Pulmonary Health Hub

DENVER – Among patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbations, acute administration of metformin had no detectable impact on clinical recovery, based on results from a single-center study.

Patients hospitalized for COPD exacerbations are more likely to have longer hospital stays and to experience adverse outcomes if their blood glucose levels are elevated, Emma H. Baker, Ph.D., said in an interview at an international conference of the American Thoracic Society.

“The aim of the current study was to see if lowering blood glucose in COPD patients would reduce adverse outcomes,” said Dr. Baker, professor of clinical pharmacology at the Institute for Infection and Immunity at St. George’s University of London. A previous study suggested that tight glycemic control with insulin improved outcomes among COPD patients in the intensive care unit; however, a large, randomized, multicenter trial showed no difference in outcomes and a risk for hypoglycemia. The researchers wanted to see whether metformin would prove a safer option.

Dr. Baker and her associates randomized 51 patients in a 2:1 fashion to receive metformin or placebo. The metformin dose was escalated to 2 g/day over 4 days and continued for 1 month. Outcome measures included the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), the COPD Assessment Test (CAT), and the rates of recurrent health care use events such as antibiotic or steroid prescription and readmission to the hospital. Of the 51 patients, 34 received metformin and 18 received placebo. The mean age of study participants was 67 years and 39% were women.

Compared with baseline, the EXACT scores improved by 4.2 points at day 5, 5-7 points at day 10, and 6.3 points at day 28 (P < .05 for all). However, the researchers observed no significance differences between the metformin and placebo groups in terms of improvements on EXACT scores. Similarly, CAT scores improved by a mean of 4.2 points over the course of the study, largely during the time between baseline and hospital discharge. There were no significant differences between the metformin and placebo groups at any time point. Meanwhile, the median time to a recurrent health care use event was similar between the groups (46 days in the metformin group, compared with 40 days in the placebo group; P = .682).

“Metformin works through reducing hepatic glucose output and increasing insulin sensitivity – and the effect may take several months,” Dr. Baker said. “What we did show is that metformin seems to be safe in COPD patients,” with no evidence of lactic acidosis.

Diabetes and hyperglycemia are very common in COPD, and were associated with more frequent COPD exacerbations and worse outcomes from exacerbations, according to Dr. Baker.

The study was sponsored by the Medical Research Council of the United Kingdom and the British Lung Foundation. Dr. Baker reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

DENVER – Among patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbations, acute administration of metformin had no detectable impact on clinical recovery, based on results from a single-center study.

Patients hospitalized for COPD exacerbations are more likely to have longer hospital stays and to experience adverse outcomes if their blood glucose levels are elevated, Emma H. Baker, Ph.D., said in an interview at an international conference of the American Thoracic Society.

“The aim of the current study was to see if lowering blood glucose in COPD patients would reduce adverse outcomes,” said Dr. Baker, professor of clinical pharmacology at the Institute for Infection and Immunity at St. George’s University of London. A previous study suggested that tight glycemic control with insulin improved outcomes among COPD patients in the intensive care unit; however, a large, randomized, multicenter trial showed no difference in outcomes and a risk for hypoglycemia. The researchers wanted to see whether metformin would prove a safer option.

Dr. Baker and her associates randomized 51 patients in a 2:1 fashion to receive metformin or placebo. The metformin dose was escalated to 2 g/day over 4 days and continued for 1 month. Outcome measures included the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), the COPD Assessment Test (CAT), and the rates of recurrent health care use events such as antibiotic or steroid prescription and readmission to the hospital. Of the 51 patients, 34 received metformin and 18 received placebo. The mean age of study participants was 67 years and 39% were women.

Compared with baseline, the EXACT scores improved by 4.2 points at day 5, 5-7 points at day 10, and 6.3 points at day 28 (P < .05 for all). However, the researchers observed no significance differences between the metformin and placebo groups in terms of improvements on EXACT scores. Similarly, CAT scores improved by a mean of 4.2 points over the course of the study, largely during the time between baseline and hospital discharge. There were no significant differences between the metformin and placebo groups at any time point. Meanwhile, the median time to a recurrent health care use event was similar between the groups (46 days in the metformin group, compared with 40 days in the placebo group; P = .682).

“Metformin works through reducing hepatic glucose output and increasing insulin sensitivity – and the effect may take several months,” Dr. Baker said. “What we did show is that metformin seems to be safe in COPD patients,” with no evidence of lactic acidosis.

Diabetes and hyperglycemia are very common in COPD, and were associated with more frequent COPD exacerbations and worse outcomes from exacerbations, according to Dr. Baker.

The study was sponsored by the Medical Research Council of the United Kingdom and the British Lung Foundation. Dr. Baker reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

DENVER – Among patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbations, acute administration of metformin had no detectable impact on clinical recovery, based on results from a single-center study.

Patients hospitalized for COPD exacerbations are more likely to have longer hospital stays and to experience adverse outcomes if their blood glucose levels are elevated, Emma H. Baker, Ph.D., said in an interview at an international conference of the American Thoracic Society.

“The aim of the current study was to see if lowering blood glucose in COPD patients would reduce adverse outcomes,” said Dr. Baker, professor of clinical pharmacology at the Institute for Infection and Immunity at St. George’s University of London. A previous study suggested that tight glycemic control with insulin improved outcomes among COPD patients in the intensive care unit; however, a large, randomized, multicenter trial showed no difference in outcomes and a risk for hypoglycemia. The researchers wanted to see whether metformin would prove a safer option.

Dr. Baker and her associates randomized 51 patients in a 2:1 fashion to receive metformin or placebo. The metformin dose was escalated to 2 g/day over 4 days and continued for 1 month. Outcome measures included the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), the COPD Assessment Test (CAT), and the rates of recurrent health care use events such as antibiotic or steroid prescription and readmission to the hospital. Of the 51 patients, 34 received metformin and 18 received placebo. The mean age of study participants was 67 years and 39% were women.

Compared with baseline, the EXACT scores improved by 4.2 points at day 5, 5-7 points at day 10, and 6.3 points at day 28 (P < .05 for all). However, the researchers observed no significance differences between the metformin and placebo groups in terms of improvements on EXACT scores. Similarly, CAT scores improved by a mean of 4.2 points over the course of the study, largely during the time between baseline and hospital discharge. There were no significant differences between the metformin and placebo groups at any time point. Meanwhile, the median time to a recurrent health care use event was similar between the groups (46 days in the metformin group, compared with 40 days in the placebo group; P = .682).

“Metformin works through reducing hepatic glucose output and increasing insulin sensitivity – and the effect may take several months,” Dr. Baker said. “What we did show is that metformin seems to be safe in COPD patients,” with no evidence of lactic acidosis.

Diabetes and hyperglycemia are very common in COPD, and were associated with more frequent COPD exacerbations and worse outcomes from exacerbations, according to Dr. Baker.

The study was sponsored by the Medical Research Council of the United Kingdom and the British Lung Foundation. Dr. Baker reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

GAITHERSBURG, MD. – The biologic agent mepolizumab was unanimously recommended for approval as a treatment for severe asthma in adults at a June 4 meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee.

All 14 members of the advisory panel agreed that the efficacy data provide substantial evidence of a clinically meaningful benefit of mepolizumab for the treatment of severe asthma in adults; 13 of the 14 members agreed that the data adequately demonstrated safety in adults. However, only four panel members recommended approval for adolescents aged 12-17 years, with the majority of panel members citing concerns that the low number of adolescents studied to date did not allow safety to be adequately evaluated in a younger population, especially for a medication that would be taken for many years – perhaps for a lifetime.

