Low-dose theophylline in mild to moderate Chronic Obstructive Pulmonary Disease: A randomized clinical trial in China

Low-dose theophylline has anti-inflammatory effects, but its efficacy in mild to moderate COPD remains controversial.

Is low dose theophylline effective and safe in patients with mild to moderate COPD?

In this prospective, parallel-group, randomised, double-blind, placebo-controlled trial across ten centres in China, subjects with mild to moderate COPD were randomized 2:1 to oral low-dose theophylline sustained-release tablets (100 mg twice daily) or matching placebo for 12 months. Primary endpoints were between-group differences in pre-bronchodilator FEV₁ change from baseline to 12 months and annual exacerbation rate.

734 subjects were randomized; 615 completed the study. Compared with placebo, low-dose theophylline significantly ameliorated FEV₁ before bronchodilator use by 30 ml [95% CI, 3 to 57 ml] (p = 0.031) at month 12, with a between-group difference in mean change from baseline of 28 ml/year [95% CI, -2 to 58 ml/year] (p = 0.063). The annual exacerbation rate did not differ between groups (0.46 ± 0.03 vs 0.43 ± 0.04 per patient-year; RR, 1.07 [95% CI, 0.84 to 1.36]; p = 0.607). In addition, the incidence of adverse events was comparable between both groups.

In mild to moderate COPD, low-dose theophylline was well-tolerated but did not reduce exacerbation rates. A modest improvement in pre-bronchodilator FEV₁ was observed, though its magnitude was limited. Larger trials are needed to further evaluate its potential to improve lung function in this population.