Abstract Background The management of inflammatory bowel disease in patients with primary sclerosing cholangitis (PSC-IBD) remains challenging, and the effectiveness of advanced therapies in this phenotype is not well understood. This systematic review and meta-analysis evaluated IBD-specific efficacy and safety outcomes across biologic and small-molecule therapies. Methods Electronic databases including PubMed, Embase, SCOPUS and CENTRAL were searched for studies reporting clinical or endoscopic IBD outcomes in adults with PSC-IBD treated with advanced therapies including biologics and small molecules. Pooled proportions were calculated using random-effects models with logit transformation using R’s “meta” package. Primary outcomes were clinical remission and mucosal healing; secondary outcomes included endoscopic improvement, any adverse event, treatment discontinuation due to adverse events, and acute cholangitis during therapy. Subgroup analysis was conducted stratifying results based on therapeutic class and chi-squared statistics was used to quantify differences. Results Upon screening eight studies (n = 512) were included in the review. The pooled clinical remission rate was 38% (95% CI 31–45; I² = 40%), and endoscopic remission occurred in 26% (95% CI 18–36; I² = 58%). Endoscopic improvement was observed in a larger proportion at 57% (95% CI 0.50–0.63; I² = 32%). Across studies, any adverse event occurred in 30% (95% CI 0.24–0.37; I² = 55%) and treatment discontinuation due to such adverse events was reported in 14% (95% CI 0.11–0.18; I² = 47%) of the pooled cohorts. Acute cholangitis developed in 19% (95% CI 0.10–0.35; I² = 91%). Subgroup analyses showed significant, therapeutic class specific variation in both discontinuation and adverse-event rates (p = 0.019 and p = 0.045) amplifying the significance of tailored therapeutic selection in PSC-IBD, however no such significant difference was seen in subgroup analysis in the context of efficacy endpoints. The substantial heterogeneity seen in many of the outcomes reflects differences in study design, follow-up duration and variation in outcome definitions across studies. Conclusion Advanced therapies offer clinical and endoscopic benefit in PSC-IBD, although remission rates remain moderate. Safety outcomes align with existing experience, but cholangitis, treatment discontinuation, and subgroup differences highlight the need for careful therapeutic selection and monitoring. Given the observational nature of available evidence, these findings should be interpreted cautiously, and prospective trials are essential to guide optimal management of this complex condition. Conflict of interest: Dey, Pritom: No conflict of interest Bhanderi, Bhuvan: No conflict of interest Da’Costa, Jedd: No conflict of interest Joshi, Deepak: No conflict of interest Kent, Alexandra: I have received honoraria/Consultancy/Sponsorship fees from: Lilly, AbbVie, Coloplast, J & J, Pfizer, Takeda, Tillotts, Dr Falk, Galapagos/AlfaSigma Pavlidis, Polychronis: Advisory services/ speaker fees/ conference sponsorship/ research grants: Abbvie, Alfasigma, DrFalk, J & J, Pfizer, Roche, Takeda, Teva
Dey et al. (Thu,) studied this question.