Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

TOPLINE:

Methylphenidate was associated with a small increased risk for cardiovascular events in individuals taking the drug for more than 6 months in a new cohort study.

METHODOLOGY:

• The retrospective, population-based cohort study was based on national Swedish registry data and included 26,710 patients with attention-deficit/hyperactivity disorder (ADHD) aged 12-60 years (median age 20) who had been prescribed methylphenidate between 2007 and 2012. They were each matched on birth date, sex, and county with up to 10 nonusers without ADHD (a total of 225,672 controls).
• Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a Bayesian within-individual design.

TAKEAWAY:

• The overall incidence of cardiovascular events was 1.51 per 10,000 person-weeks for individuals receiving methylphenidate and 0.77 for the matched controls.
• Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41) than matched controls (IRR, 1.18).
• Individuals taking methylphenidate had a 70% posterior probability for a greater than 10% increased risk for cardiovascular events than controls and a 49% posterior probability for an increased risk larger than 20%.
• No difference was found in this risk between individuals with and without a history of cardiovascular disease.

IN PRACTICE:

The researchers concluded that these results support a small (10%) increased risk for cardiovascular events in individuals receiving methylphenidate compared with matched controls after 6 months of treatment. The probability of finding a difference in risk between users and nonusers decreased when considering risk for 20% or larger, with no evidence of differences between those with and without a history of cardiovascular disease. They said the findings suggest the decision to initiate methylphenidate should incorporate considerations of potential adverse cardiovascular effects among the broader benefits and risks for treatment for individual patients.

SOURCE:

The study, led by Miguel Garcia-Argibay, PhD, Örebro University, Örebro, Sweden, was published online in JAMA Network Open on March 6.

LIMITATIONS:

The data were observational, and thus, causality could not be inferred. Lack of information on methylphenidate dose meant that it was not possible to assess a dose effect. Compliance with the medication was also not known, and the association may therefore have been underestimated. The findings of this study were based on data collected from a Swedish population, which may not be representative of other populations.

DISCLOSURES:

The study received funding from the European Union’s Horizon 2020 research and innovation program and the Swedish Research Council for Health, Working Life, and Welfare.

A version of this article appeared on Medscape.com.

Weight loss drugs have surged in popularity — in part because they work. Patients on glucagon-like peptide 1 (GLP-1) agonists like liraglutide, semaglutide, and tirzepatide (which is technically also a glucose-dependent insulinotropic polypeptide agonist) can lose 10%, 20%, or even 25% of their body weight.

But if those patients stop taking GLP-1s, they tend to regain most of that weight within a year, studies showed.

“These drugs work inside the person from a biologic point of view to alter appetite,” said Robert Kushner, MD, an endocrinologist and professor at Northwestern University Feinberg School of Medicine, Chicago, Illinois, who specializes in obesity medicine. “And when the drug is gone, that disease comes back.” 

Ongoing treatment may seem like the obvious solution, but reality can complicate that. High costs, supply shortages, and faltering insurance coverage can render the drugs inaccessible.

Often, “patients are told by their insurers that they are no longer going to cover a GLP-1 for obesity,” said Carolyn Bramante, MD, MPH, an assistant professor at the University of Minnesota Medical School, Minneapolis, Minnesota, who sees patients at the M Health Fairview weight management clinic.

Other barriers include side effects like nausea, diarrhea, stomach pain, and vomiting. Some patients simply don’t want to take a medication forever, instead choosing to take their chances keeping the weight off sans drug.

If your patient must stop GLP-1s, or really wants to, here’s how to help.

Find out why the patient wants to go off the GLP-1. Ask them to help you understand, suggested Jaime Almandoz, MD, associate professor of internal medicine and medical director of the University of Texas Southwestern Medical Center’s Weight Wellness Program. Sometimes, the patient or family members worry about safety, Dr. Almandoz said. “They may be concerned about the risks and may not have had an opportunity to ask questions.” Dr. Almandoz reviews the drug safety data and tells patients that studies show, on average, people gain back two-thirds of the weight they’ve lost within a year. You’re not trying to persuade them, only to equip them to make a well-informed choice.

Don’t let bias affect treatment decisions. Patients on GLP-1s often ask: How long will I have to take this? The reason: “We’re biased to believe that this is not a disease state, that this is a character flaw,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for weight management in Burlington, Ontario, Canada. Remind your patient that obesity is not a personal failure but rather a complex mix of genetic and biological factors.

Give patients a primer on the biology of obesity. Science shows that when we lose weight, our bodies fight back, trying to return to our highest-ever fat mass. Changes in neurohormones, gut hormones, satiety mechanisms, metabolism, and muscle function all converge to promote weight recurrence, Dr. Almandoz said. To explain this to patients, Dr. Almandoz compares gaining fat to depositing money in a savings account. “When we try to lose weight, it isn’t as simple as withdrawing this money,” he’ll tell them. “It is almost like the money that we put into the savings account is now tied up in investments that we can’t liquidate easily.”

Prepare patients for an uptick in appetite. When patients stop GLP-1s, their hunger and food cravings tend to increase. “I explain that GLP-1 medications mimic a hormone that is released from our intestines when they sense we have eaten,” said Dr. Almandoz. This signals the brain and body that food is on board, decreasing appetite and cravings. Ask patients what hungry and full feel like on the medication, Dr. Almandoz suggested. “Many will report that their hunger and cravings are low, that they now have an indifference to foods,” said Dr. Almandoz. Such probing questions can help patients be more aware of the medication’s effects. “This positions a more informed conversation if medications are to be discontinued,” Dr. Almandoz said.

Help their body adjust. “Slowly wean down on the dose, if possible, to avoid a big rebound in hunger,” said Dr. Bramante. If your patient has the time — say, they received a letter from their insurance that coverage will end in 3 months — use it to taper the dose as low as possible before stopping. The slower and more gradual, the better. Dr. Almandoz checks in with patients every 4-8 weeks. If they›re maintaining weight well, he considers decreasing the dose again and repeating with follow-up visits.

Substitute one intervention for another. In general, maintaining weight loss requires some intervention, Dr. Wharton said. “But that intervention does not need to be the same as the intervention that got the weight down.” If the patient can›t continue a GLP-1, consider an alternate medication, cognitive behavioral therapy, or a combination of the two. When patients lose coverage for GLP-1s, Dr. Bramante sometimes prescribes an older, less-expensive weight loss drug, such as phentermine, topiramate, or metformin. And sometimes, insurers that don’t cover GLP-1s (like Medicare), do cover bariatric surgery, a potential option depending on the patient›s body mass index, overall health, and comorbidities, said Dr. Almandoz.

Create a habit template. Dr. Kushner asks patients who have successfully lost weight to take an inventory of everything they’re doing to support their efforts. He’ll have them describe how they plan their diet, what types of food they’re eating, how much they eat, and when they eat it. He’ll also ask about physical activity, exercise patterns, and sleep. He logs all the habits into a bulleted list in the patient’s after-visit summary and hands them a printout before they leave. “That’s your template,” he’ll tell them. “That’s what you’re going to try to maintain to the best of your ability because it’s working for you.”

Prescribe exercise. “Increasing exercise is not usually effective for initial weight loss, but it is important for maintaining weight loss,” said Dr. Bramante. Tell patients to start right away, ideally while they’re still on the drug. In a study published last month, patients on liraglutide (Saxenda) who exercised 4 days a week were much more likely to keep weight off after stopping the drug than those who didn’t work out. (The study was partially funded by Novo Nordisk Foundation, the charitable arm of Saxenda’s maker, also the maker of semaglutide meds Ozempic and Wegovy.) By establishing strong exercise habits while on the medication, they were able to sustain higher physical activity levels after they stopped. Ask your patient to identify someone or something to help them stick to their plan, “whether it’s seeing a personal trainer or being accountable to a friend or family member or to themselves through record keeping,” said Dr. Kushner. Learn more about how to prescribe exercise to patients here.

Help them create a “microenvironment” for success. Dr. Kushner asks patients which of the recommended dietary habits for weight loss are hardest to follow: Eating more plant-based foods? Cutting back on ultra-processed foods, fatty foods, fast foods, and/or sugary beverages? Depending on the patient’s answers, he tries to recommend strategies — maybe going meatless a few days a week or keeping tempting foods out of the house. “If you go off medication, food may become more enticing, and you may not feel as content eating less,” Dr. Kushner said. “Make sure your own what we call microenvironment, your home environment, is filled with healthy foods.”

Rely on multidisciplinary expertise. Obesity is a complex, multifactorial disease, so call in reinforcements. “When I see someone, I’m always evaluating what other team members they would benefit from,” said Dr. Kushner. If the patient lacks nutrition knowledge, he refers them to a registered dietitian. If they struggle with self-blame, low self-esteem, and emotional eating, he’ll refer them to a psychologist. It can make a difference: A 2023 study showed that people who lost weight and received support from professionals like trainers, dietitians, and mental health therapists regained less weight over 2 years than those who did not receive the same help.

Reassure patients you will help them no matter what. Ask patients to follow-up within the first month of quitting medication or to call back sooner if they gain 5 pounds. People who stop taking GLP-1s often report less satisfaction with eating, or that they think about food more. That’s when Dr. Kushner asks whether they want to go back on the medication or focus on other strategies. Sometimes, patients who gain weight feel embarrassed and delay their follow-up visits. If that happens, welcome them back and let them know that all chronic conditions ebb and flow. “I constantly remind them that I am here to help you, and there are many tools or resources that will help you,” Dr. Kushner said. “And dispel the notion that it’s somehow your fault.”

Dr. Kushner reported participation on the medical advisory board or consultancy with Novo Nordisk, WeightWatchers, Eli Lilly and Company, Boehringer Ingelheim, Structure Therapeutics, and Altimmune. He added he does not own stock or participate in any speaker’s bureau. Dr. Almandoz reported participation on advisory boards with Novo Nordisk, Boehringer Ingelheim, and Eli Lilly and Company. Dr. Wharton reported participation on advisory boards and honoraria for academic talks and clinical research with Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Amgen, Regeneron, and BioHaven.

A version of this article appeared on Medscape.com.

Weight loss drugs have surged in popularity — in part because they work. Patients on glucagon-like peptide 1 (GLP-1) agonists like liraglutide, semaglutide, and tirzepatide (which is technically also a glucose-dependent insulinotropic polypeptide agonist) can lose 10%, 20%, or even 25% of their body weight.

But if those patients stop taking GLP-1s, they tend to regain most of that weight within a year, studies showed.

“These drugs work inside the person from a biologic point of view to alter appetite,” said Robert Kushner, MD, an endocrinologist and professor at Northwestern University Feinberg School of Medicine, Chicago, Illinois, who specializes in obesity medicine. “And when the drug is gone, that disease comes back.” 

Ongoing treatment may seem like the obvious solution, but reality can complicate that. High costs, supply shortages, and faltering insurance coverage can render the drugs inaccessible.

Often, “patients are told by their insurers that they are no longer going to cover a GLP-1 for obesity,” said Carolyn Bramante, MD, MPH, an assistant professor at the University of Minnesota Medical School, Minneapolis, Minnesota, who sees patients at the M Health Fairview weight management clinic.

Other barriers include side effects like nausea, diarrhea, stomach pain, and vomiting. Some patients simply don’t want to take a medication forever, instead choosing to take their chances keeping the weight off sans drug.

If your patient must stop GLP-1s, or really wants to, here’s how to help.

Find out why the patient wants to go off the GLP-1. Ask them to help you understand, suggested Jaime Almandoz, MD, associate professor of internal medicine and medical director of the University of Texas Southwestern Medical Center’s Weight Wellness Program. Sometimes, the patient or family members worry about safety, Dr. Almandoz said. “They may be concerned about the risks and may not have had an opportunity to ask questions.” Dr. Almandoz reviews the drug safety data and tells patients that studies show, on average, people gain back two-thirds of the weight they’ve lost within a year. You’re not trying to persuade them, only to equip them to make a well-informed choice.

Don’t let bias affect treatment decisions. Patients on GLP-1s often ask: How long will I have to take this? The reason: “We’re biased to believe that this is not a disease state, that this is a character flaw,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for weight management in Burlington, Ontario, Canada. Remind your patient that obesity is not a personal failure but rather a complex mix of genetic and biological factors.

