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The outcomes of “GOLD 2017”
After the Global Initiative for Chronic Obstructive Lung Disease released updated recommendations for grading COPD patients’ level of disease in November of 2016, Imran Iftikhar, MD, tried to incorporate them into his practice, but he encountered problems.
For one thing, the new classification system, which became known as GOLD 2017, uncoupled spirometry results from the ABCD treatment algorithm. “I found it wasn’t really helping me in terms of prognostication or COPD management,” said Dr. Iftikhar, section chief of pulmonary and critical care at Emory Saint Joseph’s Hospital, Atlanta. “Although the purpose of the GOLD classification was not really meant for prognostication, most practicing physicians are frequently asked about prognosis by patients, and I am not sure if the 2017 reclassification really helps with that.”
The GOLD 2017 classification simplified the chronic obstructive pulmonary disease staging that was available from 2011 to 2015 from three variables (spirometry thresholds, exacerbation risk, and dyspnea scale) to two variables (exacerbation risk and dyspnea scale). In the 2017 report, authors of the new guidelines characterized forced expiratory volume in 1 second (FEV1) as “a poor predictor of disease status” and proposed that clinicians derive ABCD groups exclusively from patient symptoms and their exacerbations. FEV1 is an “important parameter at the population level” in predicting hospitalization and mortality, the authors wrote, but keeping results separate “acknowledges the limitations of FEV1 in making treatment decisions for individualized patient care and highlights the importance of patient symptoms and exacerbation risks in guiding therapies in COPD.”
According to Meilan Han, MD, MS, a member of the GOLD Science Committee, since release of the 2017 guidelines, “clinicians have indicated that they like the flexibility the system provides in separating spirometry, symptoms, and exacerbation risk as this more accurately reflects the heterogeneity we see in the COPD patient population.” Nevertheless, how this approach influences long-term outcomes remains unclear.
Daniel Ouellette, MD, FCCP, a pulmonologist with the Henry Ford Health System in Detroit, described the GOLD 2017 criteria as “a good step forward” but said he wasn’t sure if the optimal or perfect tool exists for categorizing COPD patients’ level of disease.
“I think what we see is an effort to use all of these criteria to help us better treat our patients. I think ,” he said in an interview.
“All guidelines need to be modified as further research becomes available. I think that the frontiers of this area are going to be to incorporate new elements such as tobacco history, more emphasis on clinical signs and symptoms, and use of markers other than spirometry, such as eosinophil count, to categorize patients with COPD,” Dr. Ouellette added.
In an analysis of the GOLD 2017 criteria applied to 819 COPD patients in Spain and the United States, published online Nov. 3, 2017, in the American Journal of Respiratory and Critical Care Medicine, Carlos Cabrera López, MD, and his colleagues concluded that the mortality risk was better predicted by the 2015 GOLD classification system than by the 2017 iteration (Am J Respir Crit Care Med. 2018 Feb. doi: 10.101164/rccm.201707-1363OC).
The distribution of Charlson index scores also changed. Whereas group D was higher than B in 2015, they became similar in the 2017 system. For her part, Dr. Han emphasized that the primary goal of the GOLD ABCD classification system is to categorize patients with respect to treatment groups. “Current therapy targets symptoms and exacerbations, which are the key current elements of the classification schema,” she said in an interview. “The results of the Cabrera Lopez analysis are not necessarily unexpected, as FEV1 is associated with mortality.”
In a prospective, multicenter analysis, Portuguese researchers compared the performance of GOLD 2011 and 2017 in terms of how 200 COPD patients were reclassified, the level of agreement between the two iterations, and the performance of each to predict future exacerbations (COPD. 2018 Feb;15[1]; 21-6). They found that about half of patients classified as GOLD D under the 2011 guidelines became classified as GOLD B when the 2017 version was used, and the extent of agreement between the two iterations was moderate (P less than .001). They also found that the two versions of the guidelines were equivalently effective at predicting exacerbations (69.7% vs. 67.6% in the 2011 and 2017 iterations, respectively). In addition, patients who met the criteria for a GOLD B grouping in the 2017 iteration exacerbated 17% more often and had a lower percent predicted post bronchodilator FEV1 than did those who met the criteria for a GOLD B classification under the 2011 guidelines.
Dr. Han, who is also an associate professor of medicine at the University of Michigan Hospital, acknowledged that GOLD 2017 has resulted in the reclassification of some previously group D patients as group B patients. “Our primary goal is to aid clinicians with the diagnosis and management of patients with COPD,” she said. “We look forward to additional data coming in from ongoing clinical trials that will provide longer term data to further refine treatment algorithms.”
In a recent study of more than 33,000 Danish patients older than age 30 with COPD, researchers led by Anne Gedebjerg, MD, found that the GOLD 2017 ABCD classification did not predict all-cause and respiratory mortality more accurately than previous GOLD iterations from 2007 and 2011. Area under the curve for all-cause mortality was 0.61 for GOLD 2007, 0.61 for GOLD 2011, and 0.63 for GOLD 2017, while the area under the curve for respiratory mortality was 0.64 for GOLD 2007, 0.63 for GOLD 2011, and 0.65 for GOLD 2017 (Lancet Respir Med. 2018 Jan;6[3]:204-12).
However, when the spirometric stages 1-4 were combined with the A to D groupings based on symptoms and exacerbations, the 2017 classification predicted mortality with greater accuracy, compared with previous iterations (P less than .0001). “My practice is very much like this paper,” Dr. Iftikhar said. “I use both the spirometric grade and the ABCD grouping to specify which ‘group’ and ‘grade’ my patient belongs to. I think future investigators need to combine ABCD with spirometry classification to see how we can improve the classification system.”
In a commentary published in the same issue of the Lancet Respiratory Medicine as the large Danish study, Joan B. Soriano, MD, PhD, wrote that the 2011 GOLD guideline’s collapse of four spirometric thresholds (greater than 80%, 50%-80%, 30%-50%, and less than 30%) into just two (greater than 50% or 50% or less) “reduced the system’s ability to inform and predict mortality from the short term up to 10 years” (Lancet Respir Med. 2018 Jan;6[3]:165-6).
Lung function remains the best available biomarker for life expectancy in both patients with COPD and the general population,” wrote Dr. Soriano, a respiratory medicine researcher based in Madrid, Spain.
Additional important outcomes
Dr. Ouellette noted that while mortality is an important outcome for COPD patients, it’s not the only outcome of interest. “In addition to [trying to] help people live longer, which is certainly a desirable goal, we also want to make people be able to be more functional during their life, have fewer hospitalizations, and have less of a need of other types of supportive medical care for worsening of their disease,” he said. “The fact that the current guidelines don’t improve mortality more than the previous ones may not be a negative thing. It may tell us that the previous guidelines already did a pretty good job of helping us to improve mortality.”
Dr. Ouellette was quick to add that none of inhaled drugs currently available to treat COPD have been conclusively shown to improve mortality. “The only things we know that improve mortality for COPD patients are quitting smoking and using oxygen if a patient meets predefined goals for oxygen,” he said. “So the fact that GOLD criteria doesn’t improve mortality shouldn’t make us think that it’s not a useful tool. We already know that the medicines may not help people live longer.”
Dr. Han pointed out that spirometry “is still used to further clarify the choice of therapy recommended based on the nature and degree of airflow obstruction in light of severity of patient symptoms. The data are still designed to be used in conjunction to personalize therapy for patients.”
She added that the GOLD Science Committee “welcomes additional data analyses so that future recommendations can be further refined.”
Dr. Han disclosed that she has consulted for Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline. She has also received in-kind research support from Novartis and Sunovion.
Dr. Iftikhar reported having no financial disclosures. Dr. Ouellette is a member of CHEST® Physician’s editorial advisory board. He disclosed being part of a federally funded study being carried out by the Patient-Centered Outcomes Research Institute.
There was no industry involvement in the GOLD 2017 report, but many of its authors and board members had pharmaceutical company ties, and GOLD’s treatment advice relies on data from industry-sponsored studies.
After the Global Initiative for Chronic Obstructive Lung Disease released updated recommendations for grading COPD patients’ level of disease in November of 2016, Imran Iftikhar, MD, tried to incorporate them into his practice, but he encountered problems.
For one thing, the new classification system, which became known as GOLD 2017, uncoupled spirometry results from the ABCD treatment algorithm. “I found it wasn’t really helping me in terms of prognostication or COPD management,” said Dr. Iftikhar, section chief of pulmonary and critical care at Emory Saint Joseph’s Hospital, Atlanta. “Although the purpose of the GOLD classification was not really meant for prognostication, most practicing physicians are frequently asked about prognosis by patients, and I am not sure if the 2017 reclassification really helps with that.”
The GOLD 2017 classification simplified the chronic obstructive pulmonary disease staging that was available from 2011 to 2015 from three variables (spirometry thresholds, exacerbation risk, and dyspnea scale) to two variables (exacerbation risk and dyspnea scale). In the 2017 report, authors of the new guidelines characterized forced expiratory volume in 1 second (FEV1) as “a poor predictor of disease status” and proposed that clinicians derive ABCD groups exclusively from patient symptoms and their exacerbations. FEV1 is an “important parameter at the population level” in predicting hospitalization and mortality, the authors wrote, but keeping results separate “acknowledges the limitations of FEV1 in making treatment decisions for individualized patient care and highlights the importance of patient symptoms and exacerbation risks in guiding therapies in COPD.”
According to Meilan Han, MD, MS, a member of the GOLD Science Committee, since release of the 2017 guidelines, “clinicians have indicated that they like the flexibility the system provides in separating spirometry, symptoms, and exacerbation risk as this more accurately reflects the heterogeneity we see in the COPD patient population.” Nevertheless, how this approach influences long-term outcomes remains unclear.
Daniel Ouellette, MD, FCCP, a pulmonologist with the Henry Ford Health System in Detroit, described the GOLD 2017 criteria as “a good step forward” but said he wasn’t sure if the optimal or perfect tool exists for categorizing COPD patients’ level of disease.
“I think what we see is an effort to use all of these criteria to help us better treat our patients. I think ,” he said in an interview.
“All guidelines need to be modified as further research becomes available. I think that the frontiers of this area are going to be to incorporate new elements such as tobacco history, more emphasis on clinical signs and symptoms, and use of markers other than spirometry, such as eosinophil count, to categorize patients with COPD,” Dr. Ouellette added.
In an analysis of the GOLD 2017 criteria applied to 819 COPD patients in Spain and the United States, published online Nov. 3, 2017, in the American Journal of Respiratory and Critical Care Medicine, Carlos Cabrera López, MD, and his colleagues concluded that the mortality risk was better predicted by the 2015 GOLD classification system than by the 2017 iteration (Am J Respir Crit Care Med. 2018 Feb. doi: 10.101164/rccm.201707-1363OC).
The distribution of Charlson index scores also changed. Whereas group D was higher than B in 2015, they became similar in the 2017 system. For her part, Dr. Han emphasized that the primary goal of the GOLD ABCD classification system is to categorize patients with respect to treatment groups. “Current therapy targets symptoms and exacerbations, which are the key current elements of the classification schema,” she said in an interview. “The results of the Cabrera Lopez analysis are not necessarily unexpected, as FEV1 is associated with mortality.”
