Vasomotor symptoms the sudden rises in body temperature that affect about 75% of menopausal women, have drawn interest after the approval of a new oral drug and research linking hot flashes to Alzheimer’s, heart disease, and stroke. 

Now entering the discussion are researchers from the University of Massachusetts, Amherst, and Embr Labs (a Massachusetts Institute of Technology spinoff) who say they’ve developed a machine-learning algorithm that can predict a hot flash. 

Their idea is to combine this algorithm with a product called Embr Wave, a watch-like wearable that can emit coolness (or warmth) to the sensitive skin on the inside of the wrist, providing whole-body relief. The device, which sells for $299, is already touted as a way to manage menopausal hot flashes. 

But once the algorithm is added, the device will be able to “continuously monitor physiological signals – skin temperature, body temperature, sweating, activity level, or heart rate – and identify early indicators that a hot flash is building,” said Michael Busa, PhD, director of the Center for Human Health and Performance at UMass Amherst, who led the team that developed the algorithm.

That data would be sent to a computing platform in the cloud, where the algorithm can flag signs of an impending hot flash, Dr. Busa said. The device would automatically prompt cooling in less than a second, which could effectively stop the hot flash in its tracks or at least help to take the edge off. 
 

Exploring cooling therapy for hot flashes

“There is always tremendous interest in anything that is nonhormonal and effective in treatment of hot flashes,” said Karen Adams, MD, an ob.gyn. and director of the menopause and healthy aging program at Stanford (Calif.) University. (Dr. Adams was not involved in developing this technology.) 

Hormone therapy is the primary treatment, easing hot flashes in 3-4 weeks, Dr. Adams said. “But some women do not want to take estrogen, or should not due to medical contraindications.” 

Hormone therapy is generally not recommended for people with a history of breast cancer, blood clots, or diseases of their heart or blood vessels. Recent research presented at the annual meeting of the Menopause Society found that hormone therapy may not work as well in women with obesity. 

For nonhormonal treatments, the Food and Drug Administration cleared the oral med fezolinetant (Veozah) in May. Antidepressant medications can also be used as a first-line treatment in those who can’t take estrogen. Another oral drug, elinzanetant, is in late-stage clinical trials. 

But there has been little clinical investigation – only two small studies, Dr. Adams said – examining cooling therapy as a treatment for hot flashes. That’s something the makers of this device hope to change. 

“Despite the fact that seeking cooling relief is a woman’s immediate natural response to the onset of a hot flash, there is limited work done to understand the benefits of this natural therapy,” said Matthew Smith, PhD, chief technology officer at Embr Labs. “This is in part because the technology didn’t exist to deliver cooling in an immediate, reproducible manner.”

The algorithm’s performance has been benchmarked using data from women having hot flashes, Dr. Smith said. Results have been submitted for publication.

The Embr Wave has been shown to help menopausal women with hot flashes sleep better. It has also been tested as a therapy for hot flashes related to cancer treatment. 

But to truly evaluate the device as a treatment for hot flashes, it should be tested in randomized trials including a “sham treatment arm” – where some people get the real treatment while others get the sham treatment, Dr. Adams said. 

“Device studies tend to have high placebo response rates that can only be truly evaluated when there is a sham treatment in the study,” she said. “If such a device were shown to be safe and effective, we would absolutely recommend it. But we’re a long way from that.”

A version of this article appeared on WebMD.com.

Vasomotor symptoms the sudden rises in body temperature that affect about 75% of menopausal women, have drawn interest after the approval of a new oral drug and research linking hot flashes to Alzheimer’s, heart disease, and stroke. 

Now entering the discussion are researchers from the University of Massachusetts, Amherst, and Embr Labs (a Massachusetts Institute of Technology spinoff) who say they’ve developed a machine-learning algorithm that can predict a hot flash. 

Their idea is to combine this algorithm with a product called Embr Wave, a watch-like wearable that can emit coolness (or warmth) to the sensitive skin on the inside of the wrist, providing whole-body relief. The device, which sells for $299, is already touted as a way to manage menopausal hot flashes. 

But once the algorithm is added, the device will be able to “continuously monitor physiological signals – skin temperature, body temperature, sweating, activity level, or heart rate – and identify early indicators that a hot flash is building,” said Michael Busa, PhD, director of the Center for Human Health and Performance at UMass Amherst, who led the team that developed the algorithm.

That data would be sent to a computing platform in the cloud, where the algorithm can flag signs of an impending hot flash, Dr. Busa said. The device would automatically prompt cooling in less than a second, which could effectively stop the hot flash in its tracks or at least help to take the edge off. 
 

Exploring cooling therapy for hot flashes

“There is always tremendous interest in anything that is nonhormonal and effective in treatment of hot flashes,” said Karen Adams, MD, an ob.gyn. and director of the menopause and healthy aging program at Stanford (Calif.) University. (Dr. Adams was not involved in developing this technology.) 

Hormone therapy is the primary treatment, easing hot flashes in 3-4 weeks, Dr. Adams said. “But some women do not want to take estrogen, or should not due to medical contraindications.” 

Hormone therapy is generally not recommended for people with a history of breast cancer, blood clots, or diseases of their heart or blood vessels. Recent research presented at the annual meeting of the Menopause Society found that hormone therapy may not work as well in women with obesity. 

For nonhormonal treatments, the Food and Drug Administration cleared the oral med fezolinetant (Veozah) in May. Antidepressant medications can also be used as a first-line treatment in those who can’t take estrogen. Another oral drug, elinzanetant, is in late-stage clinical trials. 

But there has been little clinical investigation – only two small studies, Dr. Adams said – examining cooling therapy as a treatment for hot flashes. That’s something the makers of this device hope to change. 

“Despite the fact that seeking cooling relief is a woman’s immediate natural response to the onset of a hot flash, there is limited work done to understand the benefits of this natural therapy,” said Matthew Smith, PhD, chief technology officer at Embr Labs. “This is in part because the technology didn’t exist to deliver cooling in an immediate, reproducible manner.”

The algorithm’s performance has been benchmarked using data from women having hot flashes, Dr. Smith said. Results have been submitted for publication.

The Embr Wave has been shown to help menopausal women with hot flashes sleep better. It has also been tested as a therapy for hot flashes related to cancer treatment. 

