There’s an unexpected treatment for hot flashes and other menopause symptoms that’s getting more popular: clinical hypnosis. 

Hypnosis is a state of highly focused attention that works through disassociating, or putting aside your conscious awareness of things that would ordinarily be in your consciousness, said David Spiegel, MD, a psychiatrist with Stanford Medical School in Califonrnia. 

“It increases your cognitive flexibility – a way to approach an old problem from a new point of view and just let go of your older ways of thinking about it,” he said. 

Usually around age 50, women have menopause, which is the end of their menstrual cycles. Estrogen levels drop, and hot flashes can happen 12-15 times per day, said Gary Elkins, PhD, a psychology and neuroscience professor at Baylor University in Waco, Texas.

Both clinical hypnosis and cognitive-behavioral therapy, a common form of talk therapy, have been shown to work as non-hormonal treatments for hot flashes, particularly for women who are unable to take hormones for health reasons, such as having a history with an estrogen-sensitive cancer (like breast cancer), according to research published by the Menopause Society in 2023. 

A new review presented at the 2024 annual meeting of the Menopause Society in Chicago analyzed 23 studies from 1996 to 2022 and compared how well clinical hypnosis and cognitive behavioral therapy worked as treatments for hot flashes and other menopause symptoms. Researchers found that clinical hypnosis is better at helping make hot flashes less frequent and less intense, even reducing symptoms by 60%. Findings on cognitive-behavioral therapy, on the other hand, showed only slight hot flash reduction, though it helped reduce daily stress linked with hot flashes. 

Hypnosis can address the “perfect storm” of mental and physical issues that come with menopause symptoms, explained Dr. Spiegel, who created a popular self-hypnosis app called Reveri. “You’re having a reduction in your levels of estrogen and progesterone, but it’s also a reminder that you’re going into a different stage of life where you’re no longer fertile, you’re getting older,” he said. “[With hypnosis], you can disassociate pain and your awareness of things that ordinarily would impede your consciousness and make you miserable.”

A hypnosis session can help you separate psychological discomfort from physical discomfort, Dr. Spiegel said. “Typically, people in hypnosis dealing with menopause will imagine they’re floating in a lake, feeling cool, tingling, numbness. They can literally change how hot they feel. They can change the hot flash and imagine themselves cool, comfortable. If they’re worried about something, picture it on an imaginary screen. Just picture it, but not feel it.”
 

Hypnosis for Sleep

Hot flashes that happen at night are called night sweats and can hinder your sleep. Hypnotherapy can help reduce both hot flashes and night sweats, to the point where sleep is not interrupted, Dr. Elkins said. “While sleep improves with the hypnotherapy intervention, it also involves general relaxation,” said Dr. Elkins, who is the director of the Mind-Body Medicine Research Laboratory at Baylor University. “As women practice self-hypnosis at night, they’re entering a more calm and relaxed state, which also may facilitate good sleep or improve sleep duration and sleep quality.”

Our subconscious mind influences our sleep patterns largely through experiences vs. words or thoughts, according to Emilie Leyes, a certified hypnotherapist based in Philadelphia. This explains why simply reciting the words “I’m relaxed,” when you’re stressed, is often less effective than a few deep breaths or a warm hug from a family member or friend, said Ms. Leyes, who hosts a brain-training podcast for mindset transformation called How to Like Your Life.

“In a similar way, hypnosis, which directly accesses the subconscious, allows us to offer our minds new, powerful experiences to reduce our stress, improve our mood, and increase our access to positive emotions,” she said. “Repeatedly exposing ourselves to these positive experiences in our minds can increase our capacity to feel good, and impact how we feel in our everyday lives.”
 

Your First Hypnosis Session

A hypnosis session always begins with deep relaxation, which can help your mind and body grow accustomed to what it’s like to feel calm, said Ms. Leyes. “By giving the brain and body experiences of safety, relaxation, and inner peace, we can more easily let go of our stressful thoughts of the day and drift off to sleep with ease at night.”

You will often start by sitting or lying in a comfortable position, and then the hypnotic induction begins with a focus of attention, according to Dr. Elkins. The person concentrates, with their eyelids closed, and then are given suggestions for deepening their relaxed state. “Usually that’s a safe, pleasant place, such as walking through the mountains or being near a beach,” he said. “And within that, suggestions are given that target the mechanism that underlies the symptoms [such as hot flashes].”

Dr. Spiegel usually starts off with a neutral test that can help measure how hypnotizable a person is on a 0-to-10 scale. For example, instructing the client to imagine that their hand is floating in the air. If they pull their hand down and it floats back up, the client finds they can “actually dissociate the psychological from the physiological aspects of their experience – their left hand feels different from their right hand,” Dr. Spiegel said. “I use that as an example for them to say, ‘look how you can change how your body feels. Now, let’s use it to help you with your anxiety with your menopausal symptoms.’ ”

A version of this article appeared on WebMD.com.

There’s an unexpected treatment for hot flashes and other menopause symptoms that’s getting more popular: clinical hypnosis. 

Hypnosis is a state of highly focused attention that works through disassociating, or putting aside your conscious awareness of things that would ordinarily be in your consciousness, said David Spiegel, MD, a psychiatrist with Stanford Medical School in Califonrnia. 

“It increases your cognitive flexibility – a way to approach an old problem from a new point of view and just let go of your older ways of thinking about it,” he said. 

Usually around age 50, women have menopause, which is the end of their menstrual cycles. Estrogen levels drop, and hot flashes can happen 12-15 times per day, said Gary Elkins, PhD, a psychology and neuroscience professor at Baylor University in Waco, Texas.

Both clinical hypnosis and cognitive-behavioral therapy, a common form of talk therapy, have been shown to work as non-hormonal treatments for hot flashes, particularly for women who are unable to take hormones for health reasons, such as having a history with an estrogen-sensitive cancer (like breast cancer), according to research published by the Menopause Society in 2023. 

A new review presented at the 2024 annual meeting of the Menopause Society in Chicago analyzed 23 studies from 1996 to 2022 and compared how well clinical hypnosis and cognitive behavioral therapy worked as treatments for hot flashes and other menopause symptoms. Researchers found that clinical hypnosis is better at helping make hot flashes less frequent and less intense, even reducing symptoms by 60%. Findings on cognitive-behavioral therapy, on the other hand, showed only slight hot flash reduction, though it helped reduce daily stress linked with hot flashes. 

Hypnosis can address the “perfect storm” of mental and physical issues that come with menopause symptoms, explained Dr. Spiegel, who created a popular self-hypnosis app called Reveri. “You’re having a reduction in your levels of estrogen and progesterone, but it’s also a reminder that you’re going into a different stage of life where you’re no longer fertile, you’re getting older,” he said. “[With hypnosis], you can disassociate pain and your awareness of things that ordinarily would impede your consciousness and make you miserable.”

A hypnosis session can help you separate psychological discomfort from physical discomfort, Dr. Spiegel said. “Typically, people in hypnosis dealing with menopause will imagine they’re floating in a lake, feeling cool, tingling, numbness. They can literally change how hot they feel. They can change the hot flash and imagine themselves cool, comfortable. If they’re worried about something, picture it on an imaginary screen. Just picture it, but not feel it.”
 