In a prospective, multicenter analysis, Portuguese researchers compared the performance of GOLD 2011 and 2017 in terms of how 200 COPD patients were reclassified, the level of agreement between the two iterations, and the performance of each to predict future exacerbations (COPD. 2018 Feb;15[1]; 21-6). They found that about half of patients classified as GOLD D under the 2011 guidelines became classified as GOLD B when the 2017 version was used, and the extent of agreement between the two iterations was moderate (P less than .001). They also found that the two versions of the guidelines were equivalently effective at predicting exacerbations (69.7% vs. 67.6% in the 2011 and 2017 iterations, respectively). In addition, patients who met the criteria for a GOLD B grouping in the 2017 iteration exacerbated 17% more often and had a lower percent predicted post bronchodilator FEV1 than did those who met the criteria for a GOLD B classification under the 2011 guidelines.
Dr. Han, who is also an associate professor of medicine at the University of Michigan Hospital, acknowledged that GOLD 2017 has resulted in the reclassification of some previously group D patients as group B patients. “Our primary goal is to aid clinicians with the diagnosis and management of patients with COPD,” she said. “We look forward to additional data coming in from ongoing clinical trials that will provide longer term data to further refine treatment algorithms.”
In a recent study of more than 33,000 Danish patients older than age 30 with COPD, researchers led by Anne Gedebjerg, MD, found that the GOLD 2017 ABCD classification did not predict all-cause and respiratory mortality more accurately than previous GOLD iterations from 2007 and 2011. Area under the curve for all-cause mortality was 0.61 for GOLD 2007, 0.61 for GOLD 2011, and 0.63 for GOLD 2017, while the area under the curve for respiratory mortality was 0.64 for GOLD 2007, 0.63 for GOLD 2011, and 0.65 for GOLD 2017 (Lancet Respir Med. 2018 Jan;6[3]:204-12).
However, when the spirometric stages 1-4 were combined with the A to D groupings based on symptoms and exacerbations, the 2017 classification predicted mortality with greater accuracy, compared with previous iterations (P less than .0001). “My practice is very much like this paper,” Dr. Iftikhar said. “I use both the spirometric grade and the ABCD grouping to specify which ‘group’ and ‘grade’ my patient belongs to. I think future investigators need to combine ABCD with spirometry classification to see how we can improve the classification system.”
In a commentary published in the same issue of the Lancet Respiratory Medicine as the large Danish study, Joan B. Soriano, MD, PhD, wrote that the 2011 GOLD guideline’s collapse of four spirometric thresholds (greater than 80%, 50%-80%, 30%-50%, and less than 30%) into just two (greater than 50% or 50% or less) “reduced the system’s ability to inform and predict mortality from the short term up to 10 years” (Lancet Respir Med. 2018 Jan;6[3]:165-6).
Lung function remains the best available biomarker for life expectancy in both patients with COPD and the general population,” wrote Dr. Soriano, a respiratory medicine researcher based in Madrid, Spain.
Additional important outcomes
Dr. Ouellette noted that while mortality is an important outcome for COPD patients, it’s not the only outcome of interest. “In addition to [trying to] help people live longer, which is certainly a desirable goal, we also want to make people be able to be more functional during their life, have fewer hospitalizations, and have less of a need of other types of supportive medical care for worsening of their disease,” he said. “The fact that the current guidelines don’t improve mortality more than the previous ones may not be a negative thing. It may tell us that the previous guidelines already did a pretty good job of helping us to improve mortality.”
Dr. Ouellette was quick to add that none of inhaled drugs currently available to treat COPD have been conclusively shown to improve mortality. “The only things we know that improve mortality for COPD patients are quitting smoking and using oxygen if a patient meets predefined goals for oxygen,” he said. “So the fact that GOLD criteria doesn’t improve mortality shouldn’t make us think that it’s not a useful tool. We already know that the medicines may not help people live longer.”
Dr. Han pointed out that spirometry “is still used to further clarify the choice of therapy recommended based on the nature and degree of airflow obstruction in light of severity of patient symptoms. The data are still designed to be used in conjunction to personalize therapy for patients.”
She added that the GOLD Science Committee “welcomes additional data analyses so that future recommendations can be further refined.”
Dr. Han disclosed that she has consulted for Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline. She has also received in-kind research support from Novartis and Sunovion.
Dr. Iftikhar reported having no financial disclosures. Dr. Ouellette is a member of CHEST® Physician’s editorial advisory board. He disclosed being part of a federally funded study being carried out by the Patient-Centered Outcomes Research Institute.
There was no industry involvement in the GOLD 2017 report, but many of its authors and board members had pharmaceutical company ties, and GOLD’s treatment advice relies on data from industry-sponsored studies.
After the Global Initiative for Chronic Obstructive Lung Disease released updated recommendations for grading COPD patients’ level of disease in November of 2016, Imran Iftikhar, MD, tried to incorporate them into his practice, but he encountered problems.
For one thing, the new classification system, which became known as GOLD 2017, uncoupled spirometry results from the ABCD treatment algorithm. “I found it wasn’t really helping me in terms of prognostication or COPD management,” said Dr. Iftikhar, section chief of pulmonary and critical care at Emory Saint Joseph’s Hospital, Atlanta. “Although the purpose of the GOLD classification was not really meant for prognostication, most practicing physicians are frequently asked about prognosis by patients, and I am not sure if the 2017 reclassification really helps with that.”
The GOLD 2017 classification simplified the chronic obstructive pulmonary disease staging that was available from 2011 to 2015 from three variables (spirometry thresholds, exacerbation risk, and dyspnea scale) to two variables (exacerbation risk and dyspnea scale). In the 2017 report, authors of the new guidelines characterized forced expiratory volume in 1 second (FEV1) as “a poor predictor of disease status” and proposed that clinicians derive ABCD groups exclusively from patient symptoms and their exacerbations. FEV1 is an “important parameter at the population level” in predicting hospitalization and mortality, the authors wrote, but keeping results separate “acknowledges the limitations of FEV1 in making treatment decisions for individualized patient care and highlights the importance of patient symptoms and exacerbation risks in guiding therapies in COPD.”
According to Meilan Han, MD, MS, a member of the GOLD Science Committee, since release of the 2017 guidelines, “clinicians have indicated that they like the flexibility the system provides in separating spirometry, symptoms, and exacerbation risk as this more accurately reflects the heterogeneity we see in the COPD patient population.” Nevertheless, how this approach influences long-term outcomes remains unclear.
Daniel Ouellette, MD, FCCP, a pulmonologist with the Henry Ford Health System in Detroit, described the GOLD 2017 criteria as “a good step forward” but said he wasn’t sure if the optimal or perfect tool exists for categorizing COPD patients’ level of disease.
“I think what we see is an effort to use all of these criteria to help us better treat our patients. I think ,” he said in an interview.
“All guidelines need to be modified as further research becomes available. I think that the frontiers of this area are going to be to incorporate new elements such as tobacco history, more emphasis on clinical signs and symptoms, and use of markers other than spirometry, such as eosinophil count, to categorize patients with COPD,” Dr. Ouellette added.
In an analysis of the GOLD 2017 criteria applied to 819 COPD patients in Spain and the United States, published online Nov. 3, 2017, in the American Journal of Respiratory and Critical Care Medicine, Carlos Cabrera López, MD, and his colleagues concluded that the mortality risk was better predicted by the 2015 GOLD classification system than by the 2017 iteration (Am J Respir Crit Care Med. 2018 Feb. doi: 10.101164/rccm.201707-1363OC).
The distribution of Charlson index scores also changed. Whereas group D was higher than B in 2015, they became similar in the 2017 system. For her part, Dr. Han emphasized that the primary goal of the GOLD ABCD classification system is to categorize patients with respect to treatment groups. “Current therapy targets symptoms and exacerbations, which are the key current elements of the classification schema,” she said in an interview. “The results of the Cabrera Lopez analysis are not necessarily unexpected, as FEV1 is associated with mortality.”
In a prospective, multicenter analysis, Portuguese researchers compared the performance of GOLD 2011 and 2017 in terms of how 200 COPD patients were reclassified, the level of agreement between the two iterations, and the performance of each to predict future exacerbations (COPD. 2018 Feb;15[1]; 21-6). They found that about half of patients classified as GOLD D under the 2011 guidelines became classified as GOLD B when the 2017 version was used, and the extent of agreement between the two iterations was moderate (P less than .001). They also found that the two versions of the guidelines were equivalently effective at predicting exacerbations (69.7% vs. 67.6% in the 2011 and 2017 iterations, respectively). In addition, patients who met the criteria for a GOLD B grouping in the 2017 iteration exacerbated 17% more often and had a lower percent predicted post bronchodilator FEV1 than did those who met the criteria for a GOLD B classification under the 2011 guidelines.
Dr. Han, who is also an associate professor of medicine at the University of Michigan Hospital, acknowledged that GOLD 2017 has resulted in the reclassification of some previously group D patients as group B patients. “Our primary goal is to aid clinicians with the diagnosis and management of patients with COPD,” she said. “We look forward to additional data coming in from ongoing clinical trials that will provide longer term data to further refine treatment algorithms.”
In a recent study of more than 33,000 Danish patients older than age 30 with COPD, researchers led by Anne Gedebjerg, MD, found that the GOLD 2017 ABCD classification did not predict all-cause and respiratory mortality more accurately than previous GOLD iterations from 2007 and 2011. Area under the curve for all-cause mortality was 0.61 for GOLD 2007, 0.61 for GOLD 2011, and 0.63 for GOLD 2017, while the area under the curve for respiratory mortality was 0.64 for GOLD 2007, 0.63 for GOLD 2011, and 0.65 for GOLD 2017 (Lancet Respir Med. 2018 Jan;6[3]:204-12).
However, when the spirometric stages 1-4 were combined with the A to D groupings based on symptoms and exacerbations, the 2017 classification predicted mortality with greater accuracy, compared with previous iterations (P less than .0001). “My practice is very much like this paper,” Dr. Iftikhar said. “I use both the spirometric grade and the ABCD grouping to specify which ‘group’ and ‘grade’ my patient belongs to. I think future investigators need to combine ABCD with spirometry classification to see how we can improve the classification system.”
In a commentary published in the same issue of the Lancet Respiratory Medicine as the large Danish study, Joan B. Soriano, MD, PhD, wrote that the 2011 GOLD guideline’s collapse of four spirometric thresholds (greater than 80%, 50%-80%, 30%-50%, and less than 30%) into just two (greater than 50% or 50% or less) “reduced the system’s ability to inform and predict mortality from the short term up to 10 years” (Lancet Respir Med. 2018 Jan;6[3]:165-6).
Lung function remains the best available biomarker for life expectancy in both patients with COPD and the general population,” wrote Dr. Soriano, a respiratory medicine researcher based in Madrid, Spain.
Additional important outcomes
Dr. Ouellette noted that while mortality is an important outcome for COPD patients, it’s not the only outcome of interest. “In addition to [trying to] help people live longer, which is certainly a desirable goal, we also want to make people be able to be more functional during their life, have fewer hospitalizations, and have less of a need of other types of supportive medical care for worsening of their disease,” he said. “The fact that the current guidelines don’t improve mortality more than the previous ones may not be a negative thing. It may tell us that the previous guidelines already did a pretty good job of helping us to improve mortality.”
Dr. Ouellette was quick to add that none of inhaled drugs currently available to treat COPD have been conclusively shown to improve mortality. “The only things we know that improve mortality for COPD patients are quitting smoking and using oxygen if a patient meets predefined goals for oxygen,” he said. “So the fact that GOLD criteria doesn’t improve mortality shouldn’t make us think that it’s not a useful tool. We already know that the medicines may not help people live longer.”
