他克莫司治疗全身型重症肌无力的有效性及安全性评价
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摘要
目的评估他克莫司在全身型重症肌无力患者中的疗效和安全性。方法回顾2011年6月～2017年1月广州中医药大学第一附属医院收治的重症肌无力患者的病历资料,纳入符合标准的患者。于2017年9月通过电话回访对他克莫司联合糖皮质激素治疗的患者与未使用他克莫司治疗的患者在重症肌无力日常生活量表评分(MG-activities of daily living,MG-ADL)、Osserman分型、重症肌无力相关的住院次数、危象发生次数、死亡人数方面进行疗效评价,并记录他克莫司相关的药物不良反应。结果共有231例全身型重症肌无力患者完成随访。他克莫司组的ADL评分差值(随访结束时评分-纳入时评分)显著大于对照组(P=0. 001);他克莫司组患者住院次数显著少于与对照组(P=0. 004)。两组患者在随访结束时Osserman分型、肌无力危象次数和死亡人数方面无显著差异(P均> 0. 05)。他克莫司组有19例患者出现药物不良反应,对照组有30例患者出现药物不良反应,无严重的药物不良反应出现。结论他克莫司联合糖皮质激素治疗全身型重症肌无力与对照组相比在改善ADL评分及减少住院次数方面有显著优势并且具有较高的安全性。
Objective The aim of our study was to evaluate the efficacy and safety of tacrolimus in generalized myasthenia gravis( MG) patients. Methods MG patients admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine between June 2011 and January 2017 with generalized myasthenia gravis according to the modified Osserman scale were recruited and received a telephone follow-up in September 2017. Patients treated with tacrolimus plus prednisone were compared with those treated without tacrolimus. The efficacy of tacrolimus was assessed using MG-activities of daily living( MG-ADL) score,Osserman classification,the number of hospitalizations,the number of myasthenic crises and deaths. The adverse drug effects of tacrolimus were monitored. Results A total of 231 patients were included. The difference of MG-ADL score between baseline and after follow-up was significantly greater in the tacrolimus group than the control group( P = 0. 001). The number of hospital admissions was fewer in the tacrolimus group than the control group( P =0. 004). The Osserman classification,the number of myasthenic crises and deaths did not differ significantly between the two groups( P > 0. 05). Nineteen patients in the tacrolimus group and thirty patients in the control group had adverse drug reactions,but no severe adverse effects appeared. Conclusion Our study suggested that tacrolimus could be an effective and safe treatment for generalized MG patients.
Objective The aim of our study was to evaluate the efficacy and safety of tacrolimus in generalized myasthenia gravis( MG) patients. Methods MG patients admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine between June 2011 and January 2017 with generalized myasthenia gravis according to the modified Osserman scale were recruited and received a telephone follow-up in September 2017. Patients treated with tacrolimus plus prednisone were compared with those treated without tacrolimus. The efficacy of tacrolimus was assessed using MG-activities of daily living( MG-ADL) score,Osserman classification,the number of hospitalizations,the number of myasthenic crises and deaths. The adverse drug effects of tacrolimus were monitored. Results A total of 231 patients were included. The difference of MG-ADL score between baseline and after follow-up was significantly greater in the tacrolimus group than the control group( P = 0. 001). The number of hospital admissions was fewer in the tacrolimus group than the control group( P =0. 004). The Osserman classification,the number of myasthenic crises and deaths did not differ significantly between the two groups( P > 0. 05). Nineteen patients in the tacrolimus group and thirty patients in the control group had adverse drug reactions,but no severe adverse effects appeared. Conclusion Our study suggested that tacrolimus could be an effective and safe treatment for generalized MG patients.
引文
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[5]Lewis RA.Myasthenia gravis:new therapeutic approaches based on pathophysiology[J].J Neurol Sci,2013,333(2):93-98.
[6]中华医学会神经病学分会神经免疫学组.中国重症肌无力诊断和治疗指南2015[J].中华神经科杂志,2015,48(11):934-940.
[7]Pascuzzi RM,Coslett HB,Johns TR.Long-term corticosteroid treatment of myasthenia gravis:report of 116 patients[J].Ann Neurol,1984,15(3):291-298.
[8]Cruz JL,Wolff ML,Vanderman AJ,et al.The emerging role of tacrolimus in myasthenia gravis[J].Ther Adv Neurol Disord,2015,8(2):92-103.
[9]Ho S,Clipstone N,Timmermann L,et al.The mechanism of action of cyclosporin A and FK506[J].Clin Immunol Immunopathol,1996,80(3):40-45.
[10]Banerji SS,Parsons JN,Tocci MJ.The immunosuppressant FK-506 specifically inhibits mitogen-induced activation of the interleukin-2promoter and the isolated enhancer elements NFIL-2A and NF-AT1[J].Mol Cell Biol,1991,11(8):4074-4087.
[11]Yoshikawa H,Kiuchi T,Saida T,et al.Randomised,double-blind,placebo-controlled study of tacrolimus in myasthenia gravis[J].JNeurol Neurosurg Psychiatry,2011,82(9):970-977.
[12]Osserman KE,Kornfeld P,Cohen E,et al.Studies in myasthenia gravis;review of two hundred eighty-two cases at the Mount Sinai Hospital,New York City[J].Ama Arch Intern Med,1958,102(1):72-81.
