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.