Araştırma Makalesi
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Miyastenia Gravis’in Serolojik Alttiplerinde Rituksimabın Uzun Dönem Klinik Sonuçları

Yıl 2025, Cilt: 51 Sayı: 3, 559 - 564, 08.12.2025
https://doi.org/10.32708/uutfd.1796880

Öz

Rituksimab, B hücrelerini tüketen bir monoklonal antikor olarak, özellikle tedaviye dirençli olgularda miyastenia gravis (MG) tedavisinde giderek artan bir ilgi görmektedir. Ancak, farklı serolojik alt tiplerdeki uzun dönem etkinliği hâlen araştırılmaktadır. Bu çalışma, anti–asetilkolin reseptörü (AChR) antikorları, anti–kas-spesifik kinaz (MuSK) antikorları ve çift seronegatif profilleri içeren jeneralize miyastenia gravis (MG) hastalarında rituksimab tedavisinin uzun dönem klinik sonuçlarını değerlendirmeyi amaçlamıştır. 2012–2024 yılları arasında Nöromüsküler Ünitede retrospektif, kesitsel bir çalışma yürütülmüştür. Rituksimab tedavisi alan ve en az 12 aylık takip süresi bulunan 36 hasta çalışmaya dahil edilmiştir. Tedavi sonuçları, başlangıçta, 6. ayda ve son değerlendirmede MGFA ve MGFA-PIS skorları kullanılarak değerlendirilmiştir. Antikor durumuna göre alt grup analizleri yapılmıştır. Tüm serolojik alt gruplarda kalıcı klinik iyileşme gözlenmiştir. Altıncı ayda hastaların %70’i MGFA-PIS’e göre iyileşme veya remisyon göstermiş olup, bu oran son değerlendirmede %100’e yükselmiştir. AChR+ ve MuSK+ hastalar erken ve kalıcı yanıt gösterirken, çift seronegatif hastalarda gecikmiş ancak anlamlı bir fayda saptanmıştır. Rituksimab, tüm ana antikor alt tiplerinde yarar sağlayan, jeneralize MG için güvenli ve etkili bir uzun dönem tedavi seçeneği olarak görünmektedir. AChR+ ve MuSK+ hastalarda 6. ay ile son takip arasındaki farkın anlamlı olmaması, erken dönemde elde edilen iyileşmenin uzun dönemde de sürdüğünü göstermektedir.

Etik Beyan

Bu çalışma, Uludağ Üniversitesi Tıp Fakültesi Etik Kurulu tarafından onaylanmıştır (Onay No: 2025/5-6). Çalışma, Helsinki Bildirgesi ilkelerine uygun olarak yürütülmüştür.

Destekleyen Kurum

Bu çalışma, herhangi bir kurum veya kuruluştan mali destek almamıştır.

