Sustained and Clinically Meaningful Improvements in Moderate to Severe Pruritus Patients With PBC Treated With Seladelpar: Results From the ASSURE Study Up to 30 Months

Cholestatic pruritus is common in PBC, occurring in up to 80% of patients. This pruritus is often debilitating and negatively affects quality of life. Current treatment options for cholestatic pruritus, including bile acid sequestrants, anti-histamines, and off-label rifampin, have limited efficacy or challenges with toxicity.¹ In the RESPONSE and ASSURE trials, seladelpar demonstrated significant improvements in biochemical markers and pruritus in patients with PBC.^2,3 Among patients with a baseline moderate to severe pruritus (NRS ≥4) in the RESPONSE trial, seladelpar 10 mg (n=49) was associated with significant improvements in itch over placebo (n=23), with differences that reached statistical significance at 6 months (P<.005) and were sustained at 12 months (P<.005). In the overall patient population in RESPONSE (n=193), seladelpar was associated with a significant benefit over placebo in itch reduction starting at 1 month (P<.05) that was maintained over 12 months.² In the ASSURE trial, declines in pruritus initially observed in the RESPONSE trial were maintained after 6 additional months of treatment. Patients who entered the ASSURE OLE from legacy trials also showed similar declines in itching as assessed by NRS.³

Hirschfield and colleagues presented updated interim long-term results related to pruritus outcomes in the ASSURE trial among patients initially in the RESPONSE study.⁴ Baseline characteristics for the subset of patients with moderate to severe pruritus (NRS ≥4) were balanced between the seladelpar 10 mg arm (n=49) and the placebo arm (n=23), with mean pruritus NRS scores of 6.1 and 6.6, respectively, mean 5-D Itch total scores of 16.2 and 16.4, respectively, and mean PBC-40 itch domain scores of 8.7 and 9.6, respectively.

Assessments of NRS scores over time found clinically meaningful changes in pruritus NRS scores among patients receiving seladelpar. These improvements were sustained with a follow-up of up to 30 months in the ASSURE trial (Figure 3). In this cohort of patients (with a baseline pruritus NRS ≥4), more than half attained clinically meaningful improvements in pruritus (defined as an NRS improvement of ≥3 points), including 56% of patients in both the continuous seladelpar arm and the crossover arm at 30 months. Seladelpar was also associated with durable improvements in pruritus in patients with moderate to severe pruritus as assessed by the 5-D Itch total score and the PBC-40 itch score.

Figure 3.

Mean change in NRS scores in the ASSURE study after treatment with seladelpar 10 mg in patients with primary biliary cholangitis and moderate to severe pruritus (defined as baseline pruritus NRS ≥4 in the RESPONSE trial).

NRS, numeric rating scale; SE, standard error.

Adapted from Hirschfield GM, et al. Abstract 5015. Presented at: AASLD 2025; November 7-11, 2025; Washington, DC.⁴

Investigators also assessed the comparability of single-visit pruritus NRS compared with weekly averaged NRS outcomes in the ASSURE trial. A regression analysis found that both methods of assessing pruritus were comparable, with an r value of 0.93 (95% CI, 0.90-0.95), and a plot of mean NRS over time with single-visit vs weekly average scores yielded similar outcomes. The results demonstrated sustained clinically relevant improvements in pruritus with seladelpar after up to 30 months of treatment in the ASSURE study. More than half of patients with moderate to severe itch attained meaningful improvements in pruritus NRS, 5-D itch, and PBC-40 itch domain scores.

This study further confirms the addition of pruritus management to the seladelpar label. The authors demonstrate continued pruritus benefit over time and clinically meaningful improvement in pruritus in the patients with moderate to severe itch with seladelpar, as assessed by 3 different pruritus scales. These benefits occurred in both the continuous and crossover study arms. Regression analysis of the NRS scores over time further validated these findings. The results will help clinically, as management of itch is of great importance to patients.

—Robert G. Gish, MD