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Fatigue and pruritus are common symptoms in PBC. In the phase III ELATIVE® trial ( NCT04526665), elafibranor significantly improved biomarkers of cholestasis in PBC. Here, we report the impact of elafibranor vs placebo on fatigue, and the association between fatigue and pruritus.Patients with PBC were randomized 2:1 to elafibranor 80 mg (n=108) or placebo (n=53). Fatigue was assessed via the Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a (PFSF 7a) and PBC-40 Fatigue domain. Data are reported for patients with moderate-to-severe fatigue at baseline (PFSF 7a score ≥60; PBC-40 Fatigue domain score ≥29). Changes to Week 52 were summarized as categorical changes, percentage changes, and minimal clinically important differences (MCIDs; PFSF 7a: ≥3; PBC-40 Fatigue domain: ≥5). Spearman’s correlation coefficients were calculated between fatigue (PFSF 7a and PBC-40 Fatigue domain) and pruritus (5-D Itch and PBC-40 Itch domain) patient-reported outcomes (PROs) for scores at baseline and change from baseline to Week 52. Patients with missing data at baseline and/or Week 52 were excluded.For PFSF 7a, 42/95 (44.2%) patients receiving elafibranor and 16/46 (34.8%) receiving placebo had moderate-to-severe fatigue at baseline. By Week 52, 18/42 (42.9%) patients receiving elafibranor vs 5/16 (31.3%) receiving placebo improved to mild/normal fatigue. Mean (95% CI) percentage change in PFSF 7a score was greater with elafibranor (−9.5% [−12.9%, −6.2%]) vs placebo (−4.2% [−9.6%, 1.2%]). Patients with an improvement ≥MCID at Week 52: elafibranor, n=28/42 (66.7%); placebo, n=5/16 (31.3%). For the PBC-40 Fatigue domain, 53/95 (55.8%) patients receiving elafibranor and 26/46 (56.5%) receiving placebo had moderate-to-severe fatigue at baseline. By Week 52, 12/53 (22.6%) patients receiving elafibranor vs 4/26 (15.4%) receiving placebo improved to mild/no fatigue. Mean (95% CI) percentage change in PBC-40 Fatigue domain score was greater with elafibranor (−9.8% [−15.4%, −4.1%]) vs placebo (−5.8% [−12.0%, 0.4%]). Patients with an improvement ≥MCID at Week 52: elafibranor, n=21/53 (39.6%); placebo, n=7/26 (26.9%). At baseline, fatigue and pruritus PRO scores had a weak correlation (r=0.25–0.35), suggesting pruritus was not a main driver of fatigue. Similarly, changes in fatigue and pruritus PROs from baseline to Week 52 did not demonstrate a strong correlation (r=0.26–0.33), and they could improve independently of one another.Elafibranor resulted in clinically meaningful improvements in fatigue, with greater improvements vs placebo. A weak correlation between fatigue and pruritus PROs at baseline, and in improvements over time, suggests that elafibranor can improve these debilitating PBC symptoms independently of each other.