News

Lung cancer screening with low-dose CT can detect extensive coronary artery calcium (CAC), an independent predictor of all-cause death and cardiovascular events, new research suggested.

“The high prevalence of asymptomatic coronary artery disease (83%) was surprising, as was the prevalence of extensive CAC (30%),” principal investigator Gary Small, MBChB, PhD, a cardiologist at the University of Ottawa Heart Institute in Ontario, Canada, said in an interview.

“The size of effect was also surprising, as was the persistence of the effect even in the presence of elevated mortality risk from other causes,” he said. “Extensive coronary disease was associated with a twofold increase in risk for death or cardiovascular events over 4 years of follow-up,” even after adjustment for risk for death from cancer and other comorbidities such as chronic obstructive pulmonary disease.

“CAC as reported on chest CT exams is often ignored and not factored into clinical practice,” he noted. “The presence of CAC, however, provides a very real and very personal perspective on an individual’s cardiovascular risk. It is a true example of personalized medicine.”

The study was published online in The Canadian Medical Association Journal.

 

Potential Risk Reduction 

In March 2017, Ontario Health launched a pilot low-dose CT lung cancer screening program for high-risk individuals between the ages of 55 and 74 years, Small explained. As CAC, a marker of coronary artery disease, is seen easily during such a scan, the researchers analyzed the lung CTs to determine the prevalence of coronary artery disease and whether CAC was associated with increased risk.

The team quantified CAC using an estimated Agatston score and identified the composite primary outcome of all-cause death and cardiovascular events using linked electronic medical record data from Ottawa Hospital up to December 2023. Among the 1486 people who underwent screening (mean age, 66 years; 52% men; 68% current smokers), CAC was detected in 1232 (82.9%). CAC was mild to moderate in 793 participants (53.4%) and extensive in 439 (29.5%). No CAC was detected in 254 (17.1%) participants.

At follow-up, 78 participants (5.2%) experienced the primary composite outcome, including 39 (8.9%) with extensive CAC, 32 (4.0%) with mild to moderate CAC, and 7 (2.8%) with no CAC.

A total of 49 deaths occurred, including 16 cardiovascular deaths and 19 cancer deaths, of which 10 were from lung cancer. Cardiovascular events included sudden cardiac death (eight participants), fatal stroke (six participants), and one each from heart failure and peripheral vascular disease.

On multivariable analysis, extensive CAC was associated with the composite primary outcome (adjusted hazard ratio [aHR], 2.13), all-cause mortality (aHR, 2.39), and cardiovascular events (aHR, 2.06).

Extensive CAC remained predictive of cardiovascular events even after adjustment for noncardiovascular death as a competing risk (HR, 2.05).

“Our data highlight to lung cancer screening professionals the prevalence of this silent risk factor and re-emphasize the importance of this finding [ie, CAC] as an opportunity for risk reduction,” Small said.

“In terms of next steps, the journey toward cardiovascular risk reduction begins with a clear report of CAC on the lung cancer screening record,” he noted. “Following this step, professionals involved in the lung cancer screening program might consider a local management pathway to ensure that this opportunity for health improvement is not lost or ignored. Preventive medicine of this type would typically involve primary care.”

 

Managing Other Findings

Commenting on the study, Anna Bader, MD, assistant professor of radiology and biomedical imaging at the Yale School of Medicine in New Haven, Connecticut, said that “low-dose CT for lung cancer screening offers valuable insights beyond nodule detection, with CAC being among the most significant incidental findings.”

However, she added, a “robust mechanism” to effectively manage other findings — such as thoracic aortic disease, low bone density, and abnormalities in the thyroid or upper abdominal organs — without overdiagnosis, is needed. A mechanism also is needed to notify cardiologists or primary care providers about severe CAC findings.

Challenges that need to be overcome before such mechanisms can be put in place, she said, “include ensuring standardized CAC reporting, avoiding overburdening healthcare providers, mitigating the risk of excessive downstream testing, and ensuring equitable access to follow-up care for underserved and rural communities.”

Providers involved in lung cancer screening “must be trained to recognize the importance of CAC findings and act upon them,” she added. “Awareness campaigns or continuing medical education modules could address this.”

Multidisciplinary lung cancer screening programs can help with patient education, she noted. “Clear communication about potential findings, including the significance of incidental CAC, should be prioritized and addressed proactively, ideally before the exam, to enhance patient understanding and engagement.”

Matthew Tomey, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City, said that, “as a practicing cardiologist, I find it very helpful to look at my patients’ recent or past CT scans to look for vascular calcification. Whether or not a scan is specifically protocoled as a cardiac study, we can often appreciate vascular calcification when it is present. I would encourage every physician involved in helping their patients to prevent heart disease to take advantage of looking at any prior CT scans for evidence of vascular calcification.

