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Elafibranor is a dual PPAR-α/δ agonist recently licenced for treatment of Primary Biliary Cholangitis (PBC). It inhibits bile acid synthesis, enhances detoxification, and reduces toxicity, with anti-inflammatory effects via NF-κB and AP-1 pathway inhibition. The ELATIVE trial1 showed significant liver biochemistry improvements, though real-world data are limited. We describe early clinical experience from a regional UK PBC network, highlighting elafibranor’s potential role in treatment sequencing for challenging cases.Method We conducted a retrospective analysis of patients initiated on elafibranor between January and April 2025 in a regional PBC network. Data collected included patient’s demographic, fibrosis status, PBC treatment history, comorbidities, concomitant medication, treatment duration and standard of care blood tests at base line and after one month.Results 12 patients (11 female, 1 male) were initiated on elafibrinor in the period reviewed. All met the NICE TA recommendation as not achieving biochemical response (ALP 1.67 poise) with ursodeoxycholic acid (UDCA) monotherapy or being intolerant to UDCA. Mean age was 59.8 ± 12.8 years. Two individuals had cirrhosis (both Child-Pugh A5). A decrease in ALP value was observed after 1 month in 9 patients (81%). Mean ALP prior to commencing elafibrinor was 352U/L ± 209 and after 1 month of treatment was 248U/L ± 77. The mean change in ALP value was 104U/L ± 163 with an average 16% reduction. elafibrinor was generally well tolerated: one patient stopped treatment due to increased fatigue and confusion, one patient reported diarrhoea which resolved and ALT elevation was noted in one case. Of patients included in the sample, five had previously received second-line therapy with obeticholic acid (OCA). Three had discontinued OCA due to intolerability and two due to an inadequate biochemical response. A decrease in ALP value was seen in four with mean ALT reduction of 31.84% ± 19.34%.Conclusion Data is limited but our observations suggest elafibrinor treatment is well tolerated and improves liver biochemistry early in treatment in a real-world setting. In particular, we have observed improved liver biochemistry in the initial stage of treatment for PBC patients who are suboptimal responders or intolerant to other second line therapies. These observations support further exploration of elafibranor as a potential option in the therapeutic sequence for managing difficult-to-treat PBC. Further data is required to assess long term tolerability and response in real-world settings.References Kowdley KV, Bowlus CL, Levy C, Akarca US, Alvares-da-Silva MR, Andreone P, Arrese M, Corpechot C, Francque SM, Heneghan MA, Invernizzi P, Jones D, Kruger FC, Lawitz E, Mayo MJ, Shiffman ML, Swain MG, Valera JM, Vargas V, Vierling JM, Villamil A, Addy C, Dietrich J, Germain JM, Mazain S, Rafailovic D, Taddé B, Miller B, Shu J, Zein CO, Schattenberg JM; ELATIVE Study Investigators’ Group; ELATIVE Study Investigators’ Group. Efficacy and safety of elafibranor in primary biliary cholangitis. N Engl J Med. 2024 Feb 29;390(9):795–805. doi: 10.1056/NEJMoa2306185. Epub 2023 Nov 13. PMID: 37962077.National Institute for Clinical Excellence. Elafibranor for previously treated primary biliary cholangitis (2024). NICE technology appraisal guideline 1016.