Conference Coverage

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

The arteries of members of an indigenous community in the Bolivian Amazon, dubbed “the world’s healthiest,” have remarkably low rates of coronary atherosclerosis, compared with those of other populations. These arteries recently were found to be exceptionally elastic and to age more gradually, according to a study presented at the annual scientific sessions of the American Heart Association.

The lead researcher, Michael Gurven, PhD, director of the Integrative Anthropological Sciences Unit at the University of California, Santa Barbara, said in an interview that the study “provides additional evidence that lifestyle modifications can improve arterial health.”

An Ancient Lifestyle

The study focused on the Tsimané or Chimane people, an indigenous community in Bolivia that sustains itself through ancestral practices like slash-and-burn agriculture (mainly involving plantains, rice, sweet cassava, and maize), river fishing, hunting neotropical mammals, and gathering seasonal fruits, honey, and nuts. They are inactive only 10% of their daily time and adhere to a low-fat, low-processed carbohydrate diet.

Over the past decade, numerous studies in this community documented a lower prevalence of arterial hypertension, atrial fibrillation, type 2 diabetes, obesity, smoking, sedentary lifestyle, and more recently, minimal cognitive dysfunction and dementia.

In 2017, Dr. Gurven led a cross-sectional study showing that Tsimané individuals over age 40 years had very low coronary artery calcium scores, which are a marker for coronary atherosclerosis. The finding strongly suggests that healthy lifestyle habits genuinely work in cardiovascular prevention. The mechanisms involved and their evolution with age needed further exploration, however.

The new research, led by Dr. Gurven’s student Tianyu Cao, delved into arterial elasticity, particularly in the carotid and femoral arteries, as a measure of potential arterial stiffening and atherosclerosis. The study included around 500 adults of both sexes.

Aging and Arterial Elasticity

The findings revealed that Tsimané arteries are less rigid than those in various urban and sedentary populations that have been studied previously. For instance, the elasticity of large and small arteries in 491 Tsimané individuals (average age: 55.3 years) was 57%-86% higher than that observed in adult men and women in the United States in the Multi-Ethnic Study of Atherosclerosis.

Similarly, the carotid-femoral pulse wave velocity, a direct indicator of arterial stiffness, was determined in 89 Tsimané individuals (average age: 53.1 years, 54% women). The average value was 6.34 m/s, which is approximately 25% lower than the average for a healthy Brazilian population aged 35-74 years.

Dr. Gurven noted that Tsimané arteries remain more elastic for a longer period than in other populations. However, by age 70 years, the arteries also start to harden. “In other words, Tsimané cannot indefinitely delay arterial aging,” he said.

“The minimal and delayed increase in arterial stiffness related to age could contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimané,” wrote the researchers.

Pedro Forcada, MD, a cardiologist and professor at the University Austral in Buenos Aires, who was not involved in the study, emphasized the impact of epigenetics on atherosclerosis and accelerated vascular aging. He referred to the SUPERNOVA phenomenon in Europe and Japan, where exceptionally low arterial stiffness characterizes very long-lived individuals.

“This indicates that we must not only understand accelerated vascular aging but also study protective factors. Lifestyle, according to these recent studies, would play a significant role,” he stated.

Dr. Gurven and Dr. Forcada declared no relevant economic conflicts of interest.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

The myriad of clinical tools available for assessing patients with atopic dermatitis may leave clinicians wondering how to best incorporate the tools into the daily clinical workflow.

“It can be overwhelming because there are many choices but so little time,” Jonathan I. Silverberg, MD, PhD, MPH, associate professor and director of clinical research in the dermatology department at George Washington University, Washington, DC, said at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Assessment tools such as the Eczema Area and Severity Index (EASI), the Numeric Rating scale for itch (NRS-itch), and the Dermatology Life Quality Index (DLQI) “all correlate, but they’re all different, and there is value in all of them,” said Dr. Silverberg. “Of course, you’re not going to use all of them, but which ones should you use?”

He favors a structured approach that considers signs, symptoms, and quality of life, a framework that he and Shanthi Narla, MD, proposed in an article published online in Dermatitis. In the United States, he said, the Investigator’s Global Assessment scale (IGA) and BSA are the preferred tools for assessing the clinical severity of AD.

“If you go to Australia and New Zealand, they love EASI, while in Western Europe, they love the SCORAD [SCORing Atopic Dermatitis] tool because they’ve been using it since the 1990s,” Dr. Silverberg said. “So whatever works for you, pick it. But just use something that’s going to work within your practice setting. The IGA and the BSA are the easiest to do and the fastest to do in clinical practice. You’re going to have to document disease severity anyway if you’re going to get systemic therapies approved,” he said, referring to approval for coverage by the patient’s health insurance drug formulary.
 

Several Recommendations

Based on his clinical experience, Dr. Silverberg recommended certain assessment tools as “feasible” to use in daily practice. In the domain of clinical signs, “the IGA and the BSA are the most useful,” he said. “If the patient is gowned up, it probably takes about 30 seconds to do an IGA scale, and a BSA can be done in under a minute, easily.”

In the domain of symptoms, he recommends having the patient or caregiver complete at least one of the following patient-reported outcome measures (PROMs): the NRS-itch, the NRS-pain, the NRS-Sleep Disturbance, the Patient Health Questionnaire-2 (PHQ-2), and either the Patient Global Assessment (PtGA) or the Patient-Reported Global AD Severity (PrtGA).

“Pick one or two that reflect what you can do in clinical practice,” Dr. Silverberg advised. “The NRS-itch is clinically meaningful and takes 10 seconds to do. Or you can just ask the patient, ‘How do you rate your itch? Clear, mild, moderate, or severe?’ A verbal rating scale, like a Likert scale, would also work. Again, this takes 10 seconds to assess. This is not slowing you down in practice; it will speed you up in the long run.”

He favors the NRS scale assessments, “because the 2023 AAD guidelines for AD advocate for open-ended questions,” he said. “I can tell you from personal experience that when you go down that rabbit hole of open-ended questions, you’re never getting out of that exam room. If you ask a patient how AD affects their life, you might as well just plan on a 30- to 40-minute visit. But if you use structured questions, you can get the information you need so dearly to make the right assessments, but you can keep the visit moving efficiently.”

He noted that the NRS-itch or the PtGA and PrtGA tools “each take about 10 seconds to complete. I would argue that you could probably have the patient [complete all of these PROMs], and you’re still in under a minute, and you get incredibly rich information.”

In the quality-of-life domain, Dr. Silverberg recommends that the patient or caregiver complete the DLQI. If there is additional time, he also suggests the Atopic Dermatitis Control Tool (ADCT) to gain further insight on symptomatology.

“The DLQI takes about a minute or minute-and-a-half to complete, while the ADCT takes about a minute,” he said. “It measures overall disease control, and there are some interesting individual questions there, such as how AD bothers them, how it impacts their sleep, how it impacts them emotionally.”

To optimize efficiency, Dr. Silverberg recommends that patients or caregivers complete PROMs prior to the patient encounter by e-mail or on the patient’s online portal the night before. Freely available smart phone applications designed for AD patients can help them track their disease symptoms, such as EczemaWise from the National Eczema Association.

“[The PROMs] can even be completed in the waiting area; a lot of times we’re running behind anyway,” he said. “Even if we’re not, it can be done in a minute or two while they’re filling out their insurance paperwork or whatever. Patient-reported outcomes can also be collected by the medical assistant or nursing while rooming the patient.”

Administering such structured assessments prior to the actual patient encounter “seems counterintuitive because you’re asking seemingly more information, but that doesn’t matter, because you are asking it in an efficient, structured manner, and you are getting the information you need,” he noted. “These tools can also help fill in the gaps of telehealth encounters.”

Dr. Silverberg reported being a consultant and/or an adviser for many pharmaceutical companies. He has also received grant or research support from Galderma and Pfizer.

The myriad of clinical tools available for assessing patients with atopic dermatitis may leave clinicians wondering how to best incorporate the tools into the daily clinical workflow.

“It can be overwhelming because there are many choices but so little time,” Jonathan I. Silverberg, MD, PhD, MPH, associate professor and director of clinical research in the dermatology department at George Washington University, Washington, DC, said at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Assessment tools such as the Eczema Area and Severity Index (EASI), the Numeric Rating scale for itch (NRS-itch), and the Dermatology Life Quality Index (DLQI) “all correlate, but they’re all different, and there is value in all of them,” said Dr. Silverberg. “Of course, you’re not going to use all of them, but which ones should you use?”

He favors a structured approach that considers signs, symptoms, and quality of life, a framework that he and Shanthi Narla, MD, proposed in an article published online in Dermatitis. In the United States, he said, the Investigator’s Global Assessment scale (IGA) and BSA are the preferred tools for assessing the clinical severity of AD.

“If you go to Australia and New Zealand, they love EASI, while in Western Europe, they love the SCORAD [SCORing Atopic Dermatitis] tool because they’ve been using it since the 1990s,” Dr. Silverberg said. “So whatever works for you, pick it. But just use something that’s going to work within your practice setting. The IGA and the BSA are the easiest to do and the fastest to do in clinical practice. You’re going to have to document disease severity anyway if you’re going to get systemic therapies approved,” he said, referring to approval for coverage by the patient’s health insurance drug formulary.
 

Several Recommendations

Based on his clinical experience, Dr. Silverberg recommended certain assessment tools as “feasible” to use in daily practice. In the domain of clinical signs, “the IGA and the BSA are the most useful,” he said. “If the patient is gowned up, it probably takes about 30 seconds to do an IGA scale, and a BSA can be done in under a minute, easily.”

In the domain of symptoms, he recommends having the patient or caregiver complete at least one of the following patient-reported outcome measures (PROMs): the NRS-itch, the NRS-pain, the NRS-Sleep Disturbance, the Patient Health Questionnaire-2 (PHQ-2), and either the Patient Global Assessment (PtGA) or the Patient-Reported Global AD Severity (PrtGA).

“Pick one or two that reflect what you can do in clinical practice,” Dr. Silverberg advised. “The NRS-itch is clinically meaningful and takes 10 seconds to do. Or you can just ask the patient, ‘How do you rate your itch? Clear, mild, moderate, or severe?’ A verbal rating scale, like a Likert scale, would also work. Again, this takes 10 seconds to assess. This is not slowing you down in practice; it will speed you up in the long run.”

He favors the NRS scale assessments, “because the 2023 AAD guidelines for AD advocate for open-ended questions,” he said. “I can tell you from personal experience that when you go down that rabbit hole of open-ended questions, you’re never getting out of that exam room. If you ask a patient how AD affects their life, you might as well just plan on a 30- to 40-minute visit. But if you use structured questions, you can get the information you need so dearly to make the right assessments, but you can keep the visit moving efficiently.”

He noted that the NRS-itch or the PtGA and PrtGA tools “each take about 10 seconds to complete. I would argue that you could probably have the patient [complete all of these PROMs], and you’re still in under a minute, and you get incredibly rich information.”

In the quality-of-life domain, Dr. Silverberg recommends that the patient or caregiver complete the DLQI. If there is additional time, he also suggests the Atopic Dermatitis Control Tool (ADCT) to gain further insight on symptomatology.

“The DLQI takes about a minute or minute-and-a-half to complete, while the ADCT takes about a minute,” he said. “It measures overall disease control, and there are some interesting individual questions there, such as how AD bothers them, how it impacts their sleep, how it impacts them emotionally.”

To optimize efficiency, Dr. Silverberg recommends that patients or caregivers complete PROMs prior to the patient encounter by e-mail or on the patient’s online portal the night before. Freely available smart phone applications designed for AD patients can help them track their disease symptoms, such as EczemaWise from the National Eczema Association.

“[The PROMs] can even be completed in the waiting area; a lot of times we’re running behind anyway,” he said. “Even if we’re not, it can be done in a minute or two while they’re filling out their insurance paperwork or whatever. Patient-reported outcomes can also be collected by the medical assistant or nursing while rooming the patient.”

Administering such structured assessments prior to the actual patient encounter “seems counterintuitive because you’re asking seemingly more information, but that doesn’t matter, because you are asking it in an efficient, structured manner, and you are getting the information you need,” he noted. “These tools can also help fill in the gaps of telehealth encounters.”

Dr. Silverberg reported being a consultant and/or an adviser for many pharmaceutical companies. He has also received grant or research support from Galderma and Pfizer.

The myriad of clinical tools available for assessing patients with atopic dermatitis may leave clinicians wondering how to best incorporate the tools into the daily clinical workflow.