“Systems of care to facilitate recognition of patients with incidentally discovered vascular calcification would be welcome and, on a large scale, could help prevent cardiovascular events,” he noted. “Such a system might involve facilitating referral to a prevention specialist. It could involve evidence-based guidance for referring physicians who ordered scans.”

Like Bader, he noted the importance of patient education, adding that it could be quite powerful. “We should be doing more to empower our patients to understand the findings of their imaging and to give them actionable, evidence-based guidance on how they can promote their own cardiovascular health,” he concluded.

No funding for the study was reported. Small reported receiving a research grant for amyloid research from Pfizer and honoraria from Pfizer and Alnylam (all paid to the institution, outside the submitted work). Bader and Tomey declared no relevant conflicts.

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

Lung cancer screening with low-dose CT can detect extensive coronary artery calcium (CAC), an independent predictor of all-cause death and cardiovascular events, new research suggested.

“The high prevalence of asymptomatic coronary artery disease (83%) was surprising, as was the prevalence of extensive CAC (30%),” principal investigator Gary Small, MBChB, PhD, a cardiologist at the University of Ottawa Heart Institute in Ontario, Canada, said in an interview.

“The size of effect was also surprising, as was the persistence of the effect even in the presence of elevated mortality risk from other causes,” he said. “Extensive coronary disease was associated with a twofold increase in risk for death or cardiovascular events over 4 years of follow-up,” even after adjustment for risk for death from cancer and other comorbidities such as chronic obstructive pulmonary disease.

“CAC as reported on chest CT exams is often ignored and not factored into clinical practice,” he noted. “The presence of CAC, however, provides a very real and very personal perspective on an individual’s cardiovascular risk. It is a true example of personalized medicine.”

The study was published online in The Canadian Medical Association Journal.

 

Potential Risk Reduction 

In March 2017, Ontario Health launched a pilot low-dose CT lung cancer screening program for high-risk individuals between the ages of 55 and 74 years, Small explained. As CAC, a marker of coronary artery disease, is seen easily during such a scan, the researchers analyzed the lung CTs to determine the prevalence of coronary artery disease and whether CAC was associated with increased risk.

The team quantified CAC using an estimated Agatston score and identified the composite primary outcome of all-cause death and cardiovascular events using linked electronic medical record data from Ottawa Hospital up to December 2023. Among the 1486 people who underwent screening (mean age, 66 years; 52% men; 68% current smokers), CAC was detected in 1232 (82.9%). CAC was mild to moderate in 793 participants (53.4%) and extensive in 439 (29.5%). No CAC was detected in 254 (17.1%) participants.

At follow-up, 78 participants (5.2%) experienced the primary composite outcome, including 39 (8.9%) with extensive CAC, 32 (4.0%) with mild to moderate CAC, and 7 (2.8%) with no CAC.

A total of 49 deaths occurred, including 16 cardiovascular deaths and 19 cancer deaths, of which 10 were from lung cancer. Cardiovascular events included sudden cardiac death (eight participants), fatal stroke (six participants), and one each from heart failure and peripheral vascular disease.

On multivariable analysis, extensive CAC was associated with the composite primary outcome (adjusted hazard ratio [aHR], 2.13), all-cause mortality (aHR, 2.39), and cardiovascular events (aHR, 2.06).

Extensive CAC remained predictive of cardiovascular events even after adjustment for noncardiovascular death as a competing risk (HR, 2.05).

“Our data highlight to lung cancer screening professionals the prevalence of this silent risk factor and re-emphasize the importance of this finding [ie, CAC] as an opportunity for risk reduction,” Small said.

“In terms of next steps, the journey toward cardiovascular risk reduction begins with a clear report of CAC on the lung cancer screening record,” he noted. “Following this step, professionals involved in the lung cancer screening program might consider a local management pathway to ensure that this opportunity for health improvement is not lost or ignored. Preventive medicine of this type would typically involve primary care.”

 

Managing Other Findings

Commenting on the study, Anna Bader, MD, assistant professor of radiology and biomedical imaging at the Yale School of Medicine in New Haven, Connecticut, said that “low-dose CT for lung cancer screening offers valuable insights beyond nodule detection, with CAC being among the most significant incidental findings.”

However, she added, a “robust mechanism” to effectively manage other findings — such as thoracic aortic disease, low bone density, and abnormalities in the thyroid or upper abdominal organs — without overdiagnosis, is needed. A mechanism also is needed to notify cardiologists or primary care providers about severe CAC findings.

Challenges that need to be overcome before such mechanisms can be put in place, she said, “include ensuring standardized CAC reporting, avoiding overburdening healthcare providers, mitigating the risk of excessive downstream testing, and ensuring equitable access to follow-up care for underserved and rural communities.”