Dr. Han pointed out that spirometry “is still used to further clarify the choice of therapy recommended based on the nature and degree of airflow obstruction in light of severity of patient symptoms. The data are still designed to be used in conjunction to personalize therapy for patients.”
She added that the GOLD Science Committee “welcomes additional data analyses so that future recommendations can be further refined.”
Dr. Han disclosed that she has consulted for Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline. She has also received in-kind research support from Novartis and Sunovion.
Dr. Iftikhar reported having no financial disclosures. Dr. Ouellette is a member of CHEST® Physician’s editorial advisory board. He disclosed being part of a federally funded study being carried out by the Patient-Centered Outcomes Research Institute.
There was no industry involvement in the GOLD 2017 report, but many of its authors and board members had pharmaceutical company ties, and GOLD’s treatment advice relies on data from industry-sponsored studies.
Good definitions, research lacking for COPD-asthma overlap
ORLANDO – to give clinicians data they can actually use.
The topic is even more pressing given the growing interest and research into biological treatments for asthma and consideration of their possible use in COPD, experts said at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization. Their remarks came in what was ostensibly a “debate” on whether ACOS is a distinct entity requiring special treatment but largely turned into a discussion about gaps in knowledge on the topic.
“The problem here is that it has not been defined in a way that everyone agrees on – that does create a problem because, if there’s no consensus on the diagnostic criteria, then it may be difficult to study this overlap,” said Donald Tashkin, MD, director of the pulmonary function laboratories at the University of California, Los Angeles. “Because there is no agreement on how to diagnose ACOS, it hasn’t been studied with respect to its responsiveness to different treatment options.”R. Stokes Peebles Jr., MD, professor of allergy, pulmonary, and critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., said that, although the number of published articles on ACOS has skyrocketed over the last several years, review articles have outnumbered original research articles.
There is disagreement in published definitions: One set of definitions includes a criterion of fractional exhaled nitric oxide not seen in any other definitions, whereas some other definitions require a history of smoking while others don’t, he said.
“How does one manage a disease without a definition and without clinical studies? It’s impossible for me to know,” Dr. Peebles said.
Jeffrey Drazen, MD, the Distinguished Parker B. Francis Professor of Medicine at Harvard Medical School, Boston, and the editor of the New England Journal of Medicine, also lamented the polar nature of the research.
“We all treat patients in the middle, everybody does, all the time – and we would love more guidance,” he said. “One of the reasons the number of articles has gone up is that there have been lots of case definitions. But we can’t get consensus. So who do we have to bring to the table to get a consensus definition so we can get the funding we need from the drug companies or governmental bodies to do the research that we all want?”
Dr. Tashkin said the way forward could be to draw on the points of consensus that do exist on certain criteria.
Dr. Peebles said an international panel is needed to draw up a consensus guideline, with the panel including both pulmonologists and allergists – “people experienced with clinical trials, who take care of a lot of patients.”
ORLANDO – to give clinicians data they can actually use.
The topic is even more pressing given the growing interest and research into biological treatments for asthma and consideration of their possible use in COPD, experts said at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization. Their remarks came in what was ostensibly a “debate” on whether ACOS is a distinct entity requiring special treatment but largely turned into a discussion about gaps in knowledge on the topic.
“The problem here is that it has not been defined in a way that everyone agrees on – that does create a problem because, if there’s no consensus on the diagnostic criteria, then it may be difficult to study this overlap,” said Donald Tashkin, MD, director of the pulmonary function laboratories at the University of California, Los Angeles. “Because there is no agreement on how to diagnose ACOS, it hasn’t been studied with respect to its responsiveness to different treatment options.”R. Stokes Peebles Jr., MD, professor of allergy, pulmonary, and critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., said that, although the number of published articles on ACOS has skyrocketed over the last several years, review articles have outnumbered original research articles.
There is disagreement in published definitions: One set of definitions includes a criterion of fractional exhaled nitric oxide not seen in any other definitions, whereas some other definitions require a history of smoking while others don’t, he said.
“How does one manage a disease without a definition and without clinical studies? It’s impossible for me to know,” Dr. Peebles said.
Jeffrey Drazen, MD, the Distinguished Parker B. Francis Professor of Medicine at Harvard Medical School, Boston, and the editor of the New England Journal of Medicine, also lamented the polar nature of the research.
“We all treat patients in the middle, everybody does, all the time – and we would love more guidance,” he said. “One of the reasons the number of articles has gone up is that there have been lots of case definitions. But we can’t get consensus. So who do we have to bring to the table to get a consensus definition so we can get the funding we need from the drug companies or governmental bodies to do the research that we all want?”
Dr. Tashkin said the way forward could be to draw on the points of consensus that do exist on certain criteria.
Dr. Peebles said an international panel is needed to draw up a consensus guideline, with the panel including both pulmonologists and allergists – “people experienced with clinical trials, who take care of a lot of patients.”
ORLANDO – to give clinicians data they can actually use.
The topic is even more pressing given the growing interest and research into biological treatments for asthma and consideration of their possible use in COPD, experts said at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization. Their remarks came in what was ostensibly a “debate” on whether ACOS is a distinct entity requiring special treatment but largely turned into a discussion about gaps in knowledge on the topic.
“The problem here is that it has not been defined in a way that everyone agrees on – that does create a problem because, if there’s no consensus on the diagnostic criteria, then it may be difficult to study this overlap,” said Donald Tashkin, MD, director of the pulmonary function laboratories at the University of California, Los Angeles. “Because there is no agreement on how to diagnose ACOS, it hasn’t been studied with respect to its responsiveness to different treatment options.”R. Stokes Peebles Jr., MD, professor of allergy, pulmonary, and critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., said that, although the number of published articles on ACOS has skyrocketed over the last several years, review articles have outnumbered original research articles.
There is disagreement in published definitions: One set of definitions includes a criterion of fractional exhaled nitric oxide not seen in any other definitions, whereas some other definitions require a history of smoking while others don’t, he said.
“How does one manage a disease without a definition and without clinical studies? It’s impossible for me to know,” Dr. Peebles said.
Jeffrey Drazen, MD, the Distinguished Parker B. Francis Professor of Medicine at Harvard Medical School, Boston, and the editor of the New England Journal of Medicine, also lamented the polar nature of the research.
“We all treat patients in the middle, everybody does, all the time – and we would love more guidance,” he said. “One of the reasons the number of articles has gone up is that there have been lots of case definitions. But we can’t get consensus. So who do we have to bring to the table to get a consensus definition so we can get the funding we need from the drug companies or governmental bodies to do the research that we all want?”
Dr. Tashkin said the way forward could be to draw on the points of consensus that do exist on certain criteria.
Dr. Peebles said an international panel is needed to draw up a consensus guideline, with the panel including both pulmonologists and allergists – “people experienced with clinical trials, who take care of a lot of patients.”
EXPERT ANALYSIS FROM AAAAI/WAO JOINT CONGRESS
House cleaning linked to lung function decline
that has found accelerated decline in lung function among women regularly engaged in cleaning activities.
The longitudinal population-based cohort study, published online Feb. 16 in the American Journal of Respiratory and Critical Care Medicine, looked at the lung health of 6,230 people who were followed for more than 20 years as part of the European Community Respiratory Health Survey.
Analysis based on questionnaires about cleaning practices revealed that women who were responsible for cleaning at home or who worked as professional cleaners showed significantly greater declines in maximum forced vital capacity (FVC) and maximum forced expiratory volume in 1 second (FEV1), compared with women who said they did not regularly clean.
However, there was no association between cleaning practices in men – either professional or domestic – and accelerated lung function decline. The authors suggested that the exposures experienced by men who worked as cleaners may have been different from the exposures experienced by women. They also noted that the small numbers of male cleaners meant the study wasn’t powered to pick up greater declines in lung function.
The study also showed a significant association between use of cleaning products and decline in lung function. Women who used sprays or other cleaning agents at least once a week showed significantly greater declines in FEV1 and FVC, compared with women who didn’t use cleaning products. Again, this effect was not significant in men.
“One possible mechanism for the accelerated decline in cleaners is the repetitive exposure to low-grade irritative cleaning agents over time, thereby causing persistent changes in the airways,” the authors wrote. “Repeated exposure could lead to remodelling of the airways, thereby over time causing an accelerated decline in FVC and FEV1.”
The analysis found no significant increases in the incidence of chronic airway obstruction among regular cleaners, nor among those who used cleaning products. The authors noted that while previous studies had suggested an increase in chronic obstructive pulmonary disease among occupational cleaners, their study reported relatively few cases of COPD.
While the prevalence of asthma was slightly higher in the two groups of women exposed to regular cleaning (12.3% and 13.7%, versus 9.6%), adjustment for asthma in the analysis did not change the associations. This suggests that the declines in lung function seen in regular cleaners were not mediated by cleaning-related asthma, the researchers noted.
They also noted that the women who reported not engaging in any cleaning may represent a particular socioeconomic group, but adjustment for socioeconomic status did not alter the associations.
The European Community Respiratory Health Survey is supported by the European Union, the European Commission, and the Medical Research Council. No conflicts of interest were reported.
SOURCE: Svanes Ø et al. Am J Resp Crit Care Med. 2018 Feb 16. doi: 10.1164/rccm.201706-1311OC.
that has found accelerated decline in lung function among women regularly engaged in cleaning activities.
The longitudinal population-based cohort study, published online Feb. 16 in the American Journal of Respiratory and Critical Care Medicine, looked at the lung health of 6,230 people who were followed for more than 20 years as part of the European Community Respiratory Health Survey.
Analysis based on questionnaires about cleaning practices revealed that women who were responsible for cleaning at home or who worked as professional cleaners showed significantly greater declines in maximum forced vital capacity (FVC) and maximum forced expiratory volume in 1 second (FEV1), compared with women who said they did not regularly clean.
However, there was no association between cleaning practices in men – either professional or domestic – and accelerated lung function decline. The authors suggested that the exposures experienced by men who worked as cleaners may have been different from the exposures experienced by women. They also noted that the small numbers of male cleaners meant the study wasn’t powered to pick up greater declines in lung function.
The study also showed a significant association between use of cleaning products and decline in lung function. Women who used sprays or other cleaning agents at least once a week showed significantly greater declines in FEV1 and FVC, compared with women who didn’t use cleaning products. Again, this effect was not significant in men.
“One possible mechanism for the accelerated decline in cleaners is the repetitive exposure to low-grade irritative cleaning agents over time, thereby causing persistent changes in the airways,” the authors wrote. “Repeated exposure could lead to remodelling of the airways, thereby over time causing an accelerated decline in FVC and FEV1.”
The analysis found no significant increases in the incidence of chronic airway obstruction among regular cleaners, nor among those who used cleaning products. The authors noted that while previous studies had suggested an increase in chronic obstructive pulmonary disease among occupational cleaners, their study reported relatively few cases of COPD.
While the prevalence of asthma was slightly higher in the two groups of women exposed to regular cleaning (12.3% and 13.7%, versus 9.6%), adjustment for asthma in the analysis did not change the associations. This suggests that the declines in lung function seen in regular cleaners were not mediated by cleaning-related asthma, the researchers noted.
They also noted that the women who reported not engaging in any cleaning may represent a particular socioeconomic group, but adjustment for socioeconomic status did not alter the associations.
