Objectives To systematically synthesise available evidence on the safety of advanced combination therapy (ACT) in adults with inflammatory bowel disease (IBD), with secondary exploratory evaluation of efficacy outcomes. Design Systematic review and meta-analysis. Data sources Searches of Embase (via Ovid), MEDLINE and PubMed were initially undertaken on 9 May 2025 and updated on 8 April 2026. Additional studies were identified through hand-searching and reference list screening. Eligible publications were restricted to those published between 1 January 2015 and 31 March 2026. Eligibility criteria We included randomised controlled trials as well as observational and descriptive studies. Conference abstracts, reviews, editorials and commentaries were excluded. Inclusion was restricted to publications in English. Data extraction and synthesis Two reviewers independently screened studies, extracted data and assessed risk of bias using Joanna Briggs Institute tools and Cochrane RoB-1. Pooled proportions of total adverse events (TAEs), serious adverse events (SAEs) and treatment discontinuations were calculated using random-effects meta-analysis. Subgroup analyses were conducted by drug class. Where meta-analysis was not appropriate, findings were narratively synthesised. Results Fifty-two studies (n=2022 participants) were included. The most frequent combinations were anti-TNFa plus integrin inhibitors and interleukin (IL) 23 plus integrin inhibitors. Pooled analyses demonstrated low rates of SAEs (eg, anti-TNFa plus integrin inhibitors: 2.7%, 95% CI 0.22% to 6.86%) and discontinuations (6.38%, 95% CI 2.36% to 11.58%), although heterogeneity was substantial and certainty of evidence was very low, with some analyses based on small sample sizes. Conclusion ACT may be associated with low rates of SAEs in selected patients with refractory IBD; however, the evidence is limited by small sample sizes, heterogeneity and predominantly observational designs. Robust conclusions regarding safety and efficacy cannot be made due to very low GRADE certainty. PROSPERO registration number CRD420251025883
Radford et al. (Mon,) studied this question.