OA06 Clinical outcomes of filgotinib in patients with rheumatoid arthritis aged ≥65 years: a post hoc subgroup analysis of Phase 2 and 3 clinical trials and ongoing long-term extensions
Authors: Buch Maya H , Combe Bernard , Gómez-Puerta José A , Caporali Roberto , Gottenberg Jacques-Eric , Van Hoek Paul , Rajendran Vijay , Stiers Pieter-Jan , Van Beneden Katrien , Aletaha Daniel , Burmester Gerd , Westhovens René , Tanaka Yoshiya 
Published: April 2023

Abstract

Background/Aims
Filgotinib (FIL) is a Janus kinase 1 preferential inhibitor approved for treatment of moderate-severe active RA. A numerically higher proportion of patients (pts) ≥65y vs &lt; 65y had an adverse event (AE), serious AE, or serious infection (SI) in the FIL 200 mg (FIL200) group of the pooled phase 2 and 3 safety studies. We report updated data on AEs of special interest (AESIs) and efficacy in these age groups.

Methods
This post hoc analysis assessed safety and efficacy in pts aged &lt;65y and ≥65y using data from phase 2 DARWIN 1 (NCT01888874) and 2 (NCT01894516); phase 3 FINCH 1 (NCT02889796), 2 (NCT02873936), and 3 (NCT02886728); and DARWIN 3 (NCT02065700) and FINCH 4 (NCT03025308) long-term extension (LTE) trials. All pts with RA fulfilled 2010 ACR/EULAR criteria. Data as of Jan 11, 2022 (DARWIN 3) and Jan 31, 2022 (FINCH 4). Analyses performed on an ad hoc interim analysis data set without additional cleaning. The as-treated analysis set included all available data for pts receiving ≥1 FIL dose (FIL200/FIL 100 mg [FIL100]), including those rerandomized to FIL in the LTE. Censored exposure-adjusted incidence rates (EAIRs)/100 patient-years of exposure of AESIs by age category (&lt;65y vs ≥ 65y) are presented. EAIR and 95% confidence intervals (CIs) were calculated. Proportions of pts aged &lt;65y and ≥65y achieving a 20, 50 and 70% improvement in ACR criteria (ACR20/50/70) and DAS28-CRP low disease activity (LDA) at Week 144 in FINCH 4, estimated using observed cases, are reported.

Results
Patients ≥65y had higher proportions of cardiovascular (CV) risk factors at baseline vs those &lt;65y. EAIRs of AESIs were generally higher in pts aged ≥65y than &lt;65y. In pts aged ≥65y, the EAIRs of adjudicated major adverse cardiovascular events, venous thromboembolisms, SI, and herpes zoster differed between the 2 FIL doses with partly or largely overlapping CIs. The EAIRs of nonmelanoma skin cancer (NMSC), malignancies (excluding NMSC), and treatment-emergent AE (TEAE) leading to death were numerically higher in the ≥65y age group only, with FIL200 vs FIL100. The most reported fatal outcomes with FIL200 in the ≥65y age group were malignancies, cardiac disorders, and infections and infestations. ACR20/50/70 and DAS28-CRP LDA rates in pts aged &lt;65 and ≥65y in FINCH 4 were maintained or numerically higher with FIL200 to Week 144.

Conclusion
In this post hoc integrated safety analysis, the EAIRs of AESIs were generally higher in pts aged ≥65y than &lt;65y. A numerically higher incidence of NMSC, malignancies (excluding NMSC), and TEAEs leading to death was observed in the FIL200 vs FIL100 group in pts aged ≥65y only. In FINCH 4, efficacy was maintained in both age groups. Limitations include the ad hoc nature of analysis, overlapping CIs, lack of comparator data, and potential LTE bias.
Disclosure
M.H. Buch: Other; AbbVie, Galapagos, Gilead, Pfizer, Eli Lilly, Merck-Serono, Roche, UCB. B. Combe: Other; AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, MSD, Pfizer, Roche-Chugai, Novartis. J.A. Gómez-Puerta: Other; GSK, Galapagos, Pfizer, Janssen, Sanofi, AbbVie, Bristol Myers Squibb, Lilly, Novartis, MSD, Roche. R. Caporali: Other; AbbVie, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Pfizer, Roche, UCB, Eli Lilly, Gilead, Sanofi. J. Gottenberg: Other; AbbVie, Bristol Myers Squibb, Galapagos, Gilead, Lilly, MSD, Novartis, Pfizer. P. Van Hoek: Other; Galapagos. V. Rajendran: Other; Galapagos. P. Stiers: Other; Galapagos. K. Van Beneden: Other; Galapagos. D. Aletaha: Other; Novartis, SoBi, Sanofi, Amgen, Lilly, Merck, Pfizer, Roche, Sandoz, Janssen, AbbVie. G. Burmester: Other; AbbVie, Galapagos, Lilly, MSD, Pfizer, Roche, UCB, Janssen, Gilead Sciences, Inc. R. Westhovens: Other; Celltrion, Galapagos, Gilead. Y. Tanaka: Other; Lilly, AbbVie, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Pfizer, Mitsubishi Tanabe, GlaxoSmithKline, Asahi Kasei, Takeda, Astellas, Janssen, Novartis, Sanofi, UCB, YL Biologics, MSD, Ono, Taisho Toyama, Celltrion, Gilead, Boehringer-Ingelheim, Corrona, Kowa, Amgen, AstraZeneca, AstraZeneca, Eli Lilly.