Study compares infection risk for JIA, ADHD patients

Children with juvenile idiopathic arthritis (JIA) were at twice the risk of infection compared with children with attention-deficit hyperactivity disorder (ADHD), according to a study published May 1 in Arthritis & Rheumatism. Among children with JIA, the rate of infection significantly increased with high-dose glucocorticoid use; however, the rate of infection did not increase with the use of methotrexate (MTX) or tumor necrosis factor (TNF) inhibitors.

“This finding suggests that the inflammatory or autoimmune process of JIA may predispose children to infection irrespective of therapy,” wrote Timothy Beukelman, MD, MSCE, from the University of Alabama at Birmingham, and colleagues.

Immunosuppressant therapies are commonly used to treat patients with JIA; however, their impact on serious bacterial infections has not been extensively studied. An increased rate of bacterial infections has been the most commonly reported side effect in adult patients with rheumatoid arthritis (RA) who are treated with TNF inhibitors; however, studies focusing on this relationship have reported conflicting results. And although MTX has been used for decades in the treatment of JIA, there is little information on the incidence of infection in clinical practice. Similarly, systemic glucocorticoids have been shown in studies to significantly increase the risk of infection in adult patients with RA, but there are no published studies reflecting the relationship for children with JIA.

To examine the effects of these medications, the researchers compared the incidence of hospitalized bacterial infections among children with JIA to a comparator cohort of children with ADHD and examined the effects of these medications.

Using national US Medicaid data from 2000-2005, the researchers identified 8,479 children with JIA with a total of 13,003 person-years of follow-up, and 360,489 children with ADHD with a total of 454,698 person-years of follow-up. They used pharmacy claims to determine exposures to MTX, TNF, and oral glucocorticoids, and they identified hospitalized bacterial infections using International Classification of Disease, Ninth Revision (ICD-9) coded discharge diagnoses. Finally, they calculated adjusted hazard ratios to compare the infection incidence rates by adjusting for various patient characteristics.

Of the children with JIA, the authors found that 42% used MTX and 17% used TNF inhibitors. JIA patients without current MTX or TNF inhibitor use had an increased rate of infection (aHR 2.0; 95% CI, 1.5–2.5) compared with patients identified with ADHD. Among JIA patients not using TNF inhibitor therapy, patients using MTX had a similar rate of infection compared with those not using MTX (aHR 1.2; 95% CI, 0.9–1.7). And those patients using TNF inhibitors, irrespective of MTX use, had a similar rate of infection compared to patients using MTX without TNF inhibitors (aHR 1.2; 95% CI, 0.8–1.8). With adjustment for MTX and TNF inhibitor use, high-dose glucocorticoid use (≥10 mg of prednisone daily) increased the rate of infection compared with no glucocorticoid use (aHR 3.1; 95% CI, 2.0–4.7).

Noting limitations, the authors wrote that without access to medical records, they could not directly verify the diagnoses of JIA, ADHD, or infection and they considered current medication exposure up to 30 days after a missed prescription refill.

“These data suggest the use of steroid-sparing treatment strategies may reduce the risk of serious infections in children with JIA,” they concluded.