Give patients a primer on the biology of obesity. Science shows that when we lose weight, our bodies fight back, trying to return to our highest-ever fat mass. Changes in neurohormones, gut hormones, satiety mechanisms, metabolism, and muscle function all converge to promote weight recurrence, Dr. Almandoz said. To explain this to patients, Dr. Almandoz compares gaining fat to depositing money in a savings account. “When we try to lose weight, it isn’t as simple as withdrawing this money,” he’ll tell them. “It is almost like the money that we put into the savings account is now tied up in investments that we can’t liquidate easily.”

Prepare patients for an uptick in appetite. When patients stop GLP-1s, their hunger and food cravings tend to increase. “I explain that GLP-1 medications mimic a hormone that is released from our intestines when they sense we have eaten,” said Dr. Almandoz. This signals the brain and body that food is on board, decreasing appetite and cravings. Ask patients what hungry and full feel like on the medication, Dr. Almandoz suggested. “Many will report that their hunger and cravings are low, that they now have an indifference to foods,” said Dr. Almandoz. Such probing questions can help patients be more aware of the medication’s effects. “This positions a more informed conversation if medications are to be discontinued,” Dr. Almandoz said.

Help their body adjust. “Slowly wean down on the dose, if possible, to avoid a big rebound in hunger,” said Dr. Bramante. If your patient has the time — say, they received a letter from their insurance that coverage will end in 3 months — use it to taper the dose as low as possible before stopping. The slower and more gradual, the better. Dr. Almandoz checks in with patients every 4-8 weeks. If they›re maintaining weight well, he considers decreasing the dose again and repeating with follow-up visits.

Substitute one intervention for another. In general, maintaining weight loss requires some intervention, Dr. Wharton said. “But that intervention does not need to be the same as the intervention that got the weight down.” If the patient can›t continue a GLP-1, consider an alternate medication, cognitive behavioral therapy, or a combination of the two. When patients lose coverage for GLP-1s, Dr. Bramante sometimes prescribes an older, less-expensive weight loss drug, such as phentermine, topiramate, or metformin. And sometimes, insurers that don’t cover GLP-1s (like Medicare), do cover bariatric surgery, a potential option depending on the patient›s body mass index, overall health, and comorbidities, said Dr. Almandoz.

Create a habit template. Dr. Kushner asks patients who have successfully lost weight to take an inventory of everything they’re doing to support their efforts. He’ll have them describe how they plan their diet, what types of food they’re eating, how much they eat, and when they eat it. He’ll also ask about physical activity, exercise patterns, and sleep. He logs all the habits into a bulleted list in the patient’s after-visit summary and hands them a printout before they leave. “That’s your template,” he’ll tell them. “That’s what you’re going to try to maintain to the best of your ability because it’s working for you.”

Prescribe exercise. “Increasing exercise is not usually effective for initial weight loss, but it is important for maintaining weight loss,” said Dr. Bramante. Tell patients to start right away, ideally while they’re still on the drug. In a study published last month, patients on liraglutide (Saxenda) who exercised 4 days a week were much more likely to keep weight off after stopping the drug than those who didn’t work out. (The study was partially funded by Novo Nordisk Foundation, the charitable arm of Saxenda’s maker, also the maker of semaglutide meds Ozempic and Wegovy.) By establishing strong exercise habits while on the medication, they were able to sustain higher physical activity levels after they stopped. Ask your patient to identify someone or something to help them stick to their plan, “whether it’s seeing a personal trainer or being accountable to a friend or family member or to themselves through record keeping,” said Dr. Kushner. Learn more about how to prescribe exercise to patients here.

Help them create a “microenvironment” for success. Dr. Kushner asks patients which of the recommended dietary habits for weight loss are hardest to follow: Eating more plant-based foods? Cutting back on ultra-processed foods, fatty foods, fast foods, and/or sugary beverages? Depending on the patient’s answers, he tries to recommend strategies — maybe going meatless a few days a week or keeping tempting foods out of the house. “If you go off medication, food may become more enticing, and you may not feel as content eating less,” Dr. Kushner said. “Make sure your own what we call microenvironment, your home environment, is filled with healthy foods.”

Rely on multidisciplinary expertise. Obesity is a complex, multifactorial disease, so call in reinforcements. “When I see someone, I’m always evaluating what other team members they would benefit from,” said Dr. Kushner. If the patient lacks nutrition knowledge, he refers them to a registered dietitian. If they struggle with self-blame, low self-esteem, and emotional eating, he’ll refer them to a psychologist. It can make a difference: A 2023 study showed that people who lost weight and received support from professionals like trainers, dietitians, and mental health therapists regained less weight over 2 years than those who did not receive the same help.

Reassure patients you will help them no matter what. Ask patients to follow-up within the first month of quitting medication or to call back sooner if they gain 5 pounds. People who stop taking GLP-1s often report less satisfaction with eating, or that they think about food more. That’s when Dr. Kushner asks whether they want to go back on the medication or focus on other strategies. Sometimes, patients who gain weight feel embarrassed and delay their follow-up visits. If that happens, welcome them back and let them know that all chronic conditions ebb and flow. “I constantly remind them that I am here to help you, and there are many tools or resources that will help you,” Dr. Kushner said. “And dispel the notion that it’s somehow your fault.”

Dr. Kushner reported participation on the medical advisory board or consultancy with Novo Nordisk, WeightWatchers, Eli Lilly and Company, Boehringer Ingelheim, Structure Therapeutics, and Altimmune. He added he does not own stock or participate in any speaker’s bureau. Dr. Almandoz reported participation on advisory boards with Novo Nordisk, Boehringer Ingelheim, and Eli Lilly and Company. Dr. Wharton reported participation on advisory boards and honoraria for academic talks and clinical research with Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Amgen, Regeneron, and BioHaven.

A version of this article appeared on Medscape.com.

Weight loss drugs have surged in popularity — in part because they work. Patients on glucagon-like peptide 1 (GLP-1) agonists like liraglutide, semaglutide, and tirzepatide (which is technically also a glucose-dependent insulinotropic polypeptide agonist) can lose 10%, 20%, or even 25% of their body weight.

But if those patients stop taking GLP-1s, they tend to regain most of that weight within a year, studies showed.

“These drugs work inside the person from a biologic point of view to alter appetite,” said Robert Kushner, MD, an endocrinologist and professor at Northwestern University Feinberg School of Medicine, Chicago, Illinois, who specializes in obesity medicine. “And when the drug is gone, that disease comes back.” 

Ongoing treatment may seem like the obvious solution, but reality can complicate that. High costs, supply shortages, and faltering insurance coverage can render the drugs inaccessible.

Often, “patients are told by their insurers that they are no longer going to cover a GLP-1 for obesity,” said Carolyn Bramante, MD, MPH, an assistant professor at the University of Minnesota Medical School, Minneapolis, Minnesota, who sees patients at the M Health Fairview weight management clinic.

Other barriers include side effects like nausea, diarrhea, stomach pain, and vomiting. Some patients simply don’t want to take a medication forever, instead choosing to take their chances keeping the weight off sans drug.

If your patient must stop GLP-1s, or really wants to, here’s how to help.

Find out why the patient wants to go off the GLP-1. Ask them to help you understand, suggested Jaime Almandoz, MD, associate professor of internal medicine and medical director of the University of Texas Southwestern Medical Center’s Weight Wellness Program. Sometimes, the patient or family members worry about safety, Dr. Almandoz said. “They may be concerned about the risks and may not have had an opportunity to ask questions.” Dr. Almandoz reviews the drug safety data and tells patients that studies show, on average, people gain back two-thirds of the weight they’ve lost within a year. You’re not trying to persuade them, only to equip them to make a well-informed choice.

Don’t let bias affect treatment decisions. Patients on GLP-1s often ask: How long will I have to take this? The reason: “We’re biased to believe that this is not a disease state, that this is a character flaw,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for weight management in Burlington, Ontario, Canada. Remind your patient that obesity is not a personal failure but rather a complex mix of genetic and biological factors.

Give patients a primer on the biology of obesity. Science shows that when we lose weight, our bodies fight back, trying to return to our highest-ever fat mass. Changes in neurohormones, gut hormones, satiety mechanisms, metabolism, and muscle function all converge to promote weight recurrence, Dr. Almandoz said. To explain this to patients, Dr. Almandoz compares gaining fat to depositing money in a savings account. “When we try to lose weight, it isn’t as simple as withdrawing this money,” he’ll tell them. “It is almost like the money that we put into the savings account is now tied up in investments that we can’t liquidate easily.”

Prepare patients for an uptick in appetite. When patients stop GLP-1s, their hunger and food cravings tend to increase. “I explain that GLP-1 medications mimic a hormone that is released from our intestines when they sense we have eaten,” said Dr. Almandoz. This signals the brain and body that food is on board, decreasing appetite and cravings. Ask patients what hungry and full feel like on the medication, Dr. Almandoz suggested. “Many will report that their hunger and cravings are low, that they now have an indifference to foods,” said Dr. Almandoz. Such probing questions can help patients be more aware of the medication’s effects. “This positions a more informed conversation if medications are to be discontinued,” Dr. Almandoz said.

Help their body adjust. “Slowly wean down on the dose, if possible, to avoid a big rebound in hunger,” said Dr. Bramante. If your patient has the time — say, they received a letter from their insurance that coverage will end in 3 months — use it to taper the dose as low as possible before stopping. The slower and more gradual, the better. Dr. Almandoz checks in with patients every 4-8 weeks. If they›re maintaining weight well, he considers decreasing the dose again and repeating with follow-up visits.

Substitute one intervention for another. In general, maintaining weight loss requires some intervention, Dr. Wharton said. “But that intervention does not need to be the same as the intervention that got the weight down.” If the patient can›t continue a GLP-1, consider an alternate medication, cognitive behavioral therapy, or a combination of the two. When patients lose coverage for GLP-1s, Dr. Bramante sometimes prescribes an older, less-expensive weight loss drug, such as phentermine, topiramate, or metformin. And sometimes, insurers that don’t cover GLP-1s (like Medicare), do cover bariatric surgery, a potential option depending on the patient›s body mass index, overall health, and comorbidities, said Dr. Almandoz.

Create a habit template. Dr. Kushner asks patients who have successfully lost weight to take an inventory of everything they’re doing to support their efforts. He’ll have them describe how they plan their diet, what types of food they’re eating, how much they eat, and when they eat it. He’ll also ask about physical activity, exercise patterns, and sleep. He logs all the habits into a bulleted list in the patient’s after-visit summary and hands them a printout before they leave. “That’s your template,” he’ll tell them. “That’s what you’re going to try to maintain to the best of your ability because it’s working for you.”

Prescribe exercise. “Increasing exercise is not usually effective for initial weight loss, but it is important for maintaining weight loss,” said Dr. Bramante. Tell patients to start right away, ideally while they’re still on the drug. In a study published last month, patients on liraglutide (Saxenda) who exercised 4 days a week were much more likely to keep weight off after stopping the drug than those who didn’t work out. (The study was partially funded by Novo Nordisk Foundation, the charitable arm of Saxenda’s maker, also the maker of semaglutide meds Ozempic and Wegovy.) By establishing strong exercise habits while on the medication, they were able to sustain higher physical activity levels after they stopped. Ask your patient to identify someone or something to help them stick to their plan, “whether it’s seeing a personal trainer or being accountable to a friend or family member or to themselves through record keeping,” said Dr. Kushner. Learn more about how to prescribe exercise to patients here.

Help them create a “microenvironment” for success. Dr. Kushner asks patients which of the recommended dietary habits for weight loss are hardest to follow: Eating more plant-based foods? Cutting back on ultra-processed foods, fatty foods, fast foods, and/or sugary beverages? Depending on the patient’s answers, he tries to recommend strategies — maybe going meatless a few days a week or keeping tempting foods out of the house. “If you go off medication, food may become more enticing, and you may not feel as content eating less,” Dr. Kushner said. “Make sure your own what we call microenvironment, your home environment, is filled with healthy foods.”

