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New Cancer Vaccines on the Horizon: Renewed Hope or Hype?
Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.
But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.
Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.
In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.
said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.
A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.
“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.
Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.
“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”
Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.
Then: Where We Were
Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.
In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.
Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”
In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”
Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.
In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.
In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.
That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.
In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.
And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.
But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.
When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.
But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.
Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.
“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”
A Turning Point?
Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.
Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.
Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.
Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.
Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.
“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.”
Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.
One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.
But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”
“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”
Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.
“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”
Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.
As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”
A version of this article first appeared on Medscape.com.
Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.
But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.
Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.
In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.
said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.
A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.
“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.
Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.
“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”
Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.
Then: Where We Were
Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.
In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.
Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”
In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”
Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.
In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.
In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.
That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.
In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.
And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.
But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.
When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.
But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.
Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.
“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”
A Turning Point?
Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.
Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.
Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.
Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.
Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.
“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.”
Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.
One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.
But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”
“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”
Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.
“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”
Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.
As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”
A version of this article first appeared on Medscape.com.
Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.
But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.
Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.
In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.
said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.
A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.
“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.
Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.
“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”
Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.
Then: Where We Were
Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.
In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.
Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”
In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”
Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.
In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.
In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.
That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.
In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.
And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.
But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.
When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.
But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.
Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.
“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”
A Turning Point?
Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.
Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.
Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.
Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.
Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.
“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.”
Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.
One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.
But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”
“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”
Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.
“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”
Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.
As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”
A version of this article first appeared on Medscape.com.
Mitigating risk of asthma emergencies during respiratory season
Respiratory illness, cold weather, and fluctuating temperatures can all exacerbate asthma symptoms, leading to potentially serious health complications. Understanding how to mitigate these risks is crucial for maintaining respiratory health and ensuring a safe and healthy season.
As schools across the US have just ended their fall semester, students of all ages will spend their time off away from school. Respiratory season is among us, and children with asthma are at risk for severe asthma exacerbation from viruses that may lead to hospitalization. Since students will soon return for their spring semester, it is important to be reminded of asthma care during respiratory season.
Ten percent of school-aged children in the US have a diagnosis of asthma, with a higher prevalence in lower socioeconomic populations. In a classroom of 30 students, three students carry an asthma diagnosis. Of these children, the National Institutes of Health (NIH) reports 60% will experience asthma exacerbations. These exacerbations not only cause patients with asthma to have a total of 13.8 million absences annually but also lead to approximately 767,000 emergency department visits and 74,000 hospitalizations on an annual basis.1
As we consider these statistics, safe asthma care during respiratory season requires preparation and a proactive approach. Partnering with families and school personnel will increase the likelihood that students will have a safe return for their next semester.
Patients with asthma are at higher risk for complications from respiratory illnesses such as COVID-19, influenza, respiratory syncytial virus (RSV), and streptococcal pneumonia viruses. While RSV vaccination is not widely available yet, vaccination is recommended as early as possible for influenza and COVID-19, as well as consideration for streptococcal pneumonia for patients with severe asthma. Vaccination for all family members should also be considered by the health care team. The health care team should regularly check in with families of patients with asthma to ensure they are educated about the importance of vaccinations and opportunities for immunization.2
Most children with asthma submit their asthma action plan to their school at the beginning of the year. It is important for families to be reminded that if there is a change to their asthma action plan, the updated plan should be discussed and reviewed with school personnel who are responsible for medication administration. Health care providers often will partner with schools and families to create a 504 plan. Many families may not be familiar with this plan and how to request one. Within the state of Illinois, for example, some school districts require 504 plans and others do not. It is derived from Section 504 of the Americans with Disabilities Act and is a contract outlining a child’s asthma care while at school. Families should be reminded that these 504 plans need to be updated at least once a school year.3
Asthma guidelines recommend all children with asthma have access to quick relief medications.4 While this guideline exists, we are reminded by families that their child oftentimes has difficulty obtaining their medication while at school. Despite stock albuterol programs considered by the NIH as being a safe, practical, and potentially lifesaving option for children with asthma, schools across the country are slow to adopt this practice.1 Families often express financial concern about accessing these medications, mainly due to insurance quantity limitations for either single maintenance and reliever therapy intervention or short-acting β2-agonist therapy.
While self-carry is an option in all 50 states and the District of Columbia, parents report poor memory and reliability of their child to administer their medication appropriately. Parents report their children have a poor understanding of time and may administer medication too frequently, or they lack the necessary dexterity to properly administer an inhaler. The correct use of inhalation devices and adherence to prescribed therapy are key aspects in achieving better clinical control and improved quality of life. Parents express fear associated with children having access but poor direct supervision when using their quick relief medication.5 Families need a minimum of two quick relief inhalers (one for home and one for school)—or even three in a co-parenting situation.
Stock albuterol programs mitigate the risk of quick relief medication accessibility. Families may have been required to leave a quick relief inhaler with the school nurse when school started last fall. Despite medication being available from a stock program or supplied from a family, medication expiration dates should be monitored to ensure the medication is available when needed.1 It is important to remind families to track the expiration of medication and request a refill from their asthma provider for replacement at school if a stock albuterol program is not available.
Mitigating the risk of asthma emergencies during respiratory season requires a proactive approach. By partnering with families and schools through vaccination, updating asthma action plans, creating 504 plans, and working to ensure quick relief medication is available, providers and families can work together to decrease the risk of asthma emergencies during respiratory season. Taking these steps can lead to a safer and healthier respiratory season for all.
Emily Simmons, MSN, APN, CPNP-PC, and Alexandra Kacena, MSN, APN, CPNP-PC, are advanced practice provider colleagues at Ann & Robert H. Lurie Children’s Hospital of Chicago, Division of Pulmonary & Sleep Medicine. Partnering with one of the attending pulmonologists, they provide evidence-based, state-of-the-art care to high-risk patients with severe asthma, both within the hospital and in a mobile asthma clinic setting.
References:
1. Lowe AA, Gerald JK, Clemens CJ, Stern DA, Gerald LB. Managing respiratory emergencies at school: a county-wide stock inhaler program. J Allergy Clin Immunol. 2021;148(2):420-427.e5. Preprint. Posted online February 10, 2021. doi: 10.1016/j.jaci.2021.01.028
2. 5 Reasons Why Children With Asthma Need Important Vaccines for the Back-to-School Season. Asthma and Allergy Foundation of America. https://community.aafa.org/blog/5-reasons-why-children-with-asthma-need-important-vaccines-before-heading-back-to-school
3. Dudvarski Ilic A, Zugic V, Zvezdin B, et al. Influence of inhaler technique on asthma and COPD control: a multicenter experience. Int J Chron Obstruct Pulmon Dis. 2016;11:2509-2517. doi: 10.2147/COPD.S114576
4. Volerman A, Lowe AA, Pappalardo AA, etc. Ensuring access to albuterol in schools: from policy to implementation. An official ATS/AANMA/ALA/NASN policy statement. Am J Respir Crit Care Med. 2021;204(5):508-522. doi: 10.1164/rccm.202106-1550ST
5. Volerman A, Kim TY, Sridharan G, et al. A mixed-methods study examining inhaler carry and use among children at school. J Asthma. 2020;57(10):1071-1082. Preprint. Posted online July 16, 2019. doi: 10.1080/02770903.2019.1640729
6. Toups MM, Press VG, Volerman A. National analysis of state health policies on students’ right to self-carry and self-administer asthma inhalers at school. J Sch Health. 2018;88(10):776-784. doi: 10.1111/josh.12681
7. 504 Plans for Asthma. Asthma and Allergy Foundation of America. https://aafa.org/asthma/living-with-asthma/504-plans-for-asthma/
Respiratory illness, cold weather, and fluctuating temperatures can all exacerbate asthma symptoms, leading to potentially serious health complications. Understanding how to mitigate these risks is crucial for maintaining respiratory health and ensuring a safe and healthy season.
As schools across the US have just ended their fall semester, students of all ages will spend their time off away from school. Respiratory season is among us, and children with asthma are at risk for severe asthma exacerbation from viruses that may lead to hospitalization. Since students will soon return for their spring semester, it is important to be reminded of asthma care during respiratory season.
Ten percent of school-aged children in the US have a diagnosis of asthma, with a higher prevalence in lower socioeconomic populations. In a classroom of 30 students, three students carry an asthma diagnosis. Of these children, the National Institutes of Health (NIH) reports 60% will experience asthma exacerbations. These exacerbations not only cause patients with asthma to have a total of 13.8 million absences annually but also lead to approximately 767,000 emergency department visits and 74,000 hospitalizations on an annual basis.1
As we consider these statistics, safe asthma care during respiratory season requires preparation and a proactive approach. Partnering with families and school personnel will increase the likelihood that students will have a safe return for their next semester.
Patients with asthma are at higher risk for complications from respiratory illnesses such as COVID-19, influenza, respiratory syncytial virus (RSV), and streptococcal pneumonia viruses. While RSV vaccination is not widely available yet, vaccination is recommended as early as possible for influenza and COVID-19, as well as consideration for streptococcal pneumonia for patients with severe asthma. Vaccination for all family members should also be considered by the health care team. The health care team should regularly check in with families of patients with asthma to ensure they are educated about the importance of vaccinations and opportunities for immunization.2
Most children with asthma submit their asthma action plan to their school at the beginning of the year. It is important for families to be reminded that if there is a change to their asthma action plan, the updated plan should be discussed and reviewed with school personnel who are responsible for medication administration. Health care providers often will partner with schools and families to create a 504 plan. Many families may not be familiar with this plan and how to request one. Within the state of Illinois, for example, some school districts require 504 plans and others do not. It is derived from Section 504 of the Americans with Disabilities Act and is a contract outlining a child’s asthma care while at school. Families should be reminded that these 504 plans need to be updated at least once a school year.3
Asthma guidelines recommend all children with asthma have access to quick relief medications.4 While this guideline exists, we are reminded by families that their child oftentimes has difficulty obtaining their medication while at school. Despite stock albuterol programs considered by the NIH as being a safe, practical, and potentially lifesaving option for children with asthma, schools across the country are slow to adopt this practice.1 Families often express financial concern about accessing these medications, mainly due to insurance quantity limitations for either single maintenance and reliever therapy intervention or short-acting β2-agonist therapy.
