Postoperative Outcomes in Vedolizumab-treated Crohn's Disease Patients Undergoing Major Abdominal Operations

A. L. Lightner; N. P. McKenna; C. S. Tse; L. E. Raffals; E. V. Loftus Jr.; K. L. Mathis

Disclosures

Aliment Pharmacol Ther. 2018;47(5):573-580. 

In This Article

Abstract and Introduction

Abstract

Background Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications.

Aim We sought to compare 30-day postoperative infectious complication rate among vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy.

Methods A retrospective review of all Crohn's disease patients who received vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy.

Results One hundred Crohn's disease patients received vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002).

Conclusions Twenty-six per cent of Crohn's disease patients who received vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable analysis. While vedolizumab-treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds.

Introduction

Crohn's disease is an idiopathic chronic inflammatory bowel disease characterised by transmural inflammation resulting in inflammatory, stricturing, and fistulising phenotypes. Since the Food and Drug Administration's approval of infliximab in 1998, biologic therapy has replaced corticosteroid therapy as the dominant class of therapeutics used to medically manage moderate to severe Crohn's disease. The most widely studied and prescribed have been the anti-tumour necrosis factor-alpha (TNFα) agents (infliximab, adalimumab and certolizumab pegol). Unfortunately, up to a third of anti-TNFα-treated patients have a primary nonresponse[1–4] and another third will have a secondary loss of response.[5,6] In addition, anti-TNFα agents have been associated with adverse events such as serum sickness-like reactions, drug-induced lupus, and opportunistic infections.[7–15] Therefore, ongoing investigation for additional targeted therapies with alternative mechanisms and side effect profiles has been prioritised.

There was great enthusiasm following the Food and Drug Administration's approval of vedolizumab (Entyvio™, Takeda Pharmaceuticals America, Inc., Deerfield, IL, USA), a monoclonal antibody to α4β7-integrin, for the treatment of moderately to severely active ulcerative colitis and Crohn's disease due to its gut selectivity and therefore theoretically more favourable safety profile. The pivotal GEMINI studies demonstrated both the efficacy and safety of vedolizumab in achieving clinical relevant endpoints in Crohn's disease patients who were either naïve to or had previously failed therapy with TNFα-antagonists.[16,17] Several additional reports have demonstrated safety and efficacy with vedolizumab,[18–22] offering a promising alternative to the anti-TNFα class of biologic therapy. Interestingly, despite the noted safety, the GEMINI studies suggest that patients with Crohn's disease, unlike ulcerative colitis, may have an increased number of infectious complications with taking vedolizumab.[16,17,23]

Despite biologic therapy, 60%-80% of patients with Crohn's disease will require an abdominal operation in their lifetime.[24–26] As vedolizumab becomes more widely used for the medical management of Crohn's disease, an increasing number of patients are being exposed to vedolizumab in the perioperative period. We previously reported an increased number of postoperative infectious complications among surgical patients with inflammatory bowel disease who had received vedolizumab within 12 weeks of an abdominal operation, and found vedolizumab to be an independent predictor of surgical infectious complications on multivariate analysis.[27] Due to the increased risk of infectious complications among Crohn's disease patients as compared to those with ulcerative colitis in the GEMINI trials, and the increased number of anastomoses constructed in Crohn's disease patients as compared to those with ulcerative colitis, we updated our previous database to compare the rate of postoperative infectious complications among Crohn's disease patients who had received vedolizumab within 12 weeks of a major abdominal operation to that of Crohn's disease patients who had received either TNFα inhibitors or no biologic therapy.

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