Saeed Mohammad, MD: IBAT Inhibitors for Cholestatic Disease

In only a short time since their initial US Food and Drug Administration (FDA) indications to treat pruritic symptoms in cholestatic diseases including Alagille syndrome and progressive familial intrahepatic cholestasis (PFIC), ileal bile acid transporter (IBAT) inhibitors have been leading options for the primarily pediatric patients with these rare disease.

In an interview with HCPLive during the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) 2023 Annual Meeting in San Diego this week, Saeed Mohammad, MD, MS, associate professor and director of the Pediatric Solid Organ Transplant Center at Vanderbilt University Medical Center, discussed his professional experiences in prescribing IBAT inhibitors for the treatment of patients with Alagille syndrome or PFIC with pruritus.

Starting with maralixibat, Mohammad said his patients with Alagille syndrome have experienced "dramatic improvement" in their itching symptoms within about 4 weeks. "I've been able to stop some of the other antipsychotic agents that they were on. And you know, the kids are feeling better and families are happier."

Meanwhile, his use of odevixibat, for patients with PFIC and symptoms of pruritus has resulted in similar reactions.

“We've been able to stop some other medications that they were on as well,” Mohammad said. “So that's been I'd say a game changer in the treatment of cholestatic pruritis.”

Until the introduction of IBAT inhibitors, Mohammad and his colleagues were reliant on a diverse array of treatments to treat the unique symptoms of cholestatic disease: antihistamines including rifampin, and antidepressants, to name a couple. Their benefit, though apparent, do not equate to what maralixibat and odevixibat has provided.

A common issue due to the pruritus in younger pediatric patients is a domino-like effect of sleep problems that may progress to worsened mental health.

“Some of the parents we know, they are sitting with their kids for a long time trying to put them to sleep, they're itching them so that they can fall asleep,” Mohamma explained. “Or then the kids wake up in the middle of the night very itchy and will call out to their parents. So the parents' sleep is very disturbed. If they're not sleeping well at night, then the next day, they’re tired, groggy, they’re more irritable.”

Mohammad is interested to see the affect of liver status and opportunities for “native survival” as pediatric patients with Alagille syndrome reach adulthood while receiving IBAT inhibitors.

“What the data that are coming out are showing that patients who are on an IBAT inhibitor who have had an improvement in their itch, have transplant-free survival,” he said. “So, the ones who have improvements in their itch after over I think 5 or 6 years have not required a liver transplant. That's a tremendous change from what we're seeing where 60 - 75% are needing a liver transplant.”

Though it’s been essentially 7 years’ worth of clinical and real-world data now available for the drug class, there’s more to learn about their interaction with cholestatic disease long-term. Specifically within Alagille syndrome, there’s much more investigators want to understand about its pathophysiology and how symptoms like pruritus persist; a highly efficacious drug class like IBAT inhibitors may aid that understanding.

“It's going to be very hard to figure out, but the more we study bilirubin, metabolism, bile acids, I think the more we're going to learn,” Mohammad said. “And I think the next step where we're looking at this for biliary atresia, which is the most common cause of for liver transplantation in North American children—and then other rare diseases like primary sclerosing cholangitis—I think those trials are going to make us understand even more about what these medications can and can't do.”