Observational data show IBAT inhibitor promise for pruritus in late-onset PFIC and ICP

Presenting the findings for late-onset PFIC in a poster at the EASL Congess 2026 in Barcelona, Spain, Marlyn Mayo (UT Southwestern Medical Center, Dallas, Texas, United States) and colleagues explain that “maralixibat is a minimally absorbed IBAT inhibitor that prevents enterohepatic bile acid recirculation and is approved for the treatment of PFIC in patients ≥3 months of age in the European Union and for the treatment of cholestatic pruritus in patients with PFIC ≥12 months of age in the US.”

Real-world evidence for maralixibat response in adults with late-onset PFIC

Mayo et al retrospectively reviewed the medical records of six patients who received maralixibat either through a compassionate use program or private insurance coverage.

Most of the patients were women (n=4) and the median age at PFIC diagnosis was 12.0 years, ranging from 3.0 years to 60.0 years. The participants were aged a median of 17.5 years at the onset of pruritus, and 25.9 years when maralixibat was initiated.

In terms of the types of PFIC, two patients had bile salt export pump, two had multidrug resistance 3, one had familial intrahepatic cholestasis 1, and one was heterozygous for a chromosome 17 deletion in the HNF1B gene.  

The initial maralixibat dose given ranged from 190 µg/kg once daily to 570 µg/kg twice daily, with the final dose ranging from 380 µg/kg once daily to 20 mg twice daily.

Most of the patients had received other antipriuritic drugs prior to starting maralixibat, primarily ursodeoxycholic acid (83%), antihistamines (83%), or cholestyramine (67%).

At the time of maralixibat treatment, one patient was being evaluated for liver transplant and one was on the waitlist.

The researchers report that during a median 8.5 months of maralixibat treatment “all patients showed complete or near-complete resolution of pruritus.”

Specifically, three patients with pre-treatment Clinician Scratch Scale (CSS) scores of 2 (active scratching without abrasions), 3 (abrasions), or 4 (cutaneous mutilations, hemorrhage, scarring) achieved scores of 0 (no pruritus) with maralixibat treatment.

A further two patients had at least a 2-point reduction in CSS score with treatment, from a score of 4 to 2 or 1, while the score in the sixth patient fell from 2 to 1. The investigators note that “a ≥ 1-point reduction in CSS is considered clinically meaningful.”

Among five patients who had serum bile acid data available, median levels fell from 217 µmol/L at baseline to 16 µmol/L at the last follow-up, and “bilirubin and liver enzymes remained stable or decreased” in most of the patients, says the team.

The treatment was well tolerated. Adverse events were reported in half of the patients, including diarrhea in three patients, an increase in transaminase levels in two patients that normalized by the last follow-up, an increase in bilirubin in one patient, and abdominal pain in one patient.

Mayo and co-investigators note that none of the patients discontinued treatment due to severe liver events, such as decompensation, and the two patients who were being considered for liver transplant before treatment were no longer being so after maralixibat treatment.

They conclude that “these real-world results suggest IBAT inhibitors may offer benefit in this group,” and add that “additional studies evaluating longer follow-up in a larger cohort are warranted to better characterise the potential benefits of maralixibat in late-onset PFIC.”

Case series of maralixibat treatment in women with ICP

Catherine Williamson (King’s College Hospital NHS Trust, London, UK) and colleagues studied the effects of maralixibat in four women aged between 36 and 42 years, who had severe, recurrent ICP with marked hypercholanaemia, with or without pruritus, and an insufficient response to ursodeoxycholic acid (UDCA) treatment.

A genetic predisposition to cholestasis was identified in three of the women, one woman had pruritus, and total serum bile acid (SBA) levels before maralixibat treatment were between 118 µmol/L and 237 µmol/L.

The women started maralixibat at gestational weeks 18 to 28 at daily doses of 70 µg/kg in two women, which were uptitrated to 175 µg/kg and 210 µg/kg per day, while the remaining two women received daily doses of 140 µg/kg and 300 µg/kg. All of the women concomitantly received UDCA.

Two women, neither of whom had pruritus, experienced an improvement in total SBA levels to below 40 µmol/L, from pretreatment levels of 118 µmol/L and 237 µmol/L.

The researchers describe the improvement in total SBA in the remaining two women as “limited.” One woman developed pruritus at 17 weeks and had elevated total SBA levels of 219 µmol/L at 28 weeks’ gestation, both of which improved when she started maralixibat at 28 weeks plus 5 days gestation; however, SBA levels increased again with advancing gestation.

Similarly, in the second woman, her total SBA level was elevated (148 μmol/L) from 9 weeks’ gestation. This fell to 52–93 μmol/L with the initiation of maralixibat at 18 weeks’ gestation, but it rose again to 125 μmol/L at 31 weeks.

Williamson and team report that “all patients had good neonatal outcomes.” Three women experienced mild gastrointestinal events during maralixibat treatment, but they say that these were “manageable.”

The researchers conclude that “treatment with maralixibat may effectively manage ICP by lowering SBA and improving pruritus.”