POS0235 INTEGRATED SAFETY ANALYSIS UPDATE FOR FILGOTINIB (FIL) IN PATIENTS (PTS) WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS (RA) RECEIVING TREATMENT OVER A MEDIAN OF 2.2 YEARS (Y)

Abstract

BackgroundThe preferential Janus kinase-1 inhibitor FIL significantly improved signs and symptoms of RA in Phase 2 and 3 trials.1–5 FIL is approved for treatment of moderate to severe active RA in Europe and Japan. Integrated safety analysis of FIL with patient data through 2019 was presented at the 2020 ACR virtual meeting.6ObjectivesTo report updated, as-treated data from the FIL integrated safety analysis with increased study drug exposure.MethodsData were integrated from 2 Phase 2 (NCT01668641, NCT01894516), 3 Phase 3 (NCT02889796, NCT02873936, NCT02886728), and 2 long-term extension (LTE) (NCT02065700, NCT03025308) trials. Phase 2 and 3 LTE data were through Nov 2020 and Jan 2021, respectively. The as-treated analysis set included all available data for pts receiving ≥1 dose FIL 200 (FIL200) or 100 mg (FIL100), including those rerandomized to FIL for LTE. Exposure-adjusted incidence rates (EAIR)/100 patient-y exposure (PYE) of treatment-emergent adverse events (TEAEs; onset after first dose and no later than 30 days after last dose or new drug first dose date −1 day) and TEAEs of special interest (AESIs) are presented.Results3691 pts received FIL200 or FIL100 for 8085.1 PYE (median 2.2, maximum 6.8 y). In the as-treated set, 61% of FIL200 and 45% of FIL100 pts received FIL for ≥2 y, 19% and 5% for ≥3 y, and 11% and 0.5% for ≥4.5 y, respectively. EAIR for TEAEs was higher with FIL100 than FIL200; EAIRs for deaths were 0.5 and 0.3 for FIL200 and FIL100 (Figure 1). Incidences of infections and serious infections were numerically greater for FIL100 vs FIL200, while EAIRs for other AESIs were comparable between doses (Table 1). EAIRs for AESIs tended to decrease since the previous update, except for venous thromboembolism (total FIL 0.1 to 0.2) and malignancies excluding NMSC (total FIL 0.5 to 0.6).Table 1.TEAEs of special interest, as-treated setTEAE, n (%) and EAIR per 100 PYE (95% CI)FIL 200 mgn=2267PYE=5302.5FIL 100 mgn=1647PYE=2782.6Total FILN=3691PYE=8085.1Infectious AEs1206 (53.2)747 (45.4)1927 (52.2)EAIR21.1 (19.7, 22.5)30.2 (26.8, 34.0)21.0 (19.9, 22.3)Serious infectious AEs80 (3.5)57 (3.5)137 (3.7)EAIR1.5 (1.1, 1.9)2.7 (1.9, 3.9)1.6 (1.3, 2.0)Opportunistic infections5 (0.2)4 (0.2)9 (0.2)EAIR0.1 (0, 0.2)*0.1 (0.1, 0.4)*0.1 (0.1, 0.2)*Active tuberculosis03 (0.2)3 (<0.1)EAIR00.1 (0, 0.3)*0 (0, 0.1)*Herpes zoster84 (3.7)30 (1.8)114 (3.1)EAIR1.6 (1.2, 2.0)1.1 (0.8, 1.5)*1.4 (1.1, 1.7)Major adverse cardiovascular eventsa19 (0.8)14 (0.9)33 (0.9)EAIR0.3 (0.2, 0.5)0.5 (0.3, 0.8)*0.4 (0.2, 0.6)Venous thromboembolismb11 (0.5)4 (0.2)15 (0.4)EAIR0.2 (0.1, 0.4)*0.1 (0.1, 0.4)*0.2 (0.1, 0.3)*Atrial systemic thrombotic eventsa1 (<0.1)1 (<0.1)2 (<0.1)EAIR0 (0, 0.1)0 (0, 0.3)0 (0, 0.1)Malignancy excluding NMSC32 (1.4)17 (1.0)49 (1.3)EAIR0.6 (0.4, 0.9)0.6 (0.4, 1.0)*0.6 (0.4, 0.8)NMSC15 (0.7)5 (0.3)20 (0.5)EAIR0.3 (0.2, 0.5)*0.2 (0.1, 0.4)*0.2 (0.2, 0.4)*Gastrointestinal perforations3 (0.1)1 (<0.1)4 (0.1)EAIR0.1 (0, 0.2)*0 (0, 0.3)*0 (0, 0.1)**Except when any study had 0 event within the treatment, the Poisson model was not adjusted by study. PYE was defined as (last dose date − first dose date + 1)/365.25.aPositively adjudicated.bAdjudicated as deep vein thrombosis or pulmonary embolism.NMSC, nonmelanoma skin cancerConclusionWith 1 additional year of exposure since the 2020 report, FIL continues to be well tolerated with no new safety concerns emerging. EAIRs of TEAEs, including deaths, and AESIs remained stable or decreased since the 2020 report, except for slight increases in rates of NMSC and malignancies excluding NMSC. In the context of demonstrated efficacy, both FIL doses had an acceptable risk/benefit profile.