小剂量环磷酰胺联合糖皮质激素治疗Ⅰ／Ⅱ型重症肌无力的疗效与安全性观察

Efficacy and safety of low-dose cyclophosphamide plus corticosteroids for type I/lI myasthenia gravis

目的评价小剂量环磷酰胺联合糖皮质激素治疗I／II型重症肌无力的疗效与安全性。方法采用前瞻、非随机、开放的研究方法，挑选来源于1999年1月至2010年10月在中山大学附属第一医院神经科就诊的160例对糖皮质激素不敏感型的I／Ⅱ型重症肌无力患者作为研究对象。予糖皮质激素＋环磷酰胺＋吡啶斯的明治疗。其中泼尼松0．5nag·kg^-1·d^-1,口服，环磷酰胺8mg·kg^-1·次。（约0．4g），静脉推注，1次／周，吡啶斯的明36mg·kg^-1·d^-1，口服。根据MG的临床绝对和相对评分法评定疗效，治疗周期为30周。结果（1）106例I型患者在30周内（环磷酰胺总量达到12g）临床相对计分达I〉95％（痊愈）者有74例，占69．9％；54例Ⅱ型患者在30周内（环磷酰胺总量达到12g）临床相对计分达≥95％（治愈）者有35例，占64．8％。两组比较差异无统计学意义（P=0．521）。（2）在治疗的30周内，所有患者均有不同程度的好转，经Mann—Whitney秩和检验，P≤0．05。（3）本组患者所出现的不良反应轻微。（4）当环磷酰胺总量达到4g时，I型患者的痊愈率较Ⅱ型患者高（P=0．000）；当环磷酰胺总量达到12g时，Ⅱ型患者的痊愈率较I型患者高（P=0．001）。（5）在I型患者中，58．4％集中在环磷酰胺用量为4—8g的范围内达到临床痊愈；而在Ⅱ型患者中，61．1％集中在8～12g的范围内达到临床痊愈。结论（1）小剂量环磷酰胺联合糖皮质激素治疗激素不敏感型（I型或Ⅱ型）重症肌无力是有效且安全的。（2）不同临床类型对环磷酰胺的敏感性不一样：I型患者较敏感，达到痊愈所需要总剂量一般在4—8g；而Ⅱ型患者达到痊愈所需要的总剂量一般在8～12g。

[ Abstract] Objective To evaluate the efficacy and safety of low-dose cyclophosphamide plus cortieosteroids for type I / 1I myasthenia gravis （MG）. Methods This trial was prospective, non-random and open-labeled. We selected 160 patients with steroid-insensitive MG from January 1999 to October 2011. Each patient received an oral dose of prednisone 0.5 mg ~ kg-1 ~ d-1 , cyclophosphamide 8 mg ~ kg-1 time- 1 once weekly intravenously and oral pyridostigmine 36 mg ~ kg- 1 . d-1. The efficacies were assessed by absolute and relative MG scores. The clinical treatment cycle was 30 weeks. Results （ 1 ） Among them, 74/106 type I MG patients （69.9%） reached clinical relative scores 〉195% in 30 weeks. The total dose of cyclophosphamide was 12 g. And 35/54 type I1 MG patients （64.8%） reached clinical relative scores t〉 95% in 30 weeks. No statistically significant difference existed between two groups （P = 0. 521 ）. （2）All patients had various degrees of improvement in 30 weeks. The difference was statistically significant by Mann-Whitney U test （ P ~〈 0.05 ）. （3） There were minor side effects in these all patients. （4） When the total dose of cyclophosphamide reached 4 g, the cure rate in type I patients was higher than that of in type II patients （P = 0. 000 ）. When the total dose of cyclophosphamide reached 12 g, the cure rate in type II patients was higher than that of in type I patients （ P = 0. 001 ）. （ 5 ） The cure dose of cyclophosphamide was 4 - 8 g in 58.4% of type I patients versus 8 - 12 g in 61.1% of type II patients. Conclusion The combined treatment of low-dose cyclophosphamide and corticosteroids in glucocorticoid-insensitive type MG （ type I / II ） is both effective and safe. And the sensitivity to cyclophosphamide varies for different clinical types. It is higher in type I than type II patients.