacy endpoint was proportion of patients achieving ACR20 response at week 12; additional clinical assessments were ACR50 and ACR70 responses, DAS28-CRP score ≤3.2 and <2.6, van der Heijde modified total Sharp score (mTSS), and patient-reported outcomes were HAQ-DI, SF-36 PCS, and FACIT-Fatigue. Safety endpoints included types and rates of adverse events. Logistic regression adjusting for stratification factors with nonresponder imputation was used for superiority test of FIL vs PBO for ACR response and other binary endpoints. Mixed-effect model adjusting for baseline value, stratification factors, treatment, visit, and treatment by visit interaction as fixed effects with observed cases was used for continuous endpoints. Non-inferiority test of FIL to ADA (preserving >50% of ADA response) was performed for DAS28-CRP ≤3.2 and <2.6.

Results Of 1,759 patients randomized, 1,755 received study drug and were analyzed, with 475 FIL 200mg; 480 FIL 100mg; 325 ADA; and 475 PBO, of which 89.5%, 90.4%, 88.9%, and 81.3%, respectively, completed week 24 study drug. Most patients (81.8%) were female, mean (standard deviation [SD]) duration of RA was 7.8 (7.6) years, and mean (SD) DAS28-CRP was 5.7 (0.9). At week 12, significantly more patients in the FIL 200mg and 100mg arms achieved an ACR20 response compared to PBO (Table 1). Similarly, compared to PBO, more patients receiving FIL achieved ACR50 and ACR70 responses, DAS28-CRP scores ≤3.2 and <2.6, had lower radiographic progression, and reported improvements in HAQ-DI, SF-36 PCS, and FACIT-Fatigue scores (Table 1). Non-inferiority of FIL 200mg to ADA was met based on DAS28-CRP ≤3.2. The FIL safety profile was consistent with prior studies through week 24 (Table 2).

Conclusions The selective JAK1 inhibitor FIL, at doses of 200mg and 100mg led to significant improvement in signs and symptoms of RA, prevented radiographic progression, and improved physical function compared to PBO, and was well tolerated among patients with RA with prior inadequate response to MTX. Efficacy of FIL 200mg was non-inferior to ADA based on DAS28-CRP ≤3.2.

Disclosure of Interests Bernard Combe Consultant for: Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche-Chugai, Sanofi, UCB, Alan Kivitz Shareholder of: Novartis, Consultant for: Abbvie, Janssen, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Boehringer Ingelheim, Sun Pharma Advanced Research, Flexion., Paid instructor for: Celgene, Horizon, Merck, Novartis, Pfizer, Genzyme, Sanofi, Regeneron, Speakers bureau: Celgene, Horizon, Merck and Genetech, Flexion, Yoshiya Tanaka Grant/research support from: Abbvie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, Taisho-Toyama, Takeda, Speakers bureau: Abbvie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai, Glaxo-Smithkline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer Japan Inc, Sanofi, Takeda, UCB, YL Biologics, Désirée van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge, Franziska Matzkies Shareholder of: Gilead, Employee of: Gilead, Beatrix Bartok Shareholder of: Gilead, Employee of: Gilead, Lei Ye Shareholder of: Gilead, Employee of: Gilead, Ying Guo Shareholder of: Gilead, Employee of: Gilead, Chantal Tasset Shareholder of: Warrants from Galapagos, Employee of: Galapagos, John Sundy Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Neelufar Mozaffarian Shareholder of: Gilead, Employee of: Gilead (former employee), Robert B.M. Landewé: None declared, Sang-Cheol Bae: None declared, Edward C. Keystone Grant/research support from: AbbVie, Amgen, Gilead Sciences, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, PuraPharm, Sanofi, Consultant for: AbbVie, Amgen, AstraZeneca Pharma, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis, Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Sanofi Genzyme, UCB, Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, MSD, Celgene, Gilead, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, MSD, Celgene, Gilead, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, MSD, Celgene, Gilead

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