Immunosuppression for myasthenia gravis

Immunosuppression is needed if myasthenia gravis is moderate to severe or if the response to pyridostigmine is incomplete (ie patient is symptomatic despite an adequate trial of pyridostigmine).

As the patient goes into remission on immunosuppression, pyridostigmine should no longer be needed. Stopping pyridostigmine avoids wrongly interpreting its adverse effects (eg muscle twitching or cramping) as disease activity. Pyridostigmine should be withdrawn over a few weeks, to ensure that myasthenia gravis is in remission.

An uncommon effect of starting a high corticosteroid dose is that symptoms can get worse in the first 3 to 7 days, but this is transient. Start therapy as an inpatient or slowly work up to the high dose as an outpatient (as in the drug recommendations below). Lower corticosteroid dosages are usual in ocular myasthenia. Start a corticosteroid-sparing drug at the same time as the corticosteroid. Use:

prednisolone (or prednisone) 5 mg orally, daily in the morning. Increase daily dose by 5 mg every 3 days to a maximum of 1 mg/kg (up to 75 mg) daily. After 4 to 6 weeks, reduce daily dose by 5 mg every 2 weeks to 25 mg daily, then reduce further according to response and tolerability1 myasthenia gravis prednis ol one    

PLUS

1 azathioprine 1.5 to 2.5 mg/kg orally, daily2  myasthenia gravis azathioprine    

OR

1 mycophenolate mofetil 500 mg orally, twice daily (maximum 1500 mg twice daily)1 myasthenia gravis mycophenolate mofetil    

OR

1 mycophenolate sodium 360 mg orally, twice daily (maximum 1080 mg twice daily)1. myasthenia gravis mycophenolate sodium mycophenolate sodium (mycophenolic acid) mycophenolate sodium (mycophenolic acid)

An alternative corticosteroid-sparing drug is methotrexate1.

In a myasthenic crisis or before an operation, IVIg or plasma exchange may be used. Randomised controlled trial evidence is insufficient to justify ongoing IVIg for chronic myasthenia, but it may be used in rare cases (eg pregnancy, severe treatment-resistant disease, intolerance to other treatments).

For refractory myasthenia (anti–Ach-R positive and anti-MuSK positive), case series show positive responses to rituximab34, and a small randomised controlled trial showed a positive response to cyclophosphamide5.

For MuSK-associated myasthenia gravis, cohort evidence supports plasma exchange (thought to be more effective than IVIg) and rituximab (which can induce remission or allow corticosteroid doses to be reduced)6.

1 Consider precautions and monitoring requirements when prescribing immunomodulatory drugs—consult local protocols or seek expert advice.Return
2 Consider precautions (eg measuring thiopurine methyltransferase [TPMT] before starting therapy) and monitoring requirements when prescribing azathioprine—consult local protocols or seek expert advice. Azathioprine therapy does not reach maximum effect for at least 6 months. Return
3 Benveniste O, Hilton-Jones D. The role of rituximab in the treatment of myasthenia gravis. European Neurological Review 2010;5(2):95-100. [URL]Return
4 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(5):259-66. [URL]Return
5 De Feo LG, Schottlender J, Martelli NA, Molfino NA. Use of intravenous pulsed cyclophosphamide in severe, generalized myasthenia gravis. Muscle Nerve 2002;26(1):31-6. [URL]Return
6 El-Salem K, Yassin A, Al-Hayk K, Yahya S, Al-Shorafat D, Dahbour SS. Treatment of MuSK-associated myasthenia gravis. Curr Treat Options Neurol 2014;16(4):283. [URL]Return