Providers involved in lung cancer screening “must be trained to recognize the importance of CAC findings and act upon them,” she added. “Awareness campaigns or continuing medical education modules could address this.”

Multidisciplinary lung cancer screening programs can help with patient education, she noted. “Clear communication about potential findings, including the significance of incidental CAC, should be prioritized and addressed proactively, ideally before the exam, to enhance patient understanding and engagement.”

Matthew Tomey, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City, said that, “as a practicing cardiologist, I find it very helpful to look at my patients’ recent or past CT scans to look for vascular calcification. Whether or not a scan is specifically protocoled as a cardiac study, we can often appreciate vascular calcification when it is present. I would encourage every physician involved in helping their patients to prevent heart disease to take advantage of looking at any prior CT scans for evidence of vascular calcification.

“Systems of care to facilitate recognition of patients with incidentally discovered vascular calcification would be welcome and, on a large scale, could help prevent cardiovascular events,” he noted. “Such a system might involve facilitating referral to a prevention specialist. It could involve evidence-based guidance for referring physicians who ordered scans.”

Like Bader, he noted the importance of patient education, adding that it could be quite powerful. “We should be doing more to empower our patients to understand the findings of their imaging and to give them actionable, evidence-based guidance on how they can promote their own cardiovascular health,” he concluded.

No funding for the study was reported. Small reported receiving a research grant for amyloid research from Pfizer and honoraria from Pfizer and Alnylam (all paid to the institution, outside the submitted work). Bader and Tomey declared no relevant conflicts.

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

Lung cancer screening with low-dose CT can detect extensive coronary artery calcium (CAC), an independent predictor of all-cause death and cardiovascular events, new research suggested.

“The high prevalence of asymptomatic coronary artery disease (83%) was surprising, as was the prevalence of extensive CAC (30%),” principal investigator Gary Small, MBChB, PhD, a cardiologist at the University of Ottawa Heart Institute in Ontario, Canada, said in an interview.

“The size of effect was also surprising, as was the persistence of the effect even in the presence of elevated mortality risk from other causes,” he said. “Extensive coronary disease was associated with a twofold increase in risk for death or cardiovascular events over 4 years of follow-up,” even after adjustment for risk for death from cancer and other comorbidities such as chronic obstructive pulmonary disease.

“CAC as reported on chest CT exams is often ignored and not factored into clinical practice,” he noted. “The presence of CAC, however, provides a very real and very personal perspective on an individual’s cardiovascular risk. It is a true example of personalized medicine.”

The study was published online in The Canadian Medical Association Journal.

 

Potential Risk Reduction 

In March 2017, Ontario Health launched a pilot low-dose CT lung cancer screening program for high-risk individuals between the ages of 55 and 74 years, Small explained. As CAC, a marker of coronary artery disease, is seen easily during such a scan, the researchers analyzed the lung CTs to determine the prevalence of coronary artery disease and whether CAC was associated with increased risk.

The team quantified CAC using an estimated Agatston score and identified the composite primary outcome of all-cause death and cardiovascular events using linked electronic medical record data from Ottawa Hospital up to December 2023. Among the 1486 people who underwent screening (mean age, 66 years; 52% men; 68% current smokers), CAC was detected in 1232 (82.9%). CAC was mild to moderate in 793 participants (53.4%) and extensive in 439 (29.5%). No CAC was detected in 254 (17.1%) participants.

At follow-up, 78 participants (5.2%) experienced the primary composite outcome, including 39 (8.9%) with extensive CAC, 32 (4.0%) with mild to moderate CAC, and 7 (2.8%) with no CAC.

A total of 49 deaths occurred, including 16 cardiovascular deaths and 19 cancer deaths, of which 10 were from lung cancer. Cardiovascular events included sudden cardiac death (eight participants), fatal stroke (six participants), and one each from heart failure and peripheral vascular disease.

On multivariable analysis, extensive CAC was associated with the composite primary outcome (adjusted hazard ratio [aHR], 2.13), all-cause mortality (aHR, 2.39), and cardiovascular events (aHR, 2.06).

Extensive CAC remained predictive of cardiovascular events even after adjustment for noncardiovascular death as a competing risk (HR, 2.05).

“Our data highlight to lung cancer screening professionals the prevalence of this silent risk factor and re-emphasize the importance of this finding [ie, CAC] as an opportunity for risk reduction,” Small said.

“In terms of next steps, the journey toward cardiovascular risk reduction begins with a clear report of CAC on the lung cancer screening record,” he noted. “Following this step, professionals involved in the lung cancer screening program might consider a local management pathway to ensure that this opportunity for health improvement is not lost or ignored. Preventive medicine of this type would typically involve primary care.”

