Background and Aims: There is still uncertainty about the efficacy and safety of subcutaneous compared to intravenous administration of biologics for inflammatory bowel disease (IBD) remission. Methods: In this systematic review and meta-analysis, we searched Cochrane, PubMed, SCOPUS, CINHAL, and preprint archives for trials that compared the efficacy and safety of subcutaneous and intravenous biologics for the induction and maintenance of IBD remission. Meta-analysis was carried out with a subgroup analysis for Crohn’s disease (CD) and Ulcerative Colitis (UC), heterogeneity using I
2, and publication bias using funnel plots. Results: A total of 14 randomized controlled trials, 9 on CD, 4 on UC, and 1 with data on both were included Subcutaneous, compared to intravenous administration, was less efficacious for the induction of remission; overall (OR 0.68, 95%CI 0.35–1.31, I
2 = 83%), worse in UC (OR 0.35, 95%CI 0.07–1.79, I
2 = 91.2%), and showed similar efficacy in CD (OR 0.97, 95%CI 0.73–1.30, I
2 = 0%). For the maintenance of remission, subcutaneous biologics were almost similar to intravenous biologics; overall (OR 0.97, 95%CI 0.63–1.49, I
2 = 57.1%), with less efficacy in UC (OR 0.82, 95%CI 0.54–1.23, I
2 = 52%), but superior efficacy in CD (OR 1.81, 95%CI 1.09–3.01, I
2 = 0%). Subcutaneous, compared to intravenous biologics, showed slightly higher odds of treatment discontinuation (OR 1.32, 95%CI 1.02–1.71, I
2 = 14.2%), worse in UC (OR 1.52, 95%CI 1.17–1.98, I
2 = 13%), and was similar to intravenous for CD (OR 1.03, 95%CI 0.65–1.62, I
2 = 0%). Conclusion: Subcutaneous administration has lower efficacy for the induction of remission but can achieve almost similar efficacy and safety in maintaining remission in IBD. Subcutaneous injection has better efficacy and safety in CD than in UC.
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