While self-carry is an option in all 50 states and the District of Columbia, parents report poor memory and reliability of their child to administer their medication appropriately. Parents report their children have a poor understanding of time and may administer medication too frequently, or they lack the necessary dexterity to properly administer an inhaler. The correct use of inhalation devices and adherence to prescribed therapy are key aspects in achieving better clinical control and improved quality of life. Parents express fear associated with children having access but poor direct supervision when using their quick relief medication.5 Families need a minimum of two quick relief inhalers (one for home and one for school)—or even three in a co-parenting situation.
Stock albuterol programs mitigate the risk of quick relief medication accessibility. Families may have been required to leave a quick relief inhaler with the school nurse when school started last fall. Despite medication being available from a stock program or supplied from a family, medication expiration dates should be monitored to ensure the medication is available when needed.1 It is important to remind families to track the expiration of medication and request a refill from their asthma provider for replacement at school if a stock albuterol program is not available.
Mitigating the risk of asthma emergencies during respiratory season requires a proactive approach. By partnering with families and schools through vaccination, updating asthma action plans, creating 504 plans, and working to ensure quick relief medication is available, providers and families can work together to decrease the risk of asthma emergencies during respiratory season. Taking these steps can lead to a safer and healthier respiratory season for all.
Emily Simmons, MSN, APN, CPNP-PC, and Alexandra Kacena, MSN, APN, CPNP-PC, are advanced practice provider colleagues at Ann & Robert H. Lurie Children’s Hospital of Chicago, Division of Pulmonary & Sleep Medicine. Partnering with one of the attending pulmonologists, they provide evidence-based, state-of-the-art care to high-risk patients with severe asthma, both within the hospital and in a mobile asthma clinic setting.
References:
1. Lowe AA, Gerald JK, Clemens CJ, Stern DA, Gerald LB. Managing respiratory emergencies at school: a county-wide stock inhaler program. J Allergy Clin Immunol. 2021;148(2):420-427.e5. Preprint. Posted online February 10, 2021. doi: 10.1016/j.jaci.2021.01.028
2. 5 Reasons Why Children With Asthma Need Important Vaccines for the Back-to-School Season. Asthma and Allergy Foundation of America. https://community.aafa.org/blog/5-reasons-why-children-with-asthma-need-important-vaccines-before-heading-back-to-school
3. Dudvarski Ilic A, Zugic V, Zvezdin B, et al. Influence of inhaler technique on asthma and COPD control: a multicenter experience. Int J Chron Obstruct Pulmon Dis. 2016;11:2509-2517. doi: 10.2147/COPD.S114576
4. Volerman A, Lowe AA, Pappalardo AA, etc. Ensuring access to albuterol in schools: from policy to implementation. An official ATS/AANMA/ALA/NASN policy statement. Am J Respir Crit Care Med. 2021;204(5):508-522. doi: 10.1164/rccm.202106-1550ST
5. Volerman A, Kim TY, Sridharan G, et al. A mixed-methods study examining inhaler carry and use among children at school. J Asthma. 2020;57(10):1071-1082. Preprint. Posted online July 16, 2019. doi: 10.1080/02770903.2019.1640729
6. Toups MM, Press VG, Volerman A. National analysis of state health policies on students’ right to self-carry and self-administer asthma inhalers at school. J Sch Health. 2018;88(10):776-784. doi: 10.1111/josh.12681
7. 504 Plans for Asthma. Asthma and Allergy Foundation of America. https://aafa.org/asthma/living-with-asthma/504-plans-for-asthma/
Respiratory illness, cold weather, and fluctuating temperatures can all exacerbate asthma symptoms, leading to potentially serious health complications. Understanding how to mitigate these risks is crucial for maintaining respiratory health and ensuring a safe and healthy season.
As schools across the US have just ended their fall semester, students of all ages will spend their time off away from school. Respiratory season is among us, and children with asthma are at risk for severe asthma exacerbation from viruses that may lead to hospitalization. Since students will soon return for their spring semester, it is important to be reminded of asthma care during respiratory season.
Ten percent of school-aged children in the US have a diagnosis of asthma, with a higher prevalence in lower socioeconomic populations. In a classroom of 30 students, three students carry an asthma diagnosis. Of these children, the National Institutes of Health (NIH) reports 60% will experience asthma exacerbations. These exacerbations not only cause patients with asthma to have a total of 13.8 million absences annually but also lead to approximately 767,000 emergency department visits and 74,000 hospitalizations on an annual basis.1
As we consider these statistics, safe asthma care during respiratory season requires preparation and a proactive approach. Partnering with families and school personnel will increase the likelihood that students will have a safe return for their next semester.
Patients with asthma are at higher risk for complications from respiratory illnesses such as COVID-19, influenza, respiratory syncytial virus (RSV), and streptococcal pneumonia viruses. While RSV vaccination is not widely available yet, vaccination is recommended as early as possible for influenza and COVID-19, as well as consideration for streptococcal pneumonia for patients with severe asthma. Vaccination for all family members should also be considered by the health care team. The health care team should regularly check in with families of patients with asthma to ensure they are educated about the importance of vaccinations and opportunities for immunization.2
Most children with asthma submit their asthma action plan to their school at the beginning of the year. It is important for families to be reminded that if there is a change to their asthma action plan, the updated plan should be discussed and reviewed with school personnel who are responsible for medication administration. Health care providers often will partner with schools and families to create a 504 plan. Many families may not be familiar with this plan and how to request one. Within the state of Illinois, for example, some school districts require 504 plans and others do not. It is derived from Section 504 of the Americans with Disabilities Act and is a contract outlining a child’s asthma care while at school. Families should be reminded that these 504 plans need to be updated at least once a school year.3
Asthma guidelines recommend all children with asthma have access to quick relief medications.4 While this guideline exists, we are reminded by families that their child oftentimes has difficulty obtaining their medication while at school. Despite stock albuterol programs considered by the NIH as being a safe, practical, and potentially lifesaving option for children with asthma, schools across the country are slow to adopt this practice.1 Families often express financial concern about accessing these medications, mainly due to insurance quantity limitations for either single maintenance and reliever therapy intervention or short-acting β2-agonist therapy.
While self-carry is an option in all 50 states and the District of Columbia, parents report poor memory and reliability of their child to administer their medication appropriately. Parents report their children have a poor understanding of time and may administer medication too frequently, or they lack the necessary dexterity to properly administer an inhaler. The correct use of inhalation devices and adherence to prescribed therapy are key aspects in achieving better clinical control and improved quality of life. Parents express fear associated with children having access but poor direct supervision when using their quick relief medication.5 Families need a minimum of two quick relief inhalers (one for home and one for school)—or even three in a co-parenting situation.
Stock albuterol programs mitigate the risk of quick relief medication accessibility. Families may have been required to leave a quick relief inhaler with the school nurse when school started last fall. Despite medication being available from a stock program or supplied from a family, medication expiration dates should be monitored to ensure the medication is available when needed.1 It is important to remind families to track the expiration of medication and request a refill from their asthma provider for replacement at school if a stock albuterol program is not available.
Mitigating the risk of asthma emergencies during respiratory season requires a proactive approach. By partnering with families and schools through vaccination, updating asthma action plans, creating 504 plans, and working to ensure quick relief medication is available, providers and families can work together to decrease the risk of asthma emergencies during respiratory season. Taking these steps can lead to a safer and healthier respiratory season for all.
Emily Simmons, MSN, APN, CPNP-PC, and Alexandra Kacena, MSN, APN, CPNP-PC, are advanced practice provider colleagues at Ann & Robert H. Lurie Children’s Hospital of Chicago, Division of Pulmonary & Sleep Medicine. Partnering with one of the attending pulmonologists, they provide evidence-based, state-of-the-art care to high-risk patients with severe asthma, both within the hospital and in a mobile asthma clinic setting.
References:
1. Lowe AA, Gerald JK, Clemens CJ, Stern DA, Gerald LB. Managing respiratory emergencies at school: a county-wide stock inhaler program. J Allergy Clin Immunol. 2021;148(2):420-427.e5. Preprint. Posted online February 10, 2021. doi: 10.1016/j.jaci.2021.01.028
2. 5 Reasons Why Children With Asthma Need Important Vaccines for the Back-to-School Season. Asthma and Allergy Foundation of America. https://community.aafa.org/blog/5-reasons-why-children-with-asthma-need-important-vaccines-before-heading-back-to-school
3. Dudvarski Ilic A, Zugic V, Zvezdin B, et al. Influence of inhaler technique on asthma and COPD control: a multicenter experience. Int J Chron Obstruct Pulmon Dis. 2016;11:2509-2517. doi: 10.2147/COPD.S114576
4. Volerman A, Lowe AA, Pappalardo AA, etc. Ensuring access to albuterol in schools: from policy to implementation. An official ATS/AANMA/ALA/NASN policy statement. Am J Respir Crit Care Med. 2021;204(5):508-522. doi: 10.1164/rccm.202106-1550ST
5. Volerman A, Kim TY, Sridharan G, et al. A mixed-methods study examining inhaler carry and use among children at school. J Asthma. 2020;57(10):1071-1082. Preprint. Posted online July 16, 2019. doi: 10.1080/02770903.2019.1640729
6. Toups MM, Press VG, Volerman A. National analysis of state health policies on students’ right to self-carry and self-administer asthma inhalers at school. J Sch Health. 2018;88(10):776-784. doi: 10.1111/josh.12681
7. 504 Plans for Asthma. Asthma and Allergy Foundation of America. https://aafa.org/asthma/living-with-asthma/504-plans-for-asthma/
Navigating new ACR/CHEST guidelines for screening, monitoring, and treatment of SARD-ILD
Interstitial lung disease (ILD) is a frequent complication of systemic autoimmune rheumatic diseases (SARDs) associated with considerable morbidity and mortality.1 The risk of ILD, however, is higher in a subset of SARDs—rheumatoid arthritis (RA), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), mixed connective tissue disease (MCTD), and Sjögren’s disease (SjD). Accordingly, the American College of Rheumatology (ACR) and American College of Chest Physicians (CHEST) jointly endorsed the recent publication of two separate guidelines detailing recommendations for (1) screening and monitoring and (2) treatment of ILD in adults with SARDs.2,3 These guidelines mark the first of their kind, aiming to promote multidisciplinary collaboration and comprehensive, standardized care. Below, we summarize the major highlights from these guidelines.
Screening and monitoring
For patients with SARD, who should be screened for ILD and how?
