Elafibranor in selected patients with primary biliary cholangitis and cirrhosis: An exploratory real-world cohort study
Nargiz Nuruzade, Ulya Oruc, Georgios Konstantis, Moritz Passenberg, Arash Dooghaie Moghadam, Jan Best, Claudia Veltkamp, Florian Alexander Seltsam, Hartmut H. Schmidt, Katharina Willuweit, Jassin Rashidi-AlavijehBackground
Patients with primary biliary cholangitis (PBC) and cirrhosis are a vulnerable population at risk of disease progression and complications. Although elafibranor has shown efficacy in patients with an inadequate response to ursodeoxycholic acid, evidence in individuals with established cirrhosis remains limited, as these patients were underrepresented in clinical trials.
Objectives
To assess the biochemical response, safety, and pruritus severity of elafibranor in patients with PBC and cirrhosis in routine clinical practice.
Design
Retrospective observational cohort study at a tertiary centre.
Methods
Patients with PBC and cirrhosis receiving elafibranor in routine care were included. Biochemical response, safety, and pruritus were assessed over a follow-up of 48 weeks. Response proportions are reported as intention-to-treat (ITT) analyses, in which discontinuations were classified as non-responders, and as available-case analyses restricted to patients remaining on treatment.
Results
Of 22 patients, 18 and 15 had available follow-up data at weeks 24 and 48, respectively; treatment was discontinued because of adverse events in four patients (18%) by week 24 and in a total of seven (32%) by week 48. Alkaline phosphatase (ALP) decreased from baseline (194.5 U/L [IQR 138.8-310.0]) to week 48 (144.5 U/L [103.0-189]; p = 0.031). At week 48, a ≥15% reduction in ALP was observed in 55% (ITT) and in 80% of those remaining on treatment, and an ALP below 1.67 × the upper limit of normal (ULN) was reached by 50% (ITT) and 73%. No hepatic decompensation, transplantation, or death occurred, nor were any serious adverse events requiring hospitalization or life-threatening complications reported. Pruritus was present in 13 of 22 patients (59%) at baseline; among 11 patients with paired assessments, pruritus improved in six, remained unchanged in one, and worsened in four, without a significant overall change (p = 0.137).
Conclusion
In this real-world cohort of patients with PBC and cirrhosis, elafibranor was associated with reductions in ALP, with no hepatic decompensation, transplantation, or death during follow-up, although treatment discontinuation due to adverse events was frequent. These exploratory findings may support further prospective evaluation but should not be interpreted as evidence of long-term clinical benefit or safety in decompensated cirrhosis.