If approved by the FDA, the biologic agent would be available as a once-monthly treatment that is injected subcutaneously by a health care professional. Mepolizumab would be marketed by Glaxo Smith Kline under the trade name Nucala. Mepolizumab is a first-in-class humanized monoclonal antibody that targets interleukin-5, a glycoprotein cytokine that mediates production of eosinophils. Elevation of eosinophils in blood and tissue is associated with an increase in cytokines and other inflammatory molecules that can trigger or exacerbate airway inflammation in asthma. One other monoclonal antibody, the anti-IgE biologic omulizimab (Xolair), has been approved to treat asthma. Glaxo Smith Kline brought mepolizumab to the FDA for use as an add-on therapy for the small subset of asthma patients whose disease remains uncontrolled despite the optimal use of inhaled corticosteroids and additional therapies such as leukotriene inhibitors or theophylline. This population experiences more frequent asthma exacerbations, has more emergency department visits and hospitalizations, and uses higher doses of oral corticosteroids. Approximately 60% of those with severe asthma have marked eosinophilia.Panel members uniformly cited the efficacy data for adults with severe asthma; several panelists also remarked on the importance of developing more steroid-sparing alternatives for this population.

The panel endorsed neither efficacy nor safety for those aged 12-17 years, with 9 of the 14 panelists voting not to endorse efficacy and 13 members voting not to endorse safety findings. Mepolizumab’s efficacy, many panelists said, was not clearly established from the data presented, which drew from small numbers of adolescents enrolled in the studies.

Dr. David Au, acting director of Health Services Research and Development at Seattle’s VA Puget Sound Health Care system, observed that “adolescents are not small adults – their lungs continue to mature over time.” Many panelists, however, also called for ongoing study, noting the significant unmet need for steroid alternatives in the adolescent population.

Several panelists advocated postmarketing surveillance for long-term use, with particular attention to those with parasitic disease, to monitoring any sign of malignancy, and to tracking opportunistic diseases such as herpes zoster.

An early clinical trial of mepolizumab, conducted in 1999, failed to show benefit for an undifferentiated population of patients with moderate to severe asthma. However, independent research later identified marked eosinophilia as a factor associated with more frequent asthma exacerbations and a series of clinical trials begun in 2011 targeted patients with severe asthma and eosinophilic inflammation. A global program was initiated, with 12% of patients overall coming from the United States.

Pivotal phase 2b/3, double blind, placebo-controlled clinical trials included a dose-ranging study tracking asthma exacerbations enrolling 616 patients for 52 weeks.

The recommended dose of 100 mg subcutaneously every 4 weeks, as well as a 75-mg IV dose, was used for an additional 576 patients for 32 weeks, with the primary outcome measure being the number of asthma exacerbations. A final 24-week study of 135 patients with severe asthma measured the reduction in oral corticosteroid use, compared with placebo, as well as the number of asthma exacerbations. In all of the studies, patients’ asthma treatment was optimized according to standard of care before adding mepolizumab.

In each study and in pooled data, mepolizumab approximately halved the number of asthma exacerbations for study participants when compared with those using placebo. A 24-week corticosteroid-sparing study showed significant reduction in oral corticosteroid use, without loss of asthma control, for the mepolizumab group. Prespecified subgroup analyses were hampered because of low participation numbers for African Americans and adolescents, and because confidence intervals for these subgroups often ranged over 1, limiting interpretation of benefit results for these groups. The overall safety profile was good, with adverse event rates similar in the treatment and placebo arms. Headache and injection-site reactions were the most commonly reported adverse events but were similar between treatment and placebo arms. No episodes of anaphylaxis were reported, and neutralizing antibodies developed in one patient total across all studies. Ongoing open-label studies continue.The FDA’s independent biostatistical analysis showed clear evidence of efficacy for mepolizumab, with demonstrated consistent, statistically significant decreases of about one exacerbation per year, according to the agency.In its analysis, the agency observed a positive association between higher eosinophil count and mepolizumab treatment effect, meaning that those with higher eosinophil counts saw a greater benefit from mepolizumab, as measured by a reduction in exacerbations.

The number of deaths was balanced across treatment arms, though a larger number of respiratory-related deaths than expected was seen overall. This higher number of deaths may reflect the severity of asthma in the study population. The respiratory-related serious adverse events, according to the FDA, favor treatment over placebo.

No treatment-related cardiovascular risks were identified.

The FDA usually follows the recommendations of its advisory panels. The FDA panelists reported no relevant conflicts of interest.

DENVER – In a year-long multicenter trial, improvements in respiratory health status were more likely to be reported by COPD patients who received nebulized arformoterol tartrate, compared with those who received placebo as part of their treatment regimen.

“We can’t say it’s a blockbuster improvement in quality of life, but it’s still good,” lead study author Dr. James F. Donohue said in an interview at an international conference of the American Thoracic Society.

Doug Brunk/Frontline Medical News

In a secondary analysis of data from a published clinical trial (Chest 2014;146:1531-42), Dr. Donohue and his associates evaluated 420 patients with moderate to severe COPD who received nebulized arformoterol 15 mcg b.i.d. and 421 who received matched placebo for 52 weeks. Eligibility criteria included being at least 40 years of age and having a documented primary diagnosis of nonasthmatic COPD. With the exception of other long-acting beta-2 agonists, treatment with other COPD medications was permitted.

At months 3, 6, and 12, patients completed the 10-item Clinical COPD Questionnaire(CCQ), a validated, self-administered instrument. Improvement of 0.4 points or more in the CCQ total score is considered clinically significant.

At baseline, the mean age of the study participants was 63 years, 43% were female, and 51% were current smokers. A total of 466 participants completed the 12-month trial, including 255 in the arformoterol group (61%) and 211 in the placebo group (51%). Compared with patients in the placebo group, those in the arformoterol group had greater improvements on CCQ total score (–0.18 vs. 0.02, respectively; P = 0.001), symptoms (–0.21 vs. 0.01; P = 0.002), functional state (–0.17 vs. 0.02; P = 0.018), and mental state (–0.20 vs. 0.02; P = 0.023) across the postbaseline visits. At the study endpoint, 38% of patients in the arformoterol group and 31% of patients in the placebo group had clinically significant improvements on the CCQ total score.

“These are good results in a 52-week study,” said Dr. Donohue, professor of pulmonary and critical care medicine at the University of North Carolina, Chapel Hill. “What we really want is to help the patient feel better, be more mentally alert, more functional, and have less symptoms.”

The study was funded by Sunovion Pharmaceuticals, the manufacturer of arformoterol. Dr. Donohue disclosed that he is a consultant for the company.

[email protected]

On Twitter @dougbrunk

DENVER – In a year-long multicenter trial, improvements in respiratory health status were more likely to be reported by COPD patients who received nebulized arformoterol tartrate, compared with those who received placebo as part of their treatment regimen.

“We can’t say it’s a blockbuster improvement in quality of life, but it’s still good,” lead study author Dr. James F. Donohue said in an interview at an international conference of the American Thoracic Society.

Doug Brunk/Frontline Medical News

In a secondary analysis of data from a published clinical trial (Chest 2014;146:1531-42), Dr. Donohue and his associates evaluated 420 patients with moderate to severe COPD who received nebulized arformoterol 15 mcg b.i.d. and 421 who received matched placebo for 52 weeks. Eligibility criteria included being at least 40 years of age and having a documented primary diagnosis of nonasthmatic COPD. With the exception of other long-acting beta-2 agonists, treatment with other COPD medications was permitted.

