Controversy of Preoperative Exposure to Tumor Necrosis Factor Inhibitors in Surgical and Infectious Complications of Inflammatory Bowel Disease

Abstract

We read with interest the article by Cohen et al,1Cohen B.L. et al.Gastroenterology. 2022; 163: 204-221Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar who evaluated whether preoperative exposure to tumor necrosis factor inhibitors (TNFis) was an independent risk factor for postoperative infectious complications of inflammatory bowel disease (IBD). They found that both patient-reported use of TNFis and detectable serum drug concentrations were not independent risk factors for any postoperative infection or surgical site infection. This was the largest multicenter prospective surgical cohort study on the topic, and the study findings are important to both current practice and future research; however, a few questions need to be considered. First, several confounding factors, such as age, surgical approach, and unfavorable abdominal conditions (abscess or fistula at the operation), are responsible of the infectious complications. More than 26% of incident IBD diagnoses occur among patients aged 65 years and older. These populations treated with surgery are at increased risks for infectious complications.2Sacleux S.C. et al.Aliment Pharmacol Ther. 2018; 47: 1652-1660Crossref PubMed Scopus (11) Google Scholar However, the study enrolled patients with a median age of 39 years, which could be an important source of selection bias, as the observed conclusion could be related to the younger age of these patients. In addition, the specific surgical approaches included should be clarified. For example, the incidence of postoperative complications is significantly increased in patients with IBD who undergo creation of an ileo-anal anastomosis and who have been receiving TNFi treatment, in which the risk of early postoperative complications increased by 3.54 times and the incidence of infection increased by 13.8 times compared with the non-TNFi treatment group.3Mor I.J. et al.Dis Colon Rectum. 2008; 51 (discussion 1207–1210): 1202-1207Crossref PubMed Scopus (5) Google Scholar The study also offered limited information regarding potential confounders such as anemia, C-reactive protein levels, and nutritional status, which have definite effects on postoperative complications in IBD.4Syed A. et al.Am J Gastroenterol. 2013; 108: 583-593Crossref PubMed Scopus (100) Google Scholar Second, from a surgical point of view, emergency surgery was the key driver for postoperative complications, and one-half of the early complications were severe and infectious. A prospective population study based on the EPIMAD (Epidemiology of Inflammatory Bowel Diseases) registry conducted from January 1988 to December 2006 showed that among 139 surgical patients diagnosed with IBD, 33.3% underwent emergency surgery.2Sacleux S.C. et al.Aliment Pharmacol Ther. 2018; 47: 1652-1660Crossref PubMed Scopus (11) Google Scholar According to the data presented, urgent/emergency surgery was performed based only on admission of 14 patients (1.5%). The reason for the low emergency rate is unclear; it may be related to lower levels of infection associated with IBD surgery and consequently better outcomes. The study reported a high incidence (47.9%) of protective stoma approach. Annually, only 0.66% of individuals with IBD in the UK and an estimated 1.5% in the USA undergo surgery that results in a permanent or temporary stoma.5Dibley L. et al.Inflamm Bowel Dis. 2018; 24: 235-246Crossref PubMed Scopus (17) Google Scholar This makes one wonder whether patients were not managed within an multidisciplinary environment, although a multidisciplinary approach has become the standard procedure to manage patients with IBD. In addition, most surgeries were performed in 13 academic centers and by different surgeons, which is an important source of bias, and the studies included retrospective cohorts, which were prone to bias even after apparently appropriate adjustments. We argue that these considerations are critical when interpreting the study results. TNFis appear to be safe for use in the perioperative period, but available data remain controversial. Multidisciplinary decisions should be made on a case-by-case basis by adapting surgical strategies according to risk factors involved. Prospective Cohort Study to Investigate the Safety of Preoperative Tumor Necrosis Factor Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal SurgeryGastroenterologyVol. 163Issue 1PreviewIn the largest multicenter prospective surgical cohort on the topic, Prospective Cohort of Ulcerative Colitis and Crohn’s Disease Patients Undergoing Surgery to Identify Risk Factors for Post-Operative INfection I (PUCCINI) showed that preoperative tumor necrosis factor inhibitor use was not associated with any postoperative infections, including surgical site infections. Full-Text PDF ReplyGastroenterologyVol. 164Issue 2PreviewWe read with great interest the letters from Zhu et al and Resegotti et al regarding our publication of the primary outcomes from the Prospective Cohort of Ulcerative Colitis and Crohn’s Disease Patients Undergoing Surgery to Identify Risk Factors for Post-Operative Infection (PUCCINI).1 We appreciate the concerns expressed by Zhu et al regarding selection bias with the PUCCINI cohort. The incident age of inflammatory bowel disease (IBD) in North America, Western Europe, and Oceania has been reported as a median 31–34 years with a peak in the age interval 20–30 years. Full-Text PDF