Immunopathology of polymyalgia rheumatica: Links to clinical manifestations and prospects for targeted therapy

Polymyalgia rheumatica (PMR) is one of the most common inflammatory rheumatic diseases affecting older adults. The aim of this review was to analyze current concepts of the immunopathogenesis of PMR and the possibilities of pathogenetic therapy for this disease. A literature search was conducted in the PubMed, Scopus, Web of Science, eLIBRARY.RU and Google Scholar databases using the following keywords: “polymyalgia rheumatica”, “immunopathogenesis”, “immunosenescence”, “methotrexate”, “biologic therapy”, “IL-6 inhibitors”, “IL-17 inhibitors”, “targeted therapy”, “tocilizumab”, “sarilumab”, “olokizumab”, “tofacitinib”, “baricitinib”, and their Russian-language equivalents. A total of 110 publications were initially identified. Following full-text assessment, 24 articles were excluded due to lack of relevance to the review topic, insufficient informativeness, or the absence of significant data regarding the immunopathogenesis and treatment of PMR. A total of 86 publications were included in the qualitative analysis, comprising randomized controlled trials, cohort studies, clinical observations, systematic reviews, and basic research studies. Twelve publications focusing on the immunopathology of PMR were used for preparation of the Introduction section. The analysis demonstrated that immunosenescence, activation of innate and adaptive immunity, disturbances in Tand B-cell immune responses, and dysregulation of the cytokine network, with a central role of interleukin-6, are key contributors to the pathogenesis of PMR. The most convincing evidence currently supports the use of interleukin-6 and interleukin-17 inhibitors, whose efficacy has been confirmed in randomized clinical trials. Expanding knowledge of the mechanisms underlying the disease contributes to the development of personalized treatment approaches for patients with PMR and to the optimization of long-term disease control.

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