But to truly evaluate the device as a treatment for hot flashes, it should be tested in randomized trials including a “sham treatment arm” – where some people get the real treatment while others get the sham treatment, Dr. Adams said. 

“Device studies tend to have high placebo response rates that can only be truly evaluated when there is a sham treatment in the study,” she said. “If such a device were shown to be safe and effective, we would absolutely recommend it. But we’re a long way from that.”

A version of this article appeared on WebMD.com.

Vasomotor symptoms the sudden rises in body temperature that affect about 75% of menopausal women, have drawn interest after the approval of a new oral drug and research linking hot flashes to Alzheimer’s, heart disease, and stroke. 

Now entering the discussion are researchers from the University of Massachusetts, Amherst, and Embr Labs (a Massachusetts Institute of Technology spinoff) who say they’ve developed a machine-learning algorithm that can predict a hot flash. 

Their idea is to combine this algorithm with a product called Embr Wave, a watch-like wearable that can emit coolness (or warmth) to the sensitive skin on the inside of the wrist, providing whole-body relief. The device, which sells for $299, is already touted as a way to manage menopausal hot flashes. 

But once the algorithm is added, the device will be able to “continuously monitor physiological signals – skin temperature, body temperature, sweating, activity level, or heart rate – and identify early indicators that a hot flash is building,” said Michael Busa, PhD, director of the Center for Human Health and Performance at UMass Amherst, who led the team that developed the algorithm.

That data would be sent to a computing platform in the cloud, where the algorithm can flag signs of an impending hot flash, Dr. Busa said. The device would automatically prompt cooling in less than a second, which could effectively stop the hot flash in its tracks or at least help to take the edge off. 
 

Exploring cooling therapy for hot flashes

“There is always tremendous interest in anything that is nonhormonal and effective in treatment of hot flashes,” said Karen Adams, MD, an ob.gyn. and director of the menopause and healthy aging program at Stanford (Calif.) University. (Dr. Adams was not involved in developing this technology.) 

Hormone therapy is the primary treatment, easing hot flashes in 3-4 weeks, Dr. Adams said. “But some women do not want to take estrogen, or should not due to medical contraindications.” 

Hormone therapy is generally not recommended for people with a history of breast cancer, blood clots, or diseases of their heart or blood vessels. Recent research presented at the annual meeting of the Menopause Society found that hormone therapy may not work as well in women with obesity. 

For nonhormonal treatments, the Food and Drug Administration cleared the oral med fezolinetant (Veozah) in May. Antidepressant medications can also be used as a first-line treatment in those who can’t take estrogen. Another oral drug, elinzanetant, is in late-stage clinical trials. 

But there has been little clinical investigation – only two small studies, Dr. Adams said – examining cooling therapy as a treatment for hot flashes. That’s something the makers of this device hope to change. 

“Despite the fact that seeking cooling relief is a woman’s immediate natural response to the onset of a hot flash, there is limited work done to understand the benefits of this natural therapy,” said Matthew Smith, PhD, chief technology officer at Embr Labs. “This is in part because the technology didn’t exist to deliver cooling in an immediate, reproducible manner.”

The algorithm’s performance has been benchmarked using data from women having hot flashes, Dr. Smith said. Results have been submitted for publication.

The Embr Wave has been shown to help menopausal women with hot flashes sleep better. It has also been tested as a therapy for hot flashes related to cancer treatment. 

But to truly evaluate the device as a treatment for hot flashes, it should be tested in randomized trials including a “sham treatment arm” – where some people get the real treatment while others get the sham treatment, Dr. Adams said. 

“Device studies tend to have high placebo response rates that can only be truly evaluated when there is a sham treatment in the study,” she said. “If such a device were shown to be safe and effective, we would absolutely recommend it. But we’re a long way from that.”

A version of this article appeared on WebMD.com.

Prescriptions for semaglutide jumped 150% in the past year, with an 80% increase in prescriptions written per provider, new data suggest.

Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.

Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.

General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.

“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.

Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”

Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
 

Are patients actually getting the prescribed medications?

However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”

Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.

Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”

Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.

Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”

Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”

The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.

A version of this article appeared on Medscape.com.

Prescriptions for semaglutide jumped 150% in the past year, with an 80% increase in prescriptions written per provider, new data suggest.

Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.

Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.

General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.

“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.

Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”

Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
 

Are patients actually getting the prescribed medications?

However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”

Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.

Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”

Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.

Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”

Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”

The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.

A version of this article appeared on Medscape.com.

Prescriptions for semaglutide jumped 150% in the past year, with an 80% increase in prescriptions written per provider, new data suggest.

Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.

Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.

General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.

“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.

Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”

Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
 

Are patients actually getting the prescribed medications?

However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”

Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.

Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”

Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.

Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”

Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”

The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.

A version of this article appeared on Medscape.com.

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

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

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

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

Should older physicians be forced to undergo cognitive tests to stay on the job? One 84-year-old ophthalmologist is suing her Michigan employer to stop the practice.

Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.

Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.

According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.

Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.

The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.

The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.

The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.

There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.

Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.

It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.

However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.

“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.

In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”

Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”

However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”

Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.

What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.

One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”

Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.

So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”

Ms. Hoffman has no disclosures.

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

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

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

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

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

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

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

The U.S. Food and Drug Administration has approved secukinumab for adults with moderate to severe hidradenitis suppurativa (HS).

The development, which was announced Oct. 31, makes secukinumab the first and only interleukin (IL)–17A inhibitor approved by the FDA for HS, which affects an estimated 1% of the worldwide population. It joins the tumor necrosis factor blocker adalimumab as the only FDA-approved treatment options for HS.

Secukinumab (Cosentyx) was previously approved by the FDA for treatment of  moderate-to-severe plaque psoriasis in adults, and several other indications including psoriatic arthritis and ankylosing spondylitis.

Approval for HS was based on the pivotal phase 3 SUNSHINE and SUNRISE trials, which had a combined enrollment of more than 1,000 patients with HS in 40 countries. The studies evaluated efficacy, safety, and tolerability of two dose regimens of the drug in adults with moderate to severe HS at 16 weeks and up to 52 weeks.

