POS1022 BIMEKIZUMAB SAFETY AND EFFICACY IN PATIENTS WITH PSORIATIC ARTHRITIS: 3-YEAR RESULTS FROM A PHASE 2b OPEN-LABEL EXTENSION STUDY

Abstract

Background:Bimekizumab (BKZ), a monoclonal antibody inhibitor of interleukin (IL)-17A and IL-17F, demonstrated clinical improvements in joint and skin outcomes up to 108 weeks (wks) in patients (pts) with active psoriatic arthritis (PsA).1,2Objectives:To report up to 3-year safety and efficacy of BKZ in pts with active PsA from a 48-week phase 2b dose-ranging study (BE ACTIVE; NCT02969525) and its open-label extension (OLE; NCT03347110).Methods:BE ACTIVE and OLE study design has been described previously.1 All OLE pts received BKZ 160 mg Q4W, irrespective of prior dosing regimen. Treatment-emergent adverse events (TEAEs) are reported for the safety set (SS; pts who received ≥1 dose BKZ in the dose-ranging study). Data are presented from dose-ranging study baseline (BL) to Wk 152. Efficacy outcomes are reported for the full analysis set (FAS): ACR50, minimal or very low disease activity (MDA/VLDA), Psoriasis Area and Severity Index (PASI) 90/100, body surface area affected by psoriasis (BSA) 0% and dactylitis/enthesitis resolution.Results:Over 152 wks, the exposure-adjusted incidence rate (EAIR) per 100 patient-years (PY) was 126.4 for all TEAEs, 4.1 for serious TEAEs, 0.7 for serious infections and 4.6 for Candida infections (Table 1). One event was adjudicated by an independent committee as inflammatory bowel disease (microscopic colitis). All Candida infections were localised, mild/moderate, and resolved with appropriate anti-fungal therapy. Overall, the proportions of patients with ACR50 response were sustained through Wk 152 (52.9%, non-responder imputation [NRI]; Figure 1). Response rates were also sustained through Wk 152 for MDA (51.5%), VLDA (30.1%), PASI90 (64.2%), PASI100 (57.7%) and resolution of dactylitis (71.2%) and enthesitis (62.6%) (NRI; Table 1).Table 1.Safety and efficacy outcomes up to 3 yearsSafety (SS)n (%) [EAIR/100 PY]BKZ160 mg [a](n=126)BKZ320 mg [b](n=78)Total(N=206)Any TEAE114 (90.5) [136.1]70 (89.7) [113.3]184 (89.3) [126.4]Serious TEAEs17 (13.5) [5.2]5 (6.4) [2.3]22 (10.7) [4.1]Key TEAEs of special monitoringSerious infections3 (2.4) [0.9]1 (1.3) [0.5]4 (1.9) [0.7]Candida infections15 (11.9) [4.7]9 (11.5) [4.4]24 (11.7) [4.6]Inflammatory bowel disease [c]1 (0.8) [0.3]01 (0.5) [0.2]Malignancies [d]1 (0.8) [0.3]01 (0.5) [0.2]Injection site reactions03 (3.8) [1.4]3 (1.5) [0.5]Suicidal ideation1 (0.8) [0.3]01 (0.5) [0.2]Liver function analyses13 (10.3) [4.1]11 (14.1) [5.3]24 (11.7) [4.6]Study discontinuation due to TEAEs12 (9.5) [3.5]4 (5.1) [1.8]16 (7.8) [2.8]Efficacy (FAS)n (%)BKZ160 mg [a](n=124)BKZ320 mg [b](n=82)Total(N=206)OCNRI, %OCNRI, %OCNRI, %MDA, Wk 15264/95 (67.4)51.642/62 (67.7)51.2106/157 (67.5)51.5VLDA, Wk 15241/95 (43.2)33.121/62 (33.9)25.662/157 (39.5)30.1PASI90 [e] Wk 15251/61 (83.6)64.637/46 (80.4)63.888/107 (82.2)64.2PASI100 [e] Wk 15247/61 (77.0)59.532/46 (69.6)55.279/107 (73.8)57.7BSA 0% [e] Wk 4848/72 (66.7)60.838/55 (69.1)65.586/127 (67.7)62.8Wk 15246/61 (75.4)58.231/45 (68.9)53.477/106 (72.6)56.2Dactylitis [f]/Enthesitis [g] resolution, Wk 48–70.6/56.9–84.0/57.1–76.3/57.0Wk 152–67.6/63.1–76.0/61.9–71.2/62.6No anaphylactic reactions or major adverse cardiac events were reported. [a] Includes pts within the indicated analysis set originally assigned to all arms who were subsequently re-randomized to 160 mg, or [b] 320 mg, after double-blind period; [c] Microscopic colitis; [d] Malignant melanoma in situ; [e] Pts with BL BSA ≥3%, NRI: n=79, 58, 137 respectively; [f] Pts with BL LDI >0, NRI: n=34, 25, 59 respectively; [g] Pts with BL MASES >0, NRI: n=65, 42, 107 respectively. LDI: Leeds Dactylitis Index; MASES: Maastricht AS Enthesitis Score; OC: observed case.Conclusion:The safety profile of BKZ in pts with PsA reflects previous observations1,2 for up to 3 years. High threshold disease control was achieved by >50% of BKZ-treated pts up to 3 years, reflected in long-term improvements in joint and skin outcomes.