Mark S. Lesney, PhD

Sepsis survivors discharged to post-acute care facilities are at high risk for mortality and hospital readmission, according to Nicholas Colucciello, MD, and few interventions have been shown to reduce these adverse outcomes.

Dr. Colucciello and colleagues compared the effects of a Sepsis Transition And Recovery (STAR) program versus Usual Care (UC) alone on 30-day mortality and hospital readmission among sepsis survivors discharged to post-acute care.

In a study presented at the annual meeting of the American College of Chest Physicians (CHEST), Dr. Colucciello, a primary care physician in Toledo, Ohio, presented data suggesting that the STAR intervention program appears beneficial for patients discharged to post-acute care facilities and may lead to decreased 30-day mortality and readmission rates.
 

Study of IMPACTS

The study was a secondary analysis of patients from the IMPACTS (Improving Morbidity During Post-Acute Care Transitions for Sepsis) randomized clinical trial, focusing only on those patients who were discharged to a post-acute care facility. IMPACTS evaluated the effectiveness of STAR, a post-sepsis transition program using nurse navigators to deliver best-practice post-sepsis care during and after hospitalization, Dr. Colucciello said. The interventions included comorbidity monitoring, medication review, evaluation for new impairments/symptoms, and goals of care assessment.

“Over one-third of sepsis survivors are discharged to post-acute care as they are not stable enough to go home,” said Dr. Colucciello, and among these patients there is a high risk for mortality and hospital readmission.

Dr. Colucciello and his colleagues randomly assigned patients hospitalized with sepsis and deemed high risk for post-discharge readmission or mortality to either STAR or usual care. The primary outcome was a composite of 30-day readmission and mortality, which was assessed from the electronic health record and social security death master file.

Of the 175 (21%) IMPACTS patients discharged to post-acute care facilities, 143 (82%) were sent to skilled nursing facilities, and 12 (7%) were sent to long-term acute care hospitals. The remaining 20 patients (11%) were sent to inpatient rehabilitation. A total of 88 of these patients received the STAR intervention and 87 received usual care.
 

Suggestive results

The study showed that the composite primary endpoint occurred in 26 (30.6%) patients in the usual care group versus 18 (20.7%) patients in the STAR group, for a risk difference of –9.9% (95% CI, –22.9 to 3.1), according to Dr. Colucciello. As individual factors, 30-day all-cause mortality was 8.2% in the UC group, compared with 5.8% in the STAR group, for a risk difference of –2.5% (95% CI, –10.1 to 5.0) and the 30-day all-cause readmission was 27.1% in the UC group, compared with 17.2% in the STAR program, for a risk difference of –9.8% (95% CI, –22.2 to 2.5). On average, patients receiving UC experienced 26.5 hospital-free days, compared with 27.4 hospital-free days in the STAR group, he added.

The biggest limitation of the study was the fact that it was underpowered to detect statistically significant differences, despite the suggestive results, said Dr. Colucciello. However, he added: “This secondary analysis of the IMPACTS randomized trial found that the STAR intervention may decrease 30-day mortality and readmission rates among sepsis patients discharged to a post-acute care facility,” he concluded.

Dr. Colucciello and colleagues report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Sepsis survivors discharged to post-acute care facilities are at high risk for mortality and hospital readmission, according to Nicholas Colucciello, MD, and few interventions have been shown to reduce these adverse outcomes.

Dr. Colucciello and colleagues compared the effects of a Sepsis Transition And Recovery (STAR) program versus Usual Care (UC) alone on 30-day mortality and hospital readmission among sepsis survivors discharged to post-acute care.

In a study presented at the annual meeting of the American College of Chest Physicians (CHEST), Dr. Colucciello, a primary care physician in Toledo, Ohio, presented data suggesting that the STAR intervention program appears beneficial for patients discharged to post-acute care facilities and may lead to decreased 30-day mortality and readmission rates.
 

Study of IMPACTS

The study was a secondary analysis of patients from the IMPACTS (Improving Morbidity During Post-Acute Care Transitions for Sepsis) randomized clinical trial, focusing only on those patients who were discharged to a post-acute care facility. IMPACTS evaluated the effectiveness of STAR, a post-sepsis transition program using nurse navigators to deliver best-practice post-sepsis care during and after hospitalization, Dr. Colucciello said. The interventions included comorbidity monitoring, medication review, evaluation for new impairments/symptoms, and goals of care assessment.

“Over one-third of sepsis survivors are discharged to post-acute care as they are not stable enough to go home,” said Dr. Colucciello, and among these patients there is a high risk for mortality and hospital readmission.

Dr. Colucciello and his colleagues randomly assigned patients hospitalized with sepsis and deemed high risk for post-discharge readmission or mortality to either STAR or usual care. The primary outcome was a composite of 30-day readmission and mortality, which was assessed from the electronic health record and social security death master file.

Of the 175 (21%) IMPACTS patients discharged to post-acute care facilities, 143 (82%) were sent to skilled nursing facilities, and 12 (7%) were sent to long-term acute care hospitals. The remaining 20 patients (11%) were sent to inpatient rehabilitation. A total of 88 of these patients received the STAR intervention and 87 received usual care.
 

Suggestive results

The study showed that the composite primary endpoint occurred in 26 (30.6%) patients in the usual care group versus 18 (20.7%) patients in the STAR group, for a risk difference of –9.9% (95% CI, –22.9 to 3.1), according to Dr. Colucciello. As individual factors, 30-day all-cause mortality was 8.2% in the UC group, compared with 5.8% in the STAR group, for a risk difference of –2.5% (95% CI, –10.1 to 5.0) and the 30-day all-cause readmission was 27.1% in the UC group, compared with 17.2% in the STAR program, for a risk difference of –9.8% (95% CI, –22.2 to 2.5). On average, patients receiving UC experienced 26.5 hospital-free days, compared with 27.4 hospital-free days in the STAR group, he added.

The biggest limitation of the study was the fact that it was underpowered to detect statistically significant differences, despite the suggestive results, said Dr. Colucciello. However, he added: “This secondary analysis of the IMPACTS randomized trial found that the STAR intervention may decrease 30-day mortality and readmission rates among sepsis patients discharged to a post-acute care facility,” he concluded.

Dr. Colucciello and colleagues report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Sepsis survivors discharged to post-acute care facilities are at high risk for mortality and hospital readmission, according to Nicholas Colucciello, MD, and few interventions have been shown to reduce these adverse outcomes.

Dr. Colucciello and colleagues compared the effects of a Sepsis Transition And Recovery (STAR) program versus Usual Care (UC) alone on 30-day mortality and hospital readmission among sepsis survivors discharged to post-acute care.

In a study presented at the annual meeting of the American College of Chest Physicians (CHEST), Dr. Colucciello, a primary care physician in Toledo, Ohio, presented data suggesting that the STAR intervention program appears beneficial for patients discharged to post-acute care facilities and may lead to decreased 30-day mortality and readmission rates.
 

Study of IMPACTS

The study was a secondary analysis of patients from the IMPACTS (Improving Morbidity During Post-Acute Care Transitions for Sepsis) randomized clinical trial, focusing only on those patients who were discharged to a post-acute care facility. IMPACTS evaluated the effectiveness of STAR, a post-sepsis transition program using nurse navigators to deliver best-practice post-sepsis care during and after hospitalization, Dr. Colucciello said. The interventions included comorbidity monitoring, medication review, evaluation for new impairments/symptoms, and goals of care assessment.

“Over one-third of sepsis survivors are discharged to post-acute care as they are not stable enough to go home,” said Dr. Colucciello, and among these patients there is a high risk for mortality and hospital readmission.

Dr. Colucciello and his colleagues randomly assigned patients hospitalized with sepsis and deemed high risk for post-discharge readmission or mortality to either STAR or usual care. The primary outcome was a composite of 30-day readmission and mortality, which was assessed from the electronic health record and social security death master file.

Of the 175 (21%) IMPACTS patients discharged to post-acute care facilities, 143 (82%) were sent to skilled nursing facilities, and 12 (7%) were sent to long-term acute care hospitals. The remaining 20 patients (11%) were sent to inpatient rehabilitation. A total of 88 of these patients received the STAR intervention and 87 received usual care.
 

Suggestive results

The study showed that the composite primary endpoint occurred in 26 (30.6%) patients in the usual care group versus 18 (20.7%) patients in the STAR group, for a risk difference of –9.9% (95% CI, –22.9 to 3.1), according to Dr. Colucciello. As individual factors, 30-day all-cause mortality was 8.2% in the UC group, compared with 5.8% in the STAR group, for a risk difference of –2.5% (95% CI, –10.1 to 5.0) and the 30-day all-cause readmission was 27.1% in the UC group, compared with 17.2% in the STAR program, for a risk difference of –9.8% (95% CI, –22.2 to 2.5). On average, patients receiving UC experienced 26.5 hospital-free days, compared with 27.4 hospital-free days in the STAR group, he added.