 

Managing Other Findings

Commenting on the study, Anna Bader, MD, assistant professor of radiology and biomedical imaging at the Yale School of Medicine in New Haven, Connecticut, said that “low-dose CT for lung cancer screening offers valuable insights beyond nodule detection, with CAC being among the most significant incidental findings.”

However, she added, a “robust mechanism” to effectively manage other findings — such as thoracic aortic disease, low bone density, and abnormalities in the thyroid or upper abdominal organs — without overdiagnosis, is needed. A mechanism also is needed to notify cardiologists or primary care providers about severe CAC findings.

Challenges that need to be overcome before such mechanisms can be put in place, she said, “include ensuring standardized CAC reporting, avoiding overburdening healthcare providers, mitigating the risk of excessive downstream testing, and ensuring equitable access to follow-up care for underserved and rural communities.”

Providers involved in lung cancer screening “must be trained to recognize the importance of CAC findings and act upon them,” she added. “Awareness campaigns or continuing medical education modules could address this.”

Multidisciplinary lung cancer screening programs can help with patient education, she noted. “Clear communication about potential findings, including the significance of incidental CAC, should be prioritized and addressed proactively, ideally before the exam, to enhance patient understanding and engagement.”

Matthew Tomey, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City, said that, “as a practicing cardiologist, I find it very helpful to look at my patients’ recent or past CT scans to look for vascular calcification. Whether or not a scan is specifically protocoled as a cardiac study, we can often appreciate vascular calcification when it is present. I would encourage every physician involved in helping their patients to prevent heart disease to take advantage of looking at any prior CT scans for evidence of vascular calcification.

“Systems of care to facilitate recognition of patients with incidentally discovered vascular calcification would be welcome and, on a large scale, could help prevent cardiovascular events,” he noted. “Such a system might involve facilitating referral to a prevention specialist. It could involve evidence-based guidance for referring physicians who ordered scans.”

Like Bader, he noted the importance of patient education, adding that it could be quite powerful. “We should be doing more to empower our patients to understand the findings of their imaging and to give them actionable, evidence-based guidance on how they can promote their own cardiovascular health,” he concluded.

No funding for the study was reported. Small reported receiving a research grant for amyloid research from Pfizer and honoraria from Pfizer and Alnylam (all paid to the institution, outside the submitted work). Bader and Tomey declared no relevant conflicts.

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

TOPLINE:

Internet use is associated with fewer depressive symptoms, higher life satisfaction, and better self-reported health among adults aged 50 years or older across 23 countries than nonuse, a new cohort study suggests.

METHODOLOGY:

• Data were examined for more than 87,000 adults aged 50 years or older across 23 countries and from six aging cohorts.
• Researchers examined the potential association between internet use and mental health outcomes, including depressive symptoms, life satisfaction, and self-reported health.
• Polygenic scores were used for subset analysis to stratify participants from England and the United States according to their genetic risk for depression.
• Participants were followed up for a median of 6 years.

TAKEAWAY:

• Internet use was linked to consistent benefits across countries, including lower depressive symptoms (pooled average marginal effect [AME], –0.09; 95% CI, –0.12 to –0.07), higher life satisfaction (pooled AME, 0.07; 95% CI, 0.05-0.10), and better self-reported health (pooled AME, 0.15; 95% CI, 0.12-0.17).
• Frequent internet users showed better mental health outcomes than nonusers, and daily internet users showed significant improvements in depressive symptoms and self-reported health in England and the United States.
• Each additional wave of internet use was associated with reduced depressive symptoms (pooled AME, –0.06; 95% CI, –0.09 to –0.04) and improved life satisfaction (pooled AME, 0.05; 95% CI, 0.03-0.07).
• Benefits of internet use were observed across all genetic risk categories for depression in England and the United States, suggesting potential utility regardless of genetic predisposition.

IN PRACTICE:

“Our findings are relevant to public health policies and practices in promoting mental health in later life through the internet, especially in countries with limited internet access and mental health services,” the investigators wrote.

SOURCE:

The study was led by Yan Luo, Department of Data Science, City University of Hong Kong, Hong Kong, China. It was published online November 18 in Nature Human Behaviour.

LIMITATIONS:

The possibility of residual confounding and reverse causation prevented the establishment of direct causality between internet use and mental health. Selection bias may have also existed due to differences in baseline characteristics between the analytic samples and entire populations. Internet use was assessed through self-reported items, which could have led to recall and information bias. Additionally, genetic data were available for participants only from England and the United States.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China. The investigators reported no conflicts of interest.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Internet use is associated with fewer depressive symptoms, higher life satisfaction, and better self-reported health among adults aged 50 years or older across 23 countries than nonuse, a new cohort study suggests.

