News

Asthma patients who struggle with poor control despite using inhaled corticosteroids can benefit from additional treatment with long-acting muscarinic antagonists (LAMAs) or single maintenance and reliever therapy, suggest data from a pair of systematic reviews and meta-analyses.

Asthma control remains a problem for many patients despite the daily use of inhaled corticosteroids. The current preferred adjunct therapy for patients aged 12 years and older is long-acting beta-agonists (LABAs), wrote Diana M. Sobieraj, PharmD, of the University of Connecticut School of Pharmacy, Storrs, and her colleagues in a study published in JAMA. The researchers examined the efficacy of other adjunct therapies and therapeutic regimes, including the use of a LAMA, in two studies of patients with persistent asthma.

MattZ90/thinkstockphotos

“Triple therapy was not significantly associated with improvements in rescue medication use vs. combined inhaled corticosteroids and LABA therapy,” the researchers added.

The review of LAMAs used as add-on therapy was limited by several factors, including a primary focus on tiotropium, a lack of analysis of harms or the costs of the various therapies, the lack of data for children, and an inability to perform a subgroup analysis, the researchers said. Although LAMA use was associated with a lower risk of asthma exacerbation, compared with placebo use, the review could not adequately compare LAMA with controllers other than LABA, they added.

In the second analysis, which also was published in JAMA, the researchers evaluated the use of inhaled corticosteroids and LABAs as both a controller and quick-relief treatment, a strategy known as SMART, or Single Maintenance and Reliever Therapy. The SMART protocol, which is not approved in the United States, involved taking a combination of the corticosteroid budesonide and the LABA formoterol in a dry-powder inhaler in most of the studies reviewed.

Overall, in the analysis of 22,524 patients aged 12 years and older, an absolute risk difference of –2.8% for asthma exacerbations was seen in those who used the SMART protocol versus those who used a higher dose of inhaled corticosteroids and inhaled LABA as controller therapy.

In addition, data from 341 children aged 4-11 years showed a –12% absolute difference in risk of asthma exacerbation with the SMART therapy.

In trials that compared patients using the SMART protocol with those taking only the dose of inhaled corticosteroids called for by SMART, the protocol was associated with an improvement in forced expiratory volume in 1 second (FEV₁) and a reduction in the need for rescue medication.

The SMART protocol also demonstrated advantages over taking the same dose of inhaled corticosteroid called for by SMART plus a LABA controller therapy or a higher dose of inhaled corticosteroids with a LABA controller therapy. Specifically, SMART patients experienced a –6.4% risk of asthma exacerbations, versus the first comparator group; and a –2.7% risk of asthma, compared with the group who took a higher dose of inhaled corticosteroids with LABA controller therapy.

No significant associations appeared in any of the studies between the SMART protocol and outcomes that included all-cause mortality or changes in FEV₁, forced vital capacity, or the percentage of predicted FEV₁, when compared with those for patients who used a LABA controller therapy plus inhaled corticosteroids at either dose.

The SMART protocol review was limited by factors that included a lack of data on adverse events, a lack of subgroup analysis, and the potential for bias, because of the open label nature of some of the studies, the researchers noted.

However, despite the limitations in both reviews, the results support the SMART strategy and LAMAs as alternatives for patients with persistent asthma, and highlight the need for further research, they noted.

The reviews were supported by the Agency for Healthcare Research and Quality. Dr. Sobieraj had no financial conflicts to disclose.

SOURCE: Sobieraj D et al. JAMA. 2018;319(14):1473-84. Sobieraj D et al. JAMA. 2018;319(14):1485-96.

Asthma patients who struggle with poor control despite using inhaled corticosteroids can benefit from additional treatment with long-acting muscarinic antagonists (LAMAs) or single maintenance and reliever therapy, suggest data from a pair of systematic reviews and meta-analyses.

Asthma control remains a problem for many patients despite the daily use of inhaled corticosteroids. The current preferred adjunct therapy for patients aged 12 years and older is long-acting beta-agonists (LABAs), wrote Diana M. Sobieraj, PharmD, of the University of Connecticut School of Pharmacy, Storrs, and her colleagues in a study published in JAMA. The researchers examined the efficacy of other adjunct therapies and therapeutic regimes, including the use of a LAMA, in two studies of patients with persistent asthma.

MattZ90/thinkstockphotos

“Triple therapy was not significantly associated with improvements in rescue medication use vs. combined inhaled corticosteroids and LABA therapy,” the researchers added.

The review of LAMAs used as add-on therapy was limited by several factors, including a primary focus on tiotropium, a lack of analysis of harms or the costs of the various therapies, the lack of data for children, and an inability to perform a subgroup analysis, the researchers said. Although LAMA use was associated with a lower risk of asthma exacerbation, compared with placebo use, the review could not adequately compare LAMA with controllers other than LABA, they added.

In the second analysis, which also was published in JAMA, the researchers evaluated the use of inhaled corticosteroids and LABAs as both a controller and quick-relief treatment, a strategy known as SMART, or Single Maintenance and Reliever Therapy. The SMART protocol, which is not approved in the United States, involved taking a combination of the corticosteroid budesonide and the LABA formoterol in a dry-powder inhaler in most of the studies reviewed.

Overall, in the analysis of 22,524 patients aged 12 years and older, an absolute risk difference of –2.8% for asthma exacerbations was seen in those who used the SMART protocol versus those who used a higher dose of inhaled corticosteroids and inhaled LABA as controller therapy.

In addition, data from 341 children aged 4-11 years showed a –12% absolute difference in risk of asthma exacerbation with the SMART therapy.

In trials that compared patients using the SMART protocol with those taking only the dose of inhaled corticosteroids called for by SMART, the protocol was associated with an improvement in forced expiratory volume in 1 second (FEV₁) and a reduction in the need for rescue medication.

The SMART protocol also demonstrated advantages over taking the same dose of inhaled corticosteroid called for by SMART plus a LABA controller therapy or a higher dose of inhaled corticosteroids with a LABA controller therapy. Specifically, SMART patients experienced a –6.4% risk of asthma exacerbations, versus the first comparator group; and a –2.7% risk of asthma, compared with the group who took a higher dose of inhaled corticosteroids with LABA controller therapy.

No significant associations appeared in any of the studies between the SMART protocol and outcomes that included all-cause mortality or changes in FEV₁, forced vital capacity, or the percentage of predicted FEV₁, when compared with those for patients who used a LABA controller therapy plus inhaled corticosteroids at either dose.

The SMART protocol review was limited by factors that included a lack of data on adverse events, a lack of subgroup analysis, and the potential for bias, because of the open label nature of some of the studies, the researchers noted.

However, despite the limitations in both reviews, the results support the SMART strategy and LAMAs as alternatives for patients with persistent asthma, and highlight the need for further research, they noted.

The reviews were supported by the Agency for Healthcare Research and Quality. Dr. Sobieraj had no financial conflicts to disclose.

SOURCE: Sobieraj D et al. JAMA. 2018;319(14):1473-84. Sobieraj D et al. JAMA. 2018;319(14):1485-96.

Asthma patients who struggle with poor control despite using inhaled corticosteroids can benefit from additional treatment with long-acting muscarinic antagonists (LAMAs) or single maintenance and reliever therapy, suggest data from a pair of systematic reviews and meta-analyses.

Asthma control remains a problem for many patients despite the daily use of inhaled corticosteroids. The current preferred adjunct therapy for patients aged 12 years and older is long-acting beta-agonists (LABAs), wrote Diana M. Sobieraj, PharmD, of the University of Connecticut School of Pharmacy, Storrs, and her colleagues in a study published in JAMA. The researchers examined the efficacy of other adjunct therapies and therapeutic regimes, including the use of a LAMA, in two studies of patients with persistent asthma.

MattZ90/thinkstockphotos

“Triple therapy was not significantly associated with improvements in rescue medication use vs. combined inhaled corticosteroids and LABA therapy,” the researchers added.

The review of LAMAs used as add-on therapy was limited by several factors, including a primary focus on tiotropium, a lack of analysis of harms or the costs of the various therapies, the lack of data for children, and an inability to perform a subgroup analysis, the researchers said. Although LAMA use was associated with a lower risk of asthma exacerbation, compared with placebo use, the review could not adequately compare LAMA with controllers other than LABA, they added.

In the second analysis, which also was published in JAMA, the researchers evaluated the use of inhaled corticosteroids and LABAs as both a controller and quick-relief treatment, a strategy known as SMART, or Single Maintenance and Reliever Therapy. The SMART protocol, which is not approved in the United States, involved taking a combination of the corticosteroid budesonide and the LABA formoterol in a dry-powder inhaler in most of the studies reviewed.

Overall, in the analysis of 22,524 patients aged 12 years and older, an absolute risk difference of –2.8% for asthma exacerbations was seen in those who used the SMART protocol versus those who used a higher dose of inhaled corticosteroids and inhaled LABA as controller therapy.

In addition, data from 341 children aged 4-11 years showed a –12% absolute difference in risk of asthma exacerbation with the SMART therapy.

In trials that compared patients using the SMART protocol with those taking only the dose of inhaled corticosteroids called for by SMART, the protocol was associated with an improvement in forced expiratory volume in 1 second (FEV₁) and a reduction in the need for rescue medication.

The SMART protocol also demonstrated advantages over taking the same dose of inhaled corticosteroid called for by SMART plus a LABA controller therapy or a higher dose of inhaled corticosteroids with a LABA controller therapy. Specifically, SMART patients experienced a –6.4% risk of asthma exacerbations, versus the first comparator group; and a –2.7% risk of asthma, compared with the group who took a higher dose of inhaled corticosteroids with LABA controller therapy.

No significant associations appeared in any of the studies between the SMART protocol and outcomes that included all-cause mortality or changes in FEV₁, forced vital capacity, or the percentage of predicted FEV₁, when compared with those for patients who used a LABA controller therapy plus inhaled corticosteroids at either dose.

The SMART protocol review was limited by factors that included a lack of data on adverse events, a lack of subgroup analysis, and the potential for bias, because of the open label nature of some of the studies, the researchers noted.

However, despite the limitations in both reviews, the results support the SMART strategy and LAMAs as alternatives for patients with persistent asthma, and highlight the need for further research, they noted.

The reviews were supported by the Agency for Healthcare Research and Quality. Dr. Sobieraj had no financial conflicts to disclose.

SOURCE: Sobieraj D et al. JAMA. 2018;319(14):1473-84. Sobieraj D et al. JAMA. 2018;319(14):1485-96.

SEATTLE – Preop thromboelastometry can identify patients who need extra anticoagulation against venous thromboembolism following bariatric surgery, according to a prospective investigation of 40 patients at Conemaugh Memorial Medical Center in Johnstown, Pa.