At months 3, 6, and 12, patients completed the 10-item Clinical COPD Questionnaire(CCQ), a validated, self-administered instrument. Improvement of 0.4 points or more in the CCQ total score is considered clinically significant.

At baseline, the mean age of the study participants was 63 years, 43% were female, and 51% were current smokers. A total of 466 participants completed the 12-month trial, including 255 in the arformoterol group (61%) and 211 in the placebo group (51%). Compared with patients in the placebo group, those in the arformoterol group had greater improvements on CCQ total score (–0.18 vs. 0.02, respectively; P = 0.001), symptoms (–0.21 vs. 0.01; P = 0.002), functional state (–0.17 vs. 0.02; P = 0.018), and mental state (–0.20 vs. 0.02; P = 0.023) across the postbaseline visits. At the study endpoint, 38% of patients in the arformoterol group and 31% of patients in the placebo group had clinically significant improvements on the CCQ total score.

“These are good results in a 52-week study,” said Dr. Donohue, professor of pulmonary and critical care medicine at the University of North Carolina, Chapel Hill. “What we really want is to help the patient feel better, be more mentally alert, more functional, and have less symptoms.”

The study was funded by Sunovion Pharmaceuticals, the manufacturer of arformoterol. Dr. Donohue disclosed that he is a consultant for the company.

[email protected]

On Twitter @dougbrunk

DENVER – In a year-long multicenter trial, improvements in respiratory health status were more likely to be reported by COPD patients who received nebulized arformoterol tartrate, compared with those who received placebo as part of their treatment regimen.

“We can’t say it’s a blockbuster improvement in quality of life, but it’s still good,” lead study author Dr. James F. Donohue said in an interview at an international conference of the American Thoracic Society.

Doug Brunk/Frontline Medical News

In a secondary analysis of data from a published clinical trial (Chest 2014;146:1531-42), Dr. Donohue and his associates evaluated 420 patients with moderate to severe COPD who received nebulized arformoterol 15 mcg b.i.d. and 421 who received matched placebo for 52 weeks. Eligibility criteria included being at least 40 years of age and having a documented primary diagnosis of nonasthmatic COPD. With the exception of other long-acting beta-2 agonists, treatment with other COPD medications was permitted.

At months 3, 6, and 12, patients completed the 10-item Clinical COPD Questionnaire(CCQ), a validated, self-administered instrument. Improvement of 0.4 points or more in the CCQ total score is considered clinically significant.

At baseline, the mean age of the study participants was 63 years, 43% were female, and 51% were current smokers. A total of 466 participants completed the 12-month trial, including 255 in the arformoterol group (61%) and 211 in the placebo group (51%). Compared with patients in the placebo group, those in the arformoterol group had greater improvements on CCQ total score (–0.18 vs. 0.02, respectively; P = 0.001), symptoms (–0.21 vs. 0.01; P = 0.002), functional state (–0.17 vs. 0.02; P = 0.018), and mental state (–0.20 vs. 0.02; P = 0.023) across the postbaseline visits. At the study endpoint, 38% of patients in the arformoterol group and 31% of patients in the placebo group had clinically significant improvements on the CCQ total score.

“These are good results in a 52-week study,” said Dr. Donohue, professor of pulmonary and critical care medicine at the University of North Carolina, Chapel Hill. “What we really want is to help the patient feel better, be more mentally alert, more functional, and have less symptoms.”

The study was funded by Sunovion Pharmaceuticals, the manufacturer of arformoterol. Dr. Donohue disclosed that he is a consultant for the company.

[email protected]

On Twitter @dougbrunk

DENVER – The rate of asthma exacerbations was reduced more among elderly patients than among younger patients treated with mepolizumab vs. placebo as part of the Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma (MENSA) trial, according to a post hoc analysis of the trial data.

The analysis also demonstrated that mepolizumab improved quality of life, compared with standard care, in both older and younger patients, although little differentiation was seen with respect to asthma control, Dr. Hector Ortega reported in a poster at an international conference of the American Thoracic Society.

A 76% greater reduction in clinically significant exacerbations was seen in 54 mepolizumab-treated patients aged 65 years and older in the trial, compared with 26 in that age group who received placebo (mean exacerbation rate per year, 0.92 vs. 1.65); a 44% greater reduction was seen in 331 mepolizumab-treated patients under age 65 years, compared with 165 in that age group who received placebo (mean exacerbation rate per year, 0.42 vs. 1.78), said Dr. Ortega, medical director at GlaxoSmithKline, Research Triangle Park, N.C.

The adjusted mean difference vs. placebo in change in St. George’s Respiratory Questionnaire scores from baseline to 32 weeks was -4.5 in the older patients, and -7.3 in the younger patients, and the adjusted mean difference vs. placebo in change in Asthma Control Questionnaire scores from baseline to 32 weeks was -0.1 and -0.5 in the older and younger patients, respectively, he noted.

The older patients, as expected, suffered more frequently from comorbidities, and this may have been accentuated by the chronic use of inhaled and oral corticosteroids in the older patients.

However, comorbidities had no impact on the response to treatment, and the safety profile of mepolizumab was similar to placebo in both age groups, he said.

Patients in the multicenter, randomized, placebo-controlled MENSA trial received high dose inhaled corticosteroids plus at least one additional controller, had a history of frequent exacerbations and a predefined eosinophilic threshold, and were randomized to receive add-on therapy with either 75 mg of intravenous mepolizumab, 100 mg subcutaneous mepolizumab, or corresponding placebo every 4 weeks for 32 weeks. In the primary planned analysis, the responses to the two doses of mepolizumab were similar, but efficacy in older patients had not been previously reported.

The MENSA trial and post hoc analysis were funded by GSK. Dr. Ortega is employed by GSK.

[email protected]

DENVER – The rate of asthma exacerbations was reduced more among elderly patients than among younger patients treated with mepolizumab vs. placebo as part of the Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma (MENSA) trial, according to a post hoc analysis of the trial data.

The analysis also demonstrated that mepolizumab improved quality of life, compared with standard care, in both older and younger patients, although little differentiation was seen with respect to asthma control, Dr. Hector Ortega reported in a poster at an international conference of the American Thoracic Society.

A 76% greater reduction in clinically significant exacerbations was seen in 54 mepolizumab-treated patients aged 65 years and older in the trial, compared with 26 in that age group who received placebo (mean exacerbation rate per year, 0.92 vs. 1.65); a 44% greater reduction was seen in 331 mepolizumab-treated patients under age 65 years, compared with 165 in that age group who received placebo (mean exacerbation rate per year, 0.42 vs. 1.78), said Dr. Ortega, medical director at GlaxoSmithKline, Research Triangle Park, N.C.

The adjusted mean difference vs. placebo in change in St. George’s Respiratory Questionnaire scores from baseline to 32 weeks was -4.5 in the older patients, and -7.3 in the younger patients, and the adjusted mean difference vs. placebo in change in Asthma Control Questionnaire scores from baseline to 32 weeks was -0.1 and -0.5 in the older and younger patients, respectively, he noted.

The older patients, as expected, suffered more frequently from comorbidities, and this may have been accentuated by the chronic use of inhaled and oral corticosteroids in the older patients.

However, comorbidities had no impact on the response to treatment, and the safety profile of mepolizumab was similar to placebo in both age groups, he said.

