Low-dose theophylline shows modest FEV improvement but no exacerbation reduction in mild to moderate COPD

This 12-month, multicenter, randomized clinical trial conducted at ten centers in China evaluated oral low-dose theophylline sustained-release tablets (100 mg twice daily) versus matching placebo in 734 patients with mild to moderate COPD; 615 subjects completed the study.

The primary outcomes were between-group differences in pre-bronchodilator FEV change from baseline to 12 months and annual exacerbation rate. At 12 months, low-dose theophylline significantly improved pre-bronchodilator FEV by 30 ml compared with placebo (95% CI, 3 to 57 ml; p=0.031). However, the between-group difference in mean FEV change from baseline per year was 28 ml/year and was not statistically significant (95% CI, -2 to 58 ml/year; p=0.063). The annual exacerbation rate did not differ between groups (rate ratio 1.07; 95% CI, 0.84 to 1.36; p=0.607), with rates of 0.46 ± 0.03 versus 0.43 ± 0.04 per patient-year for theophylline and placebo, respectively.

Safety data indicated the treatment was well-tolerated, with a comparable incidence of adverse events between groups. The study reported 119 subjects did not complete the trial. Key limitations include the publication being an abstract only, with full methodological details, serious adverse event data, and funding/conflict disclosures not reported. The practice relevance is restrained: while a statistically significant but modest improvement in pre-bronchodilator FEV was observed, the magnitude is limited (30 ml), and no benefit on exacerbation rates was demonstrated. Larger trials are needed to further evaluate its potential.