EFFICACY AND SAFETY OF FILGOTINIB IN PATIENTS AGED >= 75 YEARS: A POST HOC SUBGROUP ANALYSIS OF THE FINCH 4 LONG-TERM EXTENSION (LTE) STUDY

Background Filgotinib (FIL) is a Janus kinase 1 preferential inhibitor for the treatment of moderate to severe rheumatoid arthritis (RA) 1 . The recommended dose for adults with RA is 200 mg (FIL200); however, a starting dose of 100 mg (FIL100) is recommended for those aged ≥75 years (y) in view of limited clinical experience 1 . An important consideration is the generally higher incidence of adverse events (AEs) in the elderly due to comorbidities. Objectives To evaluate the efficacy and safety of FIL100 and FIL200 in patients with RA aged ≥75 y. Methods FINCH 4 ( NCT03025308 ) is an ongoing phase 3 open-label LTE study of FIL100 and FIL200 for RA. Eligible patients completed a prior phase 3 randomized double-blind study of FIL lasting 52 weeks (FINCH 1 or 3) or 24 weeks (FINCH 2). In this post hoc analysis, safety and efficacy were assessed in patients aged <75 and ≥75 y in FINCH 4. Efficacy measures were American College of Rheumatology (ACR)20/50/70 responses, clinical disease activity index (CDAI) ≤10/≤2.8, disease activity score (DAS)28 <2.6/≤3.2 and health assessment questionnaire-disability index (HAQ-DI). Results At LTE Week 48, 52% and 44% of patients aged <75 and ≥75 y, respectively, were on methotrexate. In both age groups, response rates for key efficacy measures at LTE Week 48 were generally maintained from LTE baseline (Figure 1) in patients with and without prior FIL exposure in FINCH 1–3, and were numerically higher with FIL200 vs FIL100. Mean change from baseline in HAQ-DI with FIL200 and FIL100 was 0.61 and 0.74 in those aged <75 y and 1.04 and 0.98 in those aged ≥75 y, respectively. Figure 1. The exposure-adjusted incidence rate (EAIR) of serious AEs and AEs of special interest (AESI) was generally higher in patients aged ≥75 y than <75 y. In those aged ≥75 y, the EAIR of AEs leading to premature study discontinuation, treatment-emergent AEs (TEAEs), and serious TEAEs was higher with FIL200 vs FIL100; the incidence of major adverse cardiovascular events, venous thrombotic and embolic events, serious infections, herpes zoster and malignancies was low in both dose groups (Table 1). Three patients died, all from the FIL200 group; each had a medical history relevant to the cause of death. Table 1. Exposure-adjusted incidence rate (95% CI) of AEs at Week 48 as events per 100 years of exposure FIL200 FIL100 Age, years <75 ≥75 <75 ≥75 n=1469 n=61 n=1136 n=63 (PYE 2253.9) (PYE 92.2) (PYE 1753.7) (PYE 98.4) With prior FIL exposure, n (%) 1142 (77.7) 53 (86.9) 830 (73.1) 33 (52.4) TEAE 48.3 (45.5, 51.3) 55.3 (42.1, 72.8) 48.7 (45.5, 52.1) 42.7 (31.6, 57.8) Serious TEAE 6.8 (5.8, 8.0) 17.4 (10.6, 28.3) 7.4 (6.2, 8.7) 14.2 (8.4, 24.0) AE leading to premature study discontinuation 2.9 (2.3, 3.7) 9.8 (5.1, 18.8) 3.9 (3.1, 5.0) 4.1 (1.5, 10.8) AE leading to death 0.5 (0.3, 0.9) 3.3 (0.7, 9.5)* 0.3 (0.2, 0.8) 0.0 (0.0, 3.8) Infections 28.8 (26.6, 31.1) 29.3 (20.1, 42.7) 27.4 (25.0, 29.9) 26.4 (18.0, 38.8) Serious infections 1.6 (1.2, 2.2) 2.2 (0.5, 8.7) 1.7 (1.1, 2.4) 3.1 (1.0, 9.5) Herpes zoster 1.6 (1.2, 2.3) 2.2 (0.5, 8.7) 1.0 (0.6, 1.6) 3.1 (1.0, 9.5) Adjudicated major adverse cardiovascular event 0.4 (0.2, 0.7) 2.2 (0.5, 8.7) 0.5 (0.2, 0.9) 1.0 (0.1, 7.2) Venous thrombotic and embolic events 0.3 (0.1, 0.6) 2.2 (0.5, 8.7) 0.2 (0.1, 0.5) 1.0 (0.1, 7.2) Malignancy excluding NMSC 0.7 (0.4, 1.2) 4.3 (1.6, 11.6) 0.7 (0.4, 1.2) 3.1 (1.0, 9.5) NMSC 0.4 (0.2, 0.8) 1.1 (0.0, 6.0) 0.2 (0.1, 0.6) 0.0 (0.0, 3.8) *Cause of death: esophageal carcinoma; cardiovascular; unknown. FIL(100/200), filgotinib (100/200 mg); NMSC, nonmelanoma skin cancer; PYE, patient years of exposure; (TE)AE, (treatment-emergent) adverse event Conclusion In the ≥75 y group, response rates for key efficacy measures remained stable to Week 48 and were generally higher with FIL200 vs FIL100. The incidence of serious AEs and AESI was higher in those aged ≥75 than <75 y. Patient numbers/exposure time may have been insufficient to show potential between-group differences in safety/efficacy outcomes. References [1]Filgotinib SmPC Acknowledgements The FINCH studies were funded by Gilead Sciences (Foster City, CA, United States). We thank the physicians and patients who participated in the studies. Medical writing support was provided by Debbie Sherwood, BSc (Aspire Scientific Ltd, Bollington, UK) and funded by Galapagos NV (Mechelen, Belgium). Disclosure of Interests Daniel Aletaha Speakers bureau: AbbVie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, and Sandoz, Consultant of: AbbVie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, and Sandoz, Grant/research support from: AbbVie, Amgen, Lilly, Novartis, Roche, SoBi, and Sanofi, Rene Westhovens Speakers bureau: Celltrion, Galapagos, and Gilead, Consultant of: Celltrion, Galapagos, and Gilead, Bernard Combe Speakers bureau: AbbVie, BMS, Celltrion, Eli Lilly, Gilead-Galapagos, Janssen, MSD, Novartis, Pfizer, and Roche-Chugai, Consultant of: AbbVie, Celltrion, Eli Lilly, Gilead-Galapagos, Janssen, and Roche-Chugai, Jacques-Eric Gottenberg Consultant of: AbbVie, BMS, Galapagos, Gilead, Lilly, and Pfizer, Grant/research support from: BMS and Pfizer, Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Galapagos, Gilead, and Pfizer, Grant/research support from: Gilead and Pfizer, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB, José A Gómez-Puerta Speakers bureau: AbbVie, BMS, Galapagos, GSK, Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi, Consultant of: GSK, Roche, and Sanofi, Paul Van Hoek Employee of: Galapagos, Vijay Rajendran Employee of: Galapagos, Pieter-Jan Stiers Shareholder of: Galapagos, Employee of: Galapagos, Thijs Hendrikx Employee of: Galapagos, Gerd Rüdiger Burmester Consultant of: AbbVie, Amgen, BMS, Galapagos, Lilly, MSD, Pfizer, Roche, and Sanofi, Yoshiya Tanaka Speakers bureau: AbbVie, Amgen, Astellas, Astra-Zeneca, Boehringer-Ingelheim, BMS, Chugai, Eisai, Eli Lilly, Gilead, Mitsubishi-Tanabe, and YL Biologics, Consultant of: AbbVie, Ayumi, Daiichi-Sankyo, Eli Lilly, GSK, Sanofi, and Taisho, Grant/research support from: AbbVie, Asahi-Kasei, Boehringer-Ingelheim, Chugai, Corrona, Daiichi-Sankyo, Eisai, Kowa, Mitsubishi-Tanabe, and Takeda