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Methotrexate as a steroid sparing agent for asthma in adults
1Respiratory Medicine, John Hunter Hospital, Locked Bag 1, Newcastle Mail Centre, Newcastle, NSW, Australia, 2310. MDPGG@mail.newcastle.edu.au
Background:
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.
Objectives:
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.
Search Strategy:
The Cochrane Airways Group trials register and reference lists of identified articles were searched.
Selection Criteria:
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.
Data Collection And Analysis:
Trial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information.
Main Results:
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.