Treatment of children with autoimmune diseases with tumor necrosis factor (TNF) inhibitors did not significantly increase the risk of malignancy, although the background risk of cancer was higher than that of the general population, a retrospective study revealed.
Among children with juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), or plaque psoriasis receiving anti-TNF therapy, the standardized incidence ratio for malignancy was 2.9 (95% CI 1.6-4.9), according to Timothy Beukelman, MD, of the University of Alabama at Birmingham, and colleagues.
Action Points
- Children with juvenile idiopathic arthritis, inflammatory bowel disease, or plaque psoriasis had an increased rate of malignancy compared with the general population, but tumor necrosis factor inhibitor (TNFi) treatment did not appear to significantly further increase the risk.
- Be aware that the potential for malignancy among patients receiving TNFi reflects concerns about blocking the effects of the cytokine TNF, which plays a crucial role in immune surveillance against cancer and infection.
And for children with these disorders who had no anti-TNF exposure, the standardized incidence ratio was 2.1 (95% CI 1.5-2.9), the researchers reported online in .
Despite nearly 20 years of experience with TNF inhibitors, concerns remain about the potential for malignancy among patients receiving them. These agents block the effects of the cytokine TNF, which plays a crucial role in immune surveillance against cancer and infection.
Eight years ago, identified 48 cases of malignancy among pediatric users of TNF inhibitors, suggesting the possibility that TNF blocker therapy is associated with cancer in young patients.
However, as Beukelman and colleagues pointed out, "This initial report had many limitations, including failure to account for a possible increased risk of malignancy associated with the underlying conditions being treated with TNF inhibitors (i.e., increased background risk of malignancy) or for a possible increased risk associated with other immunosuppressive medications."
Therefore, to provide a fuller picture of malignancy risks in the pediatric population, the team analyzed data from Medicaid for the years 2000 to 2010 and from Truven MarketScan for 2010 to 2014, to reflect both government-funded and commercial insurance data.
The rates of cancer among patients with JIA, IBD, or psoriasis with and without anti-TNF exposure were compared with the expected rates according to age, sex, and race in the Surveillance, Epidemiology, and End Results database.
The researchers identified 28,005 patients with JIA, 24,035 with IBD, and 31,438 with psoriasis in the national insurance records, with 7,419, 6,808, and 1,371 being TNF users, respectively.
The most commonly used TNF inhibitors were etanercept (Enbrel) in 37%, infliximab (Remicade) in 34%, and adalimumab (Humira) in 29%.
During 30,703 person-years of follow-up for patients exposed to TNF inhibitors, there were 15 new cases of cancer, while in 121,801 person-years among the non-exposed patients, there were 42 incident malignancies.
The malignancies in the TNF-exposed group were lymphomas in six, brain tumors in three, leukemia in two, malignant melanomas in two, and one each of bone and liver cancer.
When the three conditions were considered separately, the standardized incidence ratios for anti-TNF non-use were nearly identical -- 2.1 (95% CI 1.1-3.5) for JIA, 2.1 (95% CI 1.1-3.6) for IBD, and 2.1 (95% CI 1.1-3.5) for psoriasis. Among users, the standardized incidence ratios were 3.1 (95% CI 1.3-6.1) in JIA and 3.3 (95% CI 1.3-6.9) for IBD. No malignancies were found with anti-TNF use for psoriasis.
In adults with rheumatoid arthritis, a threefold to fourfold increased risk for lymphoma has been reported both for patients with TNF inhibitor use and those with highly active disease and no TNF inhibitor use. In the current pediatric cohort, there were three lymphomas in patients with JIA and three in those with IBD with anti-TNF use. Among nonusers, there were three lymphomas in patients with IBD and six in patients with psoriasis.
For the three conditions combined, the standardized incidence ratios for lymphoma were 6.0 (95% CI 2.4-14.5) among the anti-TNF exposed and 2.7 (95% CI 1.2-5.2) among the non-exposed. The authors noted that they were unable to adjust for disease severity and activity, which could influence lymphoma risk, and that they were therefore unable to rule out an increased risk for lymphoma.
They also pointed out that their analysis was limited by the small number of malignancies seen, but that overall, TNF inhibitor use in children did not appear to "substantially" raise the risks of cancer.
Other limitations of the study included its reliance on administrative records and the short duration of follow-up.
In conclusion, the researchers stated, "our study demonstrates that being diagnosed with JIA, pediatric IBD, or plaque psoriasis increases the risk of incident malignancy and that the use of TNF inhibitors does not appear to significantly further this increase in risk in the first few years after use, with the possible exception of lymphoma."
Disclosures
The study was funded by the United States Agency for Healthcare Research and Quality.
The authors reported financial relationships with UCB, Genentech/Roche, Novartis, Bristol-Myers Squibb, Sobi, Takeda, Pfizer, Lilly, Gilead, Johnson & Johnson, Samsung Bioepis, AbbVie, Merck, Abbott, Amgen, Ardea/AstraZeneca, Crealta, Janssen, and Crescendo.
Primary Source
Annals of the Rheumatic Diseases
Beukelman T, et al "Risk of malignancy associated with pediatric use of tumor necrosis factor inhibitors" Ann Rheum Dis 2018; DOI:10.1136/annrheumdis-2017-212613.