The prevalence of ILD is not equally distributed amongst those with SARDs, and the heterogeneity poses a challenge when creating guidelines applicable to all.4 The ACR/CHEST guidelines focus on recommendations for those with SARDs at highest risk of ILD (RA, SSc, IIM, MCTD, and SjD), while excluding pediatric SARDs, sarcoidosis, interstitial pneumonia with autoimmune features, vasculitides, systemic lupus erythematosus, and unclassifiable ILD.2,3 As the guidelines’ recommendations are all conditional and based on low-quality evidence, an individualized ILD screening approach should be implemented for patients with SARDs with regard to risk.
For patients with these high-risk SARDs, screening for ILD with pulmonary function testing (PFT) and high-resolution chest tomography (HRCT) is conditionally recommended at the time of diagnosis. This recommendation was founded on observational studies showing PFTs have low sensitivity and high specificity while HRCT has high sensitivity and low specificity for detection of ILD. The combination was also favored, as it provides complementary information on functional impact (PFTs) and radiologic pattern (HRCT).
The guideline committee conditionally recommended against several routine tests due to poor performance—chest radiography, six-minute walk distance, ambulatory desaturation testing, and bronchoscopy. There was a strong recommendation against pursuing surgical lung biopsy due to high-quality evidence for harm and low-quality evidence for benefit. If initial screening is negative, repeat screening is left to the discretion of the treating physician; nevertheless, for patients with high-risk features, yearly rescreening should be considered through shared decision-making.
How should patients with SARD-ILD be monitored?
Disease monitoring following a SARD-ILD diagnosis is important. PFTs and HRCT were conditionally recommended over PFTs alone; however, the consensus was that HRCT should be less frequent than PFTs. Ambulatory desaturation monitoring was also conditionally recommended. The committee conditionally recommended against chest radiography, six-minute walk distance, and bronchoscopy for screening.
The frequency of monitoring should be guided by patient symptoms, risk profile, and treatment response due to substantial clinical variation. For this reason, the committee made suggestions only to steer clinicians. For patients with IIM-ILD and SSc-ILD, more frequent PFT monitoring was suggested given the high risk of early, aggressive disease. For all SARD-ILDs, more frequent PFT monitoring was suggested early after diagnosis; less frequent testing should be considered for those with stable disease. No suggestion regarding the frequency of monitoring with HRCT was made; however, HRCT may be useful as a complementary test to PFTs in situations of uncertainty.
Treatment
First-line treatment
What are considerations when using glucocorticoids in patients with SARD-ILD?
The decision to treat SARD-ILD should incorporate patient symptoms, disease activity, risk of progression, and goals of care. For almost all SARD-ILDs, short-term glucocorticoids (ie, <3 months) are considered first-line treatment. The exception is SSc-ILD, for which there is a strong recommendation against glucocorticoids as first-line therapy due to concern for precipitating scleroderma renal crisis. Similarly, glucocorticoids should be used cautiously in those patients with MCTD and SSc features or IIM-ILD with SSc antibodies, though they are not strictly contraindicated.
What are the recommended options for a steroid-sparing approach?
An important goal in the treatment of SARD-ILD is tapering off glucocorticoids to avoid toxicity. Steroid-sparing is used for those requiring long-term immunosuppression. Considerations when choosing steroid-sparing agents include contraindications, side-effect profile, and effect on active extrapulmonary symptoms.
The committee conditionally recommended a hierarchy of first-line steroid-sparing agents via a voting consensus. Mycophenolate was conditionally recommended as the preferred agent in all SARD-ILDs for several reasons: (1) positive outcomes in trials of SSc-ILD, (2) additional limited data in other SARDs, (3) favorable side-effect profile, and (4) physicians’ familiarity. Multiple other first-line agents were recommended by disease type. These are summarized in Figure 1.
Progression on first-line treatment
What are considerations for patients with progression despite first-line ILD treatment?
The goal of first-line treatment is to improve or stabilize lung function and symptoms. Unfortunately, some patients with SARD-ILD will progress despite appropriate first-line therapy. Progression of ILD was defined using criteria from the INBUILD trial—a decline in FVC >10% predicted or a FVC decline between 5% and 10% accompanied by worsening respiratory symptoms or radiologic fibrosis within a 24-month period.5 When progression is diagnosed, the goal is to add on or switch to an agent based on patient-specific factors or preferences.
Short-term steroids may have a role, particularly if a patient is experiencing an acute exacerbation; however, long-term steroid therapy (at least three to six months) is not recommended. For those who are on full-dose, first-line therapy but still progressing, addition of an alternative agent should be considered. In some instances, addition of an antifibrotic agent is recommended. If progression continues despite multiple agents, referral for lung transplantation should be discussed.
What are some of the management options for patients with rapidly progressive ILD?
Rapidly progressive (RP)-ILD is considered when a patient exhibits rapid progression in supplemental oxygen needs within days to weeks without an alternative cause. First-line treatment is typically pulse IV methylprednisolone in addition to one to two other immunosuppressive medications; nonsteroidal immunosuppressive options include rituximab, cyclophosphamide, IV immunoglobulin, tacrolimus, mycophenolate, or Janus kinase inhibitors. The guidelines conditionally recommend double or triple therapy for most patients with SARD and RP-ILD (combination of steroids and one or two of the listed agents). For patients with confirmed or suspected anti-melanoma differentiation-associated gene 5 (MDA-5) RP-ILD, triple therapy is conditionally recommended (steroids and two additional agents) due to substantial risk of death. Of note, for patients with SSc and RP-ILD, there is no consensus on whether corticosteroids should be used. Treatment selection ultimately depends on disease severity, concern for infection, and suspected or confirmed MDA-5 RP-ILD. Finally, the committee recommended early referral for lung transplantation for patients whose disease progresses while on optimal medical treatment.
Conclusion
SARDs represent a diverse group of rheumatologic diseases associated with high risk of ILD. The ACR/CHEST guidelines are a first attempt to provide clinicians with evidence-based recommendations for screening, monitoring, and treatment of SARD-ILD. They represent an essential tool for management of SARD-ILD . The studies utilized to create them were mostly observational, and none had examined the relationship between disease screening, monitoring, and patient-centered outcomes. As a result, the recommendations are largely conditional. Additional studies are needed to examine the impact of surveillance in different populations, determine risk factors for RP-ILD in patients with SARD, and further investigate the most effective treatments.
Dr. Castellanos and Dr. Esposito are with the Division of Pulmonary and Critical Care, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. Dr. Zhao is with the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
References
1. Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet. 2012;380(9842):689-698.
2. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1070-1082.
3. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1051-1069.
4. Jeganathan N, Sathananthan M. Connective tissue disease-related interstitial lung disease: prevalence, patterns, predictors, prognosis, and treatment. Lung. 2020;198(5):735-759.
5. Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727.
Interstitial lung disease (ILD) is a frequent complication of systemic autoimmune rheumatic diseases (SARDs) associated with considerable morbidity and mortality.1 The risk of ILD, however, is higher in a subset of SARDs—rheumatoid arthritis (RA), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), mixed connective tissue disease (MCTD), and Sjögren’s disease (SjD). Accordingly, the American College of Rheumatology (ACR) and American College of Chest Physicians (CHEST) jointly endorsed the recent publication of two separate guidelines detailing recommendations for (1) screening and monitoring and (2) treatment of ILD in adults with SARDs.2,3 These guidelines mark the first of their kind, aiming to promote multidisciplinary collaboration and comprehensive, standardized care. Below, we summarize the major highlights from these guidelines.
Screening and monitoring
For patients with SARD, who should be screened for ILD and how?
The prevalence of ILD is not equally distributed amongst those with SARDs, and the heterogeneity poses a challenge when creating guidelines applicable to all.4 The ACR/CHEST guidelines focus on recommendations for those with SARDs at highest risk of ILD (RA, SSc, IIM, MCTD, and SjD), while excluding pediatric SARDs, sarcoidosis, interstitial pneumonia with autoimmune features, vasculitides, systemic lupus erythematosus, and unclassifiable ILD.2,3 As the guidelines’ recommendations are all conditional and based on low-quality evidence, an individualized ILD screening approach should be implemented for patients with SARDs with regard to risk.
For patients with these high-risk SARDs, screening for ILD with pulmonary function testing (PFT) and high-resolution chest tomography (HRCT) is conditionally recommended at the time of diagnosis. This recommendation was founded on observational studies showing PFTs have low sensitivity and high specificity while HRCT has high sensitivity and low specificity for detection of ILD. The combination was also favored, as it provides complementary information on functional impact (PFTs) and radiologic pattern (HRCT).
The guideline committee conditionally recommended against several routine tests due to poor performance—chest radiography, six-minute walk distance, ambulatory desaturation testing, and bronchoscopy. There was a strong recommendation against pursuing surgical lung biopsy due to high-quality evidence for harm and low-quality evidence for benefit. If initial screening is negative, repeat screening is left to the discretion of the treating physician; nevertheless, for patients with high-risk features, yearly rescreening should be considered through shared decision-making.
How should patients with SARD-ILD be monitored?
Disease monitoring following a SARD-ILD diagnosis is important. PFTs and HRCT were conditionally recommended over PFTs alone; however, the consensus was that HRCT should be less frequent than PFTs. Ambulatory desaturation monitoring was also conditionally recommended. The committee conditionally recommended against chest radiography, six-minute walk distance, and bronchoscopy for screening.
The frequency of monitoring should be guided by patient symptoms, risk profile, and treatment response due to substantial clinical variation. For this reason, the committee made suggestions only to steer clinicians. For patients with IIM-ILD and SSc-ILD, more frequent PFT monitoring was suggested given the high risk of early, aggressive disease. For all SARD-ILDs, more frequent PFT monitoring was suggested early after diagnosis; less frequent testing should be considered for those with stable disease. No suggestion regarding the frequency of monitoring with HRCT was made; however, HRCT may be useful as a complementary test to PFTs in situations of uncertainty.
Treatment
First-line treatment
What are considerations when using glucocorticoids in patients with SARD-ILD?
The decision to treat SARD-ILD should incorporate patient symptoms, disease activity, risk of progression, and goals of care. For almost all SARD-ILDs, short-term glucocorticoids (ie, <3 months) are considered first-line treatment. The exception is SSc-ILD, for which there is a strong recommendation against glucocorticoids as first-line therapy due to concern for precipitating scleroderma renal crisis. Similarly, glucocorticoids should be used cautiously in those patients with MCTD and SSc features or IIM-ILD with SSc antibodies, though they are not strictly contraindicated.
