AUSTIN, Texas — The risk for lymphoma in children treated with TNF inhibitors is very low, according to a study of more than 9000 insurance claims.
TNF inhibitors have become the most effective way to treat children with inflammatory bowel disease, but concerns that they are linked to lymphoma keep some physicians from prescribing them, said Matthew Egberg, MD, a pediatric gastroenterologist at the University of North Carolina Hospitals in Chapel Hill.
His team found an absolute risk for lymphoma in their study cohort of 0.3 × 10–3, Egberg reported during an oral presentation here at the Crohn's and Colitis Congress 2020.
They identified three cases of lymphoma over 25,413 person-years of follow-up, for an incidence rate of 11.8 cases per 100,000 person-years. They found no cases of hepatosplenic T-cell lymphoma in their analysis.
Poorly treated IBD can be far more problematic.
The findings show that "there is a small, measurable risk that patients, families and clinicians need to be aware of," Egberg said. But, he added, that risk must be weighed against other options.
"Poorly treated IBD can be far more problematic," he told Medscape Medical News. "Intestines that are constantly inflamed over the course of years can raise your chance of intestinal cancers."
Concerns about cancer have been raised in previous studies of TNF inhibitors, he explained, but researchers have found it difficult to control for exposure to thiopurines, which have been shown to have consistent association with lymphoma.
Worry set in when a 2010 study showed that the association between TNF inhibitors and a very rare form of cancer — hepatosplenic T-cell lymphoma — was inconclusive.
"There is evidence that treatment with TNF blockers in children may increase the risk of malignancy. However, the cases were confounded by the potential risk of malignancy associated with underlying illnesses and the use of concomitant immunosuppressants; therefore, a clear causal relationship could not be established," the authors of that study explain in their conclusion.
As Egberg pointed out, "thiopurines work on a completely different mechanism of the body. It's not uncommon for kids to have been exposed to a thiopurine in addition to anti-TNF agents."
His team analyzed data from the IQVIA Legacy PharMetrics Administrative Claims Database, a geographically diverse insurance claims database that contains information from more than 100 plans. They looked at 9284 people 18 years and younger who had Crohn's disease (62%) or ulcerative colitis, and were enrolled from 2007 to 2016. The mean age of the cohort was 13.7 years, and 47% was female.
Over a median follow-up of 2 years, 21% of the patients were treated with a TNF inhibitor and 38% were treated with an immune modulator (thiopurine or methotrexate).
But the results are not definitive, he said. Although the researchers could identify medications, surgeries, and the reason for seeing a pediatrician from the database, there are many factors they could not determine, such as family history and disease severity. Plus, he added, the population was commercially insured.
Most treatments we use do not have official pediatric approval.
This study is particularly important because it provides additional safety data to show that the absolute risk for lymphoma in children treated with TNF inhibitors is low, said Stacy Kahn, MD, from Boston Children's Hospital, Harvard Medical School.
Although the large database is an advantage, the retrospective nature of the study could have led to the failure to identify or the overidentification of patients because the follow-up was just 2 years, she pointed out.
"That said, it is a very large study and allows for the identification of a rare outcome; in this case, lymphoma," she said.
"Most treatments we use do not have official pediatric approval," Kahn told Medscape Medical News. The approval of treatment for children "lags years behind the approval for the same treatment in adults. My hope is that this study will foster more studies that help us to better understand the medications we use to treat IBD and how to optimally use them."
Crohn's and Colitis Congress (CCC) 2020: Abstract 1. Presented January 23, 2020.