METHODOLOGY:

• Data were examined for more than 87,000 adults aged 50 years or older across 23 countries and from six aging cohorts.
• Researchers examined the potential association between internet use and mental health outcomes, including depressive symptoms, life satisfaction, and self-reported health.
• Polygenic scores were used for subset analysis to stratify participants from England and the United States according to their genetic risk for depression.
• Participants were followed up for a median of 6 years.

TAKEAWAY:

• Internet use was linked to consistent benefits across countries, including lower depressive symptoms (pooled average marginal effect [AME], –0.09; 95% CI, –0.12 to –0.07), higher life satisfaction (pooled AME, 0.07; 95% CI, 0.05-0.10), and better self-reported health (pooled AME, 0.15; 95% CI, 0.12-0.17).
• Frequent internet users showed better mental health outcomes than nonusers, and daily internet users showed significant improvements in depressive symptoms and self-reported health in England and the United States.
• Each additional wave of internet use was associated with reduced depressive symptoms (pooled AME, –0.06; 95% CI, –0.09 to –0.04) and improved life satisfaction (pooled AME, 0.05; 95% CI, 0.03-0.07).
• Benefits of internet use were observed across all genetic risk categories for depression in England and the United States, suggesting potential utility regardless of genetic predisposition.

IN PRACTICE:

“Our findings are relevant to public health policies and practices in promoting mental health in later life through the internet, especially in countries with limited internet access and mental health services,” the investigators wrote.

SOURCE:

The study was led by Yan Luo, Department of Data Science, City University of Hong Kong, Hong Kong, China. It was published online November 18 in Nature Human Behaviour.

LIMITATIONS:

The possibility of residual confounding and reverse causation prevented the establishment of direct causality between internet use and mental health. Selection bias may have also existed due to differences in baseline characteristics between the analytic samples and entire populations. Internet use was assessed through self-reported items, which could have led to recall and information bias. Additionally, genetic data were available for participants only from England and the United States.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China. The investigators reported no conflicts of interest.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Internet use is associated with fewer depressive symptoms, higher life satisfaction, and better self-reported health among adults aged 50 years or older across 23 countries than nonuse, a new cohort study suggests.

METHODOLOGY:

• Data were examined for more than 87,000 adults aged 50 years or older across 23 countries and from six aging cohorts.
• Researchers examined the potential association between internet use and mental health outcomes, including depressive symptoms, life satisfaction, and self-reported health.
• Polygenic scores were used for subset analysis to stratify participants from England and the United States according to their genetic risk for depression.
• Participants were followed up for a median of 6 years.

TAKEAWAY:

• Internet use was linked to consistent benefits across countries, including lower depressive symptoms (pooled average marginal effect [AME], –0.09; 95% CI, –0.12 to –0.07), higher life satisfaction (pooled AME, 0.07; 95% CI, 0.05-0.10), and better self-reported health (pooled AME, 0.15; 95% CI, 0.12-0.17).
• Frequent internet users showed better mental health outcomes than nonusers, and daily internet users showed significant improvements in depressive symptoms and self-reported health in England and the United States.
• Each additional wave of internet use was associated with reduced depressive symptoms (pooled AME, –0.06; 95% CI, –0.09 to –0.04) and improved life satisfaction (pooled AME, 0.05; 95% CI, 0.03-0.07).
• Benefits of internet use were observed across all genetic risk categories for depression in England and the United States, suggesting potential utility regardless of genetic predisposition.

IN PRACTICE:

“Our findings are relevant to public health policies and practices in promoting mental health in later life through the internet, especially in countries with limited internet access and mental health services,” the investigators wrote.

SOURCE:

The study was led by Yan Luo, Department of Data Science, City University of Hong Kong, Hong Kong, China. It was published online November 18 in Nature Human Behaviour.

LIMITATIONS:

The possibility of residual confounding and reverse causation prevented the establishment of direct causality between internet use and mental health. Selection bias may have also existed due to differences in baseline characteristics between the analytic samples and entire populations. Internet use was assessed through self-reported items, which could have led to recall and information bias. Additionally, genetic data were available for participants only from England and the United States.

DISCLOSURES:

The study was funded in part by the National Natural Science Foundation of China. The investigators reported no conflicts of interest.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

They’re literally not better. Idealistically, sure, but literally not. And there’s really no debate. Meaning there’s never been a reproducible diet and exercise intervention that has led to anywhere near the average weight lost by those taking obesity medications. Furthermore, when it comes to the durability of weight lost, the gulf between outcomes with diet and exercise vs obesity medications is even more dramatic.

Looking to the literature, one of the most trotted out studies on lifestyle’s impact on weight over time is the Look AHEAD trial. Before useful obesity medications came on the scene, I trotted it out myself. Why? Because it was heartening when faced with the societal refrain that diet and exercise never worked to be able to show that yes, in fact they do. But how well?