Enoxaparin 40 mg twice daily just wasn’t enough for people who were hypercoagulable before surgery. The goal of the study was to find the best way to prevent venous thromboembolism (VTE) after weight loss surgery. At present, there’s no consensus on prophylaxis dosing, timing, duration, or even what agent to use for these patients. Conemaugh uses postop enoxaparin, a low-molecular-weight heparin. Among many other options, some hospitals opt for preop dosing with traditional heparin, which is less expensive.

jacoblund/Thinkstock

aotto@mdedge.com

SOURCE: Urias D et al. World Congress of Endoscopic Surgery hosted by SAGES & CAGS abstract S023.

SEATTLE – Preop thromboelastometry can identify patients who need extra anticoagulation against venous thromboembolism following bariatric surgery, according to a prospective investigation of 40 patients at Conemaugh Memorial Medical Center in Johnstown, Pa.

Enoxaparin 40 mg twice daily just wasn’t enough for people who were hypercoagulable before surgery. The goal of the study was to find the best way to prevent venous thromboembolism (VTE) after weight loss surgery. At present, there’s no consensus on prophylaxis dosing, timing, duration, or even what agent to use for these patients. Conemaugh uses postop enoxaparin, a low-molecular-weight heparin. Among many other options, some hospitals opt for preop dosing with traditional heparin, which is less expensive.

jacoblund/Thinkstock

aotto@mdedge.com

SOURCE: Urias D et al. World Congress of Endoscopic Surgery hosted by SAGES & CAGS abstract S023.

SEATTLE – Preop thromboelastometry can identify patients who need extra anticoagulation against venous thromboembolism following bariatric surgery, according to a prospective investigation of 40 patients at Conemaugh Memorial Medical Center in Johnstown, Pa.

Enoxaparin 40 mg twice daily just wasn’t enough for people who were hypercoagulable before surgery. The goal of the study was to find the best way to prevent venous thromboembolism (VTE) after weight loss surgery. At present, there’s no consensus on prophylaxis dosing, timing, duration, or even what agent to use for these patients. Conemaugh uses postop enoxaparin, a low-molecular-weight heparin. Among many other options, some hospitals opt for preop dosing with traditional heparin, which is less expensive.

jacoblund/Thinkstock

aotto@mdedge.com

SOURCE: Urias D et al. World Congress of Endoscopic Surgery hosted by SAGES & CAGS abstract S023.

Triple therapy for chronic obstructive pulmonary disease (COPD) achieved reductions in moderate to severe exacerbations when compared with two kinds of dual therapy, in a study published online in the New England Journal of Medicine.

The trial compared the outcomes of COPD patients using an inhaled therapy comprising a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the outcomes of similar patients taking one of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. This trial – Informing the Pathway of COPD Treatment (IMPACT) – included 10,355 patients with symptomatic COPD in 37 countries, according to David A. Lipson, MD, and his colleagues (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901).

copyright designer491/Thinkstock

After 1 year, the rate of moderate to severe COPD exacerbations in the triple-therapy group was 0.91 per year, compared with 1.07 in the fluticasone furoate–vilanterol group and 1.21 in the vilanterol-umeclidinium group. This translated to a 15% reduction with triple therapy compared with fluticasone furoate–vilanterol and a 25% reduction compared with vilanterol-umeclidinium (P less than .001 for both).

When the analysis was limited to severe exacerbations alone, the difference was significant only between the triple therapy, which GSK is marketing as Trelegy Ellipta, and the vilanterol-umeclidinium dual therapy.

Dr. Lipson, of GSK and the University of Pennsylvania, and his coauthors noted that their finding of a greater benefit with the glucocorticoid-containing dual-therapy compared with the LABA-LAMA vilanterol-umeclidinium combination contradicted the findings of the earlier FLAME trial. This was likely due to differences in patient populations and design, as all patients in the FLAME trial had a 1-month run-in treatment with the bronchodilator tiotropium, the researchers explained.

“Therefore any patients who would require an inhaled glucocorticoid may have had an increase in exacerbations and a decrease in lung function during the run-in period and would have been forced to leave the trial,” they wrote.

Patients with higher eosinophil levels seemed to do even better with triple therapy. In those with eosinophil levels of 150 cells per microliter or above, the annual rate of moderate to severe exacerbations was 0.95 with triple therapy, 1.08 with fluticasone furoate–vilanterol, and 1.39 with vilanterol-umeclidinium.

Triple therapy also was associated with a significantly longer time to first event and greater improvements in quality of life, compared with the dual therapies.

Overall, the adverse event profile of triple therapy was similar to that of dual therapy. Contrasting that finding were differences in the incidences of physician-diagnosed pneumonia between the treatment groups. Physician-diagnosed pneumonia was 53% higher among patients who received fluticasone furoate – either in dual or triple therapy combinations. Eight percent of patients in the triple therapy group experienced pneumonia, compared with 7% of patients in the fluticasone furoate–vilanterol group and 5% in the vilanterol-umeclidinium group.

All-cause mortality was significantly lower in patients who received the inhaled glucocorticoid, although the authors said this finding was “fragile” and needed further investigation.

The rate of discontinuation or withdrawal from the trial was 6% for the triple therapy group, 8% for the fluticasone furoate–vilanterol group, and 9% for the vilanterol-umeclidinium group. The rates of serious adverse events in each group were 22%, 21%, and 23%, respectively.

At trial entry, 38% of patients were already receiving triple therapy and 29% were taking an inhaled glucocorticoid. The authors noted that any patients taking an inhaled glucocorticoid who were randomized to the vilanterol-umeclidinium group would have had to abruptly stop taking their inhaled glucocorticoids.

“It is unknown whether the abrupt discontinuation of inhaled glucocorticoids would have contributed to our finding of a lower rate of exacerbations in the inhaled glucocorticoid groups than in the LAMA-LABA group,” they wrote.

Fernando Martinez, MD, chief of the division of pulmonary and critical care medicine at New York–Presbyterian Hospital/Weill Cornell Medical Center, said the study advanced the understanding of COPD management by addressing some key evidence gaps, in a statement issued by GSK.

“By comparing various combinations of effective medications in the same device the study clarifies which type of patient gains greatest benefit from each class of medicine,” Dr Martinez said in the statement. “As many patients experience frequent exacerbations or ‘flare ups,’ which can often result in hospitalization, these data will be highly relevant to patients and clinicians as they consider the optimal treatment.”

The study was funded by GSK, which manufactures Trelegy Ellipta triple therapy for COPD. Eight authors were employees of GSK and two were on advisory boards for the company. Seven authors declared funding from a range of pharmaceutical companies including GSK. One author had no conflicts of interest to declare.

SOURCE: Lipson D et al. N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901.

Triple therapy for chronic obstructive pulmonary disease (COPD) achieved reductions in moderate to severe exacerbations when compared with two kinds of dual therapy, in a study published online in the New England Journal of Medicine.

The trial compared the outcomes of COPD patients using an inhaled therapy comprising a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the outcomes of similar patients taking one of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. This trial – Informing the Pathway of COPD Treatment (IMPACT) – included 10,355 patients with symptomatic COPD in 37 countries, according to David A. Lipson, MD, and his colleagues (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901).

copyright designer491/Thinkstock

After 1 year, the rate of moderate to severe COPD exacerbations in the triple-therapy group was 0.91 per year, compared with 1.07 in the fluticasone furoate–vilanterol group and 1.21 in the vilanterol-umeclidinium group. This translated to a 15% reduction with triple therapy compared with fluticasone furoate–vilanterol and a 25% reduction compared with vilanterol-umeclidinium (P less than .001 for both).

When the analysis was limited to severe exacerbations alone, the difference was significant only between the triple therapy, which GSK is marketing as Trelegy Ellipta, and the vilanterol-umeclidinium dual therapy.

Dr. Lipson, of GSK and the University of Pennsylvania, and his coauthors noted that their finding of a greater benefit with the glucocorticoid-containing dual-therapy compared with the LABA-LAMA vilanterol-umeclidinium combination contradicted the findings of the earlier FLAME trial. This was likely due to differences in patient populations and design, as all patients in the FLAME trial had a 1-month run-in treatment with the bronchodilator tiotropium, the researchers explained.

“Therefore any patients who would require an inhaled glucocorticoid may have had an increase in exacerbations and a decrease in lung function during the run-in period and would have been forced to leave the trial,” they wrote.

Patients with higher eosinophil levels seemed to do even better with triple therapy. In those with eosinophil levels of 150 cells per microliter or above, the annual rate of moderate to severe exacerbations was 0.95 with triple therapy, 1.08 with fluticasone furoate–vilanterol, and 1.39 with vilanterol-umeclidinium.

Triple therapy also was associated with a significantly longer time to first event and greater improvements in quality of life, compared with the dual therapies.

Overall, the adverse event profile of triple therapy was similar to that of dual therapy. Contrasting that finding were differences in the incidences of physician-diagnosed pneumonia between the treatment groups. Physician-diagnosed pneumonia was 53% higher among patients who received fluticasone furoate – either in dual or triple therapy combinations. Eight percent of patients in the triple therapy group experienced pneumonia, compared with 7% of patients in the fluticasone furoate–vilanterol group and 5% in the vilanterol-umeclidinium group.

All-cause mortality was significantly lower in patients who received the inhaled glucocorticoid, although the authors said this finding was “fragile” and needed further investigation.

The rate of discontinuation or withdrawal from the trial was 6% for the triple therapy group, 8% for the fluticasone furoate–vilanterol group, and 9% for the vilanterol-umeclidinium group. The rates of serious adverse events in each group were 22%, 21%, and 23%, respectively.

At trial entry, 38% of patients were already receiving triple therapy and 29% were taking an inhaled glucocorticoid. The authors noted that any patients taking an inhaled glucocorticoid who were randomized to the vilanterol-umeclidinium group would have had to abruptly stop taking their inhaled glucocorticoids.

“It is unknown whether the abrupt discontinuation of inhaled glucocorticoids would have contributed to our finding of a lower rate of exacerbations in the inhaled glucocorticoid groups than in the LAMA-LABA group,” they wrote.

Fernando Martinez, MD, chief of the division of pulmonary and critical care medicine at New York–Presbyterian Hospital/Weill Cornell Medical Center, said the study advanced the understanding of COPD management by addressing some key evidence gaps, in a statement issued by GSK.

“By comparing various combinations of effective medications in the same device the study clarifies which type of patient gains greatest benefit from each class of medicine,” Dr Martinez said in the statement. “As many patients experience frequent exacerbations or ‘flare ups,’ which can often result in hospitalization, these data will be highly relevant to patients and clinicians as they consider the optimal treatment.”

The study was funded by GSK, which manufactures Trelegy Ellipta triple therapy for COPD. Eight authors were employees of GSK and two were on advisory boards for the company. Seven authors declared funding from a range of pharmaceutical companies including GSK. One author had no conflicts of interest to declare.

SOURCE: Lipson D et al. N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901.

Triple therapy for chronic obstructive pulmonary disease (COPD) achieved reductions in moderate to severe exacerbations when compared with two kinds of dual therapy, in a study published online in the New England Journal of Medicine.

