Early IL-1 Inhibition in Still's Disease: A Window of Opportunity for Improving Outcomes.

Objective: Still's disease is a complex, multisystemic disorder requiring prompt diagnosis and treatment. This study provides a general assessment of a Still's disease cohort aiming to evaluate the efficacy of early intervention with interleukin-1 inhibitors (IL-1i) in achieving clinical inactive disease (CID) and reducing glucocorticoid use in patients with Still's disease.

Methods: We retrospectively analyzed 42 adult patients diagnosed with Still's disease after 2010 and treated with IL-1i. Patients were categorized as early treated (IL-1i started before six months from symptom onset) or late treated (IL-1i started after 6 months). CID achievement, glucocorticoid use, flares, and imaging findings were assessed. The chi-square test was employed as a statistical test, and P < 0.05 was considered significant. GraphPad Prism 8 was used for statistical analysis.

Results: The median time from symptom onset to IL-1i introduction was six months (interquartile range: 2-19). Overall, 55% of patients achieved CID at six months. Early treated patients showed a trend toward higher proportion of CID achievement compared to that of late-treated patients (67% vs 38%; P = 0.17). A meta-analysis including our cohort and two other observational studies showed that early treatment was associated with an odds ratio of 6.73 (95% confidence interval: 2.31-19.64) in comparison to late treatment. All our patients initially received glucocorticoids, with 48% of those achieving CID able to discontinue glucocorticoids within six months. Ten major flares were observed, with 62% occurring after IL-1i suspension or spacing. At baseline, F-fluorodeoxyglucose positron emission tomography (PET)-computed tomography (CT) or magnetic resonance (MR) scans revealed hypermetabolic areas primarily in the bone marrow, spleen, and lymph nodes. After IL-1i introduction, these hypermetabolic regions generally showed a reduction in activity.

Conclusions: Early introduction of IL-1i in patients with Still's disease may lead to higher rates of CID achievement and glucocorticoid discontinuation. PET-CT/MR imaging may be valuable in assessing disease activity and guiding treatment decisions. These findings support the concept of a "window of opportunity" in Still's disease management, emphasizing the importance of prompt diagnosis and treatment initiation.