P20 Effect of elafibranor on pruritus in primary biliary cholangitis: symptom severity and quality of life measurements from the phase III ELATIVE® trial

<h3>Introduction</h3> Pruritis is a common symptom of primary biliary cholangitis (PBC) that negatively impacts quality of life (QoL). In the phase III ELATIVE® trial (NCT04526665), elafibranor, a dual peroxisome proliferator-activated receptor-alpha/delta agonist, significantly improved prognostic biomarkers of cholestasis in PBC. We report the effect of elafibranor on patient-reported pruritus from ELATIVE®. <h3>Methods</h3> Patients with PBC, randomised to elafibranor 80mg or placebo, completed 5-D Itch and PBC-40 questionnaires at each study visit. The five 5-D Itch domains each score between 1 and 5; total score ranging 5 (no pruritus) to 25 (most severe). ‘Itch’ is one of six PBC-40 domains and comprises 3 questions with a maximum score of 15 (most severe). Change from baseline to Week 52 in 5-D Itch and PBC-40 Itch in patients with moderate-to-severe pruritus (baseline PBC Worst Itch Numeric Rating Scale [PBC WI-NRS] ≥4/10) is reported. Analyses of total scores used a mixed model for repeated measures (fixed factors: treatment, visits until Week 52, treatment by visit interaction) and adjusted for baseline scores and stratification factors; P values are nominal. Shifts in responses (baseline to Week 52) for selected 5-D Itch domains/questions and PBC-40 Itch questions were analysed post hoc. <h3>Results</h3> Of 161 randomised patients, 66 (41%) had moderate-to-severe pruritus at baseline (elafibranor: 44; placebo: 22). At Week 52, reductions in 5-D Itch total score were greater with elafibranor than placebo (LS mean difference [95% confidence interval: −3.0 [−5.5, −0.5]; P=0.0199). For the Duration domain, 14/24 (58%) patients receiving elafibranor had itching duration reduced from ≥6 to &lt;6 hours/day from baseline to Week 52 vs 3/11 (27%) receiving placebo. In response to the Disability domain’s sleep question, 20/25 (80%) patients receiving elafibranor with at least frequently delayed sleep (score ≥3) improved to occasionally delayed sleep or no disturbance (score &lt;3) from baseline to Week 52 vs 3/10 (30%) receiving placebo. Patients receiving elafibranor had greater, clinically meaningful^{1 2} reductions at Week 52 in PBC-40 Itch total score vs placebo (LS mean difference [95% confidence interval]: −2.3 [−4.0, −0.7]; P=0.0070). Similar reductions to those observed in 5-D Itch domains were seen in mean scores for the individual PBC-40 Itch questions with elafibranor vs placebo. <h3>Discussion</h3> In patients with PBC, elafibranor improved 5-D Itch and PBC-40 Itch scores emphasising its potential to reduce pruritus severity and to positively impact QoL. <h3>References</h3> Jones D. <i>Hepatol Commun</i>. 2023;<b>7</b>(3):e0057. Jopson L. <i>BMJ Open</i>. 2015;<b>5</b>(8):e007985. Study sponsor: GENFIT; secondary analysis, publication sponsor: Ipsen.