According to a press release from Novartis announcing the approval, results at week 16 showed that a significantly higher proportion of patients achieved a Hidradenitis Suppurativa Clinical Response (HiSCR) when treated with secukinumab 300 mg every 2 weeks, compared with placebo: 44.5% vs. 29.4%, respectively, in the SUNSHINE trial and 38.3.% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

Similarly, results at week 16 showed that a significantly higher proportion of patients achieved an HiSCR when treated with secukinumab 300 mg every 4 weeks, compared with placebo: 41.3% vs. 29.4% in the SUNSHINE trial and 42.5% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

In addition, in an exploratory analysis out to 52 weeks, HiSCR values observed at week 16 following either dose regimen of secukinumab were improved over time up to week 52. In SUNSHINE, the values improved by 56.4% in patients treated with secukinumab every 3 weeks and by 56.3% in those treated with secukinumab every 4 weeks. In SUNRISE, the values improved by 65% in patients who were treated with secukinumab every 2 weeks and by 62.2% in those who were treated with the drug every 4 weeks.

In an interview, Haley Naik, MD, a dermatologist who directs the hidradenitis suppurativa program at the University of California, San Francisco, characterized the approval as a win for HS patients. “Patients now not only have a second option for approved therapy for HS, but also an option that raises the bar for what we can expect from therapeutic response,” she told this news organization. “I am excited to see a novel therapy that improves HS and quality of life for patients make it through the regulatory pipeline.”

Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, Union Chimique Belge, and Novartis; investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.

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

The U.S. Food and Drug Administration has approved secukinumab for adults with moderate to severe hidradenitis suppurativa (HS).

The development, which was announced Oct. 31, makes secukinumab the first and only interleukin (IL)–17A inhibitor approved by the FDA for HS, which affects an estimated 1% of the worldwide population. It joins the tumor necrosis factor blocker adalimumab as the only FDA-approved treatment options for HS.

Secukinumab (Cosentyx) was previously approved by the FDA for treatment of  moderate-to-severe plaque psoriasis in adults, and several other indications including psoriatic arthritis and ankylosing spondylitis.

Approval for HS was based on the pivotal phase 3 SUNSHINE and SUNRISE trials, which had a combined enrollment of more than 1,000 patients with HS in 40 countries. The studies evaluated efficacy, safety, and tolerability of two dose regimens of the drug in adults with moderate to severe HS at 16 weeks and up to 52 weeks.

According to a press release from Novartis announcing the approval, results at week 16 showed that a significantly higher proportion of patients achieved a Hidradenitis Suppurativa Clinical Response (HiSCR) when treated with secukinumab 300 mg every 2 weeks, compared with placebo: 44.5% vs. 29.4%, respectively, in the SUNSHINE trial and 38.3.% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

Similarly, results at week 16 showed that a significantly higher proportion of patients achieved an HiSCR when treated with secukinumab 300 mg every 4 weeks, compared with placebo: 41.3% vs. 29.4% in the SUNSHINE trial and 42.5% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

In addition, in an exploratory analysis out to 52 weeks, HiSCR values observed at week 16 following either dose regimen of secukinumab were improved over time up to week 52. In SUNSHINE, the values improved by 56.4% in patients treated with secukinumab every 3 weeks and by 56.3% in those treated with secukinumab every 4 weeks. In SUNRISE, the values improved by 65% in patients who were treated with secukinumab every 2 weeks and by 62.2% in those who were treated with the drug every 4 weeks.

In an interview, Haley Naik, MD, a dermatologist who directs the hidradenitis suppurativa program at the University of California, San Francisco, characterized the approval as a win for HS patients. “Patients now not only have a second option for approved therapy for HS, but also an option that raises the bar for what we can expect from therapeutic response,” she told this news organization. “I am excited to see a novel therapy that improves HS and quality of life for patients make it through the regulatory pipeline.”

Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, Union Chimique Belge, and Novartis; investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.

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

The U.S. Food and Drug Administration has approved secukinumab for adults with moderate to severe hidradenitis suppurativa (HS).

The development, which was announced Oct. 31, makes secukinumab the first and only interleukin (IL)–17A inhibitor approved by the FDA for HS, which affects an estimated 1% of the worldwide population. It joins the tumor necrosis factor blocker adalimumab as the only FDA-approved treatment options for HS.

Secukinumab (Cosentyx) was previously approved by the FDA for treatment of  moderate-to-severe plaque psoriasis in adults, and several other indications including psoriatic arthritis and ankylosing spondylitis.

Approval for HS was based on the pivotal phase 3 SUNSHINE and SUNRISE trials, which had a combined enrollment of more than 1,000 patients with HS in 40 countries. The studies evaluated efficacy, safety, and tolerability of two dose regimens of the drug in adults with moderate to severe HS at 16 weeks and up to 52 weeks.

According to a press release from Novartis announcing the approval, results at week 16 showed that a significantly higher proportion of patients achieved a Hidradenitis Suppurativa Clinical Response (HiSCR) when treated with secukinumab 300 mg every 2 weeks, compared with placebo: 44.5% vs. 29.4%, respectively, in the SUNSHINE trial and 38.3.% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

Similarly, results at week 16 showed that a significantly higher proportion of patients achieved an HiSCR when treated with secukinumab 300 mg every 4 weeks, compared with placebo: 41.3% vs. 29.4% in the SUNSHINE trial and 42.5% vs. 26.1% in the SUNRISE trial (P < .05 for both associations).

In addition, in an exploratory analysis out to 52 weeks, HiSCR values observed at week 16 following either dose regimen of secukinumab were improved over time up to week 52. In SUNSHINE, the values improved by 56.4% in patients treated with secukinumab every 3 weeks and by 56.3% in those treated with secukinumab every 4 weeks. In SUNRISE, the values improved by 65% in patients who were treated with secukinumab every 2 weeks and by 62.2% in those who were treated with the drug every 4 weeks.

In an interview, Haley Naik, MD, a dermatologist who directs the hidradenitis suppurativa program at the University of California, San Francisco, characterized the approval as a win for HS patients. “Patients now not only have a second option for approved therapy for HS, but also an option that raises the bar for what we can expect from therapeutic response,” she told this news organization. “I am excited to see a novel therapy that improves HS and quality of life for patients make it through the regulatory pipeline.”

Dr. Naik disclosed that she has received grant support from AbbVie; consulting fees from 23andme, AbbVie, Aristea Therapeutics, Nimbus Therapeutics, Medscape, Sonoma Biotherapeutics, DAVA Oncology, Boehringer Ingelheim, Union Chimique Belge, and Novartis; investigator fees from Pfizer; and holds shares in Radera. She is also an associate editor for JAMA Dermatology and a board member of the Hidradenitis Suppurativa Foundation.

