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Could Mobile Tech Help to Minimize COPD Exacerbations?
Could mobile technology help patients with chronic obstructive pulmonary disease (COPD) who may not seek care until they experience an exacerbation?
Self-management interventions for COPD can potentially improve quality of life and reduce hospitalizations, wrote Robert Wu, MD, associate professor in the Department of Medicine at the University of Toronto, and colleagues. However, data on the use of devices and apps to manage COPD by providing reminders for self-care, predicting early exacerbations, and facilitating communication with healthcare providers are limited, they said.
In a study published in COPD: Journal of Chronic Obstructive Pulmonary Disease, the researchers reported details from interviews with 26 adult patients with COPD who used a wearable device and app for 6 months to help manage their condition. The interviews were part of a larger cohort study.
“The motivation for this study was to understand the patient perspective on using wearables to help support their chronic lung condition,” Dr. Wu said in an interview. “People with COPD can be at high risk of being admitted to hospital, so it is important to see if innovative technology like wearables or remote monitoring can help them,” he said.
Individuals with COPD tend to be older and less technologically adept, and they may be less willing to adopt new technology, he added. “We wanted to understand what would make people use a self-management app,” he said.
On enrollment in the study, patients received a smartwatch and a smartphone with a preinstalled app for COPD management. The app included daily reminders to take medication, perform guided breathing sessions, check blood oxygen on the smartwatch or an oximeter, and complete a symptom questionnaire. The app also allowed participants to record when they exercised and provided feedback on heart rate and daily activity, including passive step counts. Participants earned stars for meeting daily exercise goals of active minutes and total steps.
Participants received training in the use of the app from members of the research team and completed semi-structured interviews after using the items for 6 months.
The researchers divided their findings into four main themes: information, support and reassurance; barriers to adoption; impact on communication with healthcare providers; and opportunities for improvement.
Overall, most patients reported that the feedback they received through the app was useful. In particular, participants reported that the app and smartwatch provided reassurance and feedback about stable vitals during exercise, which encouraged some to adhere to regular exercise routines. Approximately two thirds (65%) said that the daily exercise reminders were motivational. In addition, 20% reported that they interpreted vital data, including heart rate, as a signal to slow down.
Participants rated medication reminders and the option to create an action plan for COPD management as the least useful features; 69% said that they already had medication reminders in place.
A total of four patients experienced technical difficulties with the app that kept it from impacting their disease management. Some of the suggestions from participants for improvement included adding information about food intake, weight, blood pressure, and temperature to the health information being tracked, as well as restoring the oxygen saturation measure, which had been disabled because of accuracy concerns. Barriers to use of the device and app included the bulkiness of the device as well as the reported technical malfunctions.
The findings were limited by several factors, including the small sample size and likely focus on early adopters of technology, which may not represent most patients with COPD, the researchers noted. Other limitations included the recruitment of most patients after the start of the COVID-19 pandemic, which may have affected their experience and also limited the assessment of the app on communication with healthcare providers, the researchers noted. The study also did not address financial or social barriers.
However, the results suggest that patients with COPD identified the potential value of wearable devices for disease management and that improved technology could promote patient empowerment and lifestyle changes, the researchers concluded.
Technology Can Augment Care and Connections
“As clinicians and researchers, we have ideas about what patients would want, but it is always better to get their feedback of what they really want and what they would use,” Dr. Wu told this news organization. “We thought older adults with COPD would be less likely to engage with the technology. We found that many wanted to have their data to help make connections with their condition, and some purchased smartwatches after the study to make these connections,” he said.
The takeaway message from the current study is that people with COPD may benefit from self-management apps, but they would like to use them in collaboration with their healthcare team, said Dr. Wu. “Clinicians may see more of their patients bringing in data from wearables and apps,” he noted.
Concerns persist that using technology to help support people with COPD could increase the “digital divide” and that those with lower digital literacy, financial insecurity, or English as a second language could be left behind, and it is important to remain attentive to equity in pursuing the use of devices and apps, Dr. Wu told this news organization.
Looking ahead, research involving self-management, remote monitoring, and wearable devices has focused on other conditions such as heart failure and diabetes, and more work is needed to examine how these technologies can improve care for patients with COPD, said Dr. Wu. “We see this study as one important step — to understand what will motivate people to use self-management apps and wearables,” he said.
“Acute exacerbations of COPD are very important events that can alter quality of life, lung function, and even mortality in COPD,” said Nathaniel Marchetti, DO, medical director of the Respiratory Intensive Care Unit at Temple University Hospital, Philadelphia, in an interview.
“Many of these exacerbations are not recognized by clinicians or even patients until they present late and end up in an urgent office visit with a physician or in the emergency room [ER], so addressing exacerbations earlier has the potential to avoid ER visits or hospitalizations,” he said.
The study identified areas for further research, Dr. Marchetti said. “More information would be needed to determine if the use of an app to monitor heart rate, symptoms, and oxygen saturation could alter important outcomes in COPD such as exacerbations,” he noted.
As for limitations, “no one wants to carry two smartphones,” said Dr. Marchetti. “Future devices need to be easy to use and available on the patient’s own phone,” he said. Patients should be able to choose a smartwatch or possibly a bracelet that can be synced to a smartphone, he added. The current study also failed to address what would be done with collected data, such as link them to health professionals who would offer treatment when needed, he said.
Overall, the data from the current study suggest that patients with COPD would like some device that monitors symptoms and vital signs and offers suggestions/incentives to exercise and take medications, Dr. Marchetti told this news organization. “A larger study will be needed that compares how such a device could improve outcomes of COPD; outcomes could include admissions/ER visits, exercise performance, or compliance with medication,” he said. In addition, clinical algorithms for the identification and treatment of acute exacerbations of COPD would be needed, Dr. Marchetti noted. These algorithms would determine whether treatment decisions would be initiated by a clinical team of health professionals or whether clinicians would provide medications that the patients would then decide to take based on data collected on the app, using the investigator-provided algorithms, he said.
The study was supported in part by Samsung Research America (SRA) and was initiated by Dr. Wu with input from SRA, but the company had no role in the methods or results. The study also was supported by grants from the National Natural Science Foundation of China.
Dr. Marchetti had no relevant financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Could mobile technology help patients with chronic obstructive pulmonary disease (COPD) who may not seek care until they experience an exacerbation?
Self-management interventions for COPD can potentially improve quality of life and reduce hospitalizations, wrote Robert Wu, MD, associate professor in the Department of Medicine at the University of Toronto, and colleagues. However, data on the use of devices and apps to manage COPD by providing reminders for self-care, predicting early exacerbations, and facilitating communication with healthcare providers are limited, they said.
In a study published in COPD: Journal of Chronic Obstructive Pulmonary Disease, the researchers reported details from interviews with 26 adult patients with COPD who used a wearable device and app for 6 months to help manage their condition. The interviews were part of a larger cohort study.
“The motivation for this study was to understand the patient perspective on using wearables to help support their chronic lung condition,” Dr. Wu said in an interview. “People with COPD can be at high risk of being admitted to hospital, so it is important to see if innovative technology like wearables or remote monitoring can help them,” he said.
Individuals with COPD tend to be older and less technologically adept, and they may be less willing to adopt new technology, he added. “We wanted to understand what would make people use a self-management app,” he said.
On enrollment in the study, patients received a smartwatch and a smartphone with a preinstalled app for COPD management. The app included daily reminders to take medication, perform guided breathing sessions, check blood oxygen on the smartwatch or an oximeter, and complete a symptom questionnaire. The app also allowed participants to record when they exercised and provided feedback on heart rate and daily activity, including passive step counts. Participants earned stars for meeting daily exercise goals of active minutes and total steps.
Participants received training in the use of the app from members of the research team and completed semi-structured interviews after using the items for 6 months.
The researchers divided their findings into four main themes: information, support and reassurance; barriers to adoption; impact on communication with healthcare providers; and opportunities for improvement.
Overall, most patients reported that the feedback they received through the app was useful. In particular, participants reported that the app and smartwatch provided reassurance and feedback about stable vitals during exercise, which encouraged some to adhere to regular exercise routines. Approximately two thirds (65%) said that the daily exercise reminders were motivational. In addition, 20% reported that they interpreted vital data, including heart rate, as a signal to slow down.
Participants rated medication reminders and the option to create an action plan for COPD management as the least useful features; 69% said that they already had medication reminders in place.
A total of four patients experienced technical difficulties with the app that kept it from impacting their disease management. Some of the suggestions from participants for improvement included adding information about food intake, weight, blood pressure, and temperature to the health information being tracked, as well as restoring the oxygen saturation measure, which had been disabled because of accuracy concerns. Barriers to use of the device and app included the bulkiness of the device as well as the reported technical malfunctions.
The findings were limited by several factors, including the small sample size and likely focus on early adopters of technology, which may not represent most patients with COPD, the researchers noted. Other limitations included the recruitment of most patients after the start of the COVID-19 pandemic, which may have affected their experience and also limited the assessment of the app on communication with healthcare providers, the researchers noted. The study also did not address financial or social barriers.
However, the results suggest that patients with COPD identified the potential value of wearable devices for disease management and that improved technology could promote patient empowerment and lifestyle changes, the researchers concluded.
Technology Can Augment Care and Connections
“As clinicians and researchers, we have ideas about what patients would want, but it is always better to get their feedback of what they really want and what they would use,” Dr. Wu told this news organization. “We thought older adults with COPD would be less likely to engage with the technology. We found that many wanted to have their data to help make connections with their condition, and some purchased smartwatches after the study to make these connections,” he said.
The takeaway message from the current study is that people with COPD may benefit from self-management apps, but they would like to use them in collaboration with their healthcare team, said Dr. Wu. “Clinicians may see more of their patients bringing in data from wearables and apps,” he noted.
Concerns persist that using technology to help support people with COPD could increase the “digital divide” and that those with lower digital literacy, financial insecurity, or English as a second language could be left behind, and it is important to remain attentive to equity in pursuing the use of devices and apps, Dr. Wu told this news organization.
Looking ahead, research involving self-management, remote monitoring, and wearable devices has focused on other conditions such as heart failure and diabetes, and more work is needed to examine how these technologies can improve care for patients with COPD, said Dr. Wu. “We see this study as one important step — to understand what will motivate people to use self-management apps and wearables,” he said.
“Acute exacerbations of COPD are very important events that can alter quality of life, lung function, and even mortality in COPD,” said Nathaniel Marchetti, DO, medical director of the Respiratory Intensive Care Unit at Temple University Hospital, Philadelphia, in an interview.
“Many of these exacerbations are not recognized by clinicians or even patients until they present late and end up in an urgent office visit with a physician or in the emergency room [ER], so addressing exacerbations earlier has the potential to avoid ER visits or hospitalizations,” he said.
The study identified areas for further research, Dr. Marchetti said. “More information would be needed to determine if the use of an app to monitor heart rate, symptoms, and oxygen saturation could alter important outcomes in COPD such as exacerbations,” he noted.
As for limitations, “no one wants to carry two smartphones,” said Dr. Marchetti. “Future devices need to be easy to use and available on the patient’s own phone,” he said. Patients should be able to choose a smartwatch or possibly a bracelet that can be synced to a smartphone, he added. The current study also failed to address what would be done with collected data, such as link them to health professionals who would offer treatment when needed, he said.
Overall, the data from the current study suggest that patients with COPD would like some device that monitors symptoms and vital signs and offers suggestions/incentives to exercise and take medications, Dr. Marchetti told this news organization. “A larger study will be needed that compares how such a device could improve outcomes of COPD; outcomes could include admissions/ER visits, exercise performance, or compliance with medication,” he said. In addition, clinical algorithms for the identification and treatment of acute exacerbations of COPD would be needed, Dr. Marchetti noted. These algorithms would determine whether treatment decisions would be initiated by a clinical team of health professionals or whether clinicians would provide medications that the patients would then decide to take based on data collected on the app, using the investigator-provided algorithms, he said.
The study was supported in part by Samsung Research America (SRA) and was initiated by Dr. Wu with input from SRA, but the company had no role in the methods or results. The study also was supported by grants from the National Natural Science Foundation of China.
Dr. Marchetti had no relevant financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Could mobile technology help patients with chronic obstructive pulmonary disease (COPD) who may not seek care until they experience an exacerbation?
Self-management interventions for COPD can potentially improve quality of life and reduce hospitalizations, wrote Robert Wu, MD, associate professor in the Department of Medicine at the University of Toronto, and colleagues. However, data on the use of devices and apps to manage COPD by providing reminders for self-care, predicting early exacerbations, and facilitating communication with healthcare providers are limited, they said.
In a study published in COPD: Journal of Chronic Obstructive Pulmonary Disease, the researchers reported details from interviews with 26 adult patients with COPD who used a wearable device and app for 6 months to help manage their condition. The interviews were part of a larger cohort study.
“The motivation for this study was to understand the patient perspective on using wearables to help support their chronic lung condition,” Dr. Wu said in an interview. “People with COPD can be at high risk of being admitted to hospital, so it is important to see if innovative technology like wearables or remote monitoring can help them,” he said.
Individuals with COPD tend to be older and less technologically adept, and they may be less willing to adopt new technology, he added. “We wanted to understand what would make people use a self-management app,” he said.
On enrollment in the study, patients received a smartwatch and a smartphone with a preinstalled app for COPD management. The app included daily reminders to take medication, perform guided breathing sessions, check blood oxygen on the smartwatch or an oximeter, and complete a symptom questionnaire. The app also allowed participants to record when they exercised and provided feedback on heart rate and daily activity, including passive step counts. Participants earned stars for meeting daily exercise goals of active minutes and total steps.