“It can be overwhelming because there are many choices but so little time,” Jonathan I. Silverberg, MD, PhD, MPH, associate professor and director of clinical research in the dermatology department at George Washington University, Washington, DC, said at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Assessment tools such as the Eczema Area and Severity Index (EASI), the Numeric Rating scale for itch (NRS-itch), and the Dermatology Life Quality Index (DLQI) “all correlate, but they’re all different, and there is value in all of them,” said Dr. Silverberg. “Of course, you’re not going to use all of them, but which ones should you use?”

He favors a structured approach that considers signs, symptoms, and quality of life, a framework that he and Shanthi Narla, MD, proposed in an article published online in Dermatitis. In the United States, he said, the Investigator’s Global Assessment scale (IGA) and BSA are the preferred tools for assessing the clinical severity of AD.

“If you go to Australia and New Zealand, they love EASI, while in Western Europe, they love the SCORAD [SCORing Atopic Dermatitis] tool because they’ve been using it since the 1990s,” Dr. Silverberg said. “So whatever works for you, pick it. But just use something that’s going to work within your practice setting. The IGA and the BSA are the easiest to do and the fastest to do in clinical practice. You’re going to have to document disease severity anyway if you’re going to get systemic therapies approved,” he said, referring to approval for coverage by the patient’s health insurance drug formulary.
 

Several Recommendations

Based on his clinical experience, Dr. Silverberg recommended certain assessment tools as “feasible” to use in daily practice. In the domain of clinical signs, “the IGA and the BSA are the most useful,” he said. “If the patient is gowned up, it probably takes about 30 seconds to do an IGA scale, and a BSA can be done in under a minute, easily.”

In the domain of symptoms, he recommends having the patient or caregiver complete at least one of the following patient-reported outcome measures (PROMs): the NRS-itch, the NRS-pain, the NRS-Sleep Disturbance, the Patient Health Questionnaire-2 (PHQ-2), and either the Patient Global Assessment (PtGA) or the Patient-Reported Global AD Severity (PrtGA).

“Pick one or two that reflect what you can do in clinical practice,” Dr. Silverberg advised. “The NRS-itch is clinically meaningful and takes 10 seconds to do. Or you can just ask the patient, ‘How do you rate your itch? Clear, mild, moderate, or severe?’ A verbal rating scale, like a Likert scale, would also work. Again, this takes 10 seconds to assess. This is not slowing you down in practice; it will speed you up in the long run.”

He favors the NRS scale assessments, “because the 2023 AAD guidelines for AD advocate for open-ended questions,” he said. “I can tell you from personal experience that when you go down that rabbit hole of open-ended questions, you’re never getting out of that exam room. If you ask a patient how AD affects their life, you might as well just plan on a 30- to 40-minute visit. But if you use structured questions, you can get the information you need so dearly to make the right assessments, but you can keep the visit moving efficiently.”

He noted that the NRS-itch or the PtGA and PrtGA tools “each take about 10 seconds to complete. I would argue that you could probably have the patient [complete all of these PROMs], and you’re still in under a minute, and you get incredibly rich information.”

In the quality-of-life domain, Dr. Silverberg recommends that the patient or caregiver complete the DLQI. If there is additional time, he also suggests the Atopic Dermatitis Control Tool (ADCT) to gain further insight on symptomatology.

“The DLQI takes about a minute or minute-and-a-half to complete, while the ADCT takes about a minute,” he said. “It measures overall disease control, and there are some interesting individual questions there, such as how AD bothers them, how it impacts their sleep, how it impacts them emotionally.”

To optimize efficiency, Dr. Silverberg recommends that patients or caregivers complete PROMs prior to the patient encounter by e-mail or on the patient’s online portal the night before. Freely available smart phone applications designed for AD patients can help them track their disease symptoms, such as EczemaWise from the National Eczema Association.

“[The PROMs] can even be completed in the waiting area; a lot of times we’re running behind anyway,” he said. “Even if we’re not, it can be done in a minute or two while they’re filling out their insurance paperwork or whatever. Patient-reported outcomes can also be collected by the medical assistant or nursing while rooming the patient.”

Administering such structured assessments prior to the actual patient encounter “seems counterintuitive because you’re asking seemingly more information, but that doesn’t matter, because you are asking it in an efficient, structured manner, and you are getting the information you need,” he noted. “These tools can also help fill in the gaps of telehealth encounters.”

Dr. Silverberg reported being a consultant and/or an adviser for many pharmaceutical companies. He has also received grant or research support from Galderma and Pfizer.

Selecting a treatment plan to deal with acute migraine attacks can be like putting together a toolkit of possible therapies, individualized for each patient, one expert said.

The toolkit should comprise reliable treatments that patients know are going to work and that act quickly, allowing them to get back to functioning normally in their daily lives, said Jessica Ailani, MD, during a talk at the 17th European Headache Congress held recently in Barcelona, Spain. 

“Everyone with migraine needs acute treatment,” Dr. Ailani, who is a clinical professor of neurology at MedStar Georgetown University Hospital and director of the Georgetown Headache Center, Washington, DC, noted. “Sometimes we can reduce acute treatment with preventative agents, but some disability will remain, so we have to focus on good acute treatment, and this becomes more complex if a person has a lot of comorbidities, which is common in older patients.” 

In selecting suitable treatments for migraine, consideration has to be given to the patient profile, any other conditions they have, speed of onset of the migraine attack, length of the attack, associated symptoms, and side effects of the medications, she said. 
 

A Complex Case

As an example, Dr. Ailani described the process she used to treat one of her patients who had frequent severe migraines and other issues causing difficult decisions when selecting medications — a woman in her late 60s with several other comorbidities.

“This is the kind of case I see on a daily basis and which keeps me up at night,” she said. “Many times in clinical practice, we see complex cases like this, and through the course of a year, we may try every treatment option we have in a patient like this.”

On the first presentation, the patient had a chronic migraine with severe headaches every day. She had a history of previous cervical discectomy with fusion surgery; uncontrolled hypertension, for which she was taking an angiotensin blocker; high cholesterol, for which she was taking a statin; and diabetes with an A1c of 8. She did not smoke or drink alcohol, exercised moderately, and her body mass index was in a good range. 

“Before a patient ever sees a doctor for their migraine, they will have already tried a lot of different things. Most people are already using NSAIDs and acetaminophen, the most commonly used treatments for acute migraine,” Dr. Ailani explains.

Her patient was taking a triptan and the barbiturate, butalbital. Dr. Ailani notes that the triptan is very effective, but in the United States, they are not available over the counter, and the patient is only allowed nine doses per month on her insurance, so she was supplementing with butalbital. 

Over the course of a year, Dr. Ailani got her off the butalbital and started her on onabotulinum toxin A for migraine prevention, which reduced her headache days to about 15 per month (8 severe). She then added the anti-calcitonin gene-related peptide (CGRP) monoclonal antibody, galcanezumab, as another preventative, which further reduced the headache days down to 8-10 days per month (all migraine). 

The attacks are rapid onset and can last multiple days. They come with photophobia and phonophobia and cause her to be bedridden, she noted. 

“I was still worried about this frequency of headache and the fact she was using a triptan for acute treatment when she had uncontrolled hypertension and other cardiovascular risk factors, Dr. Ailani commented. 

She explained that triptans are generally not used in individuals aged over 65 years because of a lack of data in this age group. They are also contraindicated in patients with cardiovascular (CV) disease, and caution is advised in patients with CV risk factors. Noting that migraine is an independent risk factor for stroke in healthy individuals, and this patient already had three other major risk factors for stroke, Dr. Ailani said she did not think a triptan was the best option. 

When triptans do not work, Dr. Ailani said she thinks about dihydroergotamine, which she describes as “a great drug for long-lasting migraine” as it tends to have a sustained response. But it also has vasoconstrictive effects and can increase blood pressure, so it was not suitable for this patient. 

CV risk is also an issue with nonsteroidal anti-inflammatory drugs (NSAIDs), one of the staple treatments for acute migraine.

“NSAIDs are available over the counter, inexpensive, quite effective, and have minimal immediate side effects,” Dr. Ailani said. But long-term adverse events include CV events, particularly in those who already have CV risk factors, and it is now thought that NSAIDs actually carry more CV risk than triptans.

She noted that out of all the NSAIDs, celecoxib carries the lowest CV risk, and in the United States, it is available as a liquid formulation. There is also a study of ketorolac nasal spray showing it to be as effective as sumatriptan nasal spray for acute migraine.

As her patient was still going to the emergency room (ER) quite frequently at this point, Dr. Ailani prescribed ketorolac nasal spray as an emergency rescue medication, which did help to reduce ER visits but did not solve the acute treatment problem.

The next option she tried was the CGRP antagonists or “gepants” because of their good tolerability.

Because her patient had long attacks, Dr. Ailani said her first choice gepant was rimegepant as it has a long half-life.

She noted that in patients who have frequent migraine attacks (> 6 migraine days per month), using rimegepant as needed has been shown to lead to migraine frequency declining over time. “This shows that if we treat acute attacks properly, we can minimize the risk of chronic migraine.”

She pointed out that if a patient has prodrome that is easy to identify or has short attacks, ubrogepant may be a good option, having shown effectiveness in preventing or reducing the onset of the headache in the recently reported PRODROME trial when given the day before migraine starts.

Then there is also zavegepant, which is available as a nasal spray, so it is a good option for patients with nausea and vomiting. Dr. Ailani suggested that zavegepant as a third-generation gepant may be worth trying in patients who have tried the other gepants, as it is a different type of molecule.

For this patient, neither rimegepant nor ubrogepant worked. “We tried treating in the prodrome, when the pain was starting, adding to other treatments, but she is not a ‘gepant’ responder. We have yet to try zavegepant,” she said.

The next consideration was lasmiditan. “This patient is a triptan responder and lasmiditan is a 5HT1 agonist, so it makes sense to try this. Also, it doesn’t have a vasoconstrictor effect as it doesn’t work on the blood vessels, so it is safe for patients with high blood pressure,” Dr. Ailani noted.

She pointed out, however, that lasmiditan has become a rescue medication in her practice because of side effect issues such as dizziness and sleepiness.

But Dr. Ailani said she has learned how to use the medication to minimize the side effects, by increasing the dose slowly and advising patients to take it later in the day.

“We start with 50 mg for a few doses then increase to 100 mg. This seems to build tolerability.”

Her patient has found good relief from lasmiditan 100 mg, but she can’t take it during the day as it makes her sleepy.

As a last resort, Dr. Ailani went back to metoclopramide, which she described as “a tried and tested old-time drug.”

While this does not make the patient sleepy, it has other adverse effects limiting the frequency of its use, she noted. “I ask her to try to limit it to twice a week, and this has been pretty effective. She can function when she uses it.” 

Dr. Ailani also points out that neuromodulation should be in everyone’s tool kit. “So, we added an external combined occipital and trigeminal (eCOT device) neurostimulation device.”

The patient’s tool kit now looks like this:

• Neuromodulation device and meditation at first sign of an attack.
• Add metoclopramide 10 mg and acetaminophen 1000 mg.
• If the attack lasts into the second day, add lasmiditan 100 mg in the evening of the second day (limit 8 days a month).
• If the patient has a sudden onset severe migraine with nausea and vomiting that might make her go to the ER, add in ketorolac nasal spray (not > 5 days per month).

Dr. Ailani noted that other patients will need different toolkits, and in most cases, it is recommended to think about “situational prevention” for times when migraine attacks are predictable, which may include air travel, high-stress times (holidays, etc.), occasions when alcohol will be consumed, and at times of certain weather triggers.

Dr. Ailani disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Selecting a treatment plan to deal with acute migraine attacks can be like putting together a toolkit of possible therapies, individualized for each patient, one expert said.

The toolkit should comprise reliable treatments that patients know are going to work and that act quickly, allowing them to get back to functioning normally in their daily lives, said Jessica Ailani, MD, during a talk at the 17th European Headache Congress held recently in Barcelona, Spain. 

“Everyone with migraine needs acute treatment,” Dr. Ailani, who is a clinical professor of neurology at MedStar Georgetown University Hospital and director of the Georgetown Headache Center, Washington, DC, noted. “Sometimes we can reduce acute treatment with preventative agents, but some disability will remain, so we have to focus on good acute treatment, and this becomes more complex if a person has a lot of comorbidities, which is common in older patients.” 

In selecting suitable treatments for migraine, consideration has to be given to the patient profile, any other conditions they have, speed of onset of the migraine attack, length of the attack, associated symptoms, and side effects of the medications, she said. 
 