Rely on multidisciplinary expertise. Obesity is a complex, multifactorial disease, so call in reinforcements. “When I see someone, I’m always evaluating what other team members they would benefit from,” said Dr. Kushner. If the patient lacks nutrition knowledge, he refers them to a registered dietitian. If they struggle with self-blame, low self-esteem, and emotional eating, he’ll refer them to a psychologist. It can make a difference: A 2023 study showed that people who lost weight and received support from professionals like trainers, dietitians, and mental health therapists regained less weight over 2 years than those who did not receive the same help.

Reassure patients you will help them no matter what. Ask patients to follow-up within the first month of quitting medication or to call back sooner if they gain 5 pounds. People who stop taking GLP-1s often report less satisfaction with eating, or that they think about food more. That’s when Dr. Kushner asks whether they want to go back on the medication or focus on other strategies. Sometimes, patients who gain weight feel embarrassed and delay their follow-up visits. If that happens, welcome them back and let them know that all chronic conditions ebb and flow. “I constantly remind them that I am here to help you, and there are many tools or resources that will help you,” Dr. Kushner said. “And dispel the notion that it’s somehow your fault.”

Dr. Kushner reported participation on the medical advisory board or consultancy with Novo Nordisk, WeightWatchers, Eli Lilly and Company, Boehringer Ingelheim, Structure Therapeutics, and Altimmune. He added he does not own stock or participate in any speaker’s bureau. Dr. Almandoz reported participation on advisory boards with Novo Nordisk, Boehringer Ingelheim, and Eli Lilly and Company. Dr. Wharton reported participation on advisory boards and honoraria for academic talks and clinical research with Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Amgen, Regeneron, and BioHaven.

A version of this article appeared on Medscape.com.

While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.

This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.

A Common and Costly Problem

Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.

Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.

“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.

In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.

While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.

This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.

A Common and Costly Problem

Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.

Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.

“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.

In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.

While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.

This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.

A Common and Costly Problem

Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.

Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.

“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.

In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.

TOPLINE: 

The spices and aromatic herbs of the Mediterranean diet with significant benefits in improving glycemic health in type 2 diabetes are limited to ginger, cinnamon, black cumin, turmeric, and saffron, with ginger, black cumin, and cinnamon having the strongest effects on fasting glucose, according to a systematic review and meta-analysis of research.

The meta-analysis also evaluated clove, thyme, turmeric, and various other spices and herbs common in the diet but showed no other correlations with glycemic benefits. 

METHODOLOGY:

• In the analysis of 77 studies, 45, involving 3050 participants, were included in the meta-analysis and 32 studies in the systematic review.
• The studies’ inclusion criteria included adult patients with type 2 diabetes, with data on fasting glucose and/or A1c and/or , and involving any supplementation with black cumin, clove, , saffron, thyme, ginger, black pepper, , curcumin, cinnamon, basil, and/or oregano.
• The number of studies involving clove, parsley, thyme, black pepper, rosemary, basil, or oregano and their association with glycemic factors in people with type 2 diabetes was insufficient, hence the analysis primarily focused on the remaining five ingredients of cinnamon, curcumin, ginger, black cumin, saffron, and rosemary.

TAKEAWAY: 

• Improvements in fasting glucose of subjects with type 2 diabetes were observed with all five ingredients of cinnamon, turmeric, ginger, black cumin, and saffron.
• However, the most significant decreases in fasting glucose, between 17 mg/dL and 27 mg/dL, occurred after supplementation with black cumin, followed by cinnamon and ginger.
• Notably, only ginger and black cumin were associated with a significant improvement in A1c.
• Only cinnamon and ginger were associated with a significant decrease in insulin values.
• Of the 11 studies including cinnamon in the meta-analysis, 6 reported significant differences in fasting glucose, while 4 had differences in A1c after the supplementation.
• However, ginger was the only component associated with a significant decrease in each of the 3 outcomes examined of fasting glucose, A1c, and insulin.

IN PRACTICE:

“The Mediterranean Diet is the dietary pattern par excellence for managing and preventing metabolic diseases, such as type 2 diabetes,” the authors reported.

“As far as we are aware, this is the first systematic review and meta-analysis aiming to evaluate the effect of aromatic herbs and spices included in the Mediterranean Diet, such as black cumin, clove [and others], on the glycemic profile of individuals with type 2 diabetes,” they added.

“When focusing on HbA1c, only ginger and black cumin demonstrated therapeutic effects,” the authors noted. “However, our meta-analysis highlights ginger as an herb with substantial translational potential for diabetes treatment, impacting all three glycemic parameters.”

“Regarding clove, parsley, thyme, black pepper, rosemary, basil, and oregano, more studies are needed to analyze the effect of these herbs on the glycemic profile in type 2 diabetes subjects,” the authors concluded.

SOURCE:

The study was published on March 7, 2024, in Nutrients. The first author was Maria Carmen Garza, PhD, of the Department of Human Anatomy and Histology, School Medicine, University of Zaragoza, Zaragoza, Spain.

LIMITATIONS:

Despite the results, a variety of other factors can affect fasting glucose levels, including changes in body weight or body mass index, as well as the combination of spice or aromatic herb supplementation with physical activity or lifestyle changes, the authors noted.

Due to the studies’ differences, the determination of effective dosages of the herbs and spices was not possible.

Furthermore, the studies had wide variations in quality, with few studies including adequate statistical analysis.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE: 

The spices and aromatic herbs of the Mediterranean diet with significant benefits in improving glycemic health in type 2 diabetes are limited to ginger, cinnamon, black cumin, turmeric, and saffron, with ginger, black cumin, and cinnamon having the strongest effects on fasting glucose, according to a systematic review and meta-analysis of research.

The meta-analysis also evaluated clove, thyme, turmeric, and various other spices and herbs common in the diet but showed no other correlations with glycemic benefits. 

METHODOLOGY:

• In the analysis of 77 studies, 45, involving 3050 participants, were included in the meta-analysis and 32 studies in the systematic review.
• The studies’ inclusion criteria included adult patients with type 2 diabetes, with data on fasting glucose and/or A1c and/or , and involving any supplementation with black cumin, clove, , saffron, thyme, ginger, black pepper, , curcumin, cinnamon, basil, and/or oregano.
• The number of studies involving clove, parsley, thyme, black pepper, rosemary, basil, or oregano and their association with glycemic factors in people with type 2 diabetes was insufficient, hence the analysis primarily focused on the remaining five ingredients of cinnamon, curcumin, ginger, black cumin, saffron, and rosemary.

TAKEAWAY: 

• Improvements in fasting glucose of subjects with type 2 diabetes were observed with all five ingredients of cinnamon, turmeric, ginger, black cumin, and saffron.
• However, the most significant decreases in fasting glucose, between 17 mg/dL and 27 mg/dL, occurred after supplementation with black cumin, followed by cinnamon and ginger.
• Notably, only ginger and black cumin were associated with a significant improvement in A1c.
• Only cinnamon and ginger were associated with a significant decrease in insulin values.
• Of the 11 studies including cinnamon in the meta-analysis, 6 reported significant differences in fasting glucose, while 4 had differences in A1c after the supplementation.
• However, ginger was the only component associated with a significant decrease in each of the 3 outcomes examined of fasting glucose, A1c, and insulin.

IN PRACTICE:

“The Mediterranean Diet is the dietary pattern par excellence for managing and preventing metabolic diseases, such as type 2 diabetes,” the authors reported.

“As far as we are aware, this is the first systematic review and meta-analysis aiming to evaluate the effect of aromatic herbs and spices included in the Mediterranean Diet, such as black cumin, clove [and others], on the glycemic profile of individuals with type 2 diabetes,” they added.

“When focusing on HbA1c, only ginger and black cumin demonstrated therapeutic effects,” the authors noted. “However, our meta-analysis highlights ginger as an herb with substantial translational potential for diabetes treatment, impacting all three glycemic parameters.”

“Regarding clove, parsley, thyme, black pepper, rosemary, basil, and oregano, more studies are needed to analyze the effect of these herbs on the glycemic profile in type 2 diabetes subjects,” the authors concluded.

SOURCE:

The study was published on March 7, 2024, in Nutrients. The first author was Maria Carmen Garza, PhD, of the Department of Human Anatomy and Histology, School Medicine, University of Zaragoza, Zaragoza, Spain.

LIMITATIONS:

Despite the results, a variety of other factors can affect fasting glucose levels, including changes in body weight or body mass index, as well as the combination of spice or aromatic herb supplementation with physical activity or lifestyle changes, the authors noted.

Due to the studies’ differences, the determination of effective dosages of the herbs and spices was not possible.

Furthermore, the studies had wide variations in quality, with few studies including adequate statistical analysis.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE: 

The spices and aromatic herbs of the Mediterranean diet with significant benefits in improving glycemic health in type 2 diabetes are limited to ginger, cinnamon, black cumin, turmeric, and saffron, with ginger, black cumin, and cinnamon having the strongest effects on fasting glucose, according to a systematic review and meta-analysis of research.

The meta-analysis also evaluated clove, thyme, turmeric, and various other spices and herbs common in the diet but showed no other correlations with glycemic benefits. 

METHODOLOGY:

• In the analysis of 77 studies, 45, involving 3050 participants, were included in the meta-analysis and 32 studies in the systematic review.
• The studies’ inclusion criteria included adult patients with type 2 diabetes, with data on fasting glucose and/or A1c and/or , and involving any supplementation with black cumin, clove, , saffron, thyme, ginger, black pepper, , curcumin, cinnamon, basil, and/or oregano.
• The number of studies involving clove, parsley, thyme, black pepper, rosemary, basil, or oregano and their association with glycemic factors in people with type 2 diabetes was insufficient, hence the analysis primarily focused on the remaining five ingredients of cinnamon, curcumin, ginger, black cumin, saffron, and rosemary.

TAKEAWAY: 

• Improvements in fasting glucose of subjects with type 2 diabetes were observed with all five ingredients of cinnamon, turmeric, ginger, black cumin, and saffron.
• However, the most significant decreases in fasting glucose, between 17 mg/dL and 27 mg/dL, occurred after supplementation with black cumin, followed by cinnamon and ginger.
• Notably, only ginger and black cumin were associated with a significant improvement in A1c.
• Only cinnamon and ginger were associated with a significant decrease in insulin values.
• Of the 11 studies including cinnamon in the meta-analysis, 6 reported significant differences in fasting glucose, while 4 had differences in A1c after the supplementation.
• However, ginger was the only component associated with a significant decrease in each of the 3 outcomes examined of fasting glucose, A1c, and insulin.

IN PRACTICE:

“The Mediterranean Diet is the dietary pattern par excellence for managing and preventing metabolic diseases, such as type 2 diabetes,” the authors reported.

“As far as we are aware, this is the first systematic review and meta-analysis aiming to evaluate the effect of aromatic herbs and spices included in the Mediterranean Diet, such as black cumin, clove [and others], on the glycemic profile of individuals with type 2 diabetes,” they added.

“When focusing on HbA1c, only ginger and black cumin demonstrated therapeutic effects,” the authors noted. “However, our meta-analysis highlights ginger as an herb with substantial translational potential for diabetes treatment, impacting all three glycemic parameters.”

“Regarding clove, parsley, thyme, black pepper, rosemary, basil, and oregano, more studies are needed to analyze the effect of these herbs on the glycemic profile in type 2 diabetes subjects,” the authors concluded.

SOURCE:

The study was published on March 7, 2024, in Nutrients. The first author was Maria Carmen Garza, PhD, of the Department of Human Anatomy and Histology, School Medicine, University of Zaragoza, Zaragoza, Spain.

LIMITATIONS:

Despite the results, a variety of other factors can affect fasting glucose levels, including changes in body weight or body mass index, as well as the combination of spice or aromatic herb supplementation with physical activity or lifestyle changes, the authors noted.

Due to the studies’ differences, the determination of effective dosages of the herbs and spices was not possible.

Furthermore, the studies had wide variations in quality, with few studies including adequate statistical analysis.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Depression is linked to a significantly increased risk for cardiovascular disease (CVD), particularly in women, new data from a large retrospective cohort study show. Researchers suggest that screening and treating patients for depression may lead to a decreased incidence of CVD.

