Meta‐Analysis: Safety and Effectiveness of Advanced Therapies in Inflammatory Bowel Disease Patients With Concomitant Primary Sclerosing Cholangitis
Amera Elzubeir, Anjana Kumar, Alistair McArdle, Emily Holden, Leo Alexandre, Simon Rushbrook, Kate D. LynchABSTRACT
Background
Inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC) is a distinct phenotype (PSC‐IBD). Data on the safety and effectiveness of advanced IBD therapies on IBD outcomes in PSC‐IBD remain limited.
Methods
A systematic review and meta‐analysis assessed the safety and effectiveness of advanced therapies in adults with PSC‐IBD. MEDLINE, Embase, Cochrane databases and Web of Science were searched to July 2026. The primary outcome was IBD clinical remission. Secondary outcomes included clinical response, corticosteroid‐free remission, mucosal healing, adverse event‐related treatment discontinuation and colorectal neoplasia. A random‐effects model was used for pooled estimates.
Results
Five retrospective case‐series ( n = 394) evaluating infliximab, adalimumab, vedolizumab and tofacitinib were included (median follow‐up of 18.4 months). Pooled clinical remission rates were 24.7% (95% CI: 17.2%–33.0%) at 3 months and 28.6% (95% CI: 16.3%–42.6%) at 6–12 months. Corticosteroid‐free remission was achieved in 45.4% (95% CI: 33.1%–57.9%) and mucosal healing in 25.6% (95% CI: 13.6%–39.5%). Tofacitinib was associated with a clinical response rate of 59.3% (95% CI: 40.0%–77.2%) and low adverse event rate, in a single available study. Adverse event‐related discontinuation occurred in 9.1% (95% CI: 4.4%–15.1%), while 31.8% (95% CI: 25.5%–38.5%) experienced primary non‐response or secondary loss of response. The pooled proportion of colorectal neoplasia was 10.5% (12/112; 95% CI: 5.3%–17.1%). Five patients developed colorectal cancer (5/112; 4.3%) and two (2/177; 0.8%) cholangiocarcinoma.
Conclusion
Advanced IBD therapies demonstrate modest but encouraging effectiveness and an acceptable safety profile in PSC‐IBD; however, the available evidence is limited by retrospective study designs, small sample sizes and substantial clinical and methodological heterogeneity. Prospective controlled studies using standardised IBD outcomes are needed to inform optimal therapeutic strategies in this high‐risk population.
Trial Registration
PROSPERO: CRD42024580296