A Complex Case

As an example, Dr. Ailani described the process she used to treat one of her patients who had frequent severe migraines and other issues causing difficult decisions when selecting medications — a woman in her late 60s with several other comorbidities.

“This is the kind of case I see on a daily basis and which keeps me up at night,” she said. “Many times in clinical practice, we see complex cases like this, and through the course of a year, we may try every treatment option we have in a patient like this.”

On the first presentation, the patient had a chronic migraine with severe headaches every day. She had a history of previous cervical discectomy with fusion surgery; uncontrolled hypertension, for which she was taking an angiotensin blocker; high cholesterol, for which she was taking a statin; and diabetes with an A1c of 8. She did not smoke or drink alcohol, exercised moderately, and her body mass index was in a good range. 

“Before a patient ever sees a doctor for their migraine, they will have already tried a lot of different things. Most people are already using NSAIDs and acetaminophen, the most commonly used treatments for acute migraine,” Dr. Ailani explains.

Her patient was taking a triptan and the barbiturate, butalbital. Dr. Ailani notes that the triptan is very effective, but in the United States, they are not available over the counter, and the patient is only allowed nine doses per month on her insurance, so she was supplementing with butalbital. 

Over the course of a year, Dr. Ailani got her off the butalbital and started her on onabotulinum toxin A for migraine prevention, which reduced her headache days to about 15 per month (8 severe). She then added the anti-calcitonin gene-related peptide (CGRP) monoclonal antibody, galcanezumab, as another preventative, which further reduced the headache days down to 8-10 days per month (all migraine). 

The attacks are rapid onset and can last multiple days. They come with photophobia and phonophobia and cause her to be bedridden, she noted. 

“I was still worried about this frequency of headache and the fact she was using a triptan for acute treatment when she had uncontrolled hypertension and other cardiovascular risk factors, Dr. Ailani commented. 

She explained that triptans are generally not used in individuals aged over 65 years because of a lack of data in this age group. They are also contraindicated in patients with cardiovascular (CV) disease, and caution is advised in patients with CV risk factors. Noting that migraine is an independent risk factor for stroke in healthy individuals, and this patient already had three other major risk factors for stroke, Dr. Ailani said she did not think a triptan was the best option. 

When triptans do not work, Dr. Ailani said she thinks about dihydroergotamine, which she describes as “a great drug for long-lasting migraine” as it tends to have a sustained response. But it also has vasoconstrictive effects and can increase blood pressure, so it was not suitable for this patient. 

CV risk is also an issue with nonsteroidal anti-inflammatory drugs (NSAIDs), one of the staple treatments for acute migraine.

“NSAIDs are available over the counter, inexpensive, quite effective, and have minimal immediate side effects,” Dr. Ailani said. But long-term adverse events include CV events, particularly in those who already have CV risk factors, and it is now thought that NSAIDs actually carry more CV risk than triptans.

She noted that out of all the NSAIDs, celecoxib carries the lowest CV risk, and in the United States, it is available as a liquid formulation. There is also a study of ketorolac nasal spray showing it to be as effective as sumatriptan nasal spray for acute migraine.

As her patient was still going to the emergency room (ER) quite frequently at this point, Dr. Ailani prescribed ketorolac nasal spray as an emergency rescue medication, which did help to reduce ER visits but did not solve the acute treatment problem.

The next option she tried was the CGRP antagonists or “gepants” because of their good tolerability.

Because her patient had long attacks, Dr. Ailani said her first choice gepant was rimegepant as it has a long half-life.

She noted that in patients who have frequent migraine attacks (> 6 migraine days per month), using rimegepant as needed has been shown to lead to migraine frequency declining over time. “This shows that if we treat acute attacks properly, we can minimize the risk of chronic migraine.”

She pointed out that if a patient has prodrome that is easy to identify or has short attacks, ubrogepant may be a good option, having shown effectiveness in preventing or reducing the onset of the headache in the recently reported PRODROME trial when given the day before migraine starts.

Then there is also zavegepant, which is available as a nasal spray, so it is a good option for patients with nausea and vomiting. Dr. Ailani suggested that zavegepant as a third-generation gepant may be worth trying in patients who have tried the other gepants, as it is a different type of molecule.

For this patient, neither rimegepant nor ubrogepant worked. “We tried treating in the prodrome, when the pain was starting, adding to other treatments, but she is not a ‘gepant’ responder. We have yet to try zavegepant,” she said.

The next consideration was lasmiditan. “This patient is a triptan responder and lasmiditan is a 5HT1 agonist, so it makes sense to try this. Also, it doesn’t have a vasoconstrictor effect as it doesn’t work on the blood vessels, so it is safe for patients with high blood pressure,” Dr. Ailani noted.

She pointed out, however, that lasmiditan has become a rescue medication in her practice because of side effect issues such as dizziness and sleepiness.

But Dr. Ailani said she has learned how to use the medication to minimize the side effects, by increasing the dose slowly and advising patients to take it later in the day.

“We start with 50 mg for a few doses then increase to 100 mg. This seems to build tolerability.”

Her patient has found good relief from lasmiditan 100 mg, but she can’t take it during the day as it makes her sleepy.

As a last resort, Dr. Ailani went back to metoclopramide, which she described as “a tried and tested old-time drug.”

While this does not make the patient sleepy, it has other adverse effects limiting the frequency of its use, she noted. “I ask her to try to limit it to twice a week, and this has been pretty effective. She can function when she uses it.” 

Dr. Ailani also points out that neuromodulation should be in everyone’s tool kit. “So, we added an external combined occipital and trigeminal (eCOT device) neurostimulation device.”

The patient’s tool kit now looks like this:

• Neuromodulation device and meditation at first sign of an attack.
• Add metoclopramide 10 mg and acetaminophen 1000 mg.
• If the attack lasts into the second day, add lasmiditan 100 mg in the evening of the second day (limit 8 days a month).
• If the patient has a sudden onset severe migraine with nausea and vomiting that might make her go to the ER, add in ketorolac nasal spray (not > 5 days per month).

Dr. Ailani noted that other patients will need different toolkits, and in most cases, it is recommended to think about “situational prevention” for times when migraine attacks are predictable, which may include air travel, high-stress times (holidays, etc.), occasions when alcohol will be consumed, and at times of certain weather triggers.

Dr. Ailani disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Selecting a treatment plan to deal with acute migraine attacks can be like putting together a toolkit of possible therapies, individualized for each patient, one expert said.

The toolkit should comprise reliable treatments that patients know are going to work and that act quickly, allowing them to get back to functioning normally in their daily lives, said Jessica Ailani, MD, during a talk at the 17th European Headache Congress held recently in Barcelona, Spain. 

“Everyone with migraine needs acute treatment,” Dr. Ailani, who is a clinical professor of neurology at MedStar Georgetown University Hospital and director of the Georgetown Headache Center, Washington, DC, noted. “Sometimes we can reduce acute treatment with preventative agents, but some disability will remain, so we have to focus on good acute treatment, and this becomes more complex if a person has a lot of comorbidities, which is common in older patients.” 

In selecting suitable treatments for migraine, consideration has to be given to the patient profile, any other conditions they have, speed of onset of the migraine attack, length of the attack, associated symptoms, and side effects of the medications, she said. 
 

A Complex Case

As an example, Dr. Ailani described the process she used to treat one of her patients who had frequent severe migraines and other issues causing difficult decisions when selecting medications — a woman in her late 60s with several other comorbidities.

“This is the kind of case I see on a daily basis and which keeps me up at night,” she said. “Many times in clinical practice, we see complex cases like this, and through the course of a year, we may try every treatment option we have in a patient like this.”

On the first presentation, the patient had a chronic migraine with severe headaches every day. She had a history of previous cervical discectomy with fusion surgery; uncontrolled hypertension, for which she was taking an angiotensin blocker; high cholesterol, for which she was taking a statin; and diabetes with an A1c of 8. She did not smoke or drink alcohol, exercised moderately, and her body mass index was in a good range. 

“Before a patient ever sees a doctor for their migraine, they will have already tried a lot of different things. Most people are already using NSAIDs and acetaminophen, the most commonly used treatments for acute migraine,” Dr. Ailani explains.

Her patient was taking a triptan and the barbiturate, butalbital. Dr. Ailani notes that the triptan is very effective, but in the United States, they are not available over the counter, and the patient is only allowed nine doses per month on her insurance, so she was supplementing with butalbital. 

Over the course of a year, Dr. Ailani got her off the butalbital and started her on onabotulinum toxin A for migraine prevention, which reduced her headache days to about 15 per month (8 severe). She then added the anti-calcitonin gene-related peptide (CGRP) monoclonal antibody, galcanezumab, as another preventative, which further reduced the headache days down to 8-10 days per month (all migraine). 

The attacks are rapid onset and can last multiple days. They come with photophobia and phonophobia and cause her to be bedridden, she noted. 

“I was still worried about this frequency of headache and the fact she was using a triptan for acute treatment when she had uncontrolled hypertension and other cardiovascular risk factors, Dr. Ailani commented. 

She explained that triptans are generally not used in individuals aged over 65 years because of a lack of data in this age group. They are also contraindicated in patients with cardiovascular (CV) disease, and caution is advised in patients with CV risk factors. Noting that migraine is an independent risk factor for stroke in healthy individuals, and this patient already had three other major risk factors for stroke, Dr. Ailani said she did not think a triptan was the best option. 

When triptans do not work, Dr. Ailani said she thinks about dihydroergotamine, which she describes as “a great drug for long-lasting migraine” as it tends to have a sustained response. But it also has vasoconstrictive effects and can increase blood pressure, so it was not suitable for this patient. 

CV risk is also an issue with nonsteroidal anti-inflammatory drugs (NSAIDs), one of the staple treatments for acute migraine.

“NSAIDs are available over the counter, inexpensive, quite effective, and have minimal immediate side effects,” Dr. Ailani said. But long-term adverse events include CV events, particularly in those who already have CV risk factors, and it is now thought that NSAIDs actually carry more CV risk than triptans.

She noted that out of all the NSAIDs, celecoxib carries the lowest CV risk, and in the United States, it is available as a liquid formulation. There is also a study of ketorolac nasal spray showing it to be as effective as sumatriptan nasal spray for acute migraine.

As her patient was still going to the emergency room (ER) quite frequently at this point, Dr. Ailani prescribed ketorolac nasal spray as an emergency rescue medication, which did help to reduce ER visits but did not solve the acute treatment problem.

The next option she tried was the CGRP antagonists or “gepants” because of their good tolerability.

Because her patient had long attacks, Dr. Ailani said her first choice gepant was rimegepant as it has a long half-life.

She noted that in patients who have frequent migraine attacks (> 6 migraine days per month), using rimegepant as needed has been shown to lead to migraine frequency declining over time. “This shows that if we treat acute attacks properly, we can minimize the risk of chronic migraine.”

She pointed out that if a patient has prodrome that is easy to identify or has short attacks, ubrogepant may be a good option, having shown effectiveness in preventing or reducing the onset of the headache in the recently reported PRODROME trial when given the day before migraine starts.

Then there is also zavegepant, which is available as a nasal spray, so it is a good option for patients with nausea and vomiting. Dr. Ailani suggested that zavegepant as a third-generation gepant may be worth trying in patients who have tried the other gepants, as it is a different type of molecule.

For this patient, neither rimegepant nor ubrogepant worked. “We tried treating in the prodrome, when the pain was starting, adding to other treatments, but she is not a ‘gepant’ responder. We have yet to try zavegepant,” she said.

The next consideration was lasmiditan. “This patient is a triptan responder and lasmiditan is a 5HT1 agonist, so it makes sense to try this. Also, it doesn’t have a vasoconstrictor effect as it doesn’t work on the blood vessels, so it is safe for patients with high blood pressure,” Dr. Ailani noted.

She pointed out, however, that lasmiditan has become a rescue medication in her practice because of side effect issues such as dizziness and sleepiness.

But Dr. Ailani said she has learned how to use the medication to minimize the side effects, by increasing the dose slowly and advising patients to take it later in the day.

“We start with 50 mg for a few doses then increase to 100 mg. This seems to build tolerability.”

Her patient has found good relief from lasmiditan 100 mg, but she can’t take it during the day as it makes her sleepy.

As a last resort, Dr. Ailani went back to metoclopramide, which she described as “a tried and tested old-time drug.”

While this does not make the patient sleepy, it has other adverse effects limiting the frequency of its use, she noted. “I ask her to try to limit it to twice a week, and this has been pretty effective. She can function when she uses it.” 

Dr. Ailani also points out that neuromodulation should be in everyone’s tool kit. “So, we added an external combined occipital and trigeminal (eCOT device) neurostimulation device.”

