[Randomized controlled clinical trial of middle-dose cyclophosphamide plus methylprednisolone for myasthenia gravis patients in crisis].

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of middle-dose cyclophosphamide plus methylprednisolone for myasthenia gravis (MG) patients in crisis. METHODS: For this prospective, open, parallel, randomized controlled trial, we recruited a total of 156 MG patients in crisis from January 1999 to October 2011 at Department of Neurology, First Affiliated Hospital, Sun Yat-sen University. They were divided into two groups of cyclophosphamide and control (n = 78 each). In the cyclophosphamide group, each received methylprednisolone 500 mg/d for 3 days, then tapered to 250 mg/d and tapered half every 3 days until 62.5 mg/d. Afterward an oral dose of prednisone was prescribed at 30 mg/d until the end of the trial. At the same time, an intravenous injection of cyclophosphamide was offered at 0.4 g/d for 3 days and then 0.4 g/d every 3 days. In the control group, each received methylprednisolone alone. And the efficacies were assessed by absolute and relative MG scores. RESULTS: (1) There were 54 (69.2%) patients off-ventilation in 3 days in the cyclophosphamide group versus 36 (46.2%) patients in 8 - 14 days in the control group. Notable statistical significance existed between two groups (P = 0.000). (2) More than half of the patients in cyclophosphamide group with extremity weakness (n = 44, 56%) and dysphagia (n = 47, 60.3%) significantly improved in 10 - 14 days versus 28 days in the control group. Notable statistical significance existed between two groups (P = 0.000). (3) In the cyclophosphamide group, dyspnea disappeared in 54 (69.2%) patients when the dose reached 1.2 g. The recovery of dysphagia (n = 47, 60.3%) and extremity weakness (n = 44, 56.4%) occurred in more than half of the patients when the dose reached 2.8 g. Notable statistical significance existed among three groups (P = 0.000). (4) During the treatment period, there were 17 cases (21.8%) with pulmonary infection in the cyclophosphamide group versus 53 cases (67.9%) in the control group. Notable statistical significance existed between two groups (P = 0.000). (5) Brief and minor side effects appeared in the patients of the cyclophosphamide group. CONCLUSION: (1) The combined treatment of middle-dose cyclophosphamide and methylprednisolone for MG patients in crisis is both effective and safe. (2) When combined with methylprednisolone, 90% of patients with MG crisis are successfully off-ventilation when the dose of cyclophosphamide reaches 1.6 g.