J Pediatr Gastroenterol Nutr. 2024 Feb 9. doi: 10.1002/jpn3.12101. Online ahead of print.

Ryan Himes ¹, Philip Rosenthal ², Natasha Dilwali ³, Kathryn Smith ³, Robert Venick ⁴, Regino P Gonzalez-Peralta ⁵

Author information

¹Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Ochsner Health Center for Children, New Orleans, Louisiana, USA.

²Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California, San Francisco, California, USA.

³Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Johns Hopkins Children's Center, Baltimore, Maryland, USA.

⁴Department of Pediatric Gastroenterology, University of California Los Angeles, Los Angeles, California, USA.

⁵Pediatric Gastroenterology, Hepatology, and Liver Transplant, AdventHealth for Children and AdventHealth Transplant Institute, Orlando, Florida, USA.

Abstract

Objective: Maralixibat, an ileal bile acid transporter inhibitor, is the first drug approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients aged ≥3 months with Alagille syndrome (ALGS). Approval was based on reductions in pruritus from the pivotal ICONIC trial, information from two additional trials (ITCH and IMAGO), and long-term extension studies. Although participants in these trials met strict inclusion and exclusion criteria, patients have received maralixibat under broader circumstances as part of an expanded access program or commercially. The expanded access and postapproval settings inform a real-world understanding of effectiveness and safety. The objective was to report on the use of maralixibat in the real-world setting in eight patients who otherwise would not have met entrance criteria for the clinical trials, providing unique insights into its effectiveness in the management of ALGS.

Methods: We reviewed records of patients with ALGS who received maralixibat but would have been excluded from trials due to surgical biliary diversion, reduction of antipruritic/cholestatic concomitant medications, administration of medication through a gastrostomy or nasogastric tube, or use in patients under consideration for transplantation.

Results: Maralixibat appeared to be effective with reductions in pruritus compared to baseline. Consistent with clinical trials, maralixibat was well tolerated without appreciable gastrointestinal complications. Liver enzyme elevations were observed but were interpreted as consistent with normal fluctuations observed in ALGS, with no increases in bilirubin.

Conclusion: Maralixibat may be effective and well tolerated in patients with ALGS in broader clinical contexts than previously reported.