The trial compared the outcomes of COPD patients using an inhaled therapy comprising a corticosteroid, a long-acting muscarinic antagonist (LAMA), and a long-acting beta2-agonist (LABA) with the outcomes of similar patients taking one of two other therapy combinations – a corticosteroid and a LABA, or a LABA and a LAMA. This trial – Informing the Pathway of COPD Treatment (IMPACT) – included 10,355 patients with symptomatic COPD in 37 countries, according to David A. Lipson, MD, and his colleagues (N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901).

copyright designer491/Thinkstock

After 1 year, the rate of moderate to severe COPD exacerbations in the triple-therapy group was 0.91 per year, compared with 1.07 in the fluticasone furoate–vilanterol group and 1.21 in the vilanterol-umeclidinium group. This translated to a 15% reduction with triple therapy compared with fluticasone furoate–vilanterol and a 25% reduction compared with vilanterol-umeclidinium (P less than .001 for both).

When the analysis was limited to severe exacerbations alone, the difference was significant only between the triple therapy, which GSK is marketing as Trelegy Ellipta, and the vilanterol-umeclidinium dual therapy.

Dr. Lipson, of GSK and the University of Pennsylvania, and his coauthors noted that their finding of a greater benefit with the glucocorticoid-containing dual-therapy compared with the LABA-LAMA vilanterol-umeclidinium combination contradicted the findings of the earlier FLAME trial. This was likely due to differences in patient populations and design, as all patients in the FLAME trial had a 1-month run-in treatment with the bronchodilator tiotropium, the researchers explained.

“Therefore any patients who would require an inhaled glucocorticoid may have had an increase in exacerbations and a decrease in lung function during the run-in period and would have been forced to leave the trial,” they wrote.

Patients with higher eosinophil levels seemed to do even better with triple therapy. In those with eosinophil levels of 150 cells per microliter or above, the annual rate of moderate to severe exacerbations was 0.95 with triple therapy, 1.08 with fluticasone furoate–vilanterol, and 1.39 with vilanterol-umeclidinium.

Triple therapy also was associated with a significantly longer time to first event and greater improvements in quality of life, compared with the dual therapies.

Overall, the adverse event profile of triple therapy was similar to that of dual therapy. Contrasting that finding were differences in the incidences of physician-diagnosed pneumonia between the treatment groups. Physician-diagnosed pneumonia was 53% higher among patients who received fluticasone furoate – either in dual or triple therapy combinations. Eight percent of patients in the triple therapy group experienced pneumonia, compared with 7% of patients in the fluticasone furoate–vilanterol group and 5% in the vilanterol-umeclidinium group.

All-cause mortality was significantly lower in patients who received the inhaled glucocorticoid, although the authors said this finding was “fragile” and needed further investigation.

The rate of discontinuation or withdrawal from the trial was 6% for the triple therapy group, 8% for the fluticasone furoate–vilanterol group, and 9% for the vilanterol-umeclidinium group. The rates of serious adverse events in each group were 22%, 21%, and 23%, respectively.

At trial entry, 38% of patients were already receiving triple therapy and 29% were taking an inhaled glucocorticoid. The authors noted that any patients taking an inhaled glucocorticoid who were randomized to the vilanterol-umeclidinium group would have had to abruptly stop taking their inhaled glucocorticoids.

“It is unknown whether the abrupt discontinuation of inhaled glucocorticoids would have contributed to our finding of a lower rate of exacerbations in the inhaled glucocorticoid groups than in the LAMA-LABA group,” they wrote.

Fernando Martinez, MD, chief of the division of pulmonary and critical care medicine at New York–Presbyterian Hospital/Weill Cornell Medical Center, said the study advanced the understanding of COPD management by addressing some key evidence gaps, in a statement issued by GSK.

“By comparing various combinations of effective medications in the same device the study clarifies which type of patient gains greatest benefit from each class of medicine,” Dr Martinez said in the statement. “As many patients experience frequent exacerbations or ‘flare ups,’ which can often result in hospitalization, these data will be highly relevant to patients and clinicians as they consider the optimal treatment.”

The study was funded by GSK, which manufactures Trelegy Ellipta triple therapy for COPD. Eight authors were employees of GSK and two were on advisory boards for the company. Seven authors declared funding from a range of pharmaceutical companies including GSK. One author had no conflicts of interest to declare.

SOURCE: Lipson D et al. N Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMoa1713901.

It might only take 1 month of antibiotics, not 9, to prevent tuberculosis in people with HIV, according to National Institute of Allergy and Infectious Diseases (NIAID) researchers.

A phase 3 trial, ACTG 5279, enrolled 3,000 people aged ≥ 13 years living with HIV. All participants lived in an area with a high tuberculosis (TB) burden or had a skin or blood test indicating latent infection. Among people with latent TB infection, HIV infection is the greatest risk factor for progression to active TB disease. About half were taking antiretroviral therapy (ART). The participants were randomly assigned to a 1-month course of rifapentine and isoniazid or 9 months of isoniazid. They were monitored for an average of 3 years.

Tuberculosis incidence was lower than expected and similar in both treatment groups: 32 participants in the 1-month group and 33 in the 9-month group developed active TB. Regardless of treatment, TB rates were higher among participants who were not taking ART when the study began, and among those with positive TB tests.

Adherence was high in both groups, but it was significantly better in the group with the shorter regimen. Nearly all (97%) of those in the 1-month group finished the full antibiotic course, compared with 90% in the 9-month group.

Few adverse events were reported in the 1-month group.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and Robert Eisinger, PhD, special assistant for scientific projects at NIAID, have called for systems biology approaches using large datasets and modeling to understand how Mycobacterium tuberculosis infection causes disease. Noting that lengthy and complex treatment regimens make the disease increasingly difficult to cure, they say the ultimate treatment goal should be drug combinations administered for shorter time periods, as well as, a safe and more broadly effective vaccine and rapid, inexpensive diagnostic tests for drug-resistant TB.

It might only take 1 month of antibiotics, not 9, to prevent tuberculosis in people with HIV, according to National Institute of Allergy and Infectious Diseases (NIAID) researchers.

A phase 3 trial, ACTG 5279, enrolled 3,000 people aged ≥ 13 years living with HIV. All participants lived in an area with a high tuberculosis (TB) burden or had a skin or blood test indicating latent infection. Among people with latent TB infection, HIV infection is the greatest risk factor for progression to active TB disease. About half were taking antiretroviral therapy (ART). The participants were randomly assigned to a 1-month course of rifapentine and isoniazid or 9 months of isoniazid. They were monitored for an average of 3 years.

Tuberculosis incidence was lower than expected and similar in both treatment groups: 32 participants in the 1-month group and 33 in the 9-month group developed active TB. Regardless of treatment, TB rates were higher among participants who were not taking ART when the study began, and among those with positive TB tests.

Adherence was high in both groups, but it was significantly better in the group with the shorter regimen. Nearly all (97%) of those in the 1-month group finished the full antibiotic course, compared with 90% in the 9-month group.

Few adverse events were reported in the 1-month group.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and Robert Eisinger, PhD, special assistant for scientific projects at NIAID, have called for systems biology approaches using large datasets and modeling to understand how Mycobacterium tuberculosis infection causes disease. Noting that lengthy and complex treatment regimens make the disease increasingly difficult to cure, they say the ultimate treatment goal should be drug combinations administered for shorter time periods, as well as, a safe and more broadly effective vaccine and rapid, inexpensive diagnostic tests for drug-resistant TB.

It might only take 1 month of antibiotics, not 9, to prevent tuberculosis in people with HIV, according to National Institute of Allergy and Infectious Diseases (NIAID) researchers.

A phase 3 trial, ACTG 5279, enrolled 3,000 people aged ≥ 13 years living with HIV. All participants lived in an area with a high tuberculosis (TB) burden or had a skin or blood test indicating latent infection. Among people with latent TB infection, HIV infection is the greatest risk factor for progression to active TB disease. About half were taking antiretroviral therapy (ART). The participants were randomly assigned to a 1-month course of rifapentine and isoniazid or 9 months of isoniazid. They were monitored for an average of 3 years.

Tuberculosis incidence was lower than expected and similar in both treatment groups: 32 participants in the 1-month group and 33 in the 9-month group developed active TB. Regardless of treatment, TB rates were higher among participants who were not taking ART when the study began, and among those with positive TB tests.

Adherence was high in both groups, but it was significantly better in the group with the shorter regimen. Nearly all (97%) of those in the 1-month group finished the full antibiotic course, compared with 90% in the 9-month group.

Few adverse events were reported in the 1-month group.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and Robert Eisinger, PhD, special assistant for scientific projects at NIAID, have called for systems biology approaches using large datasets and modeling to understand how Mycobacterium tuberculosis infection causes disease. Noting that lengthy and complex treatment regimens make the disease increasingly difficult to cure, they say the ultimate treatment goal should be drug combinations administered for shorter time periods, as well as, a safe and more broadly effective vaccine and rapid, inexpensive diagnostic tests for drug-resistant TB.

Starting antiretroviral therapy (ART) right after diagnosis does not prevent the depletion of CD4+ T cells from the gut or help restore them—and researchers at the National Institutes of Health (NIH) may have found the reason. For the first time, the NIH says, scientists have shown a relationship between high levels of a “gut-homing” protein called α4β7 and HIV health outcomes.

The researchers found that women who had more CD4+ T cells with high levels of α4β7 were more likely to become infected with HIV, and the virus damaged their immune systems more rapidly than it did in women with fewer such cells.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID) and coauthor of the study paper found that HIV “preferentially infects” those cells. That leads to more HIV-infected CD4+ T cells moving to the gut, which in turn leads to extensive damage to gut-based immune cells.

In the study, which compared blood samples from 59 women shortly before they acquired HIV to those of 106 women who remained HIV negative, the risk of HIV acquisition rose by 18% for each 1% increase in α4β7 protein.

The α4β7 cells also “strongly affected” how quickly HIV damaged the immune system. CD4+ T-cell levels dropped twice as fast among women with higher pre-infection levels of α4β7. Within a few months, those women also had more HIV in the blood. The researchers say the mechanism for immune system damage was likely HIV-related damage to the gut, because higher pre-infection levels of α4β7 were associated with higher levels of a biologic marker of gut damage.

The study findings suggest that ART alone may not be enough; people with HIV may also benefit from interventions to restore CD4+ T cells in their gastrointestinal tracts. One possible solution could be vedolizumab, an anti- α4β7 antibody approved for treatment of ulcerative colitis and Crohn disease. In animal studies, vedolizumab contributed to “near replenishment” of CD4+ T cells.

To determine whether short-term treatment with vedolizumab in combination with ART could generate sustained HIV remission, NIAID has initiated an early-phase clinical trial.

