Toward a personalized therapy of still's disease based on immunologic endotypes: a narrative review

Accumulative evidence indicates that both innate and adaptive immunity are involved in pathogenesis of Still's disease, an autoinflammatory disease. With Increasing insights into the pathogenesis of Still's disease coupled with the availability of emerging targeted therapeutics, it may be the unmet need for personalizing therapy and achieving a treat-to-target goal. We aim to summarize the available evidence regarding immunopathogenesis of Still's disease and therapeutic strategies based on immunologic endotypes.

We searched MEDLINE database using the PubMed interface and reviewed relevant English-language literature from 1971 to 2024. This review focuses on the existing evidence on pathophysiology and immunological endotypes of Still's disease and their implications for personalized strategies for patients with this disease.

Targeting the complex immunopathogenesis of Still's disease, emerging new agents are available for treatment, including biologic disease-modifying anti-rheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) such as Janus kinase inhibitors (JAKi). According to the updated evidence, meta-analyses, and recommendations, we propose a flow chart emphasizing personalized therapeutic strategies based on immunological endotypes. Hopefully, the therapeutic strategy might help guide the optimal selection of b/tsDMARDs to achieve a 'treat-to-target' goal in Still's disease. This proposed flow chart will be updated as newer evidence emerges.