Long-acting beta2-agonists versus theophylline for maintenance treatment of asthma

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Abstract
Background Theophylline and long acting beta‐2 agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side‐effect profiles. Objectives To assess the comparative efficacy, safety and side‐effects of long‐acting beta‐2 agonists and theophylline in the maintenance treatment of adults and adolescents with asthma. Search methods We searched the Cochrane Airways Group trials register and reference lists of articles. We also contacted authors of identified RCTs for other relevant published and unpublished studies and pharmaceutical manufacturers. Most recent search: April 2004. Selection criteria All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long‐acting beta‐2 agonist. Data collection and analysis In original review, two reviewers independently assessed trial quality and extracted data, in the update only one reviewer undertook this. Study authors were contacted for additional information. Main results Twelve studies with a total of 1329 participants met the inclusion criteria of the review. They were of varying quality. Salmeterol improved forced expiratory volume in one second (FEV1) significantly more than theophylline in five studies and salmeterol use was associated with significantly more symptom free nights in all the studies comparing these agents. Formoterol, used in two studies was reported to be as effective as theophylline. Bitolterol, used in only one study, was reported to be less effective than theophylline. Participants taking salmeterol experienced fewer adverse events than those using theophylline (Parallel studies: Relative Risk 0.44; 95% confidence interval (CI) 0.30 to 0.63), Risk Difference ‐0.11; 95% CI ‐0.16 to ‐0.07), Numbers Needed to Treat (NNT) 9; 95% CI 6 to 14. Significant reductions were reported for central nervous system adverse events (Relative Risk 0.50; 95% CI 0.29 to 0.86), Risk Difference ‐0.07; 95% CI ‐0.12 to ‐0.02), NNT 14; 95% CI 8 to 50) and gastrointestinal adverse events (Relative Risk 0.30; 95% CI 0.17 to 0.55), Risk Difference ‐0.11; 95% CI ‐0.16 to ‐0.06), NNT 9; 95% CI 6 to 16). An update search conducted in April 2004 did not identify any further studies for inclusion. Authors' conclusions Long‐acting beta‐2 agonists are at least as effective than theophylline in reducing asthma symptoms including night waking and improving lung function. Fewer adverse events occurred in participants using long‐acting beta‐2 agonists(salmeterol and formoterol) as compared to theophylline.