Efficacy of Roflumilast in the COPD Frequent Exacerbator Phenotype
Background COPD exacerbations are associated with increased morbidity and mortality and can accelerate disease progression. The best predictor of future exacerbations is a history of previous exacerbations, which helps identify a frequent exacerbator phenotype. This post hoc analysis evaluated the e...
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| Veröffentlicht in: | Chest 2013-05, Vol.143 (5), p.1302-1311 |
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| creator | Wedzicha, Jadwiga A., MD Rabe, Klaus F., MD Martinez, Fernando J., MD Bredenbröker, Dirk, MD Brose, Manja, MS Goehring, Udo-Michael, MD Calverley, Peter M.A., MD |
| description | Background COPD exacerbations are associated with increased morbidity and mortality and can accelerate disease progression. The best predictor of future exacerbations is a history of previous exacerbations, which helps identify a frequent exacerbator phenotype. This post hoc analysis evaluated the effect of roflumilast, a drug known to reduce the COPD exacerbation rate, on exacerbation status. Methods Pooled data from two 1-year, placebo-controlled, roflumilast (500 μg once daily) studies in patients with symptomatic COPD and severe airflow obstruction were evaluated (studies M2-124 and M2-125, ClinicalTrials.gov identifiers NCT00297102 and NCT00297115 ). A total of 3,091 patients were included in this analysis (62.5% with GOLD [Global Initiative for Chronic Obstructive Lung Disease] III COPD and 29.2% with GOLD 4 COPD). Based on their exacerbation frequency status in the previous year, patients were classified as frequent (two or more events) or infrequent (fewer than two events) exacerbators. Exacerbation frequency was analyzed at baseline and at year 1. Results Among frequent exacerbators treated with roflumilast, 32.0% still had frequent exacerbations at year 1 compared with 40.8% of placebo-treated patients (risk ratio, 0.799; P = .0148). Among infrequent exacerbators, 17.5% of roflumilast-treated patients became frequent exacerbators at year 1 compared with 22.9% of those taking placebo (risk ratio, 0.768; P = .0018). The reduction in severe exacerbations leading to hospitalization/death was similar between subgroups and occurred independently of concomitant long-acting β2 -agonists or previous inhaled corticosteroid treatment. When analyzed by severity of airflow limitation, 26.4% of roflumilast-treated frequent exacerbators with GOLD III COPD remained frequent exacerbators at year 1 compared with 38.9% of those taking placebo ( P = .0042). Conclusions Treatment with roflumilast shifts patients from the frequent to the more stable infrequent exacerbator state. Trial registry ClinicalTrials.gov ; No.: NCT00297102 and NCT00297115 ; URL: www.clinicaltrials.gov |
| doi_str_mv | 10.1378/chest.12-1489 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1378_chest_12_1489</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0012369213603281</els_id><sourcerecordid>1_s2_0_S0012369213603281</sourcerecordid><originalsourceid>FETCH-LOGICAL-c414t-6766a9bdf96f960aedc8d9952b224d3d7e337160b629d61f1f613b1f68b0023f3</originalsourceid><addsrcrecordid>eNo9kN9LwzAQgIMobk4ffZX8A525pEubF0HnpsJgwx_PIW0vrLNrZ9KK_e_NnArHHXd8HHcfIZfAxiCS9Dpfo2_HwCOIU3VEhqAERGISi2MyZCzMhVR8QM6837DQg5KnZMAFQAJpOiR3M2vL3OQ9bSx9bmzVbcvK-JaWNW3XSKfL1T2dO_zosG7p7Mvk6DLTNo6u1lg3bb_Dc3JiTeXx4reOyNt89jp9jBbLh6fp7SLKY4jbSCZSGpUVVskQzGCRp4VSE55xHheiSFCIBCTLJFeFBAtWgshCTjPGuLBiRKLD3tw13ju0eufKrXG9Bqb3LvSPCw1c710E_urA77psi8U__fd8AG4OAIarP0t0Oq_KOtio3rFHv2k6V4eHNGjPNdMve517myAkEzwF8Q0w-27j</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Efficacy