Patients in the multicenter, randomized, placebo-controlled MENSA trial received high dose inhaled corticosteroids plus at least one additional controller, had a history of frequent exacerbations and a predefined eosinophilic threshold, and were randomized to receive add-on therapy with either 75 mg of intravenous mepolizumab, 100 mg subcutaneous mepolizumab, or corresponding placebo every 4 weeks for 32 weeks. In the primary planned analysis, the responses to the two doses of mepolizumab were similar, but efficacy in older patients had not been previously reported.

The MENSA trial and post hoc analysis were funded by GSK. Dr. Ortega is employed by GSK.

[email protected]

DENVER – The rate of asthma exacerbations was reduced more among elderly patients than among younger patients treated with mepolizumab vs. placebo as part of the Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma (MENSA) trial, according to a post hoc analysis of the trial data.

The analysis also demonstrated that mepolizumab improved quality of life, compared with standard care, in both older and younger patients, although little differentiation was seen with respect to asthma control, Dr. Hector Ortega reported in a poster at an international conference of the American Thoracic Society.

A 76% greater reduction in clinically significant exacerbations was seen in 54 mepolizumab-treated patients aged 65 years and older in the trial, compared with 26 in that age group who received placebo (mean exacerbation rate per year, 0.92 vs. 1.65); a 44% greater reduction was seen in 331 mepolizumab-treated patients under age 65 years, compared with 165 in that age group who received placebo (mean exacerbation rate per year, 0.42 vs. 1.78), said Dr. Ortega, medical director at GlaxoSmithKline, Research Triangle Park, N.C.

The adjusted mean difference vs. placebo in change in St. George’s Respiratory Questionnaire scores from baseline to 32 weeks was -4.5 in the older patients, and -7.3 in the younger patients, and the adjusted mean difference vs. placebo in change in Asthma Control Questionnaire scores from baseline to 32 weeks was -0.1 and -0.5 in the older and younger patients, respectively, he noted.

The older patients, as expected, suffered more frequently from comorbidities, and this may have been accentuated by the chronic use of inhaled and oral corticosteroids in the older patients.

However, comorbidities had no impact on the response to treatment, and the safety profile of mepolizumab was similar to placebo in both age groups, he said.

Patients in the multicenter, randomized, placebo-controlled MENSA trial received high dose inhaled corticosteroids plus at least one additional controller, had a history of frequent exacerbations and a predefined eosinophilic threshold, and were randomized to receive add-on therapy with either 75 mg of intravenous mepolizumab, 100 mg subcutaneous mepolizumab, or corresponding placebo every 4 weeks for 32 weeks. In the primary planned analysis, the responses to the two doses of mepolizumab were similar, but efficacy in older patients had not been previously reported.

The MENSA trial and post hoc analysis were funded by GSK. Dr. Ortega is employed by GSK.

[email protected]

Patients with knee osteoarthritis and poor sleep habits suffered greater central sensitization to pain than other individuals, especially if they tended to ruminate about their pain, a case-control study found. 

The study is the largest to date to examine sleep, catastrophizing, and central sensitization in knee osteoarthritis, said Claudia Campbell, Ph.D., of Johns Hopkins University, Baltimore. “While we were underpowered to fully examine all possible data described, we hope that these data serve as a platform for future studies to adequately power themselves and explore potential differences.”

©pixologicstudio/thinkstockphotos.com

Patients with osteoarthritis often report poor sleep, and studies show that many of these patients also have central sensitization, or hyperexcitability of nociceptive nerve pathways, a phenomenon that tends to amplify and prolong pain. Catastrophizing – a “persistently negative cognitive affective style” in which patients feel helpless, and magnify and ruminate about their pain – predicts worse pain outcomes in osteoarthritis and other painful conditions, the investigators noted (Arthritis Care Res. 2015 June 4 [doi: 10.1002/acr.22609]).Dr. Campbell and her colleagues categorized 208 adults into four groups: those with insomnia and knee osteoarthritis, those with one or the other of the disorders, and those with neither condition (healthy controls). More than 70% of participants were female, and individuals with knee osteoarthritis were significantly older than the rest. The investigators matched the groups with knee osteoarthritis based on radiographic severity.

Quantitative sensory testing showed that patients with knee osteoarthritis and insomnia had significantly greater central sensitization, compared with healthy controls, the researchers reported. Low sleep efficiency (a measure of self-perceived sleep quality) was linked to heightened central sensitization, but only when patients scored more 7.4 on the 13-item Pain Catastrophizing Scale, they added. In all 56% of the sample met that threshold, as did 77% of participants who had both insomnia and knee osteoarthritis.

Central sensitization also correlated positively with clinical pain. “Clinical implications of these findings suggest that treatment options for osteoarthritis patients could include sleep and/or intervention for catastrophizing, both modifiable risk factors, [which] may aid in reducing central sensitization and decrease clinical pain,” the researchers noted.

The study was the first part of a randomized trial that is examining cognitive behavioral therapy for insomnia in patients with osteoarthritis.

The National Institutes of Arthritis and Musculoskeletal and Skin Disease and the National Institutes of Health supported the study. The investigators reported having no relevant conflicts of interest.

Patients with knee osteoarthritis and poor sleep habits suffered greater central sensitization to pain than other individuals, especially if they tended to ruminate about their pain, a case-control study found. 

The study is the largest to date to examine sleep, catastrophizing, and central sensitization in knee osteoarthritis, said Claudia Campbell, Ph.D., of Johns Hopkins University, Baltimore. “While we were underpowered to fully examine all possible data described, we hope that these data serve as a platform for future studies to adequately power themselves and explore potential differences.”

©pixologicstudio/thinkstockphotos.com

Patients with osteoarthritis often report poor sleep, and studies show that many of these patients also have central sensitization, or hyperexcitability of nociceptive nerve pathways, a phenomenon that tends to amplify and prolong pain. Catastrophizing – a “persistently negative cognitive affective style” in which patients feel helpless, and magnify and ruminate about their pain – predicts worse pain outcomes in osteoarthritis and other painful conditions, the investigators noted (Arthritis Care Res. 2015 June 4 [doi: 10.1002/acr.22609]).Dr. Campbell and her colleagues categorized 208 adults into four groups: those with insomnia and knee osteoarthritis, those with one or the other of the disorders, and those with neither condition (healthy controls). More than 70% of participants were female, and individuals with knee osteoarthritis were significantly older than the rest. The investigators matched the groups with knee osteoarthritis based on radiographic severity.

Quantitative sensory testing showed that patients with knee osteoarthritis and insomnia had significantly greater central sensitization, compared with healthy controls, the researchers reported. Low sleep efficiency (a measure of self-perceived sleep quality) was linked to heightened central sensitization, but only when patients scored more 7.4 on the 13-item Pain Catastrophizing Scale, they added. In all 56% of the sample met that threshold, as did 77% of participants who had both insomnia and knee osteoarthritis.

Central sensitization also correlated positively with clinical pain. “Clinical implications of these findings suggest that treatment options for osteoarthritis patients could include sleep and/or intervention for catastrophizing, both modifiable risk factors, [which] may aid in reducing central sensitization and decrease clinical pain,” the researchers noted.

The study was the first part of a randomized trial that is examining cognitive behavioral therapy for insomnia in patients with osteoarthritis.

The National Institutes of Arthritis and Musculoskeletal and Skin Disease and the National Institutes of Health supported the study. The investigators reported having no relevant conflicts of interest.

