甲氨碟呤在激素依赖型哮喘中的疗效研究及安全性评价

Efficacy and Adverse Effects of Methotrexate in the Treatment of Steroid-dependent Asthma

目的 通过随机、对照、双盲的临床实验研究低剂量甲氨碟呤 (MTX)在激素依赖型哮喘中的疗效并评价其安全性。方法 按照随机 ,对照 ,双盲的设计 ,5 0例激素依赖型哮喘患者分两组 (治疗组和安慰剂组 ) ,分别予甲氨碟呤 ( 15mg·周 -1)与安慰剂治疗 12周 ,治疗前后记录强的松日用量 ,哮喘症状评分 ,β -R兴奋剂日用频率 ,测定肺功能一秒钟用力呼气容积 (FEV1)、以及峰流速 (PEF) ,治疗过程中记录哮喘急性发作频率及监测MTX的不良反应。结果 45例完成试验。治疗组 2 4例 ,对照组 2 1例。治疗组予MTX治疗后患者的强的松日需用量明显减少 [治疗前 ( 14 3 8± 4 90 )mg·d-1;治疗后 ( 10 63± 5 77)mg·d-1,P <0 0 0 1] ,哮喘症状评分 [治疗前 ( 2 0 4± 1 0 0 )分 ;治疗后 ( 1 46± 0 88)分 ,P <0 0 1] ,β -R兴奋剂日用频率 [治疗前 ( 6 3 1± 1 45 ) ;治疗后 ( 4 5 0± 1 0 6) ,P <0 0 0 1]明显下降 ,FEV1,PEF无显著改变 (P >0 0 5 )。治疗组哮喘急性发作频率较对照组明显减少 (治疗组 :1 0 8± 0 62 ;对照组 :1 62± 0 80 ,P <0 0 5 )。治疗过程中未发现与MTX有关的严重副作用。对照组治疗前后各项指标无明显变化 (P >0 0 5 )。结论 低剂量MTX可明显减少激素依赖型哮喘患者的激素用量 ,?

Objective To investigate the efficacy and adverse effects of methotrexate(MTX) in the treatment of steroid-dependent asthma.Methods By a randomized, double-blind scheme,50 patients with steroid dependent asthma were divided into two group:MTX group and placebo group:MTX(15mg·week -1 ) and placebo agent were given respectively for 12 weeks.The dose of oral steroid daily,symptom scores, peak flow rates, spirometry, β-agonist frequency were monitored before and after treatment. During the treatment,frequency of asthma attack,adverse events of MTX were noted,and blood routine examination,liver function test,kidney function test were performed.Results 45 subjects completed the study. Compared with before treatment,the MTX significantly decreased daily steroid dosage(14 38±4 90mg·d -1 versus 10 63±5 77mg·d -1 ,P<0 001).Furthermore, during MTX treatment,the patients experienced significantly less symptom scores(2 04±1 00 versus 1 46±0 88,P<0 01),less frequency of β-agonist (6 31±1 45 versus 4 50±1 06,P<0 001);Less frequency of exacerbation of asthma was noted in MTX group,compared with placebo group(1 08±0 62 versus 1 62±0 80,P<0 05).FEV 1 and PEF values were unchanged in MTX group or Placebo group(P>0 05).No serious adverse effects of MTX were found during the study.Conclusion We consider that low-dose MTX may be beneficial for steroid-dependent asthma and that this therapy is well tolerated by patients.