The Devastating Impact of Severe Pruritus in Primary Biliary Cholangitis

Introduction: Pruritus associated with PBC affects sleep and, social and emotional wellbeing. The impact of itch severity on quality of life (QoL) using the EuroQol-5-Dimension 5-Level (EQ-5D-5L) health utility score was assessed in a post hoc analysis of the Phase 2b GLIMMER study (NCT02966834). Pruritus (particularly severe itch) had a significant negative impact on QoL and health utility. Here we examine (post hoc) factors impacting QoL in patients with PBC and pruritus. Methods: Pts in GLIMMER completed the EQ-5D-5L and Beck Depression Inventory (BDI-II) at baseline (BL), which followed a 4-week single-blind placebo run-in period. EQ-5D-5L is a standardized health-related QoL instrument; scores range from 1 “perfect health” to 0 “death”. BDI is a 21-item, self-rated scale that evaluates key depression symptoms. Pts were classified as having mild (< 4, BL all mild were ≥ 3–< 4), moderate (≥ 4–< 7) or severe pruritus (≥7–10) using the weekly itch score. Sleep interference severity was based on the same numerical rating scale thresholds as those used for pruritus. Results: There were striking associations between itch severity, sleep interference and health utility, and between itch severity, depression and health utility. Overall mean (standard deviation) health utility was highest in patients with mild sleep interference 0.83 (0.126). Those with severe sleep interference had a much lower score, and those with severe itch and severe sleep interference even lower (0.52 [0.30] and 0.47 [0.31], respectively). Interestingly, no patients with mild itch had severe sleep interference and no patients with severe itch had mild sleep interference. As might be expected, health utility was lower with worse depression; from 0.78 (0.17) with no/minimal depression to 0.40 (0.29) for those with severe depression; amongst those with depression the impact of severe pruritus on health utility was striking, with utilities of 0.28, 0.29, and 0.30, for patients with mild, moderate, and severe depression, respectively. In mild and moderate itch, the distribution of depression severity was similar, with > 80% having minimal or mild depression. However, in the group with severe itch, 43% had moderate or severe depression. Conclusion: Pruritus in PBC significantly impacts QoL. Severe sleep interference and severe depression were far more common in patients with severe pruritus. In patients suffering with both severe pruritus and depression, health utility was severely impaired. This is a modified version of an abstract presented at EASL & UEGW 2023 (Figure 1).Figure 1.: Proportion of patients with depression by itch severity (A) and proportion of patients with sleep interference by itch severity (B).