The European Community Respiratory Health Survey is supported by the European Union, the European Commission, and the Medical Research Council. No conflicts of interest were reported.
SOURCE: Svanes Ø et al. Am J Resp Crit Care Med. 2018 Feb 16. doi: 10.1164/rccm.201706-1311OC.
that has found accelerated decline in lung function among women regularly engaged in cleaning activities.
The longitudinal population-based cohort study, published online Feb. 16 in the American Journal of Respiratory and Critical Care Medicine, looked at the lung health of 6,230 people who were followed for more than 20 years as part of the European Community Respiratory Health Survey.
Analysis based on questionnaires about cleaning practices revealed that women who were responsible for cleaning at home or who worked as professional cleaners showed significantly greater declines in maximum forced vital capacity (FVC) and maximum forced expiratory volume in 1 second (FEV1), compared with women who said they did not regularly clean.
However, there was no association between cleaning practices in men – either professional or domestic – and accelerated lung function decline. The authors suggested that the exposures experienced by men who worked as cleaners may have been different from the exposures experienced by women. They also noted that the small numbers of male cleaners meant the study wasn’t powered to pick up greater declines in lung function.
The study also showed a significant association between use of cleaning products and decline in lung function. Women who used sprays or other cleaning agents at least once a week showed significantly greater declines in FEV1 and FVC, compared with women who didn’t use cleaning products. Again, this effect was not significant in men.
“One possible mechanism for the accelerated decline in cleaners is the repetitive exposure to low-grade irritative cleaning agents over time, thereby causing persistent changes in the airways,” the authors wrote. “Repeated exposure could lead to remodelling of the airways, thereby over time causing an accelerated decline in FVC and FEV1.”
The analysis found no significant increases in the incidence of chronic airway obstruction among regular cleaners, nor among those who used cleaning products. The authors noted that while previous studies had suggested an increase in chronic obstructive pulmonary disease among occupational cleaners, their study reported relatively few cases of COPD.
While the prevalence of asthma was slightly higher in the two groups of women exposed to regular cleaning (12.3% and 13.7%, versus 9.6%), adjustment for asthma in the analysis did not change the associations. This suggests that the declines in lung function seen in regular cleaners were not mediated by cleaning-related asthma, the researchers noted.
They also noted that the women who reported not engaging in any cleaning may represent a particular socioeconomic group, but adjustment for socioeconomic status did not alter the associations.
The European Community Respiratory Health Survey is supported by the European Union, the European Commission, and the Medical Research Council. No conflicts of interest were reported.
SOURCE: Svanes Ø et al. Am J Resp Crit Care Med. 2018 Feb 16. doi: 10.1164/rccm.201706-1311OC.
FROM AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Key clinical point: Women – but not men – who regularly clean homes either domestically or professionally show accelerated declines in lung function.
Major finding: Women who work as cleaners or clean their own homes regularly show greater declines in FEV1 and FVC, compared with women who do not clean regularly.
Data source: Longitudinal cohort study of 6,230 individuals in the European Community Respiratory Health Survey.
Disclosures: The European Community Respiratory Health Survey is supported by the European Union, the European Commission, and the Medical Research Council. No conflicts of interest were provided.
Source: Svanes Ø et al. Am J Resp Crit Care Med. 2018 Feb. 16. doi: 10.1164/rccm.201706-1311OC.
FDA’s standards for approving generics are questioned
TORONTO – The Food and Drug Administration’s standards for demonstrating pharmacokinetic bioequivalence between two inhaled products, which allow for single batch comparisons of approved and generic candidate products, need to be revised to address batch to batch variability, suggested a presenter at the CHEST annual meeting.
Marketing approval of a new generic drug in the United States, including orally inhaled products, generally requires a demonstration of pharmacokinetic bioequivalence to a reference listed product. The standard criterion for statistical bioequivalence applied by the FDA requires the pharmacokinetics of the generic to be within about 10% of the branded product.
In early pharmacokinetic bioequivalence studies, Elise Burmeister Getz, PhD, and her colleagues compared single batches of their generic candidate OT329 Solis 100/50 to single batches of Advair Diskus 100/50 in five individual studies and single batches of Advair Diskus 100/50 to single batches of the same drug. They also found Advair Diskus 100/50 batches that were more than 30% different from each other. 
“When patients differ from one another, we put many patients in the trial. And when batches differ from one another, we should be putting many batches in the trial,” Dr. Burmeister Getz, director of clinical pharmacology at Oriel Therapeutics, said at the CHEST meeting. “If we want a robust assessment of bioequivalence and not just a check the box exercise, we really need to have product sampling that’s aligned with product variability.”
When the researchers combined the data in a meta-analysis, bioequivalence was demonstrated, but the pooled analysis could not be used for FDA registration because of its retrospective nature.
They later conducted a prospective study with multiple batches of both the generic and branded drugs. This multiple-batch bioequivalence study involved 96 healthy subjects using 16 batches each of Advair Diskus and Oriel’s OT329 Solis 100/50. A single inhalation was administered to healthy adult subjects in a randomized crossover design and blood samples were collected pre dose and up to 48 hours after inhalation.
With the FDA’s definition of bioequivalence, the generic candidate fell within the bioequivalence goalposts, Dr. Burmeister Getz noted.
The issue of pharmacokinetic variance is not unique to Advair Diskus, but she and her colleagues don’t understand why different batches show such wide variability, Dr. Burmeister Getz noted.
“The advantage of this multibatch approach is that the results of the bioequivalence assessment aren’t dependent on the single batch that happened to be chosen for the study. They are generalizable to the product because the product has been robustly represented in the study,” Dr. Burmeister Getz told attendees.
Oriel makes OT329 Solis 100/50, a fully substitutable generic to Advair Diskus 100/50, which is indicated for treating asthma. Both are multidose dry powder oral inhalation products containing fluticasone propionate, to reduce inflammation in the lungs, and salmeterol, to relax muscles in the airways, for the maintenance treatment of asthma. Advair Diskus at higher doses is indicated for asthma and COPD.
An FDA response?
Asked what the FDA makes of the batch-to-batch variability data, Dr. Burmeister Getz answered simply, “We don’t know.” Before she and her colleagues ran the 16 batch per product study, they submitted their protocol to the FDA for review, but 1 year later, they still hadn’t heard any response.
“Sponsors are apparently allowed to simply pick their batch in a careful and, dare I say manipulative way, to gain the result they want. With a single batch study the selection of batch will absolutely determine the outcome of the study.”
In vitro bioequivalence studies are already required to use multiple batches, she noted.
This research was funded by Oriel Therapeutics, an indirect wholly-owned subsidiary of Novartis AG.
TORONTO – The Food and Drug Administration’s standards for demonstrating pharmacokinetic bioequivalence between two inhaled products, which allow for single batch comparisons of approved and generic candidate products, need to be revised to address batch to batch variability, suggested a presenter at the CHEST annual meeting.
Marketing approval of a new generic drug in the United States, including orally inhaled products, generally requires a demonstration of pharmacokinetic bioequivalence to a reference listed product. The standard criterion for statistical bioequivalence applied by the FDA requires the pharmacokinetics of the generic to be within about 10% of the branded product.
In early pharmacokinetic bioequivalence studies, Elise Burmeister Getz, PhD, and her colleagues compared single batches of their generic candidate OT329 Solis 100/50 to single batches of Advair Diskus 100/50 in five individual studies and single batches of Advair Diskus 100/50 to single batches of the same drug. They also found Advair Diskus 100/50 batches that were more than 30% different from each other.
“When patients differ from one another, we put many patients in the trial. And when batches differ from one another, we should be putting many batches in the trial,” Dr. Burmeister Getz, director of clinical pharmacology at Oriel Therapeutics, said at the CHEST meeting. “If we want a robust assessment of bioequivalence and not just a check the box exercise, we really need to have product sampling that’s aligned with product variability.”
When the researchers combined the data in a meta-analysis, bioequivalence was demonstrated, but the pooled analysis could not be used for FDA registration because of its retrospective nature.
They later conducted a prospective study with multiple batches of both the generic and branded drugs. This multiple-batch bioequivalence study involved 96 healthy subjects using 16 batches each of Advair Diskus and Oriel’s OT329 Solis 100/50. A single inhalation was administered to healthy adult subjects in a randomized crossover design and blood samples were collected pre dose and up to 48 hours after inhalation.
With the FDA’s definition of bioequivalence, the generic candidate fell within the bioequivalence goalposts, Dr. Burmeister Getz noted.
The issue of pharmacokinetic variance is not unique to Advair Diskus, but she and her colleagues don’t understand why different batches show such wide variability, Dr. Burmeister Getz noted.
“The advantage of this multibatch approach is that the results of the bioequivalence assessment aren’t dependent on the single batch that happened to be chosen for the study. They are generalizable to the product because the product has been robustly represented in the study,” Dr. Burmeister Getz told attendees.
Oriel makes OT329 Solis 100/50, a fully substitutable generic to Advair Diskus 100/50, which is indicated for treating asthma. Both are multidose dry powder oral inhalation products containing fluticasone propionate, to reduce inflammation in the lungs, and salmeterol, to relax muscles in the airways, for the maintenance treatment of asthma. Advair Diskus at higher doses is indicated for asthma and COPD.
An FDA response?
Asked what the FDA makes of the batch-to-batch variability data, Dr. Burmeister Getz answered simply, “We don’t know.” Before she and her colleagues ran the 16 batch per product study, they submitted their protocol to the FDA for review, but 1 year later, they still hadn’t heard any response.
“Sponsors are apparently allowed to simply pick their batch in a careful and, dare I say manipulative way, to gain the result they want. With a single batch study the selection of batch will absolutely determine the outcome of the study.”
In vitro bioequivalence studies are already required to use multiple batches, she noted.
This research was funded by Oriel Therapeutics, an indirect wholly-owned subsidiary of Novartis AG.
TORONTO – The Food and Drug Administration’s standards for demonstrating pharmacokinetic bioequivalence between two inhaled products, which allow for single batch comparisons of approved and generic candidate products, need to be revised to address batch to batch variability, suggested a presenter at the CHEST annual meeting.
Marketing approval of a new generic drug in the United States, including orally inhaled products, generally requires a demonstration of pharmacokinetic bioequivalence to a reference listed product. The standard criterion for statistical bioequivalence applied by the FDA requires the pharmacokinetics of the generic to be within about 10% of the branded product.
In early pharmacokinetic bioequivalence studies, Elise Burmeister Getz, PhD, and her colleagues compared single batches of their generic candidate OT329 Solis 100/50 to single batches of Advair Diskus 100/50 in five individual studies and single batches of Advair Diskus 100/50 to single batches of the same drug. They also found Advair Diskus 100/50 batches that were more than 30% different from each other.
“When patients differ from one another, we put many patients in the trial. And when batches differ from one another, we should be putting many batches in the trial,” Dr. Burmeister Getz, director of clinical pharmacology at Oriel Therapeutics, said at the CHEST meeting. “If we want a robust assessment of bioequivalence and not just a check the box exercise, we really need to have product sampling that’s aligned with product variability.”
When the researchers combined the data in a meta-analysis, bioequivalence was demonstrated, but the pooled analysis could not be used for FDA registration because of its retrospective nature.
They later conducted a prospective study with multiple batches of both the generic and branded drugs. This multiple-batch bioequivalence study involved 96 healthy subjects using 16 batches each of Advair Diskus and Oriel’s OT329 Solis 100/50. A single inhalation was administered to healthy adult subjects in a randomized crossover design and blood samples were collected pre dose and up to 48 hours after inhalation.