What are the recommended options for a steroid-sparing approach?
An important goal in the treatment of SARD-ILD is tapering off glucocorticoids to avoid toxicity. Steroid-sparing is used for those requiring long-term immunosuppression. Considerations when choosing steroid-sparing agents include contraindications, side-effect profile, and effect on active extrapulmonary symptoms.
The committee conditionally recommended a hierarchy of first-line steroid-sparing agents via a voting consensus. Mycophenolate was conditionally recommended as the preferred agent in all SARD-ILDs for several reasons: (1) positive outcomes in trials of SSc-ILD, (2) additional limited data in other SARDs, (3) favorable side-effect profile, and (4) physicians’ familiarity. Multiple other first-line agents were recommended by disease type. These are summarized in Figure 1.
Progression on first-line treatment
What are considerations for patients with progression despite first-line ILD treatment?
The goal of first-line treatment is to improve or stabilize lung function and symptoms. Unfortunately, some patients with SARD-ILD will progress despite appropriate first-line therapy. Progression of ILD was defined using criteria from the INBUILD trial—a decline in FVC >10% predicted or a FVC decline between 5% and 10% accompanied by worsening respiratory symptoms or radiologic fibrosis within a 24-month period.5 When progression is diagnosed, the goal is to add on or switch to an agent based on patient-specific factors or preferences.
Short-term steroids may have a role, particularly if a patient is experiencing an acute exacerbation; however, long-term steroid therapy (at least three to six months) is not recommended. For those who are on full-dose, first-line therapy but still progressing, addition of an alternative agent should be considered. In some instances, addition of an antifibrotic agent is recommended. If progression continues despite multiple agents, referral for lung transplantation should be discussed.
What are some of the management options for patients with rapidly progressive ILD?
Rapidly progressive (RP)-ILD is considered when a patient exhibits rapid progression in supplemental oxygen needs within days to weeks without an alternative cause. First-line treatment is typically pulse IV methylprednisolone in addition to one to two other immunosuppressive medications; nonsteroidal immunosuppressive options include rituximab, cyclophosphamide, IV immunoglobulin, tacrolimus, mycophenolate, or Janus kinase inhibitors. The guidelines conditionally recommend double or triple therapy for most patients with SARD and RP-ILD (combination of steroids and one or two of the listed agents). For patients with confirmed or suspected anti-melanoma differentiation-associated gene 5 (MDA-5) RP-ILD, triple therapy is conditionally recommended (steroids and two additional agents) due to substantial risk of death. Of note, for patients with SSc and RP-ILD, there is no consensus on whether corticosteroids should be used. Treatment selection ultimately depends on disease severity, concern for infection, and suspected or confirmed MDA-5 RP-ILD. Finally, the committee recommended early referral for lung transplantation for patients whose disease progresses while on optimal medical treatment.
Conclusion
SARDs represent a diverse group of rheumatologic diseases associated with high risk of ILD. The ACR/CHEST guidelines are a first attempt to provide clinicians with evidence-based recommendations for screening, monitoring, and treatment of SARD-ILD. They represent an essential tool for management of SARD-ILD . The studies utilized to create them were mostly observational, and none had examined the relationship between disease screening, monitoring, and patient-centered outcomes. As a result, the recommendations are largely conditional. Additional studies are needed to examine the impact of surveillance in different populations, determine risk factors for RP-ILD in patients with SARD, and further investigate the most effective treatments.
Dr. Castellanos and Dr. Esposito are with the Division of Pulmonary and Critical Care, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. Dr. Zhao is with the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
References
1. Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet. 2012;380(9842):689-698.
2. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1070-1082.
3. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1051-1069.
4. Jeganathan N, Sathananthan M. Connective tissue disease-related interstitial lung disease: prevalence, patterns, predictors, prognosis, and treatment. Lung. 2020;198(5):735-759.
5. Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727.
Interstitial lung disease (ILD) is a frequent complication of systemic autoimmune rheumatic diseases (SARDs) associated with considerable morbidity and mortality.1 The risk of ILD, however, is higher in a subset of SARDs—rheumatoid arthritis (RA), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), mixed connective tissue disease (MCTD), and Sjögren’s disease (SjD). Accordingly, the American College of Rheumatology (ACR) and American College of Chest Physicians (CHEST) jointly endorsed the recent publication of two separate guidelines detailing recommendations for (1) screening and monitoring and (2) treatment of ILD in adults with SARDs.2,3 These guidelines mark the first of their kind, aiming to promote multidisciplinary collaboration and comprehensive, standardized care. Below, we summarize the major highlights from these guidelines.
Screening and monitoring
For patients with SARD, who should be screened for ILD and how?
The prevalence of ILD is not equally distributed amongst those with SARDs, and the heterogeneity poses a challenge when creating guidelines applicable to all.4 The ACR/CHEST guidelines focus on recommendations for those with SARDs at highest risk of ILD (RA, SSc, IIM, MCTD, and SjD), while excluding pediatric SARDs, sarcoidosis, interstitial pneumonia with autoimmune features, vasculitides, systemic lupus erythematosus, and unclassifiable ILD.2,3 As the guidelines’ recommendations are all conditional and based on low-quality evidence, an individualized ILD screening approach should be implemented for patients with SARDs with regard to risk.
For patients with these high-risk SARDs, screening for ILD with pulmonary function testing (PFT) and high-resolution chest tomography (HRCT) is conditionally recommended at the time of diagnosis. This recommendation was founded on observational studies showing PFTs have low sensitivity and high specificity while HRCT has high sensitivity and low specificity for detection of ILD. The combination was also favored, as it provides complementary information on functional impact (PFTs) and radiologic pattern (HRCT).
The guideline committee conditionally recommended against several routine tests due to poor performance—chest radiography, six-minute walk distance, ambulatory desaturation testing, and bronchoscopy. There was a strong recommendation against pursuing surgical lung biopsy due to high-quality evidence for harm and low-quality evidence for benefit. If initial screening is negative, repeat screening is left to the discretion of the treating physician; nevertheless, for patients with high-risk features, yearly rescreening should be considered through shared decision-making.
How should patients with SARD-ILD be monitored?
Disease monitoring following a SARD-ILD diagnosis is important. PFTs and HRCT were conditionally recommended over PFTs alone; however, the consensus was that HRCT should be less frequent than PFTs. Ambulatory desaturation monitoring was also conditionally recommended. The committee conditionally recommended against chest radiography, six-minute walk distance, and bronchoscopy for screening.
The frequency of monitoring should be guided by patient symptoms, risk profile, and treatment response due to substantial clinical variation. For this reason, the committee made suggestions only to steer clinicians. For patients with IIM-ILD and SSc-ILD, more frequent PFT monitoring was suggested given the high risk of early, aggressive disease. For all SARD-ILDs, more frequent PFT monitoring was suggested early after diagnosis; less frequent testing should be considered for those with stable disease. No suggestion regarding the frequency of monitoring with HRCT was made; however, HRCT may be useful as a complementary test to PFTs in situations of uncertainty.
Treatment
First-line treatment
What are considerations when using glucocorticoids in patients with SARD-ILD?
The decision to treat SARD-ILD should incorporate patient symptoms, disease activity, risk of progression, and goals of care. For almost all SARD-ILDs, short-term glucocorticoids (ie, <3 months) are considered first-line treatment. The exception is SSc-ILD, for which there is a strong recommendation against glucocorticoids as first-line therapy due to concern for precipitating scleroderma renal crisis. Similarly, glucocorticoids should be used cautiously in those patients with MCTD and SSc features or IIM-ILD with SSc antibodies, though they are not strictly contraindicated.
What are the recommended options for a steroid-sparing approach?
An important goal in the treatment of SARD-ILD is tapering off glucocorticoids to avoid toxicity. Steroid-sparing is used for those requiring long-term immunosuppression. Considerations when choosing steroid-sparing agents include contraindications, side-effect profile, and effect on active extrapulmonary symptoms.
The committee conditionally recommended a hierarchy of first-line steroid-sparing agents via a voting consensus. Mycophenolate was conditionally recommended as the preferred agent in all SARD-ILDs for several reasons: (1) positive outcomes in trials of SSc-ILD, (2) additional limited data in other SARDs, (3) favorable side-effect profile, and (4) physicians’ familiarity. Multiple other first-line agents were recommended by disease type. These are summarized in Figure 1.
Progression on first-line treatment
What are considerations for patients with progression despite first-line ILD treatment?
The goal of first-line treatment is to improve or stabilize lung function and symptoms. Unfortunately, some patients with SARD-ILD will progress despite appropriate first-line therapy. Progression of ILD was defined using criteria from the INBUILD trial—a decline in FVC >10% predicted or a FVC decline between 5% and 10% accompanied by worsening respiratory symptoms or radiologic fibrosis within a 24-month period.5 When progression is diagnosed, the goal is to add on or switch to an agent based on patient-specific factors or preferences.
Short-term steroids may have a role, particularly if a patient is experiencing an acute exacerbation; however, long-term steroid therapy (at least three to six months) is not recommended. For those who are on full-dose, first-line therapy but still progressing, addition of an alternative agent should be considered. In some instances, addition of an antifibrotic agent is recommended. If progression continues despite multiple agents, referral for lung transplantation should be discussed.
What are some of the management options for patients with rapidly progressive ILD?
Rapidly progressive (RP)-ILD is considered when a patient exhibits rapid progression in supplemental oxygen needs within days to weeks without an alternative cause. First-line treatment is typically pulse IV methylprednisolone in addition to one to two other immunosuppressive medications; nonsteroidal immunosuppressive options include rituximab, cyclophosphamide, IV immunoglobulin, tacrolimus, mycophenolate, or Janus kinase inhibitors. The guidelines conditionally recommend double or triple therapy for most patients with SARD and RP-ILD (combination of steroids and one or two of the listed agents). For patients with confirmed or suspected anti-melanoma differentiation-associated gene 5 (MDA-5) RP-ILD, triple therapy is conditionally recommended (steroids and two additional agents) due to substantial risk of death. Of note, for patients with SSc and RP-ILD, there is no consensus on whether corticosteroids should be used. Treatment selection ultimately depends on disease severity, concern for infection, and suspected or confirmed MDA-5 RP-ILD. Finally, the committee recommended early referral for lung transplantation for patients whose disease progresses while on optimal medical treatment.
