Devereux G, et al. - Authors assessed the efficacy of adding low-dose theophylline to inhaled corticosteroids in patients with chronic obstructive pulmonary disease (COPD). Over a 1-year period, the addition of low-dose theophylline did not reduce the number COPD exacerbations among adults with COPD at high risk of exacerbation treated with inhaled corticosteroids vs placebo. Thus, study findings did not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations.

Methods

• This pragmatic, double-blind, placebo-controlled, randomized clinical trial involved 1,578 patients with COPD (enrolled February 6, 2014, to August 31, 2016).
• Patients were followed up until August 31, 2017.
• Patients had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV₁/FVC) of < 0.7 with ≥ 2 exacerbations (treated with antibiotics, oral corticosteroids, or both) in the previous year and were using an inhaled corticosteroid.
• Researchers randomized the participants to receive low-dose theophylline (200 mg once or twice per day) to provide plasma concentrations of 1 to 5 mg/L (determined by ideal body weight and smoking status; n=791) or placebo (n=787).
• Main outcomes and measures included the number of participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids, or both over the 1-year treatment period.

Results

• Following 11 post-randomization exclusions, a total of 1,567 participants were included in the analysis (theophylline, n=788; placebo, n=779; mean [SD] age: 68.4 (8.4) years; 54% men).
• Data for evaluation of the primary outcome were available for 1,536 participants (98%; theophylline group, n=772; placebo group, n=764).
• Findings suggested that, there were 3,430 exacerbations: 1,727 in the theophylline group (mean, 2.24 [95% CI, 2.10-2.38] exacerbations per year) vs 1,703 in the placebo group (mean, 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference, 0.01 (95% CI, -0.19 to 0.21) and adjusted incidence rate ratio, 0.99 (95% CI, 0.91-1.08).
• Cardiac, 2.4% vs 3.4%; gastrointestinal, 2.7% vs 1.3%; and adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%) were included in serious adverse events in the theophylline and placebo groups.
• Serious adverse events in the theophylline and placebo groups included cardiac (2.4% vs 3.4%) and gastrointestinal (2.7% vs 1.3%), as well as adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%).