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Biomedicines
Volume 13
Issue 10
10.3390/biomedicines13102429
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Review

Effects of Janus Kinase Inhibitors on Rheumatoid Arthritis Pain: Clinical Evidence and Mechanistic Pathways

by
Andrej Belančić
1,*,†,
Seher Sener
2,†,
Yusuf Ziya Sener
3,
Almir Fajkić
4,
Marijana Vučković
5,
Antonio Markotić
6,
Mirjana Stanić Benić
7,
Ines Potočnjak
8,
Marija Rogoznica Pavlović
9,
Josipa Radić
5,10 and
Mislav Radić
10,11,*
1
Department of Basic and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia
2
Department of Pediatric Rheumatology, Adana City Training and Research Hospital, Adana 01370, Türkiye
3
Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, 3000 CB Rotterdam, The Netherlands
4
Department of Pathophysiology, Faculty of Medicine, University of Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina
5
Department of Internal Medicine, Division of Nephrology and Dialysis, University Hospital of Split, 21000 Split, Croatia
6
Department of Physiology, School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina
7
Department of Internal Medicine, General Hospital “Dr. Josip Benčević” Slavonski Brod, Andrije Štampara 42, 35000 Slavonski Brod, Croatia
8
Institute for Clinical Medical Research and Education, Sestre Milosrdnice University Hospital Center, School of Medicine Catholic University of Croatia, 10000 Zagreb, Croatia
9
Hospital for Medical Rehabilitation of Heart and Lung Diseases and Rheumatism ‘Thalassotherapia-Opatija’, 51410 Opatija, Croatia
10
Internal Medicine Department, School of Medicine, University of Split, 21000 Split, Croatia
11
Department of Internal Medicine, Division of Rheumatology, Allergology and Clinical Immunology, Center of Excellence for Systemic Sclerosis in Croatia, University Hospital of Split, 21000 Split, Croatia
 
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*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2025, 13(10), 2429; https://doi.org/10.3390/biomedicines13102429 (registering DOI)
Submission received: 9 August 2025 / Revised: 29 September 2025 / Accepted: 2 October 2025 / Published: 5 October 2025
(This article belongs to the Section Cell Biology and Pathology)
Versions Notes

Abstract

Pain remains one of the most burdensome symptoms in rheumatoid arthritis (RA), often persisting despite inflammatory remission and profoundly impairing quality of life. This review aimed to evaluate the clinical efficacy and mechanistic pathways by which Janus kinase (JAK) inhibitors alleviate RA-related pain. Evidence from randomized clinical trials demonstrates that JAK inhibitors have demonstrated rapid and significant pain relief, often exceeding that of methotrexate or biologic DMARDs. Improvements in patient-reported pain scores seem to typically emerge within 1–2 weeks and are sustained over time. Beyond anti-inflammatory effects, JAK inhibitors modulate central sensitization and nociceptive signaling by attenuating IL-6 and GM-CSF activity, reducing astrocyte and microglial activation, and downregulating nociceptor excitability in dorsal root ganglia and spinal pathways. Preclinical models further suggest that JAK inhibition interrupts neuroimmune feedback loops critical to chronic pain maintenance. Comparative and network meta-analyses consistently position JAK inhibitors among the most effective agents for pain control in RA. However, individual variability in response, partly due to differential JAK-STAT activation and cytokine receptor uncoupling, underscores the need for biomarker-guided treatment approaches. JAK inhibitors represent a mechanistically distinct and clinically impactful class of therapies that target both inflammatory and non-inflammatory pain in RA. Their integration into personalized pain management strategies offers a promising path to address one of RA’s most persistent unmet needs.
Keywords: disease-modifying antirheumatic drugs; rheumatoid arthritis; JAK inhibitors; JAK-STAT pathway; pain modulation disease-modifying antirheumatic drugs; rheumatoid arthritis; JAK inhibitors; JAK-STAT pathway; pain modulation

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MDPI and ACS Style

Belančić, A.; Sener, S.; Sener, Y.Z.; Fajkić, A.; Vučković, M.; Markotić, A.; Benić, M.S.; Potočnjak, I.; Pavlović, M.R.; Radić, J.; et al. Effects of Janus Kinase Inhibitors on Rheumatoid Arthritis Pain: Clinical Evidence and Mechanistic Pathways. Biomedicines 2025, 13, 2429. https://doi.org/10.3390/biomedicines13102429

AMA Style

Belančić A, Sener S, Sener YZ, Fajkić A, Vučković M, Markotić A, Benić MS, Potočnjak I, Pavlović MR, Radić J, et al. Effects of Janus Kinase Inhibitors on Rheumatoid Arthritis Pain: Clinical Evidence and Mechanistic Pathways. Biomedicines. 2025; 13(10):2429. https://doi.org/10.3390/biomedicines13102429

Chicago/Turabian Style

Belančić, Andrej, Seher Sener, Yusuf Ziya Sener, Almir Fajkić, Marijana Vučković, Antonio Markotić, Mirjana Stanić Benić, Ines Potočnjak, Marija Rogoznica Pavlović, Josipa Radić, and et al. 2025. "Effects of Janus Kinase Inhibitors on Rheumatoid Arthritis Pain: Clinical Evidence and Mechanistic Pathways" Biomedicines 13, no. 10: 2429. https://doi.org/10.3390/biomedicines13102429

APA Style

Belančić, A., Sener, S., Sener, Y. Z., Fajkić, A., Vučković, M., Markotić, A., Benić, M. S., Potočnjak, I., Pavlović, M. R., Radić, J., & Radić, M. (2025). Effects of Janus Kinase Inhibitors on Rheumatoid Arthritis Pain: Clinical Evidence and Mechanistic Pathways. Biomedicines, 13(10), 2429. https://doi.org/10.3390/biomedicines13102429

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