EVIDENCE-BASED ANSWER
Nedocromil (Tilade) is effective for the treatment of mild persistent asthma. It has not been shown to be effective in more severe forms of asthma for both children and adults. Although no studies looked specifically at exacerbation rates, multiple clinical and biologic outcomes (symptom scores, quality of life measures, bronchodilator use, forced expiratory flow in 1 second [FEV1], and peak expiratory flow rate [PEFR]) improved with nedocromil use compared with placebo.
The most effective dose for preventing exacerbations appears to be 4 mg (2 puffs) 4 times a day (SOR: A, multiple randomized controlled trials [RCTs] and meta-analyses). More severe forms of asthma respond better to inhaled steroids than to nedocromil (SOR: A, multiple RCTs). Nedocromil may allow some patients with severe asthma to use lower doses of inhaled steroids (SOR: C, conflicting RCTs). Nedocromil is also effective for the treatment of exercise-induced asthma (SOR: A, multiple RCTs and meta-analyses).
In general, about 50% to 70% of patients respond to nedocromil (SOR: A, multiple RCTs and meta-analyses). Unfortunately, which patients respond is not predictable from clinical parameters.1 Nedocromil is worth trying in mild persistent asthma, particularly for children where the parents are worried about the growth issues associated with inhaled steroids. Side effects (sore throat, nausea, and headache) are mild and infrequent. Maximal efficacy is usually seen after 6 to 8 weeks.
Evidence summary
A systematic review encompassing 127 trial centers and 4723 patients concluded that inhaled nedocromil was effective for a variety of patients with asthma. Significant improvements were noted in FEV1, PEFR, use of bronchodilators, symptom scores, and quality of life scores. The reviewers found nedocromil to be most effective for patients with moderate disease already taking bronchodilators,2 corresponding to the “mild persistent asthma” category ( Table ).
A contemporaneous European RCT, not included in the review, compared 4 mg of inhaled nedocromil 4 times daily with inhaled placebo among 209 asthmatic children for 12 weeks.3 After 8 weeks, they found a statistically significant reduction in total daily asthma symptom scores (50% nedocromil vs 9% placebo; P<.01). The proportion of parents and children rating treatment as moderately or very effective was 78% in the treatment group and 59% in the placebo group (number needed to treat [NNT]=5.2; P<.01); clinicians’ ratings were 73% for nedocromil and 50% for placebo (NNT=4.3; P<.01). The frequency of side effects—including nausea, headache, and sleepiness—did not reach statistical significance; however, the nedocromil group reported up to a 20% incidence of sore throat. Most of the studies reported no dropouts due to side effects.
When patients are already using inhaled steroids, the evidence is less clear whether nedocromil confers additional benefits, such as fewer exacerbations or lower inhaled steroid doses. Two small studies of patients either already on inhaled steroids4 or considered to be steroid-resistant5 found nonsignificant trends towards reductions in bronchodilator use, increased PEFR, increased FEV1, and improved quality of life. Although both studies were underpowered, the study on steroid-resistant asthma did find a statistically significant 20% improvement in PEFR and decreased bronchodilator use for 50% of patients at 8 and 12 weeks.