Treatment of pediatric inflammatory bowel disease (pIBD) with tumor necrosis factor inhibitors (TNFi) does not increase the risk for malignancy, researchers report.
The study with that finding, “Risk of malignancy associated with paediatric use of tumour necrosis factor inhibitors,” was published in the journal Annals of the Rheumatic Disease.
TNF is a pro-inflammatory cytokine, which is a type of molecule released by immune cells. Treatment with TNFi inhibitors is effective in pIBD, as well as in juvenile idiopathic arthritis (JIA) and pediatric plaque psoriasis (pPsO).
Despite the clinical benefit, concerns over the potential increase in the rate of malignant tumors in children due to TNFi use are well-known. These concerns first appeared in a 2009 report from the U.S. Food and Drug Administration, which demonstrated an increased risk of lymphoma with using Remicade (infliximab, by Janssen).
However, that initial study did not account for the effect of the underlying disease in malignancy risk, or the risk associated with other immunosuppressive medications, the researchers noted. Evidence shows that the use of the immunosuppressive IBD medication thiopurine, which often is prescribed prior to TNFi, is linked with malignancy, particularly lymphoma, in adult IBD patients.
The very low incidence of pediatric malignancy and the limited number of children treated with TNFi have hampered definitive conclusions about their potential link.
Therefore, the investigators used data from administrative claims in the U.S. to evaluate rates of malignancy in children with pIBD, JIA, and pPsO treated with TNFi.
The team collected Medicaid (2000-2010) and commercial health insurance (2010-2014) data, which resulted in 24,035 patients with pIBD, 28,005 patients with JIA, and 31,438 patients with PsO.
The proportion of TNFi users was greater in pIBD (28%) and JIA (26%) patients, than in those with pPsO (4%), for an overall total of 15,598 children using these medications. Then, the scientists calculated the standardized incidence ratios (SIRs), which compared the observed number of malignancies with their expected numbers according to cancer surveillance data.
Results exhibited 15 malignancies among children using TNFi and 42 among those not using TNFi. Among the patients using TNFi, the observed malignancies were six lymphoma, three brain, two leukemia, two malignant melanoma, one bone, and one liver.
In pIBD patients, combined use of TNFi plus thiopurine was associated with a higher SIR than use of TNFi without thiopurine. This result matches earlier findings in adults with IBD.
Overall, the results revealed that TNFi use is not associated with increased risk of malignancy compared to no use in patients with pIBD, JIA, and pPsO.
The study also showed greater incidence of malignancy in patients with either of these diseases compared with the general population. This finding is in line with prior evidence in patients with pIBD and JIA. Conversely, there are no previous results from large studies exploring the risk of malignancy in patients with pPsO, the authors observed.
Among the study’s limitations, the authors mentioned the lack of access to healthcare records to confirm the indications for TNFi and the diagnosis of malignancy, as well as the limited duration of follow-up after TNFi exposure.
“In conclusion, our study demonstrates that being diagnosed with JIA, pIBD or pPsO increases the risk of incident malignancy and that use of TNFi does not appear to significantly further increase this risk in the first few years after use, with the possible exception of lymphoma,” the scientists wrote.