Patients with knee osteoarthritis and poor sleep habits suffered greater central sensitization to pain than other individuals, especially if they tended to ruminate about their pain, a case-control study found. 

The study is the largest to date to examine sleep, catastrophizing, and central sensitization in knee osteoarthritis, said Claudia Campbell, Ph.D., of Johns Hopkins University, Baltimore. “While we were underpowered to fully examine all possible data described, we hope that these data serve as a platform for future studies to adequately power themselves and explore potential differences.”

©pixologicstudio/thinkstockphotos.com

Patients with osteoarthritis often report poor sleep, and studies show that many of these patients also have central sensitization, or hyperexcitability of nociceptive nerve pathways, a phenomenon that tends to amplify and prolong pain. Catastrophizing – a “persistently negative cognitive affective style” in which patients feel helpless, and magnify and ruminate about their pain – predicts worse pain outcomes in osteoarthritis and other painful conditions, the investigators noted (Arthritis Care Res. 2015 June 4 [doi: 10.1002/acr.22609]).Dr. Campbell and her colleagues categorized 208 adults into four groups: those with insomnia and knee osteoarthritis, those with one or the other of the disorders, and those with neither condition (healthy controls). More than 70% of participants were female, and individuals with knee osteoarthritis were significantly older than the rest. The investigators matched the groups with knee osteoarthritis based on radiographic severity.

Quantitative sensory testing showed that patients with knee osteoarthritis and insomnia had significantly greater central sensitization, compared with healthy controls, the researchers reported. Low sleep efficiency (a measure of self-perceived sleep quality) was linked to heightened central sensitization, but only when patients scored more 7.4 on the 13-item Pain Catastrophizing Scale, they added. In all 56% of the sample met that threshold, as did 77% of participants who had both insomnia and knee osteoarthritis.

Central sensitization also correlated positively with clinical pain. “Clinical implications of these findings suggest that treatment options for osteoarthritis patients could include sleep and/or intervention for catastrophizing, both modifiable risk factors, [which] may aid in reducing central sensitization and decrease clinical pain,” the researchers noted.

The study was the first part of a randomized trial that is examining cognitive behavioral therapy for insomnia in patients with osteoarthritis.

The National Institutes of Arthritis and Musculoskeletal and Skin Disease and the National Institutes of Health supported the study. The investigators reported having no relevant conflicts of interest.

DENVER – Obstructive sleep apnea was common among patients in the multinational Sleep and Stent Study who underwent successful percutaneous coronary intervention, but most of those affected had no daytime sleepiness, and only about half had positive findings on the Berlin Questionnaire.

Further, findings at up to 4 years of follow-up show that coronary artery disease patients with vs. without obstructive sleep apnea (OSA) had nearly twice the risk of adverse events.

The findings suggest that OSA has important clinical implications for coronary artery disease (CAD), and that validated tools for identifying OSA risk in the general population may not be useful in those with cardiovascular disease, Sofia Furlan, Ph.D. said in a press briefing at an international conference of the American Thoracic Society.

Of 1,305 patients included in the ongoing observational study, 45% had OSA, including 21.8% who had severe OSA defined by an apnea-hypopnea index of 30 or more events/hour. Excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of greater than 10, was identified in 24.5% of the OSA patients, and a Berlin Questionnaire score indicative of high risk for OSA was found in 54.3% of patients with OSA, said Dr. Furlan of the University of Sao Paulo, Brazil.

The adverse event rate was 11% in CAD patients with OSA, compared with 6.5% in those without OSA – a significant difference thus far in the study, Dr. Furlan noted.

Patients in the Sleep and Stent Study, which was designed to look at the relationships between OSA and cardiovascular outcomes in adults treated with percutaneous coronary intervention, were aged 18-80 years and were enrolled from eight centers in five countries: Singapore, China and Hong Kong, India, Myanmar, and Brazil.

Indications for percutaneous coronary intervention included ST segment elevation myocardial infarction in 33% of subjects, non-ST segment elevation myocardial infarction in 20% of subjects, unstable angina in 16% of subjects, and stable angina in 31% of subjects. All patients underwent an overnight sleep study using a level-3 portable diagnostic device prior to hospital discharge, and the tracings were analyzed by a blinded sleep physician.

The prevalence of OSA was comparable across study sites, Dr. Furlan said.

The findings reinforce the known association between OSA and cardiovascular disease, lead researcher Dr. Luciano Drager, also of the University of Sao Paulo, said in a press statement.

“Earlier studies have shown strong relationships between sleep apnea and a number of cardiovascular conditions, including high blood pressure, arrhythmia, stroke, and heart failure. Our study supports this strong association between OSA and heart disease and also suggests that the methods used to screen for OSA in patients with cardiovascular disease need to be improved,” Dr. Drager said.

Given the apparent association between sleep apnea and adverse outcomes in patients with CAD, and the fact that sleep apnea is underdiagnosed, it may be time to consider monitoring for sleep apnea in CAD patients, Dr. Furlan added.

Non–sleep related predictors of OSA in patients with cardiovascular disease also should be explored, she said.

Press briefing moderator Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, noted that other studies also have suggested that coexistent OSA manifests differently in different disease states.

“This is a very good example. Whereas in the general population sleepiness is one of the major presenting symptoms, in this particularly vulnerable population with heart attacks and severe coronary artery disease, these people are not sleepy, ” she said, adding that “current screening questionnaires, which are relatively widely used in clinical populations, may not do the job.”

In fact, if traditional criteria for diagnosis are used, a large proportion of patients with OSA will be missed, she said.

“To me as a clinician, this is the major take-home message: Don’t rely on symptoms, because we will miss a large proportion of patients simply based on that.”

The investigators reported having no disclosures. The Sleep and Stent Study is sponsored by Boston Scientific Corporation.

DENVER – Obstructive sleep apnea was common among patients in the multinational Sleep and Stent Study who underwent successful percutaneous coronary intervention, but most of those affected had no daytime sleepiness, and only about half had positive findings on the Berlin Questionnaire.

Further, findings at up to 4 years of follow-up show that coronary artery disease patients with vs. without obstructive sleep apnea (OSA) had nearly twice the risk of adverse events.

The findings suggest that OSA has important clinical implications for coronary artery disease (CAD), and that validated tools for identifying OSA risk in the general population may not be useful in those with cardiovascular disease, Sofia Furlan, Ph.D. said in a press briefing at an international conference of the American Thoracic Society.

Of 1,305 patients included in the ongoing observational study, 45% had OSA, including 21.8% who had severe OSA defined by an apnea-hypopnea index of 30 or more events/hour. Excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of greater than 10, was identified in 24.5% of the OSA patients, and a Berlin Questionnaire score indicative of high risk for OSA was found in 54.3% of patients with OSA, said Dr. Furlan of the University of Sao Paulo, Brazil.

The adverse event rate was 11% in CAD patients with OSA, compared with 6.5% in those without OSA – a significant difference thus far in the study, Dr. Furlan noted.

Patients in the Sleep and Stent Study, which was designed to look at the relationships between OSA and cardiovascular outcomes in adults treated with percutaneous coronary intervention, were aged 18-80 years and were enrolled from eight centers in five countries: Singapore, China and Hong Kong, India, Myanmar, and Brazil.

Indications for percutaneous coronary intervention included ST segment elevation myocardial infarction in 33% of subjects, non-ST segment elevation myocardial infarction in 20% of subjects, unstable angina in 16% of subjects, and stable angina in 31% of subjects. All patients underwent an overnight sleep study using a level-3 portable diagnostic device prior to hospital discharge, and the tracings were analyzed by a blinded sleep physician.

