RATIONALE: Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations. Further characterization of patients most likely to benefit is warranted. OBJECTIVES: Define characteristics that most robustly identify patients who derive greatest exacerbation risk reduction with roflumilast. METHODS: Predefined, pooled analyses of REACT (NCT01329029) and RE(2)SPOND (NCT01443845) multicenter, randomized, double-blind, placebo-controlled studies. The primary endpoint was rate of moderate or severe exacerbations per patient per year. MAIN RESULTS: In the overall intention-to-treat population (n=4,287), roflumilast reduced moderate or severe exacerbations by 12.3% (rate ratio 0.88 [95% confidence interval: 0.80-0.97], p=0.0086) and severe exacerbations by 16.1% (0.84 [0.71-0.99], p=0.0409) vs. placebo. The reduction in the rate of moderate or severe exacerbations with roflumilast was most pronounced in subgroups of patients who had either been hospitalized for an exacerbation in the prior year (0.74 [0.63-0.88], p=0.0005), had >2 exacerbations in the prior year (0.79 [0.65- 0.96], p=0.0160), or had baseline eosinophils >/=150x10(6)/L (0.81 [0.71-0.93], p=0.0020) or >/=300x10(6)/L (0.77 [0.61- 0.97], p=0.0264). Similar subgroup results were noted for severe exacerbations. In patients with characteristics of prior hospitalization and elevated levels of baseline blood eosinophils, roflumilast reduced the rate of moderate or severe exacerbations by 34.5% at the >/=150x10(6)/L threshold (0.65 [0.52-0.82], p=0.0003) and 42.7% at the >/=300x10(6)/L threshold (0.57 [0.37-0.88], p=0.0111) vs. placebo. CONCLUSIONS: This pre-specified, pooled analysis confirms the benefit of roflumilast in decreasing exacerbations in patients with prior hospitalization for exacerbation, greater exacerbation frequency, and elevated (>300x10(6)/L) baseline blood eosinophil count. Clinical trial registration available at www.clinicaltrials.gov, IDs NCT01329029 and NCT01443845.
- Martinez, F. J.
- Rabe, K. F.
- Calverley, P. M. A.
- Fabbri, L. M.
- Sethi, S.
- Pizzichini, E.
- McIvor, A.
- Anzueto, A.
- Alagappan, V. K. T.
- Siddiqui, S.
- Reisner, C.
- Zetterstrand, S.
- Roman, J.
- Purkayastha, D.
- Bagul, N.
- Rennard, S. I.
Keywords
- *cigarette smoking
- *cough
- *glucocorticosteroids
- *inflammation
- *sputum
