Efficacy of Medical Therapies for Fistulizing Crohn's Disease: Systematic Review and Meta-analysis

BACKGROUND & AIMS: Fistulas are debilitating complications of Crohn's disease (CD) that affect up to 50% of patients. We conducted a systematic review and meta-analysis of randomized controlled trials to assess the efficacy of treatments for fistulizing CD. METHODS: We searched publication databases from inception through December 13, 2016 for trials comparing the efficacy of a therapeutic agent (single or combination) with placebo or another active therapy in adult patients with any form of fistulizing CD. The Cochrane risk of bias tool was used to assess the methodological quality of trials; the overall quality of evidence was evaluated using GRADE. Primary outcomes included induction and maintenance of fistula response and remission. Pooled risk ratios (RRs) and 95% CIs were calculated for each outcome. RESULTS: We analyzed data from 27 trials; most studies (21/27) focused on patients with perianal fistulizing CD. We found moderate-quality evidence to support the efficacy of tumor necrosis factor (TNF) antagonists (RR, 2.01; 95% CI, 1.36-2.97), particularly infliximab, ustekinumab (RR, 1.77; 95% CI, 0.93-3.37), and mesenchymal stem cell therapy (RR, 1.31; 95% CI, 0.98-1.73) for induction of fistula remission. We found low-quality evidence for the efficacy of vedolizumab and immunosuppressives. There was also low-quality evidence to support the efficacy of combination therapy with TNF antagonists and antibiotics vs a TNF antagonist alone. CONCLUSION: In a systematic review and meta-analysis of 27 controlled trials, we found TNF antagonists to be effective for induction and maintenance of perianal fistula response and remission. There are few data on the effects on internal fistulae. Further studies are needed, particularly for ustekinumab, vedolizumab, and stem cell therapies, in patients with fistulizing CD.