Methotrexate in asthma. A safety perspective.

The inflammatory process underlying bronchial asthma is well established and has prompted clinical interest in nonsteroidal anti-inflammatory forms of treatment. Although unproven, it has been suggested that effective treatment of allergic inflammation may prevent long term consequences of asthma and avert deterioration in pulmonary function. Methotrexate has potent anti-inflammatory actions, even at low doses, and was judged to be a suitable candidate drug for asthma treatment if it could demonstrate an acceptable tolerability profile. Low dose methotrexate has been investigated in both noncomparative studies and in placebo-controlled studies of severe asthma. In general, such studies have suggested that methotrexate may have steroid-sparing benefits coupled to generally mild adverse events; although adverse effects were not of a serious nature they were observed in up to one-third of patients. Rare but potentially life-threatening adverse effects involving the pulmonary, hepatic and haematological systems remain of particular concern. Methotrexate should therefore be considered as an adjunct to high dose inhaled corticosteroids in patients who require more than 10mg of prednisolone daily, and who experience severe and unacceptable steroid-related adverse effects. Treatment should only be initiated by physicians with experience in the use of the drug, and the relevant safety parameters should be closely monitored.