METHODOLOGY:

• Researchers analyzed health insurance claims from more than 4 million Japanese patients filed between 2005 and 2022.
• Participants were 18-75 (median age, 44) without a history of CVD or stroke, heart failure, or atrial fibrillation.
• Investigators followed participants for a mean period of 2.5-3.5 years to observe the number of CVD events in those who had a diagnosis of depression.
• During the follow-up period, there were 119,000 CVD events in men (14 per 10,000 person-years) and 61,800 CVD events in women (111 per 10,000 person-years).

TAKEAWAY:

• Compared with women without depression, those with depression had a 64% higher risk for CVD (hazard ratio [HR], 1.64), while men with depression had a 39% higher risk for CVD vs their counterparts without depression (HR, 1.39; P < .001).
• This association was significant even after controlling for various factors such as body mass index, diabetes, smoking, alcohol consumption, and physical inactivity.
• Investigators offered several theories about the increased risk for CVD in women with depression, including how depression during hormonal shifts can contribute to a greater impact on cardiovascular health.

IN PRACTICE:

“Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management,” study author Hidehiro Kaneko, MD, said in a press release. “Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.”

SOURCE:

Keitaro Senoo, MD, of the Kyoto Prefectural University of Medicine, Kyoto, Japan, led the study, which was published online on March 12 in JACC: Asia.

LIMITATIONS:

The study is observational, so causality between depression and subsequent CVD events cannot be established. In addition, depression severity is unknown.

DISCLOSURES:

The study was funded by the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science, and Technology, Japan. There were no disclosures reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Depression is linked to a significantly increased risk for cardiovascular disease (CVD), particularly in women, new data from a large retrospective cohort study show. Researchers suggest that screening and treating patients for depression may lead to a decreased incidence of CVD.

METHODOLOGY:

• Researchers analyzed health insurance claims from more than 4 million Japanese patients filed between 2005 and 2022.
• Participants were 18-75 (median age, 44) without a history of CVD or stroke, heart failure, or atrial fibrillation.
• Investigators followed participants for a mean period of 2.5-3.5 years to observe the number of CVD events in those who had a diagnosis of depression.
• During the follow-up period, there were 119,000 CVD events in men (14 per 10,000 person-years) and 61,800 CVD events in women (111 per 10,000 person-years).

TAKEAWAY:

• Compared with women without depression, those with depression had a 64% higher risk for CVD (hazard ratio [HR], 1.64), while men with depression had a 39% higher risk for CVD vs their counterparts without depression (HR, 1.39; P < .001).
• This association was significant even after controlling for various factors such as body mass index, diabetes, smoking, alcohol consumption, and physical inactivity.
• Investigators offered several theories about the increased risk for CVD in women with depression, including how depression during hormonal shifts can contribute to a greater impact on cardiovascular health.

IN PRACTICE:

“Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management,” study author Hidehiro Kaneko, MD, said in a press release. “Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.”

SOURCE:

Keitaro Senoo, MD, of the Kyoto Prefectural University of Medicine, Kyoto, Japan, led the study, which was published online on March 12 in JACC: Asia.

LIMITATIONS:

The study is observational, so causality between depression and subsequent CVD events cannot be established. In addition, depression severity is unknown.

DISCLOSURES:

The study was funded by the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science, and Technology, Japan. There were no disclosures reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Depression is linked to a significantly increased risk for cardiovascular disease (CVD), particularly in women, new data from a large retrospective cohort study show. Researchers suggest that screening and treating patients for depression may lead to a decreased incidence of CVD.

METHODOLOGY:

• Researchers analyzed health insurance claims from more than 4 million Japanese patients filed between 2005 and 2022.
• Participants were 18-75 (median age, 44) without a history of CVD or stroke, heart failure, or atrial fibrillation.
• Investigators followed participants for a mean period of 2.5-3.5 years to observe the number of CVD events in those who had a diagnosis of depression.
• During the follow-up period, there were 119,000 CVD events in men (14 per 10,000 person-years) and 61,800 CVD events in women (111 per 10,000 person-years).

TAKEAWAY:

• Compared with women without depression, those with depression had a 64% higher risk for CVD (hazard ratio [HR], 1.64), while men with depression had a 39% higher risk for CVD vs their counterparts without depression (HR, 1.39; P < .001).
• This association was significant even after controlling for various factors such as body mass index, diabetes, smoking, alcohol consumption, and physical inactivity.
• Investigators offered several theories about the increased risk for CVD in women with depression, including how depression during hormonal shifts can contribute to a greater impact on cardiovascular health.

IN PRACTICE:

“Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management,” study author Hidehiro Kaneko, MD, said in a press release. “Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.”

SOURCE:

Keitaro Senoo, MD, of the Kyoto Prefectural University of Medicine, Kyoto, Japan, led the study, which was published online on March 12 in JACC: Asia.

LIMITATIONS:

The study is observational, so causality between depression and subsequent CVD events cannot be established. In addition, depression severity is unknown.

DISCLOSURES:

The study was funded by the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science, and Technology, Japan. There were no disclosures reported.

A version of this article appeared on Medscape.com.

Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.

I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).

So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.

But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.

I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.

Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?

Medicine, unfortunately, is littered with ideas that should have worked, but either didn’t, or at least aren’t as good as we thought they should have been. Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.

At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.

They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.

Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.

It’s just a reminder that, here in 2024, we still have a lot to learn.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.

I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).

So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.

But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.

I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.

Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?

Medicine, unfortunately, is littered with ideas that should have worked, but either didn’t, or at least aren’t as good as we thought they should have been. Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.

At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.

They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.

Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.

It’s just a reminder that, here in 2024, we still have a lot to learn.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.

I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).

So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.

But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.

I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.

Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?

Medicine, unfortunately, is littered with ideas that should have worked, but either didn’t, or at least aren’t as good as we thought they should have been. Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.

At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.

They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.

Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.

It’s just a reminder that, here in 2024, we still have a lot to learn.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Cells in the human body chat with each other all the time. One major way they communicate is by releasing tiny spheres called exosomes. These carry fats, proteins, and genetic material that help regulate everything from pregnancy and immune responses to heart health and kidney function.

Now, a new Columbia University study in Nature Nanotechnology demonstrated that these «nanobubbles» can deliver potent immunotherapy directly to tough-to-treat lung cancer tumors via inhalation.

“Exosomes work like text messages between cells , sending and receiving information,” said lead researcher Ke Cheng, PhD, professor of biomedical engineering at Columbia. “The significance of this study is that exosomes can bring mRNA-based treatment to lung cancer cells locally, unlike systemic chemotherapy that can have side effects throughout the body. And inhalation is totally noninvasive. You don’t need a nurse to use an IV needle to pierce your skin.”

Dr. Cheng expects a human trial could launch within 5 years. For now, his study is attracting attention because it marks an advance in three areas of intense interest by researchers and biotech companies alike: Therapeutic uses of exosomes, inhalable treatments for lung conditions, and the safe delivery of powerful interleukin-12 (IL-12) immunotherapy.

Inside the Study

Dr. Cheng, who has been developing exosome and stem cell therapies for more than 15 years, and his lab team focused on lung cancer because the disease, often detected in later stages, “has a huge mortality rate,” he said. “Therapies have been suboptimal and leave the organ so damaged.”

He wanted to explore new alternatives to systemic treatments. Most are given intravenously, but Dr. Cheng thinks exosomes — also called extracellular vesicles (EVs) — could change that.

“One of the advantages of exosomes is that they are naturally secreted by the body or cultured cells,” he noted. “They have low toxicity and have multiple ways of getting their message into cells.”

The scientists borrowed an approach that captured public attention during the pandemic: Using messenger RNA, which directs cells to make proteins for tasks — including boosting immune response.

IL-12 has shown promise against cancer for decades, but early human trials triggered serious side effects and several deaths. Researchers are now trying new delivery methods that target tumor cells without affecting healthy tissue. Dr. Cheng’s team took a new approach, inserting mRNA for IL-12 into exosomes.

One aim of the study was to compare the effectiveness of inhaled exosomes vs inhaled liposomes, engineered fat droplets also under investigation as drug carriers. The team’s question: Which would work better at introducing IL-12 to the lungs to affect cancer, without triggering side effects?

After lab mice inhaled the particles through the nose, the researchers found that exosomes delivered more mRNA into cancer cells in the lungs and fought lung cancer with few side effects. Three days after treatment, researchers saw an influx of cancer-fighting T cells within tumors — with higher levels for exosome-based treatment. Plus, the exosomes led to more cancer-destroying nature killer cells and more monocytes, a sign of immune-system activation.

Researchers also found the treatment acted as a vaccine, training the immune system to battle newly introduced cancers. Little of the exosome-delivered drug escaped into the bloodstream, and the study found minimal side effects. Inhalation didn’t affect normal breathing, Dr. Cheng added.

The study’s use of inhaled exosomes makes it significant, said Raghu Kalluri, MD, PhD, professor and chair of the Department of Cancer Biology at MD Anderson Cancer Center. “This is an interesting study that explores the inhalable delivery of engineered EVs for the treatment of lung cancer and offers insights into focused delivery of EV-based drugs…with implications for diseases beyond cancer,” he said. Dr. Kalluri is also an exosome researcher.

New Frontiers

Once seen as a “quirky biological phenomenon” or just cellular trash, exosomes are now the subject of intense medical research for their potential as drug carriers, as treatments in their own right for everything from wound healing and pneumonia to heart attacks and bowel disorders, and as measurable biological markers that could lead to new tests for cancer and other conditions. One exosome-based prostate cancer test, the ExoDx Prostate Test, is already on the market.

The explosion in exosome research — the number of published studies has grown from just a handful in the early 1980s to more than 9000  — spotlights a particular focus on cancer. According to a 2021 paper in Annals of Oncology, clinical trials for exosomes in cancer treatments and tests far out-paces those for diabetes, heart disease, or neurologic conditions. Currently, 52 clinical trials using exosomes in cancer diagnosis or treatment have been completed, are underway, or are looking for participants, according to clinicaltrials.gov.

Dr. Cheng’s approach could also be used to deliver other drugs to the lungs and other organs via inhalation. “We’re testing inhalation for a different type of lung disease, acute lung injury,” Dr. Cheng said. Other potential targets include lung disorders like pulmonary hypertension. Inhaled exosomes could potentially reach the brain via the olfactory bulb or the heart as it receives oxygenated blood from the lungs.

Breathing in Medicine

So far, inhalable cancer treatments are not available outside research studies in the United States or Europe , said Remi Rosiere, PhD, a lecturer at the Université libre de Bruxelles in Brussels, Belgium, and chief scientific officer of InhaTarget Therapeutics, a company developing its own inhaled treatments for severe respiratory diseases. “Oncologists are very interested,” he said. “If you concentrate the drug on the tumor site, you can avoid distribution to the body.”

Early research into inhalable chemotherapy began in the 1960s but was unsuccessful because breathing equipment dispersed toxic cancer drugs into the air or delivered only small amounts to the lungs, he said.

New delivery techniques aim to change that. Dr. Rosiere’s company is starting a human trial of a dry powder inhaler with the chemotherapy drug cisplatin for lung cancer. Also in the pipeline is an immunotherapy treatment for lung cancer inserted in lipid nanoparticles, which are tiny fat particles similar to liposomes.

He said Dr. Cheng’s study shows the advantages of sending in exosomes. “The data are very persuasive,” Dr. Rosier said of the study. “Exosomes have a good safety profile and are able to remain in the lung for quite a long time. This prolongs exposure to the drug for greater effectiveness, without causing toxicities.”

Getting from a mouse study to a human trial will take time. “You need to understand this is very early stage,” Dr. Rosiere added. “There will be many challenges to overcome.”

One is purely practical: If the drug approaches human trials, he said, regulators will ask whether the exosomes can be produced in large quantities to meet the huge demand for new lung cancer treatments. “Lung cancer is the number one fatal cancer in the world,” Dr. Rosiere said.

A New Route for ‘Powerful’ Cancer Treatment

Meanwhile, the Columbia University study showed that inhalable exosomes are a unique delivery method for IL-12 — and could help solve a major problem that’s plagued this promising cancer treatment for decades.