Conclusion
SARDs represent a diverse group of rheumatologic diseases associated with high risk of ILD. The ACR/CHEST guidelines are a first attempt to provide clinicians with evidence-based recommendations for screening, monitoring, and treatment of SARD-ILD. They represent an essential tool for management of SARD-ILD . The studies utilized to create them were mostly observational, and none had examined the relationship between disease screening, monitoring, and patient-centered outcomes. As a result, the recommendations are largely conditional. Additional studies are needed to examine the impact of surveillance in different populations, determine risk factors for RP-ILD in patients with SARD, and further investigate the most effective treatments.
Dr. Castellanos and Dr. Esposito are with the Division of Pulmonary and Critical Care, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. Dr. Zhao is with the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
References
1. Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet. 2012;380(9842):689-698.
2. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1070-1082.
3. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1051-1069.
4. Jeganathan N, Sathananthan M. Connective tissue disease-related interstitial lung disease: prevalence, patterns, predictors, prognosis, and treatment. Lung. 2020;198(5):735-759.
5. Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727.
Top reads from the CHEST journal portfolio
Top reads from the CHEST journal portfolio
Journal CHEST®
Nocturnal Cardiac Arrhythmias in Heart Failure With Obstructive and Central Sleep Apnea
By Christian M. Horvath, MD, and colleagues
Horvath et al’s ancillary analysis to the ADVENT-HF trial highlights a significant association between sleep apnea (OSA and CSA) and increased nocturnal cardiac arrhythmias in heart failure patients with reduced ejection fraction (HFrEF). While ADVENT-HF showed no impact of adaptive servo-ventilation on survival and hospitalization, this subanalysis reveals a higher prevalence of arrhythmias, such as excessive supraventricular ectopic activity and atrial fibrillation/flutter (AF), in these patients. Notably, OSA severity was linked to increased atrial ectopy, though not to persistent arrhythmias like AF, contrasting with prior studies, notably from the Sleep Heart Health Study (Mehra et al, AJRCCM. 2006;173(8)). This suggests a complex interplay between OSA/CSA and AF, perhaps mediated by factors such as sympathetic tone and cardiac remodeling. Clinically, these findings underscore the value of targeted sleep apnea screening in patients with HFrEF and suggest the need for individualized arrhythmia risk profiles. Future research should investigate how additional factors mediate sleep apnea’s arrhythmic impact.
– Commentary by Shyam Subramanian, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
Improving Spontaneous Breathing Trials With a Respiratory Therapist-Driven Protocol
By Christopher A. Linke, RN, MHI, CSSBB, and colleagues
Use of respiratory therapist (RT)-driven spontaneous breathing trial (SBT) protocols are known to improve patient outcomes related to extubation from mechanical ventilation. The authors of this study asked whether an RT-driven SBT protocol could be consistently implemented and sustained to improve outcomes. This single-site quality improvement (QI) project aimed to standardize and re-establish an RT-driven protocol for screening patients for SBT readiness and administering SBTs to appropriate patients in an academic ICU. One hundred twenty-eight patients representing 759 safety screen weaning assessment opportunities were included over a baseline sample and three plan-do-study-act (PDSA) cycles. A key takeaway from this QI project is that consistent use of an RT-driven SBT protocol results in improved use and documentation of an SBT safety screening and completion of an SBT earlier in the day. Despite multiple obstacles, including staffing and communication challenges and poor understanding of terminology, standardization of an RT-driven SBT protocol is achievable.
– Commentary by Mary Jo Farmer, MD, PhD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Pulmonary
Navigational Bronchoscopy vs CT Scan-Guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules
By Robert J. Lentz, MD, and colleagues
, which will evaluate navigational bronchoscopy (NB) and CT-guided transthoracic needle biopsy (CT-TTNB) for diagnosing indeterminate pulmonary nodules. Although the results are not yet available, this group’s work highlights an emphasis to develop multicenter randomized controlled trials with multidisciplinary teams and clinical impactful data with a primary outcome of diagnostic accuracy (diagnostic results that remain accurate through 12 months of clinical follow-up). If NB proves to be a noninferior alternative to CT-TTNB, then it may be a safer option with a lower complication rate (particularly for pneumothorax). We look forward to the final results from the trial, and future studies incorporating newer technologies, including robotic bronchoscopy, will be a welcome adjunct as well.
– Commentary by Saadia A. Faiz, MD, FCCP, Member of the CHEST Physician Editorial Board
Journal CHEST®
Nocturnal Cardiac Arrhythmias in Heart Failure With Obstructive and Central Sleep Apnea
By Christian M. Horvath, MD, and colleagues
Horvath et al’s ancillary analysis to the ADVENT-HF trial highlights a significant association between sleep apnea (OSA and CSA) and increased nocturnal cardiac arrhythmias in heart failure patients with reduced ejection fraction (HFrEF). While ADVENT-HF showed no impact of adaptive servo-ventilation on survival and hospitalization, this subanalysis reveals a higher prevalence of arrhythmias, such as excessive supraventricular ectopic activity and atrial fibrillation/flutter (AF), in these patients. Notably, OSA severity was linked to increased atrial ectopy, though not to persistent arrhythmias like AF, contrasting with prior studies, notably from the Sleep Heart Health Study (Mehra et al, AJRCCM. 2006;173(8)). This suggests a complex interplay between OSA/CSA and AF, perhaps mediated by factors such as sympathetic tone and cardiac remodeling. Clinically, these findings underscore the value of targeted sleep apnea screening in patients with HFrEF and suggest the need for individualized arrhythmia risk profiles. Future research should investigate how additional factors mediate sleep apnea’s arrhythmic impact.
– Commentary by Shyam Subramanian, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
Improving Spontaneous Breathing Trials With a Respiratory Therapist-Driven Protocol
By Christopher A. Linke, RN, MHI, CSSBB, and colleagues
Use of respiratory therapist (RT)-driven spontaneous breathing trial (SBT) protocols are known to improve patient outcomes related to extubation from mechanical ventilation. The authors of this study asked whether an RT-driven SBT protocol could be consistently implemented and sustained to improve outcomes. This single-site quality improvement (QI) project aimed to standardize and re-establish an RT-driven protocol for screening patients for SBT readiness and administering SBTs to appropriate patients in an academic ICU. One hundred twenty-eight patients representing 759 safety screen weaning assessment opportunities were included over a baseline sample and three plan-do-study-act (PDSA) cycles. A key takeaway from this QI project is that consistent use of an RT-driven SBT protocol results in improved use and documentation of an SBT safety screening and completion of an SBT earlier in the day. Despite multiple obstacles, including staffing and communication challenges and poor understanding of terminology, standardization of an RT-driven SBT protocol is achievable.
– Commentary by Mary Jo Farmer, MD, PhD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Pulmonary
Navigational Bronchoscopy vs CT Scan-Guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules
By Robert J. Lentz, MD, and colleagues
, which will evaluate navigational bronchoscopy (NB) and CT-guided transthoracic needle biopsy (CT-TTNB) for diagnosing indeterminate pulmonary nodules. Although the results are not yet available, this group’s work highlights an emphasis to develop multicenter randomized controlled trials with multidisciplinary teams and clinical impactful data with a primary outcome of diagnostic accuracy (diagnostic results that remain accurate through 12 months of clinical follow-up). If NB proves to be a noninferior alternative to CT-TTNB, then it may be a safer option with a lower complication rate (particularly for pneumothorax). We look forward to the final results from the trial, and future studies incorporating newer technologies, including robotic bronchoscopy, will be a welcome adjunct as well.
– Commentary by Saadia A. Faiz, MD, FCCP, Member of the CHEST Physician Editorial Board
Journal CHEST®
Nocturnal Cardiac Arrhythmias in Heart Failure With Obstructive and Central Sleep Apnea
By Christian M. Horvath, MD, and colleagues
Horvath et al’s ancillary analysis to the ADVENT-HF trial highlights a significant association between sleep apnea (OSA and CSA) and increased nocturnal cardiac arrhythmias in heart failure patients with reduced ejection fraction (HFrEF). While ADVENT-HF showed no impact of adaptive servo-ventilation on survival and hospitalization, this subanalysis reveals a higher prevalence of arrhythmias, such as excessive supraventricular ectopic activity and atrial fibrillation/flutter (AF), in these patients. Notably, OSA severity was linked to increased atrial ectopy, though not to persistent arrhythmias like AF, contrasting with prior studies, notably from the Sleep Heart Health Study (Mehra et al, AJRCCM. 2006;173(8)). This suggests a complex interplay between OSA/CSA and AF, perhaps mediated by factors such as sympathetic tone and cardiac remodeling. Clinically, these findings underscore the value of targeted sleep apnea screening in patients with HFrEF and suggest the need for individualized arrhythmia risk profiles. Future research should investigate how additional factors mediate sleep apnea’s arrhythmic impact.
– Commentary by Shyam Subramanian, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
Improving Spontaneous Breathing Trials With a Respiratory Therapist-Driven Protocol
By Christopher A. Linke, RN, MHI, CSSBB, and colleagues
Use of respiratory therapist (RT)-driven spontaneous breathing trial (SBT) protocols are known to improve patient outcomes related to extubation from mechanical ventilation. The authors of this study asked whether an RT-driven SBT protocol could be consistently implemented and sustained to improve outcomes. This single-site quality improvement (QI) project aimed to standardize and re-establish an RT-driven protocol for screening patients for SBT readiness and administering SBTs to appropriate patients in an academic ICU. One hundred twenty-eight patients representing 759 safety screen weaning assessment opportunities were included over a baseline sample and three plan-do-study-act (PDSA) cycles. A key takeaway from this QI project is that consistent use of an RT-driven SBT protocol results in improved use and documentation of an SBT safety screening and completion of an SBT earlier in the day. Despite multiple obstacles, including staffing and communication challenges and poor understanding of terminology, standardization of an RT-driven SBT protocol is achievable.
– Commentary by Mary Jo Farmer, MD, PhD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Pulmonary
Navigational Bronchoscopy vs CT Scan-Guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules
By Robert J. Lentz, MD, and colleagues
, which will evaluate navigational bronchoscopy (NB) and CT-guided transthoracic needle biopsy (CT-TTNB) for diagnosing indeterminate pulmonary nodules. Although the results are not yet available, this group’s work highlights an emphasis to develop multicenter randomized controlled trials with multidisciplinary teams and clinical impactful data with a primary outcome of diagnostic accuracy (diagnostic results that remain accurate through 12 months of clinical follow-up). If NB proves to be a noninferior alternative to CT-TTNB, then it may be a safer option with a lower complication rate (particularly for pneumothorax). We look forward to the final results from the trial, and future studies incorporating newer technologies, including robotic bronchoscopy, will be a welcome adjunct as well.