The biggest limitation of the study was the fact that it was underpowered to detect statistically significant differences, despite the suggestive results, said Dr. Colucciello. However, he added: “This secondary analysis of the IMPACTS randomized trial found that the STAR intervention may decrease 30-day mortality and readmission rates among sepsis patients discharged to a post-acute care facility,” he concluded.

Dr. Colucciello and colleagues report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This column presents a sampling of new and still-recruiting trials of interest to pulmonologists and their patients.

Trials are selected based primarily on these conditions: idiopathic pulmonary fibrosis/interstitial lung disease; chronic obstructive pulmonary disease (COPD); asthma; cystic fibrosis; infectious lung diseases; pulmonary artery hypertension; and lung cancer. Links to the studies and contact information are provided for each.

Idiopathic pulmonary fibrosis/interstitial lung disease

A Study to Evaluate Long-term Safety of Nintedanib in Children and Adolescents With Interstitial Lung Disease (InPedILD™-ON): NCT05285982

This nonrandomized, phase 3 study is open to children and adolescents between 6 and 17 years old who have interstitial lung disease with lung fibrosis. It is designed to test how well long-term treatment with nintedanib (a drug already used to treat lung fibrosis in adults) is tolerated in children and adolescents.

A total of 60 study participants will take nintedanib capsules twice a day for at least 2 years or until nintedanib or other treatment options become available outside of the study. There will be 9-11 site visits during the first 2 years and site visits every 3 months afterward.

Study physicians will collect information on any health problems of the participants. The primary outcome measure will be the incidence of treatment-emergent adverse events.
 

Location: 26 locations in the United States and internationally

Sponsor: Boehringer Ingelheim

Contact: clintriage.rdg@boehringer-ingelheim.com

Study start date: April 2022

Expected completion Date: May 2026

Asthma

A Phase 2, Single-Dose, Randomized, Active and Placebo Controlled, Four-Period, Cross-Over Study of the Safety and Efficacy of Intranasal Epinephrine After Administration of ARS-1 or Albuterol in Subjects With Persistent Asthma: NCT05363670

ARS-1 is a novel aqueous formulation of epinephrine nasal spray. The primary outcomes of this study will be the effect of ARS-1 versus albuterol and placebo from baseline to 1 hour on the difference in forced expiratory volume in 1 second based on area under the curve.

A total of 30 study participants (ages 12-65 years) will be recruited.
 

Location: Three U.S. locations in Florida, Maryland, and Ohio.

Sponsor: ARS Pharmaceuticals

Contact: rhasson@pacificlinkconsulting.com

Study start date: July 2022

Expected completion Date: November 2022

COPD

Treatment of Pneumocystitis in COPD (the TOPIC Study): NCT05418777

In this randomized, double-blind, placebo-controlled study, the primary outcome will be to determine if treating Pneumocystis jirovecii in acute exacerbations of COPD with confirmed P. jirovecii colonization has a beneficial clinical impact. As a secondary goal of the study, it will be determined if the addition of trimethoprim-sulfamethoxazole (TMP-SMX) to standard of care can decolonize these patients and if the decolonization is durable for at least 3 months.
 

A total of 30 participants aged 40-89 years will be randomized to receive either a suspension with the equivalent of one double-strength TMP-SMX or a suspension with placebo by mouth every 12 hours. If the participant is discharged prior to completing the 10-day course of the medication, they will be sent home with the remaining study medication and a medication diary which will be collected.
 

Location: William Beaumont Hospital, Royal Oak, Mich.

Sponsor: William Beaumont Hospitals

Contact: matthew.sims@beaumont.edu

Study start date: July 2022

Expected completion Date: August 2023

Inter-lobar Fissure Completion in Patients With Failed Bronchoscopic Lung Volume Reduction (SAVED-1): NCT05257681

This study is intended to be a pilot prospective controlled clinical trial to evaluate the potential role of a lung fissure completion with pleural adhesiolysis strategy (experimental intervention) in severe emphysema/COPD patients with failed bronchoscopic lung volume reduction via the use of endobronchial valves therapy.

In 20 select patients (ages 40-75 years), the lung fissure completion with adhesiolysis strategy will be performed by video-assisted thoracoscopic surgery guided stapling along the lung fissures to reduce collateral ventilation with adhesions removal. The primary outcomes will be to prove that interlobar fissures can be completed to at least 95% in severe emphysema patients with previously failed bronchoscopic lung volume reduction over a 2 year period and the occurrence of adverse events in that period. The surgery will be considered feasible if the target inter-lobar fissure can be completed in at least 90% of the patients enrolled. Secondary outcomes over 2 years will include quality of life improvement and the percentage of patients with significant changes in pulmonary function testing.
 

Location: Beth Deaconess Medical Center, Boston

Sponsor: Beth Israel Deaconess Medical Center

Contact: amajid@bidmc.harvard.edu

Study start date: May 2022

Expected completion Date: May 2024

This column presents a sampling of new and still-recruiting trials of interest to pulmonologists and their patients.

Trials are selected based primarily on these conditions: idiopathic pulmonary fibrosis/interstitial lung disease; chronic obstructive pulmonary disease (COPD); asthma; cystic fibrosis; infectious lung diseases; pulmonary artery hypertension; and lung cancer. Links to the studies and contact information are provided for each.

Idiopathic pulmonary fibrosis/interstitial lung disease

A Study to Evaluate Long-term Safety of Nintedanib in Children and Adolescents With Interstitial Lung Disease (InPedILD™-ON): NCT05285982

This nonrandomized, phase 3 study is open to children and adolescents between 6 and 17 years old who have interstitial lung disease with lung fibrosis. It is designed to test how well long-term treatment with nintedanib (a drug already used to treat lung fibrosis in adults) is tolerated in children and adolescents.

A total of 60 study participants will take nintedanib capsules twice a day for at least 2 years or until nintedanib or other treatment options become available outside of the study. There will be 9-11 site visits during the first 2 years and site visits every 3 months afterward.

Study physicians will collect information on any health problems of the participants. The primary outcome measure will be the incidence of treatment-emergent adverse events.
 

Location: 26 locations in the United States and internationally

Sponsor: Boehringer Ingelheim

Contact: clintriage.rdg@boehringer-ingelheim.com

Study start date: April 2022

Expected completion Date: May 2026

Asthma

A Phase 2, Single-Dose, Randomized, Active and Placebo Controlled, Four-Period, Cross-Over Study of the Safety and Efficacy of Intranasal Epinephrine After Administration of ARS-1 or Albuterol in Subjects With Persistent Asthma: NCT05363670

ARS-1 is a novel aqueous formulation of epinephrine nasal spray. The primary outcomes of this study will be the effect of ARS-1 versus albuterol and placebo from baseline to 1 hour on the difference in forced expiratory volume in 1 second based on area under the curve.

A total of 30 study participants (ages 12-65 years) will be recruited.
 

Location: Three U.S. locations in Florida, Maryland, and Ohio.

Sponsor: ARS Pharmaceuticals

Contact: rhasson@pacificlinkconsulting.com

Study start date: July 2022

Expected completion Date: November 2022

COPD

Treatment of Pneumocystitis in COPD (the TOPIC Study): NCT05418777

In this randomized, double-blind, placebo-controlled study, the primary outcome will be to determine if treating Pneumocystis jirovecii in acute exacerbations of COPD with confirmed P. jirovecii colonization has a beneficial clinical impact. As a secondary goal of the study, it will be determined if the addition of trimethoprim-sulfamethoxazole (TMP-SMX) to standard of care can decolonize these patients and if the decolonization is durable for at least 3 months.
 

A total of 30 participants aged 40-89 years will be randomized to receive either a suspension with the equivalent of one double-strength TMP-SMX or a suspension with placebo by mouth every 12 hours. If the participant is discharged prior to completing the 10-day course of the medication, they will be sent home with the remaining study medication and a medication diary which will be collected.
 

Location: William Beaumont Hospital, Royal Oak, Mich.

Sponsor: William Beaumont Hospitals

Contact: matthew.sims@beaumont.edu

Study start date: July 2022

Expected completion Date: August 2023

Inter-lobar Fissure Completion in Patients With Failed Bronchoscopic Lung Volume Reduction (SAVED-1): NCT05257681

This study is intended to be a pilot prospective controlled clinical trial to evaluate the potential role of a lung fissure completion with pleural adhesiolysis strategy (experimental intervention) in severe emphysema/COPD patients with failed bronchoscopic lung volume reduction via the use of endobronchial valves therapy.

In 20 select patients (ages 40-75 years), the lung fissure completion with adhesiolysis strategy will be performed by video-assisted thoracoscopic surgery guided stapling along the lung fissures to reduce collateral ventilation with adhesions removal. The primary outcomes will be to prove that interlobar fissures can be completed to at least 95% in severe emphysema patients with previously failed bronchoscopic lung volume reduction over a 2 year period and the occurrence of adverse events in that period. The surgery will be considered feasible if the target inter-lobar fissure can be completed in at least 90% of the patients enrolled. Secondary outcomes over 2 years will include quality of life improvement and the percentage of patients with significant changes in pulmonary function testing.
 

