Quality of life and clinical outcomes in people with Primary Biliary Cholangitis treated with obeticholic acid: results of a phase 4 real-life observational trial.

Introduction: Primary biliary cholangitis (PBC) can be associated with impaired health-related quality of life (HRQoL) caused by symptoms, mainly pruritus and fatigue, and eventually depression. Treatment confidence is a significant and modifiable variable in HRQoL of PBC people, and UDCA has been reported to be a positive factor in enhancing trust therapy. No real-life data on this and HRQoL exist regarding obeticholic acid (OCA), a second-line therapy, which can also lead to new-onset or worsening of pruritus. Aim: To assess the impact of OCA on biochemistry, patients’ illness perception and HRQoL of PBC patients. Methods: We designed a phase 4 observational open label study (Protocol AOP1515) and collected at baseline and every 6 months from starting OCA, biochemistry, adverse events, reported symptoms and the results of following questionnaires: PBC-40, Fatigue Impact Scale (FIS), 5-D Itch scale, EuroQoL-5D-5L. Changes in symptoms after OCA introduction were assessed by Wilcoxon paired rank test. Results: Nineteen (4 with cirrhosis) over 32 patients who started OCA treatment between March 2018 and April 2022 for insufficient response to UDCA agreed to participate. The median duration of OCA treatment was 32 (15-53) months with no drug discontinuation due to adverse events. A decrease of alkaline phosphatase below 1.5 x ULN and 1 x ULN was observed in 47%, 67%, 64%, 67% and 16%, 21%, 35%, 17% patients at 6, 12, 18, 24 months, respectively. After 6,12,18 and 24 months of treatment 26.7%, 33.3%, 33.3% and 50.0% of patients matched POISE primary end point criteria. At the time of starting OCA, significant (moderate and severe) pruritus, fatigue, cognitive and social dysfunction, emotional impairment, and general symptoms were present in 5%, 32%, 11%, 53%, 37%, 21% patients, respectively. During periodical clinical assessments, all patients reported a significant and persistent general improvement after OCA introduction. No severe aggravation of itch nor other symptoms was observed after OCA introduction, except for a transient aggravation in emotional domain at 12 months (8[5-10] vs.14[9-19], p<0.01) but not confirmed in subsequent follow-up. A trend over a significant reduction of fatigue evaluated by FIS at 36 months was also observed (45[0-82] vs.10.5[0-42], p=0.06). Three patients experienced new onset of pruritus of mild severity after OCA introduction that required starting specific therapy (1 fibrate, 1 sertraline and 1 cholestyramine), but in none OCA reduction was needed. Cirrhotic patients reported a slightly lower, although non significantly, quality of life assessed by EQ-5D-5L compared to non-cirrhotic both before (4.5±3.50 vs. 3.43±4.19, p=0.75) and 18 months after starting OCA therapy (5.00±3.99 vs 2.63±5.52, p=0.46). Conclusion: People with PBC and insufficient response to UDCA experienced a biochemical and subjective improvement after OCA introduction and no significant aggravation of objectively assessed HRQoL.