The patient’s tool kit now looks like this:

• Neuromodulation device and meditation at first sign of an attack.
• Add metoclopramide 10 mg and acetaminophen 1000 mg.
• If the attack lasts into the second day, add lasmiditan 100 mg in the evening of the second day (limit 8 days a month).
• If the patient has a sudden onset severe migraine with nausea and vomiting that might make her go to the ER, add in ketorolac nasal spray (not > 5 days per month).

Dr. Ailani noted that other patients will need different toolkits, and in most cases, it is recommended to think about “situational prevention” for times when migraine attacks are predictable, which may include air travel, high-stress times (holidays, etc.), occasions when alcohol will be consumed, and at times of certain weather triggers.

Dr. Ailani disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

With so many treatment options available for atopic dermatitis (AD) and more in the pipeline, one common question Raj Chovatiya, MD, PhD, hears from his fellow dermatologists is: How do I choose the right therapy for my patients?

“There isn’t going to be a one-size-fits-all approach, and it may be impossible to differentiate, given that these agents are not likely to be studied head-to-head,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Dr. Chovatiya

He shared a list of factors to consider when engaged in shared decision-making with patients about their AD treatment options. These include:

• Severity of disease (mild vs moderate vs severe).
• Extent of disease (low vs high body surface area).
• Rapidity of drug onset (hours vs days vs weeks).
• Depth of response based on different endpoints such as itch and number of lesions.
• Long-term efficacy (durability on treatment vs off treatment).
• Adverse events (cutaneous vs systemic).
• Black box warnings (present vs absent).
• Tolerance (selective areas vs the entire skin).
• Vehicle (ointment vs cream).
• Patient preference. “This may be the biggest driver; what do patients want?” Dr. Chovatiya said.
• Access to the drug. Is it easily obtainable for the patient?

He concluded his remarks by posing a question to attendees: “Are we closer to living in a topical steroid–free world for AD? Is that what we want?” he asked. “I wholeheartedly say that’s what we’ve been working toward all these years, and we should keep up the good fight. We have more data for targeted therapy to treat very specific disease with very specific outcomes and endpoints, because I think that’s [what] we all dream about in dermatology.”

Dr. Chovatiya disclosed that he is speaker for and/or a consultant and advisory board member to many pharmaceutical companies.

With so many treatment options available for atopic dermatitis (AD) and more in the pipeline, one common question Raj Chovatiya, MD, PhD, hears from his fellow dermatologists is: How do I choose the right therapy for my patients?

“There isn’t going to be a one-size-fits-all approach, and it may be impossible to differentiate, given that these agents are not likely to be studied head-to-head,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Dr. Chovatiya

He shared a list of factors to consider when engaged in shared decision-making with patients about their AD treatment options. These include:

• Severity of disease (mild vs moderate vs severe).
• Extent of disease (low vs high body surface area).
• Rapidity of drug onset (hours vs days vs weeks).
• Depth of response based on different endpoints such as itch and number of lesions.
• Long-term efficacy (durability on treatment vs off treatment).
• Adverse events (cutaneous vs systemic).
• Black box warnings (present vs absent).
• Tolerance (selective areas vs the entire skin).
• Vehicle (ointment vs cream).
• Patient preference. “This may be the biggest driver; what do patients want?” Dr. Chovatiya said.
• Access to the drug. Is it easily obtainable for the patient?

He concluded his remarks by posing a question to attendees: “Are we closer to living in a topical steroid–free world for AD? Is that what we want?” he asked. “I wholeheartedly say that’s what we’ve been working toward all these years, and we should keep up the good fight. We have more data for targeted therapy to treat very specific disease with very specific outcomes and endpoints, because I think that’s [what] we all dream about in dermatology.”

Dr. Chovatiya disclosed that he is speaker for and/or a consultant and advisory board member to many pharmaceutical companies.

With so many treatment options available for atopic dermatitis (AD) and more in the pipeline, one common question Raj Chovatiya, MD, PhD, hears from his fellow dermatologists is: How do I choose the right therapy for my patients?

“There isn’t going to be a one-size-fits-all approach, and it may be impossible to differentiate, given that these agents are not likely to be studied head-to-head,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Dr. Chovatiya

He shared a list of factors to consider when engaged in shared decision-making with patients about their AD treatment options. These include:

• Severity of disease (mild vs moderate vs severe).
• Extent of disease (low vs high body surface area).
• Rapidity of drug onset (hours vs days vs weeks).
• Depth of response based on different endpoints such as itch and number of lesions.
• Long-term efficacy (durability on treatment vs off treatment).
• Adverse events (cutaneous vs systemic).
• Black box warnings (present vs absent).
• Tolerance (selective areas vs the entire skin).
• Vehicle (ointment vs cream).
• Patient preference. “This may be the biggest driver; what do patients want?” Dr. Chovatiya said.
• Access to the drug. Is it easily obtainable for the patient?

He concluded his remarks by posing a question to attendees: “Are we closer to living in a topical steroid–free world for AD? Is that what we want?” he asked. “I wholeheartedly say that’s what we’ve been working toward all these years, and we should keep up the good fight. We have more data for targeted therapy to treat very specific disease with very specific outcomes and endpoints, because I think that’s [what] we all dream about in dermatology.”

Dr. Chovatiya disclosed that he is speaker for and/or a consultant and advisory board member to many pharmaceutical companies.

Safety data spanning up to 5 years from clinical trials of adolescents and adults using 15 mg or 30 mg of upadacitinib to treat moderate to severe atopic dermatitis (AD) indicates that rates of treatment-emergent adverse events remained low and consistent, with no new safety risks identified, underscoring the medication’s stable safety profile over an extended duration.

Those are among the key findings from an integrated analysis of long-term upadacitinib use presented by Christopher G. Bunick, MD, PhD, during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis Virtual Conference. Upadacitinib (Rinvoq) is an oral Janus kinase (JAK) inhibitor, approved by the Food and Drug Administration for adults and pediatric patients aged 12 years of age and older with refractory, moderate to severe AD in January 2022.

“What makes this study special is that these patients are followed for 260 weeks, or 5 years, and it encompasses over 7,000 patient-years of exposure,” said Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut. “This is a milestone because it’s the longest safety study ever published for any systemic drug for AD.”

He and his colleagues evaluated the safety data for up to 5 years of upadacitinib 15 mg and 30 mg use in adolescents and adults with moderate to severe AD, based on the results of integrated data from three ongoing global multicenter phase 3 trials: Measure Up 1, Measure Up 2, and AD Up. Patients in the trials were randomized 1:1:1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily alone (Measure Up 1 and 2) or with concomitant topical corticosteroids (AD Up). At week 16, patients receiving 15 mg or 30 mg upadacitinib during the double-blind period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were randomized 1:1 to receive either 15 mg or 30 mg upadacitinib in the BE period. The integrated analysis included 2683 patients (529 adolescents and 2154 adults) who received at least one dose of upadacitinib. Of these, 1337 received the 15-mg dose, while 1346 received the 30-mg dose. The researchers analyzed treatment-emergent events of special interest as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different follow-up durations.

According to Dr. Bunick, researchers often refer to “100 patient-years” in safety analyses to measure how common certain events are. “It is a straightforward way to convey the collective experience of the study’s participants over time,” he told this news organization. “For instance, if 100 patients are each monitored for 1 year, or 50 patients for 2 years each, both scenarios amount to 100 patient-years. This metric allows clinicians to understand how often certain adverse events occur across a diverse group over a specific time frame, providing a clear picture of long-term safety.”

Upadacitinib trials in atopic dermatitis have included diverse patient groups with varying risk factors. “Patients were not cherry-picked,” he said. “What I mean by that is that about 50% of patients enrolled in these trials had, at baseline, at least one cardiovascular risk factor: about 30% used tobacco; 10% had hypertension, and 5% had a history of a cardiovascular event.” In addition, about 15% were over age 50 with one cardiovascular risk factor and about 20% had a body mass index (BMI) greater than 30 kg/m². Among women in the study, about 20% were on oral contraceptives, yet none developed a venous thromboembolism (VTE).

In the integrated analysis, the rate of treatment-emergent adverse events that led to discontinuation of upadacitinib was about 4.2 events per 100 PY, “meaning that this medicine shows durability,” Dr. Bunick said. “Very few people are discontinuing due to adverse events.”

Serious and opportunistic infections ranged from 1.6 to 2.8 events per 100 PY, but these were stable across the 1- to 5-year time points. The rates of active TB were less than 0.1 per 100 PY, while the rates of herpes zoster ranged from 3.5 to 5.5 events per 100 PY. “The key take-home point here is that 5% or less of the patients at baseline had received the shingles vaccine, so it’s very important to talk to patients about receiving the shingles vaccine before they go on upadacitinib,” Dr. Bunick advised, because “this could reduce risk of herpes zoster occurring in upadacitinib-treated patients substantially.”

In other findings, incidence rates of nonmelanoma skin cancer (NMSC) ranged between 0.3 and 0.4 per 100 PY, while the rate of malignancy excluding NMSC ranged between 0.3 and 0.4 per 100 PY. Meanwhile, the rates of gastrointestinal perforations and VTE stood at 0.1 per 100 PY or lower, and MACE incidence rates ranged from 0.1 to 0.2 per 100 PY.

During his presentation, Dr. Bunick compared findings related to malignancy (excluding NMSC), MACE, and VTE to other published real-world background rates observed in moderate to severe AD populations. He noted that, while the malignancy rate in the current trial ranged from 0.3 to 0.4 per 100 PY, an observational study of more than 66,000 AD patients in the United Kingdom reported a malignancy (excluding NMSC) background incidence rate of 0.33 per 100 PY, and SEER data estimate that the malignancy incidence rate in the US general population is 0.45 per 100 PY. “Therefore, patients on upadacitinib at the 5-year mark are right at the AD population baseline risk,” he said.

And while the incidence rate of MACE in the current trial ranged from less than 0.1 to 0.2 per 100 PY, the background incidence rate of MACE in a Danish observational study of more than 2,500 patients with moderate to severe AD was 0.63 per 100 PY. “This suggests that there may be an anti-inflammatory and even a cardiovascular protective effect for patients on upadacitinib,” Dr. Bunick said.

As for VTE, the incidence rate in the current trial was 0.1 per 100 PY, but VTE background incidence rate observed in a moderate to severe AD population in the United States is 0.31 per 100 PY. “Again, this suggests anti-inflammatory and cardiovascular protective effects of upadacitinib in AD patients at the 5-year mark,” he said. “Reporting of MACE, VTE, and malignancy (excluding NMSC) in upadacitinib phase 3 clinical trials for AD generally reflects the background observations of these events in the AD population.”

He acknowledged certain limitations of the study, including the fact that observational data may overestimate the risk of adverse events.

Discussing the incidence rates for MACE, VTE, and malignancy in upadacitinib AD trials, Dr. Bunick remarked, “these are rock-bottom rates that have been low through 5 years of treatment.”

Dr. Bunick disclosed that he has received grant or research support from AbbVie (the manufacturer of upadacitinib), Almirall, Ortho Dermatologics, Timber, and Palvella. He is also a consultant and/or an adviser to AbbVie, Almirall, Apogee, Connect Bropharma, Arcutis, Eli Lilly, Novartis, Pfizer, Sanofi-Regeneron, Ortho Dermatologics, Leo Pharma, and UCB.

Safety data spanning up to 5 years from clinical trials of adolescents and adults using 15 mg or 30 mg of upadacitinib to treat moderate to severe atopic dermatitis (AD) indicates that rates of treatment-emergent adverse events remained low and consistent, with no new safety risks identified, underscoring the medication’s stable safety profile over an extended duration.

Those are among the key findings from an integrated analysis of long-term upadacitinib use presented by Christopher G. Bunick, MD, PhD, during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis Virtual Conference. Upadacitinib (Rinvoq) is an oral Janus kinase (JAK) inhibitor, approved by the Food and Drug Administration for adults and pediatric patients aged 12 years of age and older with refractory, moderate to severe AD in January 2022.

“What makes this study special is that these patients are followed for 260 weeks, or 5 years, and it encompasses over 7,000 patient-years of exposure,” said Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut. “This is a milestone because it’s the longest safety study ever published for any systemic drug for AD.”