of Roflumilast in the COPD Frequent Exacerbator Phenotype</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>Journals@Ovid Complete</source><creator>Wedzicha, Jadwiga A., MD ; Rabe, Klaus F., MD ; Martinez, Fernando J., MD ; Bredenbröker, Dirk, MD ; Brose, Manja, MS ; Goehring, Udo-Michael, MD ; Calverley, Peter M.A., MD</creator><creatorcontrib>Wedzicha, Jadwiga A., MD ; Rabe, Klaus F., MD ; Martinez, Fernando J., MD ; Bredenbröker, Dirk, MD ; Brose, Manja, MS ; Goehring, Udo-Michael, MD ; Calverley, Peter M.A., MD</creatorcontrib><description>Background COPD exacerbations are associated with increased morbidity and mortality and can accelerate disease progression. The best predictor of future exacerbations is a history of previous exacerbations, which helps identify a frequent exacerbator phenotype. This post hoc analysis evaluated the effect of roflumilast, a drug known to reduce the COPD exacerbation rate, on exacerbation status. Methods Pooled data from two 1-year, placebo-controlled, roflumilast (500 μg once daily) studies in patients with symptomatic COPD and severe airflow obstruction were evaluated (studies M2-124 and M2-125, ClinicalTrials.gov identifiers NCT00297102 and NCT00297115 ). A total of 3,091 patients were included in this analysis (62.5% with GOLD [Global Initiative for Chronic Obstructive Lung Disease] III COPD and 29.2% with GOLD 4 COPD). Based on their exacerbation frequency status in the previous year, patients were classified as frequent (two or more events) or infrequent (fewer than two events) exacerbators. Exacerbation frequency was analyzed at baseline and at year 1. Results Among frequent exacerbators treated with roflumilast, 32.0% still had frequent exacerbations at year 1 compared with 40.8% of placebo-treated patients (risk ratio, 0.799; P = .0148). Among infrequent exacerbators, 17.5% of roflumilast-treated patients became frequent exacerbators at year 1 compared with 22.9% of those taking placebo (risk ratio, 0.768; P = .0018). The reduction in severe exacerbations leading to hospitalization/death was similar between subgroups and occurred independently of concomitant long-acting β2 -agonists or previous inhaled corticosteroid treatment. When analyzed by severity of airflow limitation, 26.4% of roflumilast-treated frequent exacerbators with GOLD III COPD remained frequent exacerbators at year 1 compared with 38.9% of those taking placebo ( P = .0042). Conclusions Treatment with roflumilast shifts patients from the frequent to the more stable infrequent exacerbator state. Trial registry ClinicalTrials.gov ; No.: NCT00297102 and NCT00297115 ; URL: www.clinicaltrials.gov</description><identifier>ISSN: 0012-3692</identifier><identifier>EISSN: 1931-3543</identifier><identifier>DOI: 10.1378/chest.12-1489</identifier><identifier>PMID: 23117188</identifier><language>eng</language><publisher>United States</publisher><subject>Aged ; Aminopyridines - adverse effects ; Aminopyridines - pharmacology ; Aminopyridines - therapeutic use ; Benzamides - adverse effects ; Benzamides - pharmacology ; Benzamides - therapeutic use ; Cyclopropanes - adverse effects ; Cyclopropanes - pharmacology ; Cyclopropanes - therapeutic use ; Diarrhea - chemically induced ; Diarrhea - epidemiology ; Disease Progression ; Double-Blind Method ; Endpoint Determination ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Phenotype ; Phosphodiesterase 4 Inhibitors - adverse effects ; Phosphodiesterase 4 Inhibitors - pharmacology ; Phosphodiesterase 4 Inhibitors - therapeutic use ; Pulmonary Disease, Chronic Obstructive - drug therapy ; Pulmonary/Respiratory ; Treatment Outcome ; Weight Loss - drug effects</subject><ispartof>Chest, 2013-05, Vol.143 (5), p.1302-1311</ispartof><rights>The American College of Chest Physicians</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-6766a9bdf96f960aedc8d9952b224d3d7e337160b629d61f1f613b1f68b0023f3</citedby><cites>FETCH-LOGICAL-c414t-6766a9bdf96f960aedc8d9952b224d3d7e337160b629d61f1f613b1f68b0023f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23117188$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wedzicha, Jadwiga A., MD</creatorcontrib><creatorcontrib>Rabe, Klaus F., MD</creatorcontrib><creatorcontrib>Martinez, Fernando J., MD</creatorcontrib><creatorcontrib>Bredenbröker, Dirk, MD</creatorcontrib><creatorcontrib>Brose, Manja, MS</creatorcontrib><creatorcontrib>Goehring, Udo-Michael, MD</creatorcontrib><creatorcontrib>Calverley, Peter M.A., MD</creatorcontrib><title>Efficacy of Roflumilast in the COPD Frequent Exacerbator Phenotype</title><title>Chest</title><addtitle>Chest</addtitle><description>Background COPD exacerbations are associated with increased morbidity and mortality and can accelerate disease progression. The best predictor of future exacerbations is a history of previous exacerbations, which helps identify a frequent exacerbator phenotype. This post hoc analysis evaluated the effect of roflumilast, a drug known to reduce the COPD exacerbation rate, on exacerbation status. Methods Pooled data from two 1-year, placebo-controlled, roflumilast (500 μg once daily) studies in patients with symptomatic COPD and severe airflow obstruction were evaluated (studies M2-124 and M2-125, ClinicalTrials.gov identifiers NCT00297102 and NCT00297115 ). A total of 3,091 patients were included in this analysis (62.5% with GOLD [Global Initiative for Chronic Obstructive Lung Disease] III COPD and 29.2% with GOLD 4 COPD). Based on their exacerbation frequency status in the previous year, patients were classified as frequent (two or more events) or infrequent (fewer than two events) exacerbators. Exacerbation frequency was analyzed at baseline and at year 1. Results Among frequent exacerbators treated with roflumilast, 32.0% still had frequent exacerbations at year 1 compared with 40.8% of placebo-treated patients (risk ratio, 0.799; P = .0148). Among infrequent exacerbators, 17.5% of roflumilast-treated patients became frequent exacerbators at year 1 compared with 22.9% of those taking placebo (risk ratio, 0.768; P = .0018). The reduction in severe exacerbations leading to hospitalization/death was similar between subgroups and occurred independently of concomitant long-acting β2 -agonists or previous inhaled corticosteroid treatment. When analyzed by severity of airflow limitation, 26.4% of roflumilast-treated frequent exacerbators with GOLD III COPD remained frequent exacerbators at year 1 compared with 38.9% of those taking placebo ( P = .0042). Conclusions Treatment with roflumilast shifts patients from the frequent to the more stable infrequent exacerbator state. Trial registry ClinicalTrials.gov ; No.: NCT00297102 and NCT00297115 ; URL: www.clinicaltrials.gov</description><subject>Aged</subject><subject>Aminopyridines - adverse effects</subject><subject>Aminopyridines - pharmacology</subject><subject>Aminopyridines - therapeutic use</subject><subject>Benzamides - adverse effects</subject><subject>Benzamides - pharmacology</subject><subject>Benzamides - therapeutic use</subject><subject>Cyclopropanes - adverse effects</subject><subject>Cyclopropanes - pharmacology</subject><subject>Cyclopropanes - therapeutic use</subject><subject>Diarrhea - chemically induced</subject><subject>Diarrhea - epidemiology</subject><subject>Disease Progression</subject><subject>Double-Blind Method</subject><subject>Endpoint Determination</subject><subject>Female</subject><subject>Humans</subject><subject>Incidence</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Phenotype</subject><subject>Phosphodiesterase 4 Inhibitors - adverse effects</subject><subject>Phosphodiesterase 4 Inhibitors - pharmacology</subject><subject>Phosphodiesterase 4 Inhibitors - therapeutic use</subject><subject>Pulmonary Disease, Chronic Obstructive - drug therapy</subject><subject>Pulmonary/Respiratory</subject><subject>Treatment Outcome</subject><subject>Weight Loss - drug effects</subject><issn>0012-3692</issn><issn>1931-3543</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kN9LwzAQgIMobk4ffZX8A525pEubF0HnpsJgwx_PIW0vrLNrZ9KK_e_NnArHHXd8HHcfIZfAxiCS9Dpfo2_HwCOIU3VEhqAERGISi2MyZCzMhVR8QM6837DQg5KnZMAFQAJpOiR3M2vL3OQ9bSx9bmzVbcvK-JaWNW3XSKfL1T2dO_zosG7p7Mvk6DLTNo6u1lg3bb_Dc3JiTeXx4reOyNt89jp9jBbLh6fp7SLKY4jbSCZSGpUVVskQzGCRp4VSE55xHheiSFCIBCTLJFeFBAtWgshCTjPGuLBiRKLD3tw13ju0eufKrXG9Bqb3LvSPCw1c710E_urA77psi8U__fd8AG4OAIarP0t0Oq_KOtio3rFHv2k6V4eHNGjPNdMve517myAkEzwF8Q0w-27j</recordid><startdate>20130501</startdate><enddate>20130501</enddate><creator>Wedzicha, Jadwiga A., MD</creator><creator>Rabe, Klaus F., MD</creator><creator>Martinez, Fernando J., MD</creator><creator>Bredenbröker, Dirk, MD</creator><creator>Brose, Manja, MS</creator><creator>Goehring, Udo-Michael, MD</creator><creator>Calverley, Peter M.A., MD</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20130501</creationdate><title>Efficacy of Roflumilast in the COPD Frequent Exacerbator Phenotype</title><author>Wedzicha, Jadwiga A., MD ; Rabe, Klaus F., MD ; Martinez, Fernando J., MD ; Bredenbröker, Dirk, MD ; Brose, Manja, MS ; Goehring, Udo-Michael, MD ; Calverley, Peter M.A., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c414t-6766a9bdf96f960aedc8d9952b224d3d7e337160b629d61f1f613b1f68b0023f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aged</topic><topic>Aminopyridines - adverse effects</topic><topic>Aminopyridines - pharmacology</topic><topic>Aminopyridines - therapeutic use</topic><topic>Benzamides - adverse effects</topic><topic>Benzamides - pharmacology</topic><topic>Benzamides - therapeutic use</topic><topic>Cyclopropanes - adverse effects</topic><topic>Cyclopropanes - pharmacology</topic><topic>Cyclopropanes - therapeutic use</topic><topic>Diarrhea - chemically induced</topic><topic>Diarrhea - epidemiology</topic><topic>Disease Progression</topic><topic>Double-Blind Method</topic><topic>Endpoint Determination</topic><topic>Female</topic><topic>Humans</topic><topic>Incidence</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Phenotype</topic><topic>Phosphodiesterase 4 Inhibitors - adverse effects</topic><topic>Phosphodiesterase 4 Inhibitors - pharmacology</topic><topic>Phosphodiesterase 4 Inhibitors - therapeutic use</topic><topic>Pulmonary Disease, Chronic Obstructive - drug therapy</topic><topic>Pulmonary/Respiratory</topic><topic>Treatment Outcome</topic><topic>Weight Loss - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wedzicha, Jadwiga A., MD</creatorcontrib><creatorcontrib>Rabe, Klaus F., MD</creatorcontrib><creatorcontrib>Martinez, Fernando J., MD</creatorcontrib><creatorcontrib>Bredenbröker, Dirk, MD</creatorcontrib><creatorcontrib>Brose, Manja, MS</creatorcontrib><creatorcontrib>Goehring, Udo-Michael, MD</creatorcontrib><creatorcontrib>Calverley, Peter M.A., MD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Chest</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wedzicha, Jadwiga A., MD</au><au>Rabe, Klaus