Yıl: 2024 Cilt: 16 Sayı: 1 Sayfa Aralığı: 25 - 31 Metin Dili: İngilizce DOI: 10.4274/raed.galenos.2023.41636 İndeks Tarihi: 11-06-2024

Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience

Öz:
Objective: To assess the adverse events (AEs) of tofacitinib in rheumatoid arthritis (RA) patients and to present real-life experiences. Methods: Data on the demographic characteristics, comorbidities, and the AEs of 71 RA patients using tofacitinib was collected. Coronary artery disease, cerebrovascular disease, pulmonary embolism, malignancy, and mortality were defined as serious AEs. The risk factors for serious AEs were defined. Results: Infections were the most common drug-related AEs, most of which were upper respiratory and urinary tract infections. Malignancy was detected in 3 patients in follow-up. No significant difference was found in the rates of overall AEs except urinary tract infections, between patients <65 years and those ≥65 years of age. However, serious AEs were observed more frequently in patients aged ≥65 years (p=0.019). Older age, male gender, pre-existing hyperlipidemia, and the initial year of tofacitinib treatment were significantly associated with developing serious AEs. Four patients (median age= 65.9 years) died. Conclusion: Real-life data on the safety profile of tofacitinib in RA was presented in this study. Male gender was an independent risk factor for serious AEs in subjects receiving tofacitinib. Patients with older age, male gender, those with hyperlipidemia, and those in their first year of treatment should also be closely monitored for serious AEs.
Anahtar Kelime: Tofacitinib adverse events rheumatoid arthritis older age

Romatoid artrit hastalarında tofasitinibin güvenlik profili: tek merkez deneyimi

Öz:
Amaç: Romatoid artrit (RA) hastalarında tofasitinibin yan etkilerini (YE) değerlendirmeyi ve gerçek yaşam verilerini sunmayı amaçladık. Yöntem: Tofacitinib kullanan 71 RA hastasının demografik özellikleri, komorbiditeleri ve YE’leri değerlendirildi. Koroner arter hastalığı, serebrovasküler hastalık, pulmoner emboli, malignite ve mortalite ciddi YE olarak gruplandırıldı. Ciddi YE’ler için risk faktörleri tanımlandı. Bulgular: Enfeksiyonlar ilaca bağlı en yaygın YE’ler olup, bunların çoğu üst solunum yolu ve idrar yolu enfeksiyonlarıydı. Takipte 3 hastada malignite tespit edildi. <65 yaş ve ≥65 yaş hastalar arasında idrar yolu enfeksiyonları dışındaki genel YE oranlarında anlamlı bir fark bulunmadı. Ancak 65 yaş ve üzeri hastalarda ciddi YE’ler daha sık görüldü (p=0,019). İleri yaş, erkek cinsiyet, hiperlipidemi varlığı ve tofasitinib tedavisinin ilk yılı ciddi YE’lerin gelişmesiyle anlamlı düzeyde ilişkiliydi. Ortanca yaşları 65,9 olan 4 hasta hayatını kaybetti. Sonuç: Bu çalışmada tofasitinibin RA’daki güvenlik profiline ilişkin gerçek yaşam verileri sunulmuştur. Erkek cinsiyet, tofacitinib kullanan hastalarda ciddi YE’ler için bağımsız bir risk faktörüydü. İleri yaş, erkek cinsiyet, hiperlipidemisi olan ve tedavinin ilk yılında olan hastalar ciddi YE’ler açısından yakın izlenmelidir.
Anahtar Kelime: Tofasitinib yan etkiler romatoid artrit ileri yaş