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

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

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

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

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

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

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

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Key data on lung cancer presented at the American College of Chest Physicians (CHEST) 2023 meeting focused on eligibility for lung cancer screening, nonadherence to follow-up scans, and race-neutral interpretations of pulmonary function tests in preparation for lobectomy, as reported by Dr Lynn Tanoue of the Yale School of Medicine. Dr Tanoue discusses a study of 1 million people screened for lung cancer using low-dose CT imaging. The study found that 38% of those who did not meet the 2013 United States Preventive Services Task Force (USPTF) criteria for screening would now be eligible under the updated 2021 USPTF recommendations.  

The study also showed a lack of adherence to follow-up screening, indicating that only 22% of screened persons returned after 1 year for a subsequent scan. Nonadherence was more common in Black individuals, Hispanic individuals, and individuals without insurance. Dr Tanoue highlights the importance of adherence for return screening, noting that two thirds of cancers detected in the National Lung Screening Trial were diagnosed after the initial scan. 

Dr Tanoue also reviews a study examining the implications of adopting a race-neutral interpretation of pulmonary function tests for patients being considered for thoracic surgery. The study looked at data for 3,000 patients who underwent lobectomy at MD Anderson Cancer Center over 20 years and found that 85% were White individuals. Of importance, no difference was found between race-neutral or race-specific models in the association of lung function with risk for pulmonary complications. 

--

Lynn T. Tanoue, MD, FCCP, Professor, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut 

Lynn T. Tanoue, MD, FCCP, has disclosed no relevant financial relationships. 

Key data on lung cancer presented at the American College of Chest Physicians (CHEST) 2023 meeting focused on eligibility for lung cancer screening, nonadherence to follow-up scans, and race-neutral interpretations of pulmonary function tests in preparation for lobectomy, as reported by Dr Lynn Tanoue of the Yale School of Medicine. Dr Tanoue discusses a study of 1 million people screened for lung cancer using low-dose CT imaging. The study found that 38% of those who did not meet the 2013 United States Preventive Services Task Force (USPTF) criteria for screening would now be eligible under the updated 2021 USPTF recommendations.  

The study also showed a lack of adherence to follow-up screening, indicating that only 22% of screened persons returned after 1 year for a subsequent scan. Nonadherence was more common in Black individuals, Hispanic individuals, and individuals without insurance. Dr Tanoue highlights the importance of adherence for return screening, noting that two thirds of cancers detected in the National Lung Screening Trial were diagnosed after the initial scan. 

Dr Tanoue also reviews a study examining the implications of adopting a race-neutral interpretation of pulmonary function tests for patients being considered for thoracic surgery. The study looked at data for 3,000 patients who underwent lobectomy at MD Anderson Cancer Center over 20 years and found that 85% were White individuals. Of importance, no difference was found between race-neutral or race-specific models in the association of lung function with risk for pulmonary complications. 

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Lynn T. Tanoue, MD, FCCP, Professor, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut 

Lynn T. Tanoue, MD, FCCP, has disclosed no relevant financial relationships. 

Key data on lung cancer presented at the American College of Chest Physicians (CHEST) 2023 meeting focused on eligibility for lung cancer screening, nonadherence to follow-up scans, and race-neutral interpretations of pulmonary function tests in preparation for lobectomy, as reported by Dr Lynn Tanoue of the Yale School of Medicine. Dr Tanoue discusses a study of 1 million people screened for lung cancer using low-dose CT imaging. The study found that 38% of those who did not meet the 2013 United States Preventive Services Task Force (USPTF) criteria for screening would now be eligible under the updated 2021 USPTF recommendations.  

The study also showed a lack of adherence to follow-up screening, indicating that only 22% of screened persons returned after 1 year for a subsequent scan. Nonadherence was more common in Black individuals, Hispanic individuals, and individuals without insurance. Dr Tanoue highlights the importance of adherence for return screening, noting that two thirds of cancers detected in the National Lung Screening Trial were diagnosed after the initial scan. 

Dr Tanoue also reviews a study examining the implications of adopting a race-neutral interpretation of pulmonary function tests for patients being considered for thoracic surgery. The study looked at data for 3,000 patients who underwent lobectomy at MD Anderson Cancer Center over 20 years and found that 85% were White individuals. Of importance, no difference was found between race-neutral or race-specific models in the association of lung function with risk for pulmonary complications. 

--

Lynn T. Tanoue, MD, FCCP, Professor, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut 

Lynn T. Tanoue, MD, FCCP, has disclosed no relevant financial relationships. 

In patients with node-positive and locally advanced breast cancer (BC), postmastectomy radiation therapy (PMRT) decreases risk for recurrence and improves survival (Mutter et al). Proton therapy is an attractive newer way to deliver PMRT compared with photon-based methods and allows improved sparing of cardiopulmonary and other normal tissue. The phase 2 MC1631 trial included 82 patients with BC who underwent mastectomy with or without immediate breast reconstruction and who were randomly assigned to receive either conventional fractionated (50 Gy in 25 fractions of 2 Gy) or hypofractionated (40.05 Gy in 15 fractions of 2.67 Gy) proton PMRT. At a median follow-up of 39.3 months, both conventional fractionated and hypofractionated proton PMRT had similar complication rates (15% vs 20%; absolute difference 4.9%; one-sided 95% CI 18.5; P = .27), with most complications occurring in patients with immediate expander or implant-based reconstruction. Noninferiority of the hypofractionation group could not be determined after a median follow-up of 39 months. However, no isolated local regional recurrences in either treatment arm were seen. This study provides the first prospective, randomized data of hypofractionated proton PMRT. Further data are awaited to support this approach. 

In patients with metastatic hormone receptor (HR)–positive, PIK3CA-mutant BC, the combination of fulvestrant with alpelisib improves progression-free survival per the SOLAR-1 study.1 Higher rates of hyperglycemia observed among patients treated with alpelisib have led to alpelisib dose reductions, treatment delays, and discontinuation of the drug. In a retrospective cohort study of 247 patients with metastatic BC who received alpelisib either as standard care (n = 147) or in a clinical trial setting (n = 100), 61.5% of patients developed any-grade hyperglycemia (Shen et al). The rate of hyperglycemia was considerably higher in patients who received alpelisib as part of standard care vs clinical trial (80.3% vs 34.0%). Baseline body mass index ≥ 25 (P = .036) and A1c levels in the prediabetes and diabetes range were significantly associated with the development of any-grade hyperglycemia (P = .036 and P < .001, respectively) and grade 3-4 hyperglycemia (P < .001 for both). A total of 4.5% of patients discontinued alpelisib owing to hyperglycemia, 17% of patients required dose reductions, and in 27% of patients alpelisib was held until resolution of hyperglycemia. This study highlights the importance of the management of comorbidities before alpelisib treatment to ensure lower rates of adverse events. 