Source:
US Department of Health and Human Services. National Institutes of Health. https://www.nih.gov/news-events/news-releases/study-links-gut-homing-protein-levels-hiv-infection-risk-disease-progression. Published January 24, 2018. Accessed April 19, 2018.

Starting antiretroviral therapy (ART) right after diagnosis does not prevent the depletion of CD4+ T cells from the gut or help restore them—and researchers at the National Institutes of Health (NIH) may have found the reason. For the first time, the NIH says, scientists have shown a relationship between high levels of a “gut-homing” protein called α4β7 and HIV health outcomes.

The researchers found that women who had more CD4+ T cells with high levels of α4β7 were more likely to become infected with HIV, and the virus damaged their immune systems more rapidly than it did in women with fewer such cells.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID) and coauthor of the study paper found that HIV “preferentially infects” those cells. That leads to more HIV-infected CD4+ T cells moving to the gut, which in turn leads to extensive damage to gut-based immune cells.

In the study, which compared blood samples from 59 women shortly before they acquired HIV to those of 106 women who remained HIV negative, the risk of HIV acquisition rose by 18% for each 1% increase in α4β7 protein.

The α4β7 cells also “strongly affected” how quickly HIV damaged the immune system. CD4+ T-cell levels dropped twice as fast among women with higher pre-infection levels of α4β7. Within a few months, those women also had more HIV in the blood. The researchers say the mechanism for immune system damage was likely HIV-related damage to the gut, because higher pre-infection levels of α4β7 were associated with higher levels of a biologic marker of gut damage.

The study findings suggest that ART alone may not be enough; people with HIV may also benefit from interventions to restore CD4+ T cells in their gastrointestinal tracts. One possible solution could be vedolizumab, an anti- α4β7 antibody approved for treatment of ulcerative colitis and Crohn disease. In animal studies, vedolizumab contributed to “near replenishment” of CD4+ T cells.

To determine whether short-term treatment with vedolizumab in combination with ART could generate sustained HIV remission, NIAID has initiated an early-phase clinical trial.

Source:
US Department of Health and Human Services. National Institutes of Health. https://www.nih.gov/news-events/news-releases/study-links-gut-homing-protein-levels-hiv-infection-risk-disease-progression. Published January 24, 2018. Accessed April 19, 2018.

Starting antiretroviral therapy (ART) right after diagnosis does not prevent the depletion of CD4+ T cells from the gut or help restore them—and researchers at the National Institutes of Health (NIH) may have found the reason. For the first time, the NIH says, scientists have shown a relationship between high levels of a “gut-homing” protein called α4β7 and HIV health outcomes.

The researchers found that women who had more CD4+ T cells with high levels of α4β7 were more likely to become infected with HIV, and the virus damaged their immune systems more rapidly than it did in women with fewer such cells.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID) and coauthor of the study paper found that HIV “preferentially infects” those cells. That leads to more HIV-infected CD4+ T cells moving to the gut, which in turn leads to extensive damage to gut-based immune cells.

In the study, which compared blood samples from 59 women shortly before they acquired HIV to those of 106 women who remained HIV negative, the risk of HIV acquisition rose by 18% for each 1% increase in α4β7 protein.

The α4β7 cells also “strongly affected” how quickly HIV damaged the immune system. CD4+ T-cell levels dropped twice as fast among women with higher pre-infection levels of α4β7. Within a few months, those women also had more HIV in the blood. The researchers say the mechanism for immune system damage was likely HIV-related damage to the gut, because higher pre-infection levels of α4β7 were associated with higher levels of a biologic marker of gut damage.

The study findings suggest that ART alone may not be enough; people with HIV may also benefit from interventions to restore CD4+ T cells in their gastrointestinal tracts. One possible solution could be vedolizumab, an anti- α4β7 antibody approved for treatment of ulcerative colitis and Crohn disease. In animal studies, vedolizumab contributed to “near replenishment” of CD4+ T cells.

To determine whether short-term treatment with vedolizumab in combination with ART could generate sustained HIV remission, NIAID has initiated an early-phase clinical trial.

Source:
US Department of Health and Human Services. National Institutes of Health. https://www.nih.gov/news-events/news-releases/study-links-gut-homing-protein-levels-hiv-infection-risk-disease-progression. Published January 24, 2018. Accessed April 19, 2018.

When Surgeon General Jerome Adams issued an advisory calling for more people to carry naloxone – not just people at overdose risk, but also friends and family – experts and advocates were almost giddy.

This is an “unequivocally positive” step forward, said Leo Beletsky, an associate professor of law and health sciences at Northeastern University.

And not necessarily a surprise. Dr. Adams, who previously was Indiana’s health commissioner, was recruited to be the nation’s top doctor in part because of his work with then-Gov. Mike Pence, now the vice president. In Indiana, Dr. Adams pushed for harm-reduction approaches, which included expanded access to naloxone and the implementation of a needle exchange to combat the state’s much-publicized HIV outbreak, which began in 2015 and was linked to injection drug use.

Others cautioned, though, that his have-naloxone-will-carry recommendation is at best limited in what it can achieve, in part because the drug is relatively expensive.

Kaiser Health News breaks down what the advisory means, experts’ concerns, and what policy approaches may be in the pipeline.

Many public health advocates applaud the surgeon general’s position

Naloxone, which is a drug that can keep drug users alive by reversing opioid overdoses, is viewed by many as the cornerstone of the harm-reduction approach to the epidemic. Experts say people with addiction problems should carry it, and so should their family, friends and acquaintances.

“We want to put it more in reach,” said Traci Green, PhD, an associate professor of emergency medicine and community health sciences at Boston University, who has extensively researched the opioid abuse crisis. “It could not have been a better endorsement.”

Others, including Diane Goodman, who penned a recent Medscape commentary reflecting on the advisory, wonder whether this is a “rational” response to the scourge, since opioid addiction is one of many health problems people might encounter in everyday life and for which treatment options are still limited.

“I’m not sure it makes much more sense than any of us carrying a bottle of nitroglycerin to treat patients with end-stage angina,” wrote Ms. Goodman, an acute-care nurse practitioner.

“What, exactly, are we offering to addicts once their condition has been reversed?” she asked, noting that, without treatment and therapy programs that help wean people from addiction, “the odds of survival for any length of time remain low, no matter how much reversal medication is kept nearby.”

Results would likely be limited by naloxone’s price tag

Take Baltimore, which has been hit particularly hard by the opioid epidemic. Its health department already has pushed for more people to carry naloxone.

But the drug’s price is an issue, said Leana Wen, MD, the city’s health commissioner, and an emergency physician. She suggested that the federal government negotiate directly for a lower price, or give more money to organizations and agencies like hers so they can afford to maintain an adequate supply.

“Every day, people are calling us at the Baltimore City Health Department and requesting naloxone, and I have to tell them I can’t afford for them to have it,” Dr. Wen said.

The drug is available in generic form, which can be stored in a vial and injected via a needle, as well as in patented products, such as the nasal spray Narcan, sold by ADAPT Pharmaceuticals, and Kaleo’s Evzio, a talking auto-injector.

Generic naloxone costs $20-$40 per dose. Narcan, the nasal spray, costs $125 for a two-dose carton, according to ADAPT’s website. A two-pack of Evzio costs close to $4,000, according to GoodRx.

Health departments and first responders qualify for a discounted rate of $75 per carton of Narcan. Kaleo has made Evzio coupons available to consumers, so that some will not have a copay, and it advertises a discount for federal and state agencies.

Skeptics point out that similar methods have been used to build brand loyalty and potentially make a particular product a household name. That’s how Epi-Pen became synonymous with epinephrine for the treatment of anaphylactic shock.

“There’s clearly some overlap” here between the pricing strategies used by naloxone manufacturers and Epi-Pen distributor Mylan, said Richard Evans, cofounder of SSR Health, which tracks the pharmaceutical industry.

But it’s not a perfect comparison. The presence of low-cost generics changes the calculus, he said, as does the different level of demand.

Nonprofit organizations and health care providers keenly feel the pressures of increasing demand and cost

Experts say price breaks on naloxone are not sufficient to cover the costs on the ground.

“Sixty-four thousand people lost their lives [nationally in 2016] — that’s someone every 12 minutes,” said Justin Phillips, executive director of Overdose Lifeline, an Indianapolis-based nonprofit. “Ten free kits is not going to be enough.”

Ms. Phillips said her organization relies on generic naloxone, which is the least expensive formulation. It’s the only feasible option, using dedicated grant money the group received from the state attorney general’s office as part of a program funded by a settlement with pharmaceutical companies.

But that money is almost dried up. “We need to be able to access naloxone – which I’m told is pennies to make – for the pennies it cost to make it,” she said.

Ms. Phillips, who worked with Dr. Adams when he ran Indiana’s health department, said she has discussed the need for naloxone funding with the surgeon general, but never its price.
 

Pharmacies assess the hurdles of distribution

Local pharmacies are key in this chain, but the overdose antidote is new territory for many pharmacists, said Randy Hitchens, the executive vice president of the Indiana Pharmacists Alliance. He said in 2015, when Adams began his push to get naloxone into the hands of drug users and their families, only one or two retail pharmacies carried it.

“This has always been an emergency room drug. Retail pharmacists typically were not used to dealing with [it],” Mr. Hitchens said. “A lot were probably saying, ‘What in the devil is naloxone?’”

Today, he estimates 60%-70% of Indiana’s more than 1,100 retail pharmacies carry the drug. Walgreens has committed to stocking Narcan.

Access, though, is always subject to retail pressures.

“If pharmacies are not seeing a steady stream coming in asking for it, they won’t be incentivized to carry it on their shelves,” said Daniel Raymond, the deputy director of policy and planning for the Harm Reduction Coalition.

A patchwork of other decentralized sources for naloxone exist: syringe-exchange vans, county and state health departments, churches and community centers, all trying to find ways to get overdose medication into the hands of people who need it.

That supply stream “meets people where they are,” Mr. Raymond said, but those little programs don’t have the muscle to negotiate discounted prices.

“Individual health programs are trying to navigate the crisis on their own, but when you see … growing demand and limited supply, it’s a role for federal intervention,” Mr. Raymond said.

He’d like to see the federal government step in to negotiate prices where smaller programs can’t.

Even as Congress crafts an opioid epidemic response package, it’s not clear it will tackle these concerns

In the House Energy and Commerce Committee, one bill being discussed would require all state Medicaid programs to cover at least one form of naloxone. Currently, not all state Medicaid programs do so.

A Senate bill would authorize $300 million annually to equip first responders with naloxone.

But critics say those approaches still don’t address the underlying problems: cost and funding.

“You can either make naloxone available, at a much discounted price, or we need to have a lot more resources in order to purchase it,” Dr. Wen said. “I don’t care which one. My only concern is the health and well-being of our residents.”
 

KHN’s coverage of prescription drug development, costs and pricing is supported by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

When Surgeon General Jerome Adams issued an advisory calling for more people to carry naloxone – not just people at overdose risk, but also friends and family – experts and advocates were almost giddy.

