Anti-Tumor Necrosis Factor Reduces Crohn’s Disease Recurrence after Surgery

Study shows value of early prophylaxis

Patients with Crohn’s disease (CD) who received anti-tumor necrosis factor (TNF) therapy within a month after undergoing ileocecal resection were less likely to experience disease recurrence than patients given no postoperative biologic prophylaxis, new Cleveland Clinic research shows.

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In contrast, patients who initiated postoperative biologic prophylaxis later than one month after surgery did not have decreased recurrence compared no biologic prophylaxis.

Two other biologics did not match anti-TNF’s ability to reduce the risk of postoperative CD recurrence, the study found, although that finding needs to be verified using a larger sample size.

“Postoperative recurrence of Crohn’s disease is common following surgical resection,” says Benjamin Cohen, MD, a coauthor of the study and Co-Section Head and Clinical Director for Inflammatory Bowel Diseases in Cleveland Clinic’s Department of Gastroenterology, Hepatology and Nutrition. “Our data showed that patients who started anti-TNF within four weeks had significantly lower rates of either endoscopic or radiographic recurrence of Crohn’s.”

The results were presented at the 2022 Digestive Disease Week annual meeting.

More knowledge needed

Previous research has shown that postoperative anti-TNF therapy can effectively decrease CD recurrence.

“While it didn’t meet its primary endpoint of reducing clinical recurrence, a large prospective study (PREVENT) showed significantly reduced endoscopic recurrence in patients who were randomized to receive infliximab versus no therapy postoperatively,” Dr. Cohen says. He notes that other studies such as POCER have explored the use of adalimumab among this patient population.

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However, further study is needed, especially when it comes to the efficacy of other biologic therapies as well as optimal timing of postoperative therapy initiation. To fill this knowledge gap, Dr. Cohen and colleagues initiated the current study, which aimed to compare biologic types and timing for the prevention of postoperative recurrence among adult CD patients after ileocecal resection.

Study details

The retrospective cohort study included 1,018 CD patients in two large hospital systems who underwent ileocecal resection between 2009 and 2020. Most participants were female (51.4%). Median age at surgery was 35 years. Additionally, 21.1% were active smokers, 93.8% had stricturing and/or penetrating CD and 49.5% had a prior resection.

Among patients who received a postoperative biologic in the 12 weeks following ileocecal resection (n=273, 26.8%), the majority were administered an anti-TNF agent (80.2%). The others were treated with ustekinumab, an interleukin-12 and -23 antagonist (n=28, 10.3%) and vedolizumab, an integrin receptor antagonist (n=26, 9.5%).

Ninety-three patients (34.1%) received postoperative biologic prophylaxis within four weeks after ileocecal resection while 180 patients (65.9%) were administered the treatment between 4 and 12 weeks after surgery.

The reduced risk of postoperative CD recurrence associated with early anti-TNF therapy that the researchers observed remained even after adjusting for known recurrence factors such as perioperative smoking, age at surgery, prior CD resections, perianal involvement and preoperative anti-TNF exposure.

Treatment with vedolizumab or ustekinumab within four weeks following ileocecal resection was not associated with a reduction in postoperative CD recurrence compared with no prophylaxis, the researchers found.

However, Dr. Cohen cautions against drawing conclusions based on that finding due to the small size of the vedolizumab and ustekinumab cohorts. Outcomes from other studies suggest those agents can be effective during the postoperative period, he says.

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Lessons from the research

“The key takeaway is to start prophylaxis as early as possible after surgery, which makes sense given what we know about how early histologic changes can occur,” Dr. Cohen say. “In terms of the specific therapy, we still need to increase our understanding and gather more data about the use of these agents.

“Another important point to consider is that, as new agents become available, they are often used in refractory patients, so we are dealing a population that tends not to respond,” he adds. “Now that these drugs have been available for a number of years, we are beginning to see them used as more early-line therapies. It is important to acknowledge this and account for it as best as possible in the research we do.”

Moving forward, Dr. Cohen and his colleagues emphasize the need for further investigation, including prospective trials, to confirm their findings.

“We need to identify high-risk patients and learn more about the appropriate strategies to effectively prevent disease postoperatively,” he says, “It is going to require a combination of real-world experience studies like what we’re trying to do with our multicenter cohort, as well as prospective studies applying the knowledge we gained from retrospective studies.”