– Commentary by Saadia A. Faiz, MD, FCCP, Member of the CHEST Physician Editorial Board
Top reads from the CHEST journal portfolio
Top reads from the CHEST journal portfolio
Dark Chocolate: A Bittersweet Remedy for Diabetes Risk
TOPLINE:
Consuming five or more servings per week of dark chocolate is associated with a lower risk for type 2 diabetes (T2D), compared with infrequent or no consumption. Conversely, a higher consumption of milk chocolate does not significantly affect the risk for diabetes and may contribute to greater weight gain.
METHODOLOGY:
- Chocolate is rich in flavanols, natural compounds known to support heart health and lower the risk for T2D. However, the link between chocolate consumption and the risk for T2D is uncertain, with inconsistent research findings that don’t distinguish between dark or milk chocolate.
- Researchers conducted a prospective cohort study to investigate the associations between dark, milk, and total chocolate consumption and the risk for T2D in three long-term US studies of female nurses and male healthcare professionals with no history of diabetes, cardiovascular disease, or cancer at baseline.
- The relationship between total chocolate consumption and the risk for diabetes was investigated in 192,208 individuals who reported their chocolate consumption using validated food frequency questionnaires every 4 years from 1986 onward.
- Information on chocolate subtypes was assessed from 2006/2007 onward in 111,654 participants.
- Participants self-reported T2D through biennial questionnaires, which was confirmed via supplementary questionnaires collecting data on glucose levels, hemoglobin A1c concentration, symptoms, and treatments; they also self-reported their body weight at baseline and during follow-ups.
TAKEAWAY:
- During 4,829,175 person-years of follow-up, researchers identified 18,862 individuals with incident T2D in the total chocolate analysis cohort.
- In the chocolate subtype cohort, 4771 incident T2D cases were identified during 1,270,348 person-years of follow-up. Having at least five servings per week of dark chocolate was associated with a 21% lower risk for T2D (adjusted hazard ratio, 0.79; P for trend = .006), while milk chocolate consumption showed no significant link (P for trend = .75).
- The risk for T2D decreased by 3% for each additional serving of dark chocolate consumed weekly, indicating a dose-response effect.
- Compared with individuals who did not change their chocolate intake, those who had an increased milk chocolate intake had greater weight gain over 4-year periods (mean difference, 0.35 kg; 95% CI, 0.27-0.43); dark chocolate showed no significant association with weight change.
IN PRACTICE:
“Even though dark and milk chocolate have similar levels of calories and saturated fat, it appears that the rich polyphenols in dark chocolate might offset the effects of saturated fat and sugar on weight gain and diabetes. It’s an intriguing difference that’s worth exploring more,” corresponding author Qi Sun from the Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts, said in a press release.
SOURCE:
This study was led by Binkai Liu, Harvard TH Chan School of Public Health. It was published online in The BMJ.
LIMITATIONS:
The relatively limited number of participants in the higher chocolate consumption groups may have reduced the statistical power for detecting modest associations between dark chocolate consumption and the risk for T2D. Additionally, the study population primarily consisted of non-Hispanic White adults older than 50 years at baseline, which, along with their professional backgrounds, may have limited the generalizability of the study findings to other populations with different socioeconomic or personal characteristics. Chocolate consumption in this study was lower than the national average of three servings per week, which may have limited the ability to assess the dose-response relationship at higher intake levels.
DISCLOSURES:
This study was supported by grants from the National Institutes of Health. Some authors reported receiving investigator-initiated grants, being on scientific advisory boards, and receiving research funding from certain institutions.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Consuming five or more servings per week of dark chocolate is associated with a lower risk for type 2 diabetes (T2D), compared with infrequent or no consumption. Conversely, a higher consumption of milk chocolate does not significantly affect the risk for diabetes and may contribute to greater weight gain.
METHODOLOGY:
- Chocolate is rich in flavanols, natural compounds known to support heart health and lower the risk for T2D. However, the link between chocolate consumption and the risk for T2D is uncertain, with inconsistent research findings that don’t distinguish between dark or milk chocolate.
- Researchers conducted a prospective cohort study to investigate the associations between dark, milk, and total chocolate consumption and the risk for T2D in three long-term US studies of female nurses and male healthcare professionals with no history of diabetes, cardiovascular disease, or cancer at baseline.
- The relationship between total chocolate consumption and the risk for diabetes was investigated in 192,208 individuals who reported their chocolate consumption using validated food frequency questionnaires every 4 years from 1986 onward.
- Information on chocolate subtypes was assessed from 2006/2007 onward in 111,654 participants.
- Participants self-reported T2D through biennial questionnaires, which was confirmed via supplementary questionnaires collecting data on glucose levels, hemoglobin A1c concentration, symptoms, and treatments; they also self-reported their body weight at baseline and during follow-ups.
TAKEAWAY:
- During 4,829,175 person-years of follow-up, researchers identified 18,862 individuals with incident T2D in the total chocolate analysis cohort.
- In the chocolate subtype cohort, 4771 incident T2D cases were identified during 1,270,348 person-years of follow-up. Having at least five servings per week of dark chocolate was associated with a 21% lower risk for T2D (adjusted hazard ratio, 0.79; P for trend = .006), while milk chocolate consumption showed no significant link (P for trend = .75).
- The risk for T2D decreased by 3% for each additional serving of dark chocolate consumed weekly, indicating a dose-response effect.
- Compared with individuals who did not change their chocolate intake, those who had an increased milk chocolate intake had greater weight gain over 4-year periods (mean difference, 0.35 kg; 95% CI, 0.27-0.43); dark chocolate showed no significant association with weight change.
IN PRACTICE:
“Even though dark and milk chocolate have similar levels of calories and saturated fat, it appears that the rich polyphenols in dark chocolate might offset the effects of saturated fat and sugar on weight gain and diabetes. It’s an intriguing difference that’s worth exploring more,” corresponding author Qi Sun from the Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts, said in a press release.
SOURCE:
This study was led by Binkai Liu, Harvard TH Chan School of Public Health. It was published online in The BMJ.
LIMITATIONS:
The relatively limited number of participants in the higher chocolate consumption groups may have reduced the statistical power for detecting modest associations between dark chocolate consumption and the risk for T2D. Additionally, the study population primarily consisted of non-Hispanic White adults older than 50 years at baseline, which, along with their professional backgrounds, may have limited the generalizability of the study findings to other populations with different socioeconomic or personal characteristics. Chocolate consumption in this study was lower than the national average of three servings per week, which may have limited the ability to assess the dose-response relationship at higher intake levels.
DISCLOSURES:
This study was supported by grants from the National Institutes of Health. Some authors reported receiving investigator-initiated grants, being on scientific advisory boards, and receiving research funding from certain institutions.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Consuming five or more servings per week of dark chocolate is associated with a lower risk for type 2 diabetes (T2D), compared with infrequent or no consumption. Conversely, a higher consumption of milk chocolate does not significantly affect the risk for diabetes and may contribute to greater weight gain.
METHODOLOGY:
- Chocolate is rich in flavanols, natural compounds known to support heart health and lower the risk for T2D. However, the link between chocolate consumption and the risk for T2D is uncertain, with inconsistent research findings that don’t distinguish between dark or milk chocolate.
- Researchers conducted a prospective cohort study to investigate the associations between dark, milk, and total chocolate consumption and the risk for T2D in three long-term US studies of female nurses and male healthcare professionals with no history of diabetes, cardiovascular disease, or cancer at baseline.
- The relationship between total chocolate consumption and the risk for diabetes was investigated in 192,208 individuals who reported their chocolate consumption using validated food frequency questionnaires every 4 years from 1986 onward.
- Information on chocolate subtypes was assessed from 2006/2007 onward in 111,654 participants.
- Participants self-reported T2D through biennial questionnaires, which was confirmed via supplementary questionnaires collecting data on glucose levels, hemoglobin A1c concentration, symptoms, and treatments; they also self-reported their body weight at baseline and during follow-ups.
TAKEAWAY:
- During 4,829,175 person-years of follow-up, researchers identified 18,862 individuals with incident T2D in the total chocolate analysis cohort.
- In the chocolate subtype cohort, 4771 incident T2D cases were identified during 1,270,348 person-years of follow-up. Having at least five servings per week of dark chocolate was associated with a 21% lower risk for T2D (adjusted hazard ratio, 0.79; P for trend = .006), while milk chocolate consumption showed no significant link (P for trend = .75).
- The risk for T2D decreased by 3% for each additional serving of dark chocolate consumed weekly, indicating a dose-response effect.
- Compared with individuals who did not change their chocolate intake, those who had an increased milk chocolate intake had greater weight gain over 4-year periods (mean difference, 0.35 kg; 95% CI, 0.27-0.43); dark chocolate showed no significant association with weight change.
IN PRACTICE:
“Even though dark and milk chocolate have similar levels of calories and saturated fat, it appears that the rich polyphenols in dark chocolate might offset the effects of saturated fat and sugar on weight gain and diabetes. It’s an intriguing difference that’s worth exploring more,” corresponding author Qi Sun from the Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts, said in a press release.
SOURCE:
This study was led by Binkai Liu, Harvard TH Chan School of Public Health. It was published online in The BMJ.
LIMITATIONS:
The relatively limited number of participants in the higher chocolate consumption groups may have reduced the statistical power for detecting modest associations between dark chocolate consumption and the risk for T2D. Additionally, the study population primarily consisted of non-Hispanic White adults older than 50 years at baseline, which, along with their professional backgrounds, may have limited the generalizability of the study findings to other populations with different socioeconomic or personal characteristics. Chocolate consumption in this study was lower than the national average of three servings per week, which may have limited the ability to assess the dose-response relationship at higher intake levels.
DISCLOSURES:
This study was supported by grants from the National Institutes of Health. Some authors reported receiving investigator-initiated grants, being on scientific advisory boards, and receiving research funding from certain institutions.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
FDA Approves Bizengri for NSCLC and Pancreatic Cancers Harboring NRG1 Gene Fusion
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Identifying the Best Upfront Regimen for Unresectable CRC Liver Metastasis
A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.
