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Effect of JAK Inhibitors on Pain Management in Patients with Rheumatoid Arthritis: A Literature Review
Aleksandra Kowalska1, Aleksandra Jawoszek1, Aleksandra Borkowska1
1Department of Mental and Psychosomatic Diseases, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland.
Abstract:
The introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) has significantly enhanced the prognosis for patients with rheumatoid arthritis (RA). Nevertheless, improving quality of life remains a major clinical challenge requiring the implementation of multidirectional therapeutic measures. Pain reduction plays a particularly important role in this context, representing one of the primary treatment goals for many patients. Scientific evidence indicates that effective pain management is a crucial predictive factor for the improvement of mental and physical health in patients with RA. The aim of this literature review was to summarise the mechanisms of action of Janus kinase inhibitors (JAKi), with particular emphasis on their modulation of pain generation and transmission. Furthermore, the study aimed to compare the results of clinical studies and assess the actual effectiveness of these drugs in reducing pain in clinical practice. JAKi exhibit peripheral analgesic effects by directly reducing the production of pro-nociceptive cytokines and modulating macrophage polarisation. Moreover, they influence central pain processing mechanisms by modulating the IL-6/JAK/STAT3 pathway and by reducing microglial and astrocyte proliferation in the dorsal horn of the spinal cord. The results of randomised clinical trials confirm that JAKi provide rapid, clinically significant pain reduction. Some studies also point to the persistence of this effect over a longer period, and to their greater efficacy compared with conventional disease-modifying antirheumatic drugs (cDMARDs) and bDMARDs. The efficacy of this group of drugs has also been noted in patients with an inadequate response to prior therapy with biological drugs. A key focus of future research remains determining the optimal timing for introducing JAKi in the treatment of RA and identifying predictive factors to enable the selection of patients most likely to benefit from this class of drugs.
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