COPD exacerbations contribute to the morbidity and mortality of COPD. A pooled post hoc analysis taking into account the frequency and duration of COPD exacerbations was conducted to determine the overall effect of cilomilast (CIL), a selective phosphodiesterase 4 inhibitor, on exacerbations.
Four 24-week, double-blind, placebo-controlled, parallel-group, multicenter studies of identical design were conducted to evaluate efficacy and safety of CIL 15mg BID. Eligible patients were 40 to 80 years of age with COPD, who were nonreversible to beta-agonists (less than 15% and/or less than 200ml increase over baseline FEV1), >10 pack-year history of smoking, a FEV1/FVC ratio less than 0.7 and FEV1 between 30% and 70% of predicted. Level 2 exacerbations were those requiring additional treatment to be prescribed as a result of a physician office visit and level 3 exacerbations were those requiring hospitalization. The probability of experiencing a level 2/3 exacerbation on any given day was compared between treatment groups using repeated measures logistic regression implemented using generalized estimating equations with model adjustments for study, age, gender, and baseline FEV1 percent predicted.
1091 placebo and 1792 CIL patients were randomized. Mean age was 64 years with postbronchodilator mean FEV1 50% of predicted. The estimated probability of experiencing a level 2/3 exacerbation on any given day, the relative risk, odds ratio with 95% confidence interval (CI) and p value comparing treatments are reported in the tableEstimated Probability of Experiencing a Level 2/3 Exacerbation on any Given DayPlaceboCIL (n=1792)RelativeOdds ratiop-value (n=1091)Risk(95% CI)3.33%2.53%76%0.75 (0.61, 0.93)0.008below.
COPD patients treated with CIL are 24% less likely to experience an exacerbation on any given day compared to placebo treated patients.
Since quality of life and progression of COPD may be linked to the rate of exacerbations, this reduction in COPD exacerbations supports the use of CIL in patients with COPD.
C. Reisner, GlaxoSmithKline, Discussion of product research or unlabeled uses of product.