Location: Beth Deaconess Medical Center, Boston

Sponsor: Beth Israel Deaconess Medical Center

Contact: amajid@bidmc.harvard.edu

Study start date: May 2022

Expected completion Date: May 2024

This column presents a sampling of new and still-recruiting trials of interest to pulmonologists and their patients.

Trials are selected based primarily on these conditions: idiopathic pulmonary fibrosis/interstitial lung disease; chronic obstructive pulmonary disease (COPD); asthma; cystic fibrosis; infectious lung diseases; pulmonary artery hypertension; and lung cancer. Links to the studies and contact information are provided for each.

Idiopathic pulmonary fibrosis/interstitial lung disease

A Study to Evaluate Long-term Safety of Nintedanib in Children and Adolescents With Interstitial Lung Disease (InPedILD™-ON): NCT05285982

This nonrandomized, phase 3 study is open to children and adolescents between 6 and 17 years old who have interstitial lung disease with lung fibrosis. It is designed to test how well long-term treatment with nintedanib (a drug already used to treat lung fibrosis in adults) is tolerated in children and adolescents.

A total of 60 study participants will take nintedanib capsules twice a day for at least 2 years or until nintedanib or other treatment options become available outside of the study. There will be 9-11 site visits during the first 2 years and site visits every 3 months afterward.

Study physicians will collect information on any health problems of the participants. The primary outcome measure will be the incidence of treatment-emergent adverse events.
 

Location: 26 locations in the United States and internationally

Sponsor: Boehringer Ingelheim

Contact: clintriage.rdg@boehringer-ingelheim.com

Study start date: April 2022

Expected completion Date: May 2026

Asthma

A Phase 2, Single-Dose, Randomized, Active and Placebo Controlled, Four-Period, Cross-Over Study of the Safety and Efficacy of Intranasal Epinephrine After Administration of ARS-1 or Albuterol in Subjects With Persistent Asthma: NCT05363670

ARS-1 is a novel aqueous formulation of epinephrine nasal spray. The primary outcomes of this study will be the effect of ARS-1 versus albuterol and placebo from baseline to 1 hour on the difference in forced expiratory volume in 1 second based on area under the curve.

A total of 30 study participants (ages 12-65 years) will be recruited.
 

Location: Three U.S. locations in Florida, Maryland, and Ohio.

Sponsor: ARS Pharmaceuticals

Contact: rhasson@pacificlinkconsulting.com

Study start date: July 2022

Expected completion Date: November 2022

COPD

Treatment of Pneumocystitis in COPD (the TOPIC Study): NCT05418777

In this randomized, double-blind, placebo-controlled study, the primary outcome will be to determine if treating Pneumocystis jirovecii in acute exacerbations of COPD with confirmed P. jirovecii colonization has a beneficial clinical impact. As a secondary goal of the study, it will be determined if the addition of trimethoprim-sulfamethoxazole (TMP-SMX) to standard of care can decolonize these patients and if the decolonization is durable for at least 3 months.
 

A total of 30 participants aged 40-89 years will be randomized to receive either a suspension with the equivalent of one double-strength TMP-SMX or a suspension with placebo by mouth every 12 hours. If the participant is discharged prior to completing the 10-day course of the medication, they will be sent home with the remaining study medication and a medication diary which will be collected.
 

Location: William Beaumont Hospital, Royal Oak, Mich.

Sponsor: William Beaumont Hospitals

Contact: matthew.sims@beaumont.edu

Study start date: July 2022

Expected completion Date: August 2023

Inter-lobar Fissure Completion in Patients With Failed Bronchoscopic Lung Volume Reduction (SAVED-1): NCT05257681

This study is intended to be a pilot prospective controlled clinical trial to evaluate the potential role of a lung fissure completion with pleural adhesiolysis strategy (experimental intervention) in severe emphysema/COPD patients with failed bronchoscopic lung volume reduction via the use of endobronchial valves therapy.

In 20 select patients (ages 40-75 years), the lung fissure completion with adhesiolysis strategy will be performed by video-assisted thoracoscopic surgery guided stapling along the lung fissures to reduce collateral ventilation with adhesions removal. The primary outcomes will be to prove that interlobar fissures can be completed to at least 95% in severe emphysema patients with previously failed bronchoscopic lung volume reduction over a 2 year period and the occurrence of adverse events in that period. The surgery will be considered feasible if the target inter-lobar fissure can be completed in at least 90% of the patients enrolled. Secondary outcomes over 2 years will include quality of life improvement and the percentage of patients with significant changes in pulmonary function testing.
 

Location: Beth Deaconess Medical Center, Boston

Sponsor: Beth Israel Deaconess Medical Center

Contact: amajid@bidmc.harvard.edu

Study start date: May 2022

Expected completion Date: May 2024

Poor sleep quality was linked to an increased risk of life-threatening exacerbations in people with chronic obstructive pulmonary disease (COPD), according to a study reported online in the journal Sleep.

Researchers followed 1,647 patients with confirmed COPD who were enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). SPIROMICS is a multicenter study funded by the National Heart, Lung, and Blood Institute and the COPD Foundation and is designed to evaluate COPD subpopulations, outcomes, and biomarkers. All participants in the study were current or former smokers with confirmed COPD.

COPD exacerbations over a 3-year follow-up period were compared against reported sleep quality. The researchers used the Pittsburgh Sleep Quality Index (PSQI), a combination of seven sleep measures, including sleep duration, timing of sleep, and frequency of disturbances. The higher the score, the worse the quality of sleep.

Individuals who self-reported having poor-quality sleep had a 25%-95% higher risk of COPD exacerbations, compared with those who reported good-quality sleep, according to the results.

There was a significant association between PSQI score and total and mean exacerbations in the unadjusted analysis (incidence rate ratios, 1.09; 95% confidence interval, 1.05-1.13) and the analysis adjusted for demographics, medical comorbidities, disease severity, medication usage, and socioeconomic environmental exposure (IRR, 1.08; 95% CI, 1.03-1.13).

In addition, the PSQI score was independently associated with an increased risk of hospitalization, with a 7% increase in risk of hospitalization with each 1-point increase in PSQI, according to the researchers.
 

Surprising findings

These findings suggest that sleep quality may be a better predictor of flare-ups than the patient’s history of smoking, according to the researchers.

“Among those who already have COPD, knowing how they sleep at night will tell me much more about their risk of a flare-up than knowing whether they smoked for 40 versus 60 years. … That is very surprising and is not necessarily what I expected going into this study. Smoking is such a central process to COPD that I would have predicted it would be the more important predictor in the case of exacerbations,” said lead study author Aaron Baugh, MD, a practicing pulmonologist, and a clinical fellow at the University of California, San Francisco, in a National Institutes of Health press release on the study.

The study findings were applicable to all races and ethnicities studied, however the results may be particularly relevant to Black Americans, Dr. Baugh indicated, because past studies have shown that Black Americans tend to have poorer sleep quality than other races and ethnicities. With poorer sleep linked to worse COPD outcomes, the current study may help explain why Black Americans as a group tend to do worse when they have COPD, compared with other racial and ethnic groups, the researchers suggested.

The study was supported by the National Institutes of Health and the COPD Foundation. SPIROMICS was supported by NIH and the COPD Foundation as well as numerous pharmaceutical and biotechnology companies. The authors reported no other financial disclosures.

Poor sleep quality was linked to an increased risk of life-threatening exacerbations in people with chronic obstructive pulmonary disease (COPD), according to a study reported online in the journal Sleep.

Researchers followed 1,647 patients with confirmed COPD who were enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). SPIROMICS is a multicenter study funded by the National Heart, Lung, and Blood Institute and the COPD Foundation and is designed to evaluate COPD subpopulations, outcomes, and biomarkers. All participants in the study were current or former smokers with confirmed COPD.

COPD exacerbations over a 3-year follow-up period were compared against reported sleep quality. The researchers used the Pittsburgh Sleep Quality Index (PSQI), a combination of seven sleep measures, including sleep duration, timing of sleep, and frequency of disturbances. The higher the score, the worse the quality of sleep.

Individuals who self-reported having poor-quality sleep had a 25%-95% higher risk of COPD exacerbations, compared with those who reported good-quality sleep, according to the results.

There was a significant association between PSQI score and total and mean exacerbations in the unadjusted analysis (incidence rate ratios, 1.09; 95% confidence interval, 1.05-1.13) and the analysis adjusted for demographics, medical comorbidities, disease severity, medication usage, and socioeconomic environmental exposure (IRR, 1.08; 95% CI, 1.03-1.13).

In addition, the PSQI score was independently associated with an increased risk of hospitalization, with a 7% increase in risk of hospitalization with each 1-point increase in PSQI, according to the researchers.
 

Surprising findings

These findings suggest that sleep quality may be a better predictor of flare-ups than the patient’s history of smoking, according to the researchers.