He and his colleagues evaluated the safety data for up to 5 years of upadacitinib 15 mg and 30 mg use in adolescents and adults with moderate to severe AD, based on the results of integrated data from three ongoing global multicenter phase 3 trials: Measure Up 1, Measure Up 2, and AD Up. Patients in the trials were randomized 1:1:1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily alone (Measure Up 1 and 2) or with concomitant topical corticosteroids (AD Up). At week 16, patients receiving 15 mg or 30 mg upadacitinib during the double-blind period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were randomized 1:1 to receive either 15 mg or 30 mg upadacitinib in the BE period. The integrated analysis included 2683 patients (529 adolescents and 2154 adults) who received at least one dose of upadacitinib. Of these, 1337 received the 15-mg dose, while 1346 received the 30-mg dose. The researchers analyzed treatment-emergent events of special interest as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different follow-up durations.

According to Dr. Bunick, researchers often refer to “100 patient-years” in safety analyses to measure how common certain events are. “It is a straightforward way to convey the collective experience of the study’s participants over time,” he told this news organization. “For instance, if 100 patients are each monitored for 1 year, or 50 patients for 2 years each, both scenarios amount to 100 patient-years. This metric allows clinicians to understand how often certain adverse events occur across a diverse group over a specific time frame, providing a clear picture of long-term safety.”

Upadacitinib trials in atopic dermatitis have included diverse patient groups with varying risk factors. “Patients were not cherry-picked,” he said. “What I mean by that is that about 50% of patients enrolled in these trials had, at baseline, at least one cardiovascular risk factor: about 30% used tobacco; 10% had hypertension, and 5% had a history of a cardiovascular event.” In addition, about 15% were over age 50 with one cardiovascular risk factor and about 20% had a body mass index (BMI) greater than 30 kg/m². Among women in the study, about 20% were on oral contraceptives, yet none developed a venous thromboembolism (VTE).

In the integrated analysis, the rate of treatment-emergent adverse events that led to discontinuation of upadacitinib was about 4.2 events per 100 PY, “meaning that this medicine shows durability,” Dr. Bunick said. “Very few people are discontinuing due to adverse events.”

Serious and opportunistic infections ranged from 1.6 to 2.8 events per 100 PY, but these were stable across the 1- to 5-year time points. The rates of active TB were less than 0.1 per 100 PY, while the rates of herpes zoster ranged from 3.5 to 5.5 events per 100 PY. “The key take-home point here is that 5% or less of the patients at baseline had received the shingles vaccine, so it’s very important to talk to patients about receiving the shingles vaccine before they go on upadacitinib,” Dr. Bunick advised, because “this could reduce risk of herpes zoster occurring in upadacitinib-treated patients substantially.”

In other findings, incidence rates of nonmelanoma skin cancer (NMSC) ranged between 0.3 and 0.4 per 100 PY, while the rate of malignancy excluding NMSC ranged between 0.3 and 0.4 per 100 PY. Meanwhile, the rates of gastrointestinal perforations and VTE stood at 0.1 per 100 PY or lower, and MACE incidence rates ranged from 0.1 to 0.2 per 100 PY.

During his presentation, Dr. Bunick compared findings related to malignancy (excluding NMSC), MACE, and VTE to other published real-world background rates observed in moderate to severe AD populations. He noted that, while the malignancy rate in the current trial ranged from 0.3 to 0.4 per 100 PY, an observational study of more than 66,000 AD patients in the United Kingdom reported a malignancy (excluding NMSC) background incidence rate of 0.33 per 100 PY, and SEER data estimate that the malignancy incidence rate in the US general population is 0.45 per 100 PY. “Therefore, patients on upadacitinib at the 5-year mark are right at the AD population baseline risk,” he said.

And while the incidence rate of MACE in the current trial ranged from less than 0.1 to 0.2 per 100 PY, the background incidence rate of MACE in a Danish observational study of more than 2,500 patients with moderate to severe AD was 0.63 per 100 PY. “This suggests that there may be an anti-inflammatory and even a cardiovascular protective effect for patients on upadacitinib,” Dr. Bunick said.

As for VTE, the incidence rate in the current trial was 0.1 per 100 PY, but VTE background incidence rate observed in a moderate to severe AD population in the United States is 0.31 per 100 PY. “Again, this suggests anti-inflammatory and cardiovascular protective effects of upadacitinib in AD patients at the 5-year mark,” he said. “Reporting of MACE, VTE, and malignancy (excluding NMSC) in upadacitinib phase 3 clinical trials for AD generally reflects the background observations of these events in the AD population.”

He acknowledged certain limitations of the study, including the fact that observational data may overestimate the risk of adverse events.

Discussing the incidence rates for MACE, VTE, and malignancy in upadacitinib AD trials, Dr. Bunick remarked, “these are rock-bottom rates that have been low through 5 years of treatment.”

Dr. Bunick disclosed that he has received grant or research support from AbbVie (the manufacturer of upadacitinib), Almirall, Ortho Dermatologics, Timber, and Palvella. He is also a consultant and/or an adviser to AbbVie, Almirall, Apogee, Connect Bropharma, Arcutis, Eli Lilly, Novartis, Pfizer, Sanofi-Regeneron, Ortho Dermatologics, Leo Pharma, and UCB.

Safety data spanning up to 5 years from clinical trials of adolescents and adults using 15 mg or 30 mg of upadacitinib to treat moderate to severe atopic dermatitis (AD) indicates that rates of treatment-emergent adverse events remained low and consistent, with no new safety risks identified, underscoring the medication’s stable safety profile over an extended duration.

Those are among the key findings from an integrated analysis of long-term upadacitinib use presented by Christopher G. Bunick, MD, PhD, during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis Virtual Conference. Upadacitinib (Rinvoq) is an oral Janus kinase (JAK) inhibitor, approved by the Food and Drug Administration for adults and pediatric patients aged 12 years of age and older with refractory, moderate to severe AD in January 2022.

“What makes this study special is that these patients are followed for 260 weeks, or 5 years, and it encompasses over 7,000 patient-years of exposure,” said Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut. “This is a milestone because it’s the longest safety study ever published for any systemic drug for AD.”

He and his colleagues evaluated the safety data for up to 5 years of upadacitinib 15 mg and 30 mg use in adolescents and adults with moderate to severe AD, based on the results of integrated data from three ongoing global multicenter phase 3 trials: Measure Up 1, Measure Up 2, and AD Up. Patients in the trials were randomized 1:1:1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily alone (Measure Up 1 and 2) or with concomitant topical corticosteroids (AD Up). At week 16, patients receiving 15 mg or 30 mg upadacitinib during the double-blind period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were randomized 1:1 to receive either 15 mg or 30 mg upadacitinib in the BE period. The integrated analysis included 2683 patients (529 adolescents and 2154 adults) who received at least one dose of upadacitinib. Of these, 1337 received the 15-mg dose, while 1346 received the 30-mg dose. The researchers analyzed treatment-emergent events of special interest as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different follow-up durations.

According to Dr. Bunick, researchers often refer to “100 patient-years” in safety analyses to measure how common certain events are. “It is a straightforward way to convey the collective experience of the study’s participants over time,” he told this news organization. “For instance, if 100 patients are each monitored for 1 year, or 50 patients for 2 years each, both scenarios amount to 100 patient-years. This metric allows clinicians to understand how often certain adverse events occur across a diverse group over a specific time frame, providing a clear picture of long-term safety.”

Upadacitinib trials in atopic dermatitis have included diverse patient groups with varying risk factors. “Patients were not cherry-picked,” he said. “What I mean by that is that about 50% of patients enrolled in these trials had, at baseline, at least one cardiovascular risk factor: about 30% used tobacco; 10% had hypertension, and 5% had a history of a cardiovascular event.” In addition, about 15% were over age 50 with one cardiovascular risk factor and about 20% had a body mass index (BMI) greater than 30 kg/m². Among women in the study, about 20% were on oral contraceptives, yet none developed a venous thromboembolism (VTE).

In the integrated analysis, the rate of treatment-emergent adverse events that led to discontinuation of upadacitinib was about 4.2 events per 100 PY, “meaning that this medicine shows durability,” Dr. Bunick said. “Very few people are discontinuing due to adverse events.”

Serious and opportunistic infections ranged from 1.6 to 2.8 events per 100 PY, but these were stable across the 1- to 5-year time points. The rates of active TB were less than 0.1 per 100 PY, while the rates of herpes zoster ranged from 3.5 to 5.5 events per 100 PY. “The key take-home point here is that 5% or less of the patients at baseline had received the shingles vaccine, so it’s very important to talk to patients about receiving the shingles vaccine before they go on upadacitinib,” Dr. Bunick advised, because “this could reduce risk of herpes zoster occurring in upadacitinib-treated patients substantially.”

In other findings, incidence rates of nonmelanoma skin cancer (NMSC) ranged between 0.3 and 0.4 per 100 PY, while the rate of malignancy excluding NMSC ranged between 0.3 and 0.4 per 100 PY. Meanwhile, the rates of gastrointestinal perforations and VTE stood at 0.1 per 100 PY or lower, and MACE incidence rates ranged from 0.1 to 0.2 per 100 PY.

During his presentation, Dr. Bunick compared findings related to malignancy (excluding NMSC), MACE, and VTE to other published real-world background rates observed in moderate to severe AD populations. He noted that, while the malignancy rate in the current trial ranged from 0.3 to 0.4 per 100 PY, an observational study of more than 66,000 AD patients in the United Kingdom reported a malignancy (excluding NMSC) background incidence rate of 0.33 per 100 PY, and SEER data estimate that the malignancy incidence rate in the US general population is 0.45 per 100 PY. “Therefore, patients on upadacitinib at the 5-year mark are right at the AD population baseline risk,” he said.

And while the incidence rate of MACE in the current trial ranged from less than 0.1 to 0.2 per 100 PY, the background incidence rate of MACE in a Danish observational study of more than 2,500 patients with moderate to severe AD was 0.63 per 100 PY. “This suggests that there may be an anti-inflammatory and even a cardiovascular protective effect for patients on upadacitinib,” Dr. Bunick said.

As for VTE, the incidence rate in the current trial was 0.1 per 100 PY, but VTE background incidence rate observed in a moderate to severe AD population in the United States is 0.31 per 100 PY. “Again, this suggests anti-inflammatory and cardiovascular protective effects of upadacitinib in AD patients at the 5-year mark,” he said. “Reporting of MACE, VTE, and malignancy (excluding NMSC) in upadacitinib phase 3 clinical trials for AD generally reflects the background observations of these events in the AD population.”

He acknowledged certain limitations of the study, including the fact that observational data may overestimate the risk of adverse events.

Discussing the incidence rates for MACE, VTE, and malignancy in upadacitinib AD trials, Dr. Bunick remarked, “these are rock-bottom rates that have been low through 5 years of treatment.”

Dr. Bunick disclosed that he has received grant or research support from AbbVie (the manufacturer of upadacitinib), Almirall, Ortho Dermatologics, Timber, and Palvella. He is also a consultant and/or an adviser to AbbVie, Almirall, Apogee, Connect Bropharma, Arcutis, Eli Lilly, Novartis, Pfizer, Sanofi-Regeneron, Ortho Dermatologics, Leo Pharma, and UCB.

In the treatment of acute lymphoblastic leukemia/lymphoma (ALL), benefits observed in children and adults with an intensive regimen utilizing asparaginase extend to the adolescent and young adult population in a real-world setting.

“These findings of a large cohort of adolescents and young adults treated at a variety of U.S. centers confirm the findings of the clinical trial and also provide confidence that patients remaining on this regimen have very excellent 3-year outcomes,” senior author Lori S. Muffly, MD, associate professor of medicine at Stanford University in the Division of Blood and Marrow Transplantation and Cellular Therapy, in Stanford, California, said in an interview.

The study was presented at the American Society of Hematology annual meeting. In the Cancer and Leukemia Group B 10403 trial, the intensive asparaginase pediatric regimen, used in the adult oncology treatment setting, showed benefits in the adolescent and young adult population, with a 3-year event-free survival (EFS) rate of 59% and an overall survival rate of 73%.

Based on the results, the regimen has gained widespread utilization in the United States. However, evidence of the therapy’s safety and efficacy in real-world practice, outside of the controlled clinical trial setting, has been lacking.

To investigate, first author Dr. Muffly, along with coauthor Brandon DaSilva, MD, and colleagues at Stanford University School of Medicine conducted a retrospective analysis of 101 adolescent and young adult patients aged 17 to 40 with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL (B-ALL) or T-cell ALL (T-ALL).

The patients had been treated with the C10403 regimen off-trial at five U.S. centers between October 2012 and July 2020.

