High‐dose cyclophosphamide in refractory myasthenia gravis with MuSK antibodies

Abstract

We describe a 48-year-old woman with seronegative myasthenia gravis (MG) and high-titer of anti-MuSK antibody. She had severe bulbar and respiratory weakness with minimal limb weakness for 2 years. Her disease responded poorly to all the conventional immunosuppressive regimens. Treatment with immunoablative dose of cyclophosphamide led to dramatic and sustained remission of her symptoms. High-dose cyclophosphamide is an effective alternative in patients with unusually refractory disease.

Rituximab for myasthenia gravis

“…Several authors have already reported encouraging anecdotal experience with rituximab, with no serious side effects, good tolerability, and marked clinical improvement in almost all cases [4][5][6][7][8][9][10][11][12]. In fact, we found only one report on a MG patient in whom rituximab was considered inefficacious [15]. However, publication bias may account for this impressive record of rituximab, i.e.…”

“…4-weekly 375 mg/m 2 infusions. Following this, investigators have used different regimens, ranging from no further infusions to a fixed second course of 4-weekly infusions or monthly infusions over two to five months [5,6,8,9,11,15]. Others have used B cell counts during follow-up to guide treatment with rituximab [7,12].…”

Medical treatment options for ocular myasthenia gravis

“…Cyclophosphamide is an alkylating agent, which, given in high doses, rapidly kills lymphocytes and committed hematopoietic progenitors with resultant stem-cell proliferation, immune system reconstitution, and induction of tolerance to pathogenic autoantigens [57,58]. Administration of intravenous pulses of high-dose cyclophosphamide (50 mg/kg of body weight over 1 h for 4 days) in six cases of severe refractory myasthenia gravis [57,58] resulted in clinical improvement by the second month (peaked at 3-12 months), but AChR antibodies or antiMuSK antibodies were not totally eliminated.…”

Long-term efficacy and limitations of cyclophosphamide in myasthenia gravis

“…The treatment protocols used in MG have been extrapolated from studies conducted in other autoimmune disorders. Various dosage schedules have been used ranging from a low dose of 2-6 mg/kg to high dose of greater than 1600 mg/m 2 body surface area [18,19]. In lupus nephritis, it has been demonstrated that IV low dose cyclophosphamide is as effective as high dose cyclophosphamide, with the former regimen having fewer associated side effects [4].…”