Hypnosis for Sleep

Hot flashes that happen at night are called night sweats and can hinder your sleep. Hypnotherapy can help reduce both hot flashes and night sweats, to the point where sleep is not interrupted, Dr. Elkins said. “While sleep improves with the hypnotherapy intervention, it also involves general relaxation,” said Dr. Elkins, who is the director of the Mind-Body Medicine Research Laboratory at Baylor University. “As women practice self-hypnosis at night, they’re entering a more calm and relaxed state, which also may facilitate good sleep or improve sleep duration and sleep quality.”

Our subconscious mind influences our sleep patterns largely through experiences vs. words or thoughts, according to Emilie Leyes, a certified hypnotherapist based in Philadelphia. This explains why simply reciting the words “I’m relaxed,” when you’re stressed, is often less effective than a few deep breaths or a warm hug from a family member or friend, said Ms. Leyes, who hosts a brain-training podcast for mindset transformation called How to Like Your Life.

“In a similar way, hypnosis, which directly accesses the subconscious, allows us to offer our minds new, powerful experiences to reduce our stress, improve our mood, and increase our access to positive emotions,” she said. “Repeatedly exposing ourselves to these positive experiences in our minds can increase our capacity to feel good, and impact how we feel in our everyday lives.”
 

Your First Hypnosis Session

A hypnosis session always begins with deep relaxation, which can help your mind and body grow accustomed to what it’s like to feel calm, said Ms. Leyes. “By giving the brain and body experiences of safety, relaxation, and inner peace, we can more easily let go of our stressful thoughts of the day and drift off to sleep with ease at night.”

You will often start by sitting or lying in a comfortable position, and then the hypnotic induction begins with a focus of attention, according to Dr. Elkins. The person concentrates, with their eyelids closed, and then are given suggestions for deepening their relaxed state. “Usually that’s a safe, pleasant place, such as walking through the mountains or being near a beach,” he said. “And within that, suggestions are given that target the mechanism that underlies the symptoms [such as hot flashes].”

Dr. Spiegel usually starts off with a neutral test that can help measure how hypnotizable a person is on a 0-to-10 scale. For example, instructing the client to imagine that their hand is floating in the air. If they pull their hand down and it floats back up, the client finds they can “actually dissociate the psychological from the physiological aspects of their experience – their left hand feels different from their right hand,” Dr. Spiegel said. “I use that as an example for them to say, ‘look how you can change how your body feels. Now, let’s use it to help you with your anxiety with your menopausal symptoms.’ ”

A version of this article appeared on WebMD.com.

There’s an unexpected treatment for hot flashes and other menopause symptoms that’s getting more popular: clinical hypnosis. 

Hypnosis is a state of highly focused attention that works through disassociating, or putting aside your conscious awareness of things that would ordinarily be in your consciousness, said David Spiegel, MD, a psychiatrist with Stanford Medical School in Califonrnia. 

“It increases your cognitive flexibility – a way to approach an old problem from a new point of view and just let go of your older ways of thinking about it,” he said. 

Usually around age 50, women have menopause, which is the end of their menstrual cycles. Estrogen levels drop, and hot flashes can happen 12-15 times per day, said Gary Elkins, PhD, a psychology and neuroscience professor at Baylor University in Waco, Texas.

Both clinical hypnosis and cognitive-behavioral therapy, a common form of talk therapy, have been shown to work as non-hormonal treatments for hot flashes, particularly for women who are unable to take hormones for health reasons, such as having a history with an estrogen-sensitive cancer (like breast cancer), according to research published by the Menopause Society in 2023. 

A new review presented at the 2024 annual meeting of the Menopause Society in Chicago analyzed 23 studies from 1996 to 2022 and compared how well clinical hypnosis and cognitive behavioral therapy worked as treatments for hot flashes and other menopause symptoms. Researchers found that clinical hypnosis is better at helping make hot flashes less frequent and less intense, even reducing symptoms by 60%. Findings on cognitive-behavioral therapy, on the other hand, showed only slight hot flash reduction, though it helped reduce daily stress linked with hot flashes. 

Hypnosis can address the “perfect storm” of mental and physical issues that come with menopause symptoms, explained Dr. Spiegel, who created a popular self-hypnosis app called Reveri. “You’re having a reduction in your levels of estrogen and progesterone, but it’s also a reminder that you’re going into a different stage of life where you’re no longer fertile, you’re getting older,” he said. “[With hypnosis], you can disassociate pain and your awareness of things that ordinarily would impede your consciousness and make you miserable.”

A hypnosis session can help you separate psychological discomfort from physical discomfort, Dr. Spiegel said. “Typically, people in hypnosis dealing with menopause will imagine they’re floating in a lake, feeling cool, tingling, numbness. They can literally change how hot they feel. They can change the hot flash and imagine themselves cool, comfortable. If they’re worried about something, picture it on an imaginary screen. Just picture it, but not feel it.”
 

Hypnosis for Sleep

Hot flashes that happen at night are called night sweats and can hinder your sleep. Hypnotherapy can help reduce both hot flashes and night sweats, to the point where sleep is not interrupted, Dr. Elkins said. “While sleep improves with the hypnotherapy intervention, it also involves general relaxation,” said Dr. Elkins, who is the director of the Mind-Body Medicine Research Laboratory at Baylor University. “As women practice self-hypnosis at night, they’re entering a more calm and relaxed state, which also may facilitate good sleep or improve sleep duration and sleep quality.”

Our subconscious mind influences our sleep patterns largely through experiences vs. words or thoughts, according to Emilie Leyes, a certified hypnotherapist based in Philadelphia. This explains why simply reciting the words “I’m relaxed,” when you’re stressed, is often less effective than a few deep breaths or a warm hug from a family member or friend, said Ms. Leyes, who hosts a brain-training podcast for mindset transformation called How to Like Your Life.

“In a similar way, hypnosis, which directly accesses the subconscious, allows us to offer our minds new, powerful experiences to reduce our stress, improve our mood, and increase our access to positive emotions,” she said. “Repeatedly exposing ourselves to these positive experiences in our minds can increase our capacity to feel good, and impact how we feel in our everyday lives.”
 

Your First Hypnosis Session

A hypnosis session always begins with deep relaxation, which can help your mind and body grow accustomed to what it’s like to feel calm, said Ms. Leyes. “By giving the brain and body experiences of safety, relaxation, and inner peace, we can more easily let go of our stressful thoughts of the day and drift off to sleep with ease at night.”

You will often start by sitting or lying in a comfortable position, and then the hypnotic induction begins with a focus of attention, according to Dr. Elkins. The person concentrates, with their eyelids closed, and then are given suggestions for deepening their relaxed state. “Usually that’s a safe, pleasant place, such as walking through the mountains or being near a beach,” he said. “And within that, suggestions are given that target the mechanism that underlies the symptoms [such as hot flashes].”

Dr. Spiegel usually starts off with a neutral test that can help measure how hypnotizable a person is on a 0-to-10 scale. For example, instructing the client to imagine that their hand is floating in the air. If they pull their hand down and it floats back up, the client finds they can “actually dissociate the psychological from the physiological aspects of their experience – their left hand feels different from their right hand,” Dr. Spiegel said. “I use that as an example for them to say, ‘look how you can change how your body feels. Now, let’s use it to help you with your anxiety with your menopausal symptoms.’ ”

A version of this article appeared on WebMD.com.

TOPLINE:

Metabolic/bariatric surgery (MBS) reduces thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) levels, and thyroid hormone resistance indices in patients with obesity, changes strongly correlated with improvement in body composition.

