Risk of Infections with Anti-TNF Agents in Patients with Crohn’s Disease After Elective Surgery

Abstract

We read with interest the article by Hanzel et al. [1] conducting a systematic review and meta-analysis to investigate the relationship between preoperative biological therapy and postoperative outcomes in inflammatory bowel disease (IBD) focusing on elective surgery. The author found that anti-tumor necrosis factor (anti-TNF) therapy prior to elective surgery may increase the odds of postoperative infection in Crohn’s disease (CD). We also read two meta-analyses about the risk of postoperative complications following preoperative anti-TNF therapy in patients with CD [2, 3]. The first meta-analysis concluded that preoperative anti-TNF therapy increases the occurrence of overall postoperative complications, and particularly infectious complications. The second meta-analysis concluded that anti-TNF therapy does not increase the risk of postoperative complications. We are confused by these different conclusions, several questions deserve attention. First, there are several limitations in these meta-analyses. The majority of the included studies in these meta-analyses were limited by small sample sizes or a retrospective design, and are not appropriately designed to evaluate the effects of anti-TNF therapy on postoperative complications. The confounding effect of concomitant medications such as corticosteroids and immunosuppressants was not analyzed in the included studies. Furthermore, other factors may be associated with the risk of postoperative complications such as nutritional status, penetrating behavior of CD, preexisting enteric fistula, and intra-abdominal abscess. Some studies found that the detrimental effects of poor nutrition on postoperative infectious complications appear to be enhanced in patients who had received preoperative anti-TNF therapy [4]. Prolonged anti-TNF therapy increases the risk of infectious complications, because it could impair nutritional and immunological status. The timing of surgery is an important issue particularly in poorly nourished patients who might be experiencing loss of response to anti-TNF therapy. Thus, the timing of surgery should be decided based on multiple factors, not only on preoperative anti-TNF therapy. But these factors were not evaluated in this meta-analysis by Hanzel et al. Second, different anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) were investigated together in this meta-analysis. The median half-lives of these agents are different, and the timing since last infusion or injection of an agent is variable in individual patients with CD. There is no evidence that prolonging the duration between the last dose and the surgery decreases the risk of postoperative infectious complications. A large multi-center cohort study [5] found that patients with CD with preoperative exposure or preoperative detectable serum levels of anti-TNF agents did not have an increase in postoperative complications. This reflects the controversy over the topic in these literatures. Therefore, the effects of an anti-TNF agent on postoperative complications are hard to estimate. In conclusion, the impact of preoperative anti-TNF therapy on postoperative complications in patients with CD remains unclear. Well-designed large prospective studies are needed to precisely evaluate the relationship between preoperative anti-TNF therapy and postoperative complications in patients with CD.