Introduction
Autoimmune cholestatic liver diseases (ACLD), including PBC and PSC, are chronic conditions causing bile acid accumulation, liver damage, and debilitating pruritus. Current treatments often fail to relieve symptoms, creating a need for new options. Ileal bile acid transporter (IBAT) inhibitors, such as maralixibat and linerixibat, offer a novel approach by reducing bile acid reabsorption. This meta-analysis evaluates their efficacy and safety in adults with ACLD.
Aims & Methods
To evaluate the efficacy and safety of ileal bile acid transporter (IBAT) inhibitors in adults with autoimmune cholestatic liver diseases (ACLD), specifically primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), focusing on patient-related and biochemical outcomes. We conducted a meta-analysis in accordance with PRISMA guidelines, registered on PROSPERO (ID: 621722). A comprehensive search of PubMed, Embase, and CENTRAL was performed from inception to January 2025 to identify randomized and observational studies evaluating IBAT inhibitors in adults with ACLD and pruritus, with a minimum follow-up of 12 weeks. The primary outcome was the change in pruritus severity measured by the 5-D Itch Scale. Secondary outcomes included: (1) changes in sleep quality assessed by the MOS Sleep Scale; (2) biochemical efficacy endpoints, including changes from baseline in serum bile acids (BA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), autotaxin (ATX), 7α-hydroxy-4-cholesten-3-one (C4), and fibroblast growth factor 19 (FGF19); and (3) safety outcomes.
Results
Three studies (2 RCTs, 1 pilot study) comprising 180 patients (153 PBC, 27 PSC) were included. Treatment involved maralixibat (n=42) and linerixibat (n=138). Pruritus severity significantly improved with IBAT inhibitors (mean difference [MD] = -4.93; 95% CI [-6.26, -3.59]; p < 0.0001) with low heterogeneity (I² = 24.6%). IBAT inhibitors significantly improved sleep quality, as measured by the MOS Sleep Scale (MD = -8.12, 95% CI [-13.54, -2.70], p = 0.0033; I² = 0%). Regarding liver function, significant reductions were observed in AST (MD = -14.74, 95% CI [-24.22, -5.27], p = 0.0023) and GGT (MD = -50.34, 95% CI [-86.48, -14.20], p = 0.0063), while changes in ALT (MD = -6.45, 95% CI [-16.43, 3.53], p = 0.2055) and bilirubin (MD = 0.09, 95% CI [-0.03, 0.21], p = 0.15) were not statistically significant. Treatment led to significant reductions in serum BA (MD = -6.81, 95% CI [-9.34, -4.28], p < 0.0001), FGF19 (MD = -51.46, 95% CI [-73.30, -29.61], p < 0.0001), and ATX (MD = -74.41, 95% CI [-118.57, -30.26], p < 0.001), along with an increase in C4 levels (MD = 25.12, 95% CI [11.84, 38.41], p < 0.0002). Adverse events were reported in 89.7% of patients, most commonly diarrhea (22.7%), abdominal pain (18.2%), and nausea (12.2%), while serious adverse events were rare (2.2%). Treatment discontinuation occurred in 8.0% of cases.
Conclusion
IBAT inhibitors are associated with clinically meaningful improvements in pruritus and sleep quality in adults with ACLD. Although adverse events are common, serious events are infrequent, supporting a favorable safety profile. These findings highlight the promise of IBAT inhibitors as an emerging therapeutic option for cholestatic pruritus, though further high-quality studies are needed to confirm long-term benefits and safety across diverse patient populations.
Disclosure
GGLC has received a research grant from IPSEN. The other authors have no conflicts of interest to declare.