METHODOLOGY:

• Recent studies have linked obesity with increased levels of TSH and thyroid hormones; however, the role that body fat distribution plays in this association remains unclear.
• This retrospective observational study evaluated the effects of MBS on thyroid hormone levels and thyroid hormone resistance in euthyroid individuals with obesity, focusing on the correlation with changes in body composition.
• Researchers included 470 patients with obesity (mean age, 33.4 years; mean body mass index [BMI], 37.9; 63.2% women) and 118 control individuals without obesity (mean BMI, 21.8), who had had normal levels of TSH, fT3, and free thyroxine.
• Among the patients with obesity, 125 underwent MBS and had thyroid tests both before and ≥ 3 months after surgery.
• Data on body composition and thyroid function were collected, and correlations between baseline and changes in thyroid function and body composition were assessed.

TAKEAWAY:

• Individuals with obesity had higher baseline TSH and fT3 levels (P < .001) and thyroid feedback quantile-based index (TFQI; P = .047) than those without obesity, with the values decreasing after MBS (all P < .001).
• Among individuals with obesity, preoperative TSH was positively correlated with the visceral fat area (VFA; P = .019) and body fat percentage (P = .013) and negatively correlated with skeletal muscle mass percentage (P = .024)
• The decrease in TSH post-surgery positively correlated with decreased VFA (P = .021) and decreased body fat percentage (P = .031).
• Decrease in VFA and body fat percentage after MBS was also associated with improved central thyroid hormone resistance indicated by TFQI.

IN PRACTICE:

“The relationship between obesity and [thyroid hormone] is bidirectional, indicating that addressing underlying thyroid disturbance could potentially benefit weight loss and metabolism,” the authors wrote.

SOURCE:

This study was led by Yu Yan, MD, Department of Pancreatic and Metabolic Surgery, Medical School of Southeast University, Nanjing Drum Tower Hospital, Nanjing, China, and published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The retrospective nature of this study limited the ability to definitively attribute changes in thyroid function and thyroid hormone resistance to changes in body composition. The relatively short duration of the study and the exclusion of individuals taking medications affecting thyroid function may also limit the generalizability of the findings.

DISCLOSURES:

This study was supported by the Fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. The authors declared no potential conflicts of interest.

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

TOPLINE:

Metabolic/bariatric surgery (MBS) reduces thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) levels, and thyroid hormone resistance indices in patients with obesity, changes strongly correlated with improvement in body composition.

METHODOLOGY:

• Recent studies have linked obesity with increased levels of TSH and thyroid hormones; however, the role that body fat distribution plays in this association remains unclear.
• This retrospective observational study evaluated the effects of MBS on thyroid hormone levels and thyroid hormone resistance in euthyroid individuals with obesity, focusing on the correlation with changes in body composition.
• Researchers included 470 patients with obesity (mean age, 33.4 years; mean body mass index [BMI], 37.9; 63.2% women) and 118 control individuals without obesity (mean BMI, 21.8), who had had normal levels of TSH, fT3, and free thyroxine.
• Among the patients with obesity, 125 underwent MBS and had thyroid tests both before and ≥ 3 months after surgery.
• Data on body composition and thyroid function were collected, and correlations between baseline and changes in thyroid function and body composition were assessed.

TAKEAWAY:

• Individuals with obesity had higher baseline TSH and fT3 levels (P < .001) and thyroid feedback quantile-based index (TFQI; P = .047) than those without obesity, with the values decreasing after MBS (all P < .001).
• Among individuals with obesity, preoperative TSH was positively correlated with the visceral fat area (VFA; P = .019) and body fat percentage (P = .013) and negatively correlated with skeletal muscle mass percentage (P = .024)
• The decrease in TSH post-surgery positively correlated with decreased VFA (P = .021) and decreased body fat percentage (P = .031).
• Decrease in VFA and body fat percentage after MBS was also associated with improved central thyroid hormone resistance indicated by TFQI.

IN PRACTICE:

“The relationship between obesity and [thyroid hormone] is bidirectional, indicating that addressing underlying thyroid disturbance could potentially benefit weight loss and metabolism,” the authors wrote.

SOURCE:

This study was led by Yu Yan, MD, Department of Pancreatic and Metabolic Surgery, Medical School of Southeast University, Nanjing Drum Tower Hospital, Nanjing, China, and published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The retrospective nature of this study limited the ability to definitively attribute changes in thyroid function and thyroid hormone resistance to changes in body composition. The relatively short duration of the study and the exclusion of individuals taking medications affecting thyroid function may also limit the generalizability of the findings.

DISCLOSURES:

This study was supported by the Fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. The authors declared no potential conflicts of interest.

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

TOPLINE:

Metabolic/bariatric surgery (MBS) reduces thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) levels, and thyroid hormone resistance indices in patients with obesity, changes strongly correlated with improvement in body composition.

METHODOLOGY:

• Recent studies have linked obesity with increased levels of TSH and thyroid hormones; however, the role that body fat distribution plays in this association remains unclear.
• This retrospective observational study evaluated the effects of MBS on thyroid hormone levels and thyroid hormone resistance in euthyroid individuals with obesity, focusing on the correlation with changes in body composition.
• Researchers included 470 patients with obesity (mean age, 33.4 years; mean body mass index [BMI], 37.9; 63.2% women) and 118 control individuals without obesity (mean BMI, 21.8), who had had normal levels of TSH, fT3, and free thyroxine.
• Among the patients with obesity, 125 underwent MBS and had thyroid tests both before and ≥ 3 months after surgery.
• Data on body composition and thyroid function were collected, and correlations between baseline and changes in thyroid function and body composition were assessed.

TAKEAWAY:

• Individuals with obesity had higher baseline TSH and fT3 levels (P < .001) and thyroid feedback quantile-based index (TFQI; P = .047) than those without obesity, with the values decreasing after MBS (all P < .001).
• Among individuals with obesity, preoperative TSH was positively correlated with the visceral fat area (VFA; P = .019) and body fat percentage (P = .013) and negatively correlated with skeletal muscle mass percentage (P = .024)
• The decrease in TSH post-surgery positively correlated with decreased VFA (P = .021) and decreased body fat percentage (P = .031).
• Decrease in VFA and body fat percentage after MBS was also associated with improved central thyroid hormone resistance indicated by TFQI.

IN PRACTICE:

“The relationship between obesity and [thyroid hormone] is bidirectional, indicating that addressing underlying thyroid disturbance could potentially benefit weight loss and metabolism,” the authors wrote.

SOURCE:

This study was led by Yu Yan, MD, Department of Pancreatic and Metabolic Surgery, Medical School of Southeast University, Nanjing Drum Tower Hospital, Nanjing, China, and published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The retrospective nature of this study limited the ability to definitively attribute changes in thyroid function and thyroid hormone resistance to changes in body composition. The relatively short duration of the study and the exclusion of individuals taking medications affecting thyroid function may also limit the generalizability of the findings.

DISCLOSURES:

This study was supported by the Fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. The authors declared no potential conflicts of interest.

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

MILAN — Psilocybin leads to a better overall outcome in the treatment of moderate to severe major depressive disorder (MDD) than the selective serotonin reuptake inhibitor (SSRI) escitalopram, results of the first long-term comparison of the two treatments suggest.

“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression,” study investigator Tommaso Barba, PhD candidate at Imperial College London in England, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work, and social functioning.”