Patritumab deruxtecan (HER3-DXd) is a novel HER3-targeted antibody-drug conjugate that is being evaluated in HER3-expressing metastatic BC. The U31402-A-J101 study is a phase 1/2 trial including 182 heavily pretreated patients (median of five prior therapies) with HER3-expressing advanced BC who received HER3-DXd (Krop et al). The objective response rate was 30.1% (95% CI 21.8%-39.4%) in HR-positive, human epidermal growth factor receptor 2 (HER2)–negative BC, 22.6% (95% CI 12.3%-36.2%) in triple-negative BC, and 42.9% (95% CI 17.1%-71.1%) in HER2-positive BC. Although 71.4% of patients reported grade ≥ 3 treatment-emergent adverse events (TEAE), the overall rate of treatment discontinuation due to TEAE was low (9.9%). These findings demonstrate an encouraging efficacy and a manageable safety profile for patritumab deruxtecan in previously treated patients with BC across all subtypes. Further studies are awaited to confirm these findings and whether prior treatment with antibody-drug conjugate will affect the activity of this drug.

A retrospective analysis of a cohort including 149 patients with metastatic BC looked at predictors of prognosis in patients who had brain metastases and underwent stereotactic radiosurgery (Depner et al). The median overall survival was 14.8 months for the entire cohort. Receptor profiles and the presence of extracranial visceral metastases were significant predictors of prognosis. Overall survival outcomes worsened in patients with estrogen receptor (ER)–negative, HER2-negative BC (hazard ratio 2.00; 95% CI 1.09-3.67) but were better in those with ER-positive, HER2-positive BC (hazard ratio 0.43; 95% CI 0.19-0.96). Furthermore, the presence of extracranial visceral metastases was associated with poor survival outcomes (hazard ratio 2.90; 95% CI 1.53-5.50)

Additional Reference
1.    André F et al, for the SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929-1940. doi: 10.1056/NEJMoa1813904
 

In patients with node-positive and locally advanced breast cancer (BC), postmastectomy radiation therapy (PMRT) decreases risk for recurrence and improves survival (Mutter et al). Proton therapy is an attractive newer way to deliver PMRT compared with photon-based methods and allows improved sparing of cardiopulmonary and other normal tissue. The phase 2 MC1631 trial included 82 patients with BC who underwent mastectomy with or without immediate breast reconstruction and who were randomly assigned to receive either conventional fractionated (50 Gy in 25 fractions of 2 Gy) or hypofractionated (40.05 Gy in 15 fractions of 2.67 Gy) proton PMRT. At a median follow-up of 39.3 months, both conventional fractionated and hypofractionated proton PMRT had similar complication rates (15% vs 20%; absolute difference 4.9%; one-sided 95% CI 18.5; P = .27), with most complications occurring in patients with immediate expander or implant-based reconstruction. Noninferiority of the hypofractionation group could not be determined after a median follow-up of 39 months. However, no isolated local regional recurrences in either treatment arm were seen. This study provides the first prospective, randomized data of hypofractionated proton PMRT. Further data are awaited to support this approach. 

In patients with metastatic hormone receptor (HR)–positive, PIK3CA-mutant BC, the combination of fulvestrant with alpelisib improves progression-free survival per the SOLAR-1 study.1 Higher rates of hyperglycemia observed among patients treated with alpelisib have led to alpelisib dose reductions, treatment delays, and discontinuation of the drug. In a retrospective cohort study of 247 patients with metastatic BC who received alpelisib either as standard care (n = 147) or in a clinical trial setting (n = 100), 61.5% of patients developed any-grade hyperglycemia (Shen et al). The rate of hyperglycemia was considerably higher in patients who received alpelisib as part of standard care vs clinical trial (80.3% vs 34.0%). Baseline body mass index ≥ 25 (P = .036) and A1c levels in the prediabetes and diabetes range were significantly associated with the development of any-grade hyperglycemia (P = .036 and P < .001, respectively) and grade 3-4 hyperglycemia (P < .001 for both). A total of 4.5% of patients discontinued alpelisib owing to hyperglycemia, 17% of patients required dose reductions, and in 27% of patients alpelisib was held until resolution of hyperglycemia. This study highlights the importance of the management of comorbidities before alpelisib treatment to ensure lower rates of adverse events. 

Patritumab deruxtecan (HER3-DXd) is a novel HER3-targeted antibody-drug conjugate that is being evaluated in HER3-expressing metastatic BC. The U31402-A-J101 study is a phase 1/2 trial including 182 heavily pretreated patients (median of five prior therapies) with HER3-expressing advanced BC who received HER3-DXd (Krop et al). The objective response rate was 30.1% (95% CI 21.8%-39.4%) in HR-positive, human epidermal growth factor receptor 2 (HER2)–negative BC, 22.6% (95% CI 12.3%-36.2%) in triple-negative BC, and 42.9% (95% CI 17.1%-71.1%) in HER2-positive BC. Although 71.4% of patients reported grade ≥ 3 treatment-emergent adverse events (TEAE), the overall rate of treatment discontinuation due to TEAE was low (9.9%). These findings demonstrate an encouraging efficacy and a manageable safety profile for patritumab deruxtecan in previously treated patients with BC across all subtypes. Further studies are awaited to confirm these findings and whether prior treatment with antibody-drug conjugate will affect the activity of this drug.

