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

backgroundSystemic 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.

methodsPatients 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.

resultsSeventy-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.

conclusionsAlthough 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. CLINICAL TRIAL NUMBER: Not applicable.