Participants received training in the use of the app from members of the research team and completed semi-structured interviews after using the items for 6 months.
The researchers divided their findings into four main themes: information, support and reassurance; barriers to adoption; impact on communication with healthcare providers; and opportunities for improvement.
Overall, most patients reported that the feedback they received through the app was useful. In particular, participants reported that the app and smartwatch provided reassurance and feedback about stable vitals during exercise, which encouraged some to adhere to regular exercise routines. Approximately two thirds (65%) said that the daily exercise reminders were motivational. In addition, 20% reported that they interpreted vital data, including heart rate, as a signal to slow down.
Participants rated medication reminders and the option to create an action plan for COPD management as the least useful features; 69% said that they already had medication reminders in place.
A total of four patients experienced technical difficulties with the app that kept it from impacting their disease management. Some of the suggestions from participants for improvement included adding information about food intake, weight, blood pressure, and temperature to the health information being tracked, as well as restoring the oxygen saturation measure, which had been disabled because of accuracy concerns. Barriers to use of the device and app included the bulkiness of the device as well as the reported technical malfunctions.
The findings were limited by several factors, including the small sample size and likely focus on early adopters of technology, which may not represent most patients with COPD, the researchers noted. Other limitations included the recruitment of most patients after the start of the COVID-19 pandemic, which may have affected their experience and also limited the assessment of the app on communication with healthcare providers, the researchers noted. The study also did not address financial or social barriers.
However, the results suggest that patients with COPD identified the potential value of wearable devices for disease management and that improved technology could promote patient empowerment and lifestyle changes, the researchers concluded.
Technology Can Augment Care and Connections
“As clinicians and researchers, we have ideas about what patients would want, but it is always better to get their feedback of what they really want and what they would use,” Dr. Wu told this news organization. “We thought older adults with COPD would be less likely to engage with the technology. We found that many wanted to have their data to help make connections with their condition, and some purchased smartwatches after the study to make these connections,” he said.
The takeaway message from the current study is that people with COPD may benefit from self-management apps, but they would like to use them in collaboration with their healthcare team, said Dr. Wu. “Clinicians may see more of their patients bringing in data from wearables and apps,” he noted.
Concerns persist that using technology to help support people with COPD could increase the “digital divide” and that those with lower digital literacy, financial insecurity, or English as a second language could be left behind, and it is important to remain attentive to equity in pursuing the use of devices and apps, Dr. Wu told this news organization.
Looking ahead, research involving self-management, remote monitoring, and wearable devices has focused on other conditions such as heart failure and diabetes, and more work is needed to examine how these technologies can improve care for patients with COPD, said Dr. Wu. “We see this study as one important step — to understand what will motivate people to use self-management apps and wearables,” he said.
“Acute exacerbations of COPD are very important events that can alter quality of life, lung function, and even mortality in COPD,” said Nathaniel Marchetti, DO, medical director of the Respiratory Intensive Care Unit at Temple University Hospital, Philadelphia, in an interview.
“Many of these exacerbations are not recognized by clinicians or even patients until they present late and end up in an urgent office visit with a physician or in the emergency room [ER], so addressing exacerbations earlier has the potential to avoid ER visits or hospitalizations,” he said.
The study identified areas for further research, Dr. Marchetti said. “More information would be needed to determine if the use of an app to monitor heart rate, symptoms, and oxygen saturation could alter important outcomes in COPD such as exacerbations,” he noted.
As for limitations, “no one wants to carry two smartphones,” said Dr. Marchetti. “Future devices need to be easy to use and available on the patient’s own phone,” he said. Patients should be able to choose a smartwatch or possibly a bracelet that can be synced to a smartphone, he added. The current study also failed to address what would be done with collected data, such as link them to health professionals who would offer treatment when needed, he said.
Overall, the data from the current study suggest that patients with COPD would like some device that monitors symptoms and vital signs and offers suggestions/incentives to exercise and take medications, Dr. Marchetti told this news organization. “A larger study will be needed that compares how such a device could improve outcomes of COPD; outcomes could include admissions/ER visits, exercise performance, or compliance with medication,” he said. In addition, clinical algorithms for the identification and treatment of acute exacerbations of COPD would be needed, Dr. Marchetti noted. These algorithms would determine whether treatment decisions would be initiated by a clinical team of health professionals or whether clinicians would provide medications that the patients would then decide to take based on data collected on the app, using the investigator-provided algorithms, he said.
The study was supported in part by Samsung Research America (SRA) and was initiated by Dr. Wu with input from SRA, but the company had no role in the methods or results. The study also was supported by grants from the National Natural Science Foundation of China.
Dr. Marchetti had no relevant financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Will Hospital-at-Home Go Mainstream?
Jordan Stohler, a 42-year-old nurse in Knoxville, Tennessee, was readmitted to Fort Sanders Medical Center in June 2023 with sepsis after a double mastectomy.
She spent 5 days in the hospital after surgery to clear up the infection. Then she was offered a choice: She could either stay in the hospital while she received IV antibiotics, or she could go home and have the antibiotics given to her there under the Advanced Care at Home program of Covenant Health, the nine-hospital system to which Fort Sanders belongs.
She opted to go home, where she knew she’d be more comfortable and would be close to her beloved dog. In the end, she was very glad she did.
“I received great care in the hospital, but to be allowed to be in the comfort of your own home, to be around my dog, who I think is therapeutic, to be able to cook my own meals, and to have the same one-on-one nursing care that I would have gotten in the hospital was great,” Ms. Stohler said. “
Being cared for at home helped her heal, she said. “I probably would have gotten a little stir crazy if I’d stayed in the hospital any longer. I received excellent care at home.”
Currently, 322 hospitals in 37 states have Medicare waivers for these kinds of programs, although not all of them are currently functioning.
A recent survey published in JAMA found that nearly half of consumers would accept hospital-at-home, and more than a third were neutral on it. Only 17% said they’d rather be cared for in a brick-and-mortar hospital.
The findings of the JAMA survey confirm those of earlier studies, said Bruce Leff, MD, a professor at Johns Hopkins Medical School in Baltimore, who has researched hospital-at-home since the 1990s. Like the new study, those trials found that the results had no relationship to individual traits, such as socioeconomic status, medical conditions, age, gender, or race.
Whether a person felt comfortable with the idea of hospital-at-home boiled down “to a preference for receiving care at home or in the hospital,” he said. Some people distrust hospitals, and others feel insecure about receiving care at home, even if it is provided by qualified health care professionals.
How Patients Are Selected
While the details of hospital-at-home vary from program to program, the basic scenario is that patients who need certain kinds of acute care can be sent home from hospitals, emergency departments, or clinics to receive that care at home. Among the kinds of conditions that make stable patients eligible are heart failure, COPD, pneumonia, cellulitis, and COVID-19, said John Busigin, MD, a hospitalist and medical director of Covenant Advanced Care at Home.
When a patient is admitted to hospital-at-home, the hospital will send along whatever equipment and medications that person needs. In some cases, this may include a hospital bed, although Ms. Stohler used her own. An IV line was put into her arm, and the IV stand was placed next to the bed.
Ms. Stohler received a computer tablet that she used to communicate with doctors and nurses in Covenant’s “command center” in Knoxville. She also wore a watch with a button she could push in case of an emergency. And she had a telephone line that went directly to her medical team, in case she had an issue and the tablet didn’t work.
Twice a day, or as needed, specially trained paramedics came to Ms. Stohler’s home. They checked on the IV line, changed the IV bag, performed tests, and uploaded vital signs from monitoring equipment to Ms. Stohler’s tablet so it could be transmitted to the command center. A physician assistant came in on the second and fourth days of her weeklong stay in the program, and she saw a hospitalist remotely every day.
While some hospital-at-home programs have registered nurses visit patients at home, RNs are in short supply. To fill this gap, Covenant’s program uses community paramedics who have been in the field for at least 5 years, doing everything from intubating patients and placing them on ventilators to providing advanced cardiac life support, Dr. Busigin said. To get certified as community paramedics, they go through a 3-month training program.
Shortly after Ms. Stohler went into hospital-at-home, she had another crisis. Excess fluid had built up in her body because of all the IV fluids she’d received in the hospital while fighting the sepsis. As a result, she became short of breath. If she had been discharged to home rather than hospital-at-home, she said, she would have had to go to the emergency room. Instead, she sent out a distress call. One of the paramedics rushed to her house and gave her an IV diuretic medication, which helped her urinate to get rid of the excess fluid.
A small number of the estimated 300 people who have gone through the program had to be admitted to the hospital, Dr. Busigin said. Nationally, he said, about 5%-10% are admitted. But readmissions among the patients in the Covenant program have been 25% lower than for patients who received conventional hospital care and had the same conditions as those in hospital-at-home.
Studies have shown that these programs not only reduce readmissions, but also cost less, on average, and create a better patient experience than traditional hospital care does. And, according to the JAMA survey, most consumers like the idea. Fifty-six percent of people who took the survey agreed with the statement that people recover faster at home than in the hospital. Fifty-nine percent agreed they’d feel safe being treated at home, and 49% said they’d be more comfortable if treated at home.
The 1134 people who took the survey were also asked about their comfort level with providing various kinds of care to their loved ones during a hospital-at-home episode. The results varied with the type of task: For example, 82% of the respondents agreed or strongly agreed they could manage a patient’s medications, while just 41% said they’d be willing to change a feeding tube. Smaller percentages were willing to change an IV bag or a catheter or do wound care.
However, hospital-at-home programs don’t allow caregivers to take part in clinical care, which is prohibited by Medicare waivers and state licensing regulations. None of the 22 health systems that use the hospital-at-home services of Medically Home, including Covenant, ask caregivers to do anything along this line, said Pippa Shulman, DO, medical director of the company, which provides equipment, technology, and protocols for hospital programs
The only exception at Covenant, Dr. Busigin said, is that the hospital may train family members to do wound care when a patient is discharged from the hospital to Advanced Care at Home. They may also prepare meals for their loved ones, although the program provides balanced meals to patients if they want them. Ms. Stohler had some of these meals, which just had to be heated up, for the first few days of hospital-at-home, and later her relatives brought meals to her house.
Challenges for the Future
The number of Medicare hospital-at-home waivers has nearly doubled since 2021. A year earlier, when Medicare began reimbursing hospitals for acute care at home to help them cope with the overflow of COVID patients, there were only about 15-20 programs in the United States, said Dr. Leff of Johns Hopkins.
A big reason for the lack of use before the pandemic, Dr. Leff said, is that there was no payment system for hospitals that offered hospital-at-home. Now, they can get paid by Medicare and 10 state Medicaid programs, and a number of private payers are also coming on board. Ms. Stohler’s private insurer covered her hospital-at-home stay, and Dr. Busigin said several plans that contract with Covenant will pay for it.
Dr. Leff said he’s cautiously optimistic Congress will extend the Medicare waiver program, which is scheduled to end in December, for another 5 years. A couple of key House committees have signed off on a bill to do that, he said, and a Congressional Budget Office report found that the program did not cost Medicare more money.
But even if the waiver is renewed, some health systems may find it tough to deliver the service. The current version of this model depends a lot on technology, because telemedicine is used and reliable communication is needed for patients in hospital-at-home. That’s why many of the hospitals hire outside vendors like Medically Home to provide the infrastructure they need.
Medically Home manages the tablets given to patients and all connection and networking services, including internet and cellphone connections. It also provides technical services in the command centers that hospitals set up for the doctors and nurses who provide care remotely.
And the firm figures out how to deliver the standard care for each condition in each hospital-at-home. “We need to make sure that the patient is going to get what they need in the time frame it needs to be delivered in, and that it’s safe and effective for the patient,” Dr. Shulman said. “So we’ve developed logistical protocols for a multitude of disease states that allow us to provide high-acuity care in the home to a variety of complex patients.”
The health care workers use the hospital electronic health record for hospital-at-home patients, and vital signs uploaded from patient tablets flow directly into the electronic health record, she said.
Rural Areas Need Help
The use of hospital-at-home in rural areas holds a lot of promise, Dr. Leff said.
“A lot of rural hospitals have been closing, and hospital-at-home could be a mechanism to create hospital-level care where facilities have closed down. It’s easier to do this in urban areas, but it can be done in rural environments as well.”
Rami Karjian, CEO of Medically Home, agreed. The firm services hospital-at-home programs in rural areas of Oklahoma and California, using cellphones and paramedics in areas that lack broadband connections and nurses, he pointed out.
“Hospital-at-home can’t just be available to people who live in big cities,” he said. “The access problems in health care are pervasive, and this is part of how we solve access problems in rural areas.”
A version of this article first appeared on WebMD.com.
Jordan Stohler, a 42-year-old nurse in Knoxville, Tennessee, was readmitted to Fort Sanders Medical Center in June 2023 with sepsis after a double mastectomy.
She spent 5 days in the hospital after surgery to clear up the infection. Then she was offered a choice: She could either stay in the hospital while she received IV antibiotics, or she could go home and have the antibiotics given to her there under the Advanced Care at Home program of Covenant Health, the nine-hospital system to which Fort Sanders belongs.
She opted to go home, where she knew she’d be more comfortable and would be close to her beloved dog. In the end, she was very glad she did.
“I received great care in the hospital, but to be allowed to be in the comfort of your own home, to be around my dog, who I think is therapeutic, to be able to cook my own meals, and to have the same one-on-one nursing care that I would have gotten in the hospital was great,” Ms. Stohler said. “
Being cared for at home helped her heal, she said. “I probably would have gotten a little stir crazy if I’d stayed in the hospital any longer. I received excellent care at home.”
