Efficacy and Tolerability of Immunoregulators and Antibiotics in Fistulizing Crohns Disease: A Systematic Review and Meta-analysis of Placebo-controlled Trials

Shekoufeh      Nikfar; Hadi      Mirfazaelian; Mohammad      Abdollahi

Abstract

Objective: This meta-analysis of randomized controlled trials was conducted to evaluate the efficacy and tolerability of two drug groups (immunoregulators and antibiotics) in the treatment of fistula in Crohns disease (CD). Methods: PubMed, Embase, Scopus, Google Scholar, and Web of Science were searched for clinical trial studies investigated the effects of immunoregulators and antibiotics in the treatment of fistulizing CD. Clinical response and adverse effects were the key outcomes of interest. Data were searched from the time period of 1966 through June 2010. Result: Eleven randomized placebo-controlled clinical trials that met our criteria (nine in different immunoregulators and two in antibiotics) were included in the analysis. Pooling of data showed that immunoregulators and antibiotics are significantly effective for at least a 50% reduction from baseline in the number of open actively draining fistulas with relative risk (RR) of 2.57 (95% CI of 1.55-4.25, P= 0.0003) in four trials and 2.05 (95% CI of 1.03-4.08, P= 0.0414) in two trials respectively. The summary of RR for complete closure of fistulas in nine trials was 2.65 with a 95% CI of 1.66-4.22 and a significant RR (P < 0.0001). In regard to the tolerability, both immunoregulators and antibiotics showed insignificant adverse effects in comparison to placebo with an RR of 1.11 (95% CI of 0.96-1.27, P= 0.1513) and 0.6 (95% CI of 0.36-1, P= 0.0515), respectively and discontinuation because of these adverse effects in drug-treated groups was the same as placebo. Data about severe adverse effects were only available for immunoregulators that showed a significantly higher incidence when compared to placebo (RR= 2.24 with a 95% CI of 1.05-4.79; significant at P= 0.0374). Conclusion: This meta-analysis demonstrates the efficacy of immunoregulators and antibiotics in fistulizing CD. Regarding the safety, mild to moderate adverse effects were the same in both antibiotic and immunoregulators groups in comparison to the placebo but incidence of severe adverse effects in immunoregulator groups was higher than that of antibiotics.

Keywords: Crohn's disease, fistula, inflammatory bowel disease, immunoregulators, antibiotic, adverse effects, meta-analysis, systematic review, Placebo-controlled Trials, granulomatous inflammation, monoclonal antibodies, perianal fistula, Der Simonian-Laird methods, Cochran Q test, Kendall's test, tumor necrosis factor alpha, Escherichia coli, Saccharomyces cerevisiae, immunoregulators (azathioprine), anti-TNF agents, sargramostim, granulocyte, –, macrophage colony-stimulating factor, TGF, corticosteroid, perianal fistulas, Gastroenterology, luminal fistulas