Filgotinib Demonstrates Efficacy in Rheumatoid Arthritis Independent of Smoking Status: Post Hoc Analysis of Phase 3 Trials and Claims-Based Analysis

Abstract

Objectives: To assess cigarette smoking's effects on efficacy of the preferential Janus kinase (JAK) 1 inhibitor filgotinib and drug persistence in patients with rheumatoid arthritis (RA).

Methods: Efficacy in non-smokers, former smokers, and current smokers from phase 3 filgotinib trials was analyzed, including patients with inadequate response (IR) to methotrexate (MTX) or biologic disease-modifying antirheumatic drugs (bDMARDs) or who were MTX-naïve. Proportions achieving Disease Activity Score in 28 joints with C-reactive protein (DAS28[CRP]) ≤ 3.2 were compared using logistic regression. Retrospective claims-based switching data were reviewed.

Results: Week 12 (W12) DAS28(CRP) ≤ 3.2 was achieved by 50, 61, and 62% of MTX-IR non-smokers, former smokers, and current smokers taking filgotinib 200 mg (FIL200) + MTX vs. 23, 16, and 32% taking placebo + MTX (p < 0.001, < 0.001, and 0.001) and 50, 34, and 33% taking adalimumab + MTX (p = 0.97, 0.013, and 0.006 vs. FIL200 + MTX). W12 DAS28(CRP) ≤ 3.2 was achieved by 46, 48, and 32% of bDMARD-IR non-smokers, former smokers, and current smokers taking FIL200 + conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) vs. 16, 23, and 5% taking placebo + csDMARD (p < 0.001, 0.077, and 0.051); 57, 58, and 59% of respective MTX-naïve smoking groups achieved W12 DAS28(CRP) ≤ 3.2 with FIL200 + MTX vs. 28, 37, and 18% with MTX (p < 0.001, 0.026, and < 0.001). Claims data showed former/current smokers were likelier than non-smokers to switch from adalimumab to other biologics or JAK inhibitors.

Conclusions: Greater proportions of MTX-IR current/former smokers responded to FIL200 + MTX vs. adalimumab + MTX. In non-smoking MTX-IR, bDMARD-IR, and MTX-naïve patients with RA, FIL200 + MTX demonstrated increased response vs. controls. Current/former smokers were likelier to discontinue adalimumab vs. non-smokers in real-world clinical settings.

Trial registration: NCT02889796, NCT02873936, NCT02886728.

Keywords: Arthritis; JAK inhibitors; Rheumatoid; Smoking; Tumor necrosis factor inhibitors.

Fig. 1

Week 12 DAS28(CRP) ≤ 3.2 response rate at week 12 by smoking status among patients with MTX-IR in a adalimumab and placebo groups, b filgotinib and adalimumab groups, and c filgotinib and placebo groups. p values refer to stratified comparison between treatment groups by smoking status (linear regression). p values are nominal, without adjustment for multiple testing. DAS28(CRP) disease activity score in 28 joints with C-reactive protein, MTX methotrexate, MTX-IR inadequate response to MTX

Fig. 2

Risk of switching from first bDMARD in patients with RA by smoker status. Estimate of > 1 represents a greater likelihood of current/former smokers switching to a second biologic compared with non-smokers. Covariates included sex, age, disease duration, prior corticosteroid use, and previous/current csDMARD use. bDMARD biologic DMARD, csDMARD conventional synthetic DMARD, CTLA4 cytotoxic T-lymphocyte associated protein 4, DMARD disease-modifying antirheumatic drug, IL6R interleukin 6 receptor, RA rheumatoid arthritis, TNF tumor necrosis factor