The prevalence of OSA was comparable across study sites, Dr. Furlan said.

The findings reinforce the known association between OSA and cardiovascular disease, lead researcher Dr. Luciano Drager, also of the University of Sao Paulo, said in a press statement.

“Earlier studies have shown strong relationships between sleep apnea and a number of cardiovascular conditions, including high blood pressure, arrhythmia, stroke, and heart failure. Our study supports this strong association between OSA and heart disease and also suggests that the methods used to screen for OSA in patients with cardiovascular disease need to be improved,” Dr. Drager said.

Given the apparent association between sleep apnea and adverse outcomes in patients with CAD, and the fact that sleep apnea is underdiagnosed, it may be time to consider monitoring for sleep apnea in CAD patients, Dr. Furlan added.

Non–sleep related predictors of OSA in patients with cardiovascular disease also should be explored, she said.

Press briefing moderator Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, noted that other studies also have suggested that coexistent OSA manifests differently in different disease states.

“This is a very good example. Whereas in the general population sleepiness is one of the major presenting symptoms, in this particularly vulnerable population with heart attacks and severe coronary artery disease, these people are not sleepy, ” she said, adding that “current screening questionnaires, which are relatively widely used in clinical populations, may not do the job.”

In fact, if traditional criteria for diagnosis are used, a large proportion of patients with OSA will be missed, she said.

“To me as a clinician, this is the major take-home message: Don’t rely on symptoms, because we will miss a large proportion of patients simply based on that.”

The investigators reported having no disclosures. The Sleep and Stent Study is sponsored by Boston Scientific Corporation.

DENVER – Obstructive sleep apnea was common among patients in the multinational Sleep and Stent Study who underwent successful percutaneous coronary intervention, but most of those affected had no daytime sleepiness, and only about half had positive findings on the Berlin Questionnaire.

Further, findings at up to 4 years of follow-up show that coronary artery disease patients with vs. without obstructive sleep apnea (OSA) had nearly twice the risk of adverse events.

The findings suggest that OSA has important clinical implications for coronary artery disease (CAD), and that validated tools for identifying OSA risk in the general population may not be useful in those with cardiovascular disease, Sofia Furlan, Ph.D. said in a press briefing at an international conference of the American Thoracic Society.

Of 1,305 patients included in the ongoing observational study, 45% had OSA, including 21.8% who had severe OSA defined by an apnea-hypopnea index of 30 or more events/hour. Excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of greater than 10, was identified in 24.5% of the OSA patients, and a Berlin Questionnaire score indicative of high risk for OSA was found in 54.3% of patients with OSA, said Dr. Furlan of the University of Sao Paulo, Brazil.

The adverse event rate was 11% in CAD patients with OSA, compared with 6.5% in those without OSA – a significant difference thus far in the study, Dr. Furlan noted.

Patients in the Sleep and Stent Study, which was designed to look at the relationships between OSA and cardiovascular outcomes in adults treated with percutaneous coronary intervention, were aged 18-80 years and were enrolled from eight centers in five countries: Singapore, China and Hong Kong, India, Myanmar, and Brazil.

Indications for percutaneous coronary intervention included ST segment elevation myocardial infarction in 33% of subjects, non-ST segment elevation myocardial infarction in 20% of subjects, unstable angina in 16% of subjects, and stable angina in 31% of subjects. All patients underwent an overnight sleep study using a level-3 portable diagnostic device prior to hospital discharge, and the tracings were analyzed by a blinded sleep physician.

The prevalence of OSA was comparable across study sites, Dr. Furlan said.

The findings reinforce the known association between OSA and cardiovascular disease, lead researcher Dr. Luciano Drager, also of the University of Sao Paulo, said in a press statement.

“Earlier studies have shown strong relationships between sleep apnea and a number of cardiovascular conditions, including high blood pressure, arrhythmia, stroke, and heart failure. Our study supports this strong association between OSA and heart disease and also suggests that the methods used to screen for OSA in patients with cardiovascular disease need to be improved,” Dr. Drager said.

Given the apparent association between sleep apnea and adverse outcomes in patients with CAD, and the fact that sleep apnea is underdiagnosed, it may be time to consider monitoring for sleep apnea in CAD patients, Dr. Furlan added.

Non–sleep related predictors of OSA in patients with cardiovascular disease also should be explored, she said.

Press briefing moderator Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, noted that other studies also have suggested that coexistent OSA manifests differently in different disease states.

“This is a very good example. Whereas in the general population sleepiness is one of the major presenting symptoms, in this particularly vulnerable population with heart attacks and severe coronary artery disease, these people are not sleepy, ” she said, adding that “current screening questionnaires, which are relatively widely used in clinical populations, may not do the job.”

In fact, if traditional criteria for diagnosis are used, a large proportion of patients with OSA will be missed, she said.

“To me as a clinician, this is the major take-home message: Don’t rely on symptoms, because we will miss a large proportion of patients simply based on that.”

The investigators reported having no disclosures. The Sleep and Stent Study is sponsored by Boston Scientific Corporation.

DENVER – Obstructive sleep apnea was common among patients in the multinational Sleep and Stent Study who underwent successful percutaneous coronary intervention, but most of those affected had no daytime sleepiness, and only about half had positive findings on the Berlin Questionnaire.

Further, findings at up to 4 years of follow-up show that coronary artery disease patients with vs. without obstructive sleep apnea (OSA) had nearly twice the risk of adverse events.

The findings suggest that OSA has important clinical implications for coronary artery disease (CAD), and that validated tools for identifying OSA risk in the general population may not be useful in those with cardiovascular disease, Sofia Furlan, Ph.D. said in a press briefing at an international conference of the American Thoracic Society.

Of 1,305 patients included in the ongoing observational study, 45% had OSA, including 21.8% who had severe OSA defined by an apnea-hypopnea index of 30 or more events/hour. Excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of greater than 10, was identified in 24.5% of the OSA patients, and a Berlin Questionnaire score indicative of high risk for OSA was found in 54.3% of patients with OSA, said Dr. Furlan of the University of Sao Paulo, Brazil.

The adverse event rate was 11% in CAD patients with OSA, compared with 6.5% in those without OSA – a significant difference thus far in the study, Dr. Furlan noted.

Patients in the Sleep and Stent Study, which was designed to look at the relationships between OSA and cardiovascular outcomes in adults treated with percutaneous coronary intervention, were aged 18-80 years and were enrolled from eight centers in five countries: Singapore, China and Hong Kong, India, Myanmar, and Brazil.

Indications for percutaneous coronary intervention included ST segment elevation myocardial infarction in 33% of subjects, non-ST segment elevation myocardial infarction in 20% of subjects, unstable angina in 16% of subjects, and stable angina in 31% of subjects. All patients underwent an overnight sleep study using a level-3 portable diagnostic device prior to hospital discharge, and the tracings were analyzed by a blinded sleep physician.

The prevalence of OSA was comparable across study sites, Dr. Furlan said.

The findings reinforce the known association between OSA and cardiovascular disease, lead researcher Dr. Luciano Drager, also of the University of Sao Paulo, said in a press statement.

“Earlier studies have shown strong relationships between sleep apnea and a number of cardiovascular conditions, including high blood pressure, arrhythmia, stroke, and heart failure. Our study supports this strong association between OSA and heart disease and also suggests that the methods used to screen for OSA in patients with cardiovascular disease need to be improved,” Dr. Drager said.

