POS0676 EFFICACY AND SAFETY OF FILGOTINIB IN PATIENTS AGED ≥75 YEARS: A POST HOC SUBGROUP ANALYSIS OF THE FINCH 4 LONG-TERM EXTENSION (LTE) STUDY

Abstract

BackgroundFilgotinib (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 experience1. An important consideration is the generally higher incidence of adverse events (AEs) in the elderly due to comorbidities.ObjectivesTo evaluate the efficacy and safety of FIL100 and FIL200 in patients with RA aged ≥75 y.MethodsFINCH 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).ResultsAt 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 exposureFIL200FIL100Age, years<75≥75<75≥75n=1469n=61n=1136n=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)TEAE48.3 (45.5, 51.3)55.3 (42.1, 72.8)48.7 (45.5, 52.1)42.7 (31.6, 57.8)Serious TEAE6.8 (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 discontinuation2.9 (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 death0.5 (0.3, 0.9)3.3 (0.7, 9.5)*0.3 (0.2, 0.8)0.0 (0.0, 3.8)Infections28.8 (26.6, 31.1)29.3 (20.1, 42.7)27.4 (25.0, 29.9)26.4 (18.0, 38.8)Serious infections1.6 (1.2, 2.2)2.2 (0.5, 8.7)1.7 (1.1, 2.4)3.1 (1.0, 9.5)Herpes zoster1.6 (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 event0.4 (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 events0.3 (0.1, 0.6)2.2 (0.5, 8.7)0.2 (0.1, 0.5)1.0 (0.1, 7.2)Malignancy excluding NMSC0.7 (0.4, 1.2)4.3 (1.6, 11.6)0.7 (0.4, 1.2)3.1 (1.0, 9.5)NMSC0.4 (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 eventConclusionIn 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.