{"id":1062,"date":"2016-06-01T19:50:42","date_gmt":"2016-06-01T19:50:42","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1062"},"modified":"2017-08-21T10:55:51","modified_gmt":"2017-08-21T10:55:51","slug":"primary-care-corner-with-geoffrey-modest-md-copd-superiority-of-laba-and-lama-combo-treatment","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/06\/01\/primary-care-corner-with-geoffrey-modest-md-copd-superiority-of-laba-and-lama-combo-treatment\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: COPD &#8211; Superiority of LABA and LAMA Combo Treatment"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>A recently released report, presented at the American\u00a0Thoracic Society, found that patients with COPD benefited more from the combination of a long-acting b-agonist (LABA) plus a long-acting anti-muscarinic (LAMA), as opposed to a LABA plus inhaled steroid\u00a0(see\u00a0DOI: 10.1056\/NEJMoa1516385). Details of the FLAME trial (drug company sponsored trial), a double-blind, double-dummy, parallel-group, non-inferiority trial:<\/p>\n<ul>\n<li>3354\u00a0patients with COPD, from 356 centers in 43 countries. Inclusion criteria: &gt;40 yo, grade 2 or greater in modified\u00a0MRC dyspnea scale (patient describing shortness of breath as\u00a0&#8220;I walk slower than people of the same age on the\u00a0level\u00a0because\u00a0of breathlessness or have to stop for breath when walking at my own pace on the level&#8221;), post-bronchodilator FEV<sub>1<\/sub> 25-60% of predicted value with FEV<sub>1<\/sub>\/FVC &lt;70%, and documentation of at least one COPD exacerbation in past year prescribed either systemic steroids, antibiotics or both<\/li>\n<li>Mean age 65, 76% male,\u00a078% white\/most of rest Asian,\u00a0duration of COPD 7 years, 56% on inhaled steroids, 40% current smokers,\u00a0predicted post-bronchodilator\u00a0FEV<sub>1<\/sub> 44%, post-bronchodilator\u00a0FEV<sub>1<\/sub>\/FVC 42%<\/li>\n<li>GOLD stage:24% Group B (low risk\/high symptom burden),\u00a075% Group D (high risk\/high symptom burden)<\/li>\n<li>Assigned to LABA-LAMA combination (indacaterol 110\u00a0mg plus glycopyrronium 50\u00a0mg) once daily, vs LABA-steroid (salmeterol 50 mg plus fluticasone 500 mg) bid, followed 52 weeks.<\/li>\n<li>Results, comparing LABA-LAMA to LABA-steroid:\n<ul>\n<li>&gt;99% adherence to each of the treatment groups<\/li>\n<li>Rate of COPD exacerbations: 3.59 vs 4.03,\u00a011% lower [RR 0.89 (0.83-0.96, p=0.003]<\/li>\n<li>Longer time to first exacerbation: 71 vs 51 days\u00a0[HR 0.84\u00a0(0.78-0.91, p&lt;0.001]<\/li>\n<li>Rate of moderate or severe exacerbations: 0.98 vs 1.19, 17% lower\u00a0[RR 0.83\u00a0(0.75-0.91, p&lt;0.001], as well as time to the first severe exacerbation<\/li>\n<li>The effect of LABA-LAMA was independent of baseline blood eosinophil count (comparing &gt;2% vs &lt;2%)<\/li>\n<li>Subgroup analysis: all showed superiority for LABA-LAMA, though some did not reach\u00a0statistical significance. Subgroups included\u00a0race, smoking status at screening, severity of airflow limitation, severity of COPD (where those with high risk\/high symptoms had the most improvement), number of COPD exacerbations in past year, or\u00a0type of\u00a0med use at screening for study)<\/li>\n<li>Change from baseline throughFEV<sub>1<\/sub> was 62 ml more in the LABA-LAMA group at week 52 (p&lt;0.001), and the standard area under the curve for\u00a0FEV<sub>1<\/sub> was 110 ml more (p&lt;0.001)<\/li>\n<li>There was a small but not clinically significant improvement in the patients&#8217; perception of their health status with LABA-LAMA, as measured by the St George&#8217;s Respiratory Questionnaire<\/li>\n<li>There was a decrease in the use of rescue medications in the LABA-LAMA group<\/li>\n<li>Incidence of adverse events was\u00a0similar, though incidence of pneumonia was 3.2% with LABA-LAMA vs 4.8% LABA-steroid (p=0.02). Rates of discontinuation of treatment were 16.6% in LABA-LAMA and 19.0% with LABA-steroids<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>So, this trial showed actual <strong>superiority of the LABA-LAMA<\/strong> combination, not just non-inferiority<\/p>\n<ul>\n<li>The combination LABA-LAMA was approved by the FDA last year, under the brand name: ultibro. (Neither drug nor\u00a0price are\u00a0available yet, though it may be cheaper to use the individual combo of tiotropium, a tried-and-true LAMA, with salmeterol or formoterol)<\/li>\n<li>Prior trials have shown rough equivalence of tiotropium (a LAMA) by itself\u00a0and the combination\u00a0LABA-steroid for prevention of COPD exacerbations, leading to the GOLD\u00a0guidelines recommending either of these therapies. Also, another study found that a LAMA-LABA combination was superior to a LAMA alone.<\/li>\n<li>There are some data suggesting that the LABA-steroid combo works better in those with high blood eosinophil counts. The FLAME\u00a0study, however,\u00a0found that even in this subgroup (examined prospectively in the trial) still found superiority of LABA-LAMA<\/li>\n<\/ul>\n<p>So, this study will change my practice, and for a few\u00a0reasons. My prior approach for those with symptomatic COPD was to use a LAMA first (specifically tiotropium). If that were insufficient, I added a combo LABA-steroid med. Now, I will still start with tiotropium, but now add a LABA as a single agent, if clinically\u00a0necessary\u00a0(though, I should note, no study compares LABA-LAMA to triple therapy with LABA-LAMA-steroid, though I will reserve this triple hit as my third string). And I am concerned about the consistent association of inhaled steroids with pneumonia, as was also the case in this trial and the last blog I sent (see <a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/17\/primary-care-corner-with-geoffrey-modest-md-copd-safety-of-labas\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/17\/primary-care-corner-with-geoffrey-modest-md-copd-safety-of-labas\/<\/a>, the SUMMIT trial,\u00a0which demonstrated\u00a0the safety of giving a LABA as sole treatment for COPD). And,\u00a0the FLAME trial showed superiority for the LABA-LAMA is many realms: decreasing COPD exacerbations in those with even severe COPD as well as decreasing the time to a first exacerbation, improving some parameters of lung function (e.g. FEV<sub>1<\/sub>), improving (though not to the point of\u00a0clinical\u00a0significance) the patients&#8217; perception of their health status, and a trend to overall fewer adverse events (and actually lower pneumonia events).<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: COPD &#8211; Superiority of LABA and LAMA Combo Treatment  [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/06\/01\/primary-care-corner-with-geoffrey-modest-md-copd-superiority-of-laba-and-lama-combo-treatment\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-1062","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1062","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=1062"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1062\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=1062"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=1062"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=1062"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}