P1117Safety of dual-targeted therapy in Inflammatory Bowel Disease: a systematic review

Background Dual-targeted therapy is an emerging strategy for managing complex or refractory inflammatory bowel disease (IBD), but data on its safety remain limited. This study aimed to systematically assess the safety of dual-targeted treatment. Methods A systematic search of PubMed and Embase (January 2020–October 2025) identified eligible randomized controlled, clinical trials and observational studies in adults with IBD. Search terms included inflammatory bowel disease, Crohn’s disease, ulcerative colitis in combination with dual therapy, combination therapy, dual-targeted therapy, combined use, co-administration. Safety outcomes, serious adverse events (SAEs), infections, deaths, were compared using χ² or Fisher’s tests with Haldane–Anscombe correction where required. Analyses were performed in RStudio. Results A total of 91 records were screened, of which 3 met the inclusion criteria. Across these, 224 patients were analyzed (Crohn’s disease, n = 113; ulcerative colitis, n = 111) with a mean follow-up of 181.6 weeks. In total, 230 dual-therapy combinations were reported: tofacitinib/tumor necrosis factor-alpha inhibitor (anti-TNFα), n = 1; tofacitinib/vedolizumab, n = 13, golimumab/guselkumab, n = 71; adalimumab/vedolizumab, n = 55; anti-TNFα/vedolizumab, n = 41; anti-TNFα/anti-interleukin (anti-IL) agent, n = 11; anti-IL/vedolizumab, n = 21; anti-IL/anti-IL, n = 1; other combinations, n = 16. Comparing small-molecule (n = 14) with non-small-molecule combinations (n = 216), rates of serious adverse events (3.33% vs 10.36%; risk ratio 0.32, CI:0.033-2.565; p = 0.372) and infections (3.33% vs 12.21%; risk ratio 0.273; CI:0.028-2.161; p = 0.375) did not differ significantly. Anti-TNFα–based combinations (n = 179), compared with regimens not containing anti-TNFα (n = 51), showed higher rates of serious adverse events (11.73% vs 1.96%; risk ratio 5.983; CI:1.091-34.083; p = 0.033) and infections (13.96% vs 1.96%; risk ratio 7.122; p = 0.03251), both of which were statistically significant. Vedolizumab-based combinations (n = 130), compared with regimens not containing vedolizumab (n = 100), demonstrated similar rates of serious adverse events (11.53% vs 7.0%; risk ratio 1.6483; CI:0.7215-3.8210; p = 0.352), but significantly fewer infections (6.15% vs 17.0%; risk ratio 0.3619; CI:0.1654-0.7856; p = 0.01612). Mortality did not differ across comparisons. Conclusion Safety outcomes varied by treatment mechanism. Anti-TNFα combinations demonstrated significantly higher SAEs rates, whereas vedolizumab-based regimens showed fewer infections. Evidence for small-molecule combinations remains limited, highlighting the need for larger prospective research. 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Goessens L, Colombel JF, Outtier A, Ferrante M, Sabino J, Judge C, Saeidi R, Rabbitt L, Armuzzi A, Domenech E, Michalopoulos G, Cremer A, García-Alonso FJ, Molnar T, Karmiris K, Gecse K, Van Oostrom J, Löwenberg M, Farkas K, Atreya R, Ribaldone DG, Selinger C, Hoentjen F, Bihin B, Sebastian S; European COMBIO study group; Rahier JF. Safety and efficacy of combining biologics or small molecules for inflammatory bowel disease or immune-mediated inflammatory diseases: A European retrospective observational study. United European Gastroenterol J. 2021 Dec;9(10):1136-1147. doi: 10.1002/ueg2.12170. Epub 2021 Oct 25. PMID: 34694746; PMCID: PMC8672088. Conflict of interest: Rellou, Sofia: No conflict of interest Kordalis, Leonidas: No conflict of interest Petrousis, Grigorios: No conflict of interest Bresso, Francesca: No conflict of interest Hedin, Charlotte Rose: Grant: C. R. H. Hedin has received specific project grants from Takeda and Tillotts. Personal Fees: C. R. H. Hedin served as a speaker and/or advisory board member for AstraZeneca, Abbvie, Dr Falk Pharma and the Falk Foundation, Galapagos, Janssen, Lilly, Pfizer, Ferring, Takeda, Tillotts Pharma, and received grant support from Tillotts and Takeda. These fees are invoiced by her employer. Bilican, Gülden: I have no conflicts of interest to declare. Haas, Stephan L.: SLH served as a speaker and/or advisory board member for Celltrion, Ferring, Janssen, Lilly, Mediahuset, Pfizer, Santax Medico, Takeda, and Tillotts Pharma.