POS0051 AN UPDATE ON THE INTEGRATED SAFETY ANALYSIS OF FILGOTINIB IN PATIENTS WITH MODERATE TO SEVERE ACTIVE RHEUMATOID ARTHRITIS OVER A MEDIAN OF 4.3 YEARS
Authors: K. L. Winthrop, D. Aletaha, R. F. Caporali, Y. Tanaka, T. Takeuchi, V. Modgill, E. V. Ekoka Omoruyi, D. De Vries, K. Van Beneden, J. E. Gottenberg, G. R. Burmester
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The oral Janus kinase 1-preferential inhibitor filgotinib (FIL) is approved at doses of 100 mg (FIL100) and 200 mg (FIL200) for the treatment of moderate to severe active rheumatoid arthritis. Previous integrated safety analyses from clinical trials have shown that safety and tolerability is broadly similar between the FIL doses, with a lower incidence of herpes zoster with FIL100 vs FIL 200.[1] <h3>Objectives:</h3> To provide an update on selected treatment-emergent adverse events for FIL up to a median (maximum) exposure of 4.3 (8.3) years. <h3>Methods:</h3> FIL rheumatoid arthritis data were integrated from 7 clinical trials: the Phase 2 DARWIN studies (NCT01888874, NCT01894516), the Phase 3 FINCH studies (NCT02889796, NCT02873936, NCT02886728) and the long-term extension studies DARWIN 3 (NCT02065700) and FINCH 4 (NCT03025308). Exposure-adjusted incidence rates (EAIRs)/100 patient-years of exposure (PYE), censored at time of first event, were determined for major adverse cardiovascular events (MACE), venous thromboembolism (VTE), arterial systemic thromboembolism (ASTE), nonmelanoma skin cancer (NMSC), malignancies (excluding NMSC), herpes zoster, serious infections and deaths. Data were from completed studies and up until May 8, 2023, for FINCH 4. MACE and VTE only include positively adjudicated events with a data cutoff of May 8, 2023. <h3>Results:</h3> In total, 3,691 patients received FIL, with a total exposure of 14,127 PYE. Median (maximum) exposure was 4.3 (8.3) years in the pooled FIL group, 3.6 (8.1) years for FIL100 and 4.4 (8.3) years for FIL200. Baseline demographics and disease characteristics were balanced between the dose groups.[2] Incidences of adverse events of special interest (AESIs), including MACE, VTE, ASTE, NMSC, malignancies (excluding NMSC), serious infections, herpes zoster and all-cause mortality, were comparable between the data cut in 2022 and the current analysis (<b>Table 1</b>). The EAIR (95% confidence interval [CI])/100 PYE of serious infections was 2.2 (1.8, 2.6) and 1.7 (1.5, 2.0) in the FIL100 and FIL200 dose groups, respectively. The EAIR (95% CI)/100 PYE of herpes zoster was 1.1 (0.8, 1.4) for FIL100 and 1.4 (1.2, 1.7) for FIL200 (<b>Table 1</b>). Owing to the study designs, duration of exposure was shorter in the FIL100 (5,202.2 PYE) than in the FIL200 group (8,924.5 PYE); comparisons of EAIRs between treatment groups should therefore be made with caution. Over 312 weeks, the risk of all-cause mortality was similar for FIL100 and FIL200 (<b>Figure 1</b>). <h3>Conclusion:</h3> In this updated integrated safety analysis, the safety profile of FIL remains stable over time and similar to that from the previous analysis. No new safety information concerning AESIs were identified in the overall rheumatoid arthritis population. <h3>REFERENCES:</h3> [1] Winthrop KL, et al. Ann Rheum Dis 2023;82:721–22. [2] Winthrop KL, et al. Ann Rheum Dis 2022;81:184–92. <h3>Acknowledgements:</h3> The FINCH and DARWIN studies were co-funded by Gilead Sciences, Inc. (Foster City, CA, USA) and Galapagos NV (Mechelen, Belgium). The authors would like to acknowledge statistical programming support provided by Benjamin Pett and Mohsine El Ghazi (Galapagos NV). Medical writing support was provided by Iain Haslam, PhD, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV. Publication coordination was provided by Jo-Ann E. West, MSc, a consultant funded by Galapagos NV. <h3>Disclosure of Interests:</h3> Kevin L. Winthrop AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB, BMS and GSK, Daniel Aletaha AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz and Sanofi, AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz and Sanofi, AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz and Sanofi, Roberto F. Caporali AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer and UCB, AbbVie, Accord, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, Novartis, Pfizer and UCB, Yoshiya Tanaka AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho and Taisho, Chugai, Eisai, Mitsubishi Tanabe and Taisho, Tsutomu Takeuchi AbbVie GK, AYUMI, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Gilead, Janssen Pharma K.K., Mitsubishi Tanabe, Pfizer Japan and Sanofi K.K., AbbVie GK, Astellas, Chugai, Eli Lilly Japan, Gilead, Janssen Pharma K.K., Mitsubishi Tanabe and Pfizer Japan, AbbVie GK, Asahi Kasei Pharma, Astellas, AYUMI, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Mitsubishi Tanabe, Nippon Kayaku and UCB Japan, Vikas Modgill Galapagos, Galapagos, Edmund V. Ekoka Omoruyi UCB, Galapagos and Janssen, Dick de Vries Galapagos, Galapagos, Katrien Van Beneden Galapagos, Galapagos, Jacques-Eric Gottenberg AbbVie, BMS, Eli Lilly, Galapagos, Gilead, MSD, Novartis and Pfizer, BMS and Pfizer, Gerd R. Burmester AbbVie, BMS, Eli Lilly, Galapagos, MSD and Pfizer, AbbVie, BMS, Eli Lilly, Galapagos, MSD and Pfizer.