Currently, 322 hospitals in 37 states have Medicare waivers for these kinds of programs, although not all of them are currently functioning.
A recent survey published in JAMA found that nearly half of consumers would accept hospital-at-home, and more than a third were neutral on it. Only 17% said they’d rather be cared for in a brick-and-mortar hospital.
The findings of the JAMA survey confirm those of earlier studies, said Bruce Leff, MD, a professor at Johns Hopkins Medical School in Baltimore, who has researched hospital-at-home since the 1990s. Like the new study, those trials found that the results had no relationship to individual traits, such as socioeconomic status, medical conditions, age, gender, or race.
Whether a person felt comfortable with the idea of hospital-at-home boiled down “to a preference for receiving care at home or in the hospital,” he said. Some people distrust hospitals, and others feel insecure about receiving care at home, even if it is provided by qualified health care professionals.
How Patients Are Selected
While the details of hospital-at-home vary from program to program, the basic scenario is that patients who need certain kinds of acute care can be sent home from hospitals, emergency departments, or clinics to receive that care at home. Among the kinds of conditions that make stable patients eligible are heart failure, COPD, pneumonia, cellulitis, and COVID-19, said John Busigin, MD, a hospitalist and medical director of Covenant Advanced Care at Home.
When a patient is admitted to hospital-at-home, the hospital will send along whatever equipment and medications that person needs. In some cases, this may include a hospital bed, although Ms. Stohler used her own. An IV line was put into her arm, and the IV stand was placed next to the bed.
Ms. Stohler received a computer tablet that she used to communicate with doctors and nurses in Covenant’s “command center” in Knoxville. She also wore a watch with a button she could push in case of an emergency. And she had a telephone line that went directly to her medical team, in case she had an issue and the tablet didn’t work.
Twice a day, or as needed, specially trained paramedics came to Ms. Stohler’s home. They checked on the IV line, changed the IV bag, performed tests, and uploaded vital signs from monitoring equipment to Ms. Stohler’s tablet so it could be transmitted to the command center. A physician assistant came in on the second and fourth days of her weeklong stay in the program, and she saw a hospitalist remotely every day.
While some hospital-at-home programs have registered nurses visit patients at home, RNs are in short supply. To fill this gap, Covenant’s program uses community paramedics who have been in the field for at least 5 years, doing everything from intubating patients and placing them on ventilators to providing advanced cardiac life support, Dr. Busigin said. To get certified as community paramedics, they go through a 3-month training program.
Shortly after Ms. Stohler went into hospital-at-home, she had another crisis. Excess fluid had built up in her body because of all the IV fluids she’d received in the hospital while fighting the sepsis. As a result, she became short of breath. If she had been discharged to home rather than hospital-at-home, she said, she would have had to go to the emergency room. Instead, she sent out a distress call. One of the paramedics rushed to her house and gave her an IV diuretic medication, which helped her urinate to get rid of the excess fluid.
A small number of the estimated 300 people who have gone through the program had to be admitted to the hospital, Dr. Busigin said. Nationally, he said, about 5%-10% are admitted. But readmissions among the patients in the Covenant program have been 25% lower than for patients who received conventional hospital care and had the same conditions as those in hospital-at-home.
Studies have shown that these programs not only reduce readmissions, but also cost less, on average, and create a better patient experience than traditional hospital care does. And, according to the JAMA survey, most consumers like the idea. Fifty-six percent of people who took the survey agreed with the statement that people recover faster at home than in the hospital. Fifty-nine percent agreed they’d feel safe being treated at home, and 49% said they’d be more comfortable if treated at home.
The 1134 people who took the survey were also asked about their comfort level with providing various kinds of care to their loved ones during a hospital-at-home episode. The results varied with the type of task: For example, 82% of the respondents agreed or strongly agreed they could manage a patient’s medications, while just 41% said they’d be willing to change a feeding tube. Smaller percentages were willing to change an IV bag or a catheter or do wound care.
However, hospital-at-home programs don’t allow caregivers to take part in clinical care, which is prohibited by Medicare waivers and state licensing regulations. None of the 22 health systems that use the hospital-at-home services of Medically Home, including Covenant, ask caregivers to do anything along this line, said Pippa Shulman, DO, medical director of the company, which provides equipment, technology, and protocols for hospital programs
The only exception at Covenant, Dr. Busigin said, is that the hospital may train family members to do wound care when a patient is discharged from the hospital to Advanced Care at Home. They may also prepare meals for their loved ones, although the program provides balanced meals to patients if they want them. Ms. Stohler had some of these meals, which just had to be heated up, for the first few days of hospital-at-home, and later her relatives brought meals to her house.
Challenges for the Future
The number of Medicare hospital-at-home waivers has nearly doubled since 2021. A year earlier, when Medicare began reimbursing hospitals for acute care at home to help them cope with the overflow of COVID patients, there were only about 15-20 programs in the United States, said Dr. Leff of Johns Hopkins.
A big reason for the lack of use before the pandemic, Dr. Leff said, is that there was no payment system for hospitals that offered hospital-at-home. Now, they can get paid by Medicare and 10 state Medicaid programs, and a number of private payers are also coming on board. Ms. Stohler’s private insurer covered her hospital-at-home stay, and Dr. Busigin said several plans that contract with Covenant will pay for it.
Dr. Leff said he’s cautiously optimistic Congress will extend the Medicare waiver program, which is scheduled to end in December, for another 5 years. A couple of key House committees have signed off on a bill to do that, he said, and a Congressional Budget Office report found that the program did not cost Medicare more money.
But even if the waiver is renewed, some health systems may find it tough to deliver the service. The current version of this model depends a lot on technology, because telemedicine is used and reliable communication is needed for patients in hospital-at-home. That’s why many of the hospitals hire outside vendors like Medically Home to provide the infrastructure they need.
Medically Home manages the tablets given to patients and all connection and networking services, including internet and cellphone connections. It also provides technical services in the command centers that hospitals set up for the doctors and nurses who provide care remotely.
And the firm figures out how to deliver the standard care for each condition in each hospital-at-home. “We need to make sure that the patient is going to get what they need in the time frame it needs to be delivered in, and that it’s safe and effective for the patient,” Dr. Shulman said. “So we’ve developed logistical protocols for a multitude of disease states that allow us to provide high-acuity care in the home to a variety of complex patients.”
The health care workers use the hospital electronic health record for hospital-at-home patients, and vital signs uploaded from patient tablets flow directly into the electronic health record, she said.
Rural Areas Need Help
The use of hospital-at-home in rural areas holds a lot of promise, Dr. Leff said.
“A lot of rural hospitals have been closing, and hospital-at-home could be a mechanism to create hospital-level care where facilities have closed down. It’s easier to do this in urban areas, but it can be done in rural environments as well.”
Rami Karjian, CEO of Medically Home, agreed. The firm services hospital-at-home programs in rural areas of Oklahoma and California, using cellphones and paramedics in areas that lack broadband connections and nurses, he pointed out.
“Hospital-at-home can’t just be available to people who live in big cities,” he said. “The access problems in health care are pervasive, and this is part of how we solve access problems in rural areas.”
A version of this article first appeared on WebMD.com.
Jordan Stohler, a 42-year-old nurse in Knoxville, Tennessee, was readmitted to Fort Sanders Medical Center in June 2023 with sepsis after a double mastectomy.
She spent 5 days in the hospital after surgery to clear up the infection. Then she was offered a choice: She could either stay in the hospital while she received IV antibiotics, or she could go home and have the antibiotics given to her there under the Advanced Care at Home program of Covenant Health, the nine-hospital system to which Fort Sanders belongs.
She opted to go home, where she knew she’d be more comfortable and would be close to her beloved dog. In the end, she was very glad she did.
“I received great care in the hospital, but to be allowed to be in the comfort of your own home, to be around my dog, who I think is therapeutic, to be able to cook my own meals, and to have the same one-on-one nursing care that I would have gotten in the hospital was great,” Ms. Stohler said. “
Being cared for at home helped her heal, she said. “I probably would have gotten a little stir crazy if I’d stayed in the hospital any longer. I received excellent care at home.”
Currently, 322 hospitals in 37 states have Medicare waivers for these kinds of programs, although not all of them are currently functioning.
A recent survey published in JAMA found that nearly half of consumers would accept hospital-at-home, and more than a third were neutral on it. Only 17% said they’d rather be cared for in a brick-and-mortar hospital.
The findings of the JAMA survey confirm those of earlier studies, said Bruce Leff, MD, a professor at Johns Hopkins Medical School in Baltimore, who has researched hospital-at-home since the 1990s. Like the new study, those trials found that the results had no relationship to individual traits, such as socioeconomic status, medical conditions, age, gender, or race.
Whether a person felt comfortable with the idea of hospital-at-home boiled down “to a preference for receiving care at home or in the hospital,” he said. Some people distrust hospitals, and others feel insecure about receiving care at home, even if it is provided by qualified health care professionals.
How Patients Are Selected
While the details of hospital-at-home vary from program to program, the basic scenario is that patients who need certain kinds of acute care can be sent home from hospitals, emergency departments, or clinics to receive that care at home. Among the kinds of conditions that make stable patients eligible are heart failure, COPD, pneumonia, cellulitis, and COVID-19, said John Busigin, MD, a hospitalist and medical director of Covenant Advanced Care at Home.
When a patient is admitted to hospital-at-home, the hospital will send along whatever equipment and medications that person needs. In some cases, this may include a hospital bed, although Ms. Stohler used her own. An IV line was put into her arm, and the IV stand was placed next to the bed.
Ms. Stohler received a computer tablet that she used to communicate with doctors and nurses in Covenant’s “command center” in Knoxville. She also wore a watch with a button she could push in case of an emergency. And she had a telephone line that went directly to her medical team, in case she had an issue and the tablet didn’t work.
Twice a day, or as needed, specially trained paramedics came to Ms. Stohler’s home. They checked on the IV line, changed the IV bag, performed tests, and uploaded vital signs from monitoring equipment to Ms. Stohler’s tablet so it could be transmitted to the command center. A physician assistant came in on the second and fourth days of her weeklong stay in the program, and she saw a hospitalist remotely every day.
While some hospital-at-home programs have registered nurses visit patients at home, RNs are in short supply. To fill this gap, Covenant’s program uses community paramedics who have been in the field for at least 5 years, doing everything from intubating patients and placing them on ventilators to providing advanced cardiac life support, Dr. Busigin said. To get certified as community paramedics, they go through a 3-month training program.
Shortly after Ms. Stohler went into hospital-at-home, she had another crisis. Excess fluid had built up in her body because of all the IV fluids she’d received in the hospital while fighting the sepsis. As a result, she became short of breath. If she had been discharged to home rather than hospital-at-home, she said, she would have had to go to the emergency room. Instead, she sent out a distress call. One of the paramedics rushed to her house and gave her an IV diuretic medication, which helped her urinate to get rid of the excess fluid.
A small number of the estimated 300 people who have gone through the program had to be admitted to the hospital, Dr. Busigin said. Nationally, he said, about 5%-10% are admitted. But readmissions among the patients in the Covenant program have been 25% lower than for patients who received conventional hospital care and had the same conditions as those in hospital-at-home.
Studies have shown that these programs not only reduce readmissions, but also cost less, on average, and create a better patient experience than traditional hospital care does. And, according to the JAMA survey, most consumers like the idea. Fifty-six percent of people who took the survey agreed with the statement that people recover faster at home than in the hospital. Fifty-nine percent agreed they’d feel safe being treated at home, and 49% said they’d be more comfortable if treated at home.
The 1134 people who took the survey were also asked about their comfort level with providing various kinds of care to their loved ones during a hospital-at-home episode. The results varied with the type of task: For example, 82% of the respondents agreed or strongly agreed they could manage a patient’s medications, while just 41% said they’d be willing to change a feeding tube. Smaller percentages were willing to change an IV bag or a catheter or do wound care.
However, hospital-at-home programs don’t allow caregivers to take part in clinical care, which is prohibited by Medicare waivers and state licensing regulations. None of the 22 health systems that use the hospital-at-home services of Medically Home, including Covenant, ask caregivers to do anything along this line, said Pippa Shulman, DO, medical director of the company, which provides equipment, technology, and protocols for hospital programs
The only exception at Covenant, Dr. Busigin said, is that the hospital may train family members to do wound care when a patient is discharged from the hospital to Advanced Care at Home. They may also prepare meals for their loved ones, although the program provides balanced meals to patients if they want them. Ms. Stohler had some of these meals, which just had to be heated up, for the first few days of hospital-at-home, and later her relatives brought meals to her house.
Challenges for the Future
The number of Medicare hospital-at-home waivers has nearly doubled since 2021. A year earlier, when Medicare began reimbursing hospitals for acute care at home to help them cope with the overflow of COVID patients, there were only about 15-20 programs in the United States, said Dr. Leff of Johns Hopkins.
A big reason for the lack of use before the pandemic, Dr. Leff said, is that there was no payment system for hospitals that offered hospital-at-home. Now, they can get paid by Medicare and 10 state Medicaid programs, and a number of private payers are also coming on board. Ms. Stohler’s private insurer covered her hospital-at-home stay, and Dr. Busigin said several plans that contract with Covenant will pay for it.
Dr. Leff said he’s cautiously optimistic Congress will extend the Medicare waiver program, which is scheduled to end in December, for another 5 years. A couple of key House committees have signed off on a bill to do that, he said, and a Congressional Budget Office report found that the program did not cost Medicare more money.
But even if the waiver is renewed, some health systems may find it tough to deliver the service. The current version of this model depends a lot on technology, because telemedicine is used and reliable communication is needed for patients in hospital-at-home. That’s why many of the hospitals hire outside vendors like Medically Home to provide the infrastructure they need.
