Cited 1 times since 2025 (2.8 per year) source: EuropePMC Gastro hep advances, Volume 5, Issue 1, 12 2 2025, Pages 100764 Comparative Efficacy of all Available Pharmaceutical Therapies for Moderate to Severe Crohn's Disease: A Systematic Review and Network Meta-Analysis. Versteegh M, Idema DL, Huygens S, Jenniskens K, Pierik M, Römkens T, van Schaik F, Wahab P, Huis In't Veld LF, Kusters M, van der Braak K, Hooft L, Damen JAA
Background and aims
The therapeutic landscape for Crohn's disease (CD) has expanded, offering increased treatment possibilities, but with limited comparative evidence.This study compares efficacy and discontinuation rates of all pharmaceutical therapies in moderate-to-severe CD.
Methods
We conducted a systematic review (until October 2023) and network meta-analyses (NMAs) of phase-III randomized controlled trials for induction and maintenance of clinical remission and drug discontinuation rates. Frequentist NMA results and surface under the cumulative ranking (SUCRA) rankings were reported for immunomodulator (IM)-naive, biologic-naive and -exposed patients. Confidence in results was evaluated using Confidence in Network Meta-Analysis.
Results
The search resulted in 3017 references, of which 77 randomized controlled trials from 1990 and later were included in the NMA. Networks were sparse and therapies had overlapping confidence intervals. The smaller IM-naive network and the larger biologic-naive network produced highly comparable relative risks. In biologic-naive patients, adalimumab (high induction regimen) had the highest SUCRA ranking for induction of clinical remission, and infliximab/azathioprine combination therapy had the highest SUCRA ranking for maintenance of remission. Among IMs, methotrexate had the highest ranking for induction and azathioprine for maintenance of remission. In biologic-exposed patients, upadacitinib had the highest SUCRA ranking for induction and maintenance of clinical remission, although for maintenance this finding may be biased due to the trial designs. Adverse event related discontinuation was numerically highest for methotrexate, azathioprine and upadacitinib. Confidence rating was moderate, low, or very low for most comparisons.
Conclusion
This NMA including IMs, biologics and small molecules, suggests that anti-tumor necrosis factor (combination) therapy is most efficacious in biologic-naive patients and upadacitinib in biologic-exposed patients. Differences in relative risks were small and confidence intervals overlapping. Findings show that conventional therapies remain important in the treatment algorithm for CD patients.
