IBD therapy with TNF-a inhibitors, immunomodulators linked to colorectal cancer

ORLANDO, Fla. — Patients with inflammatory bowel disease are at elevated risk for colorectal cancer when treated with tumor necrosis factor-alpha inhibitors and immunomodulators either alone or in combination, according to data presented at Digestive Disease Week.

Researchers evaluated incidence of solid cancers among patients with IBD treated with tumor necrosis factor-alpha (TNF-a) inhibitors alone or in addition to immunomodulators and/or systemic corticosteroids. Data was collected from the FDA Adverse Event Reporting System and included Primary Suspect (PS) adverse events reported between January 2003 and June 2012.

“Our group found increased odds of developing T-cell non-Hodgkin’s lymphoma with the use of immunomodulators alone and in combination with TNF-a inhibitors, in patients with IBD, using the same database,” researcher Eli D. Ehrenpreis, MD, head of the division of gastroenterology at NorthShore University HealthSystem, told Healio.com. “We hypothesized that immunomodulator usage alone or in combination with a TNF-a inhibitor may similarly increase the odds of developing a solid cancer during treatment for IBD.”

PS solid cancers (12% each for breast and colorectal cancer) were observed in 1,741 cases among treated IBD patients, with 83% in Crohn’s disease patients.

Only colorectal cancer development was significantly associated with the evaluated therapies (OR=4.5; 95% CI, 1.23-16.48), compared with control drugs 5-aminosalicylic acid (5-ASA) and sulphasalazine. This association was significant for monotherapy with TNF-a inhibitors (OR=1.88; 95% CI, 1.06-3.32) or immunomodulators (OR=7.46; 95% CI, 1.57-35.55), plus combination therapy with TNF-a inhibitors and immunomodulators (OR=3.24; 95% CI, 1.77-5.92), systemic corticosteroids and immunomodulators (OR=4.98; 95% CI, 1.3-19) and all three drugs (OR=3.34; 95% CI, 1.75-6.38).

“Those on TNF-a inhibitors, both on monotherapy and on dual therapy with an immunomodulator, are at an increased risk of developing malignant solid cancers, relative to those on 5-ASA,” Derrick J. Stobaugh, BA, BS, research study coordinator at NorthShore, told Healio.com. “Gastroenterologists should consider a patient’s personal history, family history and other possible risk factors before starting therapy with the aforementioned treatment.”

“Treatment for IBD requiring a TNF-a inhibitor, immunomodulator and a systemic corticosteroid may be a surrogate marker for more widespread disease and/or greater disease activity, which by itself is known to increase the risk of colorectal cancer,” said Parakkal Deepak, MD, clinical gastroenterology research fellow at NorthShore.

Disclosure: Dr. Ehrenpreis reported a patent held and filed for Pediatric Pharmaceuticals.

For more information:

Stobaugh DJ. Su1161: Risk of Solid Cancers with Tumor Necrosis Factor-Alpha Inhibitor Therapy Among Inflammatory Bowel Disease Patients: An Analysis of the FDA Adverse Event Reporting System. Presented at: Digestive Disease Week 2013; May 18-21, Orlando, Fla.