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Introduction Elafibranor (Ela), a next-generation peroxisome proliferator-activated receptor (PPAR) alpha/delta agonist, was approved for the treatment of PBC in 2024. Herein, we evaluate early real-world experiences in using Ela as a second-, third-, or fourth-line treatment for PBC.Methods The effectiveness, safety and tolerability of Ela was evaluated in patients (pts) initiating therapy in combination with ursodeoxycholic acid (UDCA), obeticholic acid (OCA), and amongst those switching from bezafibrate (BZF).Results From Dec 2024 to Nov 2025, 54 pts initiated Ela (49 women, median age 57y, median transient elastography score 11.5kPa). 18 pts had cirrhosis, 47 continued UDCA, 16 combined Ela with OCA and 29 switched from BZF to Ela. To date, n = 45, 33 and 17 have completed 1-, 3- and 6-months follow-up, respectively. 8, 4, and 2 pts discontinued Ela at the same timepoints, principally for gastrointestinal side effects (n = 7). However, 5 pts were able to restart later. In pts continuing Ela, median alkaline phosphatase (ALP) decreased from 2.47x upper limit of normal (ULN) at baseline, to 1.64x, 1.49x and 1.36x ULN at 1, 3 and 6 months respectively (p < 0.0001), with 2, 4 and 3 pts attaining normal ALP at the same points. Alanine aminotransferase (ALT) decreased from 0.99x ULN at baseline, to 0.87x, 0.80x and 0.84x ULN at 1,3 and 6 months (p < 0.03). Bilirubin was 0.62x ULN at baseline and remained stable at 1, 3 and 6 months. Pts on Ela without OCA showed similar reductions in ALP (from 2.94x ULN at baseline to 1.65x, 1.50x, and 1.32x ULN at 1, 3, and 6 months; p < 0.001) to the Ela + OCA group (ALP lowered from 1.88x ULN to 1.44x ULN at 1 month and 1.2x ULN at 3 months; p < 0.02). In pts who switched to Ela from BZF, ALP decreased from 2.68x ULN to 1.68x, 1.21x and 1.94x ULN at 1, 3 and 6 months (p < 0.008). ALP reductions were similar to those with no prior BZF exposure (2.26x ULN at baseline to 1.65x, 1.50x and 1.15x ULN at 1, 3 and 6 months; p < 0.008). No significant reductions in ALT were observed in the sub-group of pts on Ela+OCA combination therapy, nor in those with prior BZF exposure. In all, n = 21/40 pts with pruritus at baseline reported improvement, 11 no change, and 4 worsening of itch. 24 pts who switched from BZF reported pruritus at baseline, and 12 reported improvement on Ela.Conclusions Treatment with Ela in real-world PBC settings is associated with early biochemical and symptomatic improvement, including in pts previously treated with BZF, and in combination with OCA.