Findings from the 6-month follow-up study of a phase 2 double-blind, randomized, controlled trial were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and published simultaneously in The Lancet eClinicalMedicine

Addressing a Treatment ‘Mismatch’

The findings are important because they address “a mismatch” between what psychiatrists and what patients think is important, Mr. Barba said in an interview.

“Psychiatrists really focus on negative symptoms of depression. So, if you are not sad anymore, if your sleep or appetite is not impaired, they think you’re better. But if you look at what patients define as important, they say it’s the degree in which their life is meaningful, in which they can connect with people around them, in which they can function in everyday life,” Mr. Barba said.

“The study suggests that psilocybin therapy might be a more holistic treatment option for depression,” added co–first author David Erritzoe, MD, PhD, clinical director and deputy head of the Centre for Psychedelic Research, Imperial College London. “This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment.”

The initial single-center study included 59 adults with MDD (mean age, 41 years) who were randomized to receive either psilocybin or escitalopram over a 6-week period. The psilocybin arm (n = 30) received two 25-mg oral doses of psilocybin therapy (PT), and the escitalopram arm (n = 29) received 10-20 mg of daily escitalopram plus two (placebo-like) 1-mg doses of psilocybin (ET). Both groups received psychological support.

Based on change in depression scores on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, the initial study results suggested noninferiority between the two treatments in terms of depressive symptoms (primary outcome), but superiority of PT for secondary outcomes including “well-being, anhedonia, social functioning, sexual functioning, and related variables, with fewer side effects compared to ET,” the researchers noted.

The new 6-month follow-up findings, with monthly questionnaires and no additional study treatment or psychiatric treatment restrictions, measured the QIDS-SR-16, plus Work and Social Adjustment Scale (WSAS), Meaning in Life Questionnaire, Flourishing Scale (FS), and Watts Connectedness Scale (WCS).

Again, both groups maintained similar results on the QIDS-SR-16, with slightly greater reductions in depressive symptoms for PT in the first month (positive false discovery rate [pFDR] = 0.021), but not thereafter.

At both 3 and 6 months, there were greater improvements in WSAS scores for the PT group (pFDR < 0.001 and pFDR = 0.01, respectively), and also greater improvements in meaning in life across all follow-up timepoints (pFDR < 0.001).

There was also greater improvement in the PT group regarding WCS at both 3 and 6 months (pFDR = 0.02, and pFDR = 0.04) and comparable FS improvements for both groups across all timepoints.

Confounding follow-up interventions may have muddied the results, with 30.7% of PT participants and 43.5% of ET participants receiving an additional intervention during this period.

The researchers conclude that while a short course of SSRIs combined with intensive therapeutic support (around 20 hours) “might be enough to induce sustained antidepressant effects,” patients treated with psilocybin showed greater improvements in general functioning, connectedness, and meaning in life.

Although not reassessed in the follow-up, the initial study showed that adverse events, particularly sexual functioning, favored psilocybin, said Mr. Barba. “The two treatments seemed to go in opposite directions with psilocybin seeming to improve it and the antidepressant to suppress it. Other side effects associated with psilocybin were less diverse — mainly headaches at the end of the day — but with escitalopram they were way more diverse and more impairing.”

Although many therapists may be unfamiliar with psilocybin-assisted psychotherapy, “it’s not a difficult skill to master. It might require some specialization, but I think if you’re a good psychotherapist, you can learn how to implement psilocybin into your practice,” he said.

“Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to ‘let go’, or breathing exercises. The important part is the integration work that comes afterwards,” Mr. Barba added.

He said he envisions a therapy program that involves “psychiatrists working together with psychotherapists. The psychotherapists would be more in charge of the active guiding, and the psychiatrist would do the prescribing, with the follow-up psychological support on Zoom.”

He added a word of caution for therapists that “psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this.”
 

A New Treatment Paradigm?

In a comment, Johan Lundberg, MD, PhD, adjunct professor of psychiatry at the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, said the study addresses a key outstanding question about the long-term effects of one or two doses of psilocybin.

“It’s a 6-month follow-up of a short treatment intervention, so in that sense, it’s of high interest. It has been talked about that psilocybin might have a long-term effect, but this is the first study that has followed this for a longer term.”

But Dr. Lundberg also pointed out that one shortcoming of the study is the diversity of treatments following the intervention.

“They didn’t have control over whether patients received other treatments or when they started. So, that is a key concern. But they transparently reported that, and we do know there was a difference in reported ability to perform activities of daily life, and that is important.”

He added that if psilocybin is eventually approved, it would likely come with an education package for providers — “which is already the case with other treatments like ECT [electroconvulsive therapy] or TMS [transcranial magnetic stimulation] — you have to learn how to do it.”

James Rucker, MD, PhD, psychiatrist and senior clinical lecturer at King’s College London, who was not involved in the research, also noted that they have tended to attribute differences observed in this study to comparative differences between the drugs themselves.

However, he noted, it is also possible that the results reflect biased reporting between groups. This is more likely here because studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants, and study participants were unblinded during the long-term follow-up phase, so knew which condition they were allocated to.

“This said, the nature of depression varies hugely between individuals, and this calls for the development of a similarly varied suite of treatment paradigms. Psilocybin therapy is certainly a different paradigm of treatment to escitalopram. The observation of similar levels of effectiveness to antidepressants here is encouraging to see alongside the much larger trials of psilocybin currently underway here in the UK, Europe, and the US,” Dr. Rucker added.

This work was supported by The Alexander Mosley Charitable Trust and by the founding partners of Imperial College London’s Centre for Psychedelic Research.

Mr. Barba reported having received consulting fees from Adamo Bioscience. Both Dr. Lundberg and Dr. Rucker are involved in psilocybin research, but neither reported financial links.

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

MILAN — Psilocybin leads to a better overall outcome in the treatment of moderate to severe major depressive disorder (MDD) than the selective serotonin reuptake inhibitor (SSRI) escitalopram, results of the first long-term comparison of the two treatments suggest.

“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression,” study investigator Tommaso Barba, PhD candidate at Imperial College London in England, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work, and social functioning.”

Findings from the 6-month follow-up study of a phase 2 double-blind, randomized, controlled trial were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and published simultaneously in The Lancet eClinicalMedicine

Addressing a Treatment ‘Mismatch’

The findings are important because they address “a mismatch” between what psychiatrists and what patients think is important, Mr. Barba said in an interview.

“Psychiatrists really focus on negative symptoms of depression. So, if you are not sad anymore, if your sleep or appetite is not impaired, they think you’re better. But if you look at what patients define as important, they say it’s the degree in which their life is meaningful, in which they can connect with people around them, in which they can function in everyday life,” Mr. Barba said.

“The study suggests that psilocybin therapy might be a more holistic treatment option for depression,” added co–first author David Erritzoe, MD, PhD, clinical director and deputy head of the Centre for Psychedelic Research, Imperial College London. “This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment.”

The initial single-center study included 59 adults with MDD (mean age, 41 years) who were randomized to receive either psilocybin or escitalopram over a 6-week period. The psilocybin arm (n = 30) received two 25-mg oral doses of psilocybin therapy (PT), and the escitalopram arm (n = 29) received 10-20 mg of daily escitalopram plus two (placebo-like) 1-mg doses of psilocybin (ET). Both groups received psychological support.

