Understanding the immunopathophysiology of polymyalgia rheumatica: implications for treatment

Choy, Ernest H. ORCID: https://orcid.org/0000-0003-4459-8609, Unizony, Sebastian H., Wells, Alvin F., Dasgupta, Bhaskar, Buttgereit, Frank and Tanaka, Yoshiya 2025. Understanding the immunopathophysiology of polymyalgia rheumatica: implications for treatment. Annals of the Rheumatic Diseases 10.1016/j.ard.2025.09.005

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Abstract

Polymyalgia rheumatica (PMR) is one of the most common inflammatory rheumatic diseases in people aged ≥50 years and is characterised by neck pain, bilateral shoulder and hip girdle pain, and morning stiffness. It is closely interlinked with giant cell arteritis (GCA) (potentially considered the GCA-PMR spectrum) and rheumatoid arthritis and shares a common immunopathophysiology with both. Glucocorticoids (GCs) have been the standard of care for PMR for several decades (American College of Rheumatology/European Alliance of Associations for Rheumatology guidelines); however, >50% of patients cannot successfully taper GCs, and long-term treatment is associated with considerable GC-related adverse events. Immunohistological studies using biopsies from subacromial bursae have indicated that various cytokines and cells, including macrophages, interleukin-6 (IL-6), and fibroblast-like synoviocytes (FLS), play an integral role in the immunopathophysiology of PMR. Proinflammatory cytokines, including IL-1, IL-6, IL-17, and tumour necrosis factor-alpha, activate FLS which then secrete IL-6 that can further promote FLS proliferation. Activation of synoviocytes in bursae may result in bursitis which can lead to a high concentration of acute-phase reactants and systemic inflammation. IL-6 also plays a role in sleep disturbances, mood disorders, pain, and fatigue; it is often seen in PMR, via disruption of the hypothalamic-pituitary-adrenal axis, and actions on the peripheral and central pain pathways. Given the diverse roles of IL-6 in the immunopathophysiology of PMR, targeted molecular therapies such as IL-6 receptor inhibitors offer promising alternatives for disease management, distinct from the nonspecific immunosuppressive effects of GCs. In this review, we describe the immunopathophysiology of PMR and discuss unmet medical needs and therapeutic options for PMR.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Publisher:	BMJ Publishing Group
ISSN:	0003-4967
Date of First Compliant Deposit:	29 October 2025
Date of Acceptance:	11 September 2025
Last Modified:	29 Oct 2025 15:45
URI:	https://orca.cardiff.ac.uk/id/eprint/181981

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