Objective: This umbrella review aims to evaluate the current body of evidence derived from placebo-controlled trials in the management of Crohn’s disease (CD) by systematically reviewing and summarizing findings from meta-analyses.

Methods: We systematically searched databases such as PubMed, Cochrane Library, and Scopus for meta-analyses published up to January 2025, focusing on placebo-controlled trials related to Crohn’s disease treatments. We assessed the quality of the meta-analyses using the AMSTAR-2 tool and summarized the treatment efficacy, safety, and outcomes.

Results: Out of 35 included meta-analyses, the most common treatments studied were biologic agents, including TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors. Overall, biologics showed a significant benefit over placebo in inducing remission, maintaining remission, and improving quality of life. However, safety concerns were prevalent, particularly with long-term use. Other treatments, such as corticosteroids and antibiotics, were also studied but with varying efficacy and safety profiles.

Conclusions: Biologic therapies represent the most effective treatments in CD, with substantial evidence supporting their use in clinical practice. However, issues regarding long-term safety, side effects, and individual patient characteristics must be considered when deciding on treatment options. This umbrella review highlights the importance of continued research on optimal therapy duration and the potential for personalized treatment approaches.

Crohn’s disease, placebo-controlled trials, meta-analysis

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