Real-World Adult-Onset Still’s Disease Treatment Patterns

Key Takeaways

• In Italian real-world care for active AOSD, 97.7% of patients received GCs, 58.8% received csDMARDs, and 43.3% received bDMARDs. Biologic use was led by IL-1 inhibition, while IL-6 and tumor necrosis factor inhibition were used much less often.
• Most patients were judged to have clinically inactive disease after 3 months, and recorded clinical and laboratory measures improved significantly from baseline.

Active adult-onset Still’s disease often forces a sequencing decision between rapid inflammation control with steroids and earlier use of cytokine-targeted therapy. In a prospective GIRRCS-AOSD multicenter real-world cohort, Italian rheumatology units recorded care from January 2022 through December 2023. Investigators assessed 187 patients with adult-onset Still’s disease (AOSD), analyzing 173 with active disease and excluding 14 with clinically inactive disease.

All included patients met Yamaguchi criteria, were evaluated at baseline and again at 3 months, and had glucocorticoids (GCs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and biologic disease-modifying antirheumatic drugs (bDMARDs) recorded without a protocol mandate. The cohort also compared observed management with European Alliance of Associations for Rheumatology and Pediatric Rheumatology European Society (EULAR/PReS) recommendations and explored factors associated with interleukin-1 and interleukin-6 inhibitor use.

Prescribing in active AOSD was dominated by GCs, which were used in 97.7% of patients, while csDMARDs were used in 58.8% and bDMARDs in 43.3%. More than one-third received high-dose glucocorticoids, and csDMARD use centered mainly on methotrexate and cyclosporin A.

The authors interpreted the 6.0-month median time to bDMARD initiation as suggesting that biologics often entered care later rather than earlier; 22.7% of patients started within the first 3 months, and clinically inactive disease at 3 months was reported in 86.7%. Systemic manifestations, inflammatory markers, ferritin, and patient global assessment all improved significantly from baseline, and no changes in bDMARD therapy were observed during follow-up.

The authors described the cohort as observational and designed to capture therapeutic decisions rather than compare efficacy between strategies. Improvement at 3 months was not stratified by treatment approach, clinically inactive disease depended on treating-physician judgment within routine clinical documentation, and disease duration was not collected directly. They also noted that the single-country design, exclusion of patients with life-threatening complications, and underpowered exploratory analysis of interleukin-6 inhibitor use narrow generalizability, while safety outcomes were not reported.

The authors concluded that observed practice showed no concordance with EULAR/PReS positions on limiting glucocorticoid use and on earlier biologic initiation, with partial concordance for csDMARD use.

Clinician Questions

Which biologic classes were most often used in active AOSD routine care?

In the Italian active AOSD cohort, IL-1 inhibitors were used in 33.5% of patients, compared with 5.8% for IL-6 inhibitors and 4% for TNF inhibitors, showing a clear class hierarchy toward IL-1 blockade in routine biologic use.

How was clinically inactive disease defined after 3 months in this AOSD cohort?

Clinically inactive adult-onset Still’s disease was defined as absence of clinical signs and symptoms together with normalization of inflammatory markers for at least 2 consecutive months, irrespective of ongoing therapy, and this status came from treating-physician judgment within routine clinical documentation rather than a protocol-driven scheduled assessment.

What factor was linked to IL-1 inhibitor use in exploratory modeling for active AOSD?

Ferritin at or above 1225.0 ng/mL was associated with IL-1 inhibitor use in exploratory multivariable modeling, while older age was linked to IL-6 inhibitor use only in univariate analysis. Because few patients received IL-6 inhibitors, both signals should be read as exploratory and hypothesis-generating.

Which patients with AOSD were represented in this Italian real-world analysis, and who was not?

This Italian real-world analysis represented patients with active adult-onset Still’s disease in rheumatology centers who fulfilled Yamaguchi criteria and had prospective baseline and 3-month follow-up, but it did not include patients with clinically inactive disease, other inflammatory diseases, malignancies, active infections, or life-threatening complications, which narrows applicability beyond that setting.