Case series suggests IBAT inhibitor benefits in adults with hereditary BSEP deficiency

The patients showed “similar reduction in itch and SBA [serum bile acid] in response to IBAT inhibitor therapy as reported in pediatric phase III trials,” say Carola Dröge (Otto von Guericke University Magdeburg, Germany) and colleagues.

They explain that “IBAT inhibitors reduce SBA and pruritus in PFIC2 [progressive familial intrahepatic cholestasis 2] patients”; however, “[s]o far, little is known about the use of IBAT inhibitors in adults.”

To investigate, they collected clinical data on patients with intrahepatic cholestasis who presented to outpatient clinics in Germany or Australia. The team also carried out whole exome sequencing to determine underlying genetic variants.

Of the 10 participants, 60% were women. Six of the patients developed their symptoms in infancy (within 3 months of life), while the remaining four patients developed them as adolescents or adults (age range 16 to 47 years). The age at initiation of IBAT inhibitor therapy varied from 12 years to 59 years.

The participants with earlier disease onset were more likely than those with onset in adolescence and adulthood to have biallelic rather than monoallelic ABCB11 or BSEP mutations.

The starting dose of IBAT inhibitor therapy varied depending on type, from 5 µg/kg to 570 µg/kg, with seven patients starting on 40 µg/kg. Most (80%) of the patients received concomitant ursodeoxycholic acid.

Prior to IBAT inhibitor therapy, all the patients suffered from severe itch, with scores of 6 to 10 points on a visual analog scale of 0–10 points, where higher points indicate worse itch. The only exception was a patient who had already progressed to cirrhosis and was taking fibrate who had a pretreatment itch score of 1 point and did not show improvement. The pretreatment SBA levels ranged from 98–540 µmol/L.

The researchers report a “strong reduction” in both itch and SBA, with itch scores decreasing to 0 points in six patients and to between 1 and 4 points in the remaining patients.

Complete responses, defined as normalization of SBA and itch or a reduction in SBA greater than 75% (at least below 102 μmol/L) and an itch reduction of at least 2 points to 4 points or below, were achieved in 70% of patients.

Moreover, 30% of patients were able to stop taking their IBAT inhibitor due to clinical remission, the team highlights.

Dröge et al also say that “weight adjusted IBAT inhibitor dosing as used in pediatric trials was safe and well tolerated in our cohort.