This is an “unequivocally positive” step forward, said Leo Beletsky, an associate professor of law and health sciences at Northeastern University.

And not necessarily a surprise. Dr. Adams, who previously was Indiana’s health commissioner, was recruited to be the nation’s top doctor in part because of his work with then-Gov. Mike Pence, now the vice president. In Indiana, Dr. Adams pushed for harm-reduction approaches, which included expanded access to naloxone and the implementation of a needle exchange to combat the state’s much-publicized HIV outbreak, which began in 2015 and was linked to injection drug use.

Others cautioned, though, that his have-naloxone-will-carry recommendation is at best limited in what it can achieve, in part because the drug is relatively expensive.

Kaiser Health News breaks down what the advisory means, experts’ concerns, and what policy approaches may be in the pipeline.

Many public health advocates applaud the surgeon general’s position

Naloxone, which is a drug that can keep drug users alive by reversing opioid overdoses, is viewed by many as the cornerstone of the harm-reduction approach to the epidemic. Experts say people with addiction problems should carry it, and so should their family, friends and acquaintances.

“We want to put it more in reach,” said Traci Green, PhD, an associate professor of emergency medicine and community health sciences at Boston University, who has extensively researched the opioid abuse crisis. “It could not have been a better endorsement.”

Others, including Diane Goodman, who penned a recent Medscape commentary reflecting on the advisory, wonder whether this is a “rational” response to the scourge, since opioid addiction is one of many health problems people might encounter in everyday life and for which treatment options are still limited.

“I’m not sure it makes much more sense than any of us carrying a bottle of nitroglycerin to treat patients with end-stage angina,” wrote Ms. Goodman, an acute-care nurse practitioner.

“What, exactly, are we offering to addicts once their condition has been reversed?” she asked, noting that, without treatment and therapy programs that help wean people from addiction, “the odds of survival for any length of time remain low, no matter how much reversal medication is kept nearby.”

Results would likely be limited by naloxone’s price tag

Take Baltimore, which has been hit particularly hard by the opioid epidemic. Its health department already has pushed for more people to carry naloxone.

But the drug’s price is an issue, said Leana Wen, MD, the city’s health commissioner, and an emergency physician. She suggested that the federal government negotiate directly for a lower price, or give more money to organizations and agencies like hers so they can afford to maintain an adequate supply.

“Every day, people are calling us at the Baltimore City Health Department and requesting naloxone, and I have to tell them I can’t afford for them to have it,” Dr. Wen said.

The drug is available in generic form, which can be stored in a vial and injected via a needle, as well as in patented products, such as the nasal spray Narcan, sold by ADAPT Pharmaceuticals, and Kaleo’s Evzio, a talking auto-injector.

Generic naloxone costs $20-$40 per dose. Narcan, the nasal spray, costs $125 for a two-dose carton, according to ADAPT’s website. A two-pack of Evzio costs close to $4,000, according to GoodRx.

Health departments and first responders qualify for a discounted rate of $75 per carton of Narcan. Kaleo has made Evzio coupons available to consumers, so that some will not have a copay, and it advertises a discount for federal and state agencies.

Skeptics point out that similar methods have been used to build brand loyalty and potentially make a particular product a household name. That’s how Epi-Pen became synonymous with epinephrine for the treatment of anaphylactic shock.

“There’s clearly some overlap” here between the pricing strategies used by naloxone manufacturers and Epi-Pen distributor Mylan, said Richard Evans, cofounder of SSR Health, which tracks the pharmaceutical industry.

But it’s not a perfect comparison. The presence of low-cost generics changes the calculus, he said, as does the different level of demand.

Nonprofit organizations and health care providers keenly feel the pressures of increasing demand and cost

Experts say price breaks on naloxone are not sufficient to cover the costs on the ground.

“Sixty-four thousand people lost their lives [nationally in 2016] — that’s someone every 12 minutes,” said Justin Phillips, executive director of Overdose Lifeline, an Indianapolis-based nonprofit. “Ten free kits is not going to be enough.”

Ms. Phillips said her organization relies on generic naloxone, which is the least expensive formulation. It’s the only feasible option, using dedicated grant money the group received from the state attorney general’s office as part of a program funded by a settlement with pharmaceutical companies.

But that money is almost dried up. “We need to be able to access naloxone – which I’m told is pennies to make – for the pennies it cost to make it,” she said.

Ms. Phillips, who worked with Dr. Adams when he ran Indiana’s health department, said she has discussed the need for naloxone funding with the surgeon general, but never its price.
 

Pharmacies assess the hurdles of distribution

Local pharmacies are key in this chain, but the overdose antidote is new territory for many pharmacists, said Randy Hitchens, the executive vice president of the Indiana Pharmacists Alliance. He said in 2015, when Adams began his push to get naloxone into the hands of drug users and their families, only one or two retail pharmacies carried it.

“This has always been an emergency room drug. Retail pharmacists typically were not used to dealing with [it],” Mr. Hitchens said. “A lot were probably saying, ‘What in the devil is naloxone?’”

Today, he estimates 60%-70% of Indiana’s more than 1,100 retail pharmacies carry the drug. Walgreens has committed to stocking Narcan.

Access, though, is always subject to retail pressures.

“If pharmacies are not seeing a steady stream coming in asking for it, they won’t be incentivized to carry it on their shelves,” said Daniel Raymond, the deputy director of policy and planning for the Harm Reduction Coalition.

A patchwork of other decentralized sources for naloxone exist: syringe-exchange vans, county and state health departments, churches and community centers, all trying to find ways to get overdose medication into the hands of people who need it.

That supply stream “meets people where they are,” Mr. Raymond said, but those little programs don’t have the muscle to negotiate discounted prices.

“Individual health programs are trying to navigate the crisis on their own, but when you see … growing demand and limited supply, it’s a role for federal intervention,” Mr. Raymond said.

He’d like to see the federal government step in to negotiate prices where smaller programs can’t.

Even as Congress crafts an opioid epidemic response package, it’s not clear it will tackle these concerns

In the House Energy and Commerce Committee, one bill being discussed would require all state Medicaid programs to cover at least one form of naloxone. Currently, not all state Medicaid programs do so.

A Senate bill would authorize $300 million annually to equip first responders with naloxone.

But critics say those approaches still don’t address the underlying problems: cost and funding.

“You can either make naloxone available, at a much discounted price, or we need to have a lot more resources in order to purchase it,” Dr. Wen said. “I don’t care which one. My only concern is the health and well-being of our residents.”
 

KHN’s coverage of prescription drug development, costs and pricing is supported by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

When Surgeon General Jerome Adams issued an advisory calling for more people to carry naloxone – not just people at overdose risk, but also friends and family – experts and advocates were almost giddy.

This is an “unequivocally positive” step forward, said Leo Beletsky, an associate professor of law and health sciences at Northeastern University.

And not necessarily a surprise. Dr. Adams, who previously was Indiana’s health commissioner, was recruited to be the nation’s top doctor in part because of his work with then-Gov. Mike Pence, now the vice president. In Indiana, Dr. Adams pushed for harm-reduction approaches, which included expanded access to naloxone and the implementation of a needle exchange to combat the state’s much-publicized HIV outbreak, which began in 2015 and was linked to injection drug use.

Others cautioned, though, that his have-naloxone-will-carry recommendation is at best limited in what it can achieve, in part because the drug is relatively expensive.

Kaiser Health News breaks down what the advisory means, experts’ concerns, and what policy approaches may be in the pipeline.

Many public health advocates applaud the surgeon general’s position

Naloxone, which is a drug that can keep drug users alive by reversing opioid overdoses, is viewed by many as the cornerstone of the harm-reduction approach to the epidemic. Experts say people with addiction problems should carry it, and so should their family, friends and acquaintances.

“We want to put it more in reach,” said Traci Green, PhD, an associate professor of emergency medicine and community health sciences at Boston University, who has extensively researched the opioid abuse crisis. “It could not have been a better endorsement.”

Others, including Diane Goodman, who penned a recent Medscape commentary reflecting on the advisory, wonder whether this is a “rational” response to the scourge, since opioid addiction is one of many health problems people might encounter in everyday life and for which treatment options are still limited.

“I’m not sure it makes much more sense than any of us carrying a bottle of nitroglycerin to treat patients with end-stage angina,” wrote Ms. Goodman, an acute-care nurse practitioner.

“What, exactly, are we offering to addicts once their condition has been reversed?” she asked, noting that, without treatment and therapy programs that help wean people from addiction, “the odds of survival for any length of time remain low, no matter how much reversal medication is kept nearby.”

Results would likely be limited by naloxone’s price tag

Take Baltimore, which has been hit particularly hard by the opioid epidemic. Its health department already has pushed for more people to carry naloxone.

But the drug’s price is an issue, said Leana Wen, MD, the city’s health commissioner, and an emergency physician. She suggested that the federal government negotiate directly for a lower price, or give more money to organizations and agencies like hers so they can afford to maintain an adequate supply.

“Every day, people are calling us at the Baltimore City Health Department and requesting naloxone, and I have to tell them I can’t afford for them to have it,” Dr. Wen said.

The drug is available in generic form, which can be stored in a vial and injected via a needle, as well as in patented products, such as the nasal spray Narcan, sold by ADAPT Pharmaceuticals, and Kaleo’s Evzio, a talking auto-injector.

Generic naloxone costs $20-$40 per dose. Narcan, the nasal spray, costs $125 for a two-dose carton, according to ADAPT’s website. A two-pack of Evzio costs close to $4,000, according to GoodRx.

Health departments and first responders qualify for a discounted rate of $75 per carton of Narcan. Kaleo has made Evzio coupons available to consumers, so that some will not have a copay, and it advertises a discount for federal and state agencies.

Skeptics point out that similar methods have been used to build brand loyalty and potentially make a particular product a household name. That’s how Epi-Pen became synonymous with epinephrine for the treatment of anaphylactic shock.

“There’s clearly some overlap” here between the pricing strategies used by naloxone manufacturers and Epi-Pen distributor Mylan, said Richard Evans, cofounder of SSR Health, which tracks the pharmaceutical industry.

But it’s not a perfect comparison. The presence of low-cost generics changes the calculus, he said, as does the different level of demand.

Nonprofit organizations and health care providers keenly feel the pressures of increasing demand and cost

Experts say price breaks on naloxone are not sufficient to cover the costs on the ground.

“Sixty-four thousand people lost their lives [nationally in 2016] — that’s someone every 12 minutes,” said Justin Phillips, executive director of Overdose Lifeline, an Indianapolis-based nonprofit. “Ten free kits is not going to be enough.”

Ms. Phillips said her organization relies on generic naloxone, which is the least expensive formulation. It’s the only feasible option, using dedicated grant money the group received from the state attorney general’s office as part of a program funded by a settlement with pharmaceutical companies.

