Clinical Predictors of Response to Treatment with Tofacitinib (Janus Kinase Inhibitor) in Patients with Ankylosing Spondylitis

Syeda Kinza Bukhari; Javed Ahmad Khan; Zoha Hashmi; Bushra; Irfan Najam Sheen; Ishwah Akram

doi:10.70749/ijbr.v3i4.1020

Authors

Syeda Kinza Bukhari Department of Medicine, Combined Military Hospital (CMH), Multan, Punjab, Pakistan.
Javed Ahmad Khan Department of Medicine, Combined Military Hospital (CMH), Multan, Punjab, Pakistan.
Zoha Hashmi Department of Medicine, Combined Military Hospital (CMH), Multan, Punjab, Pakistan.
Bushra Department of Medicine, Combined Military Hospital (CMH), Multan, Punjab, Pakistan.
Irfan Najam Sheen Department of Medicine, Combined Military Hospital (CMH), Multan, Punjab, Pakistan.
Ishwah Akram Department of Medicine, Combined Military Hospital (CMH), Multan, Punjab, Pakistan.

DOI:

https://doi.org/10.70749/ijbr.v3i4.1020

Keywords:

Tofacitinib, Ankylosing Spondylitis, JAK Inhibitors, Efficacy, Predictors

Abstract

Objective: To evaluate the efficacy of tofacitinib in ankylosing spondylitis patients and determine the factors predicting treatment outcomes. Study Design: Quasi-experimental study. Duration and Place of Study: The study was conducted from January 2024 to November 2024 at the Department of Medicine, Combined Military Hospital (CMH), Multan. Methodology: A total of 169 patients, aged ≥18 years, with active ankylosing spondylitis fulfilling the modified New York (mNY) criteria, were enrolled through non-probability consecutive sampling. Patients with CRP values within reference range, active arthritis, and concurrent therapy with methotrexate or stable prednisone were included. All participants received 5 mg twice daily of tofacitinib for 12 weeks, followed by a 4-week washout period. The primary efficacy outcome was assessed using the ASAS20 criteria at week 12. Factors predicting treatment outcomes were also analyzed. Results: Out of 169 patients, 68% achieved an ASAS20 response after 12 weeks of tofacitinib, with a mean reduction in CRP of 35%. Higher response rates were seen in patients with moderate to severe disease (82%) and those with elevated baseline CRP (>10 mg/L, 76%). Obesity (BMI ≥30 kg/m²) and IBD were associated with lower efficacy (62% and 59%, respectively). CVD had no significant impact on treatment outcomes (68% response). Conclusion: Tofacitinib demonstrates significant therapeutic efficacy in AS patients, with baseline disease activity and elevated CRP being strong predictors of a positive treatment outcome.

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References

Agrawal, P., Tote, S., & Sapkale, B. (2024). Diagnosis and treatment of ankylosing spondylitis. Cureus, 16(1). https://doi.org/10.7759/cureus.52559

Veronesi, F., Sartori, M., Griffoni, C., Valacco, M., Tedesco, G., Davassi, P. F., Gasbarrini, A., Fini, M., & Barbanti Brodano, G. (2022). Complications in spinal fusion surgery: A systematic review of clinically used cages. Journal of Clinical Medicine, 11(21), 6279. https://doi.org/10.3390/jcm11216279

Tanios, M., Brickman, B., Norris, J., Ravi, S., Eren, E., McGarvey, C., Morris, D. J., & Elgafy, H. (2023). Spondyloarthropathies that mimic ankylosing spondylitis: A narrative review. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders, 16. https://doi.org/10.1177/11795441231186822

Kenyon, M., Maguire, S., Rueda Pujol, A., O’Shea, F., & McManus, R. (2022). The genetic backbone of ankylosing spondylitis: How knowledge of genetic susceptibility informs our understanding and management of disease. Rheumatology International, 42(12), 2085-2095. https://doi.org/10.1007/s00296-022-05174-5

Park, J., Hong, J., Kim, H., Koo, B., Kim, S., & Kwon, Y. (2020). National pharmacological treatment trends for ankylosing spondylitis in South Korea: A national health insurance database study. PLOS ONE, 15(10), e0240155. https://doi.org/10.1371/journal.pone.0240155

Danve, A., Magrey, M., & Deodhar, A. (2024). An update on the management of axial spondyloarthritis for sports medicine professionals. BMC Sports Science, Medicine and Rehabilitation, 16(1). https://doi.org/10.1186/s13102-024-00998-z

Zouris, G., Evangelopoulos, D. S., Benetos, I. S., & Vlamis, J. (2024). The use of TNF-α inhibitors in active ankylosing spondylitis treatment. Cureus, 16(6). https://doi.org/10.7759/cureus.61500

Țiburcă, L., Bembea, M., Zaha, D. C., Jurca, A. D., Vesa, C. M., Rațiu, I. A., & Jurca, C. M. (2022). The treatment with interleukin 17 inhibitors and immune-mediated inflammatory diseases. Current Issues in Molecular Biology, 44(5), 1851-1866. https://doi.org/10.3390/cimb44050127