Based on change in depression scores on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, the initial study results suggested noninferiority between the two treatments in terms of depressive symptoms (primary outcome), but superiority of PT for secondary outcomes including “well-being, anhedonia, social functioning, sexual functioning, and related variables, with fewer side effects compared to ET,” the researchers noted.

The new 6-month follow-up findings, with monthly questionnaires and no additional study treatment or psychiatric treatment restrictions, measured the QIDS-SR-16, plus Work and Social Adjustment Scale (WSAS), Meaning in Life Questionnaire, Flourishing Scale (FS), and Watts Connectedness Scale (WCS).

Again, both groups maintained similar results on the QIDS-SR-16, with slightly greater reductions in depressive symptoms for PT in the first month (positive false discovery rate [pFDR] = 0.021), but not thereafter.

At both 3 and 6 months, there were greater improvements in WSAS scores for the PT group (pFDR < 0.001 and pFDR = 0.01, respectively), and also greater improvements in meaning in life across all follow-up timepoints (pFDR < 0.001).

There was also greater improvement in the PT group regarding WCS at both 3 and 6 months (pFDR = 0.02, and pFDR = 0.04) and comparable FS improvements for both groups across all timepoints.

Confounding follow-up interventions may have muddied the results, with 30.7% of PT participants and 43.5% of ET participants receiving an additional intervention during this period.

The researchers conclude that while a short course of SSRIs combined with intensive therapeutic support (around 20 hours) “might be enough to induce sustained antidepressant effects,” patients treated with psilocybin showed greater improvements in general functioning, connectedness, and meaning in life.

Although not reassessed in the follow-up, the initial study showed that adverse events, particularly sexual functioning, favored psilocybin, said Mr. Barba. “The two treatments seemed to go in opposite directions with psilocybin seeming to improve it and the antidepressant to suppress it. Other side effects associated with psilocybin were less diverse — mainly headaches at the end of the day — but with escitalopram they were way more diverse and more impairing.”

Although many therapists may be unfamiliar with psilocybin-assisted psychotherapy, “it’s not a difficult skill to master. It might require some specialization, but I think if you’re a good psychotherapist, you can learn how to implement psilocybin into your practice,” he said.

“Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to ‘let go’, or breathing exercises. The important part is the integration work that comes afterwards,” Mr. Barba added.

He said he envisions a therapy program that involves “psychiatrists working together with psychotherapists. The psychotherapists would be more in charge of the active guiding, and the psychiatrist would do the prescribing, with the follow-up psychological support on Zoom.”

He added a word of caution for therapists that “psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this.”
 

A New Treatment Paradigm?

In a comment, Johan Lundberg, MD, PhD, adjunct professor of psychiatry at the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, said the study addresses a key outstanding question about the long-term effects of one or two doses of psilocybin.

“It’s a 6-month follow-up of a short treatment intervention, so in that sense, it’s of high interest. It has been talked about that psilocybin might have a long-term effect, but this is the first study that has followed this for a longer term.”

But Dr. Lundberg also pointed out that one shortcoming of the study is the diversity of treatments following the intervention.

“They didn’t have control over whether patients received other treatments or when they started. So, that is a key concern. But they transparently reported that, and we do know there was a difference in reported ability to perform activities of daily life, and that is important.”

He added that if psilocybin is eventually approved, it would likely come with an education package for providers — “which is already the case with other treatments like ECT [electroconvulsive therapy] or TMS [transcranial magnetic stimulation] — you have to learn how to do it.”

James Rucker, MD, PhD, psychiatrist and senior clinical lecturer at King’s College London, who was not involved in the research, also noted that they have tended to attribute differences observed in this study to comparative differences between the drugs themselves.

However, he noted, it is also possible that the results reflect biased reporting between groups. This is more likely here because studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants, and study participants were unblinded during the long-term follow-up phase, so knew which condition they were allocated to.

“This said, the nature of depression varies hugely between individuals, and this calls for the development of a similarly varied suite of treatment paradigms. Psilocybin therapy is certainly a different paradigm of treatment to escitalopram. The observation of similar levels of effectiveness to antidepressants here is encouraging to see alongside the much larger trials of psilocybin currently underway here in the UK, Europe, and the US,” Dr. Rucker added.

This work was supported by The Alexander Mosley Charitable Trust and by the founding partners of Imperial College London’s Centre for Psychedelic Research.

Mr. Barba reported having received consulting fees from Adamo Bioscience. Both Dr. Lundberg and Dr. Rucker are involved in psilocybin research, but neither reported financial links.

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

MILAN — Psilocybin leads to a better overall outcome in the treatment of moderate to severe major depressive disorder (MDD) than the selective serotonin reuptake inhibitor (SSRI) escitalopram, results of the first long-term comparison of the two treatments suggest.

“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression,” study investigator Tommaso Barba, PhD candidate at Imperial College London in England, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work, and social functioning.”

Findings from the 6-month follow-up study of a phase 2 double-blind, randomized, controlled trial were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and published simultaneously in The Lancet eClinicalMedicine

Addressing a Treatment ‘Mismatch’

The findings are important because they address “a mismatch” between what psychiatrists and what patients think is important, Mr. Barba said in an interview.

“Psychiatrists really focus on negative symptoms of depression. So, if you are not sad anymore, if your sleep or appetite is not impaired, they think you’re better. But if you look at what patients define as important, they say it’s the degree in which their life is meaningful, in which they can connect with people around them, in which they can function in everyday life,” Mr. Barba said.

“The study suggests that psilocybin therapy might be a more holistic treatment option for depression,” added co–first author David Erritzoe, MD, PhD, clinical director and deputy head of the Centre for Psychedelic Research, Imperial College London. “This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment.”

The initial single-center study included 59 adults with MDD (mean age, 41 years) who were randomized to receive either psilocybin or escitalopram over a 6-week period. The psilocybin arm (n = 30) received two 25-mg oral doses of psilocybin therapy (PT), and the escitalopram arm (n = 29) received 10-20 mg of daily escitalopram plus two (placebo-like) 1-mg doses of psilocybin (ET). Both groups received psychological support.

Based on change in depression scores on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, the initial study results suggested noninferiority between the two treatments in terms of depressive symptoms (primary outcome), but superiority of PT for secondary outcomes including “well-being, anhedonia, social functioning, sexual functioning, and related variables, with fewer side effects compared to ET,” the researchers noted.

The new 6-month follow-up findings, with monthly questionnaires and no additional study treatment or psychiatric treatment restrictions, measured the QIDS-SR-16, plus Work and Social Adjustment Scale (WSAS), Meaning in Life Questionnaire, Flourishing Scale (FS), and Watts Connectedness Scale (WCS).

Again, both groups maintained similar results on the QIDS-SR-16, with slightly greater reductions in depressive symptoms for PT in the first month (positive false discovery rate [pFDR] = 0.021), but not thereafter.

At both 3 and 6 months, there were greater improvements in WSAS scores for the PT group (pFDR < 0.001 and pFDR = 0.01, respectively), and also greater improvements in meaning in life across all follow-up timepoints (pFDR < 0.001).

There was also greater improvement in the PT group regarding WCS at both 3 and 6 months (pFDR = 0.02, and pFDR = 0.04) and comparable FS improvements for both groups across all timepoints.

Confounding follow-up interventions may have muddied the results, with 30.7% of PT participants and 43.5% of ET participants receiving an additional intervention during this period.

