0281: Clinical Outcomes of Filgotinib in Patients with RA Aged ≥65 Years: A Post Hoc Subgroup Analysis of Phase 2 and 3 Clinical Trials and Ongoing Long-Term Extensions

Maya Buch¹, BERNARD COMBE², Jose A Gomez-Puerta³, Roberto Felice Caporali⁴, jacques-eric gottenberg⁵, Paul Van Hoek⁶, Vijay Rajendran⁷, Pieter-Jan Stiers⁶, Katrien Van Beneden⁶, Daniel Aletaha⁸, Gerd Burmester⁹, Rene Westhovens¹⁰ and Yoshiya Tanaka¹¹, ¹University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester, United Kingdom, ²Montpellier University, Montpellier, France, ³Hospital Clínic de Barcelona, Barcelona, Spain, ⁴University of Milan, Milano, Italy, ⁵Strasbourg University Hospital, Strasbourg, France, ⁶Galapagos NV, Mechelen, Belgium, ⁷Galapagos NV, Gent, Belgium, ⁸Medical University Vienna, Wien, Austria, ⁹Charité University Medicine Berlin, Berlin, Germany, ¹⁰University Hospitals Leuven, Leuven, Belgium, ¹¹University of Occupational and Environmental Health, Kitakyusyu Fukuoka, Japan

Background/Purpose: Filgotinib (FIL) is a Janus kinase 1 preferential inhibitor approved for the treatment of moderate to severe active RA.¹ It was previously reported that a numerically higher proportion of patients (pts) aged ≥65 vs < 65 y had an adverse event (AE), serious AE, or serious infection in the FIL 200 mg (FIL200) group of the pooled phase 2 and 3 safety studies.² Here 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 < 65 and ≥65 y using data from the phase 2 DARWIN 1 (NCT01888874) and 2 (NCT01894516) trials; phase 3 FINCH 1 (NCT02889796), 2 (NCT02873936), and 3 (NCT02886728) trials; and DARWIN 3 (NCT02065700) and FINCH 4 (NCT03025308) long-term extension (LTE) trials. All pts with RA fulfilled 2010 ACR/EULAR criteria. Data were as of Jan 11, 2022 (DARWIN 3) and Jan 31, 2022 (FINCH 4). Analyses were 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 (< 65 vs ≥65 y) are presented. EAIR and 95% confidence intervals (CIs) were calculated. Proportions of pts aged < 65 and ≥65 y 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: In this pooled analysis, pts aged ≥65 y had higher proportions of cardiovascular (CV) risk factors at baseline vs those < 65 y (Table 1). A higher proportion of pts aged < 65 vs ≥65 y were current smokers. A larger proportion of pts in the ≥65 vs < 65 y age group were from North America. EAIRs of AESIs were generally higher in pts aged ≥65 than < 65 y (Table 2). In pts aged ≥65 y, the EAIRs of adjudicated major adverse cardiovascular events, venous thromboembolisms, serious infections, 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 ≥65 y age group, but not in the < 65 y age group, with FIL200 vs FIL100. The most reported fatal outcomes with FIL200 in the ≥65 y age group were malignancies, cardiac disorders, and infections and infestations. ACR20/50/70 and DAS28-CRP LDA rates in pts aged < 65 and ≥65 y in FINCH 4 were maintained or numerically higher with FIL200 to Week 144 (Table 3).

Conclusion: In this post hoc integrated safety analysis, the EAIRs of AESIs were generally higher in pts aged ≥65 y than < 65 y, which is to be expected in an older population. 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 ≥65 but not < 65 y. In FINCH 4, efficacy was generally maintained in both age groups. Limitations include the ad hoc nature of the analysis, overlapping CIs, lack of comparator data, and potential LTE bias.

References:
1. Jyseleca SmPC. Galapagos NV; May 2022
2. Jyseleca EPAR. Galapagos NV; Sep 2020

Table 1. Baseline demographics and disease characteristics by age category ( < 65 vs ≥65 y)

Table 2. AESIs and overview of ≥1 TEAE leading to death by age category ( < 65 vs ≥65 y; as-treated set)

Table 3. ACR20/50/70 and DAS28-CRP LDA response rates through Week 144 in FINCH 4 by age category ( < 65 vs ≥65 y; observed cases)
Disclosures: M. Buch, AbbVie, Galapagos, Gilead, Pfizer, Eli Lilly, Merck-Serono, Roche, UCB; B. COMBE, AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Janssen, Lilly, MSD, Pfizer, Roche-Chugai, Novartis; J. Gomez-Puerta, GSK, Galapagos, Pfizer, Janssen, Sanofi, AbbVie, Bristol Myers Squibb, Lilly, Novartis, MSD, Roche; R. Caporali, AbbVie, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Pfizer, Roche, UCB, Eli Lilly, Gilead, Sanofi; j. gottenberg, AbbVie, Bristol Myers Squibb, Galapagos, Gilead, Lilly, MSD, Novartis, Pfizer; P. Van Hoek, Galapagos; V. Rajendran, Galapagos; P. Stiers, Galapagos; K. Van Beneden, Galapagos; D. Aletaha, Novartis, SoBi, Sanofi, Amgen, Lilly, Merck, Pfizer, Roche, Sandoz, Janssen, AbbVie; G. Burmester, AbbVie, Galapagos, Lilly, MSD, Pfizer, Roche, UCB, Janssen, Gilead Sciences, Inc.; R. Westhovens, Celltrion, Galapagos, Gilead; Y. Tanaka, 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.