“Among those who already have COPD, knowing how they sleep at night will tell me much more about their risk of a flare-up than knowing whether they smoked for 40 versus 60 years. … That is very surprising and is not necessarily what I expected going into this study. Smoking is such a central process to COPD that I would have predicted it would be the more important predictor in the case of exacerbations,” said lead study author Aaron Baugh, MD, a practicing pulmonologist, and a clinical fellow at the University of California, San Francisco, in a National Institutes of Health press release on the study.

The study findings were applicable to all races and ethnicities studied, however the results may be particularly relevant to Black Americans, Dr. Baugh indicated, because past studies have shown that Black Americans tend to have poorer sleep quality than other races and ethnicities. With poorer sleep linked to worse COPD outcomes, the current study may help explain why Black Americans as a group tend to do worse when they have COPD, compared with other racial and ethnic groups, the researchers suggested.

The study was supported by the National Institutes of Health and the COPD Foundation. SPIROMICS was supported by NIH and the COPD Foundation as well as numerous pharmaceutical and biotechnology companies. The authors reported no other financial disclosures.

Poor sleep quality was linked to an increased risk of life-threatening exacerbations in people with chronic obstructive pulmonary disease (COPD), according to a study reported online in the journal Sleep.

Researchers followed 1,647 patients with confirmed COPD who were enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). SPIROMICS is a multicenter study funded by the National Heart, Lung, and Blood Institute and the COPD Foundation and is designed to evaluate COPD subpopulations, outcomes, and biomarkers. All participants in the study were current or former smokers with confirmed COPD.

COPD exacerbations over a 3-year follow-up period were compared against reported sleep quality. The researchers used the Pittsburgh Sleep Quality Index (PSQI), a combination of seven sleep measures, including sleep duration, timing of sleep, and frequency of disturbances. The higher the score, the worse the quality of sleep.

Individuals who self-reported having poor-quality sleep had a 25%-95% higher risk of COPD exacerbations, compared with those who reported good-quality sleep, according to the results.

There was a significant association between PSQI score and total and mean exacerbations in the unadjusted analysis (incidence rate ratios, 1.09; 95% confidence interval, 1.05-1.13) and the analysis adjusted for demographics, medical comorbidities, disease severity, medication usage, and socioeconomic environmental exposure (IRR, 1.08; 95% CI, 1.03-1.13).

In addition, the PSQI score was independently associated with an increased risk of hospitalization, with a 7% increase in risk of hospitalization with each 1-point increase in PSQI, according to the researchers.
 

Surprising findings

These findings suggest that sleep quality may be a better predictor of flare-ups than the patient’s history of smoking, according to the researchers.

“Among those who already have COPD, knowing how they sleep at night will tell me much more about their risk of a flare-up than knowing whether they smoked for 40 versus 60 years. … That is very surprising and is not necessarily what I expected going into this study. Smoking is such a central process to COPD that I would have predicted it would be the more important predictor in the case of exacerbations,” said lead study author Aaron Baugh, MD, a practicing pulmonologist, and a clinical fellow at the University of California, San Francisco, in a National Institutes of Health press release on the study.

The study findings were applicable to all races and ethnicities studied, however the results may be particularly relevant to Black Americans, Dr. Baugh indicated, because past studies have shown that Black Americans tend to have poorer sleep quality than other races and ethnicities. With poorer sleep linked to worse COPD outcomes, the current study may help explain why Black Americans as a group tend to do worse when they have COPD, compared with other racial and ethnic groups, the researchers suggested.

The study was supported by the National Institutes of Health and the COPD Foundation. SPIROMICS was supported by NIH and the COPD Foundation as well as numerous pharmaceutical and biotechnology companies. The authors reported no other financial disclosures.

The Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents (PANDA) trial was launched in order to examine the effects of treatment on children with poorly controlled allergic asthma who live in low-income urban environments in the United States, according to the National Institute of Allergy and Infectious Diseases.

Black and Hispanic children who live in these environments are at particularly high risk for asthma and are prone to attacks. These children and adolescents often have many allergies and are exposed to both high levels of indoor allergens and traffic-related pollution, which can make their asthma even more difficult to control, according to a June 2 NIAID press release.

PANDA is a multicenter, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for the reduction of asthma exacerbations in urban children and adolescents 6-17 years with T2-high exacerbation-prone asthma. Approximately 240 participants will be randomized 2:1 to one of two study arms: 1) guidelines-based asthma treatment plus dupilumab, or 2) guidelines-based asthma treatment plus placebo. The planned study treatment will continue for 1 year with an additional 3 months of follow-up following completion of study treatment, according to the study details.

In an earlier study, NIAID-supported investigators identified numerous networks of genes that are activated together and are associated with asthma attacks in minority children and adolescents living in low-income urban settings

“We need to find out how well approved asthma drugs work for disadvantaged children of color living in urban areas, and whether biological markers can help predict how the drugs affect their asthma,” NIAID director Anthony S. Fauci, MD, said in the release. “The PANDA trial is an important step toward these goals.”

Participant criteria for the study include children of either sex, ages 6-17 years, who live in prespecified urban areas. Participants must have a diagnosis of asthma and must have had at least two asthma exacerbations in the prior year (defined as a requirement for systemic corticosteroids and/or hospitalization). At the screening visit, participants must have the following requirements for asthma controller medication: For children ages 6-11 years: treatments with at least fluticasone 250 mcg dry powder inhaler (DPI) one puff twice daily or its equivalent; for children ages 12 years and older, treatment with at least fluticasone 250 mcg plus long-acting beta agonist (LABA) DPI one puff twice daily or its equivalent.
 

ClinicalTrials.gov Identifier: NCT05347771Location: The NIAID-funded Childhood Asthma in Urban Settings (CAUSE) Network is conducting the study at seven medical centers located in Aurora, Colo.; Boston; Chicago; Cincinnati; New York, and Washington, D.C.

Sponsor: NIAID, Regeneron Pharmaceuticals and Sanofi are cofunding the phase 2 trial.

Study start date: April 2022

Expected completion Date: March 31, 2025

The Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents (PANDA) trial was launched in order to examine the effects of treatment on children with poorly controlled allergic asthma who live in low-income urban environments in the United States, according to the National Institute of Allergy and Infectious Diseases.

Black and Hispanic children who live in these environments are at particularly high risk for asthma and are prone to attacks. These children and adolescents often have many allergies and are exposed to both high levels of indoor allergens and traffic-related pollution, which can make their asthma even more difficult to control, according to a June 2 NIAID press release.

PANDA is a multicenter, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for the reduction of asthma exacerbations in urban children and adolescents 6-17 years with T2-high exacerbation-prone asthma. Approximately 240 participants will be randomized 2:1 to one of two study arms: 1) guidelines-based asthma treatment plus dupilumab, or 2) guidelines-based asthma treatment plus placebo. The planned study treatment will continue for 1 year with an additional 3 months of follow-up following completion of study treatment, according to the study details.

In an earlier study, NIAID-supported investigators identified numerous networks of genes that are activated together and are associated with asthma attacks in minority children and adolescents living in low-income urban settings

“We need to find out how well approved asthma drugs work for disadvantaged children of color living in urban areas, and whether biological markers can help predict how the drugs affect their asthma,” NIAID director Anthony S. Fauci, MD, said in the release. “The PANDA trial is an important step toward these goals.”

Participant criteria for the study include children of either sex, ages 6-17 years, who live in prespecified urban areas. Participants must have a diagnosis of asthma and must have had at least two asthma exacerbations in the prior year (defined as a requirement for systemic corticosteroids and/or hospitalization). At the screening visit, participants must have the following requirements for asthma controller medication: For children ages 6-11 years: treatments with at least fluticasone 250 mcg dry powder inhaler (DPI) one puff twice daily or its equivalent; for children ages 12 years and older, treatment with at least fluticasone 250 mcg plus long-acting beta agonist (LABA) DPI one puff twice daily or its equivalent.
 

ClinicalTrials.gov Identifier: NCT05347771Location: The NIAID-funded Childhood Asthma in Urban Settings (CAUSE) Network is conducting the study at seven medical centers located in Aurora, Colo.; Boston; Chicago; Cincinnati; New York, and Washington, D.C.

Sponsor: NIAID, Regeneron Pharmaceuticals and Sanofi are cofunding the phase 2 trial.

Study start date: April 2022

Expected completion Date: March 31, 2025

The Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents (PANDA) trial was launched in order to examine the effects of treatment on children with poorly controlled allergic asthma who live in low-income urban environments in the United States, according to the National Institute of Allergy and Infectious Diseases.

Black and Hispanic children who live in these environments are at particularly high risk for asthma and are prone to attacks. These children and adolescents often have many allergies and are exposed to both high levels of indoor allergens and traffic-related pollution, which can make their asthma even more difficult to control, according to a June 2 NIAID press release.

PANDA is a multicenter, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for the reduction of asthma exacerbations in urban children and adolescents 6-17 years with T2-high exacerbation-prone asthma. Approximately 240 participants will be randomized 2:1 to one of two study arms: 1) guidelines-based asthma treatment plus dupilumab, or 2) guidelines-based asthma treatment plus placebo. The planned study treatment will continue for 1 year with an additional 3 months of follow-up following completion of study treatment, according to the study details.