Medically Home manages the tablets given to patients and all connection and networking services, including internet and cellphone connections. It also provides technical services in the command centers that hospitals set up for the doctors and nurses who provide care remotely.
And the firm figures out how to deliver the standard care for each condition in each hospital-at-home. “We need to make sure that the patient is going to get what they need in the time frame it needs to be delivered in, and that it’s safe and effective for the patient,” Dr. Shulman said. “So we’ve developed logistical protocols for a multitude of disease states that allow us to provide high-acuity care in the home to a variety of complex patients.”
The health care workers use the hospital electronic health record for hospital-at-home patients, and vital signs uploaded from patient tablets flow directly into the electronic health record, she said.
Rural Areas Need Help
The use of hospital-at-home in rural areas holds a lot of promise, Dr. Leff said.
“A lot of rural hospitals have been closing, and hospital-at-home could be a mechanism to create hospital-level care where facilities have closed down. It’s easier to do this in urban areas, but it can be done in rural environments as well.”
Rami Karjian, CEO of Medically Home, agreed. The firm services hospital-at-home programs in rural areas of Oklahoma and California, using cellphones and paramedics in areas that lack broadband connections and nurses, he pointed out.
“Hospital-at-home can’t just be available to people who live in big cities,” he said. “The access problems in health care are pervasive, and this is part of how we solve access problems in rural areas.”
A version of this article first appeared on WebMD.com.
Are Beta-Blockers Safe for COPD?
Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.
Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.
Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.
This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.
The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.
That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.
Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.
Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.
This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.
The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.
That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.
Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.
Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.
This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.
The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.
That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
A version of this article first appeared on Medscape.com.
Cost of Drugs Can Be Breathtaking for COPD Patients
For patients with chronic obstructive pulmonary disease (COPD), the Global Initiative on Obstructive Lung Disease recommends long-term term pharmacologic and nonpharmacologic therapies based on each patient’s symptoms and disease severity.
Yet even the most effective drugs work only when patients take them as directed, and according to the World Health Organization, fewer than half of all patients worldwide are fully compliant with long-term COPD drug regimens.
And as a recent cross-sectional study showed, nearly one in six patients in the United States reported missing a COPD drug dose, lowering the dose, or delaying filling a prescription for financial reasons.
“I care for patients with COPD as their pulmonologist, and this is a very common problem that we see in clinical practice,” said Meredith McCormack, MD, a pulmonary and critical care medicine physician and associate director of the Pulmonary & Critical Care Medicine Division at Johns Hopkins University in Baltimore.
Dr. McCormack, a national spokesperson for The American Lung Association, said that she shows new patients the photos of all available inhalers and asks which ones they have and how they take them.
“I would say that a majority of the time people are taking their medicines slightly differently than prescribed, and often, this is due to cost,” she said.
Serious Consequences
Cost-related medication nonadherence (CRN), as investigators term it, can have major health effects and can be significantly more costly in the long run due to increased hospitalization rates, higher morbidity, and greater risk for COPD-related death associated with suboptimal care.
“For some patients even a month or two of being off medications increases the risk of having exacerbations, having more symptoms, [and] having a decline in their lung function,” said Douglas M. Beach, MD, a pulmonologist at Beth Israel Deaconess Medical Center in Boston.
In the aforementioned cross-sectional study, published in the open access journal BMC Public Health, Xin Wen, MD, from the Jiamusi (China) University School of Public Health, and colleagues looked at data on a representative sample of US adults who participated in the US National Health Interview Survey from 2013 through 2020.
The sample included 15,928 persons aged 18 years or older with a self-reported history of COPD who completed a CRN survey including the following questions:
During the past 12 months, have you
- Skipped medication doses to save money?
- Taken less medicine than prescribed to save money?
- Delayed filling a prescription to save money?
The investigators found that a weighted 18.56% of participants representing 2.39 million persons with COPD answered “yes” to one of the questions.
Translated into representative population numbers, that works out to an estimated 1.61 million persons with COPD missing doses, 1.72 million taking lower doses than those prescribed, and 2.03 million delaying filling prescriptions to save money.
A multivariable logistic regression analysis showed that those who were most likely to be nonadherent for financial reasons were patients younger than 65 years, women, persons with low family income, those who lacked health insurance, and patients with multiple comorbidities, the authors found.
Financial Barriers
One of the biggest barriers to COPD medication adherence is, somewhat paradoxically, insurance status, particularly Medicare, said Corinne Young, MSN, FNP-C, FCCP, from Colorado Springs Pulmonary Consultants.
“What’s so unfair about Medicare is that patients have to buy a drug plan, so they have to already pay for an extra plan to have access to drugs, and the plans vary because there are so many choices,” she said in an interview.
Elderly patients may be confused about the available options and may choose the Medicare Advantage plan with the lowest monthly premiums, which have the highest annual deductibles, usually in the $5000-and-up range, she said.
In addition, the Medicare Part D prescription coverage gap, commonly known as the “donut hole,” requires patients to pay a percentage of drug costs above a certain limit ($5030 in 2024) until a yearly out-of-pocket limit (currently $8000) is reached, after which the plan will again pick up most of the costs.
Although makers of inhalers have voluntarily agreed to limit monthly co-pays to $35 for uninsured patients, Medicare plans require insured patients to shell out considerably more, with 30 days of Trelegy Ellipta (fluticasone furoate, umeclidinium, and vilanterol) setting patients back nearly $350 per month, according to a recent search of costs for a United Healthcare Medicare Advantage plan.
Chasing Lower-Cost Options
“I have a lot of patients who use Canadian pharmacies to try to get around it, and I have a lot of patients who make a trip to Mexico every year and load up. I have patients who don’t take their inhalers as they are supposed to in order to make them last longer, and I have patients who take the inhalers of other family members,” Ms. Young said.
Humayun Anjum, MD, FCCP, from Dallas Pulmonary and Critical Care in Dallas, Texas, said in an interview that when patients claim that a prescribed drug isn’t working as expected for them, financial pressures may be partly to blame.
“When you investigate a little bit more, that’s where things become a bit more clear, and the patient may say ‘yeah, I stopped using this inhaler because it was costing me 200 bucks a month and I’m already on other medications,’ ” he said.
He noted that, when possible, he will steer patients toward discount prescription services such as GoodRx, which offers discounts at local pharmacies, or Mark Cuban Cost Plus Drugs, an online pharmacy that offers generic versions of Advair Diskus (fluticasone propionate/salmeterol) at a 100-50 mcg dose for $94.70, a savings of $307.30 over retail pharmacies, according to the company’s website.
Dr. Beach noted that Beth Israel Deaconess has a pharmacist embedded in the pulmonary clinic who can help eligible patients get financial assistance to pay for their medications.
“The influencing factors of CRN are multifaceted and necessitating more rigorous research. Health policy interventions focusing on reducing drug costs, delaying disease progression, preventing exacerbations, and reducing the risk of comorbidities may improve the economic burden of COPD and its outcomes,” Dr. Wen and colleagues wrote.
The study by Dr. Wen and colleagues was funded by grants from Chinese national and academic sources. Dr. McCormack has served as a consultant to Aridis, Boehringer Ingelheim, GlaxoSmithKline, MCG Diagnostics, ndd Medical Technologies, and UpToDate. Ms. Young, Dr. Anjum, and Dr. Beach reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
For patients with chronic obstructive pulmonary disease (COPD), the Global Initiative on Obstructive Lung Disease recommends long-term term pharmacologic and nonpharmacologic therapies based on each patient’s symptoms and disease severity.
Yet even the most effective drugs work only when patients take them as directed, and according to the World Health Organization, fewer than half of all patients worldwide are fully compliant with long-term COPD drug regimens.
And as a recent cross-sectional study showed, nearly one in six patients in the United States reported missing a COPD drug dose, lowering the dose, or delaying filling a prescription for financial reasons.
“I care for patients with COPD as their pulmonologist, and this is a very common problem that we see in clinical practice,” said Meredith McCormack, MD, a pulmonary and critical care medicine physician and associate director of the Pulmonary & Critical Care Medicine Division at Johns Hopkins University in Baltimore.
Dr. McCormack, a national spokesperson for The American Lung Association, said that she shows new patients the photos of all available inhalers and asks which ones they have and how they take them.
“I would say that a majority of the time people are taking their medicines slightly differently than prescribed, and often, this is due to cost,” she said.
Serious Consequences
Cost-related medication nonadherence (CRN), as investigators term it, can have major health effects and can be significantly more costly in the long run due to increased hospitalization rates, higher morbidity, and greater risk for COPD-related death associated with suboptimal care.
“For some patients even a month or two of being off medications increases the risk of having exacerbations, having more symptoms, [and] having a decline in their lung function,” said Douglas M. Beach, MD, a pulmonologist at Beth Israel Deaconess Medical Center in Boston.
In the aforementioned cross-sectional study, published in the open access journal BMC Public Health, Xin Wen, MD, from the Jiamusi (China) University School of Public Health, and colleagues looked at data on a representative sample of US adults who participated in the US National Health Interview Survey from 2013 through 2020.
The sample included 15,928 persons aged 18 years or older with a self-reported history of COPD who completed a CRN survey including the following questions:
During the past 12 months, have you
- Skipped medication doses to save money?
- Taken less medicine than prescribed to save money?
- Delayed filling a prescription to save money?
The investigators found that a weighted 18.56% of participants representing 2.39 million persons with COPD answered “yes” to one of the questions.
Translated into representative population numbers, that works out to an estimated 1.61 million persons with COPD missing doses, 1.72 million taking lower doses than those prescribed, and 2.03 million delaying filling prescriptions to save money.
A multivariable logistic regression analysis showed that those who were most likely to be nonadherent for financial reasons were patients younger than 65 years, women, persons with low family income, those who lacked health insurance, and patients with multiple comorbidities, the authors found.
Financial Barriers
One of the biggest barriers to COPD medication adherence is, somewhat paradoxically, insurance status, particularly Medicare, said Corinne Young, MSN, FNP-C, FCCP, from Colorado Springs Pulmonary Consultants.
“What’s so unfair about Medicare is that patients have to buy a drug plan, so they have to already pay for an extra plan to have access to drugs, and the plans vary because there are so many choices,” she said in an interview.
Elderly patients may be confused about the available options and may choose the Medicare Advantage plan with the lowest monthly premiums, which have the highest annual deductibles, usually in the $5000-and-up range, she said.
In addition, the Medicare Part D prescription coverage gap, commonly known as the “donut hole,” requires patients to pay a percentage of drug costs above a certain limit ($5030 in 2024) until a yearly out-of-pocket limit (currently $8000) is reached, after which the plan will again pick up most of the costs.
Although makers of inhalers have voluntarily agreed to limit monthly co-pays to $35 for uninsured patients, Medicare plans require insured patients to shell out considerably more, with 30 days of Trelegy Ellipta (fluticasone furoate, umeclidinium, and vilanterol) setting patients back nearly $350 per month, according to a recent search of costs for a United Healthcare Medicare Advantage plan.
Chasing Lower-Cost Options
“I have a lot of patients who use Canadian pharmacies to try to get around it, and I have a lot of patients who make a trip to Mexico every year and load up. I have patients who don’t take their inhalers as they are supposed to in order to make them last longer, and I have patients who take the inhalers of other family members,” Ms. Young said.
Humayun Anjum, MD, FCCP, from Dallas Pulmonary and Critical Care in Dallas, Texas, said in an interview that when patients claim that a prescribed drug isn’t working as expected for them, financial pressures may be partly to blame.
“When you investigate a little bit more, that’s where things become a bit more clear, and the patient may say ‘yeah, I stopped using this inhaler because it was costing me 200 bucks a month and I’m already on other medications,’ ” he said.
He noted that, when possible, he will steer patients toward discount prescription services such as GoodRx, which offers discounts at local pharmacies, or Mark Cuban Cost Plus Drugs, an online pharmacy that offers generic versions of Advair Diskus (fluticasone propionate/salmeterol) at a 100-50 mcg dose for $94.70, a savings of $307.30 over retail pharmacies, according to the company’s website.
Dr. Beach noted that Beth Israel Deaconess has a pharmacist embedded in the pulmonary clinic who can help eligible patients get financial assistance to pay for their medications.
“The influencing factors of CRN are multifaceted and necessitating more rigorous research. Health policy interventions focusing on reducing drug costs, delaying disease progression, preventing exacerbations, and reducing the risk of comorbidities may improve the economic burden of COPD and its outcomes,” Dr. Wen and colleagues wrote.
The study by Dr. Wen and colleagues was funded by grants from Chinese national and academic sources. Dr. McCormack has served as a consultant to Aridis, Boehringer Ingelheim, GlaxoSmithKline, MCG Diagnostics, ndd Medical Technologies, and UpToDate. Ms. Young, Dr. Anjum, and Dr. Beach reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
For patients with chronic obstructive pulmonary disease (COPD), the Global Initiative on Obstructive Lung Disease recommends long-term term pharmacologic and nonpharmacologic therapies based on each patient’s symptoms and disease severity.
Yet even the most effective drugs work only when patients take them as directed, and according to the World Health Organization, fewer than half of all patients worldwide are fully compliant with long-term COPD drug regimens.
And as a recent cross-sectional study showed, nearly one in six patients in the United States reported missing a COPD drug dose, lowering the dose, or delaying filling a prescription for financial reasons.
“I care for patients with COPD as their pulmonologist, and this is a very common problem that we see in clinical practice,” said Meredith McCormack, MD, a pulmonary and critical care medicine physician and associate director of the Pulmonary & Critical Care Medicine Division at Johns Hopkins University in Baltimore.
