According to results of the PUCCINI trial presented at Digestive Disease Week, TNF inhibitors in patients with Crohn’s disease and ulcerative colitis administrated preoperatively did not did not increase the risk for any postoperative infections or any postoperative surgical site infections. The study was aimed to find whether exposure to TNF inhibitors is an independent risk factor for postoperative infection in intra-abdominal surgery in Crohn’s disease and ulcerative colitis.
Preoperative use of TNF inhibitors in patients with Crohn’s disease and ulcerative colitis did not increase the risk for any postoperative infections or any postoperative surgical site infections, according to results of the PUCCINI trial presented at Digestive Disease Week.
“It’s been very controversial over the years, whether there’s any risk associated with preoperative TNF inhibitor use prior to surgery and whether patients are at greater risk for post-op complications, particularly infectious complications since we know that there is some increased risk of infection in general,” Benjamin L. Cohen, MD, MAS, an assistant professor in the Dr. Henry D. Janowitz Division of Gastroenterology at Icahn School of Medicine at Mount Sinai, told Healio Gastroenterology and Liver Disease.
When the PUCCINI trial first began as a pilot study in 2012, Cohen said there was a lack of substantial data surrounding whether there were any post-operative infection risks associated with pre-operative TNF inhibitor use in patients with UC and CD.
“Multiple single-center studies had been published at that point showing conflicting results, and even now, I think the latest counts are over 30 single-center studies across both Crohn’s disease and ulcerative colitis,” he said in an interview. “These studies didn’t really get at how to answer the question because there’s significant limitations with them. Most of the studies have been retrospective, single-institution experiences, which makes it very difficult when you’re looking at disease severity, or more importantly confounding effects of other medications that IBD patients are on.”
To expand on the multitude of single-center studies, Cohen and colleagues developed the PUCCINI trial, a prospective, multi-center cohort study conducted across 17 centers from the Crohn’s & Colitis Foundation Clinical Research Alliance.
The aim of the study, according to Cohen, was to determine whether exposure to TNF inhibitors is an independent risk factor for postoperative infection in intra-abdominal surgery for patients with CD and UC.
Patients had to be aged at least 18 years and have a diagnosis of CD, UC or indeterminate colitis using standard criteria to be included in the study.
Patients were excluded if they had an operation within the previous 90 days to repair a surgical complication from a recent surgery, and if they were enrolled in a clinical trial for an investigational therapy for CD or UC.
TNF inhibitor exposure was defined by patient-reported TNF inhibitor use within 12 weeks of surgery and detectable perioperative TNF inhibitor drug levels using a homogeneous mobility shift assay (Prometheus Laboratories) for Humira (adalimumab, AbbVie) and Remicade (infliximab, Janssen).
At baseline, 573 patients (mean age, 43.05 years; 46.8% women) had no TNF inhibitor use 12 weeks prior to surgery and 382 patients (mean age, 39.2 years; 49.2% women) did.
More than half of the patients (57.1%) who had no exposure within 12 weeks of surgery had a previous abdominal surgery, and 45% of patients who had TNF inhibitor exposure within 12 weeks of surgery had a previous abdominal surgery.
The most common types of surgeries within the cohort were ileocolic resection (n = 410), segmental small bowel or colon resection (n = 175) and subtotal colectomy with Hartmann pouch and ileostomy (n = 168).
Forty percent of the cohort received a TNF inhibitor within 12 weeks of surgery and 23.7% of the cohort had a detectable TNF inhibitor level perioperatively.
Twenty percent of patients who were defined as unexposed to a TNF inhibitor prior to surgery had any infection after surgery compared with 19.4% who were exposed to a TNF inhibitor.
Frequency of any infection as defined by detectable TNF inhibitor level was 19.7% in the unexposed cohort and 19.6% in the exposed cohort.
Frequency of surgical site infection as defined by patient-reported TNF inhibitor use was 12.4% in the unexposed cohort and 11.5% in the exposed cohort. Using the detectable TNF inhibitor level exposure definition, 10.3% of the unexposed cohort and 12.1% of the exposed cohort had a surgical site infection.
Cohen noted that these results can have a big impact in changing practice.
“I think you’re going to find differences in different centers about how gastroenterologists and surgeons approach patients who are on TNF inhibitors, but our data shows that having used a TNF inhibitor within 12 weeks of surgery and even having detectable levels were not associated with any infection or surgical site infection,” he said in an interview. “If a patient is going to surgery, those factors should not impact the surgical decisions in IBD patients. There are some situations where in the past, people who believed that being on a TNF inhibitor conferred increased risk, may delay a surgery that a patient otherwise needed to decrease their exposure to the TNF inhibitor at the time of surgery. What we found is that you should not do that.” – by Ryan McDonald