[13]Wolfe GI,Herbelin L,Nations SP,et al.Myasthenia gravis activities of daily living profile[J].Neurology,1999,52(7):1487-1489.
[14]Ponseti JM,Gamez J,Azem J,et al.Post-thymectomy combined treatment of prednisone and tacrolimus versus prednisone alone for consolidation of complete stable remission in patients with myasthenia gravis:a non-randomized,non-controlled study[J].Curr Med Res Opin,2007,23(6):1269-1278.
[15]Yoshikawa H,Kiuchi T,Saida T,et al.Randomised,double-blind,placebo-controlled study of tacrolimus in myasthenia gravis[J].JNeurol Neurosurg Psychiatry,2011,82(9):970-977.
[16]Gotterer L,Li Y.Maintenance immunosuppression in myasthenia gravis[J].J Neurol Sci,2016,369(10):294-302.
[17]Ahn SW,Joo IS,Kim BJ,et al.A multicenter prospective observational study on the safety and efficacy of tacrolimus in patients with myasthenia gravis[J].J Neurol Sci,2017,379(8):271-275.
[18]Azem J,Fort JM,Codina A.Benefits of FK506(tacrolimus)for residual,cyclosporin-and prednisone-resistant myasthenia gravis:oneyear follow-up of an open-label study[J].Clin Neurol Neurosurg,2005,107(3):187-190.
[19]Sanders DB,Aarli JA,Cutter GR,et al.Long-term results of tacrolimus in cyclosporine-and prednisone-dependent myasthenia gravis[J].Neurology,2005,66(6):954-955.
[2]Gilhus NE,Verschuuren JJ.Myasthenia gravis:subgroup classification and therapeutic strategies[J].Lancet Neurol,2015,14(10):1023-1036.
[3]Fujii Y,Lindstrom J.Regulation of antibody production by helper Tcell clones in experimental autoimmune myasthenia gravis[J].J Immunol,1988,141(10):3361-3369.
[4]Cohen-Kaminsky S,Gaud C,Morel E,et al.High recombinant interleukin-2 sensitivity of peripheral blood lymphocytes from patients with myasthenia gravis:correlations with clinical parameters[J].J Autoimmun,1989,2(3):241-258.
[5]Lewis RA.Myasthenia gravis:new therapeutic approaches based on pathophysiology[J].J Neurol Sci,2013,333(2):93-98.
[6]中华医学会神经病学分会神经免疫学组.中国重症肌无力诊断和治疗指南2015[J].中华神经科杂志,2015,48(11):934-940.
[7]Pascuzzi RM,Coslett HB,Johns TR.Long-term corticosteroid treatment of myasthenia gravis:report of 116 patients[J].Ann Neurol,1984,15(3):291-298.
[8]Cruz JL,Wolff ML,Vanderman AJ,et al.The emerging role of tacrolimus in myasthenia gravis[J].Ther Adv Neurol Disord,2015,8(2):92-103.
[9]Ho S,Clipstone N,Timmermann L,et al.The mechanism of action of cyclosporin A and FK506[J].Clin Immunol Immunopathol,1996,80(3):40-45.
[10]Banerji SS,Parsons JN,Tocci MJ.The immunosuppressant FK-506 specifically inhibits mitogen-induced activation of the interleukin-2promoter and the isolated enhancer elements NFIL-2A and NF-AT1[J].Mol Cell Biol,1991,11(8):4074-4087.
[11]Yoshikawa H,Kiuchi T,Saida T,et al.Randomised,double-blind,placebo-controlled study of tacrolimus in myasthenia gravis[J].JNeurol Neurosurg Psychiatry,2011,82(9):970-977.
[12]Osserman KE,Kornfeld P,Cohen E,et al.Studies in myasthenia gravis;review of two hundred eighty-two cases at the Mount Sinai Hospital,New York City[J].Ama Arch Intern Med,1958,102(1):72-81.
[13]Wolfe GI,Herbelin L,Nations SP,et al.Myasthenia gravis activities of daily living profile[J].Neurology,1999,52(7):1487-1489.
[14]Ponseti JM,Gamez J,Azem J,et al.Post-thymectomy combined treatment of prednisone and tacrolimus versus prednisone alone for consolidation of complete stable remission in patients with myasthenia gravis:a non-randomized,non-controlled study[J].Curr Med Res Opin,2007,23(6):1269-1278.
[15]Yoshikawa H,Kiuchi T,Saida T,et al.Randomised,double-blind,placebo-controlled study of tacrolimus in myasthenia gravis[J].JNeurol Neurosurg Psychiatry,2011,82(9):970-977.
[16]Gotterer L,Li Y.Maintenance immunosuppression in myasthenia gravis[J].J Neurol Sci,2016,369(10):294-302.
[17]Ahn SW,Joo IS,Kim BJ,et al.A multicenter prospective observational study on the safety and efficacy of tacrolimus in patients with myasthenia gravis[J].J Neurol Sci,2017,379(8):271-275.
[18]Azem J,Fort JM,Codina A.Benefits of FK506(tacrolimus)for residual,cyclosporin-and prednisone-resistant myasthenia gravis:oneyear follow-up of an open-label study[J].Clin Neurol Neurosurg,2005,107(3):187-190.
[19]Sanders DB,Aarli JA,Cutter GR,et al.Long-term results of tacrolimus in cyclosporine-and prednisone-dependent myasthenia gravis[J].Neurology,2005,66(6):954-955.