In an earlier study, NIAID-supported investigators identified numerous networks of genes that are activated together and are associated with asthma attacks in minority children and adolescents living in low-income urban settings

“We need to find out how well approved asthma drugs work for disadvantaged children of color living in urban areas, and whether biological markers can help predict how the drugs affect their asthma,” NIAID director Anthony S. Fauci, MD, said in the release. “The PANDA trial is an important step toward these goals.”

Participant criteria for the study include children of either sex, ages 6-17 years, who live in prespecified urban areas. Participants must have a diagnosis of asthma and must have had at least two asthma exacerbations in the prior year (defined as a requirement for systemic corticosteroids and/or hospitalization). At the screening visit, participants must have the following requirements for asthma controller medication: For children ages 6-11 years: treatments with at least fluticasone 250 mcg dry powder inhaler (DPI) one puff twice daily or its equivalent; for children ages 12 years and older, treatment with at least fluticasone 250 mcg plus long-acting beta agonist (LABA) DPI one puff twice daily or its equivalent.
 

ClinicalTrials.gov Identifier: NCT05347771Location: The NIAID-funded Childhood Asthma in Urban Settings (CAUSE) Network is conducting the study at seven medical centers located in Aurora, Colo.; Boston; Chicago; Cincinnati; New York, and Washington, D.C.

Sponsor: NIAID, Regeneron Pharmaceuticals and Sanofi are cofunding the phase 2 trial.

Study start date: April 2022

Expected completion Date: March 31, 2025

Screening for chronic obstructive pulmonary disease (COPD) in asymptomatic adults has no net benefit, according to a U.S. Preventive Services Task Force (USPSTF) reassessment of its 2016 screening recommendations. The new recommendation is in line with the previous one and is made with moderate certainty (grade D evidence).

The USPSTF recommendation applies to adults who do not recognize or report respiratory symptoms. It does not apply to people with symptoms such as chronic cough, sputum production, difficulty breathing, or wheezing, or those known to be at very high risk for COPD. These latter include people with alpha-1 antitrypsin deficiency or workers exposed to certain toxins at their jobs, according to the report published in JAMA.

“Considering that the outcomes of several other chronic conditions, including cardiovascular disease and cancer, have been improved over the years with early detection and intervention, it is logical to ask whether screening to achieve early detection of COPD might also lead to better outcomes,” Surya P. Bhatt, MD, of the University of Alabama at Birmingham, and George T. O’Connor, MD, of the Boston University, explained in an editorial.
 

Task force assessment

The task force examined relevant publications after the 2016 deliberations and found no new studies that directly assessed the effects of screening for COPD in asymptomatic adults on morbidity, mortality, or health-related quality of life.

Although, as in their previous review, serious harms from treatment trials were not consistently reported, more recent large observational studies in screen-relevant populations suggested possible harms from the initiation of long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and the use of inhaled corticosteroids.

“In addition to potential treatment harms, there are opportunity costs to screening that may include time spent on counseling and providing services and patient referrals for diagnostic testing,” the task force stated.

Because cigarette smoking is the leading cause of COPD, the USPSTF has reiterated its recommendations for physicians to address tobacco smoking cessation in adults, including pregnant persons, as well as tobacco use in children and adolescents.
 

Not the whole story?

“Truly asymptomatic individuals with airflow obstruction do not meet criteria for COPD therapy, but sensitive questionnaires may detect symptoms not previously reported by the patient. It may be more effective to redirect the focus from screening for asymptomatic COPD to case finding using sensitive and cost-effective tools,” Dr. Bhatt and Dr. O’Connor suggested in their editorial.

“Even though available data may not support screening asymptomatic adults for COPD, there is substantial rationale for further investigation of strategies to enhance earlier detection of this condition,” they concluded.
 

More research needed

Despite the recommendation, the USPSTF indicated that further studies are needed to fill in research gaps, including:

• The effectiveness of screening asymptomatic adults for COPD to reduce morbidity or mortality or improve health-related quality of life, with long-term follow-up.
• The effectiveness of early treatment for asymptomatic, minimally symptomatic, or screen-detected populations to slow disease progression and improve health outcomes, with long-term follow-up.
• The harms of screening in and treatment of persons with asymptomatic or minimally symptomatic COPD.

The USPSTF is an independent, voluntary body, and potential conflicts of interest of the members are on file with the organization. Dr. Bhatt reported serving on an advisory board for Boehringer Ingelheim and receiving consulting fees from Sanofi/Regeneron; and Dr. O’Connor reported receiving consulting fees from Grupo Menarini and Dicerna Pharmaceuticals.

Screening for chronic obstructive pulmonary disease (COPD) in asymptomatic adults has no net benefit, according to a U.S. Preventive Services Task Force (USPSTF) reassessment of its 2016 screening recommendations. The new recommendation is in line with the previous one and is made with moderate certainty (grade D evidence).

The USPSTF recommendation applies to adults who do not recognize or report respiratory symptoms. It does not apply to people with symptoms such as chronic cough, sputum production, difficulty breathing, or wheezing, or those known to be at very high risk for COPD. These latter include people with alpha-1 antitrypsin deficiency or workers exposed to certain toxins at their jobs, according to the report published in JAMA.

“Considering that the outcomes of several other chronic conditions, including cardiovascular disease and cancer, have been improved over the years with early detection and intervention, it is logical to ask whether screening to achieve early detection of COPD might also lead to better outcomes,” Surya P. Bhatt, MD, of the University of Alabama at Birmingham, and George T. O’Connor, MD, of the Boston University, explained in an editorial.
 

Task force assessment

The task force examined relevant publications after the 2016 deliberations and found no new studies that directly assessed the effects of screening for COPD in asymptomatic adults on morbidity, mortality, or health-related quality of life.

Although, as in their previous review, serious harms from treatment trials were not consistently reported, more recent large observational studies in screen-relevant populations suggested possible harms from the initiation of long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and the use of inhaled corticosteroids.

“In addition to potential treatment harms, there are opportunity costs to screening that may include time spent on counseling and providing services and patient referrals for diagnostic testing,” the task force stated.

Because cigarette smoking is the leading cause of COPD, the USPSTF has reiterated its recommendations for physicians to address tobacco smoking cessation in adults, including pregnant persons, as well as tobacco use in children and adolescents.
 

Not the whole story?

“Truly asymptomatic individuals with airflow obstruction do not meet criteria for COPD therapy, but sensitive questionnaires may detect symptoms not previously reported by the patient. It may be more effective to redirect the focus from screening for asymptomatic COPD to case finding using sensitive and cost-effective tools,” Dr. Bhatt and Dr. O’Connor suggested in their editorial.

“Even though available data may not support screening asymptomatic adults for COPD, there is substantial rationale for further investigation of strategies to enhance earlier detection of this condition,” they concluded.
 

More research needed

Despite the recommendation, the USPSTF indicated that further studies are needed to fill in research gaps, including:

• The effectiveness of screening asymptomatic adults for COPD to reduce morbidity or mortality or improve health-related quality of life, with long-term follow-up.
• The effectiveness of early treatment for asymptomatic, minimally symptomatic, or screen-detected populations to slow disease progression and improve health outcomes, with long-term follow-up.
• The harms of screening in and treatment of persons with asymptomatic or minimally symptomatic COPD.

The USPSTF is an independent, voluntary body, and potential conflicts of interest of the members are on file with the organization. Dr. Bhatt reported serving on an advisory board for Boehringer Ingelheim and receiving consulting fees from Sanofi/Regeneron; and Dr. O’Connor reported receiving consulting fees from Grupo Menarini and Dicerna Pharmaceuticals.

Screening for chronic obstructive pulmonary disease (COPD) in asymptomatic adults has no net benefit, according to a U.S. Preventive Services Task Force (USPSTF) reassessment of its 2016 screening recommendations. The new recommendation is in line with the previous one and is made with moderate certainty (grade D evidence).

The USPSTF recommendation applies to adults who do not recognize or report respiratory symptoms. It does not apply to people with symptoms such as chronic cough, sputum production, difficulty breathing, or wheezing, or those known to be at very high risk for COPD. These latter include people with alpha-1 antitrypsin deficiency or workers exposed to certain toxins at their jobs, according to the report published in JAMA.

“Considering that the outcomes of several other chronic conditions, including cardiovascular disease and cancer, have been improved over the years with early detection and intervention, it is logical to ask whether screening to achieve early detection of COPD might also lead to better outcomes,” Surya P. Bhatt, MD, of the University of Alabama at Birmingham, and George T. O’Connor, MD, of the Boston University, explained in an editorial.
 

Task force assessment

The task force examined relevant publications after the 2016 deliberations and found no new studies that directly assessed the effects of screening for COPD in asymptomatic adults on morbidity, mortality, or health-related quality of life.

Although, as in their previous review, serious harms from treatment trials were not consistently reported, more recent large observational studies in screen-relevant populations suggested possible harms from the initiation of long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and the use of inhaled corticosteroids.

