Efficacy and Safety of Tofacitinib in Patients with Rheumatoid Arthritis

Year 2023, , 50 - 61, 28.02.2023

Doğan Bayram , Abdulsamet Erden , Gözde Sevgi Kart Bayram , Salih Başer , Şükran Erten

https://doi.org/10.19127/mbsjohs.1188195

Abstract

Objective: The aim of our study is to show the efficacy and side effects of tofacitinib in patients with rheumatoid arthritis (RA).

Methods: 66 Patients who were followed up in the rheumatology outpatient clinic, were older than 18 years, and used tofacitinib for at least three months were included. Blood count, liver transaminase levels, cholesterol and triglyceride levels, C-reactive protein (CRP) levels, and erythrocyte sedimentation rate (ESR) were determined before and at the third and sixth months of the tofacitinib treatment. Before and after treatment, DAS 28-ESR, morning stiffness duration, and VAS score were also calculated

Results: The mean age was 54.7±12.0 years, and 84.8% were women. The mean duration of tofacitinib use was 19.0±13.5 months. Duration of morning stiffness, VAS and DAS 28-ESR scores decreased significantly after tofacitinib (p<0.001). The leukocyte count after treatment also decreased significantly compared to before treatment. Side effects related to tofacitinib were seen in 33.3% of the patients. Rash, cough, and nausea were the most common side effects. Tofacitinib-associated Herpes Zoster infections were seen in 13.6% of the patients. Tofacitinib treatment was discontinued in 48.5% of patients due to adverse effects, drug ineffectiveness, and disease activation.

Conclusion: There was statistically significant decrease in RA disease activity with tofacitinib treatment. It was noteworthy that 33.3% of the patients developed adverse effects and 48.5% developed a condition requiring discontinuation of tofacitinib treatment.

Keywords

Rheumatoid Arthritis, tofacitinib, efficacy

References

• 1. Cross M, Smith E, Hoy D, Carmona L, Wolfe F, Vos T, et al. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Annals of the rheumatic diseases. 2014;73(7):1316-22.
• 2. Weyand CM, Goronzy JJ. The immunology of rheumatoid arthritis. Nature immunology. 2021;22(1):10-8.
• 3. Auréal M, Machuca-Gayet I, Coury F. Rheumatoid Arthritis in the View of Osteoimmunology. Biomolecules. 2020;11(1).
• 4. Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmunity reviews. 2005;4(3):130-6.
• 5. Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Annals of the rheumatic diseases. 2017;76(6):960-77.
• 6. Angelini J, Talotta R, Roncato R, Fornasier G, Barbiero G, Dal Cin L, et al. JAK-Inhibitors for the Treatment of Rheumatoid Arthritis: A Focus on the Present and an Outlook on the Future. Biomolecules. 2020;10(7).
• 7. van der Heijde D, Tanaka Y, Fleischmann R, Keystone E, Kremer J, Zerbini C, et al. Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis and rheumatism. 2013;65(3):559-70.
• 8. Fraenkel L, Bathon JM, England BR, St Clair EW, Arayssi T, Carandang K, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis care & research. 2021;73(7):924-39.
• 9. Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW, et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). Journal of immunology (Baltimore, Md : 1950). 2011;186(7):4234-43.
• 10. Hall S, Nash P, Rischmueller M, Bossingham D, Bird P, Cook N, et al. Tofacitinib, an Oral Janus Kinase Inhibitor: Pooled Efficacy and Safety Analyses in an Australian Rheumatoid Arthritis Population. Rheumatology and therapy. 2018;5(2):383-401.
• 11. Mueller RB, Hasler C, Popp F, Mattow F, Durmisi M, Souza A, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. Journal of clinical medicine. 2019;8(10).
• 12. Bird P, Littlejohn G, Butcher B, Smith T, da Fonseca Pereira C, Witcombe D, et al. Real-world evaluation of effectiveness, persistence, and usage patterns of tofacitinib in treatment of rheumatoid arthritis in Australia. Clinical rheumatology. 2020;39(9):2545-51.
• 13. Wollenhaupt J, Lee EB, Curtis JR, Silverfield J, Terry K, Soma K, et al. Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis research & therapy. 2019;21(1):89.
• 14. Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, et al. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD open. 2020;6(3).
• 15. Winthrop KL, Yamanaka H, Valdez H, Mortensen E, Chew R, Krishnaswami S, et al. Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis. Arthritis & rheumatology (Hoboken, NJ). 2014;66(10):2675-84.
• 16. Curtis JR, Xie F, Yang S, Bernatsky S, Chen L, Yun H, et al. Risk for Herpes Zoster in Tofacitinib-Treated Rheumatoid Arthritis Patients With and Without Concomitant Methotrexate and Glucocorticoids. Arthritis care & research. 2019;71(9):1249-54.
• 17. Kivitz AJ, Cohen S, Keystone E, van Vollenhoven RF, Haraoui B, Kaine J, et al. A pooled analysis of the safety of tofacitinib as monotherapy or in combination with background conventional synthetic disease-modifying antirheumatic drugs in a Phase 3 rheumatoid arthritis population. Seminars in arthritis and rheumatism. 2018;48(3):406-15.
• 18. Ytterberg SR, Bhatt DL, Mikuls TR, Koch GG, Fleischmann R, Rivas JL, et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. The New England journal of medicine. 2022;386(4):316-26.
• 19. Mease P, Charles-Schoeman C, Cohen S, Fallon L, Woolcott J, Yun H, et al. Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data. Annals of the rheumatic diseases. 2020;79(11):1400-13.
• 20. Desai RJ, Pawar A, Weinblatt ME, Kim SC. Comparative Risk of Venous Thromboembolism in Rheumatoid Arthritis Patients Receiving Tofacitinib Versus Those Receiving Tumor Necrosis Factor Inhibitors: An Observational Cohort Study. Arthritis & rheumatology (Hoboken, NJ). 2019;71(6):892-900.