Given the apparent association between sleep apnea and adverse outcomes in patients with CAD, and the fact that sleep apnea is underdiagnosed, it may be time to consider monitoring for sleep apnea in CAD patients, Dr. Furlan added.

Non–sleep related predictors of OSA in patients with cardiovascular disease also should be explored, she said.

Press briefing moderator Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, noted that other studies also have suggested that coexistent OSA manifests differently in different disease states.

“This is a very good example. Whereas in the general population sleepiness is one of the major presenting symptoms, in this particularly vulnerable population with heart attacks and severe coronary artery disease, these people are not sleepy, ” she said, adding that “current screening questionnaires, which are relatively widely used in clinical populations, may not do the job.”

In fact, if traditional criteria for diagnosis are used, a large proportion of patients with OSA will be missed, she said.

“To me as a clinician, this is the major take-home message: Don’t rely on symptoms, because we will miss a large proportion of patients simply based on that.”

The investigators reported having no disclosures. The Sleep and Stent Study is sponsored by Boston Scientific Corporation.

[email protected]

DENVER – Obstructive sleep apnea was common among patients in the multinational Sleep and Stent Study who underwent successful percutaneous coronary intervention, but most of those affected had no daytime sleepiness, and only about half had positive findings on the Berlin Questionnaire.

Further, findings at up to 4 years of follow-up show that coronary artery disease patients with vs. without obstructive sleep apnea (OSA) had nearly twice the risk of adverse events.

The findings suggest that OSA has important clinical implications for coronary artery disease (CAD), and that validated tools for identifying OSA risk in the general population may not be useful in those with cardiovascular disease, Sofia Furlan, Ph.D. said in a press briefing at an international conference of the American Thoracic Society.

Of 1,305 patients included in the ongoing observational study, 45% had OSA, including 21.8% who had severe OSA defined by an apnea-hypopnea index of 30 or more events/hour. Excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of greater than 10, was identified in 24.5% of the OSA patients, and a Berlin Questionnaire score indicative of high risk for OSA was found in 54.3% of patients with OSA, said Dr. Furlan of the University of Sao Paulo, Brazil.

The adverse event rate was 11% in CAD patients with OSA, compared with 6.5% in those without OSA – a significant difference thus far in the study, Dr. Furlan noted.

Patients in the Sleep and Stent Study, which was designed to look at the relationships between OSA and cardiovascular outcomes in adults treated with percutaneous coronary intervention, were aged 18-80 years and were enrolled from eight centers in five countries: Singapore, China and Hong Kong, India, Myanmar, and Brazil.

Indications for percutaneous coronary intervention included ST segment elevation myocardial infarction in 33% of subjects, non-ST segment elevation myocardial infarction in 20% of subjects, unstable angina in 16% of subjects, and stable angina in 31% of subjects. All patients underwent an overnight sleep study using a level-3 portable diagnostic device prior to hospital discharge, and the tracings were analyzed by a blinded sleep physician.

The prevalence of OSA was comparable across study sites, Dr. Furlan said.

The findings reinforce the known association between OSA and cardiovascular disease, lead researcher Dr. Luciano Drager, also of the University of Sao Paulo, said in a press statement.

“Earlier studies have shown strong relationships between sleep apnea and a number of cardiovascular conditions, including high blood pressure, arrhythmia, stroke, and heart failure. Our study supports this strong association between OSA and heart disease and also suggests that the methods used to screen for OSA in patients with cardiovascular disease need to be improved,” Dr. Drager said.

Given the apparent association between sleep apnea and adverse outcomes in patients with CAD, and the fact that sleep apnea is underdiagnosed, it may be time to consider monitoring for sleep apnea in CAD patients, Dr. Furlan added.

Non–sleep related predictors of OSA in patients with cardiovascular disease also should be explored, she said.

Press briefing moderator Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, noted that other studies also have suggested that coexistent OSA manifests differently in different disease states.

“This is a very good example. Whereas in the general population sleepiness is one of the major presenting symptoms, in this particularly vulnerable population with heart attacks and severe coronary artery disease, these people are not sleepy, ” she said, adding that “current screening questionnaires, which are relatively widely used in clinical populations, may not do the job.”

In fact, if traditional criteria for diagnosis are used, a large proportion of patients with OSA will be missed, she said.

“To me as a clinician, this is the major take-home message: Don’t rely on symptoms, because we will miss a large proportion of patients simply based on that.”

The investigators reported having no disclosures. The Sleep and Stent Study is sponsored by Boston Scientific Corporation.

[email protected]

DENVER – Obstructive sleep apnea was common among patients in the multinational Sleep and Stent Study who underwent successful percutaneous coronary intervention, but most of those affected had no daytime sleepiness, and only about half had positive findings on the Berlin Questionnaire.

Further, findings at up to 4 years of follow-up show that coronary artery disease patients with vs. without obstructive sleep apnea (OSA) had nearly twice the risk of adverse events.

The findings suggest that OSA has important clinical implications for coronary artery disease (CAD), and that validated tools for identifying OSA risk in the general population may not be useful in those with cardiovascular disease, Sofia Furlan, Ph.D. said in a press briefing at an international conference of the American Thoracic Society.

Of 1,305 patients included in the ongoing observational study, 45% had OSA, including 21.8% who had severe OSA defined by an apnea-hypopnea index of 30 or more events/hour. Excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of greater than 10, was identified in 24.5% of the OSA patients, and a Berlin Questionnaire score indicative of high risk for OSA was found in 54.3% of patients with OSA, said Dr. Furlan of the University of Sao Paulo, Brazil.

The adverse event rate was 11% in CAD patients with OSA, compared with 6.5% in those without OSA – a significant difference thus far in the study, Dr. Furlan noted.

Patients in the Sleep and Stent Study, which was designed to look at the relationships between OSA and cardiovascular outcomes in adults treated with percutaneous coronary intervention, were aged 18-80 years and were enrolled from eight centers in five countries: Singapore, China and Hong Kong, India, Myanmar, and Brazil.

Indications for percutaneous coronary intervention included ST segment elevation myocardial infarction in 33% of subjects, non-ST segment elevation myocardial infarction in 20% of subjects, unstable angina in 16% of subjects, and stable angina in 31% of subjects. All patients underwent an overnight sleep study using a level-3 portable diagnostic device prior to hospital discharge, and the tracings were analyzed by a blinded sleep physician.

The prevalence of OSA was comparable across study sites, Dr. Furlan said.

The findings reinforce the known association between OSA and cardiovascular disease, lead researcher Dr. Luciano Drager, also of the University of Sao Paulo, said in a press statement.

“Earlier studies have shown strong relationships between sleep apnea and a number of cardiovascular conditions, including high blood pressure, arrhythmia, stroke, and heart failure. Our study supports this strong association between OSA and heart disease and also suggests that the methods used to screen for OSA in patients with cardiovascular disease need to be improved,” Dr. Drager said.

Given the apparent association between sleep apnea and adverse outcomes in patients with CAD, and the fact that sleep apnea is underdiagnosed, it may be time to consider monitoring for sleep apnea in CAD patients, Dr. Furlan added.

Non–sleep related predictors of OSA in patients with cardiovascular disease also should be explored, she said.

Press briefing moderator Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, noted that other studies also have suggested that coexistent OSA manifests differently in different disease states.

“This is a very good example. Whereas in the general population sleepiness is one of the major presenting symptoms, in this particularly vulnerable population with heart attacks and severe coronary artery disease, these people are not sleepy, ” she said, adding that “current screening questionnaires, which are relatively widely used in clinical populations, may not do the job.”

