The evidence for theophylline use in asthma is limited and of poor quality. Results of head-to-head studies comparing theophylline with other add-on therapies are inconsistent and require further, more robust evaluation. Overall, theophylline appears to be more beneficial than placebo and is at best similar in effectiveness to long-acting beta2-agonists, sodium cromoglicate, and leukotriene receptor antagonists. However, increasing the dose of inhaled corticosteroids (ICS) provides better asthma control than adding in theophylline in poorly controlled asthma. In all comparison studies, theophylline is associated with an increased risk of adverse effects:
- A systematic review (search date May 2006, 35 randomized controlled trials [RCTs], n = 2754) compared oral xanthines (for example theophylline) in children aged 18 months to 18 years [Seddon et al, 2006]:
- Placebo (18 RCTs): xanthine increased the proportion of symptom-free days by 8% (95% CI 3.4 to 12.5) and decreased use of rescue medication, but symptom scores and hospitalizations did not significantly differ.
- ICS (four RCTs): exacerbations were less frequent and symptom improvements were better with ICS, and xanthines were associated with more frequent headaches and nausea. There was no significant difference in lung function.
- Regular short-acting beta2-agonists (ten RCTs): these agents did not significantly affect symptoms or use of rescue medication. They reduced hospitalizations and headaches but increased tremor.
- Sodium cromoglicate (six RCTs): no significant differences in symptoms, exacerbations, or rescue medication use were observed. Xanthines had more gastrointestinal adverse effects.
- A recent RCT (n = 489) randomized people with poorly controlled asthma to placebo, theophylline 300 mg/day, or montelukast 10 mg/day, for 24 weeks. Rates of episodes of poor asthma control, asthma symptoms, and quality of life did not differ significantly among groups. Theophylline and montelukast provided small improvements in the pre-bronchodilator forced expiratory volume in 1 second, which were of borderline significance. However, in people not taking ICS, asthma control, symptoms, and lung function improved more with low-dose theophylline than with montelukast or placebo [American Lung Association Asthma Clinical Research Centers, 2007].