Infliximab for maintenance of medically-induced remission in Crohn's disease.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 38372447 · doi:10.1002/14651858.CD012609.pub2
What was done
Authors conducted a Cochrane systematic review searching CENTRAL, Embase, MEDLINE, ClinicalTrials.gov, and WHO ICTRP through June 23, 2023. They included randomized controlled trials (RCTs) evaluating infliximab versus placebo or active comparators for maintaining remission or response in Crohn's disease. Primary and secondary outcomes (clinical relapse, loss of response, endoscopic relapse, withdrawals due to adverse events, and serious adverse events) were pooled as risk ratios (RR) with 95% confidence intervals (CI) and evaluated using GRADE.
What was found
Nine RCTs with 1,257 participants were analyzed. Infliximab was probably superior to placebo in reducing clinical relapse (56% vs 75%; RR 0.73, 95% CI 0.63 to 0.84; NNTB = 5; moderate certainty). Infliximab combined with purine analogues was probably superior to purine analogues alone in preventing clinical relapse (12% vs 59%; RR 0.20, 95% CI 0.10 to 0.42; NNTB = 2; moderate certainty). Comparisons against biosimilars showed similar relapse rates (47% vs 40%; RR 1.18, 95% CI 0.82 to 1.69; low certainty), though infliximab had higher loss of response (49% vs 32%; RR 1.50, 95% CI 1.01 to 2.23; low certainty) and higher withdrawals due to adverse events (27% vs 0%; RR 20.73, 95% CI 2.86 to 150.33; low certainty). Evidence for adverse event outcomes, adalimumab comparisons, and subcutaneous versus intravenous biosimilar formulations was of very low certainty or absent.
Why it matters
This review establishes moderate-certainty evidence that infliximab maintenance therapy—particularly when combined with purine analogues—reduces clinical relapse risk in Crohn's disease, but reveals substantial evidence gaps regarding safety profiles and relative efficacy against other active biologics.
Limits
Total participant numbers across all nine trials were modest (n = 1,257), and baseline clinical characteristics were heterogeneous (only three trials enrolled solely patients in baseline remission). Concomitant medications were permitted across all trials. Evidence for all safety endpoints and direct active comparisons (such as adalimumab) was downgraded to low or very low certainty due to severe imprecision and risk of bias. Four trials were directly funded by pharmaceutical companies.
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