Looking to Look AHEAD’s 4-year data (Obesity [Silver Spring]. 2011 Oct;19[10]:1987-1998), those randomized to the intensive lifestyle initiative arm averaged a 4.7% total body weight loss – an amount that remained the same at 8 years. But I chose 4 years because that’s a better comparison with the semaglutide SELECT trial that revealed at 4 years, the average sustained weight lost was more than double that of Look AHEAD’s, at 10.2%. Meanwhile the recently released SURMOUNT-4 study on tirzepatide reported that at 88 weeks, the average weight lost by participants was a near bariatric surgery level of 25.3% with no signs suggestive of pending regains.

Now maybe you want to cling to the notion that if you just try hard enough, your diet and exercise regime can beat our new meds. Well, it’s difficult to think of a more miserable, often actual vomit-inducing intervention, than the spectacle that used to air weekly on prime time called The Biggest Loser, where participants lived on a ranch and were berated and exercised all day long for the chance to lose the most and win a quarter of a million dollars. But even there, the meds prove to be superior. Although the short-term Biggest Loser data do look markedly better than meds (and than bariatric surgery), whereby the average participant lost 48.8% of their body weight during the grueling 7-month long, 24/7 competition, by postcompetition year 6, the average weight lost dropped to 12.7%.

Yet on November 26, when word came out that Medicare is likely to extend coverage to obesity medications for far more Americans, one of the most common refrains was something along the lines of yes, lifestyle modification is the best choice for dealing with obesity but it’s good that there will be medication options for those where that’s insufficient.

What?

The only reason that the world isn’t comfortable with the eminently provable truth that diet and exercise are inferior to obesity medications for weight management is weight bias. The message is that people simply aren’t trying hard enough. This despite our comfort in knowing that medications have more of an impact than lifestyle on pretty much every other chronic disease. Nor can I recall any other circumstance when coverage of a remarkably effective drug was qualified by the suggestion that known-to-be-inferior interventions are still the best or favored choice.

At this point, obesity medications are plainly the first-line choice of treatment. They provide not only dramatically greater and more durable weight loss than lifestyle interventions, they have also been shown to very significantly reduce the risk for an ever-growing list of other medical concerns including heart attacks, strokes, type 2 diabetes, hypertension, sleep apnea, fatty liver disease, and more, while carrying minimal risk.

Let it also be said that improvements to diet and exercise are worth striving for at any weight, though one should not lose sight of the fact that perpetual, dramatic, intentional, behavior change in the name of health requires vast amounts of wide-ranging privilege to enact — amounts far beyond the average person’s abilities or physiologies (as demonstrated with obesity by decades of disappointing long-term lifestyle outcome data). 

Let it also be said that some people will indeed find success solely through lifestyle and that not every person who meets the medical criteria for any medication’s prescription, including obesity medications, is required or encouraged to take it. The clinician’s job, however, at its most basic, is to inform patients who meet medical use criteria of their options, and if a medication is indicated, to inform them of that medication’s risks and benefits and expected outcomes, to help their patients come to their own treatment decisions.

It’s not a bad thing that we have medications that deliver better outcomes than lifestyle — in fact, it’s terrific, and thankfully that they do is true for pretty much every medical condition for which we have medication. That’s in fact why we have medications! And so this constant refrain of golly-gee wouldn’t it be better if we could just manage obesity with lifestyle changes needs to be put to rest — we literally know it wouldn’t be better, and it’s only weight bias that would lead this evidence-based statement to seem off-putting.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa, and Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He reported conflicts of interest with the Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

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

They’re literally not better. Idealistically, sure, but literally not. And there’s really no debate. Meaning there’s never been a reproducible diet and exercise intervention that has led to anywhere near the average weight lost by those taking obesity medications. Furthermore, when it comes to the durability of weight lost, the gulf between outcomes with diet and exercise vs obesity medications is even more dramatic.

Looking to the literature, one of the most trotted out studies on lifestyle’s impact on weight over time is the Look AHEAD trial. Before useful obesity medications came on the scene, I trotted it out myself. Why? Because it was heartening when faced with the societal refrain that diet and exercise never worked to be able to show that yes, in fact they do. But how well?

Looking to Look AHEAD’s 4-year data (Obesity [Silver Spring]. 2011 Oct;19[10]:1987-1998), those randomized to the intensive lifestyle initiative arm averaged a 4.7% total body weight loss – an amount that remained the same at 8 years. But I chose 4 years because that’s a better comparison with the semaglutide SELECT trial that revealed at 4 years, the average sustained weight lost was more than double that of Look AHEAD’s, at 10.2%. Meanwhile the recently released SURMOUNT-4 study on tirzepatide reported that at 88 weeks, the average weight lost by participants was a near bariatric surgery level of 25.3% with no signs suggestive of pending regains.