A retrospective analysis of a cohort including 149 patients with metastatic BC looked at predictors of prognosis in patients who had brain metastases and underwent stereotactic radiosurgery (Depner et al). The median overall survival was 14.8 months for the entire cohort. Receptor profiles and the presence of extracranial visceral metastases were significant predictors of prognosis. Overall survival outcomes worsened in patients with estrogen receptor (ER)–negative, HER2-negative BC (hazard ratio 2.00; 95% CI 1.09-3.67) but were better in those with ER-positive, HER2-positive BC (hazard ratio 0.43; 95% CI 0.19-0.96). Furthermore, the presence of extracranial visceral metastases was associated with poor survival outcomes (hazard ratio 2.90; 95% CI 1.53-5.50)

Additional Reference
1.    André F et al, for the SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929-1940. doi: 10.1056/NEJMoa1813904
 

In patients with node-positive and locally advanced breast cancer (BC), postmastectomy radiation therapy (PMRT) decreases risk for recurrence and improves survival (Mutter et al). Proton therapy is an attractive newer way to deliver PMRT compared with photon-based methods and allows improved sparing of cardiopulmonary and other normal tissue. The phase 2 MC1631 trial included 82 patients with BC who underwent mastectomy with or without immediate breast reconstruction and who were randomly assigned to receive either conventional fractionated (50 Gy in 25 fractions of 2 Gy) or hypofractionated (40.05 Gy in 15 fractions of 2.67 Gy) proton PMRT. At a median follow-up of 39.3 months, both conventional fractionated and hypofractionated proton PMRT had similar complication rates (15% vs 20%; absolute difference 4.9%; one-sided 95% CI 18.5; P = .27), with most complications occurring in patients with immediate expander or implant-based reconstruction. Noninferiority of the hypofractionation group could not be determined after a median follow-up of 39 months. However, no isolated local regional recurrences in either treatment arm were seen. This study provides the first prospective, randomized data of hypofractionated proton PMRT. Further data are awaited to support this approach. 

In patients with metastatic hormone receptor (HR)–positive, PIK3CA-mutant BC, the combination of fulvestrant with alpelisib improves progression-free survival per the SOLAR-1 study.1 Higher rates of hyperglycemia observed among patients treated with alpelisib have led to alpelisib dose reductions, treatment delays, and discontinuation of the drug. In a retrospective cohort study of 247 patients with metastatic BC who received alpelisib either as standard care (n = 147) or in a clinical trial setting (n = 100), 61.5% of patients developed any-grade hyperglycemia (Shen et al). The rate of hyperglycemia was considerably higher in patients who received alpelisib as part of standard care vs clinical trial (80.3% vs 34.0%). Baseline body mass index ≥ 25 (P = .036) and A1c levels in the prediabetes and diabetes range were significantly associated with the development of any-grade hyperglycemia (P = .036 and P < .001, respectively) and grade 3-4 hyperglycemia (P < .001 for both). A total of 4.5% of patients discontinued alpelisib owing to hyperglycemia, 17% of patients required dose reductions, and in 27% of patients alpelisib was held until resolution of hyperglycemia. This study highlights the importance of the management of comorbidities before alpelisib treatment to ensure lower rates of adverse events. 

Patritumab deruxtecan (HER3-DXd) is a novel HER3-targeted antibody-drug conjugate that is being evaluated in HER3-expressing metastatic BC. The U31402-A-J101 study is a phase 1/2 trial including 182 heavily pretreated patients (median of five prior therapies) with HER3-expressing advanced BC who received HER3-DXd (Krop et al). The objective response rate was 30.1% (95% CI 21.8%-39.4%) in HR-positive, human epidermal growth factor receptor 2 (HER2)–negative BC, 22.6% (95% CI 12.3%-36.2%) in triple-negative BC, and 42.9% (95% CI 17.1%-71.1%) in HER2-positive BC. Although 71.4% of patients reported grade ≥ 3 treatment-emergent adverse events (TEAE), the overall rate of treatment discontinuation due to TEAE was low (9.9%). These findings demonstrate an encouraging efficacy and a manageable safety profile for patritumab deruxtecan in previously treated patients with BC across all subtypes. Further studies are awaited to confirm these findings and whether prior treatment with antibody-drug conjugate will affect the activity of this drug.

A retrospective analysis of a cohort including 149 patients with metastatic BC looked at predictors of prognosis in patients who had brain metastases and underwent stereotactic radiosurgery (Depner et al). The median overall survival was 14.8 months for the entire cohort. Receptor profiles and the presence of extracranial visceral metastases were significant predictors of prognosis. Overall survival outcomes worsened in patients with estrogen receptor (ER)–negative, HER2-negative BC (hazard ratio 2.00; 95% CI 1.09-3.67) but were better in those with ER-positive, HER2-positive BC (hazard ratio 0.43; 95% CI 0.19-0.96). Furthermore, the presence of extracranial visceral metastases was associated with poor survival outcomes (hazard ratio 2.90; 95% CI 1.53-5.50)

Additional Reference
1.    André F et al, for the SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929-1940. doi: 10.1056/NEJMoa1813904
 

HONOLULU – Old habits die hard, especially when it comes to pulmonary function testing in a diverse population of patients with interstitial lung disease (ILD).

Specifically, pulmonary care clinicians may be habitually relying on outdated and inaccurate race-specific reference values when evaluating respiratory impairment in persons of African and Hispanic/Latino ancestry, which can result in underrecognition, underdiagnosis, and undertreatment, reported Ayodeji Adegunsoye, MD, from the University of Chicago, and colleagues.

“Our results make a compelling case for re-evaluating the use of race as a physiological variable, and highlight the need to offer equitable and optimal care for all patients, regardless of their race or ethnicity,” Dr. Adegunsoye said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).
 

Flawed assumptions

In an interview, Dr. Adegunsoye noted that race-specific notions, such as the automatic assumption that Black people have less lung capacity than White people, are baked into clinical practice and passed on as clinical wisdom from one generation of clinicians to the next.

Pulmonary function reference values that are used to make a diagnosis of idiopathic pulmonary fibrosis in Black or Hispanic/Latino patients “appear flawed when we use race-specific values. And beyond the diagnosis, it also appears to impact eligibility for key interventional strategies for managing the disease itself,” he said.

The use of race-specific equations can falsely inflate percent-predicted pulmonary function values in non-White patients, and make it seem as if a patient has normal lung function when in fact he may be have impaired function.

For example, using race-based reference values a Black patient and a White patient may appear to have the same absolute forced vital capacity readings, but different FVC percent predicted (FVCpp), which can mean a missed diagnosis.

Investigators who studied the association between self-identified race and visually identified emphysema among 2,674 participants in the Coronary Artery Risk Development in Young Adults study found that using standard equations to adjust for racial differences in lung-function measures appeared to miss emphysema in a significant proportion of Black patients.
 

