O2.1 Methylxanthines

Theophylline is rarely used for COPD in Australia.  A small randomised placebo controlled trial in China demonstrated that doses of 100mg twice daily reduced exacerbations compared with placebo (Zhou 2006).  In this study, patients were not on inhaled corticosteroids or long-acting bronchodilators which limits the generalisability of the study findings.  Devereux et al randomised 1,567 UK-based COPD patients with a history of exacerbations to theophylline or placebo.  All patients were receiving inhaled corticosteroids and 80% of patients were on ‘triple-therapy’ (Devereux 2018). An RCT of low dose theophylline plus low dose oral prednisone, theophylline or placebo in 1,670 patients with COPD in China found no statistically significant differences in exacerbation rates, hospitalisations, FEV1, SGRQ and CAT scores at 48 weeks (Jenkins 2020) [evidence level II].

A meta-analysis of 4 RCTs and 3 cohort studies (n=47,556) examined the addition of theophylline to inhaled corticosteroids.  Of the 7 studies reviewed, 4 used an ICS/LABA combination, 2 used ICS alone and 1 trial did not specify. Theophylline was associated with a higher hospitalization rate (HR 1.12, 95% CI 1.10-1.15), and mortality (HR 1.19, 95% CI 1.14-1.25) (Shuai 2021) [evidence level I].

Based on the available evidence, theophylline cannot be recommended for patients with COPD.