Now maybe you want to cling to the notion that if you just try hard enough, your diet and exercise regime can beat our new meds. Well, it’s difficult to think of a more miserable, often actual vomit-inducing intervention, than the spectacle that used to air weekly on prime time called The Biggest Loser, where participants lived on a ranch and were berated and exercised all day long for the chance to lose the most and win a quarter of a million dollars. But even there, the meds prove to be superior. Although the short-term Biggest Loser data do look markedly better than meds (and than bariatric surgery), whereby the average participant lost 48.8% of their body weight during the grueling 7-month long, 24/7 competition, by postcompetition year 6, the average weight lost dropped to 12.7%.

Yet on November 26, when word came out that Medicare is likely to extend coverage to obesity medications for far more Americans, one of the most common refrains was something along the lines of yes, lifestyle modification is the best choice for dealing with obesity but it’s good that there will be medication options for those where that’s insufficient.

What?

The only reason that the world isn’t comfortable with the eminently provable truth that diet and exercise are inferior to obesity medications for weight management is weight bias. The message is that people simply aren’t trying hard enough. This despite our comfort in knowing that medications have more of an impact than lifestyle on pretty much every other chronic disease. Nor can I recall any other circumstance when coverage of a remarkably effective drug was qualified by the suggestion that known-to-be-inferior interventions are still the best or favored choice.

At this point, obesity medications are plainly the first-line choice of treatment. They provide not only dramatically greater and more durable weight loss than lifestyle interventions, they have also been shown to very significantly reduce the risk for an ever-growing list of other medical concerns including heart attacks, strokes, type 2 diabetes, hypertension, sleep apnea, fatty liver disease, and more, while carrying minimal risk.

Let it also be said that improvements to diet and exercise are worth striving for at any weight, though one should not lose sight of the fact that perpetual, dramatic, intentional, behavior change in the name of health requires vast amounts of wide-ranging privilege to enact — amounts far beyond the average person’s abilities or physiologies (as demonstrated with obesity by decades of disappointing long-term lifestyle outcome data). 

Let it also be said that some people will indeed find success solely through lifestyle and that not every person who meets the medical criteria for any medication’s prescription, including obesity medications, is required or encouraged to take it. The clinician’s job, however, at its most basic, is to inform patients who meet medical use criteria of their options, and if a medication is indicated, to inform them of that medication’s risks and benefits and expected outcomes, to help their patients come to their own treatment decisions.

It’s not a bad thing that we have medications that deliver better outcomes than lifestyle — in fact, it’s terrific, and thankfully that they do is true for pretty much every medical condition for which we have medication. That’s in fact why we have medications! And so this constant refrain of golly-gee wouldn’t it be better if we could just manage obesity with lifestyle changes needs to be put to rest — we literally know it wouldn’t be better, and it’s only weight bias that would lead this evidence-based statement to seem off-putting.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa, and Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He reported conflicts of interest with the Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

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

They’re literally not better. Idealistically, sure, but literally not. And there’s really no debate. Meaning there’s never been a reproducible diet and exercise intervention that has led to anywhere near the average weight lost by those taking obesity medications. Furthermore, when it comes to the durability of weight lost, the gulf between outcomes with diet and exercise vs obesity medications is even more dramatic.

Looking to the literature, one of the most trotted out studies on lifestyle’s impact on weight over time is the Look AHEAD trial. Before useful obesity medications came on the scene, I trotted it out myself. Why? Because it was heartening when faced with the societal refrain that diet and exercise never worked to be able to show that yes, in fact they do. But how well?

Looking to Look AHEAD’s 4-year data (Obesity [Silver Spring]. 2011 Oct;19[10]:1987-1998), those randomized to the intensive lifestyle initiative arm averaged a 4.7% total body weight loss – an amount that remained the same at 8 years. But I chose 4 years because that’s a better comparison with the semaglutide SELECT trial that revealed at 4 years, the average sustained weight lost was more than double that of Look AHEAD’s, at 10.2%. Meanwhile the recently released SURMOUNT-4 study on tirzepatide reported that at 88 weeks, the average weight lost by participants was a near bariatric surgery level of 25.3% with no signs suggestive of pending regains.

Now maybe you want to cling to the notion that if you just try hard enough, your diet and exercise regime can beat our new meds. Well, it’s difficult to think of a more miserable, often actual vomit-inducing intervention, than the spectacle that used to air weekly on prime time called The Biggest Loser, where participants lived on a ranch and were berated and exercised all day long for the chance to lose the most and win a quarter of a million dollars. But even there, the meds prove to be superior. Although the short-term Biggest Loser data do look markedly better than meds (and than bariatric surgery), whereby the average participant lost 48.8% of their body weight during the grueling 7-month long, 24/7 competition, by postcompetition year 6, the average weight lost dropped to 12.7%.

