S2325 Change in Pruritus in Patients With Primary Biliary Cholangitis and Moderate to Severe Pruritus: A Pooled Analysis From the RESPONSE and ENHANCE Studies

Introduction: Primary biliary cholangitis (PBC) is a cholestatic liver disease, with pruritus occurring in up to 70% of patients, which can greatly reduce quality of life. Seladelpar (SEL) is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of PBC combined with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as a monotherapy in patients intolerant to UDCA. In 2 Phase 3, placebo (PBO)-controlled trials (ENHANCE [NCT03602560], RESPONSE [NCT04620733]), SEL significantly reduced pruritus in patients with moderate to severe pruritus (MSP) at baseline (BL; numerical rating scale [NRS] ≥4). Here, we present pooled pruritus outcomes across different measures of itch in patients with PBC from RESPONSE and ENHANCE with NRS ≥4 at BL. Methods: Patients with PBC with an inadequate response or intolerance to UDCA were randomized 1:1:1 to daily, oral SEL 5 mg, SEL 10 mg, or PBO for 52 weeks (W) in ENHANCE and 2:1 to daily, oral SEL 10 mg or PBO for 52W in RESPONSE (ENHANCE terminated early with key endpoints amended to 3 months [M]). Pooled data from patients with NRS ≥4 at BL who received SEL 10 mg or PBO in RESPONSE and at least 6M in ENHANCE were analyzed. In a post hoc analysis, changes across several measures of itch (NRS, PBC-40 itch domain, and 5-D itch scale) up to 6M were assessed. Results: Of the 126 patients with MSP, 76 and 50 patients received SEL 10 mg and PBO, respectively, in RESPONSE or ENHANCE. Most patients at BL were <50 years old at age of PBC diagnosis (73/126) and had a history of pruritus (122/126) and fatigue (77/126). NRS, PBC-40 itch domain, and 5-D itch scale scores were similar between the SEL and PBO groups at BL. At 6M, patients who received SEL experienced greater improvements in NRS scores (mean change from BL [CFB] of −3.12 vs −2.09 for SEL and PBO, respectively, P = .0004), PBC-40 itch domain scores (mean CFB of −2.26 vs −1.37 for SEL and PBO, respectively, P = .0227), 5-D itch total scores (mean CFB of −4.85 vs −2.30 for SEL and PBO, respectively, P < .0001), and 5-D itch degree domain scores (mean CFB of −0.96 vs −0.54 for SEL and PBO, respectively, P = .0005). Overall, safety profiles in patients with pruritus in the SEL and PBO groups were similar. Adverse events occurred in 58/76 (76.3%) SEL patients and 40/50 (80%) PBO patients. Conclusion: As shown in previous studies, up to 6M of SEL treatment reduced pruritus to a greater extent vs PBO in patients with PBC who had MSP when assessed across 3 different measures of itch. SEL was well tolerated in this pt population.