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Original research
Effectiveness of early cycles of fast-acting treatment in generalised myasthenia gravis
  1. Akiyuki Uzawa1,
  2. Shigeaki Suzuki2,
  3. Satoshi Kuwabara1,
  4. Hiroyuki Akamine1,
  5. Yosuke Onishi1,
  6. Manato Yasuda1,
  7. Yukiko Ozawa1,
  8. Naoki Kawaguchi3,
  9. Tomoya Kubota4,
  10. Masanori P Takahashi4,
  11. Yasushi Suzuki5,
  12. Genya Watanabe5,
  13. Takashi Kimura6,
  14. Takamichi Sugimoto7,
  15. Makoto Samukawa8,
  16. Naoya Minami9,
  17. Masayuki Masuda10,
  18. Shingo Konno11,
  19. Yuriko Nagane12,
  20. Kimiaki Utsugisawa12
  1. 1Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
  2. 2Department of Neurology, Keio University School of Medicine Graduate School of Medicine, Shinjuku-ku, Japan
  3. 3Department of Neurology, Neurology Chiba Clinic, Chiba, Japan
  4. 4Department of Clinical Laboratory and Biomedical Sciences, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
  5. 5Department of Neurology, National Hospital Organisation Sendai Medical Center, Sendai, Miyagi, Japan
  6. 6Department of Neurology, Hyogo Medical University, Nishinomiya, Hyogo, Japan
  7. 7Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Hiroshima, Japan
  8. 8Department of Neurology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
  9. 9Department of Neurology, National Hospital Organization Hokkaido Medical Center, Sapporo, Japan
  10. 10Department of Neurology, Tokyo Medical University, Tokyo, Japan
  11. 11Department of Neurology, Toho University Ohashi Medical Center, Tokyo, Japan
  12. 12Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan
  1. Correspondence to Dr Akiyuki Uzawa, Department of Neurology, Chiba University, Chiba, Japan; auzawa{at}chiba-u.jp

Abstract

Background Early fast-acting treatment (EFT) is the aggressive use of fast-acting therapies such as plasmapheresis, intravenous immunoglobulin and/or intravenous high-dose methylprednisolone (IVMP) from the early phases of treatment. EFT is reportedly beneficial for early achievement of minimal manifestations (MM) or better status with ≤5 mg/day prednisolone (MM5mg), a practical therapeutic target for myasthenia gravis (MG).

Objective The current study aimed to clarify which specific EFT regimen is efficacious and the patient characteristics that confer sensitivity to EFT.

Methods We recruited a total of 1710 consecutive patients with MG who enrolled in the Japan MG Registry for this large-cohort study. Among them, 1066 with generalised MG who had received immunotherapy were analysed. Prognostic background factors were matched in a 1:1 ratio using propensity score matching analysis between patients treated with EFT (n=350) and those treated without EFT (n=350). The clinical course and time to first achieve MM5mg after starting immunotherapy was analysed in relation to treatment combinations and patient characteristics.

Results Kaplan-Meier analyses showed that EFT had a significant effect on the achievement of MM5mg (p<0.0001, log-rank test; HR 1.82, p<0.0001). Notably, EFT was efficacious for any type of MG, and the inclusion of IVMP resulted in earlier and more frequent achievement of MM5mg (p=0.0352, log-rank test; HR 1.46, p=0.0380). In addition, early administration of calcineurin inhibitors also promoted MM5mg achievement.

Conclusion Early cycles of intervention with EFT and early use of calcineurin inhibitors provides long-term benefits in terms of achieving therapeutic targets for generalised MG, regardless of clinical subtype.

  • MYASTHENIA
  • NEUROIMMUNOLOGY
  • NEUROMUSCULAR

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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Footnotes

  • Contributors AU, SS, SK, YN and KU contributed to the study concept, design and writing of the manuscript. AU performed statistical analysis and drafted the manuscript. AU, SS, HA, YOn, MY, YOz, NK, TK, MPT, YS, GW, TK, TS, MS, NM, MM, SK, YN and KU contributed to acquisition of data and analysis. All authors were involved in drafting the article or critically revising its important intellectual content. They have read and approved the final version of the manuscript. AU is the author acting as guarantor.

  • Funding This work was partly supported in part by the Health and Labour Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) from the Ministry of Health, Labour and Welfare of Japan (20FC1030).

  • Competing interests AU has received honoraria from Alexion Pharmaceuticals and Argenx. SS received speakers’ fees from Alexion Pharmaceuticals, the Japan Blood Products Organization, Asahi Kasei Medical and Argenx and participated on advisory board meeting of Alexion Pharmaceuticals and Argenx. SK has received Research Grant on Intractable Diseases (Neuroimmunological Diseases) from the Ministry of Health, Labour and Welfare of Japan (20FC1030) and honoraria from CSL Behring. TK reports honorarium for lectures from Alexon Pharmaceuticals. MPT reports unrestricted research grants from Japan Blood Products Organization, Astellas Pharma, Mitsubishi Tanabe Pharma and Pfizer, outside the submitted work, and has served as a paid Consultant for Alexion, Argenx, Sanofi, and UCB Pharma and received honorarium for lectures from Argenx, Alexion Pharmaceuticals and UCB Pharma. MM has received speaker honoraria from Argenx, Asahi Kasei Medical, Alexion Pharmaceutical and participated on advisory board meeting of Alexion Pharmaceutical. KU has served as a paid Consultant for UCB Pharma, Janssen Pharma, Horizon Therpeutics (Viela Bio), Chugai Pharma, Hanall BioPharma and Mitsubishi Tanabe Pharma, and has received speaker honoraria from Argenx, Alexion Pharmaceuticals, UCB Pharma, and the Japan Blood Products Organisation. Other authors declare no financial or other conflicts of interest.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.