PURPOSE: Disease severity is associated with increased frequency of acute exacerbations of COPD (AECOPD). Some patients experience repeated AECOPD. These frequent AECOPD result in decreased quality of life, increased hospitalizations, and mortality. Therefore, preventing not only the first AECOPD event but also subsequent exacerbations is likely important. Roflumilast is approved to reduce the risk of AECOPD in COPD patients with severe spirometric disease, chronic bronchitis, and a history of AECOPD. This post hoc analysis examines the effect of roflumilast in delaying the time to first AECOPD and its effects on reducing the risk of subsequent AECOPD events (up to the 5th).
METHODS: Roflumilast (500 μg QD) was examined in two 52-week pivotal trials (M2-124 and M2-125) in severe-to-very severe COPD patients with ≥1 moderate or severe AECOPD in the previous year. Data were pooled for the efficacy of roflumilast compared with placebo for median days to first moderate or severe AECOPD (Kaplan-Meier estimate), and hazard ratios (HR) for first, second, third, fourth, and fifth moderate or severe AECOPD (Cox proportional hazards model).
RESULTS: A total of 3091 patients were treated with roflumilast (n=1537) or placebo (n=1554). As previously shown, the median time to first AECOPD was longer with roflumilast (303 days) than placebo (236 days). The results below enumerate the HR for time to AECOPD for roflumilast compared with placebo. 1st AECOPD HR=0.886 (95% CI 0.802-0.980; P=0.019) 2nd AECOPD HR=0.791 (95% CI 0.685-0.914; P=0.001) 3rd AECOPD HR=0.730 (95% CI 0.593-0.899; P=0.003) 4th AECOPD HR=0.596 (95% CI 0.437-0.814; P=0.001) 5th AECOPD HR=0.477 (95% CI 0.297-0.764; P=0.002)
CONCLUSIONS: Roflumilast significantly delayed time to the first AECOPD, while also decreasing the risk of up to a fifth AECOPD in severe-to-very severe COPD patients compared with placebo.
CLINICAL IMPLICATIONS: These data suggest a decrease in exacerbation burden with roflumilast therapy.
DISCLOSURE: Fernando Martinez: Consultant fee, speaker bureau, advisory committee, etc.: GSK, MedImmune/Astra Zeneca, Merck, Pearl, Novartis, UBC, Forest/Almirall, Actelion, Boehringer Ingelheim, Nycomed/Forest, Ikaria, Roche, Bayer, Schering, HLS, Talecris, Comgenix, fb Communications, BoomComm and Actelion, NACE, MedEd, Potomac, Pfizer, Schering, Vox Medic, American Lung Association, WebMD, ePocrates, Astra Zeneca, France Foundation, CMEincite and Altana/Nycomed, Grant monies (from industry related sources): Boehringer Ingelheim, Other: Associates in Medical Marketin, Castle Connolly, France Foudation, HIT Global and ePocrates
Amir Sharafkhaneh: Consultant fee, speaker bureau, advisory committee, etc.: GSK, AZ, DEY, Pfizer and BI, Grant monies (from industry related sources): GSK, AZ, DEY, Pfizer, BI and Forest
Klaus Rabe: Consultant fee, speaker bureau, advisory committee, etc.: AstraZeneca, Boehringer-Ingelheim, Chiesi Farmaceutici, Forest, GlaxoSmithKline, Merck, Novartis, Nycomed, and Pfizer, Grant monies (from industry related sources): Altana, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Roche
Udo-Michael Goehring: Employee: Nycomed GmbH
Manja Brose: Employee: Nycomed GmbH
Dirk Bredenbroeker: Employee: Nycomed GmbH
Hassan Lakkis: Employee: Forest Research Institute
Paul Rowe: Employee: Forest Research Institute
Ulo Palm: Employee: Forest Research Institute
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