Trigg C J, Davies R J
Department of Respiratory Medicine, St Bartholomew's Hospital, London, U.K.
Respir Med. 1993 Apr;87(3):211-6. doi: 10.1016/0954-6111(93)90094-g.
Methotrexate has been shown to have a steroid-sparing effect in chronic steroid-dependent asthmatics at a dose of 15 mg week-1. The aim of this study was to investigate the steroid-sparing activity and adverse events profile of methotrexate 30 mg week-1 in severe steroid-dependent asthma. Eighteen patients who had required 10-50 mg week-1 prednisolone for at least 6 months were asked to participate in a randomized, double-blind, placebo-controlled cross-over study lasting 24 weeks. Daily diary cards of symptoms, peak expiratory flow rate and medication requirements were kept and the patients attended for a chest X-ray, spirometry, lung volumes and gas transfer at commencement and after each 12-week treatment period. Every 3 weeks, adverse events were noted and blood taken for full blood count, urea and electrolytes and liver function tests. Twelve patients completed the trial. Withdrawals were due to non-compliance in two patients, pneumonia in two patients, depression in one patient (on placebo) and severe nausea in one patient. Adverse events were common, probably as a consequence of the higher dosage. Prednisolone requirements were not significantly reduced on methotrexate. Lung function improved on methotrexate with a significant rise in maximal mid-expiratory flow rate and a trend towards improvement in FEV1.
已表明甲氨蝶呤在慢性依赖类固醇的哮喘患者中，以每周15毫克的剂量具有类固醇节省效应。本研究的目的是调查每周30毫克甲氨蝶呤在严重依赖类固醇的哮喘中的类固醇节省活性和不良事件情况。18名至少6个月来每周需要10 - 50毫克泼尼松龙的患者被要求参与一项为期24周的随机、双盲、安慰剂对照交叉研究。记录每日症状、呼气峰值流速和药物需求的日记卡，并在开始时以及每个12周治疗期后让患者进行胸部X光、肺活量测定、肺容积和气体交换检查。每3周记录不良事件，并采集血液进行全血细胞计数、尿素和电解质以及肝功能检查。12名患者完成了试验。退出试验的原因是两名患者不依从、两名患者患肺炎、一名患者（服用安慰剂）出现抑郁以及一名患者出现严重恶心。不良事件很常见，可能是由于剂量较高所致。服用甲氨蝶呤时泼尼松龙的需求量没有显著减少。服用甲氨蝶呤后肺功能有所改善，最大呼气中期流速显著升高，FEV1有改善趋势。