The researchers conclude that while a short course of SSRIs combined with intensive therapeutic support (around 20 hours) “might be enough to induce sustained antidepressant effects,” patients treated with psilocybin showed greater improvements in general functioning, connectedness, and meaning in life.

Although not reassessed in the follow-up, the initial study showed that adverse events, particularly sexual functioning, favored psilocybin, said Mr. Barba. “The two treatments seemed to go in opposite directions with psilocybin seeming to improve it and the antidepressant to suppress it. Other side effects associated with psilocybin were less diverse — mainly headaches at the end of the day — but with escitalopram they were way more diverse and more impairing.”

Although many therapists may be unfamiliar with psilocybin-assisted psychotherapy, “it’s not a difficult skill to master. It might require some specialization, but I think if you’re a good psychotherapist, you can learn how to implement psilocybin into your practice,” he said.

“Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to ‘let go’, or breathing exercises. The important part is the integration work that comes afterwards,” Mr. Barba added.

He said he envisions a therapy program that involves “psychiatrists working together with psychotherapists. The psychotherapists would be more in charge of the active guiding, and the psychiatrist would do the prescribing, with the follow-up psychological support on Zoom.”

He added a word of caution for therapists that “psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this.”
 

A New Treatment Paradigm?

In a comment, Johan Lundberg, MD, PhD, adjunct professor of psychiatry at the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, said the study addresses a key outstanding question about the long-term effects of one or two doses of psilocybin.

“It’s a 6-month follow-up of a short treatment intervention, so in that sense, it’s of high interest. It has been talked about that psilocybin might have a long-term effect, but this is the first study that has followed this for a longer term.”

But Dr. Lundberg also pointed out that one shortcoming of the study is the diversity of treatments following the intervention.

“They didn’t have control over whether patients received other treatments or when they started. So, that is a key concern. But they transparently reported that, and we do know there was a difference in reported ability to perform activities of daily life, and that is important.”

He added that if psilocybin is eventually approved, it would likely come with an education package for providers — “which is already the case with other treatments like ECT [electroconvulsive therapy] or TMS [transcranial magnetic stimulation] — you have to learn how to do it.”

James Rucker, MD, PhD, psychiatrist and senior clinical lecturer at King’s College London, who was not involved in the research, also noted that they have tended to attribute differences observed in this study to comparative differences between the drugs themselves.

However, he noted, it is also possible that the results reflect biased reporting between groups. This is more likely here because studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants, and study participants were unblinded during the long-term follow-up phase, so knew which condition they were allocated to.

“This said, the nature of depression varies hugely between individuals, and this calls for the development of a similarly varied suite of treatment paradigms. Psilocybin therapy is certainly a different paradigm of treatment to escitalopram. The observation of similar levels of effectiveness to antidepressants here is encouraging to see alongside the much larger trials of psilocybin currently underway here in the UK, Europe, and the US,” Dr. Rucker added.

This work was supported by The Alexander Mosley Charitable Trust and by the founding partners of Imperial College London’s Centre for Psychedelic Research.

Mr. Barba reported having received consulting fees from Adamo Bioscience. Both Dr. Lundberg and Dr. Rucker are involved in psilocybin research, but neither reported financial links.

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

COPENHAGEN — A new investigational drug has become the first agent to slow disability in patients with nonrelapsing secondary progressive multiple sclerosis (nrSPMS).

The phase 3 HERCULES trial showed tolebrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, delayed the time to onset of 6-month confirmed disability progression by 31%, compared with placebo.

In addition, tolebrutinib almost doubled the number of patients who experienced confirmed disability improvement from 5% to 10%.

However, these benefits come with the potential safety issue of liver toxicity, with raised liver enzymes reported in 4% of patients and very severe liver enzyme rises occurring in 0.5% of patients, one of whom died after undergoing a liver transplant.  

The results were presented by Robert Fox, MD, vice chair of research at the Cleveland Clinic’s Neurological Institute in Ohio, at the 2024 ECTRIMS annual meeting. 

“We have finally found a therapy that can alter the compartmentalized inflammation that is driving progressive MS,” he said. 

Dr. Fox pointed out that the population enrolled in the HERCULES trial had stopped having clinical relapses. “These are the patients for whom current immunomodulator therapies really don’t work at all — they don’t slow disability. This trial suggests that tolebrutinib can fill that void and now we have something to offer this patient group,” he said. 

He estimated that up to 30% of patients with MS at his clinic may fall into this category. 

A typical patient with nrSPMS who was included in this trial may have experienced a gradual decline in the distance they can walk or the ease with which they could climb stairs, he explained. 

“I would project that this therapy will slow down that gradual decline, and, in some patients, it may actually stop the decline,” he added.

Dr. Fox said that BTK inhibitors are believed to have two main mechanisms of action relevant to MS — down-regulating B cells, probably mostly in the periphery, and, as these agents can cross the blood-brain barrier, they also appear to reduce the inflammatory activity of microglia and macrophages in the brain.

He noted that the disability progression in nrSPMS patients is thought to be caused by compartmentalized inflammation in the brain, which is what tolebrutinib may be targeting. 

He noted that siponimod has also shown benefit in secondary progressive MS in the EXPAND trial, but the benefit was almost entirely restricted to patients who had experienced recent relapses. 

Ocrelizumab has been shown to be beneficial in a trial in primary progressive MS, but again, a large proportion of patients in that study had active focal inflammation at baselineEngl J Med. 2017;376:209-220).
 

Trial Results 

The HERCULES trial included 1131 patients with nrSPMS, defined as having an Expanded Disability Status Scale score (EDSS) between 3.0 and 6.5, no clinical relapses in the previous 24 months, and documented evidence of disability accumulation in the previous 12 months. 

They were randomly assigned (2:1) to receive 60 mg tolebrutinib as an oral daily dose or placebo for up to approximately 48 months. This was an event-driven trial, with 288 6-month confirmed disability progression events required. 

About 23% of patients in each group discontinued treatment and 12%-17% who had confirmed disability progression elected to crossover to open-label tolebrutinib.

The study population had an average age of 49 years, had a median EDSS score of 6, and a mean time since last clinical relapse of over 7 years. 

“So, this was a really very quiescent patient population in terms of focal inflammation,” Dr. Fox noted.

Results showed that the primary endpoint showed a 31% reduction in the risk of 6-month confirmed disability progression (26.9% tolebrutinib vs. 37.2% placebo; hazard ratio [HR], 0.69; 95% CI, 0.55-0.88). 

Rates of 3-month confirmed disability progression were 32.6% in the tolebrutinib group versus 41.5% with placebo — a 24% risk reduction.

In addition, 6-month confirmed disability improvement was achieved by 10% of tolebrutinib patients versus 5% in the placebo group (HR, 1.88; 95% CI, 1.10-3.21).
 

A ‘Head-scratcher’ Finding

Surprisingly, he noted, tolebrutinib did not appear to slow brain atrophy. 

“Despite seeing a benefit on disability progression, we saw no significant slowing of brain atrophy or brain volume loss over the course of the study,” Dr. Fox reported. 

He described this discordance between disability rates and brain volume loss rates as “a bit of a head-scratcher.” 

In terms of safety, the main concern is liver enzyme elevations, which occurred at greater than three times the upper limit of normal (ULN) in 4.1% of the tolebrutinib group vs 1.6% in the placebo group.

