Major adverse cardiovascular, thromboembolic and malignancy events in the filgotinib rheumatoid arthritis and ulcerative colitis clinical development programmes

Objectives Long-term safety is fundamental for treatment decision-making. This integrated analysis of filgotinib clinical trials in rheumatoid arthritis (RA) and ulcerative colitis (UC) assessed adverse events of interest (AEI): major adverse cardiovascular events (MACE), venous thromboembolism (VTE) and malignancies. Methods Data were integrated from all phase II and III trials that have investigated filgotinib 100 mg or 200 mg once daily in RA and UC to date. Results Analyses represent >12 500 (RA) and >2800 (UC) patient-years of exposure (PYE) to filgotinib. Incidences of AEI in the integrated analysis population were low. Modest numerical increases in incidence rates occurred in patients aged >= 65 years, including MACE (patients with RA), and malignancies (excluding non-melanoma skin cancer (NMSC)) and NMSC (patients with RA or UC). VTE was rare; in patients with RA aged >= 65 years receiving filgotinib 200 mg, exposure-adjusted incidence rate (95% CI) for VTE was 0.3 (0.1, 0.8)/100 PYE; no VTE events occurred in patients with UC aged >= 65 years. In patients with RA aged >= 65 years, MACE incidence rates were identical between filgotinib 100 mg and 200 mg; rates of malignancies and NMSC were numerically higher with 200 mg compared with 100 mg. Conclusions Data are consistent with previous overall safety analyses demonstrating low rates of AEI in the overall study population. Numerically increased rates of AEI occurred in patients aged >= 65 years; further data are needed to assess the effect of CV risk factors. Overall, in this analysis, there was no consistent filgotinib dose effect on AEI.