Patients with inflammatory bowel disease (IBD) can safely take tumor necrosis factor inhibitors (TNFi) prior to abdominal surgery, a prospective, multicenter, observational study confirms.
The researchers found that exposure to TNFi in the 12 weeks prior to surgery was not associated with an increased risk of either overall infections or surgical site infections (SSI).
The findings should be “very reassuring” for clinicians, lead author Benjamin L. Cohen, MD, Cleveland Clinic Foundation, Cleveland, Ohio, told Medscape Medical News. “In the past, when clinicians were unsure about the safety of using these drugs in the perioperative period, they may have delayed surgeries or stopped medications unnecessarily.
“For me, the key take-home point of this study is that we need to plan the timing and management of medications around surgery based on factors other than the use of tumor necrosis factor inhibitors in most patients,” Cohen continued.
Ultimately, “we will help change practice in how we manage patients with IBD having surgery,” he said.
The research was published online in Gastroenterology.
No Increased Postop Infection Risk
The Prospective Cohort of Ulcerative Colitis and Crohn’s Disease Patients Undergoing Surgery to Identify Risk Factors for Post-Operative Infection I (PUCCINI) trial enrolled patients with IBD from 17 sites participating in the Crohn’s and Colitis Foundation Clinical Research Alliance between September 2014 and June 2017.
Patients had Crohn’s disease, ulcerative colitis, or indeterminate colitis, as determined by standard criteria, and planned to undergo intra-abdominal surgery or had undergone intra-abdominal surgery in the preceding 4 days.
Among the 947 patients enrolled, 47.8% were women. All were aged 18 years or older. The median disease duration was 10 years; 34.4% of patients had undergone prior bowel resection, and a further 17.5% had undergone other abdominal surgery.
Systemic corticosteroid use within 2 weeks of surgery was reported by 40.9% of patients, and 42.3% had used antibiotics.
TNFi exposure within the 12 weeks prior to surgery was reported by 40.3% of patients. Adalimumab and infliximab were the most commonly used drugs. Among those who had not used TNFi prior to surgery, 23.7% were TNFi-naive, and 36.0% had used them in the past.
The researchers report that there was no significant difference in the rate of postoperative infections between patients who reported using TNFi in the 12 weeks prior to surgery and those who did not (18.1% vs 20.2%; P = .469). There was also no difference in SSI, as defined using the Centers for Disease Control and Prevention criteria, between the two groups (12.0% vs 12.6%; P = .889)
Multivariate analysis revealed that current TNFi exposure was not associated with any infection, at an odds ratio vs no exposure of 1.050 (P = .80), or with SSI, at an odds ratio of 1.249 (P = .34).
In contrast, preoperative corticosteroid exposure, prior bowel resection, and current smoking were associated with any infection and with SSI.
Approached for comment, Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University in Chicago, Illinois, said that the current findings are consistent with those of previous studies and that their relevance extends beyond abdominal surgery.
In the past, when surgeons were “confronted with a patient on a TNF blocker, even if it’s orthopedic or plastic surgery, they recommended against using a TNF blocker, or operating at the end of the cycle when the drug levels are low,” he told Medscape Medical News.
Hanauer said such practice gets clinicians into a “bind because you’ve got a patient, for instance, who’s got a blockage with Crohn’s disease…but the only way you could manage them when the TNFi was out of their system was with steroids, which is worse” in terms of postoperative infection risk, he explained.
Prospective Studies Important
The researchers note that up to 50% of patients with IBD are exposed to TNFi prior to their first surgery. They also note that there is concern that preoperative treatment with these and other immunosuppressive medications may increase the risk of postoperative infections.
However, the evidence is inconsistent, they write, and so whether to continue or stop the drugs prior to surgery remains controversial.
“A lot of the initial studies in the perioperative population were single-center and retrospective for the most part,” Cohen said, adding that the studies used different modes of assessment and followed different time frames.
“So, there’s a lot of heterogeneity,” he said.
In addition, early studies of TNFi were often conducted with patients who were very ill and who had started receiving the drug right before surgery, and they sometimes had a complication, Cohen said. “But you don’t know if that’s because of the drug itself or because of many other factors associated with them being very sick, such as being on steroids, being very malnourished, or having other complications of disease.”
It is difficult to control for such risk factors in retrospective analyses because the information is not always available from medical records, he said. “That’s why it’s so important to study clinical questions like this in a prospective manner.”
Cohen added that it is important that studies such as theirs continue to be undertaken as new drugs become available.
“We’re entering an era of rapidly expanding drug discovery, so we’re going to have new medications available for use in our patients with IBD,” he explained. “It’s important that we continue to build prospective cohorts to look at questions such as the safety of medications in the perioperative period, rather than solely relying on retrospective data.”
The study was funded by a Crohn’s & Colitis Foundation Senior Research Award. Cohen reports relationships with AbbVie, Celgene, Bristol-Myers Squibb, Pfizer, Sublimity Therapeutics, Target RWE, Janssen, Ferring, AlphaSigma, and Takeda. Other authors report numerous financial relationships. Hanauer reports relationships with Janssen, AbbVie, Pfizer, Amgen, Genentech, and Merck.
Gastroenterol. Published online April 9, 2022. Abstract