But that money is almost dried up. “We need to be able to access naloxone – which I’m told is pennies to make – for the pennies it cost to make it,” she said.

Ms. Phillips, who worked with Dr. Adams when he ran Indiana’s health department, said she has discussed the need for naloxone funding with the surgeon general, but never its price.
 

Pharmacies assess the hurdles of distribution

Local pharmacies are key in this chain, but the overdose antidote is new territory for many pharmacists, said Randy Hitchens, the executive vice president of the Indiana Pharmacists Alliance. He said in 2015, when Adams began his push to get naloxone into the hands of drug users and their families, only one or two retail pharmacies carried it.

“This has always been an emergency room drug. Retail pharmacists typically were not used to dealing with [it],” Mr. Hitchens said. “A lot were probably saying, ‘What in the devil is naloxone?’”

Today, he estimates 60%-70% of Indiana’s more than 1,100 retail pharmacies carry the drug. Walgreens has committed to stocking Narcan.

Access, though, is always subject to retail pressures.

“If pharmacies are not seeing a steady stream coming in asking for it, they won’t be incentivized to carry it on their shelves,” said Daniel Raymond, the deputy director of policy and planning for the Harm Reduction Coalition.

A patchwork of other decentralized sources for naloxone exist: syringe-exchange vans, county and state health departments, churches and community centers, all trying to find ways to get overdose medication into the hands of people who need it.

That supply stream “meets people where they are,” Mr. Raymond said, but those little programs don’t have the muscle to negotiate discounted prices.

“Individual health programs are trying to navigate the crisis on their own, but when you see … growing demand and limited supply, it’s a role for federal intervention,” Mr. Raymond said.

He’d like to see the federal government step in to negotiate prices where smaller programs can’t.

Even as Congress crafts an opioid epidemic response package, it’s not clear it will tackle these concerns

In the House Energy and Commerce Committee, one bill being discussed would require all state Medicaid programs to cover at least one form of naloxone. Currently, not all state Medicaid programs do so.

A Senate bill would authorize $300 million annually to equip first responders with naloxone.

But critics say those approaches still don’t address the underlying problems: cost and funding.

“You can either make naloxone available, at a much discounted price, or we need to have a lot more resources in order to purchase it,” Dr. Wen said. “I don’t care which one. My only concern is the health and well-being of our residents.”
 

KHN’s coverage of prescription drug development, costs and pricing is supported by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

For patients with relapsed or refractory chronic lymphocytic leukemia despite therapy with idelalisib (Zydelig), venetoclax (Venclexta) was associated with relatively high overall response and progression-free survival rates, results of a phase 2 study show.

Among 36 patients with relapsed/refractory CLL who had received idelalisib as their most recent B-cell receptor pathway inhibitor (BCRi), the overall response rate (ORR) was 67%, and median progression-free and overall survival (PFS and OS) had not been reached after 14 months of follow-up, reported Steven Coutre, MD, of Stanford (Calif.) University, and his colleagues.

“[V]enetoclax monotherapy is active and well-tolerated in patients with CLL progression after therapy with idelalisib, including a significant number of patients who also received prior therapy with ibrutinib [Imbruvica]. These results from the first prospective trial in this high-risk population provide evidence that venetoclax should be considered as a treatment option for such patients,” the investigators wrote. The report was published in Blood.

In clinical trials with idelalisib, approximately one-third of patients with CLL experienced disease progression on therapy, and other patients had to discontinue the drug, an inhibitor of the delta isoform of phosphoinositide 3-kinase (PI3K), because of toxicities, the investigators noted.

“The optimal treatment of patients with CLL progressing after idelalisib has not been well characterized,” they wrote. “Outcomes in patients who discontinued idelalisib treatment early are poor, with one retrospective analysis reporting a median overall survival (OS) after idelalisib discontinuation of approximately 2 months (range, 0-10 months).”

Venetoclax, an inhibitor of the apoptotic BCL-2 protein, has been shown to have activity against CLL, including in patients with high-risk features such as the chromosome 17p deletion (del17p), prompting the investigators to evaluate it as a follow-on in patients with relapsed/refractory CLL treated with a B-cell receptor pathway inhibitor.

They reported on the idelalisib cohort in a phase 2 trial in which patients with CLL that progressed on either idelalisib or ibrutinib were subsequently treated with venetoclax. The patients in this analysis included those treated with idelalisib in the main study cohort or an expansion cohort.

Patients were started on venetoclax 20 mg daily, followed by weekly dose escalations to a target of 400 mg daily by week 5, or to a maximum of 600 mg for patients who did not have a response by the week 12 assessment.

The overall response rate – the primary efficacy endpoint – was 67%. There were two complete remissions (CR) and one CR with incomplete bone marrow recovery. The remaining 21 patients with responses had partial responses.

At a median of 14 months of follow-up, neither median PFS, duration of response, or OS had been reached.

The investigator-estimated 12-month PFS rate was 79%.

The most common grade 3 or 4 adverse events were neutropenia in 50% of patients, thrombocytopenia in 25%, and anemia in 17%. There were no cases of clinical tumor lysis syndrome, which has been known to occur when venetoclax is initiated at full dose without a ramp-up.

The most common adverse events of any grade included neutropenia, diarrhea, upper respiratory tract infection, thrombocytopenia, nausea, fatigue, cough, rash, and anemia.

“The low number of CRs reported at the time of analysis may be a result of the follow-up time, particularly for patients in the expansion cohort, as other clinical studies with venetoclax report CR occurring after 1 year on therapy. Patients with prior ibrutinib exposure who had progressed on idelalisib as their most recent therapy before study entry had similar efficacy results,” the investigators wrote.

Genentech and AbbVie funded the study. Dr. Coutre is an advisory board member for both companies and others, and receives institutional funding from AbbVie and others. Multiple coauthors disclosed financial relationships with AbbVie, Genentech, or both, as well as other companies.

SOURCE: Coutre S et al. Blood. 2018;131(15):1704-11.

For patients with relapsed or refractory chronic lymphocytic leukemia despite therapy with idelalisib (Zydelig), venetoclax (Venclexta) was associated with relatively high overall response and progression-free survival rates, results of a phase 2 study show.

Among 36 patients with relapsed/refractory CLL who had received idelalisib as their most recent B-cell receptor pathway inhibitor (BCRi), the overall response rate (ORR) was 67%, and median progression-free and overall survival (PFS and OS) had not been reached after 14 months of follow-up, reported Steven Coutre, MD, of Stanford (Calif.) University, and his colleagues.

“[V]enetoclax monotherapy is active and well-tolerated in patients with CLL progression after therapy with idelalisib, including a significant number of patients who also received prior therapy with ibrutinib [Imbruvica]. These results from the first prospective trial in this high-risk population provide evidence that venetoclax should be considered as a treatment option for such patients,” the investigators wrote. The report was published in Blood.

In clinical trials with idelalisib, approximately one-third of patients with CLL experienced disease progression on therapy, and other patients had to discontinue the drug, an inhibitor of the delta isoform of phosphoinositide 3-kinase (PI3K), because of toxicities, the investigators noted.

“The optimal treatment of patients with CLL progressing after idelalisib has not been well characterized,” they wrote. “Outcomes in patients who discontinued idelalisib treatment early are poor, with one retrospective analysis reporting a median overall survival (OS) after idelalisib discontinuation of approximately 2 months (range, 0-10 months).”

Venetoclax, an inhibitor of the apoptotic BCL-2 protein, has been shown to have activity against CLL, including in patients with high-risk features such as the chromosome 17p deletion (del17p), prompting the investigators to evaluate it as a follow-on in patients with relapsed/refractory CLL treated with a B-cell receptor pathway inhibitor.

They reported on the idelalisib cohort in a phase 2 trial in which patients with CLL that progressed on either idelalisib or ibrutinib were subsequently treated with venetoclax. The patients in this analysis included those treated with idelalisib in the main study cohort or an expansion cohort.

Patients were started on venetoclax 20 mg daily, followed by weekly dose escalations to a target of 400 mg daily by week 5, or to a maximum of 600 mg for patients who did not have a response by the week 12 assessment.

The overall response rate – the primary efficacy endpoint – was 67%. There were two complete remissions (CR) and one CR with incomplete bone marrow recovery. The remaining 21 patients with responses had partial responses.

At a median of 14 months of follow-up, neither median PFS, duration of response, or OS had been reached.

The investigator-estimated 12-month PFS rate was 79%.

The most common grade 3 or 4 adverse events were neutropenia in 50% of patients, thrombocytopenia in 25%, and anemia in 17%. There were no cases of clinical tumor lysis syndrome, which has been known to occur when venetoclax is initiated at full dose without a ramp-up.

The most common adverse events of any grade included neutropenia, diarrhea, upper respiratory tract infection, thrombocytopenia, nausea, fatigue, cough, rash, and anemia.

“The low number of CRs reported at the time of analysis may be a result of the follow-up time, particularly for patients in the expansion cohort, as other clinical studies with venetoclax report CR occurring after 1 year on therapy. Patients with prior ibrutinib exposure who had progressed on idelalisib as their most recent therapy before study entry had similar efficacy results,” the investigators wrote.

Genentech and AbbVie funded the study. Dr. Coutre is an advisory board member for both companies and others, and receives institutional funding from AbbVie and others. Multiple coauthors disclosed financial relationships with AbbVie, Genentech, or both, as well as other companies.

SOURCE: Coutre S et al. Blood. 2018;131(15):1704-11.

For patients with relapsed or refractory chronic lymphocytic leukemia despite therapy with idelalisib (Zydelig), venetoclax (Venclexta) was associated with relatively high overall response and progression-free survival rates, results of a phase 2 study show.

Among 36 patients with relapsed/refractory CLL who had received idelalisib as their most recent B-cell receptor pathway inhibitor (BCRi), the overall response rate (ORR) was 67%, and median progression-free and overall survival (PFS and OS) had not been reached after 14 months of follow-up, reported Steven Coutre, MD, of Stanford (Calif.) University, and his colleagues.

“[V]enetoclax monotherapy is active and well-tolerated in patients with CLL progression after therapy with idelalisib, including a significant number of patients who also received prior therapy with ibrutinib [Imbruvica]. These results from the first prospective trial in this high-risk population provide evidence that venetoclax should be considered as a treatment option for such patients,” the investigators wrote. The report was published in Blood.

In clinical trials with idelalisib, approximately one-third of patients with CLL experienced disease progression on therapy, and other patients had to discontinue the drug, an inhibitor of the delta isoform of phosphoinositide 3-kinase (PI3K), because of toxicities, the investigators noted.

“The optimal treatment of patients with CLL progressing after idelalisib has not been well characterized,” they wrote. “Outcomes in patients who discontinued idelalisib treatment early are poor, with one retrospective analysis reporting a median overall survival (OS) after idelalisib discontinuation of approximately 2 months (range, 0-10 months).”

