Expanding the therapeutic landscape of Still’s disease: the emerging role of JAK inhibitors

INTRODUCTION: Still's disease is a systemic inflammatory disorder characterized by a complex cytokine network involving interleukin (IL)-1, IL‑6, IL‑18 and interferon (IFN)-γ. Although IL‑1 and IL‑6 inhibitors represent the cornerstone of current targeted therapy, a subset of patients remains refractory or develops treatment-related limitations. JAK inhibitors, by targeting the JAK-STAT pathway, provide a broad modulation of multiple cytokine signals and have emerged as a promising strategy in difficult-to-treat disease. AREAS COVERED: We aimed to review the emerging role of Janus kinase inhibitors (JAKis) in the management of Still's disease, with a focus on their mechanistic rationale, clinical evidence, and potential positioning within current therapeutic strategies. A narrative review was conducted through a comprehensive search of MedLine via PubMed accordingly. EXPERT OPINION: Preliminary evidence, mainly derived from small observational studies, suggests that JAKis may improve systemic and articular manifestations and allow glucocorticoid sparing. In addition, agents such as ruxolitinib may have a role in macrophage activation syndrome through inhibition of IFN‑γ-dependent pathways. However, incomplete modulation of IL‑1-driven and inflammasome-dependent mechanisms may represent a potential limitation in specific disease phenotypes. JAKis represent a promising addition to the therapeutic armamentarium of Still's disease, particularly in refractory cases. However, current evidence remains limited, and their efficacy and safety are not yet fully established. A precision medicine approach, integrating clinical phenotype and underlying pathogenic pathways, will be essential to optimize their use, and further prospective studies are needed to define their role within the treatment algorithm.