Yet on November 26, when word came out that Medicare is likely to extend coverage to obesity medications for far more Americans, one of the most common refrains was something along the lines of yes, lifestyle modification is the best choice for dealing with obesity but it’s good that there will be medication options for those where that’s insufficient.

What?

The only reason that the world isn’t comfortable with the eminently provable truth that diet and exercise are inferior to obesity medications for weight management is weight bias. The message is that people simply aren’t trying hard enough. This despite our comfort in knowing that medications have more of an impact than lifestyle on pretty much every other chronic disease. Nor can I recall any other circumstance when coverage of a remarkably effective drug was qualified by the suggestion that known-to-be-inferior interventions are still the best or favored choice.

At this point, obesity medications are plainly the first-line choice of treatment. They provide not only dramatically greater and more durable weight loss than lifestyle interventions, they have also been shown to very significantly reduce the risk for an ever-growing list of other medical concerns including heart attacks, strokes, type 2 diabetes, hypertension, sleep apnea, fatty liver disease, and more, while carrying minimal risk.

Let it also be said that improvements to diet and exercise are worth striving for at any weight, though one should not lose sight of the fact that perpetual, dramatic, intentional, behavior change in the name of health requires vast amounts of wide-ranging privilege to enact — amounts far beyond the average person’s abilities or physiologies (as demonstrated with obesity by decades of disappointing long-term lifestyle outcome data). 

Let it also be said that some people will indeed find success solely through lifestyle and that not every person who meets the medical criteria for any medication’s prescription, including obesity medications, is required or encouraged to take it. The clinician’s job, however, at its most basic, is to inform patients who meet medical use criteria of their options, and if a medication is indicated, to inform them of that medication’s risks and benefits and expected outcomes, to help their patients come to their own treatment decisions.

It’s not a bad thing that we have medications that deliver better outcomes than lifestyle — in fact, it’s terrific, and thankfully that they do is true for pretty much every medical condition for which we have medication. That’s in fact why we have medications! And so this constant refrain of golly-gee wouldn’t it be better if we could just manage obesity with lifestyle changes needs to be put to rest — we literally know it wouldn’t be better, and it’s only weight bias that would lead this evidence-based statement to seem off-putting.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa, and Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He reported conflicts of interest with the Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

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.

“A focus on neoantigens that arise from driver mutations in different tumor types could allow us to make progress in creating off-the-shelf vaccines,” 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.

“A focus on neoantigens that arise from driver mutations in different tumor types could allow us to make progress in creating off-the-shelf vaccines,” 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.

“A focus on neoantigens that arise from driver mutations in different tumor types could allow us to make progress in creating off-the-shelf vaccines,” 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.

As the respiratory season approaches, the risk of asthma emergencies often increases, particularly for those with preexisting conditions. 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/

As the respiratory season approaches, the risk of asthma emergencies often increases, particularly for those with preexisting conditions. 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/

As the respiratory season approaches, the risk of asthma emergencies often increases, particularly for those with preexisting conditions. 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/

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). Prior to this year, guidelines for ILD screening, monitoring, and treatment in this high-risk population did not exist. 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). Prior to this year, guidelines for ILD screening, monitoring, and treatment in this high-risk population did not exist. 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). Prior to this year, guidelines for ILD screening, monitoring, and treatment in this high-risk population did not exist. 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.

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

In the December issue of CHEST Pulmonary, the Interventional Pulmonary Outcomes Group (IPOG) described the VERITAS trial, 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

In the December issue of CHEST Pulmonary, the Interventional Pulmonary Outcomes Group (IPOG) described the VERITAS trial, 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

In the December issue of CHEST Pulmonary, the Interventional Pulmonary Outcomes Group (IPOG) described the VERITAS trial, 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

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.

The Food and Drug Administration (FDA) has granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus) as an intravenous infusion for the treatment of certain adults with non–small cell lung cancer (NSCLC) or pancreatic adenocarcinoma.

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.

The Food and Drug Administration (FDA) has granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus) as an intravenous infusion for the treatment of certain adults with non–small cell lung cancer (NSCLC) or pancreatic adenocarcinoma.

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.

The Food and Drug Administration (FDA) has granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus) as an intravenous infusion for the treatment of certain adults with non–small cell lung cancer (NSCLC) or pancreatic adenocarcinoma.

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.

What is the best upfront chemotherapy option for patients with colorectal cancer (CRC) and unresectable liver metastases?

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.

What is the best upfront chemotherapy option for patients with colorectal cancer (CRC) and unresectable liver metastases?

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.

What is the best upfront chemotherapy option for patients with colorectal cancer (CRC) and unresectable liver metastases?

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.