Efficacy and safety of filgotinib in methotrexate-naive patients with rheumatoid arthritis with poor prognostic factors: post hoc analysis of FINCH 3

Abstract

Objective: This analysis evaluated efficacy and safety of filgotinib, a Janus-associated kinase 1-preferential inhibitor, in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) with multiple poor prognostic factors (PPFs).

Methods: This was a post hoc analysis of the phase III, randomised, double-blind, active-controlled, FINCH 3 study (clinicaltrials.gov NCT02886728). Patients received once-daily oral filgotinib 200 or 100 mg plus once-weekly oral MTX ≤20 mg (FIL200 + MTX and FIL100 + MTX), filgotinib 200 mg monotherapy (FIL200), or oral MTX monotherapy (MTX-mono) for up to 52 weeks. PPFs investigated were seropositivity for rheumatoid factor or anticyclic citrullinated peptide antibodies, high-sensitivity C reactive protein (CRP) ≥4 mg/L, Disease Activity Score in 28 joints with CRP (DAS28(CRP)) >5.1, and presence of erosions. Filgotinib efficacy and safety in patients with all four PPFs at baseline were explored versus MTX-mono within this subgroup and compared informally with the overall population.

Results: Of 1249 patients in FINCH 3, 510 (40.8%) had all PPFs. Efficacy of FIL200 + MTX among these patients was comparable to the overall population, with higher rates of 20%/50%/70% improvement from baseline by American College of Rheumatology criteria, DAS28(CRP) <2.6, and remission; greater improvement in physical function and pain; and better inhibition of structural damage relative to MTX-mono. FIL100 + MTX and FIL200 were not consistently more efficacious versus MTX-mono. Safety of filgotinib in patients with PPFs was comparable to the overall population; no new safety signals were observed.

Conclusion: FIL200 + MTX efficacy and safety in patients with multiple PPFs were similar to the overall population.

Keywords: antirheumatic agents; arthritis; rheumatoid; therapeutics.

Conflict of interest statement

Competing interests: DA reports grants or research support from AbbVie, Merck Sharp & Dohme, Novartis, and Roche; serving as a consultant for Janssen; serving on a speaker’s bureau for Bristol-Myers Squibb, Merck Sharp & Dohme and UCB; and serving as a consultant and on a speaker’s bureau for AbbVie; Amgen; Celgene; Eli Lilly; Medac; Merck; Novartis; Pfizer; Roche; Sandoz; and Sanofi/Genzyme. RW reports grant/research support from and serving as a consultant for Celltrion; Galapagos; and Gilead Sciences, Inc. CG-V reports serving as a consultant and on a speaker’s bureau for AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB. GA reports serving as a consultant for Amgen and Theramex. AM reports grants or research support from AbbVie; Bristol-Myers Squibb; Eli Lilly; Galapagos; Gilead Sciences, Inc.; GlaxoSmithKline; Janssen; Novartis; Pfizer; Sanofi; UCB; and Regeneron; and serving as a consultant for AbbVie; Gilead Sciences, Inc; GlaxoSmithKline; and Novartis. PB reports serving as a consultant and on a speaker’s bureau for AbbVie, Celgene, Eli Lilly, Janssen, Novartis and Pfizer. ODM reports serving on a speaker’s bureau for Amgen, Pfizer and Americas Health Foundation. MHB reports grants or research support from Pfizer, Roche and UCB; and serving as a consultant for AbbVie; Eli Lilly; Gilead Sciences, Inc; Serono; Sandoz; and Sanofi. BB, ZY and YG are employees and shareholders of Gilead Sciences, Inc. TH is an employee and shareholder of Galapagos BV. GRB reports serving as a consultant and on a speaker’s bureau for AbbVie; Eli Lilly; Pfizer; and Gilead Sciences, Inc.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Proportions of patients achieving ACR20/50/70 at (A) week 12, (B) week 24 and (C) week 52. Error bars represent the 95% CI. #p<0.05, ###p<0.001 versus MTX; *nominal p<0.05, **nominal p<0.01, ***nominal p<0.001 versus MTX. ACR20/50/70, 20%/50%/70% improvement from baseline in American College of Rheumatology core criteria; FIL, filgotinib; MTX, methotrexate; PPF, patients with four poor prognostic factors.

Figure 2

(A) Proportions of patients with four PPFs (left) and the overall population (right) achieving low disease activity at weeks 24 and 52. (B) Proportions of patients with four PPFs (left) and all FINCH 3 patients (right) achieving DAS28(CRP) ###p<0.001, *nominal p<0.05, **nominal p<0.01, ***nominal p<0.001 versus MTX. CDAI, Clinical Disease Activity Index; DAS28(CRP), Disease Activity Score in 28 joints with C reactive protein; FIL, filgotinib; MTX, methotrexate; PPF, patients with four poor prognostic factors; SDAI, Simplified Disease Activity Index.

Figure 3

Treatment effect of filgotinib regimens versus MTX monotherapy on change from baseline in (A) CDAI and (B) SDAI at weeks 12, 24 and 52. CDAI, Clinical Disease Activity Index; FIL, filgotinib; LSM, least squares mean; MTX, methotrexate; PPF, patients with four poor prognostic factors; SDAI, Simplified Disease Activity Index.

Figure 4

Number of patients needed to treat with (A) filgotinib 200 mg plus MTX, (B) filgotinib 100 mg plus MTX or (C) filgotinib 200 mg monotherapy versus MTX monotherapy for one additional patient to achieve clinical endpoints. 95% CI of NNT not shown where the 95% CI of the rate difference between FIL and MTX spanned 0. ACR20/50/70, 20%/50%/70% improvement from baseline in American College of Rheumatology core criteria; CDAI, Clinical Disease Activity Index; DAS28(CRP), disease activity score in 28 joints with C reactive protein; FIL, filgotinib; MTX, methotrexate; NNT, number needed to treat; PPF, patients with four poor prognostic factors; SDAI, Simplified Disease Activity Index.

Figure 5

Treatment difference versus MTX monotherapy in change from baseline in (A) HAQ-DI and (B) patient pain assessment at weeks 24 and 52. aNot adjusted for multiplicity except where indicated. bAdjusted for multiplicity. FIL, filgotinib; HAQ-DI, health assessment questionnaire-disability index; LS, least squares; MTX, methotrexate; PPF, patients with four poor prognostic factors.

Figure 6

Change in mTSS from baseline at (A) week 24 and (B) week 52. *Nominal p<0.05, **nominal p<0.01. FIL, filgotinib; LS, least squares; mTSS, van der Heijde modified total Sharp score; MTX, methotrexate.