The study excluded Ph-positive or Burkitt-type ALL patients, in addition to those who were previously treated, with the exception of treatment with hydroxyurea, steroids, one dose of single-agent therapy, or rituximab for CD20-positive B-ALL. Of the patients, about half, 54%, were between the ages of 20 and 29; 69% were male and 55% were White. Most patients (70%) had B-cell immunophenotype, and among them, 49% had CD20 expression.

Forty percent of patients had normal karyotype; 3% were hypodiploid, 7% were KMT2a-rearranged, and 30% of the 27 patients assessed had Ph-like ALL. CNS involvement was present at diagnosis among 20% (9% with CNS2, 11% with CNS3) and 14% of patients had a mediastinal mass.

Of 71 patients with B-ALL, 16 (23%) received at least one dose of rituximab.

Among the 101 patients who started induction with C10403, 72 (71%) completed induction and continued to consolidation; 51 (50%) continued beyond consolidation, while only 31 (31%) completed the entire C10403 regimen through the end of maintenance.

For the primary outcomes, overall, the rate of induction response, defined as achieving <5% blasts on bone marrow by the end of induction or extended induction, was 91% of whom 54% were measurable residual disease [MRD]-negative (threshold of at least 10^–4).

The co-primary endpoint of 3-year event-free survival was 65% and 3-year overall survival was 82.7%.

Two deaths occurred (2%) among patients who were in remission and still receiving treatment.

Overall, 44 patients (44%) were taken off C10403 while in complete remission, including 20 (20%) to receive an allogeneic hematopoietic cell transplant (HCT), 23 (23%) to receive non-HCT alternative treatments including Hyper-CVAD or blinatumomab, and 1 (1%) for patient preference.

Dr. Muffly noted that the 31% of treatment completion is about the same as that seen on the original C10403 trial.

“In clinical practice, there are a variety of reasons that these patients came off therapy — probably the most common reason is for MRD-directed therapy, such as with blinatumomab.”

“We are currently analyzing the results of the patients who came off therapy relative to those who stayed on therapy which will be interesting.”

The slightly higher real-world 3-year EFS and OS (65% and 82.7%, respectively) compared with the outcomes in the clinical trial (59% and 73%, respectively), were “very encouraging,” Dr. Muffly noted.

“A lot has changed and improved in B-ALL for adolescent/young adults since this trial closed to enrollment over 10 years ago,” she explained.

“We have better MRD methods, MRD-directed therapies, and a variety of targeted immunotherapies being used in a variety of ways,” Dr. Muffly said. “The overall outcomes for adolescent/young adult ALL patients are improving and we can see that in this data set.”

Commenting on the study, Catherine Bollard, MD, a pediatric oncologist at Children’s National Hospital in Washington, DC, noted that the study’s retrospective nature is “definitely a major caveat that needs to be considered when evaluating the impact of the data.”

Regarding the relatively low rate of regimen completion, Dr. Bollard said, “I do think the pros still outweigh the cons. But getting patients into a deep complete remission and then evaluating their outcomes after consolidation with HCT or alternative therapy is certainly an important consideration and needs to be studied further in a larger cohort.”

Overall, however, “this ‘real world’ experience validates the use of this regimen outside of the clinical trial setting,” she said.

Dr. Muffly and Dr. Bollard had no disclosures to report. Dr. Bollard is the editor-in-chief of ASH’s journal, Blood Advances.

In the treatment of acute lymphoblastic leukemia/lymphoma (ALL), benefits observed in children and adults with an intensive regimen utilizing asparaginase extend to the adolescent and young adult population in a real-world setting.

“These findings of a large cohort of adolescents and young adults treated at a variety of U.S. centers confirm the findings of the clinical trial and also provide confidence that patients remaining on this regimen have very excellent 3-year outcomes,” senior author Lori S. Muffly, MD, associate professor of medicine at Stanford University in the Division of Blood and Marrow Transplantation and Cellular Therapy, in Stanford, California, said in an interview.

The study was presented at the American Society of Hematology annual meeting. In the Cancer and Leukemia Group B 10403 trial, the intensive asparaginase pediatric regimen, used in the adult oncology treatment setting, showed benefits in the adolescent and young adult population, with a 3-year event-free survival (EFS) rate of 59% and an overall survival rate of 73%.

Based on the results, the regimen has gained widespread utilization in the United States. However, evidence of the therapy’s safety and efficacy in real-world practice, outside of the controlled clinical trial setting, has been lacking.

To investigate, first author Dr. Muffly, along with coauthor Brandon DaSilva, MD, and colleagues at Stanford University School of Medicine conducted a retrospective analysis of 101 adolescent and young adult patients aged 17 to 40 with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL (B-ALL) or T-cell ALL (T-ALL).

The patients had been treated with the C10403 regimen off-trial at five U.S. centers between October 2012 and July 2020.

The study excluded Ph-positive or Burkitt-type ALL patients, in addition to those who were previously treated, with the exception of treatment with hydroxyurea, steroids, one dose of single-agent therapy, or rituximab for CD20-positive B-ALL. Of the patients, about half, 54%, were between the ages of 20 and 29; 69% were male and 55% were White. Most patients (70%) had B-cell immunophenotype, and among them, 49% had CD20 expression.

Forty percent of patients had normal karyotype; 3% were hypodiploid, 7% were KMT2a-rearranged, and 30% of the 27 patients assessed had Ph-like ALL. CNS involvement was present at diagnosis among 20% (9% with CNS2, 11% with CNS3) and 14% of patients had a mediastinal mass.

Of 71 patients with B-ALL, 16 (23%) received at least one dose of rituximab.

Among the 101 patients who started induction with C10403, 72 (71%) completed induction and continued to consolidation; 51 (50%) continued beyond consolidation, while only 31 (31%) completed the entire C10403 regimen through the end of maintenance.

For the primary outcomes, overall, the rate of induction response, defined as achieving <5% blasts on bone marrow by the end of induction or extended induction, was 91% of whom 54% were measurable residual disease [MRD]-negative (threshold of at least 10^–4).

The co-primary endpoint of 3-year event-free survival was 65% and 3-year overall survival was 82.7%.

Two deaths occurred (2%) among patients who were in remission and still receiving treatment.

Overall, 44 patients (44%) were taken off C10403 while in complete remission, including 20 (20%) to receive an allogeneic hematopoietic cell transplant (HCT), 23 (23%) to receive non-HCT alternative treatments including Hyper-CVAD or blinatumomab, and 1 (1%) for patient preference.

Dr. Muffly noted that the 31% of treatment completion is about the same as that seen on the original C10403 trial.

“In clinical practice, there are a variety of reasons that these patients came off therapy — probably the most common reason is for MRD-directed therapy, such as with blinatumomab.”

“We are currently analyzing the results of the patients who came off therapy relative to those who stayed on therapy which will be interesting.”

The slightly higher real-world 3-year EFS and OS (65% and 82.7%, respectively) compared with the outcomes in the clinical trial (59% and 73%, respectively), were “very encouraging,” Dr. Muffly noted.

“A lot has changed and improved in B-ALL for adolescent/young adults since this trial closed to enrollment over 10 years ago,” she explained.

“We have better MRD methods, MRD-directed therapies, and a variety of targeted immunotherapies being used in a variety of ways,” Dr. Muffly said. “The overall outcomes for adolescent/young adult ALL patients are improving and we can see that in this data set.”

Commenting on the study, Catherine Bollard, MD, a pediatric oncologist at Children’s National Hospital in Washington, DC, noted that the study’s retrospective nature is “definitely a major caveat that needs to be considered when evaluating the impact of the data.”

Regarding the relatively low rate of regimen completion, Dr. Bollard said, “I do think the pros still outweigh the cons. But getting patients into a deep complete remission and then evaluating their outcomes after consolidation with HCT or alternative therapy is certainly an important consideration and needs to be studied further in a larger cohort.”

Overall, however, “this ‘real world’ experience validates the use of this regimen outside of the clinical trial setting,” she said.

Dr. Muffly and Dr. Bollard had no disclosures to report. Dr. Bollard is the editor-in-chief of ASH’s journal, Blood Advances.

In the treatment of acute lymphoblastic leukemia/lymphoma (ALL), benefits observed in children and adults with an intensive regimen utilizing asparaginase extend to the adolescent and young adult population in a real-world setting.

“These findings of a large cohort of adolescents and young adults treated at a variety of U.S. centers confirm the findings of the clinical trial and also provide confidence that patients remaining on this regimen have very excellent 3-year outcomes,” senior author Lori S. Muffly, MD, associate professor of medicine at Stanford University in the Division of Blood and Marrow Transplantation and Cellular Therapy, in Stanford, California, said in an interview.

The study was presented at the American Society of Hematology annual meeting. In the Cancer and Leukemia Group B 10403 trial, the intensive asparaginase pediatric regimen, used in the adult oncology treatment setting, showed benefits in the adolescent and young adult population, with a 3-year event-free survival (EFS) rate of 59% and an overall survival rate of 73%.

Based on the results, the regimen has gained widespread utilization in the United States. However, evidence of the therapy’s safety and efficacy in real-world practice, outside of the controlled clinical trial setting, has been lacking.

To investigate, first author Dr. Muffly, along with coauthor Brandon DaSilva, MD, and colleagues at Stanford University School of Medicine conducted a retrospective analysis of 101 adolescent and young adult patients aged 17 to 40 with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell ALL (B-ALL) or T-cell ALL (T-ALL).

The patients had been treated with the C10403 regimen off-trial at five U.S. centers between October 2012 and July 2020.

The study excluded Ph-positive or Burkitt-type ALL patients, in addition to those who were previously treated, with the exception of treatment with hydroxyurea, steroids, one dose of single-agent therapy, or rituximab for CD20-positive B-ALL. Of the patients, about half, 54%, were between the ages of 20 and 29; 69% were male and 55% were White. Most patients (70%) had B-cell immunophenotype, and among them, 49% had CD20 expression.

Forty percent of patients had normal karyotype; 3% were hypodiploid, 7% were KMT2a-rearranged, and 30% of the 27 patients assessed had Ph-like ALL. CNS involvement was present at diagnosis among 20% (9% with CNS2, 11% with CNS3) and 14% of patients had a mediastinal mass.

Of 71 patients with B-ALL, 16 (23%) received at least one dose of rituximab.

Among the 101 patients who started induction with C10403, 72 (71%) completed induction and continued to consolidation; 51 (50%) continued beyond consolidation, while only 31 (31%) completed the entire C10403 regimen through the end of maintenance.

For the primary outcomes, overall, the rate of induction response, defined as achieving <5% blasts on bone marrow by the end of induction or extended induction, was 91% of whom 54% were measurable residual disease [MRD]-negative (threshold of at least 10^–4).

The co-primary endpoint of 3-year event-free survival was 65% and 3-year overall survival was 82.7%.

Two deaths occurred (2%) among patients who were in remission and still receiving treatment.

Overall, 44 patients (44%) were taken off C10403 while in complete remission, including 20 (20%) to receive an allogeneic hematopoietic cell transplant (HCT), 23 (23%) to receive non-HCT alternative treatments including Hyper-CVAD or blinatumomab, and 1 (1%) for patient preference.

Dr. Muffly noted that the 31% of treatment completion is about the same as that seen on the original C10403 trial.

“In clinical practice, there are a variety of reasons that these patients came off therapy — probably the most common reason is for MRD-directed therapy, such as with blinatumomab.”

“We are currently analyzing the results of the patients who came off therapy relative to those who stayed on therapy which will be interesting.”

The slightly higher real-world 3-year EFS and OS (65% and 82.7%, respectively) compared with the outcomes in the clinical trial (59% and 73%, respectively), were “very encouraging,” Dr. Muffly noted.

“A lot has changed and improved in B-ALL for adolescent/young adults since this trial closed to enrollment over 10 years ago,” she explained.

“We have better MRD methods, MRD-directed therapies, and a variety of targeted immunotherapies being used in a variety of ways,” Dr. Muffly said. “The overall outcomes for adolescent/young adult ALL patients are improving and we can see that in this data set.”

Commenting on the study, Catherine Bollard, MD, a pediatric oncologist at Children’s National Hospital in Washington, DC, noted that the study’s retrospective nature is “definitely a major caveat that needs to be considered when evaluating the impact of the data.”

Regarding the relatively low rate of regimen completion, Dr. Bollard said, “I do think the pros still outweigh the cons. But getting patients into a deep complete remission and then evaluating their outcomes after consolidation with HCT or alternative therapy is certainly an important consideration and needs to be studied further in a larger cohort.”

Overall, however, “this ‘real world’ experience validates the use of this regimen outside of the clinical trial setting,” she said.

Dr. Muffly and Dr. Bollard had no disclosures to report. Dr. Bollard is the editor-in-chief of ASH’s journal, Blood Advances.

