Comparative Effectiveness and Safety of Ustekinumab versus Anti–TNF Therapy in Crohn Disease: A Systematic Review

<title>Abstract</title> <p> <bold>Purpose</bold> : The optimal sequencing of biologic therapies in Crohn disease remains uncertain, particularly when comparing anti–tumor necrosis factor (anti-TNF) agents and ustekinumab (UST). We performed a systematic review to evaluate their comparative effectiveness and safety. <bold>Methods</bold> : We conducted a systematic review following PRISMA 2020 guidelines and registered the protocol in PROSPERO (ID: 1057121). PubMed, ScienceDirect, and Cochrane Library were searched from September 17, 2024, to February 7, 2025. We included randomized and observational studies comparing UST and anti-TNF therapies in adult patients with Crohn disease. Outcomes included clinical response, remission, objective outcomes, and safety. Findings were synthesized narratively due to heterogeneity. <bold>Results</bold> : Ten studies were included, comprising retrospective cohorts and one randomized controlled trial. Early induction outcomes favored anti-TNF therapy in some studies, particularly for clinical response. However, clinical remission and objective outcomes were generally comparable across therapies. In biologic-experienced patients, UST demonstrated higher treatment persistence and lower discontinuation rates. Safety outcomes were similar across groups. <bold>Conclusions</bold> : UST and anti-TNF therapies show broadly comparable effectiveness and safety in Crohn disease. Anti-TNF agents may provide advantages in early response, while UST may offer greater durability in biologic-experienced patients. Individualized biologic selection and treatment sequencing strategies are supported by these findings. </p>