Evaluating the Efficacy of Immunomodulatory Therapies in Rheumatoid Arthritis: A Clinical Study-Scilight

Trends in Immunotherapy

Article

Evaluating the Efficacy of Immunomodulatory Therapies in Rheumatoid Arthritis: A Clinical Study

Downloads

https://doi.org/10.54963/ti.v9i2.1013
Aizhan Nurlanovna, O., Sabah Kallow , Z., Khudhair Jasim , I., Abdulwahid Salih Al-Ani, O., Magbul , G., & Zhumagaliuly, A. (2025). Evaluating the Efficacy of Immunomodulatory Therapies in Rheumatoid Arthritis: A Clinical Study. Trends in Immunotherapy, 9(2), 45–59. https://doi.org/10.54963/ti.v9i2.1013
Volume 9 Issue 2 (2025): (in progress)
Copyright (c) 2025 Omorova Aizhan Nurlanovna, Zainab Sabah Kallow , Ihsan Khudhair Jasim , Omar Abdulwahid Salih Al-Ani, Ghanim Magbul , Abzal Zhumagaliuly
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright

The authors shall retain the copyright of their work but allow the Publisher to publish, copy, distribute, and convey the work.

License

Trends in Immunotherapy (TI)  publishes accepted manuscripts under Creative Commons Attribution 4.0 International (CC BY 4.0). Authors who submit their papers for publication by TI agree to have the CC BY 4.0 license applied to their work, and that anyone is allowed to reuse the article or part of it free of charge for any purpose, including commercial use. As long as the author and original source are properly cited, anyone may copy, redistribute, reuse, and transform the content.

Authors

  • Omorova Aizhan Nurlanovna

    Department of Internal Medicine, Osh State University, Osh 723500, Kyrgyzstan
  • Zainab Sabah Kallow

    Physical Therapy Department, Al Mansour University College, Baghdad 10067, Iraq
  • Ihsan Khudhair Jasim

    Department of Pharmaceutics, Al-Turath University, Baghdad 10013, Iraq
  • Omar Abdulwahid Salih Al-Ani

    Department of Clinical Pharmacy, Al-Rafidain University College Baghdad 10064, Iraq
  • Ghanim Magbul

    Technical of Medical Instruments Engineering Department, Madenat Alelem University College, Baghdad 10006, Iraq
  • Abzal Zhumagaliuly

    B. Atchabarov scientific- research institute of fundamental and applied medicine, Asfendiyarov Kazakh National Medical University, Almaty050000, Kazakhstan

Rheumatoid arthritis (RA) is a systemic autoimmune disorder driven by aberrant cytokine-mediated signalling that perpetuates synovial inflammation and joint destruction. Baricitinib, an oral Janus kinase-1/2 inhibitor, offers a mechanism-based therapeutic option; however, comparative data clarifying its broader immunomodulatory advantages remain limited. We conducted a 24-week, multicentre, double-blind, randomised controlled trial to compare the efficacy and safety of baricitinib with the tumour-necrosis-factor inhibitor adalimumab and with placebo in adults with moderate-to-severe RA who had an inadequate response to conventional synthetic DMARDs. Three hundred participants were allocated equally (1:1:1) to once-daily baricitinib 4 mg, subcutaneous adalimumab 40 mg every other week, or matched placebo, all on stable methotrexate. Co-primary endpoints were (i) mean change from baseline in the Disease Activity Score using 28 joints and C-reactive protein (DAS28-CRP) and (ii) the proportion of patients achieving clinical remission (DAS28-CRP < 2.6) at week 24. Secondary outcomes included the Health Assessment Questionnaire-Disability Index (HAQ-DI), 36-Item Short-Form Survey (SF-36), radiographic progression via modified Total Sharp Score (mTSS), and comprehensive safety assessments. Baricitinib achieved a greater DAS28 reduction (−3.3 ± 0.9) than adalimumab (−2.9 ± 0.8) and placebo (−1.5 ± 0.7), with remission rates of 50%, 45%, and 20%, respectively. Baricitinib also produced superior improvements in HAQ-DI and SF-36 and curtailed radiographic progression versus placebo. Adverse events—predominantly mild upper-respiratory infections—were more frequent with baricitinib, yet serious events were comparable across groups.

