First-Line Biologics Reduce Glucocorticoid Exposure in Patients With Systemic Juvenile Idiopathic Arthritis

Initiation of biologics in children hospitalized with systemic juvenile idiopathic arthritis (sJIA) has both increased over time and may be associated with reduced glucocorticoid exposure, thus reducing treatment-related side effects, according to a study published in BMC.¹

Glucocorticoids are historically a driver of morbidity in this patient population, including adverse effects such as growth inhibition, osteoporosis, avascular necrosis, obesity, cataracts, hypertension, and psychologic issues. Investigators analyzed the effect of biologic therapies, such as interleukin-1 (IL-1) or interleukin-6 (IL-6), in order to determine the effectiveness of this first-line biologic approach in treating sJIA and reducing the exposure of glucocorticoids.

“The current draft of the American College of Rheumatology (ACR) 2020 JIA guidelines explicitly recommend biologic DMARDs (IL-1 and IL-6 inhibitors) as first-line monotherapy and avoidance of oral glucocorticoid monotherapy (grade C recommendations),” explained investigators. “Paralleling this recent recommendation, we have shown an increasing trend toward biologic monotherapy, which is encouraging as it should reduce the negative consequences of glucocorticoid-reliant therapeutic approaches.”

Pseudo-trials were conducted analyzing biologic initiation in children with sJIA using observational data from 52 hospitals in the Pediatric Health Information System (PHIS) between January 2008 and March 2019. Investigators collected information such as demographics, discharge disposition, dates of service, and billing data for medications. Both biologic and non-biologic cohorts were aligned for eligibility window, treatment, and start of follow-up. Covariates included demographics, hospital characteristics, year of discharge, and disease severity.

Eligible patients were required to have had no previous glucocorticoid exposure. Glucocorticoids included oral or intravenous dexamethasone, hydrocortisone, methylprednisolone, prednisolone, or prednisone.

The source population was 468 patients with sJIA who were discharged from 1 of the PHIS institutions. Within this group, 19% of patients had initial biologic therapy without initiation of immunomodulatory medications, such as methotrexate or glucocorticoids. Throughout the 12-year period, the proportion of patients initially receiving biologics increased significantly over time, culminating in approximately 40% of patients between 2017 and 2019.

The time from admission to receiving biologic medication was 4 days. A total of 51.3% of patients received glucocorticoids, with the time from admission to initiation of medication being 5 days.

A total of 1451 patients were included in 4 pseudo trails, of which 1380 were in the non-biologic cohort and 71 subjects were in the biologic cohort. There was a trend towards reducing glucocorticoid initiation in the biologic group when compared with the non-biologic group (0.13, 1.15, respectively). Exposure to methotrexate was more common in the biologic non-initiators group (8.6% vs. 2.8%, respectively). After the 4th trial, 19 patients receiving biologic therapy were added to the biologic non-initiator group. Analysis showed that these patients were less likely to receive glucocorticoids than other patients in the same cohort (36.8% vs. 56.9%, respectively).

The study was limited by its inability to evaluate treatment after patients were discharged from the hospital, however, it was designed to analyze the association of biologics on glucocorticoid exposure. The inclusion of 19 patients who started biologics after the eligibility window may have reduced investigators’ ability to detect this effect of biologics and glucocorticoid initiation. Additionally, the treatment groups were not randomized, and outcomes were limited to information provided in the administrative claims database. Macrophage activation syndrome (MAS) was not included to balance out the 2 groups as data was not clear if MAS was present before initiating biologics, however, MAS was similar in both study arms. Lastly, as only 1 patient was treated using an IL-6 inhibitor, the results may not be able to be generalized to this treatment approach.

“Our results coupled with other observational studies suggest that initial therapy with a biologic may reduce the use of glucocorticoids in hospitalized children with new onset sJIA but is only utilized in a minority of patients,” concluded investigators. “Further studies are needed to assess other important clinically relevant long-term outcomes that may be related to glucocorticoid use or avoidance in sJIA, including hospital readmissions for disease flares or infection, MAS, sJIA-related pulmonary disease, and long-term glucocorticoid toxicity. These studies will help to develop a more evidence-based approach to glucocorticoid usage in sJIA.”

Reference:

Peterson RG, Xiao R, Katcoff H, Fisher BT, Weiss PF. Effect of first-line biologic initiation on glucocorticoid exposure in children hospitalized with new-onset systemic juvenile idiopathic arthritis: emulation of a pragmatic trial using observational data. Pediatr Rheumatol Online J. 2021;19(1):109. Published 2021 Jul 5. doi:10.1186/s12969-021-00597-z