Dr. McCormack, a national spokesperson for The American Lung Association, said that she shows new patients the photos of all available inhalers and asks which ones they have and how they take them.
“I would say that a majority of the time people are taking their medicines slightly differently than prescribed, and often, this is due to cost,” she said.
Serious Consequences
Cost-related medication nonadherence (CRN), as investigators term it, can have major health effects and can be significantly more costly in the long run due to increased hospitalization rates, higher morbidity, and greater risk for COPD-related death associated with suboptimal care.
“For some patients even a month or two of being off medications increases the risk of having exacerbations, having more symptoms, [and] having a decline in their lung function,” said Douglas M. Beach, MD, a pulmonologist at Beth Israel Deaconess Medical Center in Boston.
In the aforementioned cross-sectional study, published in the open access journal BMC Public Health, Xin Wen, MD, from the Jiamusi (China) University School of Public Health, and colleagues looked at data on a representative sample of US adults who participated in the US National Health Interview Survey from 2013 through 2020.
The sample included 15,928 persons aged 18 years or older with a self-reported history of COPD who completed a CRN survey including the following questions:
During the past 12 months, have you
- Skipped medication doses to save money?
- Taken less medicine than prescribed to save money?
- Delayed filling a prescription to save money?
The investigators found that a weighted 18.56% of participants representing 2.39 million persons with COPD answered “yes” to one of the questions.
Translated into representative population numbers, that works out to an estimated 1.61 million persons with COPD missing doses, 1.72 million taking lower doses than those prescribed, and 2.03 million delaying filling prescriptions to save money.
A multivariable logistic regression analysis showed that those who were most likely to be nonadherent for financial reasons were patients younger than 65 years, women, persons with low family income, those who lacked health insurance, and patients with multiple comorbidities, the authors found.
Financial Barriers
One of the biggest barriers to COPD medication adherence is, somewhat paradoxically, insurance status, particularly Medicare, said Corinne Young, MSN, FNP-C, FCCP, from Colorado Springs Pulmonary Consultants.
“What’s so unfair about Medicare is that patients have to buy a drug plan, so they have to already pay for an extra plan to have access to drugs, and the plans vary because there are so many choices,” she said in an interview.
Elderly patients may be confused about the available options and may choose the Medicare Advantage plan with the lowest monthly premiums, which have the highest annual deductibles, usually in the $5000-and-up range, she said.
In addition, the Medicare Part D prescription coverage gap, commonly known as the “donut hole,” requires patients to pay a percentage of drug costs above a certain limit ($5030 in 2024) until a yearly out-of-pocket limit (currently $8000) is reached, after which the plan will again pick up most of the costs.
Although makers of inhalers have voluntarily agreed to limit monthly co-pays to $35 for uninsured patients, Medicare plans require insured patients to shell out considerably more, with 30 days of Trelegy Ellipta (fluticasone furoate, umeclidinium, and vilanterol) setting patients back nearly $350 per month, according to a recent search of costs for a United Healthcare Medicare Advantage plan.
Chasing Lower-Cost Options
“I have a lot of patients who use Canadian pharmacies to try to get around it, and I have a lot of patients who make a trip to Mexico every year and load up. I have patients who don’t take their inhalers as they are supposed to in order to make them last longer, and I have patients who take the inhalers of other family members,” Ms. Young said.
Humayun Anjum, MD, FCCP, from Dallas Pulmonary and Critical Care in Dallas, Texas, said in an interview that when patients claim that a prescribed drug isn’t working as expected for them, financial pressures may be partly to blame.
“When you investigate a little bit more, that’s where things become a bit more clear, and the patient may say ‘yeah, I stopped using this inhaler because it was costing me 200 bucks a month and I’m already on other medications,’ ” he said.
He noted that, when possible, he will steer patients toward discount prescription services such as GoodRx, which offers discounts at local pharmacies, or Mark Cuban Cost Plus Drugs, an online pharmacy that offers generic versions of Advair Diskus (fluticasone propionate/salmeterol) at a 100-50 mcg dose for $94.70, a savings of $307.30 over retail pharmacies, according to the company’s website.
Dr. Beach noted that Beth Israel Deaconess has a pharmacist embedded in the pulmonary clinic who can help eligible patients get financial assistance to pay for their medications.
“The influencing factors of CRN are multifaceted and necessitating more rigorous research. Health policy interventions focusing on reducing drug costs, delaying disease progression, preventing exacerbations, and reducing the risk of comorbidities may improve the economic burden of COPD and its outcomes,” Dr. Wen and colleagues wrote.
The study by Dr. Wen and colleagues was funded by grants from Chinese national and academic sources. Dr. McCormack has served as a consultant to Aridis, Boehringer Ingelheim, GlaxoSmithKline, MCG Diagnostics, ndd Medical Technologies, and UpToDate. Ms. Young, Dr. Anjum, and Dr. Beach reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
New Therapy May Provide COPD Patients With Relief, Convenience
, according to manufacturer Verona Pharma.
Ensifentrine offers a new medication and a new delivery method, according to a company press release. Ensifentrine is the first-in-class selective dual inhibitor of both phosphodiesterase 3 (PDE 3) and PDE 4, combining both bronchodilator and nonsteroidal anti-inflammatory effects in a single molecule. The drug is delivered through a standard jet nebulizer.
Disease Management Made Easier
Although currently approved therapies for COPD, such as bronchodilators and inhaled corticosteroids (ICS), have benefited many patients, additional treatment options are still needed to help those who remain symptomatic and suffer from frequent exacerbations, said Diego J. Maselli, MD, of the University of Texas Health Science Center, San Antonio.
“Ensifentrine is a new class of medication that inhibits both PDE 3 and PDE 4; this results in both bronchodilation and suppression of the inflammatory response in COPD,” said Dr. Maselli, who was not involved in studies of ensifentrine.
“Large phase III, double-blind, randomized, placebo-controlled studies have demonstrated that ensifentrine improved lung function and reduced the risk of exacerbations in patients with symptomatic moderate to severe COPD,” he said. The study participants were on no long-acting maintenance therapy, or they were receiving long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA) with or without inhaled corticosteroids, he noted.
The FDA approval was supported by data from the phase 3 ENHANCE 1 and 2 trials, which included 760 and 789 adults aged 40-80 years with moderate to severe symptomatic COPD, respectively. Participants were randomized to 3 mg ensifentrine delivered via nebulizer or a placebo twice daily.
In the studies, ensifentrine significantly improved lung function based on the primary outcome of average forced expiratory volume per second within 0-12 hours of administration compared with placebo in both studies. In ENHANCE 1, ensifentrine significantly improved symptoms and quality of life compared with placebo at 24 weeks. The ENHANCE 2 results showed similar trends in favor of ensifentrine, although the differences were not significant at 24 weeks. However, the effects of ensifentrine vs placebo were consistent overall across all symptom and quality of life endpoints at all assessments during the study period, the researchers wrote.
In addition, the inhaled drug was well tolerated, with similar proportions of ensifentrine and placebo patients reporting treatment-emergent adverse events (38.4% and 36.4%, respectively, in ENHANCE 1 and 35.3% and 35.4%, respectively, in ENHANCE 2). The most common treatment-emergent adverse events were nasopharyngitis, hypertension, and back pain, reported in < 3% of the ensifentrine group.
The safety profile of ensifentrine is a plus for patients, said Dr. Maselli. “Ensifentrine was well tolerated in these studies, and the side effect profile was similar to placebo,” he said. The “ensifentrine is delivered via nebulizer and dosed every 12 hours. Some patients may still prefer the use of inhalers, while others may feel more comfortable with this mode of delivery,” he said.
In clinical practice, “ensifentrine is a welcome addition to the current armamentarium of therapies for COPD as an option for patients who are symptomatic or who have frequent exacerbations,” Dr. Maselli emphasized.
Looking ahead, more studies are needed to evaluate ensifentrine in broader populations of COPD patients, Dr. Maselli said. For example, ensifentrine could be used as an add-on therapy for patients receiving triple therapy (ICS/LABA/LAMA) and for patients with other obstructive inflammatory diseases such as asthma, bronchiectasis, and cystic fibrosis, he noted.
Dr. Maselli disclosed serving as a consultant for GlaxoSmithKline, AstraZeneca, Amgen, and Sanofi/Regeneron; he also serves on the Editorial Board of CHEST Physician.
A version of this article appeared on Medscape.com.
, according to manufacturer Verona Pharma.
Ensifentrine offers a new medication and a new delivery method, according to a company press release. Ensifentrine is the first-in-class selective dual inhibitor of both phosphodiesterase 3 (PDE 3) and PDE 4, combining both bronchodilator and nonsteroidal anti-inflammatory effects in a single molecule. The drug is delivered through a standard jet nebulizer.
Disease Management Made Easier
Although currently approved therapies for COPD, such as bronchodilators and inhaled corticosteroids (ICS), have benefited many patients, additional treatment options are still needed to help those who remain symptomatic and suffer from frequent exacerbations, said Diego J. Maselli, MD, of the University of Texas Health Science Center, San Antonio.
“Ensifentrine is a new class of medication that inhibits both PDE 3 and PDE 4; this results in both bronchodilation and suppression of the inflammatory response in COPD,” said Dr. Maselli, who was not involved in studies of ensifentrine.
“Large phase III, double-blind, randomized, placebo-controlled studies have demonstrated that ensifentrine improved lung function and reduced the risk of exacerbations in patients with symptomatic moderate to severe COPD,” he said. The study participants were on no long-acting maintenance therapy, or they were receiving long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA) with or without inhaled corticosteroids, he noted.
The FDA approval was supported by data from the phase 3 ENHANCE 1 and 2 trials, which included 760 and 789 adults aged 40-80 years with moderate to severe symptomatic COPD, respectively. Participants were randomized to 3 mg ensifentrine delivered via nebulizer or a placebo twice daily.
In the studies, ensifentrine significantly improved lung function based on the primary outcome of average forced expiratory volume per second within 0-12 hours of administration compared with placebo in both studies. In ENHANCE 1, ensifentrine significantly improved symptoms and quality of life compared with placebo at 24 weeks. The ENHANCE 2 results showed similar trends in favor of ensifentrine, although the differences were not significant at 24 weeks. However, the effects of ensifentrine vs placebo were consistent overall across all symptom and quality of life endpoints at all assessments during the study period, the researchers wrote.
In addition, the inhaled drug was well tolerated, with similar proportions of ensifentrine and placebo patients reporting treatment-emergent adverse events (38.4% and 36.4%, respectively, in ENHANCE 1 and 35.3% and 35.4%, respectively, in ENHANCE 2). The most common treatment-emergent adverse events were nasopharyngitis, hypertension, and back pain, reported in < 3% of the ensifentrine group.
The safety profile of ensifentrine is a plus for patients, said Dr. Maselli. “Ensifentrine was well tolerated in these studies, and the side effect profile was similar to placebo,” he said. The “ensifentrine is delivered via nebulizer and dosed every 12 hours. Some patients may still prefer the use of inhalers, while others may feel more comfortable with this mode of delivery,” he said.
In clinical practice, “ensifentrine is a welcome addition to the current armamentarium of therapies for COPD as an option for patients who are symptomatic or who have frequent exacerbations,” Dr. Maselli emphasized.
Looking ahead, more studies are needed to evaluate ensifentrine in broader populations of COPD patients, Dr. Maselli said. For example, ensifentrine could be used as an add-on therapy for patients receiving triple therapy (ICS/LABA/LAMA) and for patients with other obstructive inflammatory diseases such as asthma, bronchiectasis, and cystic fibrosis, he noted.
Dr. Maselli disclosed serving as a consultant for GlaxoSmithKline, AstraZeneca, Amgen, and Sanofi/Regeneron; he also serves on the Editorial Board of CHEST Physician.
A version of this article appeared on Medscape.com.
, according to manufacturer Verona Pharma.
Ensifentrine offers a new medication and a new delivery method, according to a company press release. Ensifentrine is the first-in-class selective dual inhibitor of both phosphodiesterase 3 (PDE 3) and PDE 4, combining both bronchodilator and nonsteroidal anti-inflammatory effects in a single molecule. The drug is delivered through a standard jet nebulizer.
Disease Management Made Easier
Although currently approved therapies for COPD, such as bronchodilators and inhaled corticosteroids (ICS), have benefited many patients, additional treatment options are still needed to help those who remain symptomatic and suffer from frequent exacerbations, said Diego J. Maselli, MD, of the University of Texas Health Science Center, San Antonio.
“Ensifentrine is a new class of medication that inhibits both PDE 3 and PDE 4; this results in both bronchodilation and suppression of the inflammatory response in COPD,” said Dr. Maselli, who was not involved in studies of ensifentrine.
“Large phase III, double-blind, randomized, placebo-controlled studies have demonstrated that ensifentrine improved lung function and reduced the risk of exacerbations in patients with symptomatic moderate to severe COPD,” he said. The study participants were on no long-acting maintenance therapy, or they were receiving long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA) with or without inhaled corticosteroids, he noted.
The FDA approval was supported by data from the phase 3 ENHANCE 1 and 2 trials, which included 760 and 789 adults aged 40-80 years with moderate to severe symptomatic COPD, respectively. Participants were randomized to 3 mg ensifentrine delivered via nebulizer or a placebo twice daily.
In the studies, ensifentrine significantly improved lung function based on the primary outcome of average forced expiratory volume per second within 0-12 hours of administration compared with placebo in both studies. In ENHANCE 1, ensifentrine significantly improved symptoms and quality of life compared with placebo at 24 weeks. The ENHANCE 2 results showed similar trends in favor of ensifentrine, although the differences were not significant at 24 weeks. However, the effects of ensifentrine vs placebo were consistent overall across all symptom and quality of life endpoints at all assessments during the study period, the researchers wrote.
