Children with progressive familial intrahepatic cholestasis who received odevixibat in the 24-week PEDFIC 1 study had significant reductions vs placebo-treated patients in total serum bile acids (sBAs) and pruritus. Here, we evaluated changes in sBAs and pruritus in patients from PEDFIC 1 categorised by sBA response (R) level and by factoring in ursodeoxycholic acid (UDCA) use.
Patients eligible for PEDFIC 1 had elevated sBAs and significant pruritus at screening. Concomitant UDCA was allowed provided the patient’s dose was stable. Three categories of patients among those randomised to odevixibat (n=42) were analysed here: sBA Rs (ie, sBAs reduced ≥70% from baseline [BL] or levels ≤70 μmol/L), sBA partial Rs (PRs [ie, did not meet sBA R criteria but had sBAs reduced ≥30%), and sBA nonresponders (NRs [ie, did not meet either sBA R or PR criteria). Parameters evaluated included sBA composition (ie, total, primary, and secondary BAs, with UDCA concentration included as secondary BA) as measured by liquid chromatography−tandem mass spectrometry and pruritus as rated by caregivers (range: 0–4; higher scores indicate worse symptoms, with pruritus R defined as a ≥1-point reduction from BL); pruritus outcomes were also compared by whether patients had concomitant UDCA use and/or sBA R.
Mean BL total sBAs were higher with vs without UDCA in all 3 sBA R categories (figure 1A), which could be primarily accounted for by UDCA concentrations (66, 116, and 42 μmol/L, in sBA Rs [n=17], PRs [n=7], and NRs [n=18], respectively). During odevixibat treatment, sBA Rs had the largest decreases in total and primary sBAs, whereas sBA PRs had intermediate decreases, and sBA NRs had minimal changes. Among all odevixibat-treated patients, sBA Rs experienced greater mean reductions in monthly pruritus scores vs sBA PRs and sBA NRs (Figure, B). sBA PRs who used UDCA had smaller reductions in monthly pruritus score vs those who did not (Figure, B). Among pruritus Rs with UDCA use, the rate of sBA R, PR, and NR was 69%, 0%, and 31%, respectively; among pruritus Rs without UDCA use, these rates were 50%, 25%, and 25%.
UDCA treatment resulted in higher sBAs at BL, but this did not seem to affect sBA R to odevixibat. A sBA PR was not associated with a mean decrease in pruritus with concomitant UDCA use. All sBA R groups included patients for whom pruritus R did not correlate with sBA R.
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