TNF blockers, thiopurines may raise lymphoma risk

Last Updated: 2017-11-07

By Megan Brooks

NEW YORK (Reuters Health) - In adults with inflammatory bowel disease (IBD), treatment with a thiopurine or tumor necrosis factor (TNF) blocker, alone or together, appears to raise the risk of lymphoma, according to an observational cohort study from France.

Anti-TNF agents and thiopurines are increasingly prescribed in combination, the authors note in their November 7 online article in JAMA. An increased risk of lymphoma has been reported in IBD patients receiving thiopurines, but the risk of lymphoma associated with TNF agents, either alone or in combination with thiopurines is unclear, they point out.

To investigate, Dr. Rosemary Dray-Spira from the French drug safety group National Agency for Medicines and Health Products Safety (ANSM) and colleagues used national insurance databases to identify 189,289 adults with IBD (median age, 43; 54% women).

During a median follow-up of 6.7 years, 123,069 participants had no exposure to thiopurines of TNF agents, 50,405 were exposed to thiopurines only, 30,294 to anti-TNF agents only, and 14,229 to both agents. (A single patient could be included in more than one exposure group.)

During the follow-up, 336 lymphoma cases were documented: 220 in unexposed patients, 70 in patients exposed to thiopurine monotherapy, 32 in patients exposed to anti-TNF monotherapy and 14 in patients exposed to both. The corresponding incidence rates per 1,000 person-years were 0.26, 0.54, 0.41 and 0.95.

Lymphoma occurred mostly in men (57%) at a median age of 60. The most common subtypes were nonfollicular lymphoma (130 cases, 39%), including 83 cases of diffuse large B-cell lymphoma; Hodgkin lymphoma (55 cases, 16%); and follicular lymphoma (41, 12%). Hodgkin lymphoma made up 14% of all lymphomas among unexposed patients, 19% among patients exposed to thiopurines, 19% in those exposed to TNF blockers, and 43% in those exposed to combination therapy.

In a Cox model adjusted for confounding factors, compared with unexposed patients, the risk of lymphoma was significantly higher among those exposed to thiopurine monotherapy (adjusted hazard ratio, 2.60), anti-TNF monotherapy (aHR, 2.41), or combination therapy (aHR, 6.11).

The risk also was significantly higher in patients exposed to combination therapy than in those exposed to thiopurines only (aHR, 2.35) or anti-TNF agents only (aHR, 2.53).

"Our study provides evidence that among adults with IBD, the use of anti-TNF agents, either alone or in combination with thiopurines, is associated with a small but statistically significant increased risk of lymphoma; and this risk is higher with combination therapy than with either of these treatments used alone," Dr. Dray-Spira told Reuters Health by email. "These findings, which need to be considered against the potential benefits of successful treatment of IBD, should be accounted for in the strategy of IBD therapeutic management," she said.

The researchers caution that while the differences in the risk of lymphoma were "significant in relative terms, their absolute magnitude of less than 1 case per 1000 person-years should be considered against the potential benefit of successful treatment of IBD."

The study had no specific funding. Two authors disclosed relationships with various pharmaceutical companies.

SOURCE: http://bit.ly/2hbbEHf

JAMA 2017.