Most Kids With Severe Childhood Arthritis Improve With Biologic Drugs
Data from the FROST study highlight long-term benefits of IL-1 and IL-6 inhibitors, and reveal early clues about nonresponse
Topline:
The FROST study found that most children with newly diagnosed systemic juvenile idiopathic arthritis (sJIA) experienced clinically inactive disease by 3 years with IL-1 or IL-6 inhibitors—often without long-term glucocorticoids. New biomarker research may soon help predict who won’t respond to IL-1 inhibitors.
Study Details
Systemic juvenile idiopathic arthritis (sJIA) is a rare, often aggressive form of childhood arthritis. To understand how well current treatments work in real-world settings, the FROST (First-Line Options for Systemic JIA Treatment) study tracked outcomes in 73 children diagnosed between 2016 and 2019, comparing biologics (IL-1 and IL-6 inhibitors), glucocorticoids, and methotrexate.
Methodology
This prospective observational study followed patients for up to 3 years. Children (mean age ~9) or their caregivers recorded symptoms like rash, fever, and medication use at home. Clinical visits occurred at baseline and regular intervals to assess disease activity using the cJADAS-10 scoring system and patient-reported outcomes. Three follow-up analyses were presented at the 2025 CARRA conference.
Key Findings
1. Biologics without steroids worked well for most kids:
By 9 months, 57% of patients had clinically inactive disease without steroids. At 3 years, 65.6% remained inactive off steroids, and 87.6% had reached that state at some point.
2. Glucocorticoids may not add much benefit early on:
About half of patients received glucocorticoids early. Yet, no significant differences in fatigue, pain, or mobility were seen between those who did and didn’t take steroids when also on IL-1 or IL-6 inhibitors.
3. Biomarker clues for IL-1 inhibitor response:
Among 30 patients treated with IL-1 blockers, responders had higher neutrophil counts and lower CD25 levels at baseline. Nonresponders showed less improvement in inflammatory cytokines at 6 months.
4. Side effects were generally manageable:
Adverse events occurred in 19 of 73 children, with serious events—including infections—reported at 6.6 per 100 patient-years. One child died of acute liver failure. No cases of sJIA lung disease were reported.
Implications for Practice
For clinicians:
IL-1 and IL-6 inhibitors remain the preferred first-line therapy for sJIA.
Early glucocorticoid use might be optional if biologics are started quickly.
Biomarker-based prediction tools may soon help identify likely nonresponders to IL-1 inhibitors, enabling earlier treatment adjustments.
For patients and families:
The outlook for sJIA is much better today than in the past.
Most children in the study achieved long-term remission—even without steroids.
Ongoing studies are working to personalize treatment and avoid trial-and-error approaches.