In addition, the inhaled drug was well tolerated, with similar proportions of ensifentrine and placebo patients reporting treatment-emergent adverse events (38.4% and 36.4%, respectively, in ENHANCE 1 and 35.3% and 35.4%, respectively, in ENHANCE 2). The most common treatment-emergent adverse events were nasopharyngitis, hypertension, and back pain, reported in < 3% of the ensifentrine group.
The safety profile of ensifentrine is a plus for patients, said Dr. Maselli. “Ensifentrine was well tolerated in these studies, and the side effect profile was similar to placebo,” he said. The “ensifentrine is delivered via nebulizer and dosed every 12 hours. Some patients may still prefer the use of inhalers, while others may feel more comfortable with this mode of delivery,” he said.
In clinical practice, “ensifentrine is a welcome addition to the current armamentarium of therapies for COPD as an option for patients who are symptomatic or who have frequent exacerbations,” Dr. Maselli emphasized.
Looking ahead, more studies are needed to evaluate ensifentrine in broader populations of COPD patients, Dr. Maselli said. For example, ensifentrine could be used as an add-on therapy for patients receiving triple therapy (ICS/LABA/LAMA) and for patients with other obstructive inflammatory diseases such as asthma, bronchiectasis, and cystic fibrosis, he noted.
Dr. Maselli disclosed serving as a consultant for GlaxoSmithKline, AstraZeneca, Amgen, and Sanofi/Regeneron; he also serves on the Editorial Board of CHEST Physician.
A version of this article appeared on Medscape.com.
Expanding recommendations for RSV vaccination
AIRWAYS DISORDERS NETWORK
Asthma and COPD Section
Respiratory syncytial virus (RSV) has been increasingly recognized as a prevalent cause of lower respiratory tract infection (LRTI) among adults in the United States. The risk of hospitalization and mortality from RSV-associated respiratory failure is higher in those with chronic lung disease. In adults aged 65 years or older, RSV has shown to cause up to 160,000 hospitalizations and 10,000 deaths annually.
RSV has been well established as a major cause of LRTI and morbidity among infants. Maternal vaccination with RSVPreF in patients who are pregnant is suggested between 32 0/7 and 36 6/7 weeks of gestation if the date of delivery falls during RSV season to prevent severe illness in young infants in their first months of life. At present, there are no data supporting vaccine administration to patients who are pregnant delivering outside of the RSV season.
What about the rest of the patients? A phase 3b clinical trial to assess the safety and immunogenicity of the RSVPreF3 vaccine in individuals 18 to 49 years of age at increased risk for RSV LRTI, including those with chronic respiratory diseases, is currently underway with projected completion in April 2025 (clinical trials.gov; ID NCT06389487). Additional studies examining safety and immunogenicity combining RSV vaccines with PCV20, influenza, COVID, or Tdap vaccines are also underway. These outcomes will be significant for future recommendations to further lower the risk of developing LRTI, hospitalization, and death among patients less than the age of 60 with chronic lung diseases.
Resources
1. Melgar M, Britton A, Roper LE, et al. Use of respiratory syncytial virus vaccines in older adults: recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(29):793-801.
2. Healthcare Providers: RSV Vaccination for Adults 60 Years of Age and Over. Centers for Disease Control and Prevention. Updated March 1, 2024. https://www.cdc.gov/vaccines/vpd/rsv/hcp/older-adults.html
3. Ault KA, Hughes BL, Riley LE. Maternal Respiratory Syncytial Virus Vaccination. The American College of Obstetricians and Gynecologists. Updated December 11, 2023. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2023/09/maternal-respiratory-syncytial-virus-vaccination
AIRWAYS DISORDERS NETWORK
Asthma and COPD Section
Respiratory syncytial virus (RSV) has been increasingly recognized as a prevalent cause of lower respiratory tract infection (LRTI) among adults in the United States. The risk of hospitalization and mortality from RSV-associated respiratory failure is higher in those with chronic lung disease. In adults aged 65 years or older, RSV has shown to cause up to 160,000 hospitalizations and 10,000 deaths annually.
RSV has been well established as a major cause of LRTI and morbidity among infants. Maternal vaccination with RSVPreF in patients who are pregnant is suggested between 32 0/7 and 36 6/7 weeks of gestation if the date of delivery falls during RSV season to prevent severe illness in young infants in their first months of life. At present, there are no data supporting vaccine administration to patients who are pregnant delivering outside of the RSV season.
What about the rest of the patients? A phase 3b clinical trial to assess the safety and immunogenicity of the RSVPreF3 vaccine in individuals 18 to 49 years of age at increased risk for RSV LRTI, including those with chronic respiratory diseases, is currently underway with projected completion in April 2025 (clinical trials.gov; ID NCT06389487). Additional studies examining safety and immunogenicity combining RSV vaccines with PCV20, influenza, COVID, or Tdap vaccines are also underway. These outcomes will be significant for future recommendations to further lower the risk of developing LRTI, hospitalization, and death among patients less than the age of 60 with chronic lung diseases.
Resources
1. Melgar M, Britton A, Roper LE, et al. Use of respiratory syncytial virus vaccines in older adults: recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(29):793-801.
2. Healthcare Providers: RSV Vaccination for Adults 60 Years of Age and Over. Centers for Disease Control and Prevention. Updated March 1, 2024. https://www.cdc.gov/vaccines/vpd/rsv/hcp/older-adults.html
3. Ault KA, Hughes BL, Riley LE. Maternal Respiratory Syncytial Virus Vaccination. The American College of Obstetricians and Gynecologists. Updated December 11, 2023. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2023/09/maternal-respiratory-syncytial-virus-vaccination
AIRWAYS DISORDERS NETWORK
Asthma and COPD Section
Respiratory syncytial virus (RSV) has been increasingly recognized as a prevalent cause of lower respiratory tract infection (LRTI) among adults in the United States. The risk of hospitalization and mortality from RSV-associated respiratory failure is higher in those with chronic lung disease. In adults aged 65 years or older, RSV has shown to cause up to 160,000 hospitalizations and 10,000 deaths annually.
RSV has been well established as a major cause of LRTI and morbidity among infants. Maternal vaccination with RSVPreF in patients who are pregnant is suggested between 32 0/7 and 36 6/7 weeks of gestation if the date of delivery falls during RSV season to prevent severe illness in young infants in their first months of life. At present, there are no data supporting vaccine administration to patients who are pregnant delivering outside of the RSV season.
What about the rest of the patients? A phase 3b clinical trial to assess the safety and immunogenicity of the RSVPreF3 vaccine in individuals 18 to 49 years of age at increased risk for RSV LRTI, including those with chronic respiratory diseases, is currently underway with projected completion in April 2025 (clinical trials.gov; ID NCT06389487). Additional studies examining safety and immunogenicity combining RSV vaccines with PCV20, influenza, COVID, or Tdap vaccines are also underway. These outcomes will be significant for future recommendations to further lower the risk of developing LRTI, hospitalization, and death among patients less than the age of 60 with chronic lung diseases.
Resources
1. Melgar M, Britton A, Roper LE, et al. Use of respiratory syncytial virus vaccines in older adults: recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(29):793-801.
2. Healthcare Providers: RSV Vaccination for Adults 60 Years of Age and Over. Centers for Disease Control and Prevention. Updated March 1, 2024. https://www.cdc.gov/vaccines/vpd/rsv/hcp/older-adults.html
3. Ault KA, Hughes BL, Riley LE. Maternal Respiratory Syncytial Virus Vaccination. The American College of Obstetricians and Gynecologists. Updated December 11, 2023. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2023/09/maternal-respiratory-syncytial-virus-vaccination
Top reads from the CHEST journal portfolio
Understanding RA with COPD, lung cancer prediction models, and chronic cardiac dysfunction
Journal CHEST®
Does Rheumatoid Arthritis Increase the Risk of COPD?
By: Chiwook Chung, MD, and colleagues
Notably, individuals with seropositive RA exhibit a greater risk of COPD onset than those with seronegative RA. Although smoking history didn’t affect the relationship between RA and COPD, monitoring respiratory symptoms and pulmonary function in patients with RA, especially patients who are seropositive, is crucial. These findings underscore the importance of interdisciplinary collaboration between rheumatologists and pulmonologists to enhance early detection and management strategies for pulmonary complications in patients with RA.
– Commentary by Corinne Young, MSN, FNP-C, FCCP, Member of the CHEST Physician® Editorial Board
CHEST Pulmonary®
The Lung Cancer Prediction Model “Stress Test”
By: Brent E. Heideman, MD, and colleagues
Current lung cancer prediction models have limited utility in high-risk patients referred for diagnostic biopsy. In a study of 322 indeterminate pulmonary nodules, the Brock, Mayo Clinic, Herder, and Veterans Affairs models showed modest discrimination between benign and malignant nodules (AUCs 0.67-0.77). The models performed poorly for low-risk patients (negative predictive values 63%-71%) and suboptimally for high-risk patients (positive predictive values 73%-87%), suggesting referring physicians use additional clinical information not captured in these models to identify high-risk patients needing biopsy. New prediction models and biomarkers specifically developed and calibrated for high-risk populations are needed to better inform clinical decision-making. Incorporating interval imaging to assess changes in nodule characteristics could potentially improve model performance. Tailored risk assessment tools are crucial for optimizing management and reducing unnecessary invasive procedures in this challenging patient population.
– Commentary by Russell Miller, MD, Member of the CHEST Physician Editorial Board
CHEST Critical Care ®
Characterizing Cardiac Function in ICU Survivors of Sepsis
By: Kevin Garrity, MBChB, and colleagues
While chronic cardiac dysfunction is one of the proposed mechanisms of long-term impairment post critical illness, its prevalence, mechanisms, and associations with disability following admission for sepsis are not well understood. Garrity and colleagues describe the Characterization of Cardiovascular Function in ICU Survivors of Sepsis (CONDUCT-ICU) protocol, a prospective study including two ICUs in Scotland aimed to better define cardiovascular dysfunction in survivors of sepsis. Designed to enroll 69 patients, demographics, cardiac and inflammatory biomarkers, and echocardiograms will be obtained on ICU discharge with additional laboratory data, cardiac magnetic resonance imaging, and patient-reported outcome measures to be obtained at 6 to 10 weeks. This novel multimodal approach will provide understanding into the role of cardiovascular dysfunction following critical illness as well as offer mechanistic insights. The investigators hope to obtain operational and pilot data for larger future studies.
– Commentary by Eugene Yuriditsky, MD, FCCP, Member of the CHEST Physician Editorial Board
Understanding RA with COPD, lung cancer prediction models, and chronic cardiac dysfunction
Understanding RA with COPD, lung cancer prediction models, and chronic cardiac dysfunction
Journal CHEST®
Does Rheumatoid Arthritis Increase the Risk of COPD?
By: Chiwook Chung, MD, and colleagues
Notably, individuals with seropositive RA exhibit a greater risk of COPD onset than those with seronegative RA. Although smoking history didn’t affect the relationship between RA and COPD, monitoring respiratory symptoms and pulmonary function in patients with RA, especially patients who are seropositive, is crucial. These findings underscore the importance of interdisciplinary collaboration between rheumatologists and pulmonologists to enhance early detection and management strategies for pulmonary complications in patients with RA.
– Commentary by Corinne Young, MSN, FNP-C, FCCP, Member of the CHEST Physician® Editorial Board
CHEST Pulmonary®
The Lung Cancer Prediction Model “Stress Test”
By: Brent E. Heideman, MD, and colleagues
Current lung cancer prediction models have limited utility in high-risk patients referred for diagnostic biopsy. In a study of 322 indeterminate pulmonary nodules, the Brock, Mayo Clinic, Herder, and Veterans Affairs models showed modest discrimination between benign and malignant nodules (AUCs 0.67-0.77). The models performed poorly for low-risk patients (negative predictive values 63%-71%) and suboptimally for high-risk patients (positive predictive values 73%-87%), suggesting referring physicians use additional clinical information not captured in these models to identify high-risk patients needing biopsy. New prediction models and biomarkers specifically developed and calibrated for high-risk populations are needed to better inform clinical decision-making. Incorporating interval imaging to assess changes in nodule characteristics could potentially improve model performance. Tailored risk assessment tools are crucial for optimizing management and reducing unnecessary invasive procedures in this challenging patient population.
– Commentary by Russell Miller, MD, Member of the CHEST Physician Editorial Board
CHEST Critical Care ®
Characterizing Cardiac Function in ICU Survivors of Sepsis
By: Kevin Garrity, MBChB, and colleagues
While chronic cardiac dysfunction is one of the proposed mechanisms of long-term impairment post critical illness, its prevalence, mechanisms, and associations with disability following admission for sepsis are not well understood. Garrity and colleagues describe the Characterization of Cardiovascular Function in ICU Survivors of Sepsis (CONDUCT-ICU) protocol, a prospective study including two ICUs in Scotland aimed to better define cardiovascular dysfunction in survivors of sepsis. Designed to enroll 69 patients, demographics, cardiac and inflammatory biomarkers, and echocardiograms will be obtained on ICU discharge with additional laboratory data, cardiac magnetic resonance imaging, and patient-reported outcome measures to be obtained at 6 to 10 weeks. This novel multimodal approach will provide understanding into the role of cardiovascular dysfunction following critical illness as well as offer mechanistic insights. The investigators hope to obtain operational and pilot data for larger future studies.
