Methotrexate as a steroid sparing agent for asthma in adults

Some people with asthma need to rely on corticosteroid drugs to control their asthma. Corticosteroids reduce the inflammation (swelling) of the airways (passages to the lungs). Long-term use has serious adverse effects, so ways to try and cut down on the need for corticosteroids are sometimes tried. Methotrexate may also be able to reduce inflammation, and is sometimes used for arthritis. Its adverse effects include headaches, dizziness, fatigue and altered moods, and stomach, lung and liver complications. The review of trials found methotrexate provides little relief for asthma, and adds its own adverse effects.

Authors' 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.

Read the full abstract...

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.

Search strategy: 

The Cochrane Airways Group Specialised Register and reference lists of identified articles were searched. Searches are current as of February 2006.

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).