Paroli, M., Caccavale, R., Paroli, M. P., Spadea, L., & Accapezzato, D. (2023). Janus kinase inhibitors: A new tool for the treatment of axial Spondyloarthritis. International Journal of Molecular Sciences, 24(2), 1027. https://doi.org/10.3390/ijms24021027

Tanaka, Y., Luo, Y., O’Shea, J. J., & Nakayamada, S. (2022). Janus kinase-targeting therapies in rheumatology: A mechanisms-based approach. Nature Reviews Rheumatology, 18(3), 133-145. https://doi.org/10.1038/s41584-021-00726-8

Tóth, L., Juhász, M. F., Szabó, L., Abada, A., Kiss, F., Hegyi, P., Farkas, N., Nagy, G., & Helyes, Z. (2022). Janus kinase inhibitors improve disease activity and patient-reported outcomes in rheumatoid arthritis: A systematic review and meta-analysis of 24,135 patients. International Journal of Molecular Sciences, 23(3), 1246. https://doi.org/10.3390/ijms23031246

McInnes, I. B., Szekanecz, Z., McGonagle, D., Maksymowych, W. P., Pfeil, A., Lippe, R., Song, I., Lertratanakul, A., Sornasse, T., Biljan, A., & Deodhar, A. (2021). A review of JAK–STAT signalling in the pathogenesis of spondyloarthritis and the role of JAK inhibition. Rheumatology, 61(5), 1783-1794. https://doi.org/10.1093/rheumatology/keab740

Li, S., Li, F., Mao, N., Wang, J., & Xie, X. (2022). Efficacy and safety of Janus kinase inhibitors in patients with ankylosing spondylitis: A systematic review and meta-analysis. European Journal of Internal Medicine, 102, 47-53. https://doi.org/10.1016/j.ejim.2022.04.007

Lorenzin, M., Ometto, F., Ortolan, A., Felicetti, M., Favero, M., Doria, A., & Ramonda, R. (2020). An update on serum biomarkers to assess axial spondyloarthritis and to guide treatment decision. Therapeutic Advances in Musculoskeletal Disease, 12. https://doi.org/10.1177/1759720x20934277

Martinez-Molina, C., Gich, I., Diaz-Torné, C., Park, H. S., Feliu, A., Vidal, S., & Corominas, H. (2024). Patient-related factors influencing the effectiveness and safety of Janus kinase inhibitors in rheumatoid arthritis: A real-world study. Scientific Reports, 14(1). https://doi.org/10.1038/s41598-023-50379-8

Sugimoto, E., Matsuda, H., Shibata, S., Mizuno, Y., Koyama, A., Li, L., Taira, H., Ito, Y., Awaji, K., Yamashita, T., & Sato, S. (2023). Impact of Pretreatment systemic inflammatory markers on treatment persistence with biologics and conventional systemic therapy: A retrospective study of patients with psoriasis vulgaris and psoriatic arthritis. Journal of Clinical Medicine, 12(8), 3046. https://doi.org/10.3390/jcm12083046

Van der Heijde, D., Deodhar, A., Wei, J. C., Drescher, E., Fleishaker, D., Hendrikx, T., Li, D., Menon, S., & Kanik, K. S. (2017). Tofacitinib in patients with ankylosing spondylitis: A phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Annals of the Rheumatic Diseases, 76(8), 1340-1347. https://doi.org/10.1136/annrheumdis-2016-210322

Lee, Y. H. (2022). Comparative efficacy and safety of Janus kinase inhibitors and Secukinumab in patients with active ankylosing spondylitis: A systematic review and meta-analysis. Pharmacology, 107(11-12), 537-544. https://doi.org/10.1159/000525627

Baraliakos, X., Van der Heijde, D., Sieper, J., Inman, R. D., Kameda, H., Li, Y., Bu, X., Shmagel, A., Wung, P., Song, I., & Deodhar, A. (2023). Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study. Arthritis Research & Therapy, 25(1). https://doi.org/10.1186/s13075-023-03128-1

Toussirot, E. (2022). The use of Janus kinase inhibitors in axial Spondyloarthritis: Current insights. Pharmaceuticals, 15(3), 270. https://doi.org/10.3390/ph15030270

Hammitzsch, A., Lorenz, G., & Moog, P. (2020). Impact of Janus kinase inhibition on the treatment of axial Spondyloarthropathies. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.591176

Tian, C., Shu, J., Shao, W., Zhou, Z., Guo, H., & Wang, J. (2023). Efficacy and safety of IL inhibitors, TNF-α inhibitors, and JAK inhibitors in patients with ankylosing spondylitis: A systematic review and Bayesian network meta-analysis. Annals of Translational Medicine, 11(4), 178-178. https://doi.org/10.21037/atm-23-195

Ahmed, S., Yesudian, R., Ubaide, H., & Coates, L. C. (2024). Rationale and concerns for using JAK inhibitors in axial spondyloarthritis. Rheumatology Advances in Practice, 8(4). https://doi.org/10.1093/rap/rkae141

Daoud, A., & Magrey, M. N. (2023). Efficacy and safety of Janus kinase inhibitors in axial spondyloarthritis. Indian Journal of Dermatology, Venereology and Leprology, 90, 471-478. https://doi.org/10.25259/ijdvl_161_2023