Clinical outcomes of theophylline use as add-on therapy in patients with chronic obstructive pulmonary disease: A propensity score matching analysis.

ABSTRACT

To examine clinical outcomes of theophylline use in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA). Electronic data from five hospitals located in Northern Thailand between January 2011 and December 2015 were retrospectively collected. Propensity score (PS) matching (21 ratio) technique was used to minimize confounding factors. The primary outcome was overall exacerbations. Secondary outcomes were exacerbation not leading to hospital admission, hospitalization for exacerbation, hospitalization for pneumonia, and all-cause hospitalizations. Cox's proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI). After PS matching, of 711 patients with COPD (mean age 70.1 years; 74.4% male; 60.8% severe airflow obstruction), 474 theophylline users and 237 non-theophylline users were included. Mean follow-up time was 2.26 years. Theophylline significantly increased the risk of overall exacerbation (aHR 1.48, 95% CI 1.11-1.96; p = 0.008) and exacerbation not leading to hospital admission (aHR 1.47, 95% CI 1.06-2.03; p = 0.020). Theophylline use did not significantly increase the risk of hospitalization for exacerbation (aHR 1.11, 95% CI 0.79-1.58; p = 0.548), hospitalization for pneumonia (aHR 1.28, 95% CI 0.89-1.84; p = 0.185), and all-cause hospitalizations (aHR 1.03, 95% CI 0.80-1.33; p = 0.795). Theophylline use as add-on therapy to ICS and LABA might be associated with an increased risk for overall exacerbation in patients with COPD. A large-scale prospective study of theophylline use investigating both safety and efficacy is warranted.