• H Davies, L Olson, and P Gibson.
• Respiratory Medicine, John Hunter Hospital, Locked Bag 1, Newcastle Mail Centre, Newcastle, NSW, Australia, 2310. MDPGG@mail.newcastle.edu.au
• Cochrane Db Syst Rev. 2000 Jan 1; 1998 (2): CD000391CD000391.

BackgroundSustained 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.ObjectivesThe 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.Search StrategyThe Cochrane Airways Group trials register and reference lists of identified articles were searched.Selection CriteriaRandomised trials of the addition of methotrexate compared with placebo in adult steroid dependent asthmatics. Duration of therapy needed to be at least 12 weeks.Data Collection And AnalysisTrial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information.Main ResultsTen 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 ConclusionsMethotrexate 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.

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