Vulnerable COPD patients with comorbidities: the role of roflumilast

Figures & data

Table 1 Summary of clinical efficacy trials evaluating roflumilast

Trial	Patient population	Methods	Regimen	Results
Rabe et al 2005^Citation26	• N=1,413 • Moderate-to-severe COPD	• 24-week, Phase III, R, DB, PC, MC, MN • Primary: post-bronchodilator FEV1, SGRQ • Secondary: number of COPD exacerbations	• Roflumilast 250 μg versus roflumilast 500 μg versus placebo	• Change in FEV1 versus placebo: 74 mL for roflumilast 250 μg; 97 mL for roflumilast 500 μg (P<0.03) • Change in SGRQ versus placebo: −1.6 units for roflumilast 250 μg; −1.7 units for roflumilast 500 μg (P=0.077 and 0.053, respectively) • Mean number of exacerbations/patient: 1.3 for placebo, 1.03 for roflumilast 250 μg, and 0.75 for roflumilast 500 μg (P=0.0029)
Calverley et al 2007^Citation27	• N=1,514 • Severe-to-very severe COPD	• 1-year, Phase III, R, DB, PC, MC, MN • Primary: post-bronchodilator FEV1, number of moderate or severe exacerbations/patient/year • Secondary: SGRQ	• Roflumilast 500 μg versus placebo	• Change in FEV1 versus placebo: 39 mL (P=0.001) • Rate of exacerbations: 0.86 versus 0.92/patient/year (P=0.0451)
Calverley et al 2009^Citation28	• N=3,091 • Severe-to-very severe COPD with chronic cough and sputum production and at least one COPD exacerbation requiring systemic CS or hospitalization or both in the past year	• 1-year, Phase III, R, DB, PC, MC, MN • Primary: pre-bronchodilator FEV1, rate of moderate-to-severe exacerbations • Secondary: TDI focal score	• Roflumilast 500 μg versus placebo	• Change in FEV1 versus placebo: 48 mL (P<0.0001) • Rate of exacerbations: 1.14 versus 1.37/patient/year (P=0.003) • Change in TDI focal score versus placebo: 0.3 (P=0.0009)
Fabbri et al 2009^Citation29 (study 1)	• N=933 • Moderate-to-severe COPD	• 24-week, Phase III, R, DB, PC, MC, MN • Primary: pre-bronchodilator FEV1 • Secondary: rates of COPD exacerbations, TDI, SOBQ	• Roflumilast 500 μg + salmeterol versus placebo + salmeterol	• Change in FEV1: 49 mL versus placebo (P<0.0001) • Rate of exacerbations: 1.9 versus 2.4/patient/year (P=0.1408) • Change in TDI focal score: 0.1 versus placebo (P=0.4654) • Change in SOBQ: 0.5 versus placebo (P=0.5457)
Fabbri et al 2009^Citation29 (study 2)	• N=744 • Moderate-to-severe COPD with chronic cough and sputum production and frequent use of SABA	• 24-week, Phase III, R, DB, PC, MC, MN • Primary: pre-bronchodilator FEV1 • Secondary: rates of COPD exacerbations, TDI, SOBQ	• Roflumilast 500 μg + tiotropium versus placebo + tiotropium	• Change in FEV1: 80 mL versus placebo (P<0.0001) • Rate of exacerbations: 1.8 versus 2.2/patient/year (P=0.3573) • Change in TDI focal score: 0.4 versus placebo (P=0.0032) • Change in SOBQ: −2.6 versus placebo (P=0.0051)
Lee et al 2011^Citation31	• N=551 • Moderate-to-severe COPD	• 12-week, SB, PC • Primary: mean change in post-bronchodilator FEV1 from baseline • Secondary: mean change in pre-bronchodilator FEV1 from baseline, exacerbation rates	• Roflumilast 500 μg versus placebo	• Change in FEV1 post-bronchodilator: 79 mL versus placebo (P<0.0001) • Change in FEV1 pre-bronchodilator from baseline: 95 mL versus placebo (P<0.0001) • Rate of exacerbations: 10 (4.9%) roflumilast versus 15 (7.2%) placebo (P-value not reported)
Zheng et al 2014^Citation32	• N=626 • Severe-to-very severe COPD	• 24-week, DB, PC, MC, parallel-group • Primary: mean change in pre-bronchodilator FEV1 from baseline • Secondary: mean change in post-bronchodilator FEV1 from baseline, FVC, TDI, exacerbation rates	• Roflumilast 500 μg versus placebo	• Change in FEV1 pre-bronchodilator from baseline: 71 mL versus placebo (P<0.0001) • Change in FEV1 post-bronchodilator from baseline: 65 mL versus placebo (P<0.0001) • Change in FVC pre-bronchodilator from baseline: 109 mL versus placebo (P<0.0001) • Change in FVC post-bronchodilator from baseline: 101 mL versus placebo (P<0.0001) • Rate of exacerbations: no difference between groups (numeric values not provided) • Change in TDI score: no differences (numeric values not provided)

Abbreviations: COPD, chronic obstructive pulmonary disease; CS, corticosteroids; DB, double-blind; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; MC, multicenter; MN, multinational; PC, placebo-controlled; R, randomized; SABA, short acting beta-2 agonist; SB, single-blind; SGRQ, St George’s Respiratory Questionnaire; SOBQ, shortness of breath questionnaire; TDI, transition dyspnea index.

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