Tags

Type your tag names separated by a space and hit enter

Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials.
Lancet 2009; 374(9691):685-94Lct

Abstract

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.

Authors+Show Affiliations

School of Clinical Sciences, Liverpool, UK. pmacal@liverpool.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19716960

Citation

Calverley, Peter M A., et al. "Roflumilast in Symptomatic Chronic Obstructive Pulmonary Disease: Two Randomised Clinical Trials." Lancet (London, England), vol. 374, no. 9691, 2009, pp. 685-94.
Calverley PM, Rabe KF, Goehring UM, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009;374(9691):685-94.
Calverley, P. M., Rabe, K. F., Goehring, U. M., Kristiansen, S., Fabbri, L. M., & Martinez, F. J. (2009). Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet (London, England), 374(9691), pp. 685-94. doi:10.1016/S0140-6736(09)61255-1.
Calverley PM, et al. Roflumilast in Symptomatic Chronic Obstructive Pulmonary Disease: Two Randomised Clinical Trials. Lancet. 2009 Aug 29;374(9691):685-94. PubMed PMID: 19716960.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. AU - Calverley,Peter M A, AU - Rabe,Klaus F, AU - Goehring,Udo-Michael, AU - Kristiansen,Søren, AU - Fabbri,Leonardo M, AU - Martinez,Fernando J, AU - ,, PY - 2009/9/1/entrez PY - 2009/9/1/pubmed PY - 2009/9/12/medline SP - 685 EP - 94 JF - Lancet (London, England) JO - Lancet VL - 374 IS - 9691 N2 - 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. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/19716960/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(09)61255-1 DB - PRIME DP - Unbound Medicine ER -