Two- and 3-year outcomes of the childhood arthritis and rheumatology research alliance FiRst Line Options for sJIA Treatment (FROST) trial.

Authors

Timothy Hahn, George Tomlinson, Yukiko Kimura, Vincent Del Gaizo, Timothy Beukelman, and the CARRA FROST Investigators

Published in

Pediatric rheumatology online journal. Jul 06, 2026. Epub Jul 06, 2026.

Abstract

Systemic juvenile idiopathic arthritis (sJIA) is a severe autoinflammatory disease associated with substantial morbidity, including macrophage activation syndrome (MAS), sJIA-associated lung disease, and glucocorticoid (GC)-related toxicity. CARRA's FiRst Line Options for sJIA Treatment (FROST) study demonstrated favorable short-term outcomes with early biologic therapy, but long-term outcomes have not yet been described.
Patients with new-onset sJIA enrolled in FROST (2016-2019) were followed longitudinally through the CARRA Registry. Four consensus treatment plans (CTPs) were evaluated, including IL-1 inhibition (either anakinra or canakinumab), IL-6 inhibition (tocilizumab), and two non-biologic arms (methotrexate or GC monotherapy). Long-term follow-up occurred through 36 months. The primary outcome was achievement of clinical inactive disease (CID) by Wallace/ACR provisional criteria without concurrent GC use at 24 and 36 months. Secondary outcomes included CID irrespective of GC use, cJADAS-10 ≤ 2.5 without fever, medication utilization, and adverse events. Adverse events were expressed as events per 100 person-years.
Seventy-three patients were enrolled; 87.6% initiated biologic therapy making comparison to non-biologic therapy infeasible. At 24 and 36 months, 41 and 32 patients, respectively, had evaluable data for the primary outcome. CID without GC use was achieved by 58.5% of patients at 24 months and 65.5% at 36 months. At both time points, over 80% of patients achieved cJADAS-10 ≤ 2.5 without fever and without GC use. Nearly all patients were off GCs at 24 and 36 months (> 90%). The cumulative proportion of patients achieving CID at any time during follow-up increased to 78.8% by 24 months and 87.6% by 36 months. At last follow-up, 42.5% of patients were off all disease-modifying antirheumatic drugs (DMARDs). Over 228.2 person-years of observation, serious adverse events occurred at a rate of 6.6 per 100 person-years; MAS was the most common SAE. No cases of sJIA-associated lung disease were identified.
Although results were limited by loss to follow-up, patients enrolled in FROST demonstrated increasing rates of CID and high rates of glucocorticoid discontinuation during long-term follow-up. Serious adverse events were uncommon and largely related to disease activity. These findings support early biologic therapy as an effective and durable first-line strategy for sJIA.
Not applicable.

PMID:
42410463
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.

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