“In addition to potential treatment harms, there are opportunity costs to screening that may include time spent on counseling and providing services and patient referrals for diagnostic testing,” the task force stated.

Because cigarette smoking is the leading cause of COPD, the USPSTF has reiterated its recommendations for physicians to address tobacco smoking cessation in adults, including pregnant persons, as well as tobacco use in children and adolescents.
 

Not the whole story?

“Truly asymptomatic individuals with airflow obstruction do not meet criteria for COPD therapy, but sensitive questionnaires may detect symptoms not previously reported by the patient. It may be more effective to redirect the focus from screening for asymptomatic COPD to case finding using sensitive and cost-effective tools,” Dr. Bhatt and Dr. O’Connor suggested in their editorial.

“Even though available data may not support screening asymptomatic adults for COPD, there is substantial rationale for further investigation of strategies to enhance earlier detection of this condition,” they concluded.
 

More research needed

Despite the recommendation, the USPSTF indicated that further studies are needed to fill in research gaps, including:

• The effectiveness of screening asymptomatic adults for COPD to reduce morbidity or mortality or improve health-related quality of life, with long-term follow-up.
• The effectiveness of early treatment for asymptomatic, minimally symptomatic, or screen-detected populations to slow disease progression and improve health outcomes, with long-term follow-up.
• The harms of screening in and treatment of persons with asymptomatic or minimally symptomatic COPD.

The USPSTF is an independent, voluntary body, and potential conflicts of interest of the members are on file with the organization. Dr. Bhatt reported serving on an advisory board for Boehringer Ingelheim and receiving consulting fees from Sanofi/Regeneron; and Dr. O’Connor reported receiving consulting fees from Grupo Menarini and Dicerna Pharmaceuticals.

The U.S. Food and Drug Administration approved the first generic of Symbicort (budesonide and formoterol fumarate dihydrate) inhalation aerosol for the treatment of asthma in patients 6 years of age and older and for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

The approval was given for a complex generic drug-device combination product – a metered-dose inhaler that contains both budesonide (a corticosteroid that reduces inflammation) and formoterol (a long-acting bronchodilator that relaxes muscles in the airways to improve breathing). It is intended to be used as two inhalations, two times a day (usually morning and night, about 12 hours apart), to treat both diseases by preventing symptoms, such as wheezing for those with asthma and for improved breathing for patients with COPD.

The inhaler is approved at two strengths (160/4.5 mcg/actuation and 80/4.5 mcg/actuation), according to the March 15 FDA announcement. The device is not intended for the treatment of acute asthma.

“Today’s approval of the first generic for one of the most commonly prescribed complex drug-device combination products to treat asthma and COPD is another step forward in our commitment to bring generic copies of complex drugs to the market, which can improve quality of life and help reduce the cost of treatment,” said Sally Choe, PhD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research.

The most common side effects associated with budesonide and formoterol fumarate dihydrate oral inhalation aerosol for those with asthma are nasopharyngitis pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis (thrush). For those with COPD, the most common side effects are nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection, the FDA reported.

The approval of this generic drug-device combination was granted to Mylan Pharmaceuticals.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved the first generic of Symbicort (budesonide and formoterol fumarate dihydrate) inhalation aerosol for the treatment of asthma in patients 6 years of age and older and for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

The approval was given for a complex generic drug-device combination product – a metered-dose inhaler that contains both budesonide (a corticosteroid that reduces inflammation) and formoterol (a long-acting bronchodilator that relaxes muscles in the airways to improve breathing). It is intended to be used as two inhalations, two times a day (usually morning and night, about 12 hours apart), to treat both diseases by preventing symptoms, such as wheezing for those with asthma and for improved breathing for patients with COPD.

The inhaler is approved at two strengths (160/4.5 mcg/actuation and 80/4.5 mcg/actuation), according to the March 15 FDA announcement. The device is not intended for the treatment of acute asthma.

“Today’s approval of the first generic for one of the most commonly prescribed complex drug-device combination products to treat asthma and COPD is another step forward in our commitment to bring generic copies of complex drugs to the market, which can improve quality of life and help reduce the cost of treatment,” said Sally Choe, PhD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research.

The most common side effects associated with budesonide and formoterol fumarate dihydrate oral inhalation aerosol for those with asthma are nasopharyngitis pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis (thrush). For those with COPD, the most common side effects are nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection, the FDA reported.

The approval of this generic drug-device combination was granted to Mylan Pharmaceuticals.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved the first generic of Symbicort (budesonide and formoterol fumarate dihydrate) inhalation aerosol for the treatment of asthma in patients 6 years of age and older and for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

The approval was given for a complex generic drug-device combination product – a metered-dose inhaler that contains both budesonide (a corticosteroid that reduces inflammation) and formoterol (a long-acting bronchodilator that relaxes muscles in the airways to improve breathing). It is intended to be used as two inhalations, two times a day (usually morning and night, about 12 hours apart), to treat both diseases by preventing symptoms, such as wheezing for those with asthma and for improved breathing for patients with COPD.

The inhaler is approved at two strengths (160/4.5 mcg/actuation and 80/4.5 mcg/actuation), according to the March 15 FDA announcement. The device is not intended for the treatment of acute asthma.

“Today’s approval of the first generic for one of the most commonly prescribed complex drug-device combination products to treat asthma and COPD is another step forward in our commitment to bring generic copies of complex drugs to the market, which can improve quality of life and help reduce the cost of treatment,” said Sally Choe, PhD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research.

The most common side effects associated with budesonide and formoterol fumarate dihydrate oral inhalation aerosol for those with asthma are nasopharyngitis pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis (thrush). For those with COPD, the most common side effects are nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection, the FDA reported.

The approval of this generic drug-device combination was granted to Mylan Pharmaceuticals.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

FDA_icon3_web.jpg

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

FDA_icon3_web.jpg

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

FDA_icon3_web.jpg

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

A version of this article first appeared on Medscape.com.

Research has shown that hepatitis C virus infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. However, hemophilia was not a significant risk factor for hepatocarcinogenesis after sustained virologic response (SVR) against HCV, according to Yosuke Inukai of Nagoya (Japan) University and colleagues.

The researchers assessed 699 patients who achieved SVR after HCV antiviral treatment: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). They examined patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR, according to a report published online in Annals of Hepatology.
 

No added risk

Patients in the H-group were significantly younger and had a lower hepatic fibrosis score, compared with the NH group. Over a follow-up period of 7 years, there were no differences seen in the incidence of liver-related disease or overall death between the two groups. HCC was diagnosed in 4 patients in the H group and 36 patients in the NH group after SVR.

Multivariate analysis showed that male sex, patient age, and the presence of cirrhosis were significant risk factors for HCC incidence. However, after propensity-score matching that adjusted for the risk factors of HCC between the two groups, there was no significant difference seen in the cumulative incidence of HCC between the two groups.
 

Need for vigilance

The lack of a significant difference in the cumulative incidence of HCC after SVR or the long-term prognosis in patients with and without hemophilia, suggests that SVR could reduce the rates of liver carcinogenesis and liver disease–related mortality in both groups of patients, the researchers stated.

However: “Although there were no differences in overall survival, deaths from liver failure and bleeding events were observed in patients with hemophilia during the study period. Since the age in the H group at the time of starting antiviral treatment was 16 years younger than that in the NH group, careful observation is needed in patients with hemophilia even after eradication of HCV,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

Research has shown that hepatitis C virus infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. However, hemophilia was not a significant risk factor for hepatocarcinogenesis after sustained virologic response (SVR) against HCV, according to Yosuke Inukai of Nagoya (Japan) University and colleagues.

The researchers assessed 699 patients who achieved SVR after HCV antiviral treatment: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). They examined patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR, according to a report published online in Annals of Hepatology.
 

No added risk

Patients in the H-group were significantly younger and had a lower hepatic fibrosis score, compared with the NH group. Over a follow-up period of 7 years, there were no differences seen in the incidence of liver-related disease or overall death between the two groups. HCC was diagnosed in 4 patients in the H group and 36 patients in the NH group after SVR.

Multivariate analysis showed that male sex, patient age, and the presence of cirrhosis were significant risk factors for HCC incidence. However, after propensity-score matching that adjusted for the risk factors of HCC between the two groups, there was no significant difference seen in the cumulative incidence of HCC between the two groups.
 

Need for vigilance

The lack of a significant difference in the cumulative incidence of HCC after SVR or the long-term prognosis in patients with and without hemophilia, suggests that SVR could reduce the rates of liver carcinogenesis and liver disease–related mortality in both groups of patients, the researchers stated.

However: “Although there were no differences in overall survival, deaths from liver failure and bleeding events were observed in patients with hemophilia during the study period. Since the age in the H group at the time of starting antiviral treatment was 16 years younger than that in the NH group, careful observation is needed in patients with hemophilia even after eradication of HCV,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

Research has shown that hepatitis C virus infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. However, hemophilia was not a significant risk factor for hepatocarcinogenesis after sustained virologic response (SVR) against HCV, according to Yosuke Inukai of Nagoya (Japan) University and colleagues.

