Davies H, Olson L, Gibson P
Respiratory Medicine, John Hunter Hospital, Locked Bag 1, Newcastle Mail Centre, Newcastle, NSW, Australia, 2310.
Cochrane Database Syst Rev. 2000;1998(2):CD000391. doi: 10.1002/14651858.CD000391.
Sustained oral corticosteroid use can lead to complications, so there is interest in identifying agents that can reduce oral steroid use in people with asthma. Methotrexate has attracted attention as a possible steroid sparing agent in patients with chronic oral steroid dependent asthma.
The objective of this review was to assess the effects of adding methotrexate to oral corticosteroids in adults with stable asthma who are dependent on oral corticosteroids.
The Cochrane Airways Group trials register and reference lists of identified articles were searched.
Randomised trials of the addition of methotrexate compared with placebo in adult steroid dependent asthmatics. Duration of therapy needed to be at least 12 weeks.
Trial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information.
Ten trials involving a total of 185 people were included. Study design and quality, corticosteroid dosages and outcomes varied widely. There was a reduction in oral corticosteroid dose favouring methotrexate in parallel trials (weighted mean difference -4.1 mg per day, 95% confidence interval -6.8 to -1.3) and also in cross-over trials (weighted mean difference -2.9 mg per day, 95% confidence interval -5.9 to -0.2). There was no difference between methotrexate and placebo for forced expiratory volume in one minute (weighted mean difference 0.12 litre, 95% confidence interval -0.21 to 0.45). Hepatotoxicity was a common adverse effect with methotrexate compared to placebo (odds ratio 6.9, 95% confidence interval 3.1 to 15.5).
REVIEWER'S CONCLUSIONS: Methotrexate may have a small steroid sparing effect in adults with asthma who are dependent on oral corticosteroids. However, the overall reduction in daily steroid use is probably not large enough to reduce steroid-induced adverse effects. This small potential to reduce the impact of steroid side-effects is probably insufficient to offset the adverse effects of methotrexate.
持续口服皮质类固醇会导致并发症，因此人们对寻找能够减少哮喘患者口服类固醇药物用量的药物很感兴趣。甲氨蝶呤作为一种可能减少慢性口服类固醇依赖型哮喘患者类固醇用量的药物受到了关注。
本综述的目的是评估在依赖口服皮质类固醇的稳定型哮喘成年患者中，加用甲氨蝶呤至口服皮质类固醇治疗的效果。
检索了Cochrane Airways Group试验注册库以及已识别文章的参考文献列表。
在成年类固醇依赖型哮喘患者中，比较加用甲氨蝶呤与安慰剂的随机试验。治疗持续时间需至少12周。
由两名综述作者独立评估试验质量并进行数据提取。联系研究作者获取缺失信息。
共纳入10项试验，涉及185人。研究设计与质量、皮质类固醇剂量及结果差异很大。在平行试验中，甲氨蝶呤组的口服皮质类固醇剂量有所减少（加权平均差为每天-4.1毫克，95%置信区间为-6.8至-1.3），交叉试验中也是如此（加权平均差为每天-2.9毫克，95%置信区间为-5.9至-0.2）。甲氨蝶呤与安慰剂在一秒用力呼气量方面无差异（加权平均差为0.12升，95%置信区间为-0.21至0.45）。与安慰剂相比，甲氨蝶呤的常见不良反应是肝毒性（比值比为6.9，95%置信区间为3.1至15.5）。
甲氨蝶呤可能对依赖口服皮质类固醇的成年哮喘患者有轻微的减少类固醇用量的作用。然而，每日类固醇用量的总体减少可能不足以减少类固醇诱发的不良反应。这种减少类固醇副作用影响的微小可能性可能不足以抵消甲氨蝶呤的不良反应。
