P217 Efficacy and safety of filgotinib for patients with RA naïve to MTX therapy: FINCH3 primary outcome results
Authors: McKay Neil , van der Heijde Désirée , Westhovens Rene , Rigby William F. C , Ching Daniel W. T , Bartok Beatrix , Matzkies Franziska , Yin Zhaoyu , Guo Ying , Tasset Chantal , Sundy John S , Mozaffarian Neelufar , Messina Osvaldo D , Landewé Robert B. M , Atsumi Tatsuya , Burmester Gerd R 
Published: April 2020

Abstract

Background
Filgotinib (FIL), an orally administered, potent, selective inhibitor of janus kinase 1 (JAK1), has shown good efficacy and was well tolerated for treatment of rheumatoid arthritis (RA). The objectives of this study were to compare efficacy and safety of FIL with and without methotrexate (MTX) in patients with RA who were naïve to MTX therapy.

Methods
This Phase 3, double-blind, active-controlled study randomised patients with moderately to severely active RA (2:1:1:2) to FIL 200mg daily+MTX, FIL 100mg+MTX, FIL 200mg (+placebo [PBO]), or MTX (+PBO) up to 52 weeks; results are through week 24. Primary endpoint was proportion achieving ACR20 response at week 24. Safety endpoints included adverse events types and rates.

Results
Of 1,252 randomised patients, 1,249 received study drug (416 FIL 200mg+MTX; 207 FIL 100mg+MTX; 210 FIL 200mg monotherapy; 416 MTX monotherapy) and were analysed; 1,130 completed week 24. Most (76.9%) were female; mean time since RA diagnosis was 2.2 years (median 0.4 years); mean (standard deviation [SD]) DAS28-CRP was 5.7 (1.0); and 35.9% were using oral steroids at baseline. At week 24, significantly more patients in the FIL 200mg+MTX (81.0%; P&lt;0.001) and FIL 100mg+MTX (80.2%; P&lt;0.05) arms achieved an ACR20 response compared to MTX monotherapy (71.4%)(Table 1). Compared to MTX monotherapy, more patients receiving FIL with or without MTX achieved ACR50 and ACR70 responses, DAS28-CRP &lt;2.6 and ≤3.2, and reported improvements in SF-36 PCS (Table 1). The onset of activity was rapid, with significantly more patients achieving ACR50 and DAS28-CRP &lt;2.6 with FIL than MTX at week 2. The FIL safety profile was consistent with prior studies through week 24. Serious AEs were observed in 4.1%, 2.4%, 4.8%, and 2.9% of patients in the FIL 200mg+MTX, FIL 100mg+MTX, FIL 200mg monotherapy, and MTX monotherapy groups, respectively. There was 1 death from lupus cardiomyopathy.

Conclusion
The JAK1 inhibitor FIL in combination with MTX led to significant improvements in RA signs and symptoms, physical function, and patient-reported outcomes compared to MTX alone and was well tolerated in patients with early active RA naïve to MTX. Clinically meaningful response to FIL occurred as early as 2 weeks after treatment initiation.

Disclosures
N. McKay: None. D. van der Heijde: Corporate appointments; Director of Imaging Rheumatology bv. Consultancies; Consultant for AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda Pharmaceutical Company Ltd., UCB. R. Westhovens: Corporate appointments; Advisor for Celltrion and Galapagos/Gilead. Other; Advisor for Celltrion and Galapagos/Gilead. W.F.C. Rigby: Consultancies; Consultant for Gilead. D.W.T. Ching: Corporate appointments; Speaker for AbbVie. Member of speakers’ bureau; Speaker for AbbVie. B. Bartok: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. F. Matzkies: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Z. Yin: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. C. Tasset: Corporate appointments; Employee of Galapagos NV. J.S. Sundy: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. N. Mozaffarian: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. O.D. Messina: Honoraria; Received Honoraria from Pfizer, Amgen, and Americas Health Foundation (AHF). R.B.M. Landewé: Consultancies; Consultant for AbbVie, AstraZeneca, BMS, Galapagos, Pfizer, Eli Lilly, Novartis, and UCB. T. Atsumi: None. G.R. Burmester: Honoraria; Received Honoraria from AbbVie, Gilead, Eli Lilly, and Pfizer.