Called “one of the most powerful immunotherapy agents ever discovered” in a 2022 literature review, IL-12 showed serious side effects that stalled research in the 1980s , sparking an ongoing search for new delivery methods that continues today. In 2022 and 2023, Big Pharma companies including AstraZenca, Moderna, and Bristol Myers Squib reduced their involvement with IL-12 treatment research, leaving the field open to smaller biotech companies working on a variety of drug-delivery approaches that could make IL-12 safe and effective in humans.

These include injecting it directly into tumors, encasing it in various types of particles, masking the drug so it is activated only in cancer cells, and using IL-12 mRNA, which essentially turns tumor cells into IL-12–producing factories. Another IL-12 mRNA drug, from Pittsburgh-based Krystal Biotech, received a fast-track designation from the US Food and Drug Administration in February 2024 for an inhaled lung cancer treatment that packages mRNA for IL-12 and IL-2 inside an engineered virus.

And of course, there is Dr. Cheng’s inhalable treatment, culminating decades of work across three burgeoning fields.

A version of this article appeared on Medscape.com.

Cells in the human body chat with each other all the time. One major way they communicate is by releasing tiny spheres called exosomes. These carry fats, proteins, and genetic material that help regulate everything from pregnancy and immune responses to heart health and kidney function.

Now, a new Columbia University study in Nature Nanotechnology demonstrated that these «nanobubbles» can deliver potent immunotherapy directly to tough-to-treat lung cancer tumors via inhalation.

“Exosomes work like text messages between cells , sending and receiving information,” said lead researcher Ke Cheng, PhD, professor of biomedical engineering at Columbia. “The significance of this study is that exosomes can bring mRNA-based treatment to lung cancer cells locally, unlike systemic chemotherapy that can have side effects throughout the body. And inhalation is totally noninvasive. You don’t need a nurse to use an IV needle to pierce your skin.”

Dr. Cheng expects a human trial could launch within 5 years. For now, his study is attracting attention because it marks an advance in three areas of intense interest by researchers and biotech companies alike: Therapeutic uses of exosomes, inhalable treatments for lung conditions, and the safe delivery of powerful interleukin-12 (IL-12) immunotherapy.

Inside the Study

Dr. Cheng, who has been developing exosome and stem cell therapies for more than 15 years, and his lab team focused on lung cancer because the disease, often detected in later stages, “has a huge mortality rate,” he said. “Therapies have been suboptimal and leave the organ so damaged.”

He wanted to explore new alternatives to systemic treatments. Most are given intravenously, but Dr. Cheng thinks exosomes — also called extracellular vesicles (EVs) — could change that.

“One of the advantages of exosomes is that they are naturally secreted by the body or cultured cells,” he noted. “They have low toxicity and have multiple ways of getting their message into cells.”

The scientists borrowed an approach that captured public attention during the pandemic: Using messenger RNA, which directs cells to make proteins for tasks — including boosting immune response.

IL-12 has shown promise against cancer for decades, but early human trials triggered serious side effects and several deaths. Researchers are now trying new delivery methods that target tumor cells without affecting healthy tissue. Dr. Cheng’s team took a new approach, inserting mRNA for IL-12 into exosomes.

One aim of the study was to compare the effectiveness of inhaled exosomes vs inhaled liposomes, engineered fat droplets also under investigation as drug carriers. The team’s question: Which would work better at introducing IL-12 to the lungs to affect cancer, without triggering side effects?

After lab mice inhaled the particles through the nose, the researchers found that exosomes delivered more mRNA into cancer cells in the lungs and fought lung cancer with few side effects. Three days after treatment, researchers saw an influx of cancer-fighting T cells within tumors — with higher levels for exosome-based treatment. Plus, the exosomes led to more cancer-destroying nature killer cells and more monocytes, a sign of immune-system activation.

Researchers also found the treatment acted as a vaccine, training the immune system to battle newly introduced cancers. Little of the exosome-delivered drug escaped into the bloodstream, and the study found minimal side effects. Inhalation didn’t affect normal breathing, Dr. Cheng added.

The study’s use of inhaled exosomes makes it significant, said Raghu Kalluri, MD, PhD, professor and chair of the Department of Cancer Biology at MD Anderson Cancer Center. “This is an interesting study that explores the inhalable delivery of engineered EVs for the treatment of lung cancer and offers insights into focused delivery of EV-based drugs…with implications for diseases beyond cancer,” he said. Dr. Kalluri is also an exosome researcher.

New Frontiers

Once seen as a “quirky biological phenomenon” or just cellular trash, exosomes are now the subject of intense medical research for their potential as drug carriers, as treatments in their own right for everything from wound healing and pneumonia to heart attacks and bowel disorders, and as measurable biological markers that could lead to new tests for cancer and other conditions. One exosome-based prostate cancer test, the ExoDx Prostate Test, is already on the market.

The explosion in exosome research — the number of published studies has grown from just a handful in the early 1980s to more than 9000  — spotlights a particular focus on cancer. According to a 2021 paper in Annals of Oncology, clinical trials for exosomes in cancer treatments and tests far out-paces those for diabetes, heart disease, or neurologic conditions. Currently, 52 clinical trials using exosomes in cancer diagnosis or treatment have been completed, are underway, or are looking for participants, according to clinicaltrials.gov.

Dr. Cheng’s approach could also be used to deliver other drugs to the lungs and other organs via inhalation. “We’re testing inhalation for a different type of lung disease, acute lung injury,” Dr. Cheng said. Other potential targets include lung disorders like pulmonary hypertension. Inhaled exosomes could potentially reach the brain via the olfactory bulb or the heart as it receives oxygenated blood from the lungs.

Breathing in Medicine

So far, inhalable cancer treatments are not available outside research studies in the United States or Europe , said Remi Rosiere, PhD, a lecturer at the Université libre de Bruxelles in Brussels, Belgium, and chief scientific officer of InhaTarget Therapeutics, a company developing its own inhaled treatments for severe respiratory diseases. “Oncologists are very interested,” he said. “If you concentrate the drug on the tumor site, you can avoid distribution to the body.”

Early research into inhalable chemotherapy began in the 1960s but was unsuccessful because breathing equipment dispersed toxic cancer drugs into the air or delivered only small amounts to the lungs, he said.

New delivery techniques aim to change that. Dr. Rosiere’s company is starting a human trial of a dry powder inhaler with the chemotherapy drug cisplatin for lung cancer. Also in the pipeline is an immunotherapy treatment for lung cancer inserted in lipid nanoparticles, which are tiny fat particles similar to liposomes.

He said Dr. Cheng’s study shows the advantages of sending in exosomes. “The data are very persuasive,” Dr. Rosier said of the study. “Exosomes have a good safety profile and are able to remain in the lung for quite a long time. This prolongs exposure to the drug for greater effectiveness, without causing toxicities.”

Getting from a mouse study to a human trial will take time. “You need to understand this is very early stage,” Dr. Rosiere added. “There will be many challenges to overcome.”

One is purely practical: If the drug approaches human trials, he said, regulators will ask whether the exosomes can be produced in large quantities to meet the huge demand for new lung cancer treatments. “Lung cancer is the number one fatal cancer in the world,” Dr. Rosiere said.

A New Route for ‘Powerful’ Cancer Treatment

Meanwhile, the Columbia University study showed that inhalable exosomes are a unique delivery method for IL-12 — and could help solve a major problem that’s plagued this promising cancer treatment for decades.

Called “one of the most powerful immunotherapy agents ever discovered” in a 2022 literature review, IL-12 showed serious side effects that stalled research in the 1980s , sparking an ongoing search for new delivery methods that continues today. In 2022 and 2023, Big Pharma companies including AstraZenca, Moderna, and Bristol Myers Squib reduced their involvement with IL-12 treatment research, leaving the field open to smaller biotech companies working on a variety of drug-delivery approaches that could make IL-12 safe and effective in humans.

These include injecting it directly into tumors, encasing it in various types of particles, masking the drug so it is activated only in cancer cells, and using IL-12 mRNA, which essentially turns tumor cells into IL-12–producing factories. Another IL-12 mRNA drug, from Pittsburgh-based Krystal Biotech, received a fast-track designation from the US Food and Drug Administration in February 2024 for an inhaled lung cancer treatment that packages mRNA for IL-12 and IL-2 inside an engineered virus.

And of course, there is Dr. Cheng’s inhalable treatment, culminating decades of work across three burgeoning fields.

A version of this article appeared on Medscape.com.

Cells in the human body chat with each other all the time. One major way they communicate is by releasing tiny spheres called exosomes. These carry fats, proteins, and genetic material that help regulate everything from pregnancy and immune responses to heart health and kidney function.

Now, a new Columbia University study in Nature Nanotechnology demonstrated that these «nanobubbles» can deliver potent immunotherapy directly to tough-to-treat lung cancer tumors via inhalation.

“Exosomes work like text messages between cells , sending and receiving information,” said lead researcher Ke Cheng, PhD, professor of biomedical engineering at Columbia. “The significance of this study is that exosomes can bring mRNA-based treatment to lung cancer cells locally, unlike systemic chemotherapy that can have side effects throughout the body. And inhalation is totally noninvasive. You don’t need a nurse to use an IV needle to pierce your skin.”

Dr. Cheng expects a human trial could launch within 5 years. For now, his study is attracting attention because it marks an advance in three areas of intense interest by researchers and biotech companies alike: Therapeutic uses of exosomes, inhalable treatments for lung conditions, and the safe delivery of powerful interleukin-12 (IL-12) immunotherapy.

Inside the Study

Dr. Cheng, who has been developing exosome and stem cell therapies for more than 15 years, and his lab team focused on lung cancer because the disease, often detected in later stages, “has a huge mortality rate,” he said. “Therapies have been suboptimal and leave the organ so damaged.”

He wanted to explore new alternatives to systemic treatments. Most are given intravenously, but Dr. Cheng thinks exosomes — also called extracellular vesicles (EVs) — could change that.

“One of the advantages of exosomes is that they are naturally secreted by the body or cultured cells,” he noted. “They have low toxicity and have multiple ways of getting their message into cells.”

The scientists borrowed an approach that captured public attention during the pandemic: Using messenger RNA, which directs cells to make proteins for tasks — including boosting immune response.

IL-12 has shown promise against cancer for decades, but early human trials triggered serious side effects and several deaths. Researchers are now trying new delivery methods that target tumor cells without affecting healthy tissue. Dr. Cheng’s team took a new approach, inserting mRNA for IL-12 into exosomes.

One aim of the study was to compare the effectiveness of inhaled exosomes vs inhaled liposomes, engineered fat droplets also under investigation as drug carriers. The team’s question: Which would work better at introducing IL-12 to the lungs to affect cancer, without triggering side effects?

After lab mice inhaled the particles through the nose, the researchers found that exosomes delivered more mRNA into cancer cells in the lungs and fought lung cancer with few side effects. Three days after treatment, researchers saw an influx of cancer-fighting T cells within tumors — with higher levels for exosome-based treatment. Plus, the exosomes led to more cancer-destroying nature killer cells and more monocytes, a sign of immune-system activation.

Researchers also found the treatment acted as a vaccine, training the immune system to battle newly introduced cancers. Little of the exosome-delivered drug escaped into the bloodstream, and the study found minimal side effects. Inhalation didn’t affect normal breathing, Dr. Cheng added.

The study’s use of inhaled exosomes makes it significant, said Raghu Kalluri, MD, PhD, professor and chair of the Department of Cancer Biology at MD Anderson Cancer Center. “This is an interesting study that explores the inhalable delivery of engineered EVs for the treatment of lung cancer and offers insights into focused delivery of EV-based drugs…with implications for diseases beyond cancer,” he said. Dr. Kalluri is also an exosome researcher.

New Frontiers

Once seen as a “quirky biological phenomenon” or just cellular trash, exosomes are now the subject of intense medical research for their potential as drug carriers, as treatments in their own right for everything from wound healing and pneumonia to heart attacks and bowel disorders, and as measurable biological markers that could lead to new tests for cancer and other conditions. One exosome-based prostate cancer test, the ExoDx Prostate Test, is already on the market.

