Effect of Filgotinib on Body Mass Index (BMI) and Effect of Baseline BMI on the Efficacy and Safety of Filgotinib in Rheumatoid Arthritis

Abstract

Introduction: This post hoc analysis of the phase 3 rheumatoid arthritis (RA) filgotinib clinical trial program assessed the effect of filgotinib on body mass index (BMI) in patients with RA and the impact of BMI on the efficacy and safety of filgotinib. Methods: FINCH 1–3 were randomized, double-blind, active- or placebo-controlled phase 3 trials of filgotinib 100 and 200 mg in patients with RA (N = 3452). BMI assessments included the mean change from baseline in BMI and the proportion of patients whose BMI increased by incremental thresholds. Efficacy measures included American College of Rheumatology (ACR) 20/50/70 response and low disease activity/remission according to Disease Activity Score 28 using C-reactive protein. The exposure-adjusted incident rate (EAIR) of adverse events (AEs) was assessed by baseline BMI, using integrated data from the FINCH 1–4 and the phase 2 DARWIN 1–3 studies (total filgotinib exposure = 8085 patient-years). Results: Mean change from baseline in BMI over time was similar across treatment arms. In most patients, BMI increased by ≤ 1 or 2 kg/m2 at both weeks 12 and 24, regardless of treatment group or baseline BMI; few patients had increases of ≥ 4 kg/m2. For most efficacy measures, filgotinib 200 mg was more efficacious than filgotinib 100 mg or active comparators or placebo across BMI subgroups. For the higher filgotinib dose, the EAIR of serious treatment-emergent AEs, venous thrombotic and embolic events, and major adverse cardiovascular events increased with increasing BMI. Conclusions: Filgotinib did not lead to substantial changes in BMI, and BMI did not appear to affect the efficacy of filgotinib. Trial Registration: ClinicalTrials.gov identifiers: NCT02889796, NCT02873936, NCT02886728, NCT03025308, NCT01888874, NCT01894516, NCT02065700.