Integrated safety analysis of filgotinib in patients with moderate-to-severe rheumatoid arthritis over a treatment duration of up to 8.3 years.

Autor:	Burmester GR; Charité - Universitätsmedizin Berlin, Berlin, Germany gerd.burmester@charite.de., Gottenberg JE; Strasbourg University Hospital, Strasbourg, France., Caporali R; ASST Gaetano Pini-CTO & University of Milan, Milan, Italy., Winthrop KL; Oregon Health & Science University, Portland, Oregon, USA., Tanaka Y; University of Occupational and Environmental Health, Kitakyushu, Japan., Ekoka Omoruyi EV; Galapagos NV, Mechelen, Belgium., Rajendran V; Galapagos NV, Mechelen, Belgium., Van Hoek P; Galapagos NV, Mechelen, Belgium., Van Beneden K; Galapagos NV, Mechelen, Belgium., Takeuchi T; Keio University, Tokyo, Japan.; Saitama Medical University, Saitama, Japan., Westhovens R; Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium., Aletaha D; Medical University of Vienna, Vienna, Austria.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2024 Aug 27; Vol. 83 (9), pp. 1110-1117. Date of Electronic Publication: 2024 Aug 27.
DOI:	10.1136/ard-2024-225759
Abstrakt:	Objectives: To update the long-term safety profile of filgotinib, a Janus kinase-1 preferential inhibitor, in patients with moderate-to-severe rheumatoid arthritis. Methods: Data from seven trials were integrated (NCT01888874, NCT01894516, NCT02889796, NCT02873936, NCT02886728, NCT02065700 and NCT03025308). Patients received once-daily filgotinib 100 mg or 200 mg. Exposure-adjusted incidence rates (EAIRs)/100 patient-years of exposure (PYE) were calculated for treatment-emergent adverse events (TEAEs). Post hoc analyses assessed patients aged <65 and ≥65 years. Results: Patients (N=3691) received filgotinib for a median (maximum) of 3.8 (8.3) years (12 541 PYE). Rates of TEAEs of interest: serious infections, malignancies, major adverse cardiovascular events (MACE) and venous thromboembolism were stable over time and comparable between doses. In the overall population, numerically lower EAIR (95% CI)/100 PYE of herpes zoster was observed for filgotinib 100 mg versus 200 mg (1.1 (0.8 to 1.5) vs 1.5 (1.2 to 1.8)). Incidence of serious infections, herpes zoster, MACE, malignancies and all-cause mortality was higher in patients aged ≥65 versus <65 years. In patients aged ≥65 years, EAIRs (95% CI)/100 PYE for non-melanoma skin cancer (NMSC) (0.4 (0.1 to 1.1) vs 1.4 (0.8 to 2.2)), malignancies excluding NMSC (1.0 (0.5 to 1.9) vs 2.0 (1.3 to 2.9)) and all-cause mortality (1.3 (0.7 to 2.2) vs 1.6 (1.0 to 2.5)) were numerically lower for filgotinib 100 mg versus 200 mg. Conclusions: In the overall population, TEAEs of interest were stable over time and similar between filgotinib 100 mg and 200 mg dose groups, except for herpes zoster. A dose-dependent relationship between malignancies and all-cause mortality was suggested in patients ≥65 years old. Competing Interests: Competing interests: GRB reports consultancy fees from AbbVie, Amgen, BMS, Galapagos, Lilly, Pfizer and Sanofi; and speakers’ bureau fees from AbbVie, Amgen, BMS, Chugai, Galapagos, Lilly, Pfizer and Sanofi. J-EG reports consultancy fees from AbbVie, BMS, Galapagos, Gilead, Lilly, MSD, Novartis and Pfizer; and grant/research support from BMS and Pfizer. RC reports consultancy fees from AbbVie, Fresenius, Galapagos, Lilly, Pfizer, Novartis and UCB; speakers’ bureau fees from AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer and UCB. KLW reports consultancy fees from AbbVie, AstraZeneca, BMS, Eli Lilly & Company, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB; and grant/research support from BMS and Pfizer. YT has received speaker fees and/or honoraria from AbbVie, Asahi Kasei, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Taiho, Taisho and Pfizer; and research grants from Asahi Kasei, Chugai, Eisai, Mitsubishi Tanabe and Taisho. EVEO is a consultant for Galapagos. VR is a former employee of, and shareholder in, Galapagos. PVH is a consultant for AOP Health, Aspen and Galapagos; and a previous employee of Janssen, MSD and Schering-Plough. KVB is an employee of, and shareholder in, Galapagos. TT reports consultancy fees from AbbVie GK, Astellas, Chugai, Eli Lilly Japan, Gilead, Janssen Pharma K.K., Mitsubishi Tanabe and Pfizer Japan; speakers’ bureau fees from AbbVie GK, AYUMI, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Gilead, Janssen Pharma K.K., Mitsubishi Tanabe, Pfizer Japan and Sanofi K.K.; and research/grant support from AbbVie GK, Asahi Kasei, Astellas, AYUMI, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Mitsubishi Tanabe, Nippon Kayaku and UCB Japan. RW acted as an adviser and speaker for Celltrion, Galapagos and Gilead. DA reports consultancy fees, speakers’ bureau fees and grant/research support from AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz and Sanofi. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)
Databáze:	MEDLINE
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