Title: Real-world experience with odevixibat in children with progressive familial intrahepatic cholestasis
Source: JHEP Reports 2024, Dec 19. [E–publication]
Date of publication: December 2024
Publication type: Prospective cohort study
Abstract: Background and aims: A previously published trial demonstrated that odevixibat is effective in the treatment of cholestatic pruritus of children with progressive familial intrahepatic cholestasis (PFIC). Real-world experience is necessary to confirm the results of registration trials having selective eligibility criteria. We present our “real life experience” on odevixibat effectiveness and safety in patients with different PFIC subtypes.
Methods: Multicenter prospective study of patients with PFIC treated with odevixibat (40 or escalated to 120 μg/kg/day). Pruritus was assessed by “Physician Global Impression of Symptom” at baseline and monthly up to 6 months. Serum bile acids (sBA) responders were patients who achieved a reduction in sBA levels ≥70% from baseline (or a value <70 μmol/L) after 6 months; pruritus responders were patients who reported improvement in pruritus score.
Results: 24 patients [median age 6.6 years (3.7-12.1), M/F=11/13] were enrolled; 16 (67%) had classic PFIC types (PFIC-1=2; PFIC-2=11; PFIC-3=3), 8 (33%) had rarer forms (PFIC-4=5, PFIC-5=1; PFIC-6=1; PFIC-9=1). All had high sBA levels and 22/24 (92%) had pruritus. 4 (17%) had associated comorbidities. After 6 months of treatment, sBA decreased from a median of 317.1 μmol/L (range 82.3-369.0) to 45.6 μmol/L (range 7.2-120; p<0.001); mean change of pruritus score was -1.7. Overall, 75% of patients were sBA responders, 73% were pruritus responders; 30% required dose escalation. Reduced pruritus correlated significantly with reduced sBA (p<0.05). A cut-off value of sBA >333.5 μmol/L increased the risk of no response to odevixibat by 17 folds (p < 0.001). No serious adverse events were recorded.
Conclusions: Odevixibat is effective and safe in reducing sBA levels and improving pruritus in a real-life scenario both in patients with classic PFIC types and in other rarer subtypes. Dose escalation is required in some patients to improve the response to treatment.
Impact and implications: Published data on use of odevixibat in a real-world scenario are lacking. We explored the effectiveness of odevixibat in a heterogenous cohort of children diagnosed with PFIC (including patients with classic as well as rarer types of PFIC, with advanced liver disease and associated comorbidities). Our results demonstrate that odevixibat is effective for the treatment of cholestasis and pruritus in children with different PFIC subtypes in a real-life scenario. These results support the use of odevixibat in children with any type of PFICs, including patients with different stage of liver disease and comorbidities.