The researchers assessed 699 patients who achieved SVR after HCV antiviral treatment: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). They examined patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR, according to a report published online in Annals of Hepatology.
 

No added risk

Patients in the H-group were significantly younger and had a lower hepatic fibrosis score, compared with the NH group. Over a follow-up period of 7 years, there were no differences seen in the incidence of liver-related disease or overall death between the two groups. HCC was diagnosed in 4 patients in the H group and 36 patients in the NH group after SVR.

Multivariate analysis showed that male sex, patient age, and the presence of cirrhosis were significant risk factors for HCC incidence. However, after propensity-score matching that adjusted for the risk factors of HCC between the two groups, there was no significant difference seen in the cumulative incidence of HCC between the two groups.
 

Need for vigilance

The lack of a significant difference in the cumulative incidence of HCC after SVR or the long-term prognosis in patients with and without hemophilia, suggests that SVR could reduce the rates of liver carcinogenesis and liver disease–related mortality in both groups of patients, the researchers stated.

However: “Although there were no differences in overall survival, deaths from liver failure and bleeding events were observed in patients with hemophilia during the study period. Since the age in the H group at the time of starting antiviral treatment was 16 years younger than that in the NH group, careful observation is needed in patients with hemophilia even after eradication of HCV,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

The observed rates of intracranial hemorrhaging (ICH) in patients with hemophilia were higher compared to the general populations among all age groups examined, according to a meta-analysis of studies reported online ahead of print in Blood.

As previously reported, the risk seemed higher in the group of infants and toddlers, and neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, in the current study.

The researchers performed a literature review and assessed 45 studies that represented 54,470 patients, 809,151 person-years and 5,326 live births of patients with hemophilia. Pooled ICH incidence and mortality were calculated for three age groups: persons of all ages with hemophilia; children and young adults below 25 years of age with hemophilia; and neonates with hemophilia.
 

Overall results

Among the persons of all ages, the pooled ICH incidence and mortality rates were 2.3 (95% confidence interval, 1.2-4.8) and 0.8 (95% CI, 0.5-1.2) per 1,000 person-years, respectively, according to the authors. They found that in children and young adults, the pooled ICH incidence and mortality rates were 7.4 (95% CI, 4.9-11.1) and 0.5 (95% CI, 0.3-0.9) per 1,000 person-years, respectively. In neonates, the pooled cumulative ICH incidence was 2.1% (95% CI, 1.5-2.8) per 100 live births and the pooled ICH cumulative mortality was 0.2% (95% CI, 0.0-1.2) per 100 live births.

Overall, the occurrence of ICH was classified as spontaneous in 35%-58% of cases.
 

Neonates at risk

The observed ICH rates in hemophilia were higher compared to the general populations among the age groups assessed. Neonates showed the highest risk of ICH, which is confirmed by other studies in severe hemophilia demonstrating that neonates were at 11.2 times higher risk for ICH compared with 1- to 12-month-old children, and is also strongly increased compared to neonates in the general populations, the researchers stated.

A previous large study of term infants reported 361 intracranial bleeding episodes per 583,340 live births (0.062% per 100 live births), and comparing this to the current pooled estimate of 2.1% per 100 live births, neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, according to the researchers.
 

Monitoring and follow-up

“Our findings suggest that adequate follow-up and monitoring of patients is warranted among all ages, especially in the presence of risk factors. Prophylaxis seems to halve ICH risk in children and adults with severe hemophilia, which supports existing recommendations encouraging early initiation of prophylactic treatment,” the authors advised.

Accurate capture of the true frequency of ICH is challenged by considerable clinical heterogeneity, limiting the precision and generalizability of the pooled estimates, leading to the likelihood that ICH and mortality were underdiagnosed in this analysis, according to the authors.

“We found high ICH incidence and mortality rates in patients with hemophilia. Our findings suggest that ICH is still an important problem in hemophilia requiring adequate counseling of patients of all ages,” the researchers concluded.

This work was supported by a grant from Sobi. Some of the authors reported research, consulting or lecturing fees from a variety of pharmaceutical companies, including Sobi.

mlesney@mdedge.com

The observed rates of intracranial hemorrhaging (ICH) in patients with hemophilia were higher compared to the general populations among all age groups examined, according to a meta-analysis of studies reported online ahead of print in Blood.

As previously reported, the risk seemed higher in the group of infants and toddlers, and neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, in the current study.

The researchers performed a literature review and assessed 45 studies that represented 54,470 patients, 809,151 person-years and 5,326 live births of patients with hemophilia. Pooled ICH incidence and mortality were calculated for three age groups: persons of all ages with hemophilia; children and young adults below 25 years of age with hemophilia; and neonates with hemophilia.
 

Overall results

Among the persons of all ages, the pooled ICH incidence and mortality rates were 2.3 (95% confidence interval, 1.2-4.8) and 0.8 (95% CI, 0.5-1.2) per 1,000 person-years, respectively, according to the authors. They found that in children and young adults, the pooled ICH incidence and mortality rates were 7.4 (95% CI, 4.9-11.1) and 0.5 (95% CI, 0.3-0.9) per 1,000 person-years, respectively. In neonates, the pooled cumulative ICH incidence was 2.1% (95% CI, 1.5-2.8) per 100 live births and the pooled ICH cumulative mortality was 0.2% (95% CI, 0.0-1.2) per 100 live births.

Overall, the occurrence of ICH was classified as spontaneous in 35%-58% of cases.
 

Neonates at risk

The observed ICH rates in hemophilia were higher compared to the general populations among the age groups assessed. Neonates showed the highest risk of ICH, which is confirmed by other studies in severe hemophilia demonstrating that neonates were at 11.2 times higher risk for ICH compared with 1- to 12-month-old children, and is also strongly increased compared to neonates in the general populations, the researchers stated.

A previous large study of term infants reported 361 intracranial bleeding episodes per 583,340 live births (0.062% per 100 live births), and comparing this to the current pooled estimate of 2.1% per 100 live births, neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, according to the researchers.
 

Monitoring and follow-up

“Our findings suggest that adequate follow-up and monitoring of patients is warranted among all ages, especially in the presence of risk factors. Prophylaxis seems to halve ICH risk in children and adults with severe hemophilia, which supports existing recommendations encouraging early initiation of prophylactic treatment,” the authors advised.

Accurate capture of the true frequency of ICH is challenged by considerable clinical heterogeneity, limiting the precision and generalizability of the pooled estimates, leading to the likelihood that ICH and mortality were underdiagnosed in this analysis, according to the authors.

“We found high ICH incidence and mortality rates in patients with hemophilia. Our findings suggest that ICH is still an important problem in hemophilia requiring adequate counseling of patients of all ages,” the researchers concluded.

This work was supported by a grant from Sobi. Some of the authors reported research, consulting or lecturing fees from a variety of pharmaceutical companies, including Sobi.

mlesney@mdedge.com

The observed rates of intracranial hemorrhaging (ICH) in patients with hemophilia were higher compared to the general populations among all age groups examined, according to a meta-analysis of studies reported online ahead of print in Blood.

As previously reported, the risk seemed higher in the group of infants and toddlers, and neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, in the current study.

The researchers performed a literature review and assessed 45 studies that represented 54,470 patients, 809,151 person-years and 5,326 live births of patients with hemophilia. Pooled ICH incidence and mortality were calculated for three age groups: persons of all ages with hemophilia; children and young adults below 25 years of age with hemophilia; and neonates with hemophilia.
 

Overall results

Among the persons of all ages, the pooled ICH incidence and mortality rates were 2.3 (95% confidence interval, 1.2-4.8) and 0.8 (95% CI, 0.5-1.2) per 1,000 person-years, respectively, according to the authors. They found that in children and young adults, the pooled ICH incidence and mortality rates were 7.4 (95% CI, 4.9-11.1) and 0.5 (95% CI, 0.3-0.9) per 1,000 person-years, respectively. In neonates, the pooled cumulative ICH incidence was 2.1% (95% CI, 1.5-2.8) per 100 live births and the pooled ICH cumulative mortality was 0.2% (95% CI, 0.0-1.2) per 100 live births.

Overall, the occurrence of ICH was classified as spontaneous in 35%-58% of cases.
 

Neonates at risk

The observed ICH rates in hemophilia were higher compared to the general populations among the age groups assessed. Neonates showed the highest risk of ICH, which is confirmed by other studies in severe hemophilia demonstrating that neonates were at 11.2 times higher risk for ICH compared with 1- to 12-month-old children, and is also strongly increased compared to neonates in the general populations, the researchers stated.

A previous large study of term infants reported 361 intracranial bleeding episodes per 583,340 live births (0.062% per 100 live births), and comparing this to the current pooled estimate of 2.1% per 100 live births, neonates with hemophilia showed a 33-fold higher risk of ICH than newborns in the general population, according to the researchers.
 