With the FDA’s definition of bioequivalence, the generic candidate fell within the bioequivalence goalposts, Dr. Burmeister Getz noted.
The issue of pharmacokinetic variance is not unique to Advair Diskus, but she and her colleagues don’t understand why different batches show such wide variability, Dr. Burmeister Getz noted.
“The advantage of this multibatch approach is that the results of the bioequivalence assessment aren’t dependent on the single batch that happened to be chosen for the study. They are generalizable to the product because the product has been robustly represented in the study,” Dr. Burmeister Getz told attendees.
Oriel makes OT329 Solis 100/50, a fully substitutable generic to Advair Diskus 100/50, which is indicated for treating asthma. Both are multidose dry powder oral inhalation products containing fluticasone propionate, to reduce inflammation in the lungs, and salmeterol, to relax muscles in the airways, for the maintenance treatment of asthma. Advair Diskus at higher doses is indicated for asthma and COPD.
An FDA response?
Asked what the FDA makes of the batch-to-batch variability data, Dr. Burmeister Getz answered simply, “We don’t know.” Before she and her colleagues ran the 16 batch per product study, they submitted their protocol to the FDA for review, but 1 year later, they still hadn’t heard any response.
“Sponsors are apparently allowed to simply pick their batch in a careful and, dare I say manipulative way, to gain the result they want. With a single batch study the selection of batch will absolutely determine the outcome of the study.”
In vitro bioequivalence studies are already required to use multiple batches, she noted.
This research was funded by Oriel Therapeutics, an indirect wholly-owned subsidiary of Novartis AG.
AT CHEST 2017
Key clinical point: The FDA’s standards for demonstrating pharmacokinetic bioequivalence between two inhaled products need to be revised to address batch to batch variability.
Major finding: Investigators found Advair Diskus 100/50 batches that were more than 30% different from each other.
Data source: Pharmacokinetic bioequivalence studies comparing batches of Advair Diskus 100/50 to each other, and to batches of the generic candidate OT329 Solis 100/50.
Disclosures: This research was funded by Oriel Therapeutics, an indirect wholly-owned subsidiary of Novartis AG. Dr. Burmeister Getz is director of clinical pharmacology at Oriel Therapeutics.
FDA approves starting dose of roflumilast
The Food and Drug Administration has approved the use of a 250-mcg dose of roflumilast for patients with chronic obstructive pulmonary disease (COPD) for 4 weeks, followed by the use of 500-mcg therapeutic doses, according to a statement from the drug’s marketer, AstraZeneca.
The larger doses of roflumilast (Daliresp) are currently indicated for reducing the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations, according to the statement. The selective phosphodiesterase-4 inhibitor, roflumilast, was approved for this use in 500-mcg doses in 2011. The new smaller doses of the drug are being offered to help reduce the rate of treatment discontinuation with use of the higher therapeutic dosing. The 250-mcg doses of roflumilast are not to be used as treatment for COPD.
“As the only once-daily tablet to provide enhanced protection against COPD exacerbations when added to current bronchodilator therapy, this is an important new dosing option to help patients start and stay on treatment. Exacerbations are associated with hospitalizations and an accelerated decline in lung function, and these patients living with COPD need effective treatment options,” Tosh Butt, vice president, respiratory, at AstraZeneca, said in the press release.
The approval of use of the 250-mcg doses was based on data from the OPTIMIZE study (Evaluation of Tolerability and Pharmacokinetics of Roflumilast trial, 250 mcg and 500 mcg, as an add-on to Standard COPD Treatment to Treat Severe COPD), according to the statement.
Over 12 weeks, the percentage of patients stopping treatment was significantly lower in those first given 250 mcg of roflumilast daily for 4 weeks, followed by 500 mcg once a week for 8 weeks (18.4%), compared with those given 500 mcg of roflumilast daily for 12 weeks (24.6%; odds ratio, 0.66; 95% confidence interval, 0.47-0.93; P = .017).
In eight controlled clinical trials, the most common adverse effects were diarrhea, weight loss, nausea, headache, back pain, influenza, insomnia, dizziness, and decreased appetite.
The Food and Drug Administration has approved the use of a 250-mcg dose of roflumilast for patients with chronic obstructive pulmonary disease (COPD) for 4 weeks, followed by the use of 500-mcg therapeutic doses, according to a statement from the drug’s marketer, AstraZeneca.
The larger doses of roflumilast (Daliresp) are currently indicated for reducing the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations, according to the statement. The selective phosphodiesterase-4 inhibitor, roflumilast, was approved for this use in 500-mcg doses in 2011. The new smaller doses of the drug are being offered to help reduce the rate of treatment discontinuation with use of the higher therapeutic dosing. The 250-mcg doses of roflumilast are not to be used as treatment for COPD.
“As the only once-daily tablet to provide enhanced protection against COPD exacerbations when added to current bronchodilator therapy, this is an important new dosing option to help patients start and stay on treatment. Exacerbations are associated with hospitalizations and an accelerated decline in lung function, and these patients living with COPD need effective treatment options,” Tosh Butt, vice president, respiratory, at AstraZeneca, said in the press release.
The approval of use of the 250-mcg doses was based on data from the OPTIMIZE study (Evaluation of Tolerability and Pharmacokinetics of Roflumilast trial, 250 mcg and 500 mcg, as an add-on to Standard COPD Treatment to Treat Severe COPD), according to the statement.
Over 12 weeks, the percentage of patients stopping treatment was significantly lower in those first given 250 mcg of roflumilast daily for 4 weeks, followed by 500 mcg once a week for 8 weeks (18.4%), compared with those given 500 mcg of roflumilast daily for 12 weeks (24.6%; odds ratio, 0.66; 95% confidence interval, 0.47-0.93; P = .017).
In eight controlled clinical trials, the most common adverse effects were diarrhea, weight loss, nausea, headache, back pain, influenza, insomnia, dizziness, and decreased appetite.
The Food and Drug Administration has approved the use of a 250-mcg dose of roflumilast for patients with chronic obstructive pulmonary disease (COPD) for 4 weeks, followed by the use of 500-mcg therapeutic doses, according to a statement from the drug’s marketer, AstraZeneca.
The larger doses of roflumilast (Daliresp) are currently indicated for reducing the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations, according to the statement. The selective phosphodiesterase-4 inhibitor, roflumilast, was approved for this use in 500-mcg doses in 2011. The new smaller doses of the drug are being offered to help reduce the rate of treatment discontinuation with use of the higher therapeutic dosing. The 250-mcg doses of roflumilast are not to be used as treatment for COPD.
“As the only once-daily tablet to provide enhanced protection against COPD exacerbations when added to current bronchodilator therapy, this is an important new dosing option to help patients start and stay on treatment. Exacerbations are associated with hospitalizations and an accelerated decline in lung function, and these patients living with COPD need effective treatment options,” Tosh Butt, vice president, respiratory, at AstraZeneca, said in the press release.
The approval of use of the 250-mcg doses was based on data from the OPTIMIZE study (Evaluation of Tolerability and Pharmacokinetics of Roflumilast trial, 250 mcg and 500 mcg, as an add-on to Standard COPD Treatment to Treat Severe COPD), according to the statement.
Over 12 weeks, the percentage of patients stopping treatment was significantly lower in those first given 250 mcg of roflumilast daily for 4 weeks, followed by 500 mcg once a week for 8 weeks (18.4%), compared with those given 500 mcg of roflumilast daily for 12 weeks (24.6%; odds ratio, 0.66; 95% confidence interval, 0.47-0.93; P = .017).
In eight controlled clinical trials, the most common adverse effects were diarrhea, weight loss, nausea, headache, back pain, influenza, insomnia, dizziness, and decreased appetite.
First month of LABA/LAMA ups cardiovascular risk
New use of inhaled long-acting beta-2 agonists (LABAs) or long-acting antimuscarinic antagonists (LAMAs) was associated with a 1.5-fold increased cardiovascular risk within 30 days of initiation in patients with chronic obstructive pulmonary disease, irrespective of prior cardiovascular disease status and history of exacerbations, according to a review of more than 280,000 COPD patients in Taiwan.
The relationship between cardiovascular disease (CVD) and LABAs and LAMAs in chronic obstructive pulmonary disease (COPD) has long been debated. The new study addressed some limitations of previous studies, which had found conflicting results ranging from no increased risk to up to a 4.5-fold increased risk of cardiovascular events when the medications were used for COPD.
Previous randomized trials haven’t raised much concern, but they included prior users who may have developed tolerance to the heart effects and excluded patients with baseline CVD. “We caution physicians to closely monitor new users of LABAs or LAMAs for cardiovascular symptoms.” Health care professionals should be vigilant for any cardiovascular symptoms during the first 30 days of inhalation therapy, said investigators led by Meng-Ting Wang, PhD, of the National Defense Medical Center, Taipei.
“We suspect that there may exist a subgroup of patients with COPD who are particularly at risk of CVD with initial exposure to LABAs or LAMAs ... we suggest that the use of inhaled long-acting bronchodilators in COPD needs to be carefully assessed, and a thorough cardiovascular physical examination, especially heart rate measurement and electrocardiograms, needs to be performed” before prescribing LABAs and LAMAs, they wrote in an article in JAMA Internal Medicine.
The team identified 284,220 COPD patients in the Taiwan National Health Insurance Research Database during 2007-2011 who were new to the medications. During a mean follow-up of 2 years, 37,719 developed severe CVD requiring hospitalization or emergency care, including coronary artery disease, heart failure, ischemic stroke, and arrhythmia.
The team compared their CVD subjects with controls who did not have a heart event and found that new LABA and LAMA use in COPD was associated with a 1.50-fold (95% confidence interval, 1.35-1.67; P less than .001) and a 1.52-fold (95% CI, 1.28-1.80; P less than .001) increased cardiovascular risk within 30 days of initiation, respectively.
One severe CVD event requiring hospitalization or ED care occurred for every 406 (95% CI, 303-580) new LABA users and 391 (95% CI, 254-725) new LAMA users during the first 30 days of therapy.
The LABA- and LAMA-associated CVD risk remained significant, regardless of patients’ CVD history and COPD exacerbations. Analyses of individual CVD outcomes revealed increased risks of coronary artery disease and heart failure with LABA and LAMA treatment, and an increased risk for cardiac arrhythmias with LAMA therapy.
The cardiovascular risks peaked at around the 30th day of treatment, waned from 31-60 days of treatment, and reduced to a level lower than the baseline risk from 71-240 days.
“Given that CVD is highly prevalent among patients with COPD, clinicians should also pay attention to the management of CVD risk factors throughout the duration of LABA or LAMA therapy ... if needed, a preventive therapy for CVD should be considered during the initial treatment of inhaled long-acting bronchodilators,” the investigators said.
LABAs and LAMAs are believed to cause sympathetic overactivation by activating sympathetic beta-2 adrenergic receptors and suppressing parasympathetic muscarinic-3 receptors, which could contribute to the CVD risk. Also, LABA and LAMA use in COPD has been observed to increase inflammatory cytokine levels, which might also play a role.
The subjects were 40 years or older; the mean age was 71.4 years and 68.9% of the participants were men.
The work was supported by Taiwan’s Ministry of Science and Technology. The investigators had no disclosures.
