Tumor necrosis factor inhibitor (TNFi) medications used to treat juvenile idiopathic arthritis (JIA), pediatric inflammatory bowel disease, and pediatric plaque psoriasis are unlikely to have a substantial effect on pediatric malignancy rates, according to the results of a retrospective cohort study published in the Annals of the Rheumatic Diseases. However, children diagnosed with these diseases did have an increased incidence of childhood malignancies, regardless of TNFi exposure.

Although there have been concerns about the potential for increased malignancy in pediatric patients treated with TNFi, the overall rarity of cancer or TNFi therapy during childhood has prevented meaningful exploration of an independent relationship between the 2 variables. The researchers used 15 years of claims data to compare malignancy rates among pediatric patients with JIA, pediatric inflammatory bowel disease, and pediatric plaque psoriasis who did and did not receive TNFi treatment.


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The investigators included 15,598 children treated with TNFi therapy and 73,839 children who were not exposed to TNFi therapy, resulting in 30,703 person-years and 121,801 person-years of follow-up, respectively. After identifying 15 malignancies in the TNFi group and 42 malignancies in the non-TNFi group, researchers calculated standardized incidence ratios (SIRs) that compared observed and expected malignancy rates. Cancer surveillance data were used to calculate expected malignancy rates. Adjusted hazard ratios (aHRs) were calculated for overall malignancy incidence.

The SIR for participants receiving TNFi medications across all 3 disease states was 2.9 (95% CI, 1.6-4.9), and those not exposed to TNFi had an SIR of 2.1 (95% CI, 1.5-2.9). The corresponding aHR for TNFi use vs no TNFi use across all disease types was 1.58 (95% CI, 0.88-2.85). Additional analyses revealed that the aHR for lymphoma only was 2.64 (95% CI, 0.93-7.51) when comparing TNFi exposure with no exposure across all 3 disease states. In patients with pediatric inflammatory bowel disease, the combination of a TNFi and thiopurine resulted in an SIR of 6.0 (95% CI, 1.2-17.5), compared with 2.5 (95% CI, 0.7-6.4) for TNFi use alone, yielding a nearly 2.4-fold increased incidence for the combination treatment.

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The authors noted several study limitations, including a lack of record access that would allow confirmation of indications and diagnoses, possible misclassification of prevalent malignancies as incident cases, inability to link malignancies with specific TNFi formulations, and a limited long-term follow-up capacity that prevented adequate evaluation of any potential association between long-term TNFi therapy and malignancy incidence.

Although diagnoses of JIA, pediatric inflammatory bowel disease, and pediatric plaque psoriasis appear to increase the risk for incident malignancies in the pediatric population, the results do not indicate any further risk conferred by the use of TNFi medications to combat these diseases. Two possible exceptions exist for patients with lymphoma who are treated with TNFi and for those with pediatric inflammatory bowel disease treated with combination TNFi and thiopurine. These results support the safety of TNFi pharmacotherapy for the 3 disease states, but future studies should also focus on longer-term exposures and their related outcomes.

Reference 

Beukelman T, Xie F, Chen L, et al. Risk of malignancy associated with paediatric use of tumour necrosis factor inhibitors [published online February 9, 2018]. Ann Rheum Dis. doi:10.1136/annrheumdis-2017-212613