Background: Pruritus affects up to 80% of patients with primary biliary cholangitis (PBC) and reduces health-related quality of life (HRQoL). GLIMMER (NCT02966834) was a randomized, placebo-controlled phase IIb study of linerixibat in patients with PBC and pruritus. Using patient-reported outcome data from GLIMMER, we characterize the impact of pruritus in PBC. Methods: To objectively assess HRQoL impact, EQ-5D-5L data from GLIMMER (0-1 scale; 0 = death, 1 = perfect health) were analyzed post-hoc across pruritus severities. Inter-relationships between pruritus severity (0-10 numerical rating scale NRS), depression (Beck Depression Inventory-II, post-hoc), and sleep interference (0-10 NRS) and their impact on HRQoL were explored. Results: In patients with PBC (n = 147), severe pruritus was associated with worse HRQoL. EQ-5D-5L scores were lower in those with severe pruritus (≥7-10 NRS) versus mild/moderate pruritus (mean SD: 0.49 0.28 and 0.75 0.17/0.76 0.17, respectively). Among patients with severe pruritus, 31% had severe depression, versus 9/3% with mild/moderate pruritus. Patients with both severe pruritus and depression had a mean EQ-5D-5L score of 0.30. In those with severe pruritus, 54% reported severe sleep interference. Improvements in pruritus were accompanied by stepwise improvements in EQ-5D-5L scores. Conclusions: This analysis of patients in the largest investigational trial of cholestatic pruritus to date shows a clear association between pruritus and impaired HRQoL. Patients with severe pruritus had HRQoL comparable to patients with severe Parkinson's disease. Severe pruritus alongside depression was associated with extremely poor HRQoL, indicating the importance of evaluating itch and managing depression. Sleep interference appears to be a major cofactor for reduced HRQoL. For each 1-point improvement in NRS HRQoL improved, clinicians should offer appropriate and timely intervention.
Smith et al. (Sat,) studied this question.