A small (0.5%) proportion of patients treated with tolebrutinib experienced very severe elevations (> 20 x ULN) in liver enzymes, and one of these patients had to have a liver transplant and died because of postoperative complications, “a reminder that this can be a very serious complication of this drug,” said Dr. Fox. 

However, he noted that all the very severe liver enzyme rises occurred in the first 3 months and it is now recommended that patients undergo weekly liver enzyme monitoring for the first 12 weeks of treatment. 

Other adverse effects that were increased slightly in tolebrutinib group were upper respiratory infections and possibly hypertension.  
 

Weekly Liver Enzyme Testing 

Dr. Fox cautioned that patients starting tolebrutinib would need to undergo weekly liver enzyme testing in the first few months of treatment. “They would need to be very attentive to this monitoring, but if they are willing to do that, then I think many of these patients will be very eager to take this drug that may slow down their disability progression.”

The drug’s manufacturer, Sanofi, said the trial results will form the basis for applications to global regulatory authorities with submissions starting later in 2024. 

Commenting on the trial, Ludwig Kappos, MD, professor of neurology at University Hospital and University of Basel, Switzerland, said the trial was important as it had shown “a robust effect on confirmed disability progression in a population of secondary progressive MS with no or very low signs of focal inflammation.”

“The effect is similar and probably more pronounced than that seen in the siponimod trial also in advanced secondary progressive MS,” he added. 

Dr. Kappos believes more work will be needed to make sure the liver toxicity can be prevented, “but if that can be resolved then patients could have a significant delay in accumulating disability.”
 

GEMINI Trials Also Show Slowed Disability 

Two other phase 3 trials of tolebrutinib were presented during the same ECTRIMS session — GEMINI 1 and 2 — which compared the new drug with teriflunomide, a standard of care treatment, in participants with relapsing MS. Neither study met the primary endpoint of an improvement in annualized relapse rates, compared with teriflunomide. 

However, with respect to the key secondary endpoint, in a pooled analysis of data from GEMINI 1 and 2, tolebrutinib delayed the time to onset of 6-month confirmed disability worsening by 29%, a finding in line with the main results of the HERCULES trial. 

“The significant impact of tolebrutinib on disability accumulation versus teriflunomide, in the absence of a statistically superior impact on relapses, also suggests that tolebrutinib may address smoldering neuroinflammation, which manifests as progression independent of relapses” Dr. Fox said. 

The HERCULES trial was sponsored by Sanofi. Dr. Fox is a paid adviser to Sanofi. Dr. Kappos led the EXPAND trial of siponimod in SPMS.

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

COPENHAGEN — A new investigational drug has become the first agent to slow disability in patients with nonrelapsing secondary progressive multiple sclerosis (nrSPMS).

The phase 3 HERCULES trial showed tolebrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, delayed the time to onset of 6-month confirmed disability progression by 31%, compared with placebo.

In addition, tolebrutinib almost doubled the number of patients who experienced confirmed disability improvement from 5% to 10%.

However, these benefits come with the potential safety issue of liver toxicity, with raised liver enzymes reported in 4% of patients and very severe liver enzyme rises occurring in 0.5% of patients, one of whom died after undergoing a liver transplant.  

The results were presented by Robert Fox, MD, vice chair of research at the Cleveland Clinic’s Neurological Institute in Ohio, at the 2024 ECTRIMS annual meeting. 

“We have finally found a therapy that can alter the compartmentalized inflammation that is driving progressive MS,” he said. 

Dr. Fox pointed out that the population enrolled in the HERCULES trial had stopped having clinical relapses. “These are the patients for whom current immunomodulator therapies really don’t work at all — they don’t slow disability. This trial suggests that tolebrutinib can fill that void and now we have something to offer this patient group,” he said. 

He estimated that up to 30% of patients with MS at his clinic may fall into this category. 

A typical patient with nrSPMS who was included in this trial may have experienced a gradual decline in the distance they can walk or the ease with which they could climb stairs, he explained. 

“I would project that this therapy will slow down that gradual decline, and, in some patients, it may actually stop the decline,” he added.

Dr. Fox said that BTK inhibitors are believed to have two main mechanisms of action relevant to MS — down-regulating B cells, probably mostly in the periphery, and, as these agents can cross the blood-brain barrier, they also appear to reduce the inflammatory activity of microglia and macrophages in the brain.

He noted that the disability progression in nrSPMS patients is thought to be caused by compartmentalized inflammation in the brain, which is what tolebrutinib may be targeting. 

He noted that siponimod has also shown benefit in secondary progressive MS in the EXPAND trial, but the benefit was almost entirely restricted to patients who had experienced recent relapses. 

Ocrelizumab has been shown to be beneficial in a trial in primary progressive MS, but again, a large proportion of patients in that study had active focal inflammation at baselineEngl J Med. 2017;376:209-220).
 

Trial Results 

The HERCULES trial included 1131 patients with nrSPMS, defined as having an Expanded Disability Status Scale score (EDSS) between 3.0 and 6.5, no clinical relapses in the previous 24 months, and documented evidence of disability accumulation in the previous 12 months. 

They were randomly assigned (2:1) to receive 60 mg tolebrutinib as an oral daily dose or placebo for up to approximately 48 months. This was an event-driven trial, with 288 6-month confirmed disability progression events required. 

About 23% of patients in each group discontinued treatment and 12%-17% who had confirmed disability progression elected to crossover to open-label tolebrutinib.

The study population had an average age of 49 years, had a median EDSS score of 6, and a mean time since last clinical relapse of over 7 years. 

“So, this was a really very quiescent patient population in terms of focal inflammation,” Dr. Fox noted.

Results showed that the primary endpoint showed a 31% reduction in the risk of 6-month confirmed disability progression (26.9% tolebrutinib vs. 37.2% placebo; hazard ratio [HR], 0.69; 95% CI, 0.55-0.88). 

Rates of 3-month confirmed disability progression were 32.6% in the tolebrutinib group versus 41.5% with placebo — a 24% risk reduction.

In addition, 6-month confirmed disability improvement was achieved by 10% of tolebrutinib patients versus 5% in the placebo group (HR, 1.88; 95% CI, 1.10-3.21).
 

A ‘Head-scratcher’ Finding

Surprisingly, he noted, tolebrutinib did not appear to slow brain atrophy. 

“Despite seeing a benefit on disability progression, we saw no significant slowing of brain atrophy or brain volume loss over the course of the study,” Dr. Fox reported. 

He described this discordance between disability rates and brain volume loss rates as “a bit of a head-scratcher.” 

In terms of safety, the main concern is liver enzyme elevations, which occurred at greater than three times the upper limit of normal (ULN) in 4.1% of the tolebrutinib group vs 1.6% in the placebo group.

A small (0.5%) proportion of patients treated with tolebrutinib experienced very severe elevations (> 20 x ULN) in liver enzymes, and one of these patients had to have a liver transplant and died because of postoperative complications, “a reminder that this can be a very serious complication of this drug,” said Dr. Fox. 

However, he noted that all the very severe liver enzyme rises occurred in the first 3 months and it is now recommended that patients undergo weekly liver enzyme monitoring for the first 12 weeks of treatment. 

Other adverse effects that were increased slightly in tolebrutinib group were upper respiratory infections and possibly hypertension.  
 

Weekly Liver Enzyme Testing 

Dr. Fox cautioned that patients starting tolebrutinib would need to undergo weekly liver enzyme testing in the first few months of treatment. “They would need to be very attentive to this monitoring, but if they are willing to do that, then I think many of these patients will be very eager to take this drug that may slow down their disability progression.”