– Commentary by Eugene Yuriditsky, MD, FCCP, Member of the CHEST Physician Editorial Board
Journal CHEST®
Does Rheumatoid Arthritis Increase the Risk of COPD?
By: Chiwook Chung, MD, and colleagues
Notably, individuals with seropositive RA exhibit a greater risk of COPD onset than those with seronegative RA. Although smoking history didn’t affect the relationship between RA and COPD, monitoring respiratory symptoms and pulmonary function in patients with RA, especially patients who are seropositive, is crucial. These findings underscore the importance of interdisciplinary collaboration between rheumatologists and pulmonologists to enhance early detection and management strategies for pulmonary complications in patients with RA.
– Commentary by Corinne Young, MSN, FNP-C, FCCP, Member of the CHEST Physician® Editorial Board
CHEST Pulmonary®
The Lung Cancer Prediction Model “Stress Test”
By: Brent E. Heideman, MD, and colleagues
Current lung cancer prediction models have limited utility in high-risk patients referred for diagnostic biopsy. In a study of 322 indeterminate pulmonary nodules, the Brock, Mayo Clinic, Herder, and Veterans Affairs models showed modest discrimination between benign and malignant nodules (AUCs 0.67-0.77). The models performed poorly for low-risk patients (negative predictive values 63%-71%) and suboptimally for high-risk patients (positive predictive values 73%-87%), suggesting referring physicians use additional clinical information not captured in these models to identify high-risk patients needing biopsy. New prediction models and biomarkers specifically developed and calibrated for high-risk populations are needed to better inform clinical decision-making. Incorporating interval imaging to assess changes in nodule characteristics could potentially improve model performance. Tailored risk assessment tools are crucial for optimizing management and reducing unnecessary invasive procedures in this challenging patient population.
– Commentary by Russell Miller, MD, Member of the CHEST Physician Editorial Board
CHEST Critical Care ®
Characterizing Cardiac Function in ICU Survivors of Sepsis
By: Kevin Garrity, MBChB, and colleagues
While chronic cardiac dysfunction is one of the proposed mechanisms of long-term impairment post critical illness, its prevalence, mechanisms, and associations with disability following admission for sepsis are not well understood. Garrity and colleagues describe the Characterization of Cardiovascular Function in ICU Survivors of Sepsis (CONDUCT-ICU) protocol, a prospective study including two ICUs in Scotland aimed to better define cardiovascular dysfunction in survivors of sepsis. Designed to enroll 69 patients, demographics, cardiac and inflammatory biomarkers, and echocardiograms will be obtained on ICU discharge with additional laboratory data, cardiac magnetic resonance imaging, and patient-reported outcome measures to be obtained at 6 to 10 weeks. This novel multimodal approach will provide understanding into the role of cardiovascular dysfunction following critical illness as well as offer mechanistic insights. The investigators hope to obtain operational and pilot data for larger future studies.
– Commentary by Eugene Yuriditsky, MD, FCCP, Member of the CHEST Physician Editorial Board
COPD Highlights From ATS 2024
The latest research on treatment of patients with COPD presented at the American Thoracic Society (ATS) 2024 annual meeting is reported on by Diego J. Maselli, MD, FCCP, CHEST Physician Editorial Board Member, from UT Health San Antonio in Texas.
Dr. Maselli discusses the phase 2a COURSE study, which looked at patients with moderate to severe COPD to determine whether novel tezepelumab would help reduce exacerbations over 52 weeks. The study reached a nonsignificant numerical reduction in the annual rate vs placebo, but Dr. Maselli suggests that outcomes in patients. with high blood eosinophil counts merit further study.
Next, Dr. Maselli discusses the phase 3 NOTUS trial, looking at the efficacy and safety of the monoclonal antibody dupilumab in patients with moderate to severe COPD. The researchers found a 34% reduction in exacerbations in the dupilumab group vs placebo after 52 weeks.
He then details a 272-patient study looking at nebulized ensifentrine, a dual inhibitor of PDE3 and PDE4. The study demonstrated improved lung function as well as a reduction in exacerbation rate to patients with moderate to severe COPD treated with ensifentrined added to long-acting beta agonists-inhaled corticosteroid maintenance therapy.
Finally, Dr. Maselli highlights the MAZI study, a large retrospective analysis comparing the mortality rate in patients with COPD taking single-inhaler triple therapy (SITT) vs multiple-inhaler triple therapy (MITT). The researchers found that SITT was superior to MITT.
--
Diego J. Maselli, MD, FCCP, Professor, Chief, Division of Pulmonary Diseases & Critical Care, UT Health San Antonio, Texas
Diego J. Maselli, MD, FCCP has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: GSK; AstraZeneca; Sanofi/Regeneron; Amgen
Received research grant from: Gates Foundation; COPD Foundation; NIH
The latest research on treatment of patients with COPD presented at the American Thoracic Society (ATS) 2024 annual meeting is reported on by Diego J. Maselli, MD, FCCP, CHEST Physician Editorial Board Member, from UT Health San Antonio in Texas.
Dr. Maselli discusses the phase 2a COURSE study, which looked at patients with moderate to severe COPD to determine whether novel tezepelumab would help reduce exacerbations over 52 weeks. The study reached a nonsignificant numerical reduction in the annual rate vs placebo, but Dr. Maselli suggests that outcomes in patients. with high blood eosinophil counts merit further study.
Next, Dr. Maselli discusses the phase 3 NOTUS trial, looking at the efficacy and safety of the monoclonal antibody dupilumab in patients with moderate to severe COPD. The researchers found a 34% reduction in exacerbations in the dupilumab group vs placebo after 52 weeks.
He then details a 272-patient study looking at nebulized ensifentrine, a dual inhibitor of PDE3 and PDE4. The study demonstrated improved lung function as well as a reduction in exacerbation rate to patients with moderate to severe COPD treated with ensifentrined added to long-acting beta agonists-inhaled corticosteroid maintenance therapy.
Finally, Dr. Maselli highlights the MAZI study, a large retrospective analysis comparing the mortality rate in patients with COPD taking single-inhaler triple therapy (SITT) vs multiple-inhaler triple therapy (MITT). The researchers found that SITT was superior to MITT.
--
Diego J. Maselli, MD, FCCP, Professor, Chief, Division of Pulmonary Diseases & Critical Care, UT Health San Antonio, Texas
Diego J. Maselli, MD, FCCP has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: GSK; AstraZeneca; Sanofi/Regeneron; Amgen
Received research grant from: Gates Foundation; COPD Foundation; NIH
The latest research on treatment of patients with COPD presented at the American Thoracic Society (ATS) 2024 annual meeting is reported on by Diego J. Maselli, MD, FCCP, CHEST Physician Editorial Board Member, from UT Health San Antonio in Texas.
Dr. Maselli discusses the phase 2a COURSE study, which looked at patients with moderate to severe COPD to determine whether novel tezepelumab would help reduce exacerbations over 52 weeks. The study reached a nonsignificant numerical reduction in the annual rate vs placebo, but Dr. Maselli suggests that outcomes in patients. with high blood eosinophil counts merit further study.
Next, Dr. Maselli discusses the phase 3 NOTUS trial, looking at the efficacy and safety of the monoclonal antibody dupilumab in patients with moderate to severe COPD. The researchers found a 34% reduction in exacerbations in the dupilumab group vs placebo after 52 weeks.
He then details a 272-patient study looking at nebulized ensifentrine, a dual inhibitor of PDE3 and PDE4. The study demonstrated improved lung function as well as a reduction in exacerbation rate to patients with moderate to severe COPD treated with ensifentrined added to long-acting beta agonists-inhaled corticosteroid maintenance therapy.
Finally, Dr. Maselli highlights the MAZI study, a large retrospective analysis comparing the mortality rate in patients with COPD taking single-inhaler triple therapy (SITT) vs multiple-inhaler triple therapy (MITT). The researchers found that SITT was superior to MITT.
--
Diego J. Maselli, MD, FCCP, Professor, Chief, Division of Pulmonary Diseases & Critical Care, UT Health San Antonio, Texas
Diego J. Maselli, MD, FCCP has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: GSK; AstraZeneca; Sanofi/Regeneron; Amgen
Received research grant from: Gates Foundation; COPD Foundation; NIH
Biologics May Improve Outcomes in Overlapping COPD and Asthma
Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.
Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.
Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.
In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
Reduction in Exacerbations and Hospitalizations
The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test).
In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.
Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.
The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.
“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.
The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.
“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
Data Support the Potential of Biologics for COPD
Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.
Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”
The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.
“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.
The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.
Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.
Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.
In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
Reduction in Exacerbations and Hospitalizations
The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test).
In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.
Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.
The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.
“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.
The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.
“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
Data Support the Potential of Biologics for COPD
Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.
Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”
The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.
“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.
The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.
Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.
Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.
In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
Reduction in Exacerbations and Hospitalizations
The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test).
In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.
Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.
The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.
“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.
The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.
“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
Data Support the Potential of Biologics for COPD
Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.
Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”
The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.
“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.
The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
FROM ATS 2024
Dupilumab May Reduce Exacerbations in COPD, Type 2 Inflammation
Dupilumab significantly reduced exacerbations and improved lung function in adults with uncontrolled chronic obstructive pulmonary disease (COPD) and type 2 inflammation, based on data from more than 900 individuals.
Data from a phase 3 trial known as NOTUS were presented at the American Thoracic Society’s international conference and published simultaneously in The New England Journal of Medicine.
Dupilumab, a fully human monoclonal antibody, works by inhibiting the signaling of the interleukin 4 (IL-4) and IL-13 pathways and is approved for many conditions characterized by type 2 inflammation, wrote Surya P. Bhatt, MD, of The University of Alabama at Birmingham, and colleagues in the NEJM study.
“Last year, we showed in the BOREAS trial that dupilumab was very effective in lowering exacerbation frequency in patients with COPD who continued to have frequent exacerbations despite being on maximal inhaled therapy,” Dr. Bhatt said in an interview.
12 Months of COPD, Triple Inhaler Therapy
In the NOTUS study, the researchers randomized 470 adults with uncontrolled COPD and type 2 inflammation (defined as a blood eosinophil count of ≥ 300 cells/µL) to 300-mg subcutaneous dupilumab and 465 to a placebo every 2 weeks. Patients were enrolled between July 2020 and May 2023.
The study population included adults aged 40-85 years with physician-diagnosed COPD for at least 12 months who had received background triple inhaler therapy (an inhaled glucocorticoid agent plus long-acting muscarinic antagonist [LAMA]–long-acting beta-agonist [LABA] or LAMA-LABA alone) for at least 3 months and at a stable dose for at least 1 month. All participants were current or former smokers with a smoking history of at least 10 pack-years.
The primary endpoint was a reduction in the annualized rate of moderate or severe COPD exacerbations at 52 weeks.
Patients in the dupilumab group also saw a significantly greater improvement in lung function compared with individuals in the placebo group based on prebronchodilator forced expiratory volume in 1 second from baseline to 12 weeks (least squares mean change of 139 mL vs 57 mL). This improvement was sustained at 52 weeks (least squares mean change of 115 mL vs 54 mL).
Improvement in respiratory symptom severity based on the St. George’s Respiratory Questionnaire was another secondary endpoint, and changes in total score were greater in the dupilumab group than in the placebo group (least squares mean change of 9.8 vs 6.4).
Safety outcomes were similar between the dupilumab and placebo groups, with approximately 66% of patients in each group reporting adverse events during the 52-week study period. Serious adverse events occurred in 13% and 15.9% of dupilumab and placebo patients, respectively, and adverse events resulting in death occurred in 2.6% and 1.5%, respectively. The most common adverse events were COVID-19, which occurred in 9.4% and 8.2% of the dupilumab and placebo patients, respectively, followed by headache, COPD, and nasopharyngitis. Major adverse cardiovascular events occurred in three patients in the dupilumab group and seven patients in the placebo group.
The findings were limited by several factors including the reduced sample size for 52-week endpoints because of the earlier analysis and the primarily White study population, the researchers noted. The study was conducted in part during the COVID-19 pandemic period, which contributed to healthcare disruptions and behavior changes that decreased exposure to viral respiratory infections, they wrote in their discussion. However, the results were strengthened by the large numbers and international population without other major pulmonary diseases, such as asthma, and the 34% reduction in exacerbations with dupilumab vs placebo is clinically significant, they said.
Data May Drive US Food and Drug Administration (FDA) Approval
In the BOREAS trial, dupilumab also improved lung function and quality of life, with no notable safety concerns. “As with any trial evaluating the efficacy and safety of a medication, it is important to confirm the findings in a replicative study,” said Dr. Bhatt. “With NOTUS, we confirmed the findings of BOREAS,” and the researchers were reassured by the substantial reduction in exacerbation frequency and the replication of key secondary outcomes, he said.
With the NOTUS study, “two randomized trials have now shown near identical reductions in exacerbation frequency in a difficult-to-treat population of patients with COPD with type 2 inflammation and frequent exacerbations,” as well as a significant and meaningful improvement in lung function, Dr. Bhatt said in an interview. “We hope these trials pave for the way for regulatory body approval of dupilumab for clinical use,” he said. Looking ahead, more studies are needed to test the potential disease modification effects of dupilumab in patients with COPD, he added.
Potential Change in Patient Management
Approximately 20%-40% of patients with COPD have type 2 inflammation with elevated blood eosinophil count, and this subset of patients has an increased risk for exacerbations, with worsening lung function and quality of life, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.
Prior phase 3 studies have shown that dupilumab, a blocker of IL-4 and IL-13 pathways, could effectively reduce exacerbations and improve lung function in these patients, and the NOTUS study aimed to confirm the findings in a larger, more diverse population, said Dr. Narendra, who was not involved in the study.
