The prospects for long-term intervention in asthma with antileukotrienes

Abstract

The antileukotriene drugs are the first new therapeutic agents approved for the treatment of asthma in more than 20 years. The currently available compounds are orally active and either prevent the cysteinyl leukotrienes from binding to and activating the cysLT-1 receptor in the lung (leukotriene receptor antagonists, LTRAs) or inhibit leukotriene synthesis (leukotriene synthesis inhibitors, LTSIs). The antileukotrienes acutely bronchodilate the airways of patients with baseline bronchoconstriction, although usually not as well as beta-agonists. When used regularly they produce rapid improvements of pulmonary function and symptoms in patients with mild-to-moderate asthma, and probably of those with more severe asthma as well, which persists for the duration of treatment. Yet, individual responses to the antileukotrienes are variable and not predictable based on clinical criteria. Recent studies suggest they reduce asthmatic airway inflammation. The few comparator studies with other asthma medications indicate they are equal or more effective than cromolyn but equal or less effective than low-to-moderate doses of inhaled corticosteroids. Initial experience with the antileukotrienes reveals limited toxicity and a favourable therapeutic-to-toxic ratio. The exact role of the antileukotrienes in the treatment of asthma remains to be determined, as does the relative potency of the various agents.