P520 Thromboembolic and major adverse cardiovascular events among patients in the filgotinib clinical trial programme
van der Woude, J.(1)*;Schreiber , S.(2);Peyrin-Biroulet , L.(3);Szekanecz, Z.(4);Choy, E.H.(5);Stiers, P.J.(6);Van Hoek, P.(7);Van Beneden, K.(8);de Haas, A.(9);Rudolph , C.(10);ten Cate, H.(11);
(1)Erasmus Medical Center Hospital, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands;(2)University Hospital Schleswig-Holstein, Department Medicine I, Kiel, Germany;(3)University Hospital of Nancy, Division of Gastroenterology, Vandoeuvre-lès-Nancy, France;(4)University of Debrecen, Department of Rheumatology- Faculty of Medicine, Debrecen, Hungary;(5)Cardiff University School of Medicine, CREATE Centre- Section of Rheumatology- Division of Infection and Immunity, Cardiff, United Kingdom;(6)Galapagos NV, Biostatistics Department, Mechelen, Belgium;(7)Galapagos NV, Clinical Development Department, Mechelen, Belgium;(8)Galapagos NV, Medical Affairs Department, Mechelen, Belgium;(9)Galapagos NV, Clinical Development Department, Leiden, The Netherlands;(10)Galapagos NV, Medical Affairs Department, Leiden, The Netherlands;(11)Maastricht University Medical Centre, Department of Internal Medicine, Maastricht, The Netherlands;
Background
The once-daily, oral, Janus kinase 1 preferential inhibitor filgotinib (FIL) is approved for the treatment of moderately to severely active rheumatoid arthritis (RA) and ulcerative colitis (UC) in the UK, the EU and Japan.1 To further understand the safety profile of FIL across indications, we evaluated the risk of major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs) in patients treated with FIL 200 mg (FIL200) or FIL 100 mg (FIL100).
Methods
An integrated analysis was conducted with RA data from five phase 2/3 trials and two long-term extension (LTE) trials of FIL, and UC data from two phase 2/3 trials and one LTE trial of FIL (herein termed ‘overall’ data). Subgroup analyses by age and cardiovascular (CV) risk factors (excluding age) were conducted. Real-world data were extracted from a systematic literature review. Exposure-adjusted incidence rates (EAIRs) or incidence rates per 100 patient-years of exposure and 95% confidence intervals (CIs) were estimated for MACEs and VTEs. For clinical trial data, MACEs and VTEs included positively adjudicated events only.
Results
In pooled data, baseline characteristics were generally similar across treatment arms for RA and UC (Tables 1 and 2). In the RA data, MACE EAIRs were 0.29 and 0.41 for the overall FIL200 and FIL100 arms, respectively (Figure 1). MACE IRs were 0.45–0.77 for the general RA population. Higher MACE EAIRs were reported in the subgroup of patients with RA aged ≥65 years vs <65 years. In the RA subgroup with CV risk, MACE EAIRs were 0.53 for FIL200 and 0.64 for FIL100. VTE rates were 0.19 for both FIL200 and FIL100 overall in patients with RA, and 0.32–0.44 for the general RA population. Numerically higher VTE EAIRs with overlapping CIs were seen in patients with RA aged ≥65 years vs <65 years, and in those with vs without CV risk.
In the UC data, MACE rates were 0.29, 0.35 and 0.87 in the overall FIL200 and FIL100 arms and in the general UC population, respectively (Figure 2). VTE rates were 0.08, 0.18 and 0.39 in the overall FIL200 and FIL100 arms and in the general UC population, respectively. For both MACE and VTE EAIRs, wide CIs were reported in patients with UC aged ≥65 years and in those with CV risk, owing to low numbers of events and/or patients in these subgroups.
Conclusion
No association was identified between FIL200 treatment and an increased risk of MACEs or VTEs compared with the general RA or UC population. Patients aged ≥65 years or with CV risk had slightly higher rates of MACEs and VTEs than those in other subgroups; however, overlapping CIs suggested no real difference. Further work should examine real-world data from FIL-treated patients and longer follow-up.
1. https://www.ema.europa.eu/en/medicines/human/EPAR/jyseleca