FROST: Biologics most common initial therapy for systemic JIA
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Initial biologic therapy is now the most common treatment for children with systemic juvenile idiopathic arthritis in the Childhood Arthritis and Rheumatology Research Alliance Registry, according to data presented at ACR Convergence 2021.
In addition, most patients who did not initially start with a biologic eventually switched within a few months of their diagnosis, with up to 75% demonstrating favorable outcomes, the researchers said.
“We know from randomized clinical trials that IL-1 and IL-6 inhibitors are efficacious for the treatment of systemic JIA, but these studies did not enroll patients at the time of diagnosis,” Tim Beukelman, MD, MSCE, of the University of Alabama at Birmingham, told attendees at a virtual press conference. “Additionally, uncontrolled published report suggests that early treatment with biologic agents likely produces superior short-term outcomes, but many patients may respond well to non-biologic therapies. Therefore, the optimal treatment for systemic JIA is unclear.”
“In response to this situation, CARRA developed consensus treatment plans, or CTP, to standardize and formalize treatment practices for systemic JIA,” he added. “A group of pediatric rheumatologists work together to identify the most commonly current use treatments for systemic JIA, through a process of surveys and face to face consensus meetings, and the results and CTPs were published in 2012.”
Those four consensus treatment plans are: Initial systemic glucocorticoids, initial methotrexate with or without glucocorticoids, an initial IL-1 inhibitor with or without glucocorticoids, or an initial IL-6 inhibitor with or without glucocorticoids. To analyze the effectiveness and safety of each, Beukelman and colleagues conducted “First Line Options for sJIA Treatment,” or FROST, a prospective, observational study of data from the CARRA Registry.
The study included 73 patients with recent-onset systemic JIA who were starting treatment. Other inclusion criteria included fever for at least 2 weeks, arthritis for at least 10 days, and at least one of the following: evanescent rash, generalized lymphadenopathy, hepatomegaly, splenomegaly or serositis. Assigned treatment plans were at the discretion of each patient’s physician and family.
The primary outcome was clinically inactive disease with no glucocorticoid use at 9 months. Secondary outcomes included clinically inactive disease regardless of glucocorticoid use, and the Clinical Juvenile Arthritis Disease Activity Score (cJADAS-10) without current fever.
For this analysis, the researchers presented findings from patients who received either initial biologic therapy — interleukin-1 or IL-6 inhibitors — or initial non-biologic therapy only, as few were treated within the glucocorticoid, methotrexate and IL-6 inhibitor arms.
According to the researchers, 63 of the included patients started treatment with biologics, while 10 initially received glucocorticoids, either alone or with MTX. Biologic initiation ranged from 7 days prior to enrollment to 61 days after, with 75% starting treatment within 1 day after enrollment. Among the 59 patients who initiated IL-1 inhibitors, 14% subsequently switched to IL-6 inhibitors. No patients switched from IL-6 to IL-1 inhibitors.
Among patients who started with glucocorticoids, either with or without MTX, 50% would ultimately begin taking biologics during the study period, with time to initiation ranging from 10 to 101 days.
A total of 57 patients recorded a 9-month visit. Overall, 57% met the primary outcome, achieving clinically inactive disease without glucocorticoid use at 9 months. Meanwhile, 75% demonstrated a cJADAS-10 score of 2.5 or less with no fever and no glucocorticoid use. There were 16 reported safety events with a Common Terminology Criteria for Adverse Events (CTCAE) grade of three or higher, all within the biologic group, including six cases of macrophage activation syndrome. One patient died of acute liver failure.
“The systemic JIA treatment patterns have changed considerably since the original CTP development in 2012, with most patients now receiving biologic therapies early in the disease course,” Beukelman said. “The short-term outcomes in FROST study were generally excellent. However, assessment of long-term outcomes and confirmation of the IL-1 and IL-6 inhibitor safety are needed. These patients that participated in the FROST study are still enrolled in the CARRA registry, and so ongoing data collection continues to help answer these questions.”
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Beukelman T. Abstract 0242. Presented at: ACR Convergence 2021; November 5-9, 2021 (virtual meeting).
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