Starting with biologics in new-onset systemic JIA may reduce glucocorticoid use
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Biologic initiation in children hospitalized with new-onset systemic juvenile idiopathic arthritis increased significantly from 2008 to 2019, reaching 40% between 2017 and 2019, and may be linked with reduced glucocorticoid use, according to data.
“There is now mounting evidence that early initiation of biologic therapy (specifically IL-1 or IL-6 inhibition) not only improves disease course but also has the additive effect of reducing glucocorticoid exposure,” Rosemary G. Peterson, MD, of the Children’s Hospital of Philadelphia, and colleagues wrote in Pediatric Rheumatology. “In single-center observational studies, up to 90% of children treated with first-line IL-1 inhibition monotherapy did not require adjunctive glucocorticoid therapy after at least 1year of follow up.”
“However, it is not known whether early initiation of biologic therapy will reduce the need for glucocorticoids among children hospitalized at the onset of sJIA,” they added. “Prior work by our group found significant variation across hospitals in the use of biologic and glucocorticoid therapy for children presenting with sJIA between 2008 and 2019. This variation in practice represents an opportunity to assess whether the use of a biologic as first line therapy is causally associated with a reduction in glucocorticoid use.”
To examine the impact of early biologic initiation on glucocorticoid exposure among patients hospitalized with new-onset JIA, Peterson and colleagues emulated a pragmatic sequence of trials — or “pseudo-trials” — using diagnostic and billing records from the Pediatric Health Information System (PHIS). According to the researchers, the PHIS is an administrative database that includes inpatient, emergency department, ambulatory surgery and observation unit information from 52 not-for-profit, tertiary care pediatric hospitals. Data include demographics, dates of service, discharge disposition and daily inpatient billing data for medications.
Focusing on the period between Jan. 1, 2008, and March 31, 2019, the researchers analyzed data from 468 children discharged from a hospital with new-onset JIA. The primary outcome was the start of glucocorticoids during the index hospitalization for new-onset JIA, assessed during a period that started on day 2 of each pseudo-trial — labeled as “time zero” — and ended at discharge.
Eligibility window, treatment assignment and start of follow-up between biologic and non-biologic study arms were aligned for each pseudo-trial, with patients in the source population able to meet the eligibility criteria at several timepoints. In all, 1,451 patients were included across four pseudo-trials, with 71 assigned to the biologic arm and 1,380 assigned to the non-biologic arm. The researchers used mixed-effects logistic regression to determine the impact of biologic initiation on in-hospital glucocorticoid exposure.
According to the researchers, among the 468 children who met the eligibility criteria, 19% had a billing code for biologic therapy without preceding or concomitant adjunctive immunomodulatory medications, such as methotrexate or glucocorticoids, overall. This proportion “increased significantly” during the study period (P<.01), the researchers wrote, eventually reaching 40% between 2017 and 2019.
The median time to start a biologic medication from admission was 4days, while the median time from admission to start of glucocorticoids was 5days. In all, 51.3% of patients received glucocorticoids, including 22.5% who were treated with at least one dose of pulse dose glucocorticoids. Among those who started on glucocorticoids, 92.1% continued to receive them until hospital discharge.
Following the pseudo-trials, and after adjustments, there was a trend toward decreased odds of glucocorticoid initiation among those in the biologic arm, compared with the non-biologic group (OR = 0.39; 95% CI, 0.13-1.15).
“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,” Peterson and colleagues wrote. “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,” they added. “Finally, with continued growing evidence of improvement in clinically important outcomes in new-onset sJIA with first-line biologic therapy, future work should focus on identifying and addressing barriers to widespread implementation of this treatment strategy across diverse care settings.”
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