The prevalence of clinically meaningful conjunctivitis in patients taking dupilumab for atopic dermatitis (AD) is likely about 2%, and it most often occurs in the first 16 weeks of therapy.

Those are key findings from an analysis of published trials of dupilumab for AD and other conditions that study author Matthew Zirwas, MD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Adults with AD have a significant and disease severity–dependent increased risk of developing ocular surface diseases, including conjunctivitis and keratitis, compared with the general population and independent of any drug effect, according to Dr. Zirwas, a dermatologist with Probity Medical Research of Columbus, Ohio.

Dupilumab inhibits signaling of interleukin (IL)-4 and IL-13, which drive type 2 inflammatory diseases such as AD, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), prurigo nodularis (PN), and chronic spontaneous urticaria (CSU).

In randomized, placebo-controlled trials of dupilumab in patients with moderate to severe AD, conjunctivitis was reported in more patients who received dupilumab treatment than in placebo-treated patients.

“When it comes to dupilumab-induced conjunctivitis, we have a good idea of the etiology, but the question of how frequently it occurs versus how frequently the conjunctivitis is unrelated to dupilumab is an interesting one,” he said. “How often is it clinically meaningful? What is it that is so unique about AD patients? We’ve all heard that it is a unique adverse event that only happens to people with AD and not to people using dupilumab for other indications. Where it gets interesting to me is how do we differentiate the cases that are dupilumab induced versus the cases that are just part of the underlying AD process?”

For their analysis, Dr. Zirwas and co-authors reviewed the incidence of conjunctivitis adverse events in patients from 15 completed, randomized, double-blind placebo-controlled trials evaluating dupilumab in AD, asthma, CRSwNP, EoE, PN, and CSU, along with the severity and resolution of conjunctivitis events in adults with AD.

Of the 15 trials, 7 were conducted in patients with AD: 4 in adults, 1 in adolescents, 1 in school-aged children, and 1 in preschoolers. One of the AD trials, LIBERTY AD CHRONOS, extends 52 weeks. The remaining eight trials of patients with asthma, CRSwNP, EoE, PN, and CSU lasted 24-52 weeks.

In the non-AD trials, the researchers observed that conjunctivitis rates were generally in the 1%-3% range, with less pronounced or no differences between the dupilumab and placebo groups. In the AD trials, conjunctivitis rates were higher in patients receiving dupilumab, compared with those receiving placebo across age groups.

In the 16-week SOLO 1 & 2 and AD-1021 monotherapy trials, 12 conjunctivitis events occurred in 517 patients who received placebo (2%), compared with 103 of 1047 patients (9.84%) who received dupilumab. Of the dupilumab-associated conjunctivitis cases, 80 (78%) patients recovered by the end of the trials. Of the 23 cases of conjunctivitis that did not recover or dropped out of the trial, 15 were among the 529 patients who received 300 mg dupilumab once every 2 weeks (q2w) (3%) and eight were among the 518 who received 300 mg dupilumab once weekly (qw) (2%).

In the 52-week LIBERTY AD CHRONOS trial, 29 conjunctivitis events occurred in 315 patients who received placebo plus topical corticosteroid (TCS) (9%), compared with 113 of 425 patients (27%) who received dupilumab plus TCS. Of these, 103 (91%) recovered by the end of the trial. Of the 11 patients with conjunctivitis who did not recover or dropped out of the trial, 3 were among the 110 patients who received 300 mg dupilumab q2w plus TCS (3%), and 8 were among the 315 who received 300 mg dupilumab qw plus TCS (3%).

“When I look at all of this data, I think that about 2% of people treated with dupilumab are going to get clinically very meaningful conjunctivitis that may be therapy limiting,” Dr. Zirwas concluded. “The vast majority of those cases appear to happen in the first 16 weeks. This is just not something we see in cases of patients treated with dupilumab treated for other reasons.”

Following his presentation, a meeting attendee asked Dr. Zirwas if conjunctivitis occurs more often in patients with facial dermatitis. “My perception is that it happens more often in people who have facial or eyelid dermatitis, but I’ve seen it in plenty of people who didn’t have any facial or eyelid dermatitis,” he said. “I have seen more conjunctivitis in people with more severe AD and more severe atopic comorbidities. That is anecdotal. The data that I have seen has been back and forth on this topic.”

Dr. Zirwas disclosed that he is a speaker and consultant for Sanofi, Regeneron, Leo, Lilly, Galderma, Pfizer, and AbbVie. Several of his co-authors work for Regeneron Pharmaceuticals.

The prevalence of clinically meaningful conjunctivitis in patients taking dupilumab for atopic dermatitis (AD) is likely about 2%, and it most often occurs in the first 16 weeks of therapy.

Those are key findings from an analysis of published trials of dupilumab for AD and other conditions that study author Matthew Zirwas, MD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Adults with AD have a significant and disease severity–dependent increased risk of developing ocular surface diseases, including conjunctivitis and keratitis, compared with the general population and independent of any drug effect, according to Dr. Zirwas, a dermatologist with Probity Medical Research of Columbus, Ohio.

Dupilumab inhibits signaling of interleukin (IL)-4 and IL-13, which drive type 2 inflammatory diseases such as AD, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), prurigo nodularis (PN), and chronic spontaneous urticaria (CSU).

In randomized, placebo-controlled trials of dupilumab in patients with moderate to severe AD, conjunctivitis was reported in more patients who received dupilumab treatment than in placebo-treated patients.

“When it comes to dupilumab-induced conjunctivitis, we have a good idea of the etiology, but the question of how frequently it occurs versus how frequently the conjunctivitis is unrelated to dupilumab is an interesting one,” he said. “How often is it clinically meaningful? What is it that is so unique about AD patients? We’ve all heard that it is a unique adverse event that only happens to people with AD and not to people using dupilumab for other indications. Where it gets interesting to me is how do we differentiate the cases that are dupilumab induced versus the cases that are just part of the underlying AD process?”

For their analysis, Dr. Zirwas and co-authors reviewed the incidence of conjunctivitis adverse events in patients from 15 completed, randomized, double-blind placebo-controlled trials evaluating dupilumab in AD, asthma, CRSwNP, EoE, PN, and CSU, along with the severity and resolution of conjunctivitis events in adults with AD.

Of the 15 trials, 7 were conducted in patients with AD: 4 in adults, 1 in adolescents, 1 in school-aged children, and 1 in preschoolers. One of the AD trials, LIBERTY AD CHRONOS, extends 52 weeks. The remaining eight trials of patients with asthma, CRSwNP, EoE, PN, and CSU lasted 24-52 weeks.

In the non-AD trials, the researchers observed that conjunctivitis rates were generally in the 1%-3% range, with less pronounced or no differences between the dupilumab and placebo groups. In the AD trials, conjunctivitis rates were higher in patients receiving dupilumab, compared with those receiving placebo across age groups.

In the 16-week SOLO 1 & 2 and AD-1021 monotherapy trials, 12 conjunctivitis events occurred in 517 patients who received placebo (2%), compared with 103 of 1047 patients (9.84%) who received dupilumab. Of the dupilumab-associated conjunctivitis cases, 80 (78%) patients recovered by the end of the trials. Of the 23 cases of conjunctivitis that did not recover or dropped out of the trial, 15 were among the 529 patients who received 300 mg dupilumab once every 2 weeks (q2w) (3%) and eight were among the 518 who received 300 mg dupilumab once weekly (qw) (2%).

In the 52-week LIBERTY AD CHRONOS trial, 29 conjunctivitis events occurred in 315 patients who received placebo plus topical corticosteroid (TCS) (9%), compared with 113 of 425 patients (27%) who received dupilumab plus TCS. Of these, 103 (91%) recovered by the end of the trial. Of the 11 patients with conjunctivitis who did not recover or dropped out of the trial, 3 were among the 110 patients who received 300 mg dupilumab q2w plus TCS (3%), and 8 were among the 315 who received 300 mg dupilumab qw plus TCS (3%).

“When I look at all of this data, I think that about 2% of people treated with dupilumab are going to get clinically very meaningful conjunctivitis that may be therapy limiting,” Dr. Zirwas concluded. “The vast majority of those cases appear to happen in the first 16 weeks. This is just not something we see in cases of patients treated with dupilumab treated for other reasons.”

Following his presentation, a meeting attendee asked Dr. Zirwas if conjunctivitis occurs more often in patients with facial dermatitis. “My perception is that it happens more often in people who have facial or eyelid dermatitis, but I’ve seen it in plenty of people who didn’t have any facial or eyelid dermatitis,” he said. “I have seen more conjunctivitis in people with more severe AD and more severe atopic comorbidities. That is anecdotal. The data that I have seen has been back and forth on this topic.”

Dr. Zirwas disclosed that he is a speaker and consultant for Sanofi, Regeneron, Leo, Lilly, Galderma, Pfizer, and AbbVie. Several of his co-authors work for Regeneron Pharmaceuticals.

The prevalence of clinically meaningful conjunctivitis in patients taking dupilumab for atopic dermatitis (AD) is likely about 2%, and it most often occurs in the first 16 weeks of therapy.

Those are key findings from an analysis of published trials of dupilumab for AD and other conditions that study author Matthew Zirwas, MD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Adults with AD have a significant and disease severity–dependent increased risk of developing ocular surface diseases, including conjunctivitis and keratitis, compared with the general population and independent of any drug effect, according to Dr. Zirwas, a dermatologist with Probity Medical Research of Columbus, Ohio.

Dupilumab inhibits signaling of interleukin (IL)-4 and IL-13, which drive type 2 inflammatory diseases such as AD, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), prurigo nodularis (PN), and chronic spontaneous urticaria (CSU).

In randomized, placebo-controlled trials of dupilumab in patients with moderate to severe AD, conjunctivitis was reported in more patients who received dupilumab treatment than in placebo-treated patients.

“When it comes to dupilumab-induced conjunctivitis, we have a good idea of the etiology, but the question of how frequently it occurs versus how frequently the conjunctivitis is unrelated to dupilumab is an interesting one,” he said. “How often is it clinically meaningful? What is it that is so unique about AD patients? We’ve all heard that it is a unique adverse event that only happens to people with AD and not to people using dupilumab for other indications. Where it gets interesting to me is how do we differentiate the cases that are dupilumab induced versus the cases that are just part of the underlying AD process?”

For their analysis, Dr. Zirwas and co-authors reviewed the incidence of conjunctivitis adverse events in patients from 15 completed, randomized, double-blind placebo-controlled trials evaluating dupilumab in AD, asthma, CRSwNP, EoE, PN, and CSU, along with the severity and resolution of conjunctivitis events in adults with AD.

Of the 15 trials, 7 were conducted in patients with AD: 4 in adults, 1 in adolescents, 1 in school-aged children, and 1 in preschoolers. One of the AD trials, LIBERTY AD CHRONOS, extends 52 weeks. The remaining eight trials of patients with asthma, CRSwNP, EoE, PN, and CSU lasted 24-52 weeks.

In the non-AD trials, the researchers observed that conjunctivitis rates were generally in the 1%-3% range, with less pronounced or no differences between the dupilumab and placebo groups. In the AD trials, conjunctivitis rates were higher in patients receiving dupilumab, compared with those receiving placebo across age groups.

In the 16-week SOLO 1 & 2 and AD-1021 monotherapy trials, 12 conjunctivitis events occurred in 517 patients who received placebo (2%), compared with 103 of 1047 patients (9.84%) who received dupilumab. Of the dupilumab-associated conjunctivitis cases, 80 (78%) patients recovered by the end of the trials. Of the 23 cases of conjunctivitis that did not recover or dropped out of the trial, 15 were among the 529 patients who received 300 mg dupilumab once every 2 weeks (q2w) (3%) and eight were among the 518 who received 300 mg dupilumab once weekly (qw) (2%).

In the 52-week LIBERTY AD CHRONOS trial, 29 conjunctivitis events occurred in 315 patients who received placebo plus topical corticosteroid (TCS) (9%), compared with 113 of 425 patients (27%) who received dupilumab plus TCS. Of these, 103 (91%) recovered by the end of the trial. Of the 11 patients with conjunctivitis who did not recover or dropped out of the trial, 3 were among the 110 patients who received 300 mg dupilumab q2w plus TCS (3%), and 8 were among the 315 who received 300 mg dupilumab qw plus TCS (3%).

“When I look at all of this data, I think that about 2% of people treated with dupilumab are going to get clinically very meaningful conjunctivitis that may be therapy limiting,” Dr. Zirwas concluded. “The vast majority of those cases appear to happen in the first 16 weeks. This is just not something we see in cases of patients treated with dupilumab treated for other reasons.”