Proje Numarası

2025/5-6

Teşekkür

Teşekkür edilecek kişi veya kurum bulunmamaktadır

Kaynakça

  • 1. Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren J. Myasthenia gravis. Nat Rev Dis Primers 2019; 5: 30.
  • 2. Narayanaswami P, Sanders DB, Wolfe G, Benatar M, Cea G, Evoli A, et al. International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology 2021; 96: 114-122.
  • 3. Mantegazza R, Antozzi C. When myasthenia gravis is deemed refractory: clinical signposts and treatment strategies. Ther Adv Neurological Disord 2018; 11: 1756285617749134.
  • 4. Beecher G, Putko BN, Wagner AN, Siddiqi ZA. Therapies directed against B-cells and downstream effectors in generalized autoimmune myasthenia gravis: current status. Drugs 2019; 79: 353-364.
  • 5. Yang X, Zhang W, Guo J, Ma C, Li B. Efficacy and safety of low-dose rituximab in the treatment of myasthenia gravis: a systemic review and meta-analysis. Front Neurol 2024; 15: 1439899.
  • 6. Valaparambil KA, Sundaram S, Nair SS. Rituximab in Refractory Myasthenia Gravis - Challenges and Lessons Learnt. Ann Indian Acad Neurol 2024; 27: 706-709.
  • 7. Chayanopparat S, Banyatcharoen P, Jitprapaikulsan J, Uawithya E, Apiraksattayakul N, Viarasilpa V. Efficacy and safety of rituximab in anti-MuSK myasthenia Gravis: a systematic review and meta-analysis. Sci Rep 2025; 15: 7219.
  • 8. Meng X, Zeng Z, Wang Y, Guo S, Wang C, Wang B, et al. Efficacy and Safety of Low-Dose Rituximab in Anti-MuSK Myasthenia Gravis Patients: A Retrospective Study. Neuropsychiatr Dis Treat 2022; 18: 953-964.
  • 9. Piehl F, Eriksson-Dufva A, Budzianowska A, Feresiadou A, Hansson W, Hietala MA, et al. Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial. JAMA Neurol 2022; 79: 1105-1112.
  • 10. Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, et al. International consensus guidance for management of myasthenia gravis: Executive summary. Neurology 2016; 87: 419-425.
  • 11. Erik von Elm M, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007; 147: 573.
  • 12. Li T, Zhang GQ, Li Y, Dong SA, Wang N, Yi M,et al. Efficacy and safety of different dosages of rituximab for refractory generalized AChR myasthenia gravis: A meta-analysis. J Clin Neurosci 2021; 85: 6-12.
  • 13. Nowak RJ, Dicapua DB, Zebardast N, Goldstein JM. Response of patients with refractory myasthenia gravis to rituximab: a retrospective study. Ther Adv Neurol Disord 2011; 4: 259-266.
  • 14. Litchman T, Roy B, Kumar A, Sharma A, Njike V, Nowak RJ. Differential response to rituximab in anti-AChR and anti-MuSK positive myasthenia gravis patients: a single-center retrospective study. J Neurol Sci 2020; 411: 116690.
  • 15. Dos Santos A, Noury JB, Genestet S, Nadaj-Pakleza A, Cassereau J, Baron C, et al. Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real-life study. Eur J Neurol 2020; 27: 2277-2285.
  • 16. Beecher G, Anderson D, Siddiqi ZA. Rituximab in refractory myasthenia gravis: extended prospective study results. Muscle Nerve 2018; 58: 452-455.
  • 17. Brauner S, Eriksson-Dufva A, Hietala MA, Frisell T, Press R, Piehl F. Comparison Between Rituximab Treatment for New-Onset Generalized Myasthenia Gravis and Refractory Generalized Myasthenia Gravis. JAMA Neurol 2020; 77: 974-981.
  • 18. Robeson KR, Kumar A, Keung B, DiCapua DB, Grodinsky E, Patwa HS, et al. Durability of the Rituximab Response in Acetylcholine Receptor Autoantibody-Positive Myasthenia Gravis. JAMA Neurol 2017; 74: 60-66.
  • 19. Nowak RJ, Coffey CS, Goldstein JM, Dimachkie MM, Benatar M, Kissel JT, et al. Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study. Neurology 2022; 98: e376-e89.
  • 20. Lee DSW, Rojas OL. B cell depletion therapies in autoimmune disease: advances and mechanistic insights. Nat Rev Drug Discov 2021; 20: 179-199.
  • 21. Li H, Huang Z, Jia D, Xue H, Pan J, Zhang M, et al. Low-dose rituximab treatment for new-onset generalized myasthenia gravis. J Neuroimmunol 2021; 354: 577528.

Long-Term Clinical Outcomes of Rituximab Across Serological Subtypes of Myasthenia Gravis

Yıl 2025, Cilt: 51 Sayı: 3, 559 - 564, 08.12.2025
https://doi.org/10.32708/uutfd.1796880

Öz

Rituximab, a B-cell-depleting monoclonal antibody, has gained increasing attention as a therapeutic option for myasthenia gravis (MG), particularly in refractory cases. However, its long-term efficacy across different serological subtypes remains to be investigated. This study aimed to evaluate the long-term clinical outcomes of rituximab treatment in patients with generalized myasthenia gravis (MG), including those with anti-acetylcholine receptor (AChR) antibodies, anti-muscle-specific kinase (MuSK) antibodies, and double-seronegative profiles. A retrospective cross-sectional study was conducted at the Neuromuscular Unit between 2012 and 2024. Thirty-six patients who received rituximab and had a minimum follow-up of 12 months were included. Treatment outcomes were assessed using MGFA and MGFA-PIS scores at baseline, at 6 months, and at the final evaluation. Subgroup analyses were performed based on antibody status. Sustained clinical improvement was observed in all serological subgroups. At six months, 70% of patients showed improvement or remission according to MGFA-PIS, increasing to 100% at final evaluation. AChR+ and MuSK+ patients demonstrated early and persistent responses, while a delayed but significant benefit was seen in double-seronegative patients. Rituximab appears to be a safe and effective long-term treatment for generalized MG, with benefits observed across all major antibody subtypes. The lack of a significant difference between the 6-month and final follow-up in AChR+ and MuSK+ patients suggests that the early improvement was sustained in the long term.

Etik Beyan

This study was approved by the Ethics Committee of Uludağ University Faculty of Medicine (Approval No: 2025/5-6). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Destekleyen Kurum

This study did not receive any financial support from any institution or organization.

Proje Numarası

2025/5-6

Teşekkür

The authors declare that there are no acknowledgments.

