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

Tee A, Koh MS, Gibson PG, Lasserson TJ, Wilson A, Irving LB

Published Online:

July 8, 2009

This review compared three asthma medications, salmeterol, formoterol (both long acting beta-agonists) and theophylline. These medications are used to help control symptoms of asthma, especially those which occur during the night. This review found that salmeterol showed a greater improvement in lung function, and reduced the need for extra short-term inhalers in the day and the night. Salmeterol and formoterol are less likely to produce side-effects (such as headaches and nausea) when compared to theophylline.

Abstract (click to read)

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 strategy:

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 We also contacted authors of identified RCTs for other relevant published and unpublished studies and pharmaceutical manufacturers.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: November 2007.

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, similarly in this update two reviewers undertook this. Study authors were contacted for additional information.

Main results:

Thirteen studies with a total of 1344 participants met the inclusion criteria of the review. They were of varying quality. There was no significant difference between salmeterol and theophylline in FEV1 predicted (6.5%; 95% CI -0.84 to 13.83). However, salmeterol treatment led to significantly better morning PEF (mean difference 16.71 L/min, 95% CI 8.91 to 24.51) and evening PEF (mean difference 15.58 L/min, 95% CI 8.33 to 22.83). Salmeterol also reduced the use of rescue medication. 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% 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).

Authors' conclusions:

Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

This record should be cited as:

Tee A, Koh MS, Gibson PG, Lasserson TJ, Wilson A, Irving LB. Long-acting beta2-agonists versus theophylline for maintenance treatment of asthma. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD001281. DOI: 10.1002/14651858.CD001281.pub2

Assessed as up to date:

November 15, 2007

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Primary Review Group:

Airways Group

Asthma topics:

Treating with Medications > Chronic Asthma > Beta-agonists, long-acting

Treating with Medications > Chronic Asthma > Xanthines

Health topics:

Lungs & airways > Asthma (chronic) > Bronchodilators

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

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

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