Following his presentation, a meeting attendee asked Dr. Zirwas if conjunctivitis occurs more often in patients with facial dermatitis. “My perception is that it happens more often in people who have facial or eyelid dermatitis, but I’ve seen it in plenty of people who didn’t have any facial or eyelid dermatitis,” he said. “I have seen more conjunctivitis in people with more severe AD and more severe atopic comorbidities. That is anecdotal. The data that I have seen has been back and forth on this topic.”

Dr. Zirwas disclosed that he is a speaker and consultant for Sanofi, Regeneron, Leo, Lilly, Galderma, Pfizer, and AbbVie. Several of his co-authors work for Regeneron Pharmaceuticals.

How can we improve the detection, assessment, and treatment of female sexual dysfunction?

Charlotte Methorst, MD, a urologist from Paris, and Carol Burté, MD, a sexologist and andrologist from Nice, dealt with these themes during a session at the French Urology Association’s 2023 conference, emphasizing the need for doctors to be involved in female sexual health.

“There’s currently a real disconnect; doctors talk very little about sexual health, yet it’s a topic that patients would really like to talk about. And this is even truer for women,” said Dr. Methorst.

“We need to spot sexual dysfunction because the topic is rarely broached spontaneously by female patients (19%) and even less so by healthcare workers (9%). Nowadays, it’s a very common problem (40%). Sexual dysfunction affects quality of life and a couple’s relationship. It also can reveal other conditions,” added Dr. Burté.
 

Spot and Assess

In terms of detecting the condition, the reference tool is the self-assessed Female Sexual Function Index, which comprises 19 questions covering six areas of sexual dysfunction: Desire, subjective arousal, lubrication, orgasm, satisfaction, and pain or discomfort.

But it is also possible to use the Sexual Complaints Screener for Women that evaluates sexual health over the past 6 months, explains Dr. Burté. For example, the patient is asked if she has had a lack of or low interest in sex or sexual desire in the past 6 months and if this has been a problem. She is also asked if she has experienced any pain during or after sexual activity.

To understand the root cause of sexual dysfunction, clinicians need to investigate the patient’s sexual health and perform a medical assessment. It’s also essential to ask the patient about her previous sexual, medical, and psychological history and to evaluate the couple and contributory factors, such as stress, fatigue, etc. This approach is known as the biopsychosocial model.

Once the contributory factors have been determined, relevant information can be given to the patient about her specific sexual problem, and the most suitable therapeutic approaches can be discussed with her.
 

Which Treatment Pathway?

Some problems may be improved with simple advice and lifestyle changes, but sex therapy and medication are options in other cases, explained the two doctors. “Since the causes of sexual dysfunction in women are mostly multifactorial, an integrative approach is needed,” said Dr. Burté.

The two main types of therapy that might be proposed for sexual dysfunction are sex therapies with cognitive behavioral therapy (CBT) and certain medicines being used as first-line treatment.

Using CBT in sexology requires patients and therapists to look past prejudices, preconceived ideas, and dysfunctional patterns and learn new behavioral, cognitive, and attentional strategies in terms of sexual health, regardless of whether an individual or couple is being treated.
 

Which Medicines?

Vasoactive drugs such as phosphodiesterase 5 inhibitors and prostaglandin have produced disappointing results. Drugs that act on the central nervous system to stimulate sexual desire, such as bremelanotide and flibanserin, don’t have marketing authorization in France due to their “insufficient” risk-benefit ratio.

However, topical hormone treatments (such as estrogen and dehydroepiandrosterone) are often used, particularly for cases of recurrent cystitis, in postmenopausal women and to treat urinary incontinence. “These topical treatments are very effective and can really change the life of a woman who no longer has a sex life because she is in discomfort and simply has dryness of the vulva and vagina,” said Dr. Burté, who recommends prescribing creams, which are better tolerated than pessaries.

General hormone treatments, hormone replacement therapy (HRT), and tibolone are prescribed to postmenopausal women.

Another option not yet authorized in France is testosterone because sexual desire depends on this hormone. An international consensus (2019, 10 learned societies) and recommendations made by the International Society for the Study of Women’s Sexual Health advise treatment with testosterone in the postmenopausal period, with or without HRT. The dose prescribed is a 10th of the male dose administered subcutaneously (300 µ/d) once a woman›s blood testosterone level has been determined to make sure there is an actual deficiency and to restore her testosterone to near premenopausal levels.

Both doctors indicated that having the chance to work with other doctors as part of a network is essential, especially with a sexual health specialist, if necessary.

Dr. Burté reported no conflicts of interest regarding the content of this article. Dr. Methorst reported relationships with several pharmaceutical laboratories.

This article was translated from the Medscape French edition.

How can we improve the detection, assessment, and treatment of female sexual dysfunction?

Charlotte Methorst, MD, a urologist from Paris, and Carol Burté, MD, a sexologist and andrologist from Nice, dealt with these themes during a session at the French Urology Association’s 2023 conference, emphasizing the need for doctors to be involved in female sexual health.

“There’s currently a real disconnect; doctors talk very little about sexual health, yet it’s a topic that patients would really like to talk about. And this is even truer for women,” said Dr. Methorst.

“We need to spot sexual dysfunction because the topic is rarely broached spontaneously by female patients (19%) and even less so by healthcare workers (9%). Nowadays, it’s a very common problem (40%). Sexual dysfunction affects quality of life and a couple’s relationship. It also can reveal other conditions,” added Dr. Burté.
 

Spot and Assess

In terms of detecting the condition, the reference tool is the self-assessed Female Sexual Function Index, which comprises 19 questions covering six areas of sexual dysfunction: Desire, subjective arousal, lubrication, orgasm, satisfaction, and pain or discomfort.

But it is also possible to use the Sexual Complaints Screener for Women that evaluates sexual health over the past 6 months, explains Dr. Burté. For example, the patient is asked if she has had a lack of or low interest in sex or sexual desire in the past 6 months and if this has been a problem. She is also asked if she has experienced any pain during or after sexual activity.

To understand the root cause of sexual dysfunction, clinicians need to investigate the patient’s sexual health and perform a medical assessment. It’s also essential to ask the patient about her previous sexual, medical, and psychological history and to evaluate the couple and contributory factors, such as stress, fatigue, etc. This approach is known as the biopsychosocial model.

Once the contributory factors have been determined, relevant information can be given to the patient about her specific sexual problem, and the most suitable therapeutic approaches can be discussed with her.
 

Which Treatment Pathway?

Some problems may be improved with simple advice and lifestyle changes, but sex therapy and medication are options in other cases, explained the two doctors. “Since the causes of sexual dysfunction in women are mostly multifactorial, an integrative approach is needed,” said Dr. Burté.

The two main types of therapy that might be proposed for sexual dysfunction are sex therapies with cognitive behavioral therapy (CBT) and certain medicines being used as first-line treatment.

Using CBT in sexology requires patients and therapists to look past prejudices, preconceived ideas, and dysfunctional patterns and learn new behavioral, cognitive, and attentional strategies in terms of sexual health, regardless of whether an individual or couple is being treated.
 

Which Medicines?

Vasoactive drugs such as phosphodiesterase 5 inhibitors and prostaglandin have produced disappointing results. Drugs that act on the central nervous system to stimulate sexual desire, such as bremelanotide and flibanserin, don’t have marketing authorization in France due to their “insufficient” risk-benefit ratio.

However, topical hormone treatments (such as estrogen and dehydroepiandrosterone) are often used, particularly for cases of recurrent cystitis, in postmenopausal women and to treat urinary incontinence. “These topical treatments are very effective and can really change the life of a woman who no longer has a sex life because she is in discomfort and simply has dryness of the vulva and vagina,” said Dr. Burté, who recommends prescribing creams, which are better tolerated than pessaries.

General hormone treatments, hormone replacement therapy (HRT), and tibolone are prescribed to postmenopausal women.

Another option not yet authorized in France is testosterone because sexual desire depends on this hormone. An international consensus (2019, 10 learned societies) and recommendations made by the International Society for the Study of Women’s Sexual Health advise treatment with testosterone in the postmenopausal period, with or without HRT. The dose prescribed is a 10th of the male dose administered subcutaneously (300 µ/d) once a woman›s blood testosterone level has been determined to make sure there is an actual deficiency and to restore her testosterone to near premenopausal levels.

Both doctors indicated that having the chance to work with other doctors as part of a network is essential, especially with a sexual health specialist, if necessary.

Dr. Burté reported no conflicts of interest regarding the content of this article. Dr. Methorst reported relationships with several pharmaceutical laboratories.

This article was translated from the Medscape French edition.

How can we improve the detection, assessment, and treatment of female sexual dysfunction?

Charlotte Methorst, MD, a urologist from Paris, and Carol Burté, MD, a sexologist and andrologist from Nice, dealt with these themes during a session at the French Urology Association’s 2023 conference, emphasizing the need for doctors to be involved in female sexual health.

“There’s currently a real disconnect; doctors talk very little about sexual health, yet it’s a topic that patients would really like to talk about. And this is even truer for women,” said Dr. Methorst.

“We need to spot sexual dysfunction because the topic is rarely broached spontaneously by female patients (19%) and even less so by healthcare workers (9%). Nowadays, it’s a very common problem (40%). Sexual dysfunction affects quality of life and a couple’s relationship. It also can reveal other conditions,” added Dr. Burté.
 

Spot and Assess

In terms of detecting the condition, the reference tool is the self-assessed Female Sexual Function Index, which comprises 19 questions covering six areas of sexual dysfunction: Desire, subjective arousal, lubrication, orgasm, satisfaction, and pain or discomfort.

But it is also possible to use the Sexual Complaints Screener for Women that evaluates sexual health over the past 6 months, explains Dr. Burté. For example, the patient is asked if she has had a lack of or low interest in sex or sexual desire in the past 6 months and if this has been a problem. She is also asked if she has experienced any pain during or after sexual activity.

To understand the root cause of sexual dysfunction, clinicians need to investigate the patient’s sexual health and perform a medical assessment. It’s also essential to ask the patient about her previous sexual, medical, and psychological history and to evaluate the couple and contributory factors, such as stress, fatigue, etc. This approach is known as the biopsychosocial model.

Once the contributory factors have been determined, relevant information can be given to the patient about her specific sexual problem, and the most suitable therapeutic approaches can be discussed with her.
 

Which Treatment Pathway?

Some problems may be improved with simple advice and lifestyle changes, but sex therapy and medication are options in other cases, explained the two doctors. “Since the causes of sexual dysfunction in women are mostly multifactorial, an integrative approach is needed,” said Dr. Burté.

The two main types of therapy that might be proposed for sexual dysfunction are sex therapies with cognitive behavioral therapy (CBT) and certain medicines being used as first-line treatment.

Using CBT in sexology requires patients and therapists to look past prejudices, preconceived ideas, and dysfunctional patterns and learn new behavioral, cognitive, and attentional strategies in terms of sexual health, regardless of whether an individual or couple is being treated.
 

Which Medicines?

Vasoactive drugs such as phosphodiesterase 5 inhibitors and prostaglandin have produced disappointing results. Drugs that act on the central nervous system to stimulate sexual desire, such as bremelanotide and flibanserin, don’t have marketing authorization in France due to their “insufficient” risk-benefit ratio.

However, topical hormone treatments (such as estrogen and dehydroepiandrosterone) are often used, particularly for cases of recurrent cystitis, in postmenopausal women and to treat urinary incontinence. “These topical treatments are very effective and can really change the life of a woman who no longer has a sex life because she is in discomfort and simply has dryness of the vulva and vagina,” said Dr. Burté, who recommends prescribing creams, which are better tolerated than pessaries.

General hormone treatments, hormone replacement therapy (HRT), and tibolone are prescribed to postmenopausal women.

Another option not yet authorized in France is testosterone because sexual desire depends on this hormone. An international consensus (2019, 10 learned societies) and recommendations made by the International Society for the Study of Women’s Sexual Health advise treatment with testosterone in the postmenopausal period, with or without HRT. The dose prescribed is a 10th of the male dose administered subcutaneously (300 µ/d) once a woman›s blood testosterone level has been determined to make sure there is an actual deficiency and to restore her testosterone to near premenopausal levels.

Both doctors indicated that having the chance to work with other doctors as part of a network is essential, especially with a sexual health specialist, if necessary.

Dr. Burté reported no conflicts of interest regarding the content of this article. Dr. Methorst reported relationships with several pharmaceutical laboratories.

This article was translated from the Medscape French edition.