Effect Of Anti-TNF Agents On Postoperative Complications And Prevention Of Postoperative Recurrence In Patients With Inflammatory Bowel Disease Based On Meta-analysis

【Background】Inflammatory bowel disease (IBD) comprises two types of chronic intestinaldisorders: ulcerative colitis (UC) and Crohn’s disease (CD). Although biologics such asanti-tumor necrosis factor (anti-TNF) agents are the main evolving achievement in thetreatment of IBD, the patients with IBD have to receive surgery during their diseasecourse. Since the wide use of anti-TNF agents in the clinical practice, the safety in theperioperative setting becomes a major concern among the clinicians. This studysystematically evaluated the effect of anti-TNF agents on postoperative complications andprevention of postoperative recurrence in IBD based on meta-analysis.【Aims】1. To determine the clinical safety and efficacy of preoperative infliximab treatmentin UC patients with regard to short term outcomes following abdominal surgery.2. To determine the effect of preoperative infliximab use on early postoperativecomplications in patients with CD undergoing abdominal surgery. 3. To compare the efficacy of5-aminosalicylates, immunomodulators and biologicsfor postoperative prophylaxis of CD recurrence by using a network meta-analyticalapproach.【Methods】1. PubMed, Embase databases were searched for controlled observational studiescomparing postsurgical morbidity in UC patients receiving infliximab preoperatively withthose not on infliximab. The primary endpoint was total complication rate. Secondaryendpoints included the rate of infectious and non-infectious complications. We calculatedpooled odds ratios (ORs) with95%confidence intervals (CIs) as summary measures.2. PubMed and Embase databases were searched to identify comparative studies thatinvestigated postsurgical morbidity in CD patients receiving infliximab preoperativelywith those not on infliximab. We used meta-analysis with random-effects model tocalculate the pooled ORs with95%CIs for total complication rate as well as major, minor,infectious, and non-infectious complications.3. PubMed, Embase, and Cochrane Library were searched (update to November2013)to identify randomized placebo-controlled, or head-to-head trials among the three drugclasses for prevention of postoperative CD relapse. The primary endpoint for efficacy wasendoscopic recurrence, and the secondary outcomes were clinical recurrence and adverseevents. We conducted a Bayesian network meta-analysis with a mixed treatmentcomparisons to combine both direct and indirect evidences.【Results】1. A total of13studies involving2933patients were included in our meta-analysis.There was no significant association between infliximab therapy preoperatively and total(OR=1.09;95%CI0.87-1.37; P=0.47), infectious (OR=1.10;95%CI0.51-2.38; P=0.81),and non-infectious (OR=1.10;95%CI0.76-1.59; P=0.61) postoperative complications,respectively. Infliximab might be a protective factor against infection for the use within12weeks prior to surgery (OR=0.43;95%CI0.22-0.83; P=0.01). No publication bias wasfound. 2. A total of18studies involving5769patients included in this systematic review.There was significant association between infliximab therapy prior to surgery and total(OR=1.45;95%CI1.04-2.02;13studies,2538patients), infectious (OR=1.47;95%CI1.08-1.99;10studies,2116patients) and non-infectious (OR=2.29;95%CI1.14-4.61;3studies,729patients) postoperative complications respectively. There was no significantdisparity in the major (OR=1.39;95%CI0.85-2.27;9studies,3696patients) and minor(OR=1.39;95%CI0.57-3.40;5studies,753patients) complication rates betweeninfliximab and control groups. No publication bias was detected.3. Fifteen trials involving1507patients were included in this analysis. Biologicalagents were associated with a large and significant reduction of both endoscopic andclinical recurrence compared with placebo,5-aminosalicylates, or immunomodulators.Immunomodulators showed greater efficacy in terms of endoscopic and clinical recurrenceprophylaxis compared with5-aminosalicylates or placebo, but with higher incidence ofadverse events.5-aminosalicylates were superior to placebo for prevention of clinicalrecurrence, without increasing the rate of side effect.【Conclusions】Preoperative infliximab use does not increase the risk of early postoperativecomplications in patients with UC undergoing abdominal surgery. Preoperative infliximabuse modestly increases the risk of total early postoperative complications, and particularlyinfectious complications in CD patients.5-aminosalicylates, immunomodulators, andbiologics are more efficacious than placebo for postoperative CD prevention. Biologicsare found to be the most effective medications to prevent CD recurrence.