The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.
In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).
The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.
The analysis did not stop there in defining the optimal upfront therapy for this patient population.
In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.
Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.
In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.
Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.
Why Does This Clarity Matter?
The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.
In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.
As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.
Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.
Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.
Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.
The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.
Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.
Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).
ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.
CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.
A version of this article first appeared on Medscape.com.
A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.
The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.
In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).
The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.
The analysis did not stop there in defining the optimal upfront therapy for this patient population.
In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.
Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.
In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.
Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.
Why Does This Clarity Matter?
The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.
In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.
As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.
Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.
Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.
Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.
The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.
Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.
Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).
ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.
CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.
A version of this article first appeared on Medscape.com.
A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.
The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.
In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).
The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.
The analysis did not stop there in defining the optimal upfront therapy for this patient population.
In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.
Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.
In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.
Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.
Why Does This Clarity Matter?
The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.
In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.
As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.
Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.
Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.
Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.
The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.
Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.
Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).
ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.
CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
Has Tirzepatide Scaled the HFpEF/Obesity SUMMIT?
The results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.
Known Facts About HFpEF
HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.
Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.
GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.
This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.
The SUMMIT Trial
The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.
Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.
Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.
Tirzepatide Results
The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).
The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).
The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).
The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.
Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).
Authors’ Conclusions and Expert Comments
At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.
Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”
Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.
The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.
My Six Concerns With SUMMIT
The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.
The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.
I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.
The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.
The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.
For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.
The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.
Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.
The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.
Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.
In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.
Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.
Known Facts About HFpEF
HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.
Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.
GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.
This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.
The SUMMIT Trial
The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.
Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.
Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.
Tirzepatide Results
The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).
The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).
The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).
The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.
Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).
Authors’ Conclusions and Expert Comments
At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.
Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”
Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.
The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.
My Six Concerns With SUMMIT
The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.
The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.
I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.
The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.
The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.
For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.
The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.
Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.
The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.
Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.
In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.
Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.
Known Facts About HFpEF
HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.
Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.
GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.
This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.
The SUMMIT Trial
The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.
Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.
Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.
Tirzepatide Results
The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).
The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).
The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).
The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.
Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).
Authors’ Conclusions and Expert Comments
At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.
Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”
Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.
The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.
My Six Concerns With SUMMIT
The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.
The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.
I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.
The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.
The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.
For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.
The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.
Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.
The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.
Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.
In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.
Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rural Areas Face Steeper Decline in Hospital Obstetric Services Than Urban Centers
TOPLINE:
Between 2010 and 2022, hospital-based obstetric care declined significantly across the United States, with 52.4% of rural hospitals and 35.7% of urban hospitals not offering obstetric services by 2022. Rural hospitals experienced a steeper increase in the percentage of facilities without obstetrics than urban counterparts, despite several national maternity care access initiatives.
METHODOLOGY:
- Researchers conducted a retrospective cohort study of 4964 United States short-term acute care hospitals, including 1982 in rural counties and 2982 in urban counties, analyzing data from 2010 to 2022.
- Analysis utilized American Hospital Association annual surveys and Centers for Medicare & Medicaid Services Provider of Services files, applying an enhanced algorithm to identify hospital-based obstetric services availability.
- Hospital rurality classification followed Office of Management and Budget definitions, with urban hospitals located in metropolitan statistical areas having > 250,000 inhabitants and rural hospitals in nonmetropolitan areas with < 50,000 inhabitants.
TAKEAWAY:
- A total of 537 hospitals lost obstetric services between 2010 and 2022, with 238 rural hospitals and 299 urban hospitals affected, while only 138 hospitals gained obstetric services during this period.
- The percentage of hospitals without obstetrics increased steadily from 35.2% to 42.4% of all hospitals between 2010 and 2022, with rural hospitals consistently showing higher rates than urban facilities.
- By 2022, more than half (52.4%) of rural hospitals and over one third (35.7%) of urban hospitals did not offer obstetric care, representing a significant decline in access to maternal healthcare services.
- Urban areas showed greater potential for service recovery with 112 hospitals gaining obstetric services than only 26 rural hospitals during the study period.
IN PRACTICE:
“Access to obstetric care is an important determinant of maternal and infant health outcomes, and amidst a maternal health crisis in the US, hospital-based obstetric care has declined in both rural and urban communities,” wrote the authors of the study.
SOURCE:
The study was led by Katy B. Kozhimannil, PhD, MPA, Division of Health Policy and Management, University of Minnesota School of Public Health in Minneapolis. It was published online on December 4 in JAMA.
LIMITATIONS:
The study was limited by the lack of data on births outside hospital settings, which represent less than 2% of United States births. Additionally, the denominator for the study outcome declined each year because of hospital closures, particularly affecting rural hospitals. The researchers also noted that while rurality exists on a continuum, they applied a dichotomous county–based measure of hospital location. Furthermore, the hospital-level data did not contain patient-level information, making it impossible to analyze how changes in obstetric status affected patient outcomes.
DISCLOSURES:
This study was supported by the Federal Office of Rural Health Policy, Health Resources and Services Administration, Department of Health & Human Services under Public Health Service Cooperative Agreement. One coauthor disclosed receiving grants from the Laura and John Arnold Foundation, Ballad Health, and the Commonwealth Fund outside the submitted work. A coauthor reported receiving personal fees from the American Institute of Biological Sciences on behalf of March of Dimes as a grant reviewer. Another coauthor reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Between 2010 and 2022, hospital-based obstetric care declined significantly across the United States, with 52.4% of rural hospitals and 35.7% of urban hospitals not offering obstetric services by 2022. Rural hospitals experienced a steeper increase in the percentage of facilities without obstetrics than urban counterparts, despite several national maternity care access initiatives.
METHODOLOGY:
- Researchers conducted a retrospective cohort study of 4964 United States short-term acute care hospitals, including 1982 in rural counties and 2982 in urban counties, analyzing data from 2010 to 2022.
- Analysis utilized American Hospital Association annual surveys and Centers for Medicare & Medicaid Services Provider of Services files, applying an enhanced algorithm to identify hospital-based obstetric services availability.
- Hospital rurality classification followed Office of Management and Budget definitions, with urban hospitals located in metropolitan statistical areas having > 250,000 inhabitants and rural hospitals in nonmetropolitan areas with < 50,000 inhabitants.
TAKEAWAY:
- A total of 537 hospitals lost obstetric services between 2010 and 2022, with 238 rural hospitals and 299 urban hospitals affected, while only 138 hospitals gained obstetric services during this period.
- The percentage of hospitals without obstetrics increased steadily from 35.2% to 42.4% of all hospitals between 2010 and 2022, with rural hospitals consistently showing higher rates than urban facilities.
- By 2022, more than half (52.4%) of rural hospitals and over one third (35.7%) of urban hospitals did not offer obstetric care, representing a significant decline in access to maternal healthcare services.
- Urban areas showed greater potential for service recovery with 112 hospitals gaining obstetric services than only 26 rural hospitals during the study period.
IN PRACTICE:
“Access to obstetric care is an important determinant of maternal and infant health outcomes, and amidst a maternal health crisis in the US, hospital-based obstetric care has declined in both rural and urban communities,” wrote the authors of the study.
SOURCE:
The study was led by Katy B. Kozhimannil, PhD, MPA, Division of Health Policy and Management, University of Minnesota School of Public Health in Minneapolis. It was published online on December 4 in JAMA.
LIMITATIONS:
The study was limited by the lack of data on births outside hospital settings, which represent less than 2% of United States births. Additionally, the denominator for the study outcome declined each year because of hospital closures, particularly affecting rural hospitals. The researchers also noted that while rurality exists on a continuum, they applied a dichotomous county–based measure of hospital location. Furthermore, the hospital-level data did not contain patient-level information, making it impossible to analyze how changes in obstetric status affected patient outcomes.
DISCLOSURES:
This study was supported by the Federal Office of Rural Health Policy, Health Resources and Services Administration, Department of Health & Human Services under Public Health Service Cooperative Agreement. One coauthor disclosed receiving grants from the Laura and John Arnold Foundation, Ballad Health, and the Commonwealth Fund outside the submitted work. A coauthor reported receiving personal fees from the American Institute of Biological Sciences on behalf of March of Dimes as a grant reviewer. Another coauthor reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Between 2010 and 2022, hospital-based obstetric care declined significantly across the United States, with 52.4% of rural hospitals and 35.7% of urban hospitals not offering obstetric services by 2022. Rural hospitals experienced a steeper increase in the percentage of facilities without obstetrics than urban counterparts, despite several national maternity care access initiatives.
METHODOLOGY:
- Researchers conducted a retrospective cohort study of 4964 United States short-term acute care hospitals, including 1982 in rural counties and 2982 in urban counties, analyzing data from 2010 to 2022.
- Analysis utilized American Hospital Association annual surveys and Centers for Medicare & Medicaid Services Provider of Services files, applying an enhanced algorithm to identify hospital-based obstetric services availability.
- Hospital rurality classification followed Office of Management and Budget definitions, with urban hospitals located in metropolitan statistical areas having > 250,000 inhabitants and rural hospitals in nonmetropolitan areas with < 50,000 inhabitants.
TAKEAWAY:
- A total of 537 hospitals lost obstetric services between 2010 and 2022, with 238 rural hospitals and 299 urban hospitals affected, while only 138 hospitals gained obstetric services during this period.
- The percentage of hospitals without obstetrics increased steadily from 35.2% to 42.4% of all hospitals between 2010 and 2022, with rural hospitals consistently showing higher rates than urban facilities.
- By 2022, more than half (52.4%) of rural hospitals and over one third (35.7%) of urban hospitals did not offer obstetric care, representing a significant decline in access to maternal healthcare services.
- Urban areas showed greater potential for service recovery with 112 hospitals gaining obstetric services than only 26 rural hospitals during the study period.
IN PRACTICE:
“Access to obstetric care is an important determinant of maternal and infant health outcomes, and amidst a maternal health crisis in the US, hospital-based obstetric care has declined in both rural and urban communities,” wrote the authors of the study.
SOURCE:
The study was led by Katy B. Kozhimannil, PhD, MPA, Division of Health Policy and Management, University of Minnesota School of Public Health in Minneapolis. It was published online on December 4 in JAMA.
LIMITATIONS:
The study was limited by the lack of data on births outside hospital settings, which represent less than 2% of United States births. Additionally, the denominator for the study outcome declined each year because of hospital closures, particularly affecting rural hospitals. The researchers also noted that while rurality exists on a continuum, they applied a dichotomous county–based measure of hospital location. Furthermore, the hospital-level data did not contain patient-level information, making it impossible to analyze how changes in obstetric status affected patient outcomes.
