Real-world experience with odevixibat in children with progressive familial intrahepatic cholestasis

Background & 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 with selective eligibility criteria. We present our 'real-life experience' of the effectiveness and safety of odevixibat in patients with different PFIC subtypes. Methods: We carried out a multicenter prospective study of patients with PFIC treated with odevixibat (40 or escalated to 120 mu g/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 mu mol/L) after 6 months; pruritus responders were patients who reported improvement in their pruritus score. Results: In total, 24 patients (median age 6.6 years [3.7-12.1], male:female = 11/13) were enrolled; 16 (67%) had classic PFIC types (PFIC-1, 2; PFIC-2, 11; and PFIC-3, 3), whereas eight (33%) had rarer forms (PFIC-4, 5, PFIC-5, 1; PFIC-6, 1; and PFIC-9, 1). All had high sBA levels and 22/24 (92%) had pruritus. Four (17%) had associated comorbidities. After 6 months of treatment, sBA decreased from a median of 317.1 mu mol/L (range 82.3-369.0 mu mol/L) to 45.6 mu mol/L (range 7.2-120 mu mol/L; p <0.001); the mean change in pruritus score was -1.7. Overall, 75% of patients were sBA responders, 73% were pruritus responders, and 30% required dose escalation. Reduced pruritus correlated significantly with reduced sBA (p <0.05). A cut-off value of sBA >333.5 mu mol/L increased the risk of no response to odevixibat by 17-fold (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 in both patients with classic PFIC types and in those with other rarer subtypes. Dose escalation is required in some patients to improve the response to treatment. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).