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Clinical Trial of Low-Dose Theophylline and Montelukast in Patients with Poorly Controlled Asthma

Correspondence and requests for reprints should be addressed to Robert A. Wise, M.D., Johns Hopkins Asthma & Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail: rwise{at}jhmi.edu

Background: Asthma treatment guidelines recommend addition of controller medications for patients with poorly controlled asthma. We compared the effectiveness of once-daily oral controller therapy with either an antileukotriene receptor antagonist (montelukast) or low-dose theophylline added to existing medications in patients with poorly controlled asthma.

Methods: We conducted a randomized, double-masked, placebo-controlled trial in 489 participants with poorly controlled asthma randomly assigned to placebo, theophylline (300 mg/d), or montelukast (10 mg/d). Participants were monitored for 24 wk to measure the rate of episodes of poor asthma control (EPACs) defined by decreased peak flow, increased -agonist use, increased oral corticosteroid use, or unscheduled health care visits.

Observations: There was no significant difference in EPAC rates (events/person/yr) compared with placebo: low-dose theophylline, 4.9 (95% confidence interval [CI], 3.6–6.7; not significant); montelukast, 4.0 (95% CI, 3.0–5.4; not significant); and placebo, 4.9 (95% CI, 3.8–6.4). Both montelukast and theophylline caused small improvements in prebronchodilator FEV₁ of borderline significance. Nausea was more common with theophylline only during the first 4 wk of treatment. Neither treatment improved asthma symptoms or quality of life. However, in patients not receiving inhaled corticosteroids, addition of low-dose theophylline significantly (p < 0.002) improved asthma control and symptoms as well as lung function.

Conclusions: Neither montelukast nor low-dose theophylline lowered the EPAC rate of poor asthma control in patients with poorly controlled asthma despite improved lung function. For patients not using inhaled corticosteroids, low-dose theophylline improved asthma symptom control more than montelukast or placebo, and provides a safe and low-cost alternative asthma treatment.

Key Words: antiasthmatic agents • bronchodilator agents • clinical trial • multicenter studies

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Low-dose theophylline and montelukast are effective antiinflammatory agents that improve lung function, but their role in the treatment of poorly controlled asthma is not known. What This Study Adds to the Field This clinical trial showed that low-dose theophylline and montelukast do not improve asthma control, but that low-dose theophylline was beneficial in those patients who had not been prescribed inhaled corticosteroids.

 

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