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Original research
Induction cyclophosphamide with maintenance immunosuppression in high-risk myasthenia gravis: long-term follow-up and safety profile
  1. Fiona Chan1,
  2. Todd A Hardy2,
  3. Sameer Malik3,
  4. Sudarshini Ramanathan2,4,
  5. D Sean Riminton3,
  6. Stephen W Reddel5
  1. 1Queen Elizabeth Hospital, Birmingham, UK
  2. 2Department of Neurology, Concord Hospital, Concord, New South Wales, Australia
  3. 3Department of Immunology, Concord Hospital, Concord, New South Wales, Australia
  4. 4University of Sydney, Sydney, New South Wales, Australia
  5. 5Central Clinical School, Sydney, New South Wales, Australia
  1. Correspondence to Stephen W Reddel, Central Clinical School, Sydney, New South Wales, Australia; swreddel{at}sydneyneurology.com.au

Abstract

Background Patients with refractory or high-risk myasthenia gravis (MG) respond poorly to conventional immunosuppressive therapy, requiring rescue therapies and often experiencing treatment toxicity. Rescue and injectable therapies do not induce remission and require repetitive administration leading to significant constraints on patients and the healthcare system. This long-term follow-up study demonstrates cyclophosphamide as a rapidly effective and safe treatment in patients with refractory or high-risk MG.

Methods Retrospective cohort study of MG patients treated with cyclophosphamide between January 2000 and June 2022 conducted at a quaternary neuroimmunology clinic in New South Wales, Australia.

Results 31 patients were treated: mean age of 64 years; median follow-up 3.6 years (5 months to 11 years); 94% seropositive to acetylcholine receptor (AChR) antibodies and 45% had thymoma. A reduced intensity cyclophosphamide induction protocol followed by oral antiproliferative maintenance is described.

Median myasthenia gravis composite scores reduced by >50% after the third cycle of cyclophosphamide. Complete cessation of prednisolone was possible in 11 patients while 20 remained on prednisolone with a median daily dose of 5 mg. Plasma exchange was ceased in 62% of patients and intravenous immunoglobulin ceased in 55%. Cyclophosphamide was generally well tolerated with mild cytopenias. There were no malignancies or cases of haemorrhagic cystitis.

Conclusion We describe a large cohort of high-risk MG patients treated with cyclophosphamide in a retrospective single-clinic cohort. We suggest cyclophosphamide should be considered for rapid remission induction, corticosteroid reduction and long-term freedom from recurrent injectable therapies in selected patients, typically those with AChR antibodies.

  • MYASTHENIA
  • NEUROIMMUNOLOGY
  • IMMUNOLOGY

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Footnotes

  • X @darshi_r

  • Contributors The authors confirm their contribution to the paper as follows: study conception and design: DSR and SWR; data collection: FC; analysis and interpretation of results: FC, DSR and SWR; draft manuscript preparation: all authors. All authors reviewed the results and approved the final version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests SR has received research funding from the National Health and Medical Research Council (NHMRC, Australia), the Petre Foundation, the Brain Foundation (Australia), the Royal Australasian College of Physicians, and the University of Sydney. She is supported by an NHMRC Investigator Grant (GNT2008339). She serves as a consultant on an advisory board for UCB and Limbic Neurology. She has been an invited speaker for Biogen, Excemed, Alexion, Novartis and Limbic Neurology for research and education meetings. She is a non-remunerated member of the medical advisory board of The MOG Project and The Sumaira Foundation. SWR declares funds over the last 5 years including but not limited to travel support, honoraria, trial payments, research and clinical support to the neurology department or academic projects of which I am a member have been received from bodies and charities: NHMRC, MRFF, NBA, Myasthenia Alliance Australia, Lambert Initiative, Beeren foundation, anonymous donors; and from pharmaceutical/biological companies: Alexion, Biogen, CSL, Genzyme, Grifols, Merck, Novartis, Roche, Sandoz, Sanofi, UCB. Additional interests and potential conflicts of interest include:Co-founder/shareholder of RxPx health, National IVIG Governance Advisory Council & Specialist Working Group Australia (Neurology) (paid), Australian Medical Services Advisory Committee ad hoc subcommittee on IVIG (paid), Australian Technical Advisory Group on Immunisation Varicella Zoster working party (unpaid), Public Salary as a staff specialist neurologist from Concord Hospital Sydney Local Health District (paid), Private billings from patients and medicare Australia reimbursement as a private practice neurologist (paid), Medical advisor (unpaid) to various patient and advocacy groups. All other authors declare no competing interests for content.

  • 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.

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