Venetoclax, an inhibitor of the apoptotic BCL-2 protein, has been shown to have activity against CLL, including in patients with high-risk features such as the chromosome 17p deletion (del17p), prompting the investigators to evaluate it as a follow-on in patients with relapsed/refractory CLL treated with a B-cell receptor pathway inhibitor.

They reported on the idelalisib cohort in a phase 2 trial in which patients with CLL that progressed on either idelalisib or ibrutinib were subsequently treated with venetoclax. The patients in this analysis included those treated with idelalisib in the main study cohort or an expansion cohort.

Patients were started on venetoclax 20 mg daily, followed by weekly dose escalations to a target of 400 mg daily by week 5, or to a maximum of 600 mg for patients who did not have a response by the week 12 assessment.

The overall response rate – the primary efficacy endpoint – was 67%. There were two complete remissions (CR) and one CR with incomplete bone marrow recovery. The remaining 21 patients with responses had partial responses.

At a median of 14 months of follow-up, neither median PFS, duration of response, or OS had been reached.

The investigator-estimated 12-month PFS rate was 79%.

The most common grade 3 or 4 adverse events were neutropenia in 50% of patients, thrombocytopenia in 25%, and anemia in 17%. There were no cases of clinical tumor lysis syndrome, which has been known to occur when venetoclax is initiated at full dose without a ramp-up.

The most common adverse events of any grade included neutropenia, diarrhea, upper respiratory tract infection, thrombocytopenia, nausea, fatigue, cough, rash, and anemia.

“The low number of CRs reported at the time of analysis may be a result of the follow-up time, particularly for patients in the expansion cohort, as other clinical studies with venetoclax report CR occurring after 1 year on therapy. Patients with prior ibrutinib exposure who had progressed on idelalisib as their most recent therapy before study entry had similar efficacy results,” the investigators wrote.

Genentech and AbbVie funded the study. Dr. Coutre is an advisory board member for both companies and others, and receives institutional funding from AbbVie and others. Multiple coauthors disclosed financial relationships with AbbVie, Genentech, or both, as well as other companies.

SOURCE: Coutre S et al. Blood. 2018;131(15):1704-11.

Exercise and physical therapy in the first weeks after surgery can have a positive impact on health, physical function, and quality of life (QOL) in patients with oral cancer. The changes persist for months afterward, say researchers from Chang Gung Memorial Hospital in Taiwan.

The study involved 65 patients who had undergone reconstructive microsurgery for oral cavity squamous cell carcinoma. The time of intervention had 3 phases: early (8 days to within a month after surgery), middle (1- 3 months after surgery), and late (> 3 months after surgery). The program included pain management, temporomandibular joint exercise, and shoulder and neck exercises.

In the early phase, the main goal was to help participants deal with pain, edema, shoulder dysfunction, and other consequences of surgery. Transcutaneous electrical stimulation for 15 minutes in each treatment session was followed by gentle massage and exercise. During the middle phase, the intervention focused on impairment from surgery or radiation therapy and intensified exercise. The late phase goal was to recover residual function as much as possible.

At 1 month, 40% of patients were on a soft diet. By 6 months, all nasogastric tubes had been removed, and 53% of patients had returned to a normal diet. The researchers note that early intervention to exercise the temporomandibular joint exercise may improve mouth opening. In the advanced stage group, the maximum mouth opening reached its highest at 3 months.

Scapular muscle strength and shoulder range of motion improved progressively during the 6-month follow-up. At 1 month, the mean DASH (Disability of the Arms, Shoulder, and Hand) score showed significant improvement (dropping from 34 to 17). Health-related QOL also showed significant improvement. The predicted return-to-work rate was 80% at 1 year: Patients in skilled or semiskilled work and the self-employed had the highest rates (88% and 87%, respectively).

Source:
Chen YH, Liang WA, Hsu CY, et al. PeerJ. 2018;6e4419.
doi: 10.7717/peerj.4419.

Exercise and physical therapy in the first weeks after surgery can have a positive impact on health, physical function, and quality of life (QOL) in patients with oral cancer. The changes persist for months afterward, say researchers from Chang Gung Memorial Hospital in Taiwan.

The study involved 65 patients who had undergone reconstructive microsurgery for oral cavity squamous cell carcinoma. The time of intervention had 3 phases: early (8 days to within a month after surgery), middle (1- 3 months after surgery), and late (> 3 months after surgery). The program included pain management, temporomandibular joint exercise, and shoulder and neck exercises.

In the early phase, the main goal was to help participants deal with pain, edema, shoulder dysfunction, and other consequences of surgery. Transcutaneous electrical stimulation for 15 minutes in each treatment session was followed by gentle massage and exercise. During the middle phase, the intervention focused on impairment from surgery or radiation therapy and intensified exercise. The late phase goal was to recover residual function as much as possible.

At 1 month, 40% of patients were on a soft diet. By 6 months, all nasogastric tubes had been removed, and 53% of patients had returned to a normal diet. The researchers note that early intervention to exercise the temporomandibular joint exercise may improve mouth opening. In the advanced stage group, the maximum mouth opening reached its highest at 3 months.

Scapular muscle strength and shoulder range of motion improved progressively during the 6-month follow-up. At 1 month, the mean DASH (Disability of the Arms, Shoulder, and Hand) score showed significant improvement (dropping from 34 to 17). Health-related QOL also showed significant improvement. The predicted return-to-work rate was 80% at 1 year: Patients in skilled or semiskilled work and the self-employed had the highest rates (88% and 87%, respectively).

Source:
Chen YH, Liang WA, Hsu CY, et al. PeerJ. 2018;6e4419.
doi: 10.7717/peerj.4419.

Exercise and physical therapy in the first weeks after surgery can have a positive impact on health, physical function, and quality of life (QOL) in patients with oral cancer. The changes persist for months afterward, say researchers from Chang Gung Memorial Hospital in Taiwan.

The study involved 65 patients who had undergone reconstructive microsurgery for oral cavity squamous cell carcinoma. The time of intervention had 3 phases: early (8 days to within a month after surgery), middle (1- 3 months after surgery), and late (> 3 months after surgery). The program included pain management, temporomandibular joint exercise, and shoulder and neck exercises.

In the early phase, the main goal was to help participants deal with pain, edema, shoulder dysfunction, and other consequences of surgery. Transcutaneous electrical stimulation for 15 minutes in each treatment session was followed by gentle massage and exercise. During the middle phase, the intervention focused on impairment from surgery or radiation therapy and intensified exercise. The late phase goal was to recover residual function as much as possible.

At 1 month, 40% of patients were on a soft diet. By 6 months, all nasogastric tubes had been removed, and 53% of patients had returned to a normal diet. The researchers note that early intervention to exercise the temporomandibular joint exercise may improve mouth opening. In the advanced stage group, the maximum mouth opening reached its highest at 3 months.

Scapular muscle strength and shoulder range of motion improved progressively during the 6-month follow-up. At 1 month, the mean DASH (Disability of the Arms, Shoulder, and Hand) score showed significant improvement (dropping from 34 to 17). Health-related QOL also showed significant improvement. The predicted return-to-work rate was 80% at 1 year: Patients in skilled or semiskilled work and the self-employed had the highest rates (88% and 87%, respectively).

Source:
Chen YH, Liang WA, Hsu CY, et al. PeerJ. 2018;6e4419.
doi: 10.7717/peerj.4419.

The Indian Health Service (IHS) has announced a new tool to monitor and report information system-wide. The National Accountability Dashboard for Quality (NAD-Q) will allow IHS to report on key performance data in a “succinct and easily viewed display.”

The NAD-Q shows how IHS is functioning in the following key domains for health care systems:

• Quality (efficient, effective, and equitable);
• Accreditation;
• Workforce;
• Patient-centered care;
• Safety; and
• Timely care.

The dashboard will monitor and report on compliance with policy requirements, accreditation standards, and regulations at hospitals and ambulatory health centers. The tool also supports oversight and management, and will allow IHS to make fact-based decisions to ensure quality and safety of care.

The NAD-Q also allows IHS to share with tribes, tribal and urban Indian organizations, and Congress how well it is meeting standards and requirements

The Indian Health Service (IHS) has announced a new tool to monitor and report information system-wide. The National Accountability Dashboard for Quality (NAD-Q) will allow IHS to report on key performance data in a “succinct and easily viewed display.”

The NAD-Q shows how IHS is functioning in the following key domains for health care systems:

• Quality (efficient, effective, and equitable);
• Accreditation;
• Workforce;
• Patient-centered care;
• Safety; and
• Timely care.

The dashboard will monitor and report on compliance with policy requirements, accreditation standards, and regulations at hospitals and ambulatory health centers. The tool also supports oversight and management, and will allow IHS to make fact-based decisions to ensure quality and safety of care.

The NAD-Q also allows IHS to share with tribes, tribal and urban Indian organizations, and Congress how well it is meeting standards and requirements

The Indian Health Service (IHS) has announced a new tool to monitor and report information system-wide. The National Accountability Dashboard for Quality (NAD-Q) will allow IHS to report on key performance data in a “succinct and easily viewed display.”

The NAD-Q shows how IHS is functioning in the following key domains for health care systems:

• Quality (efficient, effective, and equitable);
• Accreditation;
• Workforce;
• Patient-centered care;
• Safety; and
• Timely care.

The dashboard will monitor and report on compliance with policy requirements, accreditation standards, and regulations at hospitals and ambulatory health centers. The tool also supports oversight and management, and will allow IHS to make fact-based decisions to ensure quality and safety of care.

The NAD-Q also allows IHS to share with tribes, tribal and urban Indian organizations, and Congress how well it is meeting standards and requirements

The American Academy of Sleep Medicine (AASM) opposes the use of medical cannabis and its synthetic extracts for treating obstructive sleep apnea, according to a position statement published in the Journal of Clinical Sleep Medicine’s April issue.

copyright designer491/Thinkstock

In the statement, the professional society recommends that state legislators, regulators, and health departments exclude obstructive sleep apnea (OSA) as an indication for medical cannabis programs.
 

The “unreliable delivery methods and insufficient evidence of treatment effectiveness, tolerability, and safety” of medical cannabis and its synthetic extracts are among the reasons the AASM gave for making its recommendations. “Further research is needed to better understand the mechanistic actions of medical cannabis and its synthetic extracts, the long-term role of these synthetic extracts on OSA treatment, and harms and benefits,” the AASM concluded in its statement, authored by Kannan Ramar, MD, and other members of a panel of experts on sleep medicine.

Dronabinol is the only cannabis product that has been tested on patients with OSA for the treatment of this disorder. While some synthetic cannabis products are approved by the Food and Drug Administration for other medical indications, the synthetic-based cannabis product dronabinol has not received FDA approval for the treatment of OSA.

Researchers have examined dronabinol’s use for treating OSA in small pilot and proof-of-concept studies and most patients in these studies reported experiencing treatment-related side effects, such as somnolence, wrote Dr. Ramar, of the division of pulmonary and critical care medicine at the Center for Sleep Medicine, Mayo Clinic, Rochester Minn., and his colleagues.

