Clinical evaluation of nedocromil sodium in asthma

Abstract

The recognition that inflammatory events in the airways play a key role in the pathogenesis of asthma has led to a relentless search for pharmacological agents which modify these processes. Nedocromil sodium (Tilade) represents one such agent. Nedocromil sodium, when inhaled by patients with asthma (0.05-0.50% nebulized, 0.5-4.0 mg m.d.i.), has been shown to inhibit immediate bronchoconstriction provoked by challenges with allergen (10 studies), exercise (five studies), isocapnic hyperventilation, fog and sulphur dioxide (one study each) and adenosine (two studies). With these challenges, inhibition of bronchoconstriction exhibited dose-dependency up to 4 mg, with nedocromil sodium being up to four times more potent than sodium cromoglycate. When inhaled prior to allergen provocation, nedocromil sodium inhibited the late asthmatic reaction; when taken regularly during the pollen season, it attenuated the allergen-induced increase in non-specific bronchial responsiveness. The efficacy of nedocromil sodium (4 mg q.i.d.) in the treatment of clinical asthma was initially shown in four open studies and subsequently confirmed in nine double-blind, placebo-controlled 4-12 week studies on patients with seasonal and perennial asthma. Further clinical trials (eight studies) identified some difficulty in replacing inhaled corticosteroids with nedocromil sodium, especially if the corticosteroids were reduced rapidly (four studies). However, two studies have shown that nedocromil sodium produced further improvement in asthma symptoms when used in addition to bronchodilators and inhaled corticosteroids. Treatment with nedocromil sodium (4 mg q.i.d.) for up to 52 weeks demonstrated a progressive reduction in bronchodilator usage throughout the whole treatment period. During clinical assessment, nedocromil sodium was well tolerated, side-effects being unpleasant taste, nausea and headache. In most cases the adverse reactions were mild and transient, although in approximately 3% of patients they resulted in withdrawal from clinical trials. Thus, nedocromil sodium is a novel drug of proven efficacy in the treatment of asthma. Its position in the therapeutic armamentarium is likely to be as an adjunct to bronchodilators and inhaled steroids, to produce improvement in symptoms beyond that achieved with the already established drugs.