Children with juvenile idiopathic arthritis using anti-tumor necrosis factor inhibitors (TNFIs) have a significantly higher risk for infection compared with children using disease-modifying antirheumatic drugs (DMARDs), according to a recent study published in Rheumatology.
Using the Truven MarketScan Commercial Claims and Encounters database, Glen T. Schumock, PharmD, MBA, PhD, from the University of Illinois in Chicago, and colleagues identified 2013 children younger than 16 years receiving DMARDs and 482 children receiving TNFIs between 2009 and 2013. The mean follow-up in the DMARD group was 255 days, whereas the mean follow-up in the TNFI group was 307 days.
“Although TNFIs are usually recommended for use in combination with DMARDs, studies have shown that TNFIs are increasingly used early in the [juvenile idiopathic arthritis (JIA)] disease course and as monotherapy,” Dr Schumock and colleagues wrote in their study. “This new treatment paradigm facilitated our comparison of the two groups, as both consisted of new initiators of therapy.”
The researchers found that 18 (0.9%) patients in the DMARD group had a serious infection (crude rate 1.28 per 100 person-years; 95% CI, 0.76-2.02) compared with 11 (2.2%) patients in the TNFI group (crude rate, 2.72 per 100 person-years; 95% CI, 1.36-4.86).
“The likely mechanism by which TNFIs increase the risk of infection is related to the role of TNF in the immune response,” Dr Schumock and colleagues wrote. “Inhibiting the action of TNF prevents the normal immune response, increasing the risk for infections. It is possible that infections are not detected until they become severe because TNFIs impede the usual clinical presentation of high fever and elevated [C-reactive protein].”
After creating an adjusted Cox proportional hazard model, patients in the TNFI group had a significantly increased risk for serious bacterial infection (hazard ratio, 2.72; 95% CI, 1.08-6.86).
“Our analysis supports the FDA warning about TNFI-associated infection in children with JIA and also provides a comparison between DMARD and TNFI monotherapy,” Dr Schumock and colleagues wrote in their study. “Future studies incorporating a larger cohort of children with JIA would help to confirm our findings and further characterize the risk of infection across individual TNFI agents. In the meantime, clinicians and patients need to balance the benefits of these highly effective drugs against the risk for infection they pose.”
Limitations & Disclosures
The researchers noted misclassification of data in administrative claims databases, confounding factors of juvenile idiopathic arthritis and infection, and poor statistical power as potential limitations in their study.
Dr Schumock reports receiving consulting or speaking fees from AbbVie Inc., Astellas Pharma US Inc., and Baxter International Inc.
Lee W-J, Lee TA, Suda KJ, et al. Risk of serious bacterial infection associated with tumour necrosis factor-alpha inhibitors in children with juvenile idiopathic arthritis [published online April 18, 2017]. Rheumatology. doi: 10.1093/rheumatology/kex049