Benefit-risk assessment of antileukotrienes in the management of asthma

Antileukotrienes are a relatively new class of anti-asthma drugs that either block leukotriene synthesis (5-lipoxygenase inhibitors) like zileuton, or antagonise the most relevant of their receptors (the cysteinyl leukotriene I receptor [CysLT1]) like montelukast, zafirlukast or pranlukast. Hence, their major effect is an anti-inflammatory one. With the exception of pranlukast, the other antileukotrienes have been studied and marketed in the US and Europe for long enough to establish that they are useful drugs in the management of asthma. Their effects, significantly better than placebo, seem more pronounced in subjective measurements (i.e. symptoms scores or quality-of-life tests) than in objective parameters (i.e. forced expiratory volume in 1 second or peak expiratory flow rate). Also, there is some evidence that these drugs work better in some subsets of patients with certain genetic polymorphisms - probably related to their leukotriene metabolism - or patients with certain asthma characteristics. There are a small number of comparative studies only, and with regard to long-term asthma control differences between the agents have not been evaluated. Nevertheless, their overall effect appears comparable with sodium cromoglycate (cromolyn sodium) or theophylline, but significantly less than low-dose inhaled corticosteroids, Antileukotrienes have been shown to have a degree of corticosteroid-sparing effect, but salmeterol appears to perform better as an add-on drug. Montelukast is probably the most useful antileukotriene for continuous treatment of exercise-induced asthma. performing as well as salmeterol without inducing any tolerance. All antileukotrienes. are taken orally; their frequency of administration is quite different ranging from four times daily (zileuton) to once daily (montelukast). Antileukotrienes are well tolerated drugs, even though Menton intake has been related to transitional liver enzyme elevations in some cases. Also Churg-Strauss syndrome (a systemic vasculitis), has been described in small numbers of patients taking CysLT1 antagonists. It is quite probable that this disease appears as a consequence of an 'unmasking' effect when, corticosteroid dosages are reduced in patients with severe asthma once CysLT1 antagonists are introduced, but more data are needed to definitely establish the mechanism behind this effect. Overall, however, the benefits of antileukotrienes in the treatment of asthma greatly outweigh their risks.