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
0
0
0
  • 1. Cross M, Smith E, Hoy D, et al. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014;73:1316-22.
  • 2. Gibofsky A. Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. Am J Manag Care 2012;18:S295-302.
  • 3. Taylor PC, Atzeni F, Balsa A, Gossec L, Müller-Ladner U, Pope J. The key comorbidities in patients with rheumatoid arthritis: a narrative review. Journal of clinical medicine 10:509. J Clin Med 2021;10:509.
  • 4. Singh JA, Saag KG, Bridges Jr SL, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2016;68:1-26.
  • 5. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2021;73:1108-23.
  • 6. Smolen JS, Landewé RB, Bijlsma JW, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020;79:685-99.
  • 7. Smolen JS, Landewé RB, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis 2023;82:3-18.
  • 8. Nagy G, Roodenrijs NM, Welsing PM, et al. EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2022;81:20-33.
  • 9. Fleischmann R, Kremer J, Cush J, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med 2012;367:495-507.
  • 10. Lee EB, Fleischmann R, Hall S, et al. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med 2014;370:2377-86.
  • 11. Vyas D, O’Dell KM, Bandy JL, Boyce EG. Tofacitinib: The First Janus Kinase (JAK) inhibitor for the treatment of rheumatoid arthritis. Ann Pharmacother 2013;47:1524-31.
  • 12. Hoisnard L, Lebrun-Vignes B, Maury S, et al. Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database. Sci Rep 2022;12:1-10.
  • 13. Dong Z, Ye X, Chen C, et al. Thromboembolic Events in JAK inhibitors: A Pharmacovigilance Study From 2012 to 2021 Based on FAERS. Br J Clin Pharmacol 2022;88:4180-90.
  • 14. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med 2022;386:316-26.
  • 15. Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/ European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569-81.
  • 16. Agency EM. EMA confirms Xeljanz to be used with caution in patients at high risk of blood clots. 2019.
  • 17. Kremer JM, Bloom BJ, Breedveld FC, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum 2009;60:1895-905.
  • 18. Kremer JM, Cohen S, Wilkinson BE, et al. A phase IIb dose- ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Arthritis Rheum 2012;64:970-81.
  • 19. Burmester GR, Blanco R, Charles-Schoeman C, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet 2013;381:451-60.
  • 20. Wollenhaupt J, Silverfield J, Lee EB, et al. Safety and efficacy of tofacitinib, an oral Janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies. J Rheumatol 2014;41:837-52.
  • 21. Tanaka Y, Takeuchi T, Yamanaka H, Nakamura H, Toyoizumi S, Zwillich S. Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study. Mod Rheumatol 2015;25:514-21.
  • 22. Fleischmann R, Cutolo M, Genovese MC, et al. Phase IIb dose- ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease- modifying antirheumatic drugs. Arthritis Rheum 2012;64:617-29.
  • 23. Curtis JR, Schulze-Koops H, Takiya L, et al. Efficacy and safety of tofacitinib in older and younger patients with rheumatoid arthritis. Clin Exp Rheumatol 2017;35:390-400.
  • 24. Cohen SB, Tanaka Y, Mariette X, 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:e001395.
  • 25. DeMizio DJ, Geraldino-Pardilla LB. Autoimmunity and inflammation link to cardiovascular disease risk in rheumatoid arthritis. Rheumatol Ther 2020;7:19-33.
  • 26. Naranjo A, Sokka T, Descalzo MA, et al. Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study. Arthritis Res Ther 2008;10:1-10.
  • 27. Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis 2017;76:1253-62.
  • 28. Winthrop KL, Citera G, Gold D, et al. Age-based (< 65 vs≥ 65 years) incidence of infections and serious infections with tofacitinib versus biological DMARDs in rheumatoid arthritis clinical trials and the US Corrona RA registry. Ann Rheum Dis 2021;80:134-6.
  • 29. Xie W, Xiao S, Huang Y, Sun X, Zhang Z. Effect of tofacitinib on cardiovascular events and all-cause mortality in patients with immune-mediated inflammatory diseases: a systematic review and meta-analysis of randomized controlled trials. Ther Adv Musculoskelet Dis 2019;11:1759720X19895492.
  • 30. Xie W, Yang X, Huang H, Gao D, Ji L, Zhang Z. Risk of malignancy with non-TNFi biologic or tofacitinib therapy in rheumatoid arthritis: a meta-analysis of observational studies. Semin Arthritis Rheum 2020;50:930-7.
  • 31. Curtis JR, Lee EB, Kaplan IV, et al. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis 2016;75:831-41.
APA Akca T, demir c, Sargin G, Çildağ S, Senturk T (2024). Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience. , 25 - 31. 10.4274/raed.galenos.2023.41636
Chicago Akca Tolgahan,demir ceren,Sargin Gokhan,Çildağ Songül,Senturk Taskin Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience. (2024): 25 - 31. 10.4274/raed.galenos.2023.41636
MLA Akca Tolgahan,demir ceren,Sargin Gokhan,Çildağ Songül,Senturk Taskin Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience. , 2024, ss.25 - 31. 10.4274/raed.galenos.2023.41636
AMA Akca T,demir c,Sargin G,Çildağ S,Senturk T Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience. . 2024; 25 - 31. 10.4274/raed.galenos.2023.41636
Vancouver Akca T,demir c,Sargin G,Çildağ S,Senturk T Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience. . 2024; 25 - 31. 10.4274/raed.galenos.2023.41636
IEEE Akca T,demir c,Sargin G,Çildağ S,Senturk T "Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience." , ss.25 - 31, 2024. 10.4274/raed.galenos.2023.41636
ISNAD Akca, Tolgahan vd. "Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience". (2024), 25-31. https://doi.org/10.4274/raed.galenos.2023.41636
APA Akca T, demir c, Sargin G, Çildağ S, Senturk T (2024). Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience. Ulusal Romatoloji Dergisi, 16(1), 25 - 31. 10.4274/raed.galenos.2023.41636
Chicago Akca Tolgahan,demir ceren,Sargin Gokhan,Çildağ Songül,Senturk Taskin Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience. Ulusal Romatoloji Dergisi 16, no.1 (2024): 25 - 31. 10.4274/raed.galenos.2023.41636
MLA Akca Tolgahan,demir ceren,Sargin Gokhan,Çildağ Songül,Senturk Taskin Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience. Ulusal Romatoloji Dergisi, vol.16, no.1, 2024, ss.25 - 31. 10.4274/raed.galenos.2023.41636
AMA Akca T,demir c,Sargin G,Çildağ S,Senturk T Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience. Ulusal Romatoloji Dergisi. 2024; 16(1): 25 - 31. 10.4274/raed.galenos.2023.41636
Vancouver Akca T,demir c,Sargin G,Çildağ S,Senturk T Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience. Ulusal Romatoloji Dergisi. 2024; 16(1): 25 - 31. 10.4274/raed.galenos.2023.41636
IEEE Akca T,demir c,Sargin G,Çildağ S,Senturk T "Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience." Ulusal Romatoloji Dergisi, 16, ss.25 - 31, 2024. 10.4274/raed.galenos.2023.41636
ISNAD Akca, Tolgahan vd. "Safety profile of tofacitinib in rheumatoid arthritis: a single-center experience". Ulusal Romatoloji Dergisi 16/1 (2024), 25-31. https://doi.org/10.4274/raed.galenos.2023.41636