Journal Article

Effect of 1-Year Treatment with Roflumilast in Severe Chronic Obstructive Pulmonary Disease

Fabbri, Leonardo M, Teichmann, Peter, Calverley, Peter M. A, Bredenbroeker, Dirk, Sanchez-Toril, Fernando, McIvor, Andrew

2007

Overview

Abstract Rationale The oral phosphodiesterase-4 (PDE4) inhibitor, roflumilast, can improve lung function in moderate chronic obstructive pulmonary disease (COPD). Whether treatment is effective in more severe COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages III and IV) over a longer period is unknown. Objectives To determine whether roflumilast improves lung function and decreases exacerbation frequency over 1 year in patients with stable COPD. Methods We conducted a randomized, placebo-controlled, double-blind, parallel-group trial for 1 year. We recruited 1,513 patients (mean post-bronchodilator FEV1 41% predicted), 760 receiving oral 500 μg roflumilast and 753 receiving placebo once daily. Measurements and Main Results We recorded post-bronchodilator FEV1, exacerbation rate, St. George's Respiratory Questionnaire total score at the study end point, and number and type of reported adverse events during treatment. Post-bronchodilator FEV1 increased by 39 ml with roflumilast compared with placebo by 52 weeks (p = 0.001). The mean exacerbation rate was low and comparable in both treatment groups (0.86 vs. 0.92 exacerbations/patient/yr for roflumilast and placebo, respectively). In a retrospective analysis, the exacerbation rate in patients in GOLD stage IV disease was 36% lower in patients treated with roflumilast than in those treated with placebo (1.01 vs. 1.59 exacerbations/patient/year, respectively; p = 0.024). The St. George's Respiratory Questionnaire total score did not differ between treatments. The commonest adverse events related to roflumilast treatment were diarrhea, nausea, and headache, which usually subsided during continued treatment. However, roflumilast resulted in more withdrawals within the first 3 to 4 weeks of administration. Conclusions In severe, stable COPD, PDE4 inhibition with roflumilast produced a modest but significant improvement in lung function without changing the exacerbation rate or health status. However, patients with very severe disease experienced fewer exacerbations with roflumilast.

• Publisher: Am Thoracic Soc,Oxford University Press,American Lung Association
• Subject: Aged / Aminopyridines - administration & dosage / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Asthma / Benzamides - administration & dosage / Biological and medical sciences / Chronic obstructive pulmonary disease / Chronic obstructive pulmonary disease, asthma / Cohort Studies / Cyclopropanes - administration & dosage / Double-Blind Method / Drug Administration Schedule / Female / Health Status / Humans / Intensive care medicine / Lung diseases / Male / Medical sciences / Middle Aged / Patients / Phosphodiesterase Inhibitors - administration & dosage / Pneumology / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - physiopathology / Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases / Quality of Life / Questionnaires / Respiratory Function Tests / Severity of Illness Index / Steroids / Treatment Outcome