The NOTUS study represents a paradigm shift in the management of COPD patients with type 2 inflammation, said Narendra. “This study validates the previous BOREAS trial and has shown that dupilumab reduces exacerbations, improves lung function and quality of life, and potentially slows disease progression,” she said.
If approved, potential barriers to the use of dupilumab in practice include cost and insurance coverage, education and dissemination of study findings, and limited data on side effects, said Dr. Narendra.
“While the NOTUS study provides valuable insights into the efficacy and safety of dupilumab over 52 weeks, longer-term studies are needed to understand the sustained benefits and risks of continued treatment,” Dr. Narendra told this news organization. “Studies comparing dupilumab with other biological agents and newer COPD treatments could provide insights into its relative efficacy and position in treatment protocols,” she said.
In addition, further research into dupilumab’s underlying mechanisms could provide deeper insights into the pathophysiology of type 2 inflammation in COPD and inform the development of new treatments, Dr. Narendra said. “These steps will help integrate dupilumab more effectively into clinical practice and optimize its use for COPD patients with type 2 inflammation,” she noted.
Dupilumab is undergoing Priority Review by the FDA as an add-on maintenance therapy for adults with uncontrolled COPD and type 2 inflammation, with a target action date of June 27, 2024, according to a company press release.
The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Narendra had no financial conflicts to disclose but serves on the Editorial Advisory Board of CHEST Physician.
A version of this article appeared on Medscape.com.
Dupilumab significantly reduced exacerbations and improved lung function in adults with uncontrolled chronic obstructive pulmonary disease (COPD) and type 2 inflammation, based on data from more than 900 individuals.
Data from a phase 3 trial known as NOTUS were presented at the American Thoracic Society’s international conference and published simultaneously in The New England Journal of Medicine.
Dupilumab, a fully human monoclonal antibody, works by inhibiting the signaling of the interleukin 4 (IL-4) and IL-13 pathways and is approved for many conditions characterized by type 2 inflammation, wrote Surya P. Bhatt, MD, of The University of Alabama at Birmingham, and colleagues in the NEJM study.
“Last year, we showed in the BOREAS trial that dupilumab was very effective in lowering exacerbation frequency in patients with COPD who continued to have frequent exacerbations despite being on maximal inhaled therapy,” Dr. Bhatt said in an interview.
12 Months of COPD, Triple Inhaler Therapy
In the NOTUS study, the researchers randomized 470 adults with uncontrolled COPD and type 2 inflammation (defined as a blood eosinophil count of ≥ 300 cells/µL) to 300-mg subcutaneous dupilumab and 465 to a placebo every 2 weeks. Patients were enrolled between July 2020 and May 2023.
The study population included adults aged 40-85 years with physician-diagnosed COPD for at least 12 months who had received background triple inhaler therapy (an inhaled glucocorticoid agent plus long-acting muscarinic antagonist [LAMA]–long-acting beta-agonist [LABA] or LAMA-LABA alone) for at least 3 months and at a stable dose for at least 1 month. All participants were current or former smokers with a smoking history of at least 10 pack-years.
The primary endpoint was a reduction in the annualized rate of moderate or severe COPD exacerbations at 52 weeks.
Patients in the dupilumab group also saw a significantly greater improvement in lung function compared with individuals in the placebo group based on prebronchodilator forced expiratory volume in 1 second from baseline to 12 weeks (least squares mean change of 139 mL vs 57 mL). This improvement was sustained at 52 weeks (least squares mean change of 115 mL vs 54 mL).
Improvement in respiratory symptom severity based on the St. George’s Respiratory Questionnaire was another secondary endpoint, and changes in total score were greater in the dupilumab group than in the placebo group (least squares mean change of 9.8 vs 6.4).
Safety outcomes were similar between the dupilumab and placebo groups, with approximately 66% of patients in each group reporting adverse events during the 52-week study period. Serious adverse events occurred in 13% and 15.9% of dupilumab and placebo patients, respectively, and adverse events resulting in death occurred in 2.6% and 1.5%, respectively. The most common adverse events were COVID-19, which occurred in 9.4% and 8.2% of the dupilumab and placebo patients, respectively, followed by headache, COPD, and nasopharyngitis. Major adverse cardiovascular events occurred in three patients in the dupilumab group and seven patients in the placebo group.
The findings were limited by several factors including the reduced sample size for 52-week endpoints because of the earlier analysis and the primarily White study population, the researchers noted. The study was conducted in part during the COVID-19 pandemic period, which contributed to healthcare disruptions and behavior changes that decreased exposure to viral respiratory infections, they wrote in their discussion. However, the results were strengthened by the large numbers and international population without other major pulmonary diseases, such as asthma, and the 34% reduction in exacerbations with dupilumab vs placebo is clinically significant, they said.
Data May Drive US Food and Drug Administration (FDA) Approval
In the BOREAS trial, dupilumab also improved lung function and quality of life, with no notable safety concerns. “As with any trial evaluating the efficacy and safety of a medication, it is important to confirm the findings in a replicative study,” said Dr. Bhatt. “With NOTUS, we confirmed the findings of BOREAS,” and the researchers were reassured by the substantial reduction in exacerbation frequency and the replication of key secondary outcomes, he said.
With the NOTUS study, “two randomized trials have now shown near identical reductions in exacerbation frequency in a difficult-to-treat population of patients with COPD with type 2 inflammation and frequent exacerbations,” as well as a significant and meaningful improvement in lung function, Dr. Bhatt said in an interview. “We hope these trials pave for the way for regulatory body approval of dupilumab for clinical use,” he said. Looking ahead, more studies are needed to test the potential disease modification effects of dupilumab in patients with COPD, he added.
Potential Change in Patient Management
Approximately 20%-40% of patients with COPD have type 2 inflammation with elevated blood eosinophil count, and this subset of patients has an increased risk for exacerbations, with worsening lung function and quality of life, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.
Prior phase 3 studies have shown that dupilumab, a blocker of IL-4 and IL-13 pathways, could effectively reduce exacerbations and improve lung function in these patients, and the NOTUS study aimed to confirm the findings in a larger, more diverse population, said Dr. Narendra, who was not involved in the study.
The NOTUS study represents a paradigm shift in the management of COPD patients with type 2 inflammation, said Narendra. “This study validates the previous BOREAS trial and has shown that dupilumab reduces exacerbations, improves lung function and quality of life, and potentially slows disease progression,” she said.
If approved, potential barriers to the use of dupilumab in practice include cost and insurance coverage, education and dissemination of study findings, and limited data on side effects, said Dr. Narendra.
“While the NOTUS study provides valuable insights into the efficacy and safety of dupilumab over 52 weeks, longer-term studies are needed to understand the sustained benefits and risks of continued treatment,” Dr. Narendra told this news organization. “Studies comparing dupilumab with other biological agents and newer COPD treatments could provide insights into its relative efficacy and position in treatment protocols,” she said.
In addition, further research into dupilumab’s underlying mechanisms could provide deeper insights into the pathophysiology of type 2 inflammation in COPD and inform the development of new treatments, Dr. Narendra said. “These steps will help integrate dupilumab more effectively into clinical practice and optimize its use for COPD patients with type 2 inflammation,” she noted.
Dupilumab is undergoing Priority Review by the FDA as an add-on maintenance therapy for adults with uncontrolled COPD and type 2 inflammation, with a target action date of June 27, 2024, according to a company press release.
The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Narendra had no financial conflicts to disclose but serves on the Editorial Advisory Board of CHEST Physician.
A version of this article appeared on Medscape.com.
Dupilumab significantly reduced exacerbations and improved lung function in adults with uncontrolled chronic obstructive pulmonary disease (COPD) and type 2 inflammation, based on data from more than 900 individuals.
Data from a phase 3 trial known as NOTUS were presented at the American Thoracic Society’s international conference and published simultaneously in The New England Journal of Medicine.
Dupilumab, a fully human monoclonal antibody, works by inhibiting the signaling of the interleukin 4 (IL-4) and IL-13 pathways and is approved for many conditions characterized by type 2 inflammation, wrote Surya P. Bhatt, MD, of The University of Alabama at Birmingham, and colleagues in the NEJM study.
“Last year, we showed in the BOREAS trial that dupilumab was very effective in lowering exacerbation frequency in patients with COPD who continued to have frequent exacerbations despite being on maximal inhaled therapy,” Dr. Bhatt said in an interview.
12 Months of COPD, Triple Inhaler Therapy
In the NOTUS study, the researchers randomized 470 adults with uncontrolled COPD and type 2 inflammation (defined as a blood eosinophil count of ≥ 300 cells/µL) to 300-mg subcutaneous dupilumab and 465 to a placebo every 2 weeks. Patients were enrolled between July 2020 and May 2023.
The study population included adults aged 40-85 years with physician-diagnosed COPD for at least 12 months who had received background triple inhaler therapy (an inhaled glucocorticoid agent plus long-acting muscarinic antagonist [LAMA]–long-acting beta-agonist [LABA] or LAMA-LABA alone) for at least 3 months and at a stable dose for at least 1 month. All participants were current or former smokers with a smoking history of at least 10 pack-years.
The primary endpoint was a reduction in the annualized rate of moderate or severe COPD exacerbations at 52 weeks.
Patients in the dupilumab group also saw a significantly greater improvement in lung function compared with individuals in the placebo group based on prebronchodilator forced expiratory volume in 1 second from baseline to 12 weeks (least squares mean change of 139 mL vs 57 mL). This improvement was sustained at 52 weeks (least squares mean change of 115 mL vs 54 mL).
Improvement in respiratory symptom severity based on the St. George’s Respiratory Questionnaire was another secondary endpoint, and changes in total score were greater in the dupilumab group than in the placebo group (least squares mean change of 9.8 vs 6.4).
Safety outcomes were similar between the dupilumab and placebo groups, with approximately 66% of patients in each group reporting adverse events during the 52-week study period. Serious adverse events occurred in 13% and 15.9% of dupilumab and placebo patients, respectively, and adverse events resulting in death occurred in 2.6% and 1.5%, respectively. The most common adverse events were COVID-19, which occurred in 9.4% and 8.2% of the dupilumab and placebo patients, respectively, followed by headache, COPD, and nasopharyngitis. Major adverse cardiovascular events occurred in three patients in the dupilumab group and seven patients in the placebo group.
The findings were limited by several factors including the reduced sample size for 52-week endpoints because of the earlier analysis and the primarily White study population, the researchers noted. The study was conducted in part during the COVID-19 pandemic period, which contributed to healthcare disruptions and behavior changes that decreased exposure to viral respiratory infections, they wrote in their discussion. However, the results were strengthened by the large numbers and international population without other major pulmonary diseases, such as asthma, and the 34% reduction in exacerbations with dupilumab vs placebo is clinically significant, they said.
Data May Drive US Food and Drug Administration (FDA) Approval
In the BOREAS trial, dupilumab also improved lung function and quality of life, with no notable safety concerns. “As with any trial evaluating the efficacy and safety of a medication, it is important to confirm the findings in a replicative study,” said Dr. Bhatt. “With NOTUS, we confirmed the findings of BOREAS,” and the researchers were reassured by the substantial reduction in exacerbation frequency and the replication of key secondary outcomes, he said.
With the NOTUS study, “two randomized trials have now shown near identical reductions in exacerbation frequency in a difficult-to-treat population of patients with COPD with type 2 inflammation and frequent exacerbations,” as well as a significant and meaningful improvement in lung function, Dr. Bhatt said in an interview. “We hope these trials pave for the way for regulatory body approval of dupilumab for clinical use,” he said. Looking ahead, more studies are needed to test the potential disease modification effects of dupilumab in patients with COPD, he added.
Potential Change in Patient Management
Approximately 20%-40% of patients with COPD have type 2 inflammation with elevated blood eosinophil count, and this subset of patients has an increased risk for exacerbations, with worsening lung function and quality of life, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.
Prior phase 3 studies have shown that dupilumab, a blocker of IL-4 and IL-13 pathways, could effectively reduce exacerbations and improve lung function in these patients, and the NOTUS study aimed to confirm the findings in a larger, more diverse population, said Dr. Narendra, who was not involved in the study.
The NOTUS study represents a paradigm shift in the management of COPD patients with type 2 inflammation, said Narendra. “This study validates the previous BOREAS trial and has shown that dupilumab reduces exacerbations, improves lung function and quality of life, and potentially slows disease progression,” she said.
If approved, potential barriers to the use of dupilumab in practice include cost and insurance coverage, education and dissemination of study findings, and limited data on side effects, said Dr. Narendra.
“While the NOTUS study provides valuable insights into the efficacy and safety of dupilumab over 52 weeks, longer-term studies are needed to understand the sustained benefits and risks of continued treatment,” Dr. Narendra told this news organization. “Studies comparing dupilumab with other biological agents and newer COPD treatments could provide insights into its relative efficacy and position in treatment protocols,” she said.
In addition, further research into dupilumab’s underlying mechanisms could provide deeper insights into the pathophysiology of type 2 inflammation in COPD and inform the development of new treatments, Dr. Narendra said. “These steps will help integrate dupilumab more effectively into clinical practice and optimize its use for COPD patients with type 2 inflammation,” she noted.
Dupilumab is undergoing Priority Review by the FDA as an add-on maintenance therapy for adults with uncontrolled COPD and type 2 inflammation, with a target action date of June 27, 2024, according to a company press release.
The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Narendra had no financial conflicts to disclose but serves on the Editorial Advisory Board of CHEST Physician.
A version of this article appeared on Medscape.com.
FROM ATS 2024