IBAT inhibitors for cholestatic disease

In only a short time since initial US Food and Drug Administration (FDA) approval to treat pruritus symptoms in cholestatic diseases, including Alagille syndrome and progressive familial intrahepatic cholestasis (PFIC), ileal bile acid transporter (IBAT) inhibitors have been used. There have been leading options for this. Primarily pediatric patients with these rare diseases.

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 Mohammed, MD, MS, associate professor and director of the Pediatric Solid Organ Transplant Center at Vanderbilt University Medical Center, led his discussion. of. Professional experience in prescribing IBAT inhibitors for the treatment of PFIC patients with Alagille syndrome or pruritus.

Starting with maralixibet, Mohammed said his patients with Alagille syndrome have experienced “dramatic improvement” in their itch symptoms within about 4 weeks. “I’ve been able to stop some of the other antipsychotic agents they were taking. And you know, the kids are feeling better and the families are happier.”

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

“We were also able to stop some of the other medications he was taking,” Mohammed said. “So I would say this is a game changer in the treatment of cholestatic pruritis.”

Until the introduction of IBAT inhibitors, Mohammed and his colleagues relied on a variety of therapies to treat the unique symptoms of cholestatic disease: antihistamines and antidepressants, including rifampin. Their benefit, although clear, is not equivalent to that provided by maralixibat and odevixibat.

A common problem with pruritus in young pediatric patients is the domino effect of sleep problems that can lead to worsening mental health.

“Some parents we know are sitting with their babies for a long time trying to get them to sleep, they are scratching them so they can sleep,” Mohamma said. “Or children will wake up in the middle of the night itching badly and call their parents. In such a situation, the sleep of the parents is greatly disturbed. “If they don’t sleep well at night, they may be tired, lethargic, and more irritable the next day.”

Mohammed is interested in looking at the impact of liver conditions and the chances of “survival” as pediatric patients with Alagille syndrome reach adulthood while receiving IBAT inhibitors.

“The data that are emerging are showing that patients who are on IBAT inhibitors who have improvement in itch have longer transplant-free survival,” he said. “So, I think people whose itching improves after more than 5 or 6 years do not need a liver transplant. This is a tremendous change from what we are seeing where 60 – 75% require a liver transplant.

Although there is now approximately 7 years of clinical and real-world data available for the drug class, there is much more to learn about their interactions with cholestatic disease in the long term. Within Alagille syndrome in particular, much investigators want to understand about its pathophysiology and how symptoms such as itching persist; Highly effective drug classes such as IBAT inhibitors may aid in 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’ll learn,” Mohammed said. “And I think the next step where we’re looking for biliary atresia, which is the most common cause of liver transplant in North American children – and then other rare diseases like primary sclerosing cholangitis – I think these trials are going to be “Are you telling us more about what these drugs can and can’t do?”

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