The explosion in exosome research — the number of published studies has grown from just a handful in the early 1980s to more than 9000  — spotlights a particular focus on cancer. According to a 2021 paper in Annals of Oncology, clinical trials for exosomes in cancer treatments and tests far out-paces those for diabetes, heart disease, or neurologic conditions. Currently, 52 clinical trials using exosomes in cancer diagnosis or treatment have been completed, are underway, or are looking for participants, according to clinicaltrials.gov.

Dr. Cheng’s approach could also be used to deliver other drugs to the lungs and other organs via inhalation. “We’re testing inhalation for a different type of lung disease, acute lung injury,” Dr. Cheng said. Other potential targets include lung disorders like pulmonary hypertension. Inhaled exosomes could potentially reach the brain via the olfactory bulb or the heart as it receives oxygenated blood from the lungs.

Breathing in Medicine

So far, inhalable cancer treatments are not available outside research studies in the United States or Europe , said Remi Rosiere, PhD, a lecturer at the Université libre de Bruxelles in Brussels, Belgium, and chief scientific officer of InhaTarget Therapeutics, a company developing its own inhaled treatments for severe respiratory diseases. “Oncologists are very interested,” he said. “If you concentrate the drug on the tumor site, you can avoid distribution to the body.”

Early research into inhalable chemotherapy began in the 1960s but was unsuccessful because breathing equipment dispersed toxic cancer drugs into the air or delivered only small amounts to the lungs, he said.

New delivery techniques aim to change that. Dr. Rosiere’s company is starting a human trial of a dry powder inhaler with the chemotherapy drug cisplatin for lung cancer. Also in the pipeline is an immunotherapy treatment for lung cancer inserted in lipid nanoparticles, which are tiny fat particles similar to liposomes.

He said Dr. Cheng’s study shows the advantages of sending in exosomes. “The data are very persuasive,” Dr. Rosier said of the study. “Exosomes have a good safety profile and are able to remain in the lung for quite a long time. This prolongs exposure to the drug for greater effectiveness, without causing toxicities.”

Getting from a mouse study to a human trial will take time. “You need to understand this is very early stage,” Dr. Rosiere added. “There will be many challenges to overcome.”

One is purely practical: If the drug approaches human trials, he said, regulators will ask whether the exosomes can be produced in large quantities to meet the huge demand for new lung cancer treatments. “Lung cancer is the number one fatal cancer in the world,” Dr. Rosiere said.

A New Route for ‘Powerful’ Cancer Treatment

Meanwhile, the Columbia University study showed that inhalable exosomes are a unique delivery method for IL-12 — and could help solve a major problem that’s plagued this promising cancer treatment for decades.

Called “one of the most powerful immunotherapy agents ever discovered” in a 2022 literature review, IL-12 showed serious side effects that stalled research in the 1980s , sparking an ongoing search for new delivery methods that continues today. In 2022 and 2023, Big Pharma companies including AstraZenca, Moderna, and Bristol Myers Squib reduced their involvement with IL-12 treatment research, leaving the field open to smaller biotech companies working on a variety of drug-delivery approaches that could make IL-12 safe and effective in humans.

These include injecting it directly into tumors, encasing it in various types of particles, masking the drug so it is activated only in cancer cells, and using IL-12 mRNA, which essentially turns tumor cells into IL-12–producing factories. Another IL-12 mRNA drug, from Pittsburgh-based Krystal Biotech, received a fast-track designation from the US Food and Drug Administration in February 2024 for an inhaled lung cancer treatment that packages mRNA for IL-12 and IL-2 inside an engineered virus.

And of course, there is Dr. Cheng’s inhalable treatment, culminating decades of work across three burgeoning fields.

A version of this article appeared on Medscape.com.

Maternal mental health has a profound impact on the health and wellbeing of the child. Since the onset of the pandemic, rates of postpartum depression have increased, affecting an estimated 1 in 5 women.¹ Numerous studies show the impact of postpartum depression on the newborn child across multiple domains, from bonding to healthy weight gain to meeting developmental milestones.

While new medications are being studied and approved to specifically target postpartum depression, these treatments are inaccessible to many because of high costs and long wait lists. Beyond medication, structural changes such as paid parental leave have been shown to have a substantial impact on maternal mental health, thus impacting the health of children as well. As physicians, it is imperative that we advocate for systems-level policy changes that have been shown to improve the health of both parent and child.

Implications for Mothers and Children

Psychiatric diagnoses such as postpartum depression are on the rise.^1,2 This is likely attributable to a combination of factors, including increased isolation since the start of the pandemic, worsening health inequities across race and socioeconomic status, and difficulty accessing mental health care.^3-5 The effect that postpartum depression has on the family is significant for the newborn as well as other children in the home.

Data suggest that postpartum depression impacts both the physical and mental health of the child. Infants of mothers with postpartum depression may experience challenges with weight gain, decreased breastfeeding, sleep disruptions, and delays in achieving developmental milestones.^6-9 They may also show decreased maternal infant bonding, challenges with cognitive development including language and IQ, and increased risk of behavioral disturbances.^10,11 These effects are likely attributable to a combination of factors, including decreased maternal responsiveness to infant cues.^7,12 Many of these effects are mediated by the chronicity and severity of depressive symptoms, suggesting the importance of screening and treatment of postpartum depression.^10,11 However, treatment for postpartum depression can be difficult to access, particularly given the increased level of need.

It is therefore critical to consider what structural interventions and policy changes can decrease the risk of developing postpartum depression. Data consistently show that access to paid parental leave improves maternal mental health outcomes. Among patients with access to parental leave, research shows that paid leave of longer duration, at least 2-3 months, is the most protective.¹³ Studies have identified decreased depressive symptoms, decreased stress, decreased use of mental health services, and decreased hospital admissions among women with longer parental leave.¹³ The positive effects of paid parental leave on maternal mental health can extend beyond the postpartum period, solidifying its impact on the long-term health outcomes of both mother and child.¹³
 

Advocacy Is Imperative

In 2024, the United States is the only high-income country, and one of only seven countries in the world, that does not guarantee access to paid parental leave. The Family Medical Leave Act is a 31-year-old federal law that requires some employers to provide unpaid leave to eligible employees. It is narrow in scope, and it excludes many low-wage workers and LGBTQ+ families. Thirteen states — California, Colorado, Connecticut, Delaware, Maine, Massachusetts, Maryland, Minnesota, New Jersey, New York, Oregon, Rhode Island, and Washington — as well as the District of Columbia, have enacted their own paid leave policies. However, there are no federal laws requiring access to paid parental leave. As of 2023, fewer than 30% of workers in the United States have access to paid parental leave, and only 16% of employees in the service industry have access to paid parental leave.¹⁴ This disproportionately affects families from lower income backgrounds, and further exacerbates socioeconomic, racial, and gender inequities. From a health systems lens, this increases risk of adverse maternal mental health outcomes among those who already have decreased access to mental health services, worsening health disparities.

Paid parental leave has strong public support across party lines, with polls showing the majority of Americans support comprehensive paid family and medical leave.¹⁵ Despite this, the United States has failed to enact legislation on this issue since 1993. Multiple attempts at expanding leave have not come to fruition. In the past year, both the house and the senate have announced bipartisan efforts to expand access to paid parental leave. However, legislative frameworks are still in early stages.

As physicians, it is crucial that we advocate for expanded access to paid parental leave. We must use our expertise to speak to the impact that paid parental leave can have on the mental and physical health of parents, children, and families. By advocating for paid parental leave, we can help create a more just and equitable healthcare system.
 

Dr. Shannon is a second-year psychiatry resident at University of California, Los Angeles. She attended Stanford University for her undergraduate degree and Dartmouth Geisel School of Medicine for medical school. Her interests include perinatal psychiatry, health systems research, and mental health policy advocacy. Dr. Richards is assistant clinical professor in the department of psychiatry and biobehavioral sciences; program director of the child and adolescent psychiatry fellowship; and associate medical director of the perinatal program at the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles.

References

1. Wang Z et al. Mapping Global Prevalence of Depression Among Postpartum Women. Transl Psychiatry. 2021 Oct 20. doi: 10.1038/s41398-021-01663-6.

2. Iyengar U et al. One Year Into the Pandemic: A Systematic Review of Perinatal Mental Health Outcomes During COVID-19. Front Psychiatry. 2021 Jun 24. doi: 10.3389/fpsyt.2021.674194.

3. World Health Organization. Mental Health and COVID-19: Early Evidence of the Pandemic’s Impact: Scientific Brief. 2022 Mar 2. www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Mental_health-2022.1.

4. Masters GA et al. Impact of the COVID-19 Pandemic on Mental Health, Access to Care, and Health Disparities in the Perinatal Period. J Psychiatr Res. 2021 May. doi: 10.1016/j.jpsychires.2021.02.056.

5. Shuffrey LC et al. Improving Perinatal Maternal Mental Health Starts With Addressing Structural Inequities. JAMA Psychiatry. 2022 May 1. doi: 10.1001/jamapsychiatry.2022.0097.

6. Lubotzky-Gete S et al. Postpartum Depression and Infant Development Up to 24 months: A Nationwide Population-Based Study. J Affect Disord. 2021 Apr 15. doi: 10.1016/j.jad.2021.02.042.

7. Saharoy R et al. Postpartum Depression and Maternal Care: Exploring the Complex Effects on Mothers and Infants. Cureus. 2023 Jul 4. doi: 10.7759/cureus.41381..

8. Gress-Smith JL et al. Postpartum Depression Prevalence and Impact on Infant Health, Weight, and Sleep in Low-Income and Ethnic Minority Women and Infants. Matern Child Health J. 2012 May. doi: 10.1007/s10995-011-0812-y.

9. Kim S et al. The Impact of Antepartum Depression and Postpartum Depression on Exclusive Breastfeeding: A Systematic Review and Meta-Analysis. Clin Nurs Res. 2022 Jun. doi: 10.1177/10547738211053507.

10. Mirhosseini H et al. Cognitive Behavioral Development in Children Following Maternal Postpartum Depression: A Review Article. Electron Physician. 2015 Dec 20. doi: 10.19082/1673.

11. Grace SL et al. The Effect of Postpartum Depression on Child Cognitive Development and Behavior: A Review and Critical Analysis of the Literature. Arch Womens Ment Health. 2003 Nov. doi: 10.1007/s00737-003-0024-6.

12. Milgrom J et al. The Mediating Role of Maternal Responsiveness in Some Longer Term Effects of Postnatal Depression on Infant Development. Infant Behavior and Development. 2004 Sep 11. doi.org/10.1016/j.infbeh.2004.03.003.

13. Heshmati A et al. The Effect of Parental Leave on Parents’ Mental Health: A Systematic Review. Lancet Public Health. 2023 Jan. doi: 10.1016/S2468-2667(22)00311-5.

14. U.S. Bureau of Labor Statistics, What Data Does the BLS Publish on Family Leave? 2023 Sept 21. www.bls.gov/ebs/factsheets/family-leave-benefits-fact-sheet.htm.

15. Horowitz JM et al. Americans Widely Support Paid Family and Medical Leave, But Differ Over Specific Policies. Pew Research Center’s Social & Demographic Trends Project, Pew Research Center. 2017 Mar 23. www.pewresearch.org/social-trends/2017/03/23/americans-widely-support-paid-family-and-medical-leave-but-differ-over-specific-policies/.

Maternal mental health has a profound impact on the health and wellbeing of the child. Since the onset of the pandemic, rates of postpartum depression have increased, affecting an estimated 1 in 5 women.¹ Numerous studies show the impact of postpartum depression on the newborn child across multiple domains, from bonding to healthy weight gain to meeting developmental milestones.

While new medications are being studied and approved to specifically target postpartum depression, these treatments are inaccessible to many because of high costs and long wait lists. Beyond medication, structural changes such as paid parental leave have been shown to have a substantial impact on maternal mental health, thus impacting the health of children as well. As physicians, it is imperative that we advocate for systems-level policy changes that have been shown to improve the health of both parent and child.

