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• Azathioprine and Myasthenia Gravis
  Bryan Lecky
  Published on: 13 April 2016

• Published on: 13 April 2016

  Azathioprine and Myasthenia Gravis

  • Bryan Lecky, Consultant Neurologist
  • Other Contributors:
    • Marguerite Hill, Morriston Hospital, Swansea, UK: Dr Jackie Palace, Oxford MGA Myasthenia Centre, John Radcliffe Hosital , Oxford, UK; David Hilton-Jones, Oxford MGA Myasthenia Centre, John Radcliffe Hosital, Oxford, UK

  Dear Editor,

  We read with interest the summary and subsequent commentary on the Cochrane review of immunosuppressant drugs for myasthenia gravis (MG) (Hart et al.2009, Celani et al, 2009). We would like to express concerns regarding the practical implications of these reviews.

  Cochrane reports are not appropriate in guiding clinical practice where highly effective treatments predated the use of randomi...

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  Dear Editor,

  We read with interest the summary and subsequent commentary on the Cochrane review of immunosuppressant drugs for myasthenia gravis (MG) (Hart et al.2009, Celani et al, 2009). We would like to express concerns regarding the practical implications of these reviews.

  Cochrane reports are not appropriate in guiding clinical practice where highly effective treatments predated the use of randomised controlled trials (RCTs) to test efficacy. For example corticosteroids are routinely used and are very effective in producing remission in the majority of patients with MG. No RCTs against placebo have been performed and comparison now would be unethical and unnecessary.

  With rare diseases, recruitment for RCTs can be very difficult and all the studies included in this analysis had difficulty recruiting adequate numbers. Only one subsequent study referred to by Celani eventually managed to get sufficient numbers. However they had to add a further 18 centers across 10 new countries and this would not be affordable with an investigator led study.Thus clinical practice has to work with the best evidence and summarising a review with a statement that ‘bigger, better designed, longer studies are needed’ may not be helpful.

  The major issue however in this review is the selection of the outcome used for meta-analysis i.e. improvement in weakness at 6 months. Of note only three of the six studies selected for inclusion recorded this outcome, thus leading to the inevitable conclusion of lack of evidence of efficacy from three studies. Assessing subtle difference in timing of early responses of immunosuppressive agents that are known to take months to work would require much larger cohorts and this question is not of prime importance in clinical practice. The main reason to use a second immunosuppressive agent in clinical practice is as a steroid-sparer and it is established that azathioprine is effective in this respect (Palace et al, 1998)1 .

  We are concerned that the conclusion, indicating that limited evidence from RCTs shows no benefit from azathioprine, is misleading and might be interpreted to suggest that azathioprine should not be used in the treatment of MG.

  References

  1. Palace J, Newsom-Davis J, Lecky B.
  A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis.
  Neurology 1998 50 1778-1783.

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  Conflict of Interest:
  None declared.

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