Targeted small molecules in Polymyalgia Rheumatica: the emerging role of jak inhibitors beyond glucocorticoids and DMARDs.

INTRODUCTION: Glucocorticoids remain the cornerstone of therapy for polymyalgia rheumatica (PMR), but their long-term use is associated with substantial toxicity. Glucocorticoid-sparing strategies, particularly anti - IL-6 therapies, are now well established. More recently, targeted small molecules such as Janus kinase (JAK) inhibitors have emerged as potential alternatives to reduce glucocorticoid exposure. AREAS COVERED: This narrative review briefly summarizes conventional and biologic therapies in PMR and focuses on JAK inhibitors, particularly baricitinib and tofacitinib. These agents target the JAK/STAT pathway, a key mediator of cytokine-driven inflammation, including IL-6 signaling. Evidence from the BACHELOR and EAST PMR trials, as well as phase II studies and real-world data, indicates that JAK inhibitors rapidly reduce disease activity, inflammatory markers, and glucocorticoid requirements. Baricitinib achieved sustained low disease activity in approximately 78% of patients at 12 weeks without concomitant glucocorticoids, while tofacitinib demonstrated efficacy comparable to glucocorticoids with significant glucocorticoid-sparing effects. EXPERT OPINION: JAK inhibitors represent a promising therapeutic option, particularly for patients with refractory disease or at high risk of glucocorticoid-related toxicity. Although short-term safety appears acceptable, long-term risks, including cardiovascular events, infections, and malignancy, require further evaluation. Ongoing phase III trials will better define their role in achieving remission without systemic glucocorticoid use and in guiding personalized treatment strategies in PMR.