Keywords:

Immunotherapy; JAK Inhibitors; Cytokine Signaling; Autoimmunity; Precision Medicine

References

  1. Peterson, D.; Poppel, M.V.; Boling , W.; et al. Clinical Safety and Feasibility of a Novel Implantable Neuroimmune Modulation Device for the Treatment of Rheumatoid Arthritis: Initial Results from the Randomized, Double-Blind, Sham-Controlled RESET-RA Study. Bioelectron. Med. 2024, 10, 8.
  2. Solomon, D.H.; Giles, J.T.; Liao, K.P.; et al. Reducing Cardiovascular Risk with Immunomodulators: A Randomised Active Comparator Trial Among Patients with Rheumatoid Arthritis. Ann. Rheum. Dis. 2023, 82, 324–330.
  3. Cohen, S.; Cannon, G.W.; Schiff, M.; et al. Two-Year, Blinded, Randomized, Controlled Trial of Treatment of Active Rheumatoid Arthritis with Leflunomide Compared with Methotrexate, Utilization of Leflunomide in the Treatment of Rheumatoid Arthritis Trial Investigator Group. Arthritis Rheum. 2001, 44, 1984–1992.
  4. Mohammadian Haftcheshmeh, S., Khosrojerdi, A., Aliabadi, A., et al. Immunomodulatory Effects of Curcumin in Rheumatoid Arthritis: Evidence from Molecular Mechanisms to Clinical Outcomes. In Reviews of Physiology, Biochemistry and Pharmacology; Pedersen, S.H.F., Eds.; Springer: Cham, Germany, 2020; 179, pp. 1–29.
  5. Zeng, L.; Yu, G.; Yang, K.; et al. Efficacy and Safety of Mesenchymal Stem Cell Transplantation in the Treatment of Autoimmune Diseases (Rheumatoid Arthritis, Systemic Lupus Erythematosus, Inflammatory Bowel Disease, Multiple Sclerosis, and Ankylosing Spondylitis): A Systematic Review and Meta-Analysis of Randomized Controlled Trial. Stem Cells Int. 2022, 2022, 9463314.
  6. Bingham, C.O.; Rizzo, W.; Kivitz, A.; et al. Humoral Immune Response to Vaccines in Patients with Rheumatoid Arthritis Treated with Tocilizumab: Results of a Randomised Controlled Trial (VISARA). Ann. Rheum. Dis. 2015, 74, 818–822.
  7. Makuch, S.; Więcek, K.; Woźniak, M. The Immunomodulatory and Anti-Inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and in Vivo Models of Rheumatoid Arthritis. Pharmaceuticals (Basel) 2021, 14, 309.
  8. Krathen, M.S.; Gottlieb, A.B.; Mease, P.J. Pharmacologic Immunomodulation and Cutaneous Malignancy in Rheumatoid Arthritis, Psoriasis, and Psoriatic Arthritis. J. Rheumatol. 2010, 37, 2205–2215.
  9. Ghoryani, M.; Shariati-Sarabi, Z.; Tavakkol-Afshari, J.; et al. Amelioration of Clinical Symptoms of Patients with Refractory Rheumatoid Arthritis Following Treatment with Autologous Bone Marrow-Derived Mesenchymal Stem Cells: A Successful Clinical Trial in Iran. Biomed. Pharmacother. 2019, 109, 1834–1840.
  10. Atabaki, M.; Shariati-Sarabi, Z.; Tavakkol-Afshari, J.; et al. Significant Immunomodulatory Properties of Curcumin in Patients with Osteoarthritis; a Successful Clinical Trial in Iran. Int. Immunopharmacol. 2020, 85, 106607.
  11. Bingham, C.O.; Looney, R.J.; Deodhar, A.; et al. Immunization Responses in Rheumatoid Arthritis Patients Treated with Rituximab: Results from a Controlled Clinical Trial. Arthritis Rheum. 2010, 62, 64–74.
  12. Rajaei, E.; Mowla, K.; Ghorbani, A.; et al. The Effect of Omega-3 Fatty Acids in Patients With Active Rheumatoid Arthritis Receiving DMARDs Therapy: Double-Blind Randomized Controlled Trial. Glob. J. Health Sci. 2015, 8, 18–25.
  13. Mowla, K.; Rajai, E.; Ghorbani, A.; et al. Effect of Atorvastatin on the Disease Activity and Severity of Rheumatoid Arthritis: Double-Blind Randomized Controlled Trial. J. Clin. Diagn. Res. 2016, 10, OC32–6.
  14. Gopinath, K.; Danda, D. Supplementation of 1,25 Dihydroxy Vitamin D3 in Patients with Treatment Naive Early Rheumatoid Arthritis: A Randomised Controlled Trial. Int. J. Rheum. Dis. 2011, 14, 332–339.
  15. Saki, A.; Rajaei, E.; Rahim, F. Safety and Efficacy of Tocilizumab for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Clinical Trial Studies. Reumatologia 2021, 59, 169–179.
