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 lg/ 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 lmol/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 lmol/L (range 82.3–369.0 lmol/L) to 45.6 lmol/L (range 7.2–120 lmol/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 lmol/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.