The Effect of Anti-Tumor Necrosis Factor Alpha Agents on Postoperative Anastomotic Complications in Crohn's Disease: a Systematic Review

BACKGROUND: Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications. OBJECTIVE: We assessed the effect of anti-tumor necrosis factor alpha on postoperative complications in patients with Crohn's disease undergoing abdominal surgery. DATA SOURCES: Studies were identified through electronic and manual searches. STUDY SELECTION: Observational studies on patients with Crohn's disease undergoing laparoscopic or open abdominal surgery were included. INTERVENTIONS: Anti-tumor necrosis factor alpha agents were administered within 3 months before surgery. MAIN OUTCOME MEASURES: The primary outcome was anastomotic complications including overt dehiscence, intra-abdominal abscess, and enteric fistulas. RESULTS: Fourteen studies on 679 patients in the intervention (anti-tumor necrosis factor alpha) group and 2363 controls were included. Random-effects meta-analysis found no difference in anastomotic complications between the 2 groups (7.6% versus 8.2%; risk ratio, 0.91; 95% CI, 0.56-1.48). There was clear heterogeneity between studies. In subgroup analyses, the anti-tumor necrosis factor alpha increased anastomotic complications in trials with a lower risk of bias, but not in the studies with a higher bias risk (risk ratio, 1.63; 95% CI, 1.03-2.60 and risk ratio, 0.17; 95% CI, 0.05-0.60). In the overall analysis and in studies with a lower bias risk, anti-tumor necrosis factor alpha agents increased the risk of nonanastomotic surgical complications, major medical complications, and minor medical complications. LIMITATIONS: Limitations of observations studies. CONCLUSIONS: In studies with a low risk of bias, antitumor necrosis factor alpha agents increased the risk of anastomotic complications. Inadequate bias control may lead to an underestimated risk of anastomotic complications.