Eli Zimmerman contributed to this report.
SOURCE: Wang MT et al. JAMA Intern Med. 2018 Jan 2. doi: 10.1001/jamainternmed.2017.7720.
Daniel R. Ouellette, MD, FCCP, comments: Long acting beta agonists (LABA) and long acting muscarinic antagonists (LAMA) are agents commonly used to treat patients with chronic obstructive pulmonary disease (COPD). These inhaled medications have been generally considered to be safe and have a favorable side-effect profile. Although there has been some speculative data that suggest that these agents may be associated with increased cardiovascular risk, prospective, controlled studies have generally suggested that the cardiovascular risk is not increased with the use of these medicines.
One strength of this study is the size of the database, which is robust, and the novel treatment that this study uses to address the research question. Weaknesses include the study's necessarily retrospective design, and the fact that the population is from a single geographic area. Further research will be needed to understand whether or not the initiation of LABA and LAMA medications in COPD patients is associated with increased cardiovascular risk.
Daniel R. Ouellette, MD, FCCP, comments: Long acting beta agonists (LABA) and long acting muscarinic antagonists (LAMA) are agents commonly used to treat patients with chronic obstructive pulmonary disease (COPD). These inhaled medications have been generally considered to be safe and have a favorable side-effect profile. Although there has been some speculative data that suggest that these agents may be associated with increased cardiovascular risk, prospective, controlled studies have generally suggested that the cardiovascular risk is not increased with the use of these medicines.
One strength of this study is the size of the database, which is robust, and the novel treatment that this study uses to address the research question. Weaknesses include the study's necessarily retrospective design, and the fact that the population is from a single geographic area. Further research will be needed to understand whether or not the initiation of LABA and LAMA medications in COPD patients is associated with increased cardiovascular risk.
Daniel R. Ouellette, MD, FCCP, comments: Long acting beta agonists (LABA) and long acting muscarinic antagonists (LAMA) are agents commonly used to treat patients with chronic obstructive pulmonary disease (COPD). These inhaled medications have been generally considered to be safe and have a favorable side-effect profile. Although there has been some speculative data that suggest that these agents may be associated with increased cardiovascular risk, prospective, controlled studies have generally suggested that the cardiovascular risk is not increased with the use of these medicines.
One strength of this study is the size of the database, which is robust, and the novel treatment that this study uses to address the research question. Weaknesses include the study's necessarily retrospective design, and the fact that the population is from a single geographic area. Further research will be needed to understand whether or not the initiation of LABA and LAMA medications in COPD patients is associated with increased cardiovascular risk.
New use of inhaled long-acting beta-2 agonists (LABAs) or long-acting antimuscarinic antagonists (LAMAs) was associated with a 1.5-fold increased cardiovascular risk within 30 days of initiation in patients with chronic obstructive pulmonary disease, irrespective of prior cardiovascular disease status and history of exacerbations, according to a review of more than 280,000 COPD patients in Taiwan.
The relationship between cardiovascular disease (CVD) and LABAs and LAMAs in chronic obstructive pulmonary disease (COPD) has long been debated. The new study addressed some limitations of previous studies, which had found conflicting results ranging from no increased risk to up to a 4.5-fold increased risk of cardiovascular events when the medications were used for COPD.
Previous randomized trials haven’t raised much concern, but they included prior users who may have developed tolerance to the heart effects and excluded patients with baseline CVD. “We caution physicians to closely monitor new users of LABAs or LAMAs for cardiovascular symptoms.” Health care professionals should be vigilant for any cardiovascular symptoms during the first 30 days of inhalation therapy, said investigators led by Meng-Ting Wang, PhD, of the National Defense Medical Center, Taipei.
“We suspect that there may exist a subgroup of patients with COPD who are particularly at risk of CVD with initial exposure to LABAs or LAMAs ... we suggest that the use of inhaled long-acting bronchodilators in COPD needs to be carefully assessed, and a thorough cardiovascular physical examination, especially heart rate measurement and electrocardiograms, needs to be performed” before prescribing LABAs and LAMAs, they wrote in an article in JAMA Internal Medicine.
The team identified 284,220 COPD patients in the Taiwan National Health Insurance Research Database during 2007-2011 who were new to the medications. During a mean follow-up of 2 years, 37,719 developed severe CVD requiring hospitalization or emergency care, including coronary artery disease, heart failure, ischemic stroke, and arrhythmia.
The team compared their CVD subjects with controls who did not have a heart event and found that new LABA and LAMA use in COPD was associated with a 1.50-fold (95% confidence interval, 1.35-1.67; P less than .001) and a 1.52-fold (95% CI, 1.28-1.80; P less than .001) increased cardiovascular risk within 30 days of initiation, respectively.
One severe CVD event requiring hospitalization or ED care occurred for every 406 (95% CI, 303-580) new LABA users and 391 (95% CI, 254-725) new LAMA users during the first 30 days of therapy.
The LABA- and LAMA-associated CVD risk remained significant, regardless of patients’ CVD history and COPD exacerbations. Analyses of individual CVD outcomes revealed increased risks of coronary artery disease and heart failure with LABA and LAMA treatment, and an increased risk for cardiac arrhythmias with LAMA therapy.
The cardiovascular risks peaked at around the 30th day of treatment, waned from 31-60 days of treatment, and reduced to a level lower than the baseline risk from 71-240 days.
“Given that CVD is highly prevalent among patients with COPD, clinicians should also pay attention to the management of CVD risk factors throughout the duration of LABA or LAMA therapy ... if needed, a preventive therapy for CVD should be considered during the initial treatment of inhaled long-acting bronchodilators,” the investigators said.
LABAs and LAMAs are believed to cause sympathetic overactivation by activating sympathetic beta-2 adrenergic receptors and suppressing parasympathetic muscarinic-3 receptors, which could contribute to the CVD risk. Also, LABA and LAMA use in COPD has been observed to increase inflammatory cytokine levels, which might also play a role.
The subjects were 40 years or older; the mean age was 71.4 years and 68.9% of the participants were men.
The work was supported by Taiwan’s Ministry of Science and Technology. The investigators had no disclosures.
Eli Zimmerman contributed to this report.
SOURCE: Wang MT et al. JAMA Intern Med. 2018 Jan 2. doi: 10.1001/jamainternmed.2017.7720.
New use of inhaled long-acting beta-2 agonists (LABAs) or long-acting antimuscarinic antagonists (LAMAs) was associated with a 1.5-fold increased cardiovascular risk within 30 days of initiation in patients with chronic obstructive pulmonary disease, irrespective of prior cardiovascular disease status and history of exacerbations, according to a review of more than 280,000 COPD patients in Taiwan.
The relationship between cardiovascular disease (CVD) and LABAs and LAMAs in chronic obstructive pulmonary disease (COPD) has long been debated. The new study addressed some limitations of previous studies, which had found conflicting results ranging from no increased risk to up to a 4.5-fold increased risk of cardiovascular events when the medications were used for COPD.
Previous randomized trials haven’t raised much concern, but they included prior users who may have developed tolerance to the heart effects and excluded patients with baseline CVD. “We caution physicians to closely monitor new users of LABAs or LAMAs for cardiovascular symptoms.” Health care professionals should be vigilant for any cardiovascular symptoms during the first 30 days of inhalation therapy, said investigators led by Meng-Ting Wang, PhD, of the National Defense Medical Center, Taipei.
“We suspect that there may exist a subgroup of patients with COPD who are particularly at risk of CVD with initial exposure to LABAs or LAMAs ... we suggest that the use of inhaled long-acting bronchodilators in COPD needs to be carefully assessed, and a thorough cardiovascular physical examination, especially heart rate measurement and electrocardiograms, needs to be performed” before prescribing LABAs and LAMAs, they wrote in an article in JAMA Internal Medicine.
The team identified 284,220 COPD patients in the Taiwan National Health Insurance Research Database during 2007-2011 who were new to the medications. During a mean follow-up of 2 years, 37,719 developed severe CVD requiring hospitalization or emergency care, including coronary artery disease, heart failure, ischemic stroke, and arrhythmia.
The team compared their CVD subjects with controls who did not have a heart event and found that new LABA and LAMA use in COPD was associated with a 1.50-fold (95% confidence interval, 1.35-1.67; P less than .001) and a 1.52-fold (95% CI, 1.28-1.80; P less than .001) increased cardiovascular risk within 30 days of initiation, respectively.
One severe CVD event requiring hospitalization or ED care occurred for every 406 (95% CI, 303-580) new LABA users and 391 (95% CI, 254-725) new LAMA users during the first 30 days of therapy.
The LABA- and LAMA-associated CVD risk remained significant, regardless of patients’ CVD history and COPD exacerbations. Analyses of individual CVD outcomes revealed increased risks of coronary artery disease and heart failure with LABA and LAMA treatment, and an increased risk for cardiac arrhythmias with LAMA therapy.
The cardiovascular risks peaked at around the 30th day of treatment, waned from 31-60 days of treatment, and reduced to a level lower than the baseline risk from 71-240 days.
“Given that CVD is highly prevalent among patients with COPD, clinicians should also pay attention to the management of CVD risk factors throughout the duration of LABA or LAMA therapy ... if needed, a preventive therapy for CVD should be considered during the initial treatment of inhaled long-acting bronchodilators,” the investigators said.
LABAs and LAMAs are believed to cause sympathetic overactivation by activating sympathetic beta-2 adrenergic receptors and suppressing parasympathetic muscarinic-3 receptors, which could contribute to the CVD risk. Also, LABA and LAMA use in COPD has been observed to increase inflammatory cytokine levels, which might also play a role.
The subjects were 40 years or older; the mean age was 71.4 years and 68.9% of the participants were men.
The work was supported by Taiwan’s Ministry of Science and Technology. The investigators had no disclosures.
Eli Zimmerman contributed to this report.
SOURCE: Wang MT et al. JAMA Intern Med. 2018 Jan 2. doi: 10.1001/jamainternmed.2017.7720.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Researchers recommend patients receive a thorough cardiovascular physical examination before they are prescribed LABAs and LAMAs.
Major finding: New irrespective of prior cardiovascular disease status and history of exacerbations.
Study details: The findings are from a review of 284,220 COPD patients in the Taiwan National Health Insurance Research Database.
Disclosures: The work was supported by Taiwan’s Ministry of Science and Technology. The investigators had no disclosures.
Source: Wang MT et al. JAMA Intern Med. 2018 Jan 2. doi: 10.1001/jamainternmed.2017.7720.
FDA axes asthma drugs’ boxed warning
The Food and Drug Administration has eliminated the boxed warning for risk of asthma-related death from the labels of products containing both an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA), the agency announced.
In 2011, the FDA required companies manufacturing fixed-dose LABA-ICS combination products to conduct 26-week clinical safety trials to evaluate the risks of serious adverse asthma-related events in patients treated with these drugs. Specifically, the companies had to compare the risks of taking a LABA in combination with an ICS with the risks of taking an ICS alone.
The removal of the boxed warning follows the FDA’s review of these trials, which found that treating asthma with LABAs in combination with ICS did not result in patients experiencing significantly more serious asthma-related side effects and asthma-related deaths, compared with those being treated with an ICS alone, according to the FDA announcement. “Results of subgroup analyses for gender, adolescents 12-18 years, and African Americans are consistent with the primary endpoint results,” the statement added.
