, et al
Risk of malignancy associated with paediatric use of tumour necrosis factor inhibitors
[published online ahead of print February 9, 2018].
Ann Rheum Dis
. doi:

Investigators from multiple institutions conducted a retrospective study to assess the risk of malignancy in children with juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), or plaque psoriasis (PsO) treated with tumor necrosis factor inhibitors (TNFi). For the study, the investigators abstracted data from a national US Medicaid database during the period 2000–2010, and from the Truven MarketScan files, which include US national claims data from employer-provided commercial insurance between 2010 and 2014. Diagnostic codes were used to identify children >6 months and <18 years old with JIA, IBD, or PsO, and prescription claim data were reviewed to determine if study children received a TNFi (including adalimumab, certolizumab, etanercept, golimumab, and infliximab). Available demographic data were also abstracted from the databases. Malignancies in study children were identified based on physician diagnostic code and evidence of treatment (chemotherapy, radiation therapy, or surgical excision).

Based on the age, sex, and race distribution of the study population, the expected number of malignancies in both children exposed to TNFi and those not exposed to these drugs was calculated using Surveillance, Epidemiology, and End Results data, a national database of US cancers. The observed versus expected number of malignancies was used to calculate the standardized incidence ratio (SIR). In addition, Cox proportional hazard models were used to estimate the increased risk of malignancy in children with JIA, IBD, and PsO receiving TNFi compared to patients not receiving these drugs; potentially confounding variables were included in the regression models.

Data were analyzed on 30,535 children with JIA; 26,857 with IBD; and 32,045 with PsO. Among these study patients, 15,598 received TNFi and 73,839 were not exposed to these drugs; 24%, 27%, and 4% of children with JIA, IBD, and PsO, respectively, received TNFi. Mean duration of study follow-up for children receiving TNFi was 1.4 years. A total of 15 malignancies were observed in children treated with TNFi during 30,703 person-years of follow-up, and 42 malignancies were identified during 121,801 person-years of follow-up in unexposed patients. The SIR in children treated with TNFi was 2.9 (95% CI, 1.6, 4.9) versus 2.1 (95% CI, 1.5, 2.9) in unexposed patients. After controlling for confounding variables, the risk of malignancy was not significantly increased in patients with JIA, IBD, or PsO receiving TNFi and unexposed patients (hazard ratio, 1.58; 95% CI, 0.88, 2.85).

The authors conclude that children with JIA, IBD, and PsO had a higher than expected rate of malignancy compared to the general population, but TNFi did not appear to further increase this risk.

Dr Higgins has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

Following approval of TNFi for children with JIA (etanercept 1999, adalimumab 2008), and with IBD and Crohn’s disease (infliximab...

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