Implications for Mothers and Children

Psychiatric diagnoses such as postpartum depression are on the rise.^1,2 This is likely attributable to a combination of factors, including increased isolation since the start of the pandemic, worsening health inequities across race and socioeconomic status, and difficulty accessing mental health care.^3-5 The effect that postpartum depression has on the family is significant for the newborn as well as other children in the home.

Data suggest that postpartum depression impacts both the physical and mental health of the child. Infants of mothers with postpartum depression may experience challenges with weight gain, decreased breastfeeding, sleep disruptions, and delays in achieving developmental milestones.^6-9 They may also show decreased maternal infant bonding, challenges with cognitive development including language and IQ, and increased risk of behavioral disturbances.^10,11 These effects are likely attributable to a combination of factors, including decreased maternal responsiveness to infant cues.^7,12 Many of these effects are mediated by the chronicity and severity of depressive symptoms, suggesting the importance of screening and treatment of postpartum depression.^10,11 However, treatment for postpartum depression can be difficult to access, particularly given the increased level of need.

It is therefore critical to consider what structural interventions and policy changes can decrease the risk of developing postpartum depression. Data consistently show that access to paid parental leave improves maternal mental health outcomes. Among patients with access to parental leave, research shows that paid leave of longer duration, at least 2-3 months, is the most protective.¹³ Studies have identified decreased depressive symptoms, decreased stress, decreased use of mental health services, and decreased hospital admissions among women with longer parental leave.¹³ The positive effects of paid parental leave on maternal mental health can extend beyond the postpartum period, solidifying its impact on the long-term health outcomes of both mother and child.¹³
 

Advocacy Is Imperative

In 2024, the United States is the only high-income country, and one of only seven countries in the world, that does not guarantee access to paid parental leave. The Family Medical Leave Act is a 31-year-old federal law that requires some employers to provide unpaid leave to eligible employees. It is narrow in scope, and it excludes many low-wage workers and LGBTQ+ families. Thirteen states — California, Colorado, Connecticut, Delaware, Maine, Massachusetts, Maryland, Minnesota, New Jersey, New York, Oregon, Rhode Island, and Washington — as well as the District of Columbia, have enacted their own paid leave policies. However, there are no federal laws requiring access to paid parental leave. As of 2023, fewer than 30% of workers in the United States have access to paid parental leave, and only 16% of employees in the service industry have access to paid parental leave.¹⁴ This disproportionately affects families from lower income backgrounds, and further exacerbates socioeconomic, racial, and gender inequities. From a health systems lens, this increases risk of adverse maternal mental health outcomes among those who already have decreased access to mental health services, worsening health disparities.

Paid parental leave has strong public support across party lines, with polls showing the majority of Americans support comprehensive paid family and medical leave.¹⁵ Despite this, the United States has failed to enact legislation on this issue since 1993. Multiple attempts at expanding leave have not come to fruition. In the past year, both the house and the senate have announced bipartisan efforts to expand access to paid parental leave. However, legislative frameworks are still in early stages.

As physicians, it is crucial that we advocate for expanded access to paid parental leave. We must use our expertise to speak to the impact that paid parental leave can have on the mental and physical health of parents, children, and families. By advocating for paid parental leave, we can help create a more just and equitable healthcare system.
 

Dr. Shannon is a second-year psychiatry resident at University of California, Los Angeles. She attended Stanford University for her undergraduate degree and Dartmouth Geisel School of Medicine for medical school. Her interests include perinatal psychiatry, health systems research, and mental health policy advocacy. Dr. Richards is assistant clinical professor in the department of psychiatry and biobehavioral sciences; program director of the child and adolescent psychiatry fellowship; and associate medical director of the perinatal program at the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles.

References

1. Wang Z et al. Mapping Global Prevalence of Depression Among Postpartum Women. Transl Psychiatry. 2021 Oct 20. doi: 10.1038/s41398-021-01663-6.

2. Iyengar U et al. One Year Into the Pandemic: A Systematic Review of Perinatal Mental Health Outcomes During COVID-19. Front Psychiatry. 2021 Jun 24. doi: 10.3389/fpsyt.2021.674194.

3. World Health Organization. Mental Health and COVID-19: Early Evidence of the Pandemic’s Impact: Scientific Brief. 2022 Mar 2. www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Mental_health-2022.1.

4. Masters GA et al. Impact of the COVID-19 Pandemic on Mental Health, Access to Care, and Health Disparities in the Perinatal Period. J Psychiatr Res. 2021 May. doi: 10.1016/j.jpsychires.2021.02.056.

5. Shuffrey LC et al. Improving Perinatal Maternal Mental Health Starts With Addressing Structural Inequities. JAMA Psychiatry. 2022 May 1. doi: 10.1001/jamapsychiatry.2022.0097.

6. Lubotzky-Gete S et al. Postpartum Depression and Infant Development Up to 24 months: A Nationwide Population-Based Study. J Affect Disord. 2021 Apr 15. doi: 10.1016/j.jad.2021.02.042.

7. Saharoy R et al. Postpartum Depression and Maternal Care: Exploring the Complex Effects on Mothers and Infants. Cureus. 2023 Jul 4. doi: 10.7759/cureus.41381..

8. Gress-Smith JL et al. Postpartum Depression Prevalence and Impact on Infant Health, Weight, and Sleep in Low-Income and Ethnic Minority Women and Infants. Matern Child Health J. 2012 May. doi: 10.1007/s10995-011-0812-y.

9. Kim S et al. The Impact of Antepartum Depression and Postpartum Depression on Exclusive Breastfeeding: A Systematic Review and Meta-Analysis. Clin Nurs Res. 2022 Jun. doi: 10.1177/10547738211053507.

10. Mirhosseini H et al. Cognitive Behavioral Development in Children Following Maternal Postpartum Depression: A Review Article. Electron Physician. 2015 Dec 20. doi: 10.19082/1673.

11. Grace SL et al. The Effect of Postpartum Depression on Child Cognitive Development and Behavior: A Review and Critical Analysis of the Literature. Arch Womens Ment Health. 2003 Nov. doi: 10.1007/s00737-003-0024-6.

12. Milgrom J et al. The Mediating Role of Maternal Responsiveness in Some Longer Term Effects of Postnatal Depression on Infant Development. Infant Behavior and Development. 2004 Sep 11. doi.org/10.1016/j.infbeh.2004.03.003.

13. Heshmati A et al. The Effect of Parental Leave on Parents’ Mental Health: A Systematic Review. Lancet Public Health. 2023 Jan. doi: 10.1016/S2468-2667(22)00311-5.

14. U.S. Bureau of Labor Statistics, What Data Does the BLS Publish on Family Leave? 2023 Sept 21. www.bls.gov/ebs/factsheets/family-leave-benefits-fact-sheet.htm.

15. Horowitz JM et al. Americans Widely Support Paid Family and Medical Leave, But Differ Over Specific Policies. Pew Research Center’s Social & Demographic Trends Project, Pew Research Center. 2017 Mar 23. www.pewresearch.org/social-trends/2017/03/23/americans-widely-support-paid-family-and-medical-leave-but-differ-over-specific-policies/.

Maternal mental health has a profound impact on the health and wellbeing of the child. Since the onset of the pandemic, rates of postpartum depression have increased, affecting an estimated 1 in 5 women.¹ Numerous studies show the impact of postpartum depression on the newborn child across multiple domains, from bonding to healthy weight gain to meeting developmental milestones.

While new medications are being studied and approved to specifically target postpartum depression, these treatments are inaccessible to many because of high costs and long wait lists. Beyond medication, structural changes such as paid parental leave have been shown to have a substantial impact on maternal mental health, thus impacting the health of children as well. As physicians, it is imperative that we advocate for systems-level policy changes that have been shown to improve the health of both parent and child.

Implications for Mothers and Children

Psychiatric diagnoses such as postpartum depression are on the rise.^1,2 This is likely attributable to a combination of factors, including increased isolation since the start of the pandemic, worsening health inequities across race and socioeconomic status, and difficulty accessing mental health care.^3-5 The effect that postpartum depression has on the family is significant for the newborn as well as other children in the home.

Data suggest that postpartum depression impacts both the physical and mental health of the child. Infants of mothers with postpartum depression may experience challenges with weight gain, decreased breastfeeding, sleep disruptions, and delays in achieving developmental milestones.^6-9 They may also show decreased maternal infant bonding, challenges with cognitive development including language and IQ, and increased risk of behavioral disturbances.^10,11 These effects are likely attributable to a combination of factors, including decreased maternal responsiveness to infant cues.^7,12 Many of these effects are mediated by the chronicity and severity of depressive symptoms, suggesting the importance of screening and treatment of postpartum depression.^10,11 However, treatment for postpartum depression can be difficult to access, particularly given the increased level of need.

It is therefore critical to consider what structural interventions and policy changes can decrease the risk of developing postpartum depression. Data consistently show that access to paid parental leave improves maternal mental health outcomes. Among patients with access to parental leave, research shows that paid leave of longer duration, at least 2-3 months, is the most protective.¹³ Studies have identified decreased depressive symptoms, decreased stress, decreased use of mental health services, and decreased hospital admissions among women with longer parental leave.¹³ The positive effects of paid parental leave on maternal mental health can extend beyond the postpartum period, solidifying its impact on the long-term health outcomes of both mother and child.¹³
 

Advocacy Is Imperative

In 2024, the United States is the only high-income country, and one of only seven countries in the world, that does not guarantee access to paid parental leave. The Family Medical Leave Act is a 31-year-old federal law that requires some employers to provide unpaid leave to eligible employees. It is narrow in scope, and it excludes many low-wage workers and LGBTQ+ families. Thirteen states — California, Colorado, Connecticut, Delaware, Maine, Massachusetts, Maryland, Minnesota, New Jersey, New York, Oregon, Rhode Island, and Washington — as well as the District of Columbia, have enacted their own paid leave policies. However, there are no federal laws requiring access to paid parental leave. As of 2023, fewer than 30% of workers in the United States have access to paid parental leave, and only 16% of employees in the service industry have access to paid parental leave.¹⁴ This disproportionately affects families from lower income backgrounds, and further exacerbates socioeconomic, racial, and gender inequities. From a health systems lens, this increases risk of adverse maternal mental health outcomes among those who already have decreased access to mental health services, worsening health disparities.

Paid parental leave has strong public support across party lines, with polls showing the majority of Americans support comprehensive paid family and medical leave.¹⁵ Despite this, the United States has failed to enact legislation on this issue since 1993. Multiple attempts at expanding leave have not come to fruition. In the past year, both the house and the senate have announced bipartisan efforts to expand access to paid parental leave. However, legislative frameworks are still in early stages.

As physicians, it is crucial that we advocate for expanded access to paid parental leave. We must use our expertise to speak to the impact that paid parental leave can have on the mental and physical health of parents, children, and families. By advocating for paid parental leave, we can help create a more just and equitable healthcare system.
 

Dr. Shannon is a second-year psychiatry resident at University of California, Los Angeles. She attended Stanford University for her undergraduate degree and Dartmouth Geisel School of Medicine for medical school. Her interests include perinatal psychiatry, health systems research, and mental health policy advocacy. Dr. Richards is assistant clinical professor in the department of psychiatry and biobehavioral sciences; program director of the child and adolescent psychiatry fellowship; and associate medical director of the perinatal program at the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles.

References

1. Wang Z et al. Mapping Global Prevalence of Depression Among Postpartum Women. Transl Psychiatry. 2021 Oct 20. doi: 10.1038/s41398-021-01663-6.

2. Iyengar U et al. One Year Into the Pandemic: A Systematic Review of Perinatal Mental Health Outcomes During COVID-19. Front Psychiatry. 2021 Jun 24. doi: 10.3389/fpsyt.2021.674194.

3. World Health Organization. Mental Health and COVID-19: Early Evidence of the Pandemic’s Impact: Scientific Brief. 2022 Mar 2. www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Mental_health-2022.1.

4. Masters GA et al. Impact of the COVID-19 Pandemic on Mental Health, Access to Care, and Health Disparities in the Perinatal Period. J Psychiatr Res. 2021 May. doi: 10.1016/j.jpsychires.2021.02.056.