  16. Chen, S.J.; Lin, G.J.; Chen, J.W.; et al. Immunopathogenic Mechanisms and Novel Immune-Modulated Therapies in Rheumatoid Arthritis. Int. J. Mol. Sci. 2019, 20, 1332.
  17. Hu, C.J.; Zhang, L.; Zhou, S.; et al., Effectiveness of Iguratimod as Monotherapy or Combined Therapy in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of RCTs. J. Orthop. Surg. Res. 2021, 16, 457.
  18. Chatzidionysiou, K.; Sfikakis, P.P. Low Rates of Remission with Methotrexate Monotherapy in Rheumatoid Arthritis: Review of Randomised Controlled Trials Could Point towards a Paradigm Shift. RMD Open 2019, 5, e000993.
  19. Shah, P.; Siddique, A.; Thakkar, A.; et al. An Update on Novel Therapeutic Intervention in Rheumatoid Arthritis. Int. Immunopharmacol. 2022, 109, 108794.
  20. Schulz, K.F.; Altman, D.G.; Consort, M.D.CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomised trials. BMJ 2010, 340, c332.
  21. Taylor, P.C. Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies. Ann. Rheum. Dis. 2018, 77, 988–95.
  22. Hernández-Cruz, B.; Kiltz, U.; Avouac, J.; et al. Systematic Literature Review of Real-World Evidence on Baricitinib for the Treatment of Rheumatoid Arthritis. Rheumatol. Ther. 2023, 10, 1417–1457.
  23. Schwartz, D.M.; Kanno, Y.; Villarino, A.; et al. JAK Inhibition as a Therapeutic Strategy for Immune and Inflammatory Diseases. Nat. Rev. Drug Discov. 2017, 17, 78.
  24. Bonelli, M. Selectivity, Efficacy and Safety of JAKinibs: New Evidence for a Still Evolving Story. Ann. Rheum. Dis. 2024, 83, 139–160.
  25. Firestein, G.S.; McInnes, I.B. Immunopathogenesis of Rheumatoid Arthritis. Immunity 2017, 46, 96.
  26. Miossec, P.; Kolls, J.K. Targeting IL-17 and TH17 Cells in Chronic Inflammation. Nat. Rev. Drug Discov. 2012, 11, 76.
  27. Cuppen, B.V.; Welsing, P.M.; Sprengers, J.J.; et al. Personalized Biological Treatment for Rheumatoid Arthritis: a Systematic Review with a Focus on Biomarkers. Rheumatology (Oxford) 2016, 55, 826–839.
  28. Fautrel, B.; Kirkham, B.; Pope, J.E.; et al. Effect of Baricitinib and Adalimumab in Reducing Pain and Improving Function in Patients with Rheumatoid Arthritis in Low Disease Activity: Exploratory Analyses from RA-BEAM. J. Clin. Med. 2019, 8, 1394.
  29. Taylor, P.C.; Keystone, E.C.; Heijde, D.; et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N. Engl. J. Med. 2017, 376, 652–662.
  30. Dougados, M., van der Heijde, D., Chen, Y.M., et al. Baricitinib in Patients with Inadequate Response or Intolerance to Conventional Synthetic DMARDs: Results from the RA-BUILD Study. Ann. Rheum. Dis. 2017, 76, 88-95.
  31. RECOVERY Collaborative Group. Baricitinib in Patients Admitted to Hospital with COVID-19 (RECOVERY): A Randomised, Controlled, Open-Label, Platform Trial and Updated Meta-Analysis. Lancet 2022, 400, 359–368.
  32. Conigliaro, P.; Triggianese, P.; De Martino, E.; et al. Challenges in the Treatment of Rheumatoid Arthritis. Autoimmun. Rev. 2019, 18, 706–713.
  33. Janke, K.; Biester, K.; Krause, D.; et al. Comparative Effectiveness of Biological Medicines in Rheumatoid arthritis: Systematic Review and Network Meta-Analysis Including Aggregate Results from Reanalysed Individual Patient data. BMJ 2020, 370, m2288.
  34. Singh, J.A.; Saag, K.G.; Bridges, S.L.J.; et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016, 68, 25.
  35. England, B.R.; Thiele, G.M.; Mikuls, T.R. Anticitrullinated Protein Antibodies: Origin and Role in the Pathophysiology of Rheumatoid Arthritis. Curr. Opin. Rheumatol. 2017, 29, 64.
  36. Smolen, J.S.; Aletaha, D.; Barton, A.; et al. Rheumatoid Arthritis. Nat. Rev. Dis. Primers 2018, 4, 18001.
  37. McInnes, I.B.; Schett, G. Pathogenetic Insights from the Treatment of Rheumatoid Arthritis. Lancet 2017, 389, 2328–2337.