REVIEW ARTICLE Anti-tumor Necrosis Factor and Postoperative Complications in Crohn’s Disease: Systematic Review and Meta-analysis Uri Kopylov, MD,* Shomron Ben-Horin, MD,* Oded Zmora, MD, † Rami Eliakim, MD,* and Lior H. Katz, MD* Background: Anti-tumor necrosis factor (TNF) antibodies are ef- ﬁcacious in patients with Crohn’s disease (CD) but the inﬂuence of these medications on surgical outcomes in CD patients has been frequently debated. The aim was to evaluate the impact of preoper- ative treatment with anti-TNF antibodies on postoperative compli- cations in CD patients undergoing abdominal surgery. Methods: A systematic review and meta-analysis of comparative cohort studies was performed assessing postoperative complica- tion rates in CD patients who were treated with anti-TNF antibod- ies within 3 months before surgery versus patients who were not. The primary outcome was overall complication rate within 1 month of surgery. Secondary outcomes included the rate of infec- tious and noninfectious complications. The quality of studies was assessed based on selection of patients and controls, comparability of the study groups, and assessment of outcomes. Odds ratios (OR) with 95% conﬁdence intervals (CIs) were computed. Results: A total of eight studies including 1641 patients were included in our meta-analysis. Preoperative inﬂiximab therapy in CD patients undergoing abdominal surgery was associated with a trend toward an increased rate of total complications (OR 1.72, 95% CI, 0.93–3.19). Anti-TNF treatments were associated with a modestly increased risk of infectious complications (OR 1.50, 95% CI 1.08–2.08), mostly remote from the surgical site (OR 2.07 95% CI 1.30–3.30) and with a trend toward a higher rate of noninfectious complications (OR 2.00, 95% CI 0.89–4.46). Conclusion: Preoperative inﬂiximab treatment is associated with an increased risk of postoperative infectious complications, mostly nonlocal. A trend toward an increased risk of noninfectious and overall complications was also observed. (Inﬂamm Bowel Dis 2012;000:000–000) Key Words: postoperative, Crohn’s disease, complications, adverse effective, infectious, anti-TNF, inﬂiximab M onoclonal anti-tumor necrosis factor (TNF) antibodies have been employed in the treatment of Crohn’s disease (CD), ulcerative colitis (UC), and other inﬂamma- tory disorders for over a decade. Inﬂiximab (IFX) therapy has proven to be effective in induction and maintenance of remission in CD patients. 1 However, this medication has also been associated with diverse adverse effects such as an increased risk of infections, infusion reactions, and a possible increased incidence of lymphoma. 2 Up to two-thirds of all CD patients are expected to require surgery at least once during the course of their dis- ease, 3,4,6 and 40% will undergo two or more surgical interventions. Surgery is an effective method for induction of remission and for treatment of CD complications. How- ever, surgical procedures may be associated with consider- able morbidity in CD patients, with a reported complication rate of up to 22%. 7–10 Nonetheless, the data concerning the inﬂuence of IFX on surgical risk in patients with inﬂamma- tory bowel disease (IBD) are equivocal. For patients with UC, a meta-analysis by Yang et al 11 pointed to an increased risk of short-term postoperative complications in patients who received preoperative IFX. Although several studies pertaining to complications of preoperative IFX therapy in CD patients have been published, the impact of anti-TNF therapy on the rate of postoperative complica- tions in CD patients remains unclear. The aim of our study was to evaluate the impact of preoperative use of anti-TNF antibodies on the rate of post- operative complications in patients with CD by conducting a systematic review and meta-analysis of the existing literature. MATERIALS AND METHODS Search Strategy We searched the PubMed database for publications from 1966 to September 2011. The search terms used were ‘‘IFX/anti-TNF; postoperative/perioperative complications (or risk), and Crohn’s disease/IBD.’’ Their MeSH terms were crossed. We manually scanned references of all included studies to identify additional relevant publications. Additional Supporting Information may be found in the online version of this article. Received for publication February 2, 2012; Accepted February 23, 2012. From the *Department of Gastroenterology, † Department of Surgery and Transplantation, Chaim Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel. Reprints: Uri Kopylov, MD, Gatroenterology Department, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, 52621, Israel (e-mail: ukopylov@gmail.com). Copyright V C 2012 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.22954 Published online in Wiley Online Library (wileyonlinelibrary.com). Inﬂamm Bowel Dis 1