PF registry study

In the current study, to see whether the use of race-neutral equations for evaluating FVCpp could change access to health care in patients with ILD, Dr. Adegunsoye and colleagues used both race-specific and race-neutral equations to calculate FVCpp values among separate cohorts of Black, Hispanic/Latino, and White patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry who had pulmonary functions test within about 90 days of enrollment.

The race-specific equations used to calculate FVCpp was that published in 1999 by Hankinson and colleagues in American Journal of Respiratory and Critical Care Medicine. The race-neutral Global Lung Function Initiative (GLI) equations by Bowerman and colleagues were developed in 2022 and published in March 2023 in the same journal.

The investigators defined access to care as enrollment in ILD clinical trials for patients with FVCpp greater than 45% but less than 90%, and US payer access to antifibrotic therapy for patients with FVCpp of greater than 55% but less than 82%.

They found that 22% of Black patients were misclassified in their eligibility for clinical trials in each of two scenarios – those who would be excluded from trials using the 1999 criteria but included using the 2022 criteria, and vice versa, that is included with 1999 criteria but excluded by the 2022 GLI criteria. In contrast, 14% of Hispanic Latino patients and 12% of White patients were misclassified.

Using the 1999 criteria to exclude patients because their values were ostensibly higher than the upper cutoff meant that 10.3% of Black patients who might benefit would be ineligible for clinical trial, compared with 0% of Hispanic/Latinos and 0.1% of Whites.

Similarly, 11.5% of Black patients but no Hispanic/Latino or White patients would be considered eligible for clinical trials using the old criteria but ineligible under the new criteria.

Regarding antifibrotic therapy eligibility, the respective misclassification rates were 21%, 17%, and 19%.­

“Our study showed that use of race-specific equations may confound lung function tests, potentially leading to misclassification, delayed diagnosis, and inadequate treatment provision. While our study suggests potential disparities in access to health care for patients with interstitial lung disease facilitated by race-specific equations, further research is required to fully comprehend the implications,” the investigators wrote.
 

ATS statement

In an interview, Juan Wisnievsky, MD, DrPh, from Mount Sinai Medical Center, New York, who also chairs the Health Equity and Diversity Committee for the American Thoracic Society, pointed to a recent ATS statement he coauthored citing evidence for replacing race and ethnicity-specific equations with race-neutral average reference equations.

“This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation,” the statement authors wrote.

“There is some agreement that race-based equations shouldn’t be used, but all the potential consequences of doing that and which equations would be the best ones to use to replace them is a bit unclear,” Dr. Wisnievsky said.

He was not involved in the study by Dr. Adegunsoye and colleagues.

Data used in the study were derived from research sponsored by F. Hoffman–La Roche and Genentech. Dr. Adegunsoye disclosed consultancy fees from AbbVie, Inogen, F. Hoffman–La Roche, Medscape, and PatientMpower; speaking/advisory fees from Boehringer Ingelheim; and grants/award from the CHEST Foundation, Pulmonary Fibrosis Foundation, and National Institutes of Health. Dr. Wisnievsky had no relevant disclosures.

HONOLULU – Old habits die hard, especially when it comes to pulmonary function testing in a diverse population of patients with interstitial lung disease (ILD).

Specifically, pulmonary care clinicians may be habitually relying on outdated and inaccurate race-specific reference values when evaluating respiratory impairment in persons of African and Hispanic/Latino ancestry, which can result in underrecognition, underdiagnosis, and undertreatment, reported Ayodeji Adegunsoye, MD, from the University of Chicago, and colleagues.

“Our results make a compelling case for re-evaluating the use of race as a physiological variable, and highlight the need to offer equitable and optimal care for all patients, regardless of their race or ethnicity,” Dr. Adegunsoye said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).
 

Flawed assumptions

In an interview, Dr. Adegunsoye noted that race-specific notions, such as the automatic assumption that Black people have less lung capacity than White people, are baked into clinical practice and passed on as clinical wisdom from one generation of clinicians to the next.

Pulmonary function reference values that are used to make a diagnosis of idiopathic pulmonary fibrosis in Black or Hispanic/Latino patients “appear flawed when we use race-specific values. And beyond the diagnosis, it also appears to impact eligibility for key interventional strategies for managing the disease itself,” he said.

The use of race-specific equations can falsely inflate percent-predicted pulmonary function values in non-White patients, and make it seem as if a patient has normal lung function when in fact he may be have impaired function.

For example, using race-based reference values a Black patient and a White patient may appear to have the same absolute forced vital capacity readings, but different FVC percent predicted (FVCpp), which can mean a missed diagnosis.

Investigators who studied the association between self-identified race and visually identified emphysema among 2,674 participants in the Coronary Artery Risk Development in Young Adults study found that using standard equations to adjust for racial differences in lung-function measures appeared to miss emphysema in a significant proportion of Black patients.
 

PF registry study

In the current study, to see whether the use of race-neutral equations for evaluating FVCpp could change access to health care in patients with ILD, Dr. Adegunsoye and colleagues used both race-specific and race-neutral equations to calculate FVCpp values among separate cohorts of Black, Hispanic/Latino, and White patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry who had pulmonary functions test within about 90 days of enrollment.

The race-specific equations used to calculate FVCpp was that published in 1999 by Hankinson and colleagues in American Journal of Respiratory and Critical Care Medicine. The race-neutral Global Lung Function Initiative (GLI) equations by Bowerman and colleagues were developed in 2022 and published in March 2023 in the same journal.

The investigators defined access to care as enrollment in ILD clinical trials for patients with FVCpp greater than 45% but less than 90%, and US payer access to antifibrotic therapy for patients with FVCpp of greater than 55% but less than 82%.

They found that 22% of Black patients were misclassified in their eligibility for clinical trials in each of two scenarios – those who would be excluded from trials using the 1999 criteria but included using the 2022 criteria, and vice versa, that is included with 1999 criteria but excluded by the 2022 GLI criteria. In contrast, 14% of Hispanic Latino patients and 12% of White patients were misclassified.

Using the 1999 criteria to exclude patients because their values were ostensibly higher than the upper cutoff meant that 10.3% of Black patients who might benefit would be ineligible for clinical trial, compared with 0% of Hispanic/Latinos and 0.1% of Whites.

Similarly, 11.5% of Black patients but no Hispanic/Latino or White patients would be considered eligible for clinical trials using the old criteria but ineligible under the new criteria.

