The risk of lymphoma is no greater in children with inflammatory bowel disease who are treated with anti–tumor necrosis factor therapy than in adults treated with anti-TNF therapies or in children treated with other therapies for IBD, according to findings from a systematic review.
The review, which included 65 studies involving a total of 5,528 patients with 9,516 patient-years of follow-up, also showed that the rate of serious infection was lower among children with IBD who were treated with anti-TNF agents than among those treated with steroids or among adults treated with anti-TNF agents, Dr. Parambir S. Dulai of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and his colleagues reported in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2014.01.021).
Source: American Gastroenterological Association
Two patients developed lymphoma, for a rate of 2.1/10,000 patient-years of follow-up (PYF), which did not differ significantly from the expected rate among children (5.8/100,000 PYF), the rate among pediatric patients receiving thiopurine monotherapy (4.5/10,000), or the rate among adults treated with anti-TNF agents (6.1/10,000), the investigators found.
The rate of serious infections was 352/10,000 PYF in pediatric patients treated with anti-TNF agents as part of prospective studies included in the review, which was similar to the expected rate in those treated with immunomodulator therapy (333/10,000 PYF), and significantly lower than the expected rate in those treated with glucocorticoids (730/10,000 PYF) and adults treated with anti-TNF agents (654/10,000 PYF).
Of seven deaths that occurred among the patients, five were considered related to treatment (four cases of sepsis, one case of arrhythmia), for a rate of 5.3/10,000 PYF.
Although anti-TNF therapy is an effective treatment option for pediatric IBD, many physicians are hesitant about prescribing anti-TNFs to children because of concerns about infection and lymphoma risk based on the adult literature and case reports of hepatosplenic T-cell lymphoma. However, the findings of this pooled analysis suggest that such concerns may be unfounded.
Older age, sex, and duration of IBD have been linked with increased risk of lymphoproliferative disorders and could help explain the observed differences between adults and pediatric IBD patients with respect to lymphoma rates after anti-TNF exposure, the investigators said.
"Overall, the risk of serious infection, lymphoma, and death with anti-TNF therapy in pediatric IBD is very low," they wrote.
However, they noted that the study is limited by a number of factors, including short duration of per-person follow-up, which means that while the data are promising, they are "not definitive in answering the question of whether anti-TNF therapy is associated with an increased risk of lymphoma, particularly with long-term use," the investigators said.
Long-term follow-up studies are needed in children to assess whether lymphoma risk is exposure dependent – as suggested by the existing literature – rather than a cumulative risk that is dependent on duration of therapy, they added.
Dr. Dulai reported having no disclosures. Coauthor Dr. Corey Siegel reported serving as an advisory board member or consultant for, and/or receiving grant support from Abbvie, Janssen, UCB, and the Agency for Healthcare Research and Quality. Dr. Marla Dubinsky serves as a consultant for Abbvie, Janssen, UCB, and Takeda.