Intravenous cyclophosphamide monthly pulses in refractory myasthenia gravis
Refractory myasthenia gravis (MG) is defined as a failure to respond adequately to conventional therapies, the inability to reduce immunosuppressive therapy without clinical relapse or the need for ongoing rescue therapy, severe adverse effects from immunosuppressive therapy (treatment intolerant) or frequent myasthenic crisis even on therapy. Cyclophosphamide (CYC) is a DNA alkylating agent that causes important interference in transcription processes and DNA replication, it has been used in refractory MG with controversial results. We aim to determine the efficacy of CYC in refractory MG in the Mexican population.
In an observational, longitudinal retrospective study, we identified eight refractory MG patients treated with 30–50 mg/kg monthly CYC for at least 6 months. The efficacy was assessed by Osserman scale considering significant improvement a ≥ 1 point reduction and Myasthenia Gravis Composite Scale. The relapse-free and remission-free period were also calculated using the Kaplan–Meier statistic.
Clinical improvement was achieved in 75% of the patients. According to the Kaplan–Meier analysis, the median progression-free survival (PFS) was 9 (6.2–11.5) months and the median time to progression (TTP) was 4 (1–8) months. Response was independent of patient's characteristics, except for the MG age of onset (p = 0.0025).
CYC was effective in all patients with refractory MG for a mean of 9 months, with worsening thereafter, which could be associated with low cumulative dose. The symptomatic improvement with CYC was noted within the 1st month. We conclude that CYC is effective as an induction to remission therapy, although our data suggest it is not effective as a long-term therapy.
Contributions V-C and L-H were in charge of the diagnosis, treatment care and follow up of the patient and supervised the elaboration of the manuscript. G-F and B-R data analysis and organization. G-T, C-U and C-L prepared the draft.
Compliance with ethical standards
Conflicts of interest
All authors declare no competing interests or external funding.
Authors have read the journal's position on issues involved in ethical publication. This study was approved by the research ethics committee of our institution.
- 8.Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A (2011) Evidence-based guideline update: plasmapheresis in neurologic disorders: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. https://doi.org/10.1212/WNL.0b013e318207b1f6 CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Zinman L, Ng E, Bril V (2007) IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial. Neurology. https://doi.org/10.1212/01.wnl.0000256698.69121.45 CrossRefPubMedGoogle Scholar
- 11.Batocchi AP, Evoli A, Di SC, Tonali P (2000) Therapeutic apheresis in myasthenia gravis. Ther Apher. https://doi.org/10.1046/j.1526-0968.2000.004004275.x CrossRefPubMedGoogle Scholar