“These trials showed that LABAs, when used with ICS, did not significantly increase the risk of asthma-related hospitalizations, the need to insert a breathing tube known as intubation, or asthma-related deaths, compared to ICS alone,” the FDA said in the statement.
The trials also demonstrated that using the combination reduced asthma exacerbations, compared with using ICS alone, and that most of the exacerbations “were those that required at least 3 days of systemic corticosteroids” – information that is being added the product labels, according to the FDA.
The products that will no longer carry this boxed warning in their labels include AstraZeneca’s budesonide/formoterol fumarate dihydrate (Symbicort) and GlaxoSmithKline’s fluticasone furoate/vilanterol (Breo Ellipta) and fluticasone propionate/salmeterol (Advair Diskus and Advair HFA).
The FDA also approved updates to the Warnings and Precautions section of labeling for the ICS/LABA class, which now includes a description of the four trials. Information on the efficacy of the drugs, found in the trials, has been added to the Clinical Studies section of the labels as well.
In a related safety announcement, the FDA stated the following: “Using LABAs alone to treat asthma without an ICS to treat lung inflammation is associated with an increased risk of asthma-related death. Therefore, the Boxed Warning stating this will remain in the labels of all single-ingredient LABA medicines, which are approved to treat asthma, chronic obstructive pulmonary disease (COPD), and wheezing caused by exercise. The labels of medicines that contain both an ICS and LABA also retain a Warning and Precaution related to the increased risk of asthma-related death when LABAs are used without an ICS to treat asthma.
The Food and Drug Administration has eliminated the boxed warning for risk of asthma-related death from the labels of products containing both an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA), the agency announced.
In 2011, the FDA required companies manufacturing fixed-dose LABA-ICS combination products to conduct 26-week clinical safety trials to evaluate the risks of serious adverse asthma-related events in patients treated with these drugs. Specifically, the companies had to compare the risks of taking a LABA in combination with an ICS with the risks of taking an ICS alone.
The removal of the boxed warning follows the FDA’s review of these trials, which found that treating asthma with LABAs in combination with ICS did not result in patients experiencing significantly more serious asthma-related side effects and asthma-related deaths, compared with those being treated with an ICS alone, according to the FDA announcement. “Results of subgroup analyses for gender, adolescents 12-18 years, and African Americans are consistent with the primary endpoint results,” the statement added.
“These trials showed that LABAs, when used with ICS, did not significantly increase the risk of asthma-related hospitalizations, the need to insert a breathing tube known as intubation, or asthma-related deaths, compared to ICS alone,” the FDA said in the statement.
The trials also demonstrated that using the combination reduced asthma exacerbations, compared with using ICS alone, and that most of the exacerbations “were those that required at least 3 days of systemic corticosteroids” – information that is being added the product labels, according to the FDA.
The products that will no longer carry this boxed warning in their labels include AstraZeneca’s budesonide/formoterol fumarate dihydrate (Symbicort) and GlaxoSmithKline’s fluticasone furoate/vilanterol (Breo Ellipta) and fluticasone propionate/salmeterol (Advair Diskus and Advair HFA).
The FDA also approved updates to the Warnings and Precautions section of labeling for the ICS/LABA class, which now includes a description of the four trials. Information on the efficacy of the drugs, found in the trials, has been added to the Clinical Studies section of the labels as well.
In a related safety announcement, the FDA stated the following: “Using LABAs alone to treat asthma without an ICS to treat lung inflammation is associated with an increased risk of asthma-related death. Therefore, the Boxed Warning stating this will remain in the labels of all single-ingredient LABA medicines, which are approved to treat asthma, chronic obstructive pulmonary disease (COPD), and wheezing caused by exercise. The labels of medicines that contain both an ICS and LABA also retain a Warning and Precaution related to the increased risk of asthma-related death when LABAs are used without an ICS to treat asthma.
The Food and Drug Administration has eliminated the boxed warning for risk of asthma-related death from the labels of products containing both an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA), the agency announced.
In 2011, the FDA required companies manufacturing fixed-dose LABA-ICS combination products to conduct 26-week clinical safety trials to evaluate the risks of serious adverse asthma-related events in patients treated with these drugs. Specifically, the companies had to compare the risks of taking a LABA in combination with an ICS with the risks of taking an ICS alone.
The removal of the boxed warning follows the FDA’s review of these trials, which found that treating asthma with LABAs in combination with ICS did not result in patients experiencing significantly more serious asthma-related side effects and asthma-related deaths, compared with those being treated with an ICS alone, according to the FDA announcement. “Results of subgroup analyses for gender, adolescents 12-18 years, and African Americans are consistent with the primary endpoint results,” the statement added.
“These trials showed that LABAs, when used with ICS, did not significantly increase the risk of asthma-related hospitalizations, the need to insert a breathing tube known as intubation, or asthma-related deaths, compared to ICS alone,” the FDA said in the statement.
The trials also demonstrated that using the combination reduced asthma exacerbations, compared with using ICS alone, and that most of the exacerbations “were those that required at least 3 days of systemic corticosteroids” – information that is being added the product labels, according to the FDA.
The products that will no longer carry this boxed warning in their labels include AstraZeneca’s budesonide/formoterol fumarate dihydrate (Symbicort) and GlaxoSmithKline’s fluticasone furoate/vilanterol (Breo Ellipta) and fluticasone propionate/salmeterol (Advair Diskus and Advair HFA).
The FDA also approved updates to the Warnings and Precautions section of labeling for the ICS/LABA class, which now includes a description of the four trials. Information on the efficacy of the drugs, found in the trials, has been added to the Clinical Studies section of the labels as well.
In a related safety announcement, the FDA stated the following: “Using LABAs alone to treat asthma without an ICS to treat lung inflammation is associated with an increased risk of asthma-related death. Therefore, the Boxed Warning stating this will remain in the labels of all single-ingredient LABA medicines, which are approved to treat asthma, chronic obstructive pulmonary disease (COPD), and wheezing caused by exercise. The labels of medicines that contain both an ICS and LABA also retain a Warning and Precaution related to the increased risk of asthma-related death when LABAs are used without an ICS to treat asthma.
Nebulized LAMA for COPD approved
The Food and Drug Administration has given the nod to the first nebulized long-acting muscarinic antagonist (LAMA) treatment for chronic obstructive pulmonary disease (COPD) in the United States.
Glycopyrrolate (Lonhala Magnair) utilizes the eFlow technology system, developed by Pari Pharma. This nebulizing system is portable, virtually silent, and delivers the drug in 2-3 minutes, according to a statement from Sunovion Pharmaceuticals.
The approval of glycopyrrolate is based on the results of the GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) trials. The GOLDEN program comprised the GOLDEN-3 and GOLDEN-4 trials, both of which were phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter safety and efficacy trials, which compared adult glycopyrrolate patients to a placebo group with moderate to severe COPD. At 12 weeks, patients receiving treatment with glycopyrrolate showed clinical and statistically significant improvements in their baseline forced expiratory volume second (FEV1), compared with placebo.
GOLDEN-5, an additional study, followed the same criteria as previous studies, but increased its length to 48 weeks to evaluate the long-term safety and patient tolerability of glycopyrrolate. It also compared treatment of COPD with glycopyrrolate to treatment of COPD with the previously approved LAMA Spiriva (tiotropium bromide), delivered by the Handihaler device. Glycopyrrolate was well tolerated, and the overall treatment emergence of adverse events for glycopyrrolate and tiotropium bromide were similar.
Sunovion expects glycopyrrolate to be available in U.S. pharmacies in early 2018, according to the statement.
The Food and Drug Administration has given the nod to the first nebulized long-acting muscarinic antagonist (LAMA) treatment for chronic obstructive pulmonary disease (COPD) in the United States.
Glycopyrrolate (Lonhala Magnair) utilizes the eFlow technology system, developed by Pari Pharma. This nebulizing system is portable, virtually silent, and delivers the drug in 2-3 minutes, according to a statement from Sunovion Pharmaceuticals.
The approval of glycopyrrolate is based on the results of the GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) trials. The GOLDEN program comprised the GOLDEN-3 and GOLDEN-4 trials, both of which were phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter safety and efficacy trials, which compared adult glycopyrrolate patients to a placebo group with moderate to severe COPD. At 12 weeks, patients receiving treatment with glycopyrrolate showed clinical and statistically significant improvements in their baseline forced expiratory volume second (FEV1), compared with placebo.
GOLDEN-5, an additional study, followed the same criteria as previous studies, but increased its length to 48 weeks to evaluate the long-term safety and patient tolerability of glycopyrrolate. It also compared treatment of COPD with glycopyrrolate to treatment of COPD with the previously approved LAMA Spiriva (tiotropium bromide), delivered by the Handihaler device. Glycopyrrolate was well tolerated, and the overall treatment emergence of adverse events for glycopyrrolate and tiotropium bromide were similar.
Sunovion expects glycopyrrolate to be available in U.S. pharmacies in early 2018, according to the statement.
The Food and Drug Administration has given the nod to the first nebulized long-acting muscarinic antagonist (LAMA) treatment for chronic obstructive pulmonary disease (COPD) in the United States.
Glycopyrrolate (Lonhala Magnair) utilizes the eFlow technology system, developed by Pari Pharma. This nebulizing system is portable, virtually silent, and delivers the drug in 2-3 minutes, according to a statement from Sunovion Pharmaceuticals.
The approval of glycopyrrolate is based on the results of the GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) trials. The GOLDEN program comprised the GOLDEN-3 and GOLDEN-4 trials, both of which were phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter safety and efficacy trials, which compared adult glycopyrrolate patients to a placebo group with moderate to severe COPD. At 12 weeks, patients receiving treatment with glycopyrrolate showed clinical and statistically significant improvements in their baseline forced expiratory volume second (FEV1), compared with placebo.
GOLDEN-5, an additional study, followed the same criteria as previous studies, but increased its length to 48 weeks to evaluate the long-term safety and patient tolerability of glycopyrrolate. It also compared treatment of COPD with glycopyrrolate to treatment of COPD with the previously approved LAMA Spiriva (tiotropium bromide), delivered by the Handihaler device. Glycopyrrolate was well tolerated, and the overall treatment emergence of adverse events for glycopyrrolate and tiotropium bromide were similar.
Sunovion expects glycopyrrolate to be available in U.S. pharmacies in early 2018, according to the statement.
Health disparities in rural America: Chronic conditions
Among rural adults, multiple chronic health conditions are most common in non-Hispanic blacks and American Indians/Alaska Natives (AI/ANs) and least common among Asians and Native Hawaiians/other Pacific Islanders (NHOPIs), according to the Centers for Disease Control and Prevention.
The order was reversed for adults reporting no chronic conditions: Asians and NHOPIs at 61.8%, Hispanics at 49.2%, whites at 37.8%, blacks at 35.4%, and AI/ANs at 34.0%, the researchers said.
For the chronic health conditions included separately in the report, blacks had the highest rate (45.9%) and Asians and NHOPIs had the lowest rate (15.5%) of obesity; AI/ANs were most likely (23.2%) and Asians and NHOPIs were least likely (5.8%) to report depressive disorder. Other conditions considered in the estimates were myocardial infarction; coronary heart disease; stroke; hypertension; asthma; skin cancer; other types of cancer; chronic obstructive pulmonary disease; kidney disease; some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia; and diabetes. Estimates for 2014 were not included because data for hypertension were not available, the investigators noted.