5. Shuffrey LC et al. Improving Perinatal Maternal Mental Health Starts With Addressing Structural Inequities. JAMA Psychiatry. 2022 May 1. doi: 10.1001/jamapsychiatry.2022.0097.

6. Lubotzky-Gete S et al. Postpartum Depression and Infant Development Up to 24 months: A Nationwide Population-Based Study. J Affect Disord. 2021 Apr 15. doi: 10.1016/j.jad.2021.02.042.

7. Saharoy R et al. Postpartum Depression and Maternal Care: Exploring the Complex Effects on Mothers and Infants. Cureus. 2023 Jul 4. doi: 10.7759/cureus.41381..

8. Gress-Smith JL et al. Postpartum Depression Prevalence and Impact on Infant Health, Weight, and Sleep in Low-Income and Ethnic Minority Women and Infants. Matern Child Health J. 2012 May. doi: 10.1007/s10995-011-0812-y.

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SAN DIEGO — Treatment with topical roflumilast, 0.05%, approved at a higher concentration for treating psoriasis, showed high levels of improvement in about a quarter of children aged 2-5 years with mild to moderate atopic dermatitis (AD), according to the results of a phase 3 study reported at the annual meeting of the American Academy of Dermatology.

Among patients treated with roflumilast cream, 0.05%, 25.4% reached the primary endpoint of “clear” or “almost clear” plus a two-grade improvement from baseline at week 4 vs 10.7% among those in the vehicle group (P < .0001) in a phase 3 randomized controlled trial of children. The findings were released in a late-breaker session at the meeting.

Roflumilast cream, 0.3% (Zoryve), is approved by the Food and Drug Administration (FDA) for treating psoriasis in patients 6 years and older, and lower doses are being evaluated for AD: 0.15% for adults and children ages 6 and older, and 0.05% for ages 2-5. Roflumilast is a phosphodiesterase-4 inhibitor. In 2023, the FDA accepted a supplemental drug application from the manufacturer, Arcutis, for roflumilast, 0.15%, for treating AD in patients ages 6 and older, based on the results from two recently published phase 3 trials, INTEGUMENT-1 and INTEGUMENT-2.

The study of younger children, INTEGUMENT-PED, recruited 652 patients aged 2-5 with mild to moderate AD, with a Validated Investigator Global Assessment scale for AD (vlGA-AD) score of 2 or 3, a mean body surface area of 22% overall (range, 3%-82%), and an Eczema Area and Severity Index (EASI) score of at least 5. Of the patients enrolled, 437 were assigned to 0.05% roflumilast cream, applied once a day for 4 weeks (mean age, 3.3 years; 51.6% male; 67.4% White; 15.6% Black; 8.5% Asian; 8.5% other or more than one race; 80.5% not Latino/Hispanic). The remaining 215 children were assigned to vehicle cream and had similar characteristics.

About 52% of the patients in both groups had an inadequate response, intolerance, or contraindications to topical corticosteroids (and about 17% for topical calcineurin inhibitors and about 9% for crisaborole).

The proportions of patients who reached “clear” (0) or “almost clear” (1) on the vlGA-AD scale were 35.4% and 14.6%, respectively, at week 4 (P < .0001) for roflumilast and vehicle, respectively, according to the lead author of the study, Lawrence M. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, who presented the results at the meeting. In addition, 39.4% and 20.6% achieved an EASI-75 (a secondary endpoint), respectively (P < .0001), and itch also improved within 24 hours of starting treatment.

With regard to safety, 29.7% of patients taking roflumilast had treatment-emergent adverse effects (including upper respiratory tract infections in 4.1%) vs 21.9% of those in the vehicle arm (including upper respiratory tract infections in 1.4%). Reports of pain at the administration site were low (1.6% for roflumilast vs 1.9% for vehicle). Only one patient, a 2-year-old girl, had a treatment-emergent serious adverse event. The child, who was in the roflumilast group, had cellulitis involving noneczematous skin and was treated with antibiotics in the hospital for 3 days. The event was not attributed to roflumilast, which was stopped for 5 days, according to Dr. Eichenfield.

In an interview, Fairfield, Connecticut–based dermatologist Brittany Craiglow, MD, who was not involved in the study, said topical roflumilast would be an “important” new treatment because there are still few nonsteroidal options for the treatment of AD in children under 12. “The excellent local tolerability combined with early improvements in itch and skin clearance will make this a particularly attractive option, if approved,” she said.

Dr. Eichenfield disclosed multiple relationships with various drugmakers. He and several other study authors are investigators and/or consultants for Arcutis and received grants/research funding and/or honoraria. Two authors are Arcutis employees. Other disclosure information for the authors was not immediately available. Dr. Craiglow had no disclosures.

A version of this article appeared on Medscape.com .

SAN DIEGO — Treatment with topical roflumilast, 0.05%, approved at a higher concentration for treating psoriasis, showed high levels of improvement in about a quarter of children aged 2-5 years with mild to moderate atopic dermatitis (AD), according to the results of a phase 3 study reported at the annual meeting of the American Academy of Dermatology.

Among patients treated with roflumilast cream, 0.05%, 25.4% reached the primary endpoint of “clear” or “almost clear” plus a two-grade improvement from baseline at week 4 vs 10.7% among those in the vehicle group (P < .0001) in a phase 3 randomized controlled trial of children. The findings were released in a late-breaker session at the meeting.

Roflumilast cream, 0.3% (Zoryve), is approved by the Food and Drug Administration (FDA) for treating psoriasis in patients 6 years and older, and lower doses are being evaluated for AD: 0.15% for adults and children ages 6 and older, and 0.05% for ages 2-5. Roflumilast is a phosphodiesterase-4 inhibitor. In 2023, the FDA accepted a supplemental drug application from the manufacturer, Arcutis, for roflumilast, 0.15%, for treating AD in patients ages 6 and older, based on the results from two recently published phase 3 trials, INTEGUMENT-1 and INTEGUMENT-2.

The study of younger children, INTEGUMENT-PED, recruited 652 patients aged 2-5 with mild to moderate AD, with a Validated Investigator Global Assessment scale for AD (vlGA-AD) score of 2 or 3, a mean body surface area of 22% overall (range, 3%-82%), and an Eczema Area and Severity Index (EASI) score of at least 5. Of the patients enrolled, 437 were assigned to 0.05% roflumilast cream, applied once a day for 4 weeks (mean age, 3.3 years; 51.6% male; 67.4% White; 15.6% Black; 8.5% Asian; 8.5% other or more than one race; 80.5% not Latino/Hispanic). The remaining 215 children were assigned to vehicle cream and had similar characteristics.

About 52% of the patients in both groups had an inadequate response, intolerance, or contraindications to topical corticosteroids (and about 17% for topical calcineurin inhibitors and about 9% for crisaborole).

The proportions of patients who reached “clear” (0) or “almost clear” (1) on the vlGA-AD scale were 35.4% and 14.6%, respectively, at week 4 (P < .0001) for roflumilast and vehicle, respectively, according to the lead author of the study, Lawrence M. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, who presented the results at the meeting. In addition, 39.4% and 20.6% achieved an EASI-75 (a secondary endpoint), respectively (P < .0001), and itch also improved within 24 hours of starting treatment.

With regard to safety, 29.7% of patients taking roflumilast had treatment-emergent adverse effects (including upper respiratory tract infections in 4.1%) vs 21.9% of those in the vehicle arm (including upper respiratory tract infections in 1.4%). Reports of pain at the administration site were low (1.6% for roflumilast vs 1.9% for vehicle). Only one patient, a 2-year-old girl, had a treatment-emergent serious adverse event. The child, who was in the roflumilast group, had cellulitis involving noneczematous skin and was treated with antibiotics in the hospital for 3 days. The event was not attributed to roflumilast, which was stopped for 5 days, according to Dr. Eichenfield.

In an interview, Fairfield, Connecticut–based dermatologist Brittany Craiglow, MD, who was not involved in the study, said topical roflumilast would be an “important” new treatment because there are still few nonsteroidal options for the treatment of AD in children under 12. “The excellent local tolerability combined with early improvements in itch and skin clearance will make this a particularly attractive option, if approved,” she said.

Dr. Eichenfield disclosed multiple relationships with various drugmakers. He and several other study authors are investigators and/or consultants for Arcutis and received grants/research funding and/or honoraria. Two authors are Arcutis employees. Other disclosure information for the authors was not immediately available. Dr. Craiglow had no disclosures.

A version of this article appeared on Medscape.com .

SAN DIEGO — Treatment with topical roflumilast, 0.05%, approved at a higher concentration for treating psoriasis, showed high levels of improvement in about a quarter of children aged 2-5 years with mild to moderate atopic dermatitis (AD), according to the results of a phase 3 study reported at the annual meeting of the American Academy of Dermatology.

Among patients treated with roflumilast cream, 0.05%, 25.4% reached the primary endpoint of “clear” or “almost clear” plus a two-grade improvement from baseline at week 4 vs 10.7% among those in the vehicle group (P < .0001) in a phase 3 randomized controlled trial of children. The findings were released in a late-breaker session at the meeting.

Roflumilast cream, 0.3% (Zoryve), is approved by the Food and Drug Administration (FDA) for treating psoriasis in patients 6 years and older, and lower doses are being evaluated for AD: 0.15% for adults and children ages 6 and older, and 0.05% for ages 2-5. Roflumilast is a phosphodiesterase-4 inhibitor. In 2023, the FDA accepted a supplemental drug application from the manufacturer, Arcutis, for roflumilast, 0.15%, for treating AD in patients ages 6 and older, based on the results from two recently published phase 3 trials, INTEGUMENT-1 and INTEGUMENT-2.

The study of younger children, INTEGUMENT-PED, recruited 652 patients aged 2-5 with mild to moderate AD, with a Validated Investigator Global Assessment scale for AD (vlGA-AD) score of 2 or 3, a mean body surface area of 22% overall (range, 3%-82%), and an Eczema Area and Severity Index (EASI) score of at least 5. Of the patients enrolled, 437 were assigned to 0.05% roflumilast cream, applied once a day for 4 weeks (mean age, 3.3 years; 51.6% male; 67.4% White; 15.6% Black; 8.5% Asian; 8.5% other or more than one race; 80.5% not Latino/Hispanic). The remaining 215 children were assigned to vehicle cream and had similar characteristics.

About 52% of the patients in both groups had an inadequate response, intolerance, or contraindications to topical corticosteroids (and about 17% for topical calcineurin inhibitors and about 9% for crisaborole).

The proportions of patients who reached “clear” (0) or “almost clear” (1) on the vlGA-AD scale were 35.4% and 14.6%, respectively, at week 4 (P < .0001) for roflumilast and vehicle, respectively, according to the lead author of the study, Lawrence M. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, who presented the results at the meeting. In addition, 39.4% and 20.6% achieved an EASI-75 (a secondary endpoint), respectively (P < .0001), and itch also improved within 24 hours of starting treatment.

With regard to safety, 29.7% of patients taking roflumilast had treatment-emergent adverse effects (including upper respiratory tract infections in 4.1%) vs 21.9% of those in the vehicle arm (including upper respiratory tract infections in 1.4%). Reports of pain at the administration site were low (1.6% for roflumilast vs 1.9% for vehicle). Only one patient, a 2-year-old girl, had a treatment-emergent serious adverse event. The child, who was in the roflumilast group, had cellulitis involving noneczematous skin and was treated with antibiotics in the hospital for 3 days. The event was not attributed to roflumilast, which was stopped for 5 days, according to Dr. Eichenfield.

In an interview, Fairfield, Connecticut–based dermatologist Brittany Craiglow, MD, who was not involved in the study, said topical roflumilast would be an “important” new treatment because there are still few nonsteroidal options for the treatment of AD in children under 12. “The excellent local tolerability combined with early improvements in itch and skin clearance will make this a particularly attractive option, if approved,” she said.

Dr. Eichenfield disclosed multiple relationships with various drugmakers. He and several other study authors are investigators and/or consultants for Arcutis and received grants/research funding and/or honoraria. Two authors are Arcutis employees. Other disclosure information for the authors was not immediately available. Dr. Craiglow had no disclosures.

A version of this article appeared on Medscape.com .