Abstract
Background
Filgotinib (FIL) is an oral, potent, selective Janus kinase 1 inhibitor that has shown good efficacy and was well tolerated for treatment of rheumatoid arthritis (RA). The objective of this study was 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 randomised patients with active RA (3:3:2:3) to FIL 200mg, FIL 100mg, adalimumab [ADA] 40mg every 2 weeks, or PBO daily for up to 52 weeks; results through week 24 are presented. Patients also received background MTX. Primary efficacy endpoint was proportion of patients achieving ACR20 at week 12; additional clinical assessments included ACR50 and ACR70 and DAS28-CRP score ≤3.2 and <2.6, and patient-reported outcomes including HAQ-DI. Safety endpoints included adverse event types and rates. Logistic regression was used for superiority test of FIL vs PBO for ACR response and other binary endpoints, while mixed-effect model for repeated measures (MMRM) were 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 randomised, 1,755 received study drug: 475 FIL 200mg; 480 FIL 100mg; 325 ADA; and 475 PBO, of which 89.5%, 90.4%, 88.9%, and 81.3%, respectively, completed 24 weeks of study drug. 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 improvement vs PBO (Table 1). More patients receiving FIL achieved ACR50 and ACR70 improvements, DAS28-CRP scores ≤3.2 and <2.6 and reported improvements in HAQ-DI scores versus PBO (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.
Conclusion
FIL 200mg and 100mg led to significant improvement in signs and symptoms of RA, prevented radiographic progression, improved physical function compared to PBO, and was well-tolerated. Efficacy of FIL 200mg was non-inferior to ADA based on DAS28-CRP ≤3.2.
Disclosures
D. Walker: Other; Received support from Lilly, Pfizer, Novartis and Roche. B.G. Combe: Honoraria; Received honoraria from AbbVie, BMS, Gilead, Janssen, Eli Lilly and Co., MSD, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB. A.J. Kivitiz: Consultancies; Consultant to AbbVie, Celgene, Horizon, Jansses, Merck, Novartis, Pfizer, UCB, Genzyme, Sanofi, Regeneron, SUN Pharma Advanced Research, Boehringer Ingelheim, Flexion and Novartis. Shareholder/stock ownership; Shareholder of Novartis. Y. Tanaka: Honoraria; Honoraria from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly ans Co., Pfizer, AbbVie, YL Biologics, BMS, Takeda, Misubishi-Tanabe, Novartis, Eisai, Janssen, Teijin. Grants/research support; Grant support from Asahi-Kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, BMS, UCB, Daiichi-Sankyo, Eisai, Ono, Astellas, Eli Lilly, Pfizer, Abbvi and YL. D. van der Heijde: Corporate appointments; Director of Imaging Rheumatology bv. Consultancies; Consultant for 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, and UCB. F. Matzkies: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. B. Bartok: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. L. Ye: 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. R.B.M. Landewé: Consultancies; Consultant for AbbVie, AstraZeneca, BMS, Galapagos, Pfizer, Eli Lilly, Novartis, and UCB.. S. Bae: None. E.C. Keystone: Consultancies; Consultant for AbbVie, Amgen, AstraZeneca Pharma, Biotest, BMS Canada, Celltrion, Crescendo, Bioscience, F.Hoffman-La Roche Inc., Genentech, Janssen, Eli Lilly and Co., Merck, Pfizer,, PuraPharm, Sandoz, Sanofi-Aventis, Sanofi-Genzyme, Samsumg Bioepsis, and UCB. P. Nash: Consultancies; Consultant for AbbVie, BMS, Jansses, Pfizer, Roche, Lilly, Sanofi, MSD, Novartis, Celgene and Gilead.
Changes in Cortical Activity in Stroke Survivors Undergoing Botulinum Neurotoxin Therapy for Treatment of Focal Spasticity