These trials involved patients having taken dronabinol pills in strengths ranging from 2.5 mg to 10 mg. One such study (Front Psychiatry. 2013 Jan 22. doi: 10.3389/fpsyt.2013.00001), authored by Bharati Prasad of the University of Illinois, Chicago, and colleagues, showed a significant improvement in apnea-hypopnea index (AHI) of 32%, after 17 patients used dronabinol for 3 weeks, when compared with baseline AHIs (–14.1; P = .007).

A placebo-controlled randomized study of 73 adults with moderate or severe OSA similarly found a 33% decline in AHI in patients following 6 weeks of treatment with 10-mg doses of dronabinol (Sleep. 2018 Jan 1. doi: 10.1093/sleep/zsx184).

In the placebo-controlled study, 73 patients were randomized to receive 2.5 mg of dronabinol or 10 mg of dronabinol daily for up to 6 weeks, or placebo. At the end of treatment, researchers saw significant increases in the AHI among the patients on placebo, while those who received dronabinol showed decreases in the number of apnea and hypopnea events per hour. Patients given the 2.5-mg dose of dronabinol had a mean decrease of 10.7 events per hour, and those on the 10-mg dose had a mean decrease of 12.9 events per hour compared with placebo. The difference between the placebo and treatment arms was significant for both dosages, and the AHI decreases were similar between the two dosages of dronabinol.

These effects were largely due to reductions in apnea events; the largest reduction was seen in the REM apnea index in patients treated with the 10-mg dose of dronabinol. However, there were few effects on the expression of hypopneas, except in the higher-dose group.

After adjustment for age, race, ethnicity, and baseline AHI, the increases seen in the placebo group were no longer significant, but the decreases from baseline seen in the treatment arms were greater. Dronabinol treatment also was associated with significant decreases, compared with placebo, in non-REM AHI and REM AHI.

Overall, nearly 90% of patients in this trial reported at least one adverse event, with the rates having not differed significantly between the treatment and placebo arms. The most frequently reported adverse events were “sleepiness/drowsiness” (n = 25; 8% of total adverse events reported), headache (n = 24; 8%), “nausea/vomiting” (n = 23; 8%), and “dizziness/lightheadedness” (n = 12; 4%). In addition, one patient experienced diarrhea and vomiting that required admission to a hospital, which was judged as possibly related to the study medication. There were six other withdrawals due to adverse events, including dizziness and vision changes, vertigo, ECG arrhythmias, and headache with dizziness and vomiting.

“Synthetic medical cannabis may have differential side effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA,” Dr. Ramar and his associates wrote.

klennon@mdedge.com

SOURCE: J Clin Sleep Med. 2018 April;14[4]:679-81.

The American Academy of Sleep Medicine (AASM) opposes the use of medical cannabis and its synthetic extracts for treating obstructive sleep apnea, according to a position statement published in the Journal of Clinical Sleep Medicine’s April issue.

copyright designer491/Thinkstock

In the statement, the professional society recommends that state legislators, regulators, and health departments exclude obstructive sleep apnea (OSA) as an indication for medical cannabis programs.
 

The “unreliable delivery methods and insufficient evidence of treatment effectiveness, tolerability, and safety” of medical cannabis and its synthetic extracts are among the reasons the AASM gave for making its recommendations. “Further research is needed to better understand the mechanistic actions of medical cannabis and its synthetic extracts, the long-term role of these synthetic extracts on OSA treatment, and harms and benefits,” the AASM concluded in its statement, authored by Kannan Ramar, MD, and other members of a panel of experts on sleep medicine.

Dronabinol is the only cannabis product that has been tested on patients with OSA for the treatment of this disorder. While some synthetic cannabis products are approved by the Food and Drug Administration for other medical indications, the synthetic-based cannabis product dronabinol has not received FDA approval for the treatment of OSA.

Researchers have examined dronabinol’s use for treating OSA in small pilot and proof-of-concept studies and most patients in these studies reported experiencing treatment-related side effects, such as somnolence, wrote Dr. Ramar, of the division of pulmonary and critical care medicine at the Center for Sleep Medicine, Mayo Clinic, Rochester Minn., and his colleagues.

These trials involved patients having taken dronabinol pills in strengths ranging from 2.5 mg to 10 mg. One such study (Front Psychiatry. 2013 Jan 22. doi: 10.3389/fpsyt.2013.00001), authored by Bharati Prasad of the University of Illinois, Chicago, and colleagues, showed a significant improvement in apnea-hypopnea index (AHI) of 32%, after 17 patients used dronabinol for 3 weeks, when compared with baseline AHIs (–14.1; P = .007).

A placebo-controlled randomized study of 73 adults with moderate or severe OSA similarly found a 33% decline in AHI in patients following 6 weeks of treatment with 10-mg doses of dronabinol (Sleep. 2018 Jan 1. doi: 10.1093/sleep/zsx184).

In the placebo-controlled study, 73 patients were randomized to receive 2.5 mg of dronabinol or 10 mg of dronabinol daily for up to 6 weeks, or placebo. At the end of treatment, researchers saw significant increases in the AHI among the patients on placebo, while those who received dronabinol showed decreases in the number of apnea and hypopnea events per hour. Patients given the 2.5-mg dose of dronabinol had a mean decrease of 10.7 events per hour, and those on the 10-mg dose had a mean decrease of 12.9 events per hour compared with placebo. The difference between the placebo and treatment arms was significant for both dosages, and the AHI decreases were similar between the two dosages of dronabinol.

These effects were largely due to reductions in apnea events; the largest reduction was seen in the REM apnea index in patients treated with the 10-mg dose of dronabinol. However, there were few effects on the expression of hypopneas, except in the higher-dose group.

After adjustment for age, race, ethnicity, and baseline AHI, the increases seen in the placebo group were no longer significant, but the decreases from baseline seen in the treatment arms were greater. Dronabinol treatment also was associated with significant decreases, compared with placebo, in non-REM AHI and REM AHI.

Overall, nearly 90% of patients in this trial reported at least one adverse event, with the rates having not differed significantly between the treatment and placebo arms. The most frequently reported adverse events were “sleepiness/drowsiness” (n = 25; 8% of total adverse events reported), headache (n = 24; 8%), “nausea/vomiting” (n = 23; 8%), and “dizziness/lightheadedness” (n = 12; 4%). In addition, one patient experienced diarrhea and vomiting that required admission to a hospital, which was judged as possibly related to the study medication. There were six other withdrawals due to adverse events, including dizziness and vision changes, vertigo, ECG arrhythmias, and headache with dizziness and vomiting.

“Synthetic medical cannabis may have differential side effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA,” Dr. Ramar and his associates wrote.

klennon@mdedge.com

SOURCE: J Clin Sleep Med. 2018 April;14[4]:679-81.

The American Academy of Sleep Medicine (AASM) opposes the use of medical cannabis and its synthetic extracts for treating obstructive sleep apnea, according to a position statement published in the Journal of Clinical Sleep Medicine’s April issue.

copyright designer491/Thinkstock

In the statement, the professional society recommends that state legislators, regulators, and health departments exclude obstructive sleep apnea (OSA) as an indication for medical cannabis programs.
 

The “unreliable delivery methods and insufficient evidence of treatment effectiveness, tolerability, and safety” of medical cannabis and its synthetic extracts are among the reasons the AASM gave for making its recommendations. “Further research is needed to better understand the mechanistic actions of medical cannabis and its synthetic extracts, the long-term role of these synthetic extracts on OSA treatment, and harms and benefits,” the AASM concluded in its statement, authored by Kannan Ramar, MD, and other members of a panel of experts on sleep medicine.

Dronabinol is the only cannabis product that has been tested on patients with OSA for the treatment of this disorder. While some synthetic cannabis products are approved by the Food and Drug Administration for other medical indications, the synthetic-based cannabis product dronabinol has not received FDA approval for the treatment of OSA.

Researchers have examined dronabinol’s use for treating OSA in small pilot and proof-of-concept studies and most patients in these studies reported experiencing treatment-related side effects, such as somnolence, wrote Dr. Ramar, of the division of pulmonary and critical care medicine at the Center for Sleep Medicine, Mayo Clinic, Rochester Minn., and his colleagues.

These trials involved patients having taken dronabinol pills in strengths ranging from 2.5 mg to 10 mg. One such study (Front Psychiatry. 2013 Jan 22. doi: 10.3389/fpsyt.2013.00001), authored by Bharati Prasad of the University of Illinois, Chicago, and colleagues, showed a significant improvement in apnea-hypopnea index (AHI) of 32%, after 17 patients used dronabinol for 3 weeks, when compared with baseline AHIs (–14.1; P = .007).

A placebo-controlled randomized study of 73 adults with moderate or severe OSA similarly found a 33% decline in AHI in patients following 6 weeks of treatment with 10-mg doses of dronabinol (Sleep. 2018 Jan 1. doi: 10.1093/sleep/zsx184).

In the placebo-controlled study, 73 patients were randomized to receive 2.5 mg of dronabinol or 10 mg of dronabinol daily for up to 6 weeks, or placebo. At the end of treatment, researchers saw significant increases in the AHI among the patients on placebo, while those who received dronabinol showed decreases in the number of apnea and hypopnea events per hour. Patients given the 2.5-mg dose of dronabinol had a mean decrease of 10.7 events per hour, and those on the 10-mg dose had a mean decrease of 12.9 events per hour compared with placebo. The difference between the placebo and treatment arms was significant for both dosages, and the AHI decreases were similar between the two dosages of dronabinol.

These effects were largely due to reductions in apnea events; the largest reduction was seen in the REM apnea index in patients treated with the 10-mg dose of dronabinol. However, there were few effects on the expression of hypopneas, except in the higher-dose group.

After adjustment for age, race, ethnicity, and baseline AHI, the increases seen in the placebo group were no longer significant, but the decreases from baseline seen in the treatment arms were greater. Dronabinol treatment also was associated with significant decreases, compared with placebo, in non-REM AHI and REM AHI.

Overall, nearly 90% of patients in this trial reported at least one adverse event, with the rates having not differed significantly between the treatment and placebo arms. The most frequently reported adverse events were “sleepiness/drowsiness” (n = 25; 8% of total adverse events reported), headache (n = 24; 8%), “nausea/vomiting” (n = 23; 8%), and “dizziness/lightheadedness” (n = 12; 4%). In addition, one patient experienced diarrhea and vomiting that required admission to a hospital, which was judged as possibly related to the study medication. There were six other withdrawals due to adverse events, including dizziness and vision changes, vertigo, ECG arrhythmias, and headache with dizziness and vomiting.

“Synthetic medical cannabis may have differential side effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA,” Dr. Ramar and his associates wrote.

klennon@mdedge.com

SOURCE: J Clin Sleep Med. 2018 April;14[4]:679-81.