A risk-benefit assessment of antileukotrienes in asthma

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) or inhibit leukotriene synthesis (leukotriene synthesis inhibitors). Studies performed in individuals without asthma and patients with asthma reveal that antileukotrienes prevent the bronchoconstriction produced by exercise, cold-air, allergen, aspirin (acetylsalicylic acid) and sulphur dioxide. Except for the setting of aspirin sensitivity where the antileukotrienes are nearly uniformly effective, individual responses to them are variable with complete protection in some, no protection in others and a modest degree of protection in the majority. The antileukotrienes bronchodilate the airways of patients with baseline bronchoconstriction, although usually not as well as beta-agonists. When given for weeks to months they rapidly improve pulmonary function and symptoms in patients with mild-to-moderate asthma, and probably in patients with more severe asthma as well, and these improvements persist for the duration of treatment. Here too, their beneficial effects are variable and not predictable based on clinical criteria. Recent studies suggest they can reduce asthma-induced airway inflammation and are equal or more effective than sodium cromoglycate, but equal or less effective than low-to-moderate dosages of inhaled corticosteroids. Initial experience with the antileukotrienes reveals limited toxicity and what appears to be a favourable therapeutic-to-toxic ratio. However, exposure of more patients with differing characteristics for longer periods of time is needed to substantiate this initial impression. The exact role of the antileukotrienes in the treatment of asthma remains to be determined, as does the relative potency of the various agents.