Kaynakça

  • 1. Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren J. Myasthenia gravis. Nat Rev Dis Primers 2019; 5: 30.
  • 2. Narayanaswami P, Sanders DB, Wolfe G, Benatar M, Cea G, Evoli A, et al. International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology 2021; 96: 114-122.
  • 3. Mantegazza R, Antozzi C. When myasthenia gravis is deemed refractory: clinical signposts and treatment strategies. Ther Adv Neurological Disord 2018; 11: 1756285617749134.
  • 4. Beecher G, Putko BN, Wagner AN, Siddiqi ZA. Therapies directed against B-cells and downstream effectors in generalized autoimmune myasthenia gravis: current status. Drugs 2019; 79: 353-364.
  • 5. Yang X, Zhang W, Guo J, Ma C, Li B. Efficacy and safety of low-dose rituximab in the treatment of myasthenia gravis: a systemic review and meta-analysis. Front Neurol 2024; 15: 1439899.
  • 6. Valaparambil KA, Sundaram S, Nair SS. Rituximab in Refractory Myasthenia Gravis - Challenges and Lessons Learnt. Ann Indian Acad Neurol 2024; 27: 706-709.
  • 7. Chayanopparat S, Banyatcharoen P, Jitprapaikulsan J, Uawithya E, Apiraksattayakul N, Viarasilpa V. Efficacy and safety of rituximab in anti-MuSK myasthenia Gravis: a systematic review and meta-analysis. Sci Rep 2025; 15: 7219.
  • 8. Meng X, Zeng Z, Wang Y, Guo S, Wang C, Wang B, et al. Efficacy and Safety of Low-Dose Rituximab in Anti-MuSK Myasthenia Gravis Patients: A Retrospective Study. Neuropsychiatr Dis Treat 2022; 18: 953-964.
  • 9. Piehl F, Eriksson-Dufva A, Budzianowska A, Feresiadou A, Hansson W, Hietala MA, et al. Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial. JAMA Neurol 2022; 79: 1105-1112.
  • 10. Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, et al. International consensus guidance for management of myasthenia gravis: Executive summary. Neurology 2016; 87: 419-425.
  • 11. Erik von Elm M, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007; 147: 573.
  • 12. Li T, Zhang GQ, Li Y, Dong SA, Wang N, Yi M,et al. Efficacy and safety of different dosages of rituximab for refractory generalized AChR myasthenia gravis: A meta-analysis. J Clin Neurosci 2021; 85: 6-12.
  • 13. Nowak RJ, Dicapua DB, Zebardast N, Goldstein JM. Response of patients with refractory myasthenia gravis to rituximab: a retrospective study. Ther Adv Neurol Disord 2011; 4: 259-266.
  • 14. Litchman T, Roy B, Kumar A, Sharma A, Njike V, Nowak RJ. Differential response to rituximab in anti-AChR and anti-MuSK positive myasthenia gravis patients: a single-center retrospective study. J Neurol Sci 2020; 411: 116690.
  • 15. Dos Santos A, Noury JB, Genestet S, Nadaj-Pakleza A, Cassereau J, Baron C, et al. Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real-life study. Eur J Neurol 2020; 27: 2277-2285.
  • 16. Beecher G, Anderson D, Siddiqi ZA. Rituximab in refractory myasthenia gravis: extended prospective study results. Muscle Nerve 2018; 58: 452-455.
  • 17. Brauner S, Eriksson-Dufva A, Hietala MA, Frisell T, Press R, Piehl F. Comparison Between Rituximab Treatment for New-Onset Generalized Myasthenia Gravis and Refractory Generalized Myasthenia Gravis. JAMA Neurol 2020; 77: 974-981.
  • 18. Robeson KR, Kumar A, Keung B, DiCapua DB, Grodinsky E, Patwa HS, et al. Durability of the Rituximab Response in Acetylcholine Receptor Autoantibody-Positive Myasthenia Gravis. JAMA Neurol 2017; 74: 60-66.
  • 19. Nowak RJ, Coffey CS, Goldstein JM, Dimachkie MM, Benatar M, Kissel JT, et al. Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study. Neurology 2022; 98: e376-e89.
  • 20. Lee DSW, Rojas OL. B cell depletion therapies in autoimmune disease: advances and mechanistic insights. Nat Rev Drug Discov 2021; 20: 179-199.
  • 21. Li H, Huang Z, Jia D, Xue H, Pan J, Zhang M, et al. Low-dose rituximab treatment for new-onset generalized myasthenia gravis. J Neuroimmunol 2021; 354: 577528.
Toplam 21 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Nöroloji ve Nöromüsküler Hastalıklar
Bölüm Araştırma Makalesi
Yazarlar

Emel Oğuz-Akarsu 0000-0002-0465-4218

Nida Meriç Koyuncu Yilmaz 0009-0003-2903-065X

Sarra Elhamida Lazrak 0000-0001-5596-5246

Yasemin Dinç 0000-0003-0342-5939

Necdet Karlı 0000-0002-7734-6451

Proje Numarası 2025/5-6
Gönderilme Tarihi 13 Ekim 2025
Kabul Tarihi 19 Kasım 2025
Yayımlanma Tarihi 8 Aralık 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 51 Sayı: 3

Kaynak Göster

AMA Oğuz-Akarsu E, Koyuncu Yilmaz NM, Lazrak SE, Dinç Y, Karlı N. Long-Term Clinical Outcomes of Rituximab Across Serological Subtypes of Myasthenia Gravis. Uludağ Tıp Derg. Aralık 2025;51(3):559-564. doi:10.32708/uutfd.1796880

ISSN: 1300-414X, e-ISSN: 2645-9027

Uludağ Üniversitesi Tıp Fakültesi Dergisi "Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License" ile lisanslanmaktadır.


Creative Commons License
Journal of Uludag University Medical Faculty is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

2023