JAK Inhibitors in Rheumatoid Arthritis: Immunomodulatory Properties and Clinical Efficacy

• Published in: International journal of molecular sciences 2024-08, Vol.25 (15), p.8327
• Main Authors: Kiełbowski, Kajetan, Plewa, Paulina, Bratborska, Aleksandra Wiktoria, Bakinowska, Estera, Pawlik, Andrzej
• Format: Article
• Language: English
• Subjects: Animals; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Arthritis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; B cells; Biological products; Cytokines; Development and progression; Disease; Fibroblasts; Genes; Growth factors; Humans; Inflammation; Interferon; JAK inhibitors; JAK/STAT pathway; Janus Kinase Inhibitors - pharmacology; Janus Kinase Inhibitors - therapeutic use; Janus Kinases - antagonists & inhibitors; Janus Kinases - metabolism; Kinases; Macrophages; Medical research; Medicine, Experimental; Pathogenesis; Phosphorylation; Proteins; Rheumatoid arthritis; Rheumatoid factor; Signal Transduction - drug effects; Skin cancer; STAT Transcription Factors - metabolism; T cells; Tofacitinib; Transcription factors; Tumor necrosis factor-TNF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25158327

Rheumatoid arthritis (RA) is a highly prevalent autoimmune disorder. The pathogenesis of the disease is complex and involves various cellular populations, including fibroblast-like synoviocytes, macrophages, and T cells, among others. Identification of signalling pathways and molecules that actively contribute to the development of the disease is crucial to understanding the mechanisms involved in the chronic inflammatory environment present in affected joints. Recent studies have demonstrated that the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway regulates the behaviour of immune cells and contributes to the progression of RA. Several JAK inhibitors, such as tofacitinib, baricitinib, upadacitinib, and filgocitinib, have been developed, and their efficacy and safety in patients with RA have been comprehensively investigated in a number of clinical trials. Consequently, JAK inhibitors have been approved and registered as a treatment for patients with RA. In this review, we discuss the involvement of JAK/STAT signalling in the pathogenesis of RA and summarise the potential beneficial effects of JAK inhibitors in cells implicated in the pathogenesis of the disease. Moreover, we present the most important phase 3 clinical trials that evaluated the use of these agents in patients.