Regarding antifibrotic therapy eligibility, the respective misclassification rates were 21%, 17%, and 19%.­

“Our study showed that use of race-specific equations may confound lung function tests, potentially leading to misclassification, delayed diagnosis, and inadequate treatment provision. While our study suggests potential disparities in access to health care for patients with interstitial lung disease facilitated by race-specific equations, further research is required to fully comprehend the implications,” the investigators wrote.
 

ATS statement

In an interview, Juan Wisnievsky, MD, DrPh, from Mount Sinai Medical Center, New York, who also chairs the Health Equity and Diversity Committee for the American Thoracic Society, pointed to a recent ATS statement he coauthored citing evidence for replacing race and ethnicity-specific equations with race-neutral average reference equations.

“This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation,” the statement authors wrote.

“There is some agreement that race-based equations shouldn’t be used, but all the potential consequences of doing that and which equations would be the best ones to use to replace them is a bit unclear,” Dr. Wisnievsky said.

He was not involved in the study by Dr. Adegunsoye and colleagues.

Data used in the study were derived from research sponsored by F. Hoffman–La Roche and Genentech. Dr. Adegunsoye disclosed consultancy fees from AbbVie, Inogen, F. Hoffman–La Roche, Medscape, and PatientMpower; speaking/advisory fees from Boehringer Ingelheim; and grants/award from the CHEST Foundation, Pulmonary Fibrosis Foundation, and National Institutes of Health. Dr. Wisnievsky had no relevant disclosures.

HONOLULU – Old habits die hard, especially when it comes to pulmonary function testing in a diverse population of patients with interstitial lung disease (ILD).

Specifically, pulmonary care clinicians may be habitually relying on outdated and inaccurate race-specific reference values when evaluating respiratory impairment in persons of African and Hispanic/Latino ancestry, which can result in underrecognition, underdiagnosis, and undertreatment, reported Ayodeji Adegunsoye, MD, from the University of Chicago, and colleagues.

“Our results make a compelling case for re-evaluating the use of race as a physiological variable, and highlight the need to offer equitable and optimal care for all patients, regardless of their race or ethnicity,” Dr. Adegunsoye said in an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).
 

Flawed assumptions

In an interview, Dr. Adegunsoye noted that race-specific notions, such as the automatic assumption that Black people have less lung capacity than White people, are baked into clinical practice and passed on as clinical wisdom from one generation of clinicians to the next.

Pulmonary function reference values that are used to make a diagnosis of idiopathic pulmonary fibrosis in Black or Hispanic/Latino patients “appear flawed when we use race-specific values. And beyond the diagnosis, it also appears to impact eligibility for key interventional strategies for managing the disease itself,” he said.

The use of race-specific equations can falsely inflate percent-predicted pulmonary function values in non-White patients, and make it seem as if a patient has normal lung function when in fact he may be have impaired function.

For example, using race-based reference values a Black patient and a White patient may appear to have the same absolute forced vital capacity readings, but different FVC percent predicted (FVCpp), which can mean a missed diagnosis.

Investigators who studied the association between self-identified race and visually identified emphysema among 2,674 participants in the Coronary Artery Risk Development in Young Adults study found that using standard equations to adjust for racial differences in lung-function measures appeared to miss emphysema in a significant proportion of Black patients.
 

PF registry study

In the current study, to see whether the use of race-neutral equations for evaluating FVCpp could change access to health care in patients with ILD, Dr. Adegunsoye and colleagues used both race-specific and race-neutral equations to calculate FVCpp values among separate cohorts of Black, Hispanic/Latino, and White patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry who had pulmonary functions test within about 90 days of enrollment.

The race-specific equations used to calculate FVCpp was that published in 1999 by Hankinson and colleagues in American Journal of Respiratory and Critical Care Medicine. The race-neutral Global Lung Function Initiative (GLI) equations by Bowerman and colleagues were developed in 2022 and published in March 2023 in the same journal.

The investigators defined access to care as enrollment in ILD clinical trials for patients with FVCpp greater than 45% but less than 90%, and US payer access to antifibrotic therapy for patients with FVCpp of greater than 55% but less than 82%.

They found that 22% of Black patients were misclassified in their eligibility for clinical trials in each of two scenarios – those who would be excluded from trials using the 1999 criteria but included using the 2022 criteria, and vice versa, that is included with 1999 criteria but excluded by the 2022 GLI criteria. In contrast, 14% of Hispanic Latino patients and 12% of White patients were misclassified.

Using the 1999 criteria to exclude patients because their values were ostensibly higher than the upper cutoff meant that 10.3% of Black patients who might benefit would be ineligible for clinical trial, compared with 0% of Hispanic/Latinos and 0.1% of Whites.

Similarly, 11.5% of Black patients but no Hispanic/Latino or White patients would be considered eligible for clinical trials using the old criteria but ineligible under the new criteria.

Regarding antifibrotic therapy eligibility, the respective misclassification rates were 21%, 17%, and 19%.­

“Our study showed that use of race-specific equations may confound lung function tests, potentially leading to misclassification, delayed diagnosis, and inadequate treatment provision. While our study suggests potential disparities in access to health care for patients with interstitial lung disease facilitated by race-specific equations, further research is required to fully comprehend the implications,” the investigators wrote.
 

ATS statement

In an interview, Juan Wisnievsky, MD, DrPh, from Mount Sinai Medical Center, New York, who also chairs the Health Equity and Diversity Committee for the American Thoracic Society, pointed to a recent ATS statement he coauthored citing evidence for replacing race and ethnicity-specific equations with race-neutral average reference equations.

“This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation,” the statement authors wrote.

“There is some agreement that race-based equations shouldn’t be used, but all the potential consequences of doing that and which equations would be the best ones to use to replace them is a bit unclear,” Dr. Wisnievsky said.

He was not involved in the study by Dr. Adegunsoye and colleagues.

Data used in the study were derived from research sponsored by F. Hoffman–La Roche and Genentech. Dr. Adegunsoye disclosed consultancy fees from AbbVie, Inogen, F. Hoffman–La Roche, Medscape, and PatientMpower; speaking/advisory fees from Boehringer Ingelheim; and grants/award from the CHEST Foundation, Pulmonary Fibrosis Foundation, and National Institutes of Health. Dr. Wisnievsky had no relevant disclosures.