Monitoring and follow-up

“Our findings suggest that adequate follow-up and monitoring of patients is warranted among all ages, especially in the presence of risk factors. Prophylaxis seems to halve ICH risk in children and adults with severe hemophilia, which supports existing recommendations encouraging early initiation of prophylactic treatment,” the authors advised.

Accurate capture of the true frequency of ICH is challenged by considerable clinical heterogeneity, limiting the precision and generalizability of the pooled estimates, leading to the likelihood that ICH and mortality were underdiagnosed in this analysis, according to the authors.

“We found high ICH incidence and mortality rates in patients with hemophilia. Our findings suggest that ICH is still an important problem in hemophilia requiring adequate counseling of patients of all ages,” the researchers concluded.

This work was supported by a grant from Sobi. Some of the authors reported research, consulting or lecturing fees from a variety of pharmaceutical companies, including Sobi.

mlesney@mdedge.com

In childhood patients with T-cell acute lymphoblastic leukemia (T-ALL) the hypomethylation status of the arginine synthetase (ASNS) gene was significantly associated with poor therapeutic outcome, according to the results of a Japanese cohort study published online in Blood Advances.

Researchers Koshi Akahane, PHD, of the University of Yamanashi, Kofu, Japan, and colleagues conducted a comprehensive genetic analysis of diagnostic samples of 22 cell lines from childhood patients with T-ALL in Japan.

They also correlated known methylation status with outcomes in two large patient cohorts of Japanese children with T-ALL: the Tokyo Children’s Cancer Study Group (n = 57) and the Japan Association of Childhood Leukemia Study Group (n = 20).
 

Methylation results

For the 22 cell lines tested, sequencing technology revealed a stepwise allele-specific methylation of the ASNS gene. Mean ASNS gene expression level was significantly upregulated in 14 weakly methylated cell lines (P = .0001), but not significantly upregulated in 3 intermediately methylated cell lines (P = .25) or in 5 highly methylated cell lines (P = .063).

Among the 77 patient cohorts, 20 (26%) samples showed high methylation (> 66.7%), while 15 (19%) samples and 42 (55%) samples showed intermediate (33.3%-66.7%) and weak (< 33.3%) methylation status, respectively.

For the 75 patients where information was provided on outcomes, 25 patients (33%) showed induction failure or disease relapse. A highly methylated status of the ASNS gene was significantly more common in non-refractory/relapse cases (18/50 cases, 36%), while intermediately or weakly methylated status was more common in refractory/relapsed cases (23/25 cases, 92 %; P = .0001). In a log-rank test, the patients with weakly methylated status of the ASNS gene showed significantly shorter event-free survival and overall survival than the patients with an intermediate or highly methylated status (P = .00012 and P = .00016, respectively).
 

Asparaginase sensitivity

Asparaginase treatment is a key component of chemotherapy for patients with T-ALL, according to the researchers. Asparaginase depletes serum asparagine by deamination into aspartic acid. While normal hematopoietic cells can survive due to ASNS activity, leukemia cells are expected to undergo apoptosis due to silencing of the ASNS gene.

ASNS hypomethylation status was significantly associated with poor therapeutic outcome, and all cases with the poor prognostic SPI1 fusion exclusively showed ASNS hypomethylation status. These observations demonstrate that ASNS hypomethylation status is associated with asparaginase resistance, the researchers stated.

“ASNS methylation status may be a clinically useful biomarker to predict sensitivity to asparaginase therapy in T-ALL patients. Considering the severe complications of asparaginase therapy particularly in adolescents and adults, stratifying prospective asparaginase therapy according to ASNS methylation status may be beneficial for safer and more effective treatment of T-ALL patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

In childhood patients with T-cell acute lymphoblastic leukemia (T-ALL) the hypomethylation status of the arginine synthetase (ASNS) gene was significantly associated with poor therapeutic outcome, according to the results of a Japanese cohort study published online in Blood Advances.

Researchers Koshi Akahane, PHD, of the University of Yamanashi, Kofu, Japan, and colleagues conducted a comprehensive genetic analysis of diagnostic samples of 22 cell lines from childhood patients with T-ALL in Japan.

They also correlated known methylation status with outcomes in two large patient cohorts of Japanese children with T-ALL: the Tokyo Children’s Cancer Study Group (n = 57) and the Japan Association of Childhood Leukemia Study Group (n = 20).
 

Methylation results

For the 22 cell lines tested, sequencing technology revealed a stepwise allele-specific methylation of the ASNS gene. Mean ASNS gene expression level was significantly upregulated in 14 weakly methylated cell lines (P = .0001), but not significantly upregulated in 3 intermediately methylated cell lines (P = .25) or in 5 highly methylated cell lines (P = .063).

Among the 77 patient cohorts, 20 (26%) samples showed high methylation (> 66.7%), while 15 (19%) samples and 42 (55%) samples showed intermediate (33.3%-66.7%) and weak (< 33.3%) methylation status, respectively.

For the 75 patients where information was provided on outcomes, 25 patients (33%) showed induction failure or disease relapse. A highly methylated status of the ASNS gene was significantly more common in non-refractory/relapse cases (18/50 cases, 36%), while intermediately or weakly methylated status was more common in refractory/relapsed cases (23/25 cases, 92 %; P = .0001). In a log-rank test, the patients with weakly methylated status of the ASNS gene showed significantly shorter event-free survival and overall survival than the patients with an intermediate or highly methylated status (P = .00012 and P = .00016, respectively).
 

Asparaginase sensitivity

Asparaginase treatment is a key component of chemotherapy for patients with T-ALL, according to the researchers. Asparaginase depletes serum asparagine by deamination into aspartic acid. While normal hematopoietic cells can survive due to ASNS activity, leukemia cells are expected to undergo apoptosis due to silencing of the ASNS gene.

ASNS hypomethylation status was significantly associated with poor therapeutic outcome, and all cases with the poor prognostic SPI1 fusion exclusively showed ASNS hypomethylation status. These observations demonstrate that ASNS hypomethylation status is associated with asparaginase resistance, the researchers stated.

“ASNS methylation status may be a clinically useful biomarker to predict sensitivity to asparaginase therapy in T-ALL patients. Considering the severe complications of asparaginase therapy particularly in adolescents and adults, stratifying prospective asparaginase therapy according to ASNS methylation status may be beneficial for safer and more effective treatment of T-ALL patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

In childhood patients with T-cell acute lymphoblastic leukemia (T-ALL) the hypomethylation status of the arginine synthetase (ASNS) gene was significantly associated with poor therapeutic outcome, according to the results of a Japanese cohort study published online in Blood Advances.

Researchers Koshi Akahane, PHD, of the University of Yamanashi, Kofu, Japan, and colleagues conducted a comprehensive genetic analysis of diagnostic samples of 22 cell lines from childhood patients with T-ALL in Japan.

They also correlated known methylation status with outcomes in two large patient cohorts of Japanese children with T-ALL: the Tokyo Children’s Cancer Study Group (n = 57) and the Japan Association of Childhood Leukemia Study Group (n = 20).
 

Methylation results

For the 22 cell lines tested, sequencing technology revealed a stepwise allele-specific methylation of the ASNS gene. Mean ASNS gene expression level was significantly upregulated in 14 weakly methylated cell lines (P = .0001), but not significantly upregulated in 3 intermediately methylated cell lines (P = .25) or in 5 highly methylated cell lines (P = .063).

Among the 77 patient cohorts, 20 (26%) samples showed high methylation (> 66.7%), while 15 (19%) samples and 42 (55%) samples showed intermediate (33.3%-66.7%) and weak (< 33.3%) methylation status, respectively.

For the 75 patients where information was provided on outcomes, 25 patients (33%) showed induction failure or disease relapse. A highly methylated status of the ASNS gene was significantly more common in non-refractory/relapse cases (18/50 cases, 36%), while intermediately or weakly methylated status was more common in refractory/relapsed cases (23/25 cases, 92 %; P = .0001). In a log-rank test, the patients with weakly methylated status of the ASNS gene showed significantly shorter event-free survival and overall survival than the patients with an intermediate or highly methylated status (P = .00012 and P = .00016, respectively).
 

Asparaginase sensitivity

Asparaginase treatment is a key component of chemotherapy for patients with T-ALL, according to the researchers. Asparaginase depletes serum asparagine by deamination into aspartic acid. While normal hematopoietic cells can survive due to ASNS activity, leukemia cells are expected to undergo apoptosis due to silencing of the ASNS gene.

ASNS hypomethylation status was significantly associated with poor therapeutic outcome, and all cases with the poor prognostic SPI1 fusion exclusively showed ASNS hypomethylation status. These observations demonstrate that ASNS hypomethylation status is associated with asparaginase resistance, the researchers stated.

“ASNS methylation status may be a clinically useful biomarker to predict sensitivity to asparaginase therapy in T-ALL patients. Considering the severe complications of asparaginase therapy particularly in adolescents and adults, stratifying prospective asparaginase therapy according to ASNS methylation status may be beneficial for safer and more effective treatment of T-ALL patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com