Of the 3,143 counties categorized by the National Center for Health Statistics’ Urban-Rural Classification Scheme for Counties, a total of 1,325 were considered rural and included 6.1% of the U.S. population, they said.
Among rural adults, multiple chronic health conditions are most common in non-Hispanic blacks and American Indians/Alaska Natives (AI/ANs) and least common among Asians and Native Hawaiians/other Pacific Islanders (NHOPIs), according to the Centers for Disease Control and Prevention.
The order was reversed for adults reporting no chronic conditions: Asians and NHOPIs at 61.8%, Hispanics at 49.2%, whites at 37.8%, blacks at 35.4%, and AI/ANs at 34.0%, the researchers said.
For the chronic health conditions included separately in the report, blacks had the highest rate (45.9%) and Asians and NHOPIs had the lowest rate (15.5%) of obesity; AI/ANs were most likely (23.2%) and Asians and NHOPIs were least likely (5.8%) to report depressive disorder. Other conditions considered in the estimates were myocardial infarction; coronary heart disease; stroke; hypertension; asthma; skin cancer; other types of cancer; chronic obstructive pulmonary disease; kidney disease; some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia; and diabetes. Estimates for 2014 were not included because data for hypertension were not available, the investigators noted.
Of the 3,143 counties categorized by the National Center for Health Statistics’ Urban-Rural Classification Scheme for Counties, a total of 1,325 were considered rural and included 6.1% of the U.S. population, they said.
Among rural adults, multiple chronic health conditions are most common in non-Hispanic blacks and American Indians/Alaska Natives (AI/ANs) and least common among Asians and Native Hawaiians/other Pacific Islanders (NHOPIs), according to the Centers for Disease Control and Prevention.
The order was reversed for adults reporting no chronic conditions: Asians and NHOPIs at 61.8%, Hispanics at 49.2%, whites at 37.8%, blacks at 35.4%, and AI/ANs at 34.0%, the researchers said.
For the chronic health conditions included separately in the report, blacks had the highest rate (45.9%) and Asians and NHOPIs had the lowest rate (15.5%) of obesity; AI/ANs were most likely (23.2%) and Asians and NHOPIs were least likely (5.8%) to report depressive disorder. Other conditions considered in the estimates were myocardial infarction; coronary heart disease; stroke; hypertension; asthma; skin cancer; other types of cancer; chronic obstructive pulmonary disease; kidney disease; some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia; and diabetes. Estimates for 2014 were not included because data for hypertension were not available, the investigators noted.
Of the 3,143 counties categorized by the National Center for Health Statistics’ Urban-Rural Classification Scheme for Counties, a total of 1,325 were considered rural and included 6.1% of the U.S. population, they said.
FROM MMWR SURVEILLANCE SUMMARIES
Omalizumab helps asthma COPD overlap patients
TORONTO – Omalizumab (Xolair, Genentech) decreased asthma exacerbations and improved symptom control to a similar extent in patients with asthma chronic obstructive pulmonary disease (ACO) overlap as seen in patients with asthma but no COPD, in a study presented at the CHEST annual meeting.
While patients with COPD typically experience annual declines in lung function, at least some of the ACO patients in this study, which included one of the largest observational cohorts to date of patients with ACO, showed preserved lung function after 48 weeks of omalizumab treatment.
Dr. Hanania presented data from the “real-world” PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab), which unlike many asthma studies, did not exclude patients with comorbid COPD. PROSPERO was a prospective, multicenter, observational, 48-week study of patients (n = 806) who were 12 years of age and older who were initiating omalizumab treatment for moderate to severe allergic asthma. Asthma control was assessed monthly using the Asthma Control Test (ACT).
Participants were identified as having ACO based on two approaches: 1. A positive medical history of asthma and COPD, or 2. A medical history of asthma (but not COPD), at least a 10-pack per year smoking history, and an forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of less than 0.7. From the 728 study participants included in this secondary analysis, 56 were classified as ACO according to the first definition (ACO cohort A) and 59 according to the second (ACO cohort B). Thirty-seven patients fell into both groups.
“All groups had a reduction in their exacerbation rates through 12 months, and it didn’t differ whether they had ACO in cohort A or cohort B, or no ACO,” Dr. Hanania reported.
Additionally, all three groups showed clinically meaningful improvements in their ACT scores, with mean improvements of 4.1, 4.7, and 4.4 units for ACO cohort A, ACO cohort B, and non-ACO patients, respectively.
Postbronchodilator FEV1 at study end was improved by 36 mL in ACO cohort A and by 23 mL in the non-ACO cohort. But a 14 mL reduction in postbronchodilator FEV1 was noted in ACO cohort B, “a reminder that the cohort B population was those patients with fixed airway obstruction and smoking history,” said Dr. Hanania.
Mean age in the non-ACO population was 50 years, rising to 57.6 years in ACO cohort A and 55 years in ACO cohort B. All three groups had three or more asthma exacerbations in the 12 months before starting omalizumab, and all groups had mean ACT scores of less than 15 at baseline, indicating that they were all symptomatic.
Adverse events were consistent with the known safety profile of omalizumab.
“The significance of this study [is that] it’s one of the largest ACO cohorts that we know of and I think it encourages all of us to look at or re-visit both COPD therapies and asthma therapies in populations [not included] in clinical trials because in real life, these are the patients we see … and we don’t have evidence,” Dr. Hanania said.
Dr. Hanania reported receiving research support from Roche/Genentech, among other companies. Three of the investigators are employees of Genentech, the study’s sponsor.
TORONTO – Omalizumab (Xolair, Genentech) decreased asthma exacerbations and improved symptom control to a similar extent in patients with asthma chronic obstructive pulmonary disease (ACO) overlap as seen in patients with asthma but no COPD, in a study presented at the CHEST annual meeting.
While patients with COPD typically experience annual declines in lung function, at least some of the ACO patients in this study, which included one of the largest observational cohorts to date of patients with ACO, showed preserved lung function after 48 weeks of omalizumab treatment.
Dr. Hanania presented data from the “real-world” PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab), which unlike many asthma studies, did not exclude patients with comorbid COPD. PROSPERO was a prospective, multicenter, observational, 48-week study of patients (n = 806) who were 12 years of age and older who were initiating omalizumab treatment for moderate to severe allergic asthma. Asthma control was assessed monthly using the Asthma Control Test (ACT).
Participants were identified as having ACO based on two approaches: 1. A positive medical history of asthma and COPD, or 2. A medical history of asthma (but not COPD), at least a 10-pack per year smoking history, and an forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of less than 0.7. From the 728 study participants included in this secondary analysis, 56 were classified as ACO according to the first definition (ACO cohort A) and 59 according to the second (ACO cohort B). Thirty-seven patients fell into both groups.
“All groups had a reduction in their exacerbation rates through 12 months, and it didn’t differ whether they had ACO in cohort A or cohort B, or no ACO,” Dr. Hanania reported.
Additionally, all three groups showed clinically meaningful improvements in their ACT scores, with mean improvements of 4.1, 4.7, and 4.4 units for ACO cohort A, ACO cohort B, and non-ACO patients, respectively.
Postbronchodilator FEV1 at study end was improved by 36 mL in ACO cohort A and by 23 mL in the non-ACO cohort. But a 14 mL reduction in postbronchodilator FEV1 was noted in ACO cohort B, “a reminder that the cohort B population was those patients with fixed airway obstruction and smoking history,” said Dr. Hanania.
Mean age in the non-ACO population was 50 years, rising to 57.6 years in ACO cohort A and 55 years in ACO cohort B. All three groups had three or more asthma exacerbations in the 12 months before starting omalizumab, and all groups had mean ACT scores of less than 15 at baseline, indicating that they were all symptomatic.
Adverse events were consistent with the known safety profile of omalizumab.
“The significance of this study [is that] it’s one of the largest ACO cohorts that we know of and I think it encourages all of us to look at or re-visit both COPD therapies and asthma therapies in populations [not included] in clinical trials because in real life, these are the patients we see … and we don’t have evidence,” Dr. Hanania said.
Dr. Hanania reported receiving research support from Roche/Genentech, among other companies. Three of the investigators are employees of Genentech, the study’s sponsor.
TORONTO – Omalizumab (Xolair, Genentech) decreased asthma exacerbations and improved symptom control to a similar extent in patients with asthma chronic obstructive pulmonary disease (ACO) overlap as seen in patients with asthma but no COPD, in a study presented at the CHEST annual meeting.
While patients with COPD typically experience annual declines in lung function, at least some of the ACO patients in this study, which included one of the largest observational cohorts to date of patients with ACO, showed preserved lung function after 48 weeks of omalizumab treatment.
Dr. Hanania presented data from the “real-world” PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab), which unlike many asthma studies, did not exclude patients with comorbid COPD. PROSPERO was a prospective, multicenter, observational, 48-week study of patients (n = 806) who were 12 years of age and older who were initiating omalizumab treatment for moderate to severe allergic asthma. Asthma control was assessed monthly using the Asthma Control Test (ACT).
Participants were identified as having ACO based on two approaches: 1. A positive medical history of asthma and COPD, or 2. A medical history of asthma (but not COPD), at least a 10-pack per year smoking history, and an forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of less than 0.7. From the 728 study participants included in this secondary analysis, 56 were classified as ACO according to the first definition (ACO cohort A) and 59 according to the second (ACO cohort B). Thirty-seven patients fell into both groups.
“All groups had a reduction in their exacerbation rates through 12 months, and it didn’t differ whether they had ACO in cohort A or cohort B, or no ACO,” Dr. Hanania reported.
Additionally, all three groups showed clinically meaningful improvements in their ACT scores, with mean improvements of 4.1, 4.7, and 4.4 units for ACO cohort A, ACO cohort B, and non-ACO patients, respectively.
Postbronchodilator FEV1 at study end was improved by 36 mL in ACO cohort A and by 23 mL in the non-ACO cohort. But a 14 mL reduction in postbronchodilator FEV1 was noted in ACO cohort B, “a reminder that the cohort B population was those patients with fixed airway obstruction and smoking history,” said Dr. Hanania.
Mean age in the non-ACO population was 50 years, rising to 57.6 years in ACO cohort A and 55 years in ACO cohort B. All three groups had three or more asthma exacerbations in the 12 months before starting omalizumab, and all groups had mean ACT scores of less than 15 at baseline, indicating that they were all symptomatic.
Adverse events were consistent with the known safety profile of omalizumab.
“The significance of this study [is that] it’s one of the largest ACO cohorts that we know of and I think it encourages all of us to look at or re-visit both COPD therapies and asthma therapies in populations [not included] in clinical trials because in real life, these are the patients we see … and we don’t have evidence,” Dr. Hanania said.
Dr. Hanania reported receiving research support from Roche/Genentech, among other companies. Three of the investigators are employees of Genentech, the study’s sponsor.
AT CHEST 2017
Key clinical point: In patients with asthma COPD overlap (ACO), treatment with omalizumab was associated with decreased asthma exacerbations and improved symptom control, similar to that seen in non-ACO asthma patients.
Major finding: Asthma exacerbation numbers were reduced from baseline levels though month 12, from 3 or more exacerbations in both ACO and non ACO groups to 1.1 or less.
Data source: Subgroup analysis from a prospective observational study of omalizumab that focused on 78 patients (from 737 total) that had asthma and comorbid COPD according to one of two definitions.
Disclosures: Dr. Hanania reported receiving research support from Roche/Genentech, among other companies. Genentech sponsored the study and employs three of the investigators.