Roflumilast, a once–daily oral selective phosphodiesterase–4 inhibitor, has been shown to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Moderate or severe exacerbations of COPD typically require alterations in treatment and can result in hospitalization. One possible symptom during an exacerbation that can lead to hospitalization is worsening dyspnea (shortness of breath); reducing the risk of exacerbations in COPD patients with a history of exacerbations may improve dyspnea. This study investigated the effect of roflumilast treatment on dyspnea–related outcomes in COPD patients.
Data is from Study M2–111 (OPUS), a 52–week randomized, double–blind, placebo–controlled, parallel group phase 3 clinical trial of roflumilast 500 mg once daily in patients with COPD. The Transition Dyspnea Index Questionnaire (TDI) focal score was used to measure breathlessness as an impairment of patients’ daily living. TDI compares the health state to that measured by the Baseline Dyspnea Index (BDI) and thus by definition it relates to changes from baseline. For TDI, a focal score =1 unit improvement is generally accepted as a minimal clinically important difference. An analysis was performed on the overall patient population, subpopulation with a history of exacerbations, and subpopulation with chronic bronchitis. In each treatment group, the proportion of patients with improvements or deteriorations in TDI focal score of =1 unit at Week 52 (last observation carried forward) was calculated and was compared using chi–square test.
A total of 1,173 COPD patients were enrolled in the trial: 567 in the roflumilast group and 606 in the placebo group. The proportion of patients with improvements in TDI focal score of =1 unit was significantly greater in the roflumilast group than in the placebo group in the overall population (38.70% vs. 30.92%, P=0.0059), subpopulation with a history of exacerbations (38.85% vs. 29.63%, P=0.0040), and subpopulation with chronic bronchitis (41.46% vs. 33.06%, P=0.0193). The proportion of patients with deteriorations in TDI focal score of =1 unit was significantly lower in the roflumilast group than in the placebo group in the overall population (16.85% vs. 25.55%, P=0.0004), subpopulation with a history of exacerbations (15.83% vs. 26.14%, P=0.0002), and subpopulation with chronic bronchitis (15.69% vs. 23.31%, P=0.0097).
An analysis of clinical trial data demonstrated that roflumilast improves dyspnea outcomes in COPD patients, particularly among those with a history of exacerbations. Reducing exacerbations for COPD patients with a history of exacerbations may improve health status.