F., MD</au><au>Martinez, Fernando J., MD</au><au>Bredenbröker, Dirk, MD</au><au>Brose, Manja, MS</au><au>Goehring, Udo-Michael, MD</au><au>Calverley, Peter M.A., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of Roflumilast in the COPD Frequent Exacerbator Phenotype</atitle><jtitle>Chest</jtitle><addtitle>Chest</addtitle><date>2013-05-01</date><risdate>2013</risdate><volume>143</volume><issue>5</issue><spage>1302</spage><epage>1311</epage><pages>1302-1311</pages><issn>0012-3692</issn><eissn>1931-3543</eissn><abstract>Background COPD exacerbations are associated with increased morbidity and mortality and can accelerate disease progression. The best predictor of future exacerbations is a history of previous exacerbations, which helps identify a frequent exacerbator phenotype. This post hoc analysis evaluated the effect of roflumilast, a drug known to reduce the COPD exacerbation rate, on exacerbation status. Methods Pooled data from two 1-year, placebo-controlled, roflumilast (500 μg once daily) studies in patients with symptomatic COPD and severe airflow obstruction were evaluated (studies M2-124 and M2-125, ClinicalTrials.gov identifiers NCT00297102 and NCT00297115 ). A total of 3,091 patients were included in this analysis (62.5% with GOLD [Global Initiative for Chronic Obstructive Lung Disease] III COPD and 29.2% with GOLD 4 COPD). Based on their exacerbation frequency status in the previous year, patients were classified as frequent (two or more events) or infrequent (fewer than two events) exacerbators. Exacerbation frequency was analyzed at baseline and at year 1. Results Among frequent exacerbators treated with roflumilast, 32.0% still had frequent exacerbations at year 1 compared with 40.8% of placebo-treated patients (risk ratio, 0.799; P = .0148). Among infrequent exacerbators, 17.5% of roflumilast-treated patients became frequent exacerbators at year 1 compared with 22.9% of those taking placebo (risk ratio, 0.768; P = .0018). The reduction in severe exacerbations leading to hospitalization/death was similar between subgroups and occurred independently of concomitant long-acting β2 -agonists or previous inhaled corticosteroid treatment. When analyzed by severity of airflow limitation, 26.4% of roflumilast-treated frequent exacerbators with GOLD III COPD remained frequent exacerbators at year 1 compared with 38.9% of those taking placebo ( P = .0042). Conclusions Treatment with roflumilast shifts patients from the frequent to the more stable infrequent exacerbator state. Trial registry ClinicalTrials.gov ; No.: NCT00297102 and NCT00297115 ; URL: www.clinicaltrials.gov</abstract><cop>United States</cop><pmid>23117188</pmid><doi>10.1378/chest.12-1489</doi><tpages>10</tpages></addata></record> |
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| subjects | Aged Aminopyridines - adverse effects Aminopyridines - pharmacology Aminopyridines - therapeutic use Benzamides - adverse effects Benzamides - pharmacology Benzamides - therapeutic use Cyclopropanes - adverse effects Cyclopropanes - pharmacology Cyclopropanes - therapeutic use Diarrhea - chemically induced Diarrhea - epidemiology Disease Progression Double-Blind Method Endpoint Determination Female Humans Incidence Male Middle Aged Phenotype Phosphodiesterase 4 Inhibitors - adverse effects Phosphodiesterase 4 Inhibitors - pharmacology Phosphodiesterase 4 Inhibitors - therapeutic use Pulmonary Disease, Chronic Obstructive - drug therapy Pulmonary/Respiratory Treatment Outcome Weight Loss - drug effects |
| title | Efficacy of Roflumilast in the COPD Frequent Exacerbator Phenotype |
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