Successful treatment of MuSK antibody-positive myasthenia gravis with rituximab

Introduction: MuSK antibody (ab)-positive patients seem to be different from those with acetylcholine receptor (AChR) ab-positive myasthenia by predominant oculobulbar involvement. Some of them poorly respond to classical immunosuppression. Although plasma exchange causes an improvement in most of these cases, other new options of immunotherapy have to be considered. Rituximab has been administered successfully in patients with AChR ab-positive myasthenia gravis, but no patients with MuSK antibodies have been published until now.

Methods: A 56-year-old patient presenting with predominantly bulbar symptoms (ptosis, diplopia, dysphagea) and respiratory insufficiency was diagnosed as MuSK ab-positive myasthenia gravis. She did not respond adequately to conventional immunosuppressive therapy (azathioprine up to 200mg daily, mycophenolate mofetil 2000mg daily, prednisolone up to 100mg daily). A transient clinical improvement was achieved with repeated plasma exchange. However, clinical stabilisation could not be maintained.

Because of refractory disease a monoclonal anti-CD20 B-cell antibody rituximab therapy was initiated. Rituximab was initially given at a dose of 375mg/m² intravenously on a weekly schedule for 4 weeks. According to protocols frequently used in lymphoma patients, rituximab was subsequently given monthly at the same dose.

Results: Within 2 months of rituximab therapy, a significant clinical benefit was observed. The patient reported less dyspnoea and improved swallowing. There was no further need for a walking aid for longer distances. After 4 months of rituximab therapy there was no more dyspnoea, speech was clear and swallowing normal. There were no ocular symptoms apart from of a mild non exercise-induced bilateral ptosis. After 5 monthly applications the interval between single rituximab courses was extended up to 8 weeks. Rituximab has now been administered for 10 months and no more plasma exchanges had been necessary. Clinical improvement was accompanied by reduction of MuSK serum antibodies whereas total serum IgG and IgM antibodies were unchanged. B-cells had decreased to undetectable levels.

Conclusion: This case illustrates the successful use of rituximab in MuSK ab-positive myasthenia gravis leading to nearly complete remission in a refractory case poorly responsive to immunosuppression before. Rituximab was well tolerated with no therapy associated side effects and proved to be efficious.