Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials.
By P. Calverley, K. Rabe, U. Goehring, S. Kristiansen, L. Fabbri, F. Martinez. The Lancet, 2009
818 citations recorded by the source corpus.
BACKGROUND The phosphodiesterase-4 inhibitor roflumilast can improve lung function and prevent exacerbations in certain patients with chronic obstructive pulmonary disease (COPD). We therefore investigated whether roflumilast would reduce the frequency of exacerbations requiring corticosteroids in patients with COPD. METHODS In two placebo-controlled, double-blind, multicentre trials (M2-124 and M2-125) with identical design that were done in two different populations in an outpatient setting, patients with COPD older than 40 years, with severe airflow limitation, bronchitic symptoms, and a history of exacerbations were randomly assigned to oral roflumilast (500 microg once per day) or placebo for 52 weeks. Primary endpoints were change in prebronchodilator forced expiratory volume in 1 s (FEV(1)) and the rate of exacerbations that were moderate (glucocorticosteroid-treated) or severe. Analysis was by intention to treat. The trials are registered with ClinicalTrials.gov, number NCT00297102 for M2-124, and NCT00297115 for M2-125. FINDINGS Patients were assigned to treatment, stratified according to smoking status and treatment with longacting beta(2) agonists, and given roflumilast (n=1537) or placebo (n=1554). In both studies, the prespecified primary endpoints were achieved and were similar in magnitude. In a pooled analysis, prebronchodilator FEV(1) increased by 48 mL with roflumilast compared with placebo (p<0.0001). The rate of exacerbations that were moderate or severe per patient per year was 1.14 with roflumilast and 1.37 with placebo (reduction 17% [95% CI 8-25], p<0.0003). Adverse events were more common with roflumilast (1040 [67%]) than with placebo (963 [62%]); 219 (14%) patients in the roflumilast group and 177 (12%) in the placebo group discontinued because of adverse events. In the pooled analysis, the difference in weight change during the study between the roflumilast and placebo groups was -2.17 kg. INTERPRETATION Since different subsets of patients exist within the broad spectrum of COPD, targeted specific therapies could improve disease management. This possibility should be explored further in prospective studies. FUNDING Nycomed.
Subfields: Molecular Biology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/4699aa798dd761c380dc6be0a65d11a53d9ea8c2
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Citations in the corpus
- Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. (2007, background): “It is also possible to add a phosphodiesterase-4 inhibitor to the treatment chosen as first choice, provided the patient has chronic bronchitis (81).”
- Chronic obstructive pulmonary disease phenotypes: the future of COPD. (2010, background): “Furthermore, a chronic bronchitic subgroup with sputum production and prior exacerbation history has recently identified a COPD cohort who experience improvement with the novel phosphodiesterase 4 inhibitor roflumilast (40).”
- Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. (2017, background): “Roflumilast reduces moderate and severe exacerbations treated with systemic corticosteroids in patients with chronic bronchitis, severe to very severe COPD, and a history of exacerbations.(158) Phosphodiesterase-4 (PDE4) inhibitors have more adverse effects than inhaled medications for COPD.”
- Editorial: Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 Guidelines for COPD, Including COVID-19, Climate Change, and Air Pollution (2023, neutral): “Рофлумиласт поз воляет снизить частоту среднетяжелых и тяжелых обост рений, при которых требуется применение ГКС, на 15–20% у пациентов с хроническим бронхитом, тяжелой и крайне тяжелой ХОБЛ и наличием обострений в анамнезе [266] (уровень доказательности А).”