In fact, if traditional criteria for diagnosis are used, a large proportion of patients with OSA will be missed, she said.

“To me as a clinician, this is the major take-home message: Don’t rely on symptoms, because we will miss a large proportion of patients simply based on that.”

The investigators reported having no disclosures. The Sleep and Stent Study is sponsored by Boston Scientific Corporation.

[email protected]

High-flow oxygen delivered via nasal cannula significantly decreased mortality and improved comfort for ICU patients with nonhypercapnic acute hypoxemic respiratory failure, according to a report published online June 4 in the New England Journal of Medicine.

High-flow oxygen didn’t reduce endotracheal 1-month intubation rates, however, as compared with standard oxygen delivery or noninvasive ventilation in a prospective randomized controlled trial comparing the three techniques at 23 ICUs across France and Belgium, said Dr. Jean-Pierre Frat of Centre Hospitalier Universitaire de Poitiers (France) and his associates.

The 2-year study included 310 adults with nonhypercapnic acute hypoxemic respiratory failure, which was usually the result of community-acquired pneumonia. Patients were randomly assigned to receive high-flow oxygen delivered continuously through large-bore nasal prongs (106 patients), standard oxygen therapy delivered continuously through a nonrebreather face mask (94 patients), or noninvasive ventilation delivered through a face mask connected to an ICU ventilator (110 patients).

Intubation rates at 30 days were 38% for high-flow oxygen, 47% for standard oxygen, and 50% for noninvasive ventilation, which are nonsignificant differences. The hazard ratio for death at 90 days was 2.01 for standard oxygen and 2.50 for noninvasive ventilation, as compared with high-flow oxygen. And the number of ventilator-free days at 1 month was significantly greater with high-flow oxygen (24 days) than with either of the other techniques (22 days and 19 days, respectively), the researchers said.

High-flow oxygen also reduced the intensity of respiratory discomfort at 1 hour to a significantly greater degree than did either of the other forms of oxygen delivery and decreased the dyspnea score as well. “These findings might result from the heating and humidification of inspired gases, which prevented thick secretions and subsequent atelectasis, but also from low levels of PEEP [positive end-expiratory pressure] generated by a high gas flow rate and flushing of upper-airway dead space,” they added (N. Engl. J. Med. 2015 June 4 [doi:10.1056/NEJMoa1503326]). Rates of complications were similar among the three study groups.

The study was supported by the French Ministry of Health’s Programme Hospitalier de Recherche Clinique Interregional 2010. Dr. Frat reported receiving travel fees from Fisher & Paykel Healthcare and personal fees from SOS Oxygene. Fisher & Paykel Healthcare donated face masks, heated humidifiers, and cannulas and provided air-oxygen blenders to the participating ICUs.

High-flow oxygen delivered via nasal cannula significantly decreased mortality and improved comfort for ICU patients with nonhypercapnic acute hypoxemic respiratory failure, according to a report published online June 4 in the New England Journal of Medicine.

High-flow oxygen didn’t reduce endotracheal 1-month intubation rates, however, as compared with standard oxygen delivery or noninvasive ventilation in a prospective randomized controlled trial comparing the three techniques at 23 ICUs across France and Belgium, said Dr. Jean-Pierre Frat of Centre Hospitalier Universitaire de Poitiers (France) and his associates.

The 2-year study included 310 adults with nonhypercapnic acute hypoxemic respiratory failure, which was usually the result of community-acquired pneumonia. Patients were randomly assigned to receive high-flow oxygen delivered continuously through large-bore nasal prongs (106 patients), standard oxygen therapy delivered continuously through a nonrebreather face mask (94 patients), or noninvasive ventilation delivered through a face mask connected to an ICU ventilator (110 patients).

Intubation rates at 30 days were 38% for high-flow oxygen, 47% for standard oxygen, and 50% for noninvasive ventilation, which are nonsignificant differences. The hazard ratio for death at 90 days was 2.01 for standard oxygen and 2.50 for noninvasive ventilation, as compared with high-flow oxygen. And the number of ventilator-free days at 1 month was significantly greater with high-flow oxygen (24 days) than with either of the other techniques (22 days and 19 days, respectively), the researchers said.

High-flow oxygen also reduced the intensity of respiratory discomfort at 1 hour to a significantly greater degree than did either of the other forms of oxygen delivery and decreased the dyspnea score as well. “These findings might result from the heating and humidification of inspired gases, which prevented thick secretions and subsequent atelectasis, but also from low levels of PEEP [positive end-expiratory pressure] generated by a high gas flow rate and flushing of upper-airway dead space,” they added (N. Engl. J. Med. 2015 June 4 [doi:10.1056/NEJMoa1503326]). Rates of complications were similar among the three study groups.

The study was supported by the French Ministry of Health’s Programme Hospitalier de Recherche Clinique Interregional 2010. Dr. Frat reported receiving travel fees from Fisher & Paykel Healthcare and personal fees from SOS Oxygene. Fisher & Paykel Healthcare donated face masks, heated humidifiers, and cannulas and provided air-oxygen blenders to the participating ICUs.

High-flow oxygen delivered via nasal cannula significantly decreased mortality and improved comfort for ICU patients with nonhypercapnic acute hypoxemic respiratory failure, according to a report published online June 4 in the New England Journal of Medicine.

High-flow oxygen didn’t reduce endotracheal 1-month intubation rates, however, as compared with standard oxygen delivery or noninvasive ventilation in a prospective randomized controlled trial comparing the three techniques at 23 ICUs across France and Belgium, said Dr. Jean-Pierre Frat of Centre Hospitalier Universitaire de Poitiers (France) and his associates.

The 2-year study included 310 adults with nonhypercapnic acute hypoxemic respiratory failure, which was usually the result of community-acquired pneumonia. Patients were randomly assigned to receive high-flow oxygen delivered continuously through large-bore nasal prongs (106 patients), standard oxygen therapy delivered continuously through a nonrebreather face mask (94 patients), or noninvasive ventilation delivered through a face mask connected to an ICU ventilator (110 patients).

Intubation rates at 30 days were 38% for high-flow oxygen, 47% for standard oxygen, and 50% for noninvasive ventilation, which are nonsignificant differences. The hazard ratio for death at 90 days was 2.01 for standard oxygen and 2.50 for noninvasive ventilation, as compared with high-flow oxygen. And the number of ventilator-free days at 1 month was significantly greater with high-flow oxygen (24 days) than with either of the other techniques (22 days and 19 days, respectively), the researchers said.

High-flow oxygen also reduced the intensity of respiratory discomfort at 1 hour to a significantly greater degree than did either of the other forms of oxygen delivery and decreased the dyspnea score as well. “These findings might result from the heating and humidification of inspired gases, which prevented thick secretions and subsequent atelectasis, but also from low levels of PEEP [positive end-expiratory pressure] generated by a high gas flow rate and flushing of upper-airway dead space,” they added (N. Engl. J. Med. 2015 June 4 [doi:10.1056/NEJMoa1503326]). Rates of complications were similar among the three study groups.

The study was supported by the French Ministry of Health’s Programme Hospitalier de Recherche Clinique Interregional 2010. Dr. Frat reported receiving travel fees from Fisher & Paykel Healthcare and personal fees from SOS Oxygene. Fisher & Paykel Healthcare donated face masks, heated humidifiers, and cannulas and provided air-oxygen blenders to the participating ICUs.