Antileukotrienes in asthma: present situation

Leukotrienes are key mediators in asthma. Over the last 5 years, several antileukotrienes, including three receptor antagonists (montelukast, pranlukast and zafirlukast) and one 5-lipoxygenase inhibitor (zileuton), have been marketed and, to date, this class of drugs is being used widely. Still, their definite place in the asthma treatment algorithm is not yet established. These novel drugs have not yet all been evaluated in the same depth, but they have all been shown to possess anti-inflammatory properties and to be effective in chronic asthma treatment. Zafirlukast and montelukast are particularly efficacious in exercise-induced asthma and zileuton appears valuable for treating aspirin-intolerant asthmatics. Clinical comparisons to other anti-asthma drugs are still sparse. The corticosteroid-sparing effect of antileukotrienes is fairly well established except for zileuton, even though this drug has been evaluated most thoroughly in terms of its anti-inflammatory effects. Montelukast is the antileukotriene most extensively evaluated in children and zafirlukast has recently been approved for use in children in the USA, although not yet in Europe. Therapeutic regimes are quite variable depending on the drug, but all of the antileukotrienes marketed to date are taken orally; hence, compliance is usually greater than that with inhaled medication. Response to antileukotrienes appears to depend on the individual patients' characteristics, in particular on genetic polymorphisms related to leukotriene metabolism. All drugs of this class are well tolerated and only in the case of zileuton is there potential for hepatic adverse effects. The diagnosis of Churg-Strauss syndrome made among patients taking antileukotrienes seems to be more related to the withdrawal of corticosteroids than to the antileukotrienes themselves.