DISCLOSURES:
This study was supported by the Federal Office of Rural Health Policy, Health Resources and Services Administration, Department of Health & Human Services under Public Health Service Cooperative Agreement. One coauthor disclosed receiving grants from the Laura and John Arnold Foundation, Ballad Health, and the Commonwealth Fund outside the submitted work. A coauthor reported receiving personal fees from the American Institute of Biological Sciences on behalf of March of Dimes as a grant reviewer. Another coauthor reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Smarter Pregnancy App Links Improved Lifestyle Habits to Lower Maternal Blood Pressure in Early Pregnancy
TOPLINE:
Digital lifestyle coaching through the Smarter Pregnancy program reduces maternal blood pressure (BP) by approximately 2 mm Hg during the first trimester of pregnancy. The program enhances lifestyle behaviors through personalized coaching on vegetable and fruit intake, smoking cessation, and alcohol abstinence.
METHODOLOGY:
- Researchers analyzed data from the Rotterdam Periconception Cohort between 2010 and 2019, including 132 pregnant women who used Smarter Pregnancy for 6-24 weeks in the intervention group and 1091 pregnant women in the control group.
- Participants’ outcomes included changes in systolic, diastolic, and mean arterial BPs between baseline and first trimester measurements, with median gestational age of 7 weeks at inclusion.
- Analysis tracked lifestyle behaviors in the intervention group at 12 and 24 weeks using risk scores for vegetables, fruits, smoking, and alcohol consumption.
- Multivariable analysis adjusted for baseline BP measurements, age, gestational age, geographic origin, parity, and conception mode to evaluate program effectiveness.
TAKEAWAY:
- The intervention group demonstrated significant reductions in systolic (beta, −2.34 mm Hg; 95% CI, −4.67 to −0.01; P = .049), diastolic (beta, −2.00 mm Hg; 95% CI, −3.57 to −0.45; P = .012), and mean arterial BP (beta, −2.22 mm Hg; 95% CI, −3.81 to −0.52; P = .011) compared with controls.
- Among women who underwent assisted reproductive technology (ART), significant reductions were observed in diastolic (beta, −2.38 mm Hg; 95% CI, −4.20 to −0.56) and mean arterial BP (beta, −2.63 mm Hg; 95% CI, −4.61 to −0.56).
- Program usage was associated with decreased lifestyle risk scores at 12 weeks (beta, −0.84; 95% CI, −1.19 to −0.49) and 24 weeks (beta, −1.07; 95% CI, −1.44 to −0.69), indicating improved lifestyle behaviors.
- Lifestyle risk scores significantly decreased in both ART and natural pregnancy subgroups after program completion.
IN PRACTICE:
“The findings suggest that Smarter Pregnancy can be used to coach women on healthy lifestyle behaviors commencing from the preconception period onwards to improve BP outcomes. Of note, although implementing the program during [the] first trimester seems easier, initiating lifestyle coaching as early as preconceptional period can act as preventive measure against adverse health outcomes,” wrote the authors of the study.
SOURCE:
The study was led by Batoul Hojeij, PhD, Erasmus University Medical Center in Rotterdam, the Netherlands. It was published online in the American Journal of Preventive Medicine.
LIMITATIONS:
According to the authors, participants in the intervention group might have had healthier lifestyles due to their motivation to use a digital coaching program. The sample size of naturally conceived pregnancies in the intervention group was small (n = 41), reducing statistical power for subgroup analysis. The high percentage of missing data for baseline BP measurements (64%) could have affected statistical power and led to potential bias, though multiple imputations were used to address this limitation.
DISCLOSURES:
This study was supported by the European Union’s Horizon 2020 research and innovation program (DohART-NET) and the Department of Obstetrics and Gynaecology of the Erasmus MC. Kevin D Sinclair, PhD, DSc, received funding from the Biotechnology and Biological Sciences Research Council.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Digital lifestyle coaching through the Smarter Pregnancy program reduces maternal blood pressure (BP) by approximately 2 mm Hg during the first trimester of pregnancy. The program enhances lifestyle behaviors through personalized coaching on vegetable and fruit intake, smoking cessation, and alcohol abstinence.
METHODOLOGY:
- Researchers analyzed data from the Rotterdam Periconception Cohort between 2010 and 2019, including 132 pregnant women who used Smarter Pregnancy for 6-24 weeks in the intervention group and 1091 pregnant women in the control group.
- Participants’ outcomes included changes in systolic, diastolic, and mean arterial BPs between baseline and first trimester measurements, with median gestational age of 7 weeks at inclusion.
- Analysis tracked lifestyle behaviors in the intervention group at 12 and 24 weeks using risk scores for vegetables, fruits, smoking, and alcohol consumption.
- Multivariable analysis adjusted for baseline BP measurements, age, gestational age, geographic origin, parity, and conception mode to evaluate program effectiveness.
TAKEAWAY:
- The intervention group demonstrated significant reductions in systolic (beta, −2.34 mm Hg; 95% CI, −4.67 to −0.01; P = .049), diastolic (beta, −2.00 mm Hg; 95% CI, −3.57 to −0.45; P = .012), and mean arterial BP (beta, −2.22 mm Hg; 95% CI, −3.81 to −0.52; P = .011) compared with controls.
- Among women who underwent assisted reproductive technology (ART), significant reductions were observed in diastolic (beta, −2.38 mm Hg; 95% CI, −4.20 to −0.56) and mean arterial BP (beta, −2.63 mm Hg; 95% CI, −4.61 to −0.56).
- Program usage was associated with decreased lifestyle risk scores at 12 weeks (beta, −0.84; 95% CI, −1.19 to −0.49) and 24 weeks (beta, −1.07; 95% CI, −1.44 to −0.69), indicating improved lifestyle behaviors.
- Lifestyle risk scores significantly decreased in both ART and natural pregnancy subgroups after program completion.
IN PRACTICE:
“The findings suggest that Smarter Pregnancy can be used to coach women on healthy lifestyle behaviors commencing from the preconception period onwards to improve BP outcomes. Of note, although implementing the program during [the] first trimester seems easier, initiating lifestyle coaching as early as preconceptional period can act as preventive measure against adverse health outcomes,” wrote the authors of the study.
SOURCE:
The study was led by Batoul Hojeij, PhD, Erasmus University Medical Center in Rotterdam, the Netherlands. It was published online in the American Journal of Preventive Medicine.
LIMITATIONS:
According to the authors, participants in the intervention group might have had healthier lifestyles due to their motivation to use a digital coaching program. The sample size of naturally conceived pregnancies in the intervention group was small (n = 41), reducing statistical power for subgroup analysis. The high percentage of missing data for baseline BP measurements (64%) could have affected statistical power and led to potential bias, though multiple imputations were used to address this limitation.
DISCLOSURES:
This study was supported by the European Union’s Horizon 2020 research and innovation program (DohART-NET) and the Department of Obstetrics and Gynaecology of the Erasmus MC. Kevin D Sinclair, PhD, DSc, received funding from the Biotechnology and Biological Sciences Research Council.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Digital lifestyle coaching through the Smarter Pregnancy program reduces maternal blood pressure (BP) by approximately 2 mm Hg during the first trimester of pregnancy. The program enhances lifestyle behaviors through personalized coaching on vegetable and fruit intake, smoking cessation, and alcohol abstinence.
METHODOLOGY:
- Researchers analyzed data from the Rotterdam Periconception Cohort between 2010 and 2019, including 132 pregnant women who used Smarter Pregnancy for 6-24 weeks in the intervention group and 1091 pregnant women in the control group.
- Participants’ outcomes included changes in systolic, diastolic, and mean arterial BPs between baseline and first trimester measurements, with median gestational age of 7 weeks at inclusion.
- Analysis tracked lifestyle behaviors in the intervention group at 12 and 24 weeks using risk scores for vegetables, fruits, smoking, and alcohol consumption.
- Multivariable analysis adjusted for baseline BP measurements, age, gestational age, geographic origin, parity, and conception mode to evaluate program effectiveness.
TAKEAWAY:
- The intervention group demonstrated significant reductions in systolic (beta, −2.34 mm Hg; 95% CI, −4.67 to −0.01; P = .049), diastolic (beta, −2.00 mm Hg; 95% CI, −3.57 to −0.45; P = .012), and mean arterial BP (beta, −2.22 mm Hg; 95% CI, −3.81 to −0.52; P = .011) compared with controls.
- Among women who underwent assisted reproductive technology (ART), significant reductions were observed in diastolic (beta, −2.38 mm Hg; 95% CI, −4.20 to −0.56) and mean arterial BP (beta, −2.63 mm Hg; 95% CI, −4.61 to −0.56).
- Program usage was associated with decreased lifestyle risk scores at 12 weeks (beta, −0.84; 95% CI, −1.19 to −0.49) and 24 weeks (beta, −1.07; 95% CI, −1.44 to −0.69), indicating improved lifestyle behaviors.
- Lifestyle risk scores significantly decreased in both ART and natural pregnancy subgroups after program completion.
IN PRACTICE:
“The findings suggest that Smarter Pregnancy can be used to coach women on healthy lifestyle behaviors commencing from the preconception period onwards to improve BP outcomes. Of note, although implementing the program during [the] first trimester seems easier, initiating lifestyle coaching as early as preconceptional period can act as preventive measure against adverse health outcomes,” wrote the authors of the study.
SOURCE:
The study was led by Batoul Hojeij, PhD, Erasmus University Medical Center in Rotterdam, the Netherlands. It was published online in the American Journal of Preventive Medicine.
LIMITATIONS:
According to the authors, participants in the intervention group might have had healthier lifestyles due to their motivation to use a digital coaching program. The sample size of naturally conceived pregnancies in the intervention group was small (n = 41), reducing statistical power for subgroup analysis. The high percentage of missing data for baseline BP measurements (64%) could have affected statistical power and led to potential bias, though multiple imputations were used to address this limitation.
DISCLOSURES:
This study was supported by the European Union’s Horizon 2020 research and innovation program (DohART-NET) and the Department of Obstetrics and Gynaecology of the Erasmus MC. Kevin D Sinclair, PhD, DSc, received funding from the Biotechnology and Biological Sciences Research Council.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.