The drug’s manufacturer, Sanofi, said the trial results will form the basis for applications to global regulatory authorities with submissions starting later in 2024. 

Commenting on the trial, Ludwig Kappos, MD, professor of neurology at University Hospital and University of Basel, Switzerland, said the trial was important as it had shown “a robust effect on confirmed disability progression in a population of secondary progressive MS with no or very low signs of focal inflammation.”

“The effect is similar and probably more pronounced than that seen in the siponimod trial also in advanced secondary progressive MS,” he added. 

Dr. Kappos believes more work will be needed to make sure the liver toxicity can be prevented, “but if that can be resolved then patients could have a significant delay in accumulating disability.”
 

GEMINI Trials Also Show Slowed Disability 

Two other phase 3 trials of tolebrutinib were presented during the same ECTRIMS session — GEMINI 1 and 2 — which compared the new drug with teriflunomide, a standard of care treatment, in participants with relapsing MS. Neither study met the primary endpoint of an improvement in annualized relapse rates, compared with teriflunomide. 

However, with respect to the key secondary endpoint, in a pooled analysis of data from GEMINI 1 and 2, tolebrutinib delayed the time to onset of 6-month confirmed disability worsening by 29%, a finding in line with the main results of the HERCULES trial. 

“The significant impact of tolebrutinib on disability accumulation versus teriflunomide, in the absence of a statistically superior impact on relapses, also suggests that tolebrutinib may address smoldering neuroinflammation, which manifests as progression independent of relapses” Dr. Fox said. 

The HERCULES trial was sponsored by Sanofi. Dr. Fox is a paid adviser to Sanofi. Dr. Kappos led the EXPAND trial of siponimod in SPMS.

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

COPENHAGEN — A new investigational drug has become the first agent to slow disability in patients with nonrelapsing secondary progressive multiple sclerosis (nrSPMS).

The phase 3 HERCULES trial showed tolebrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, delayed the time to onset of 6-month confirmed disability progression by 31%, compared with placebo.

In addition, tolebrutinib almost doubled the number of patients who experienced confirmed disability improvement from 5% to 10%.

However, these benefits come with the potential safety issue of liver toxicity, with raised liver enzymes reported in 4% of patients and very severe liver enzyme rises occurring in 0.5% of patients, one of whom died after undergoing a liver transplant.  

The results were presented by Robert Fox, MD, vice chair of research at the Cleveland Clinic’s Neurological Institute in Ohio, at the 2024 ECTRIMS annual meeting. 

“We have finally found a therapy that can alter the compartmentalized inflammation that is driving progressive MS,” he said. 

Dr. Fox pointed out that the population enrolled in the HERCULES trial had stopped having clinical relapses. “These are the patients for whom current immunomodulator therapies really don’t work at all — they don’t slow disability. This trial suggests that tolebrutinib can fill that void and now we have something to offer this patient group,” he said. 

He estimated that up to 30% of patients with MS at his clinic may fall into this category. 

A typical patient with nrSPMS who was included in this trial may have experienced a gradual decline in the distance they can walk or the ease with which they could climb stairs, he explained. 

“I would project that this therapy will slow down that gradual decline, and, in some patients, it may actually stop the decline,” he added.

Dr. Fox said that BTK inhibitors are believed to have two main mechanisms of action relevant to MS — down-regulating B cells, probably mostly in the periphery, and, as these agents can cross the blood-brain barrier, they also appear to reduce the inflammatory activity of microglia and macrophages in the brain.

He noted that the disability progression in nrSPMS patients is thought to be caused by compartmentalized inflammation in the brain, which is what tolebrutinib may be targeting. 

He noted that siponimod has also shown benefit in secondary progressive MS in the EXPAND trial, but the benefit was almost entirely restricted to patients who had experienced recent relapses. 

Ocrelizumab has been shown to be beneficial in a trial in primary progressive MS, but again, a large proportion of patients in that study had active focal inflammation at baselineEngl J Med. 2017;376:209-220).
 

Trial Results 

The HERCULES trial included 1131 patients with nrSPMS, defined as having an Expanded Disability Status Scale score (EDSS) between 3.0 and 6.5, no clinical relapses in the previous 24 months, and documented evidence of disability accumulation in the previous 12 months. 

They were randomly assigned (2:1) to receive 60 mg tolebrutinib as an oral daily dose or placebo for up to approximately 48 months. This was an event-driven trial, with 288 6-month confirmed disability progression events required. 

About 23% of patients in each group discontinued treatment and 12%-17% who had confirmed disability progression elected to crossover to open-label tolebrutinib.

The study population had an average age of 49 years, had a median EDSS score of 6, and a mean time since last clinical relapse of over 7 years. 

“So, this was a really very quiescent patient population in terms of focal inflammation,” Dr. Fox noted.

Results showed that the primary endpoint showed a 31% reduction in the risk of 6-month confirmed disability progression (26.9% tolebrutinib vs. 37.2% placebo; hazard ratio [HR], 0.69; 95% CI, 0.55-0.88). 

Rates of 3-month confirmed disability progression were 32.6% in the tolebrutinib group versus 41.5% with placebo — a 24% risk reduction.

In addition, 6-month confirmed disability improvement was achieved by 10% of tolebrutinib patients versus 5% in the placebo group (HR, 1.88; 95% CI, 1.10-3.21).
 

A ‘Head-scratcher’ Finding

Surprisingly, he noted, tolebrutinib did not appear to slow brain atrophy. 

“Despite seeing a benefit on disability progression, we saw no significant slowing of brain atrophy or brain volume loss over the course of the study,” Dr. Fox reported. 

He described this discordance between disability rates and brain volume loss rates as “a bit of a head-scratcher.” 

In terms of safety, the main concern is liver enzyme elevations, which occurred at greater than three times the upper limit of normal (ULN) in 4.1% of the tolebrutinib group vs 1.6% in the placebo group.

A small (0.5%) proportion of patients treated with tolebrutinib experienced very severe elevations (> 20 x ULN) in liver enzymes, and one of these patients had to have a liver transplant and died because of postoperative complications, “a reminder that this can be a very serious complication of this drug,” said Dr. Fox. 

However, he noted that all the very severe liver enzyme rises occurred in the first 3 months and it is now recommended that patients undergo weekly liver enzyme monitoring for the first 12 weeks of treatment. 

Other adverse effects that were increased slightly in tolebrutinib group were upper respiratory infections and possibly hypertension.  
 

Weekly Liver Enzyme Testing 

Dr. Fox cautioned that patients starting tolebrutinib would need to undergo weekly liver enzyme testing in the first few months of treatment. “They would need to be very attentive to this monitoring, but if they are willing to do that, then I think many of these patients will be very eager to take this drug that may slow down their disability progression.”

The drug’s manufacturer, Sanofi, said the trial results will form the basis for applications to global regulatory authorities with submissions starting later in 2024. 

Commenting on the trial, Ludwig Kappos, MD, professor of neurology at University Hospital and University of Basel, Switzerland, said the trial was important as it had shown “a robust effect on confirmed disability progression in a population of secondary progressive MS with no or very low signs of focal inflammation.”

“The effect is similar and probably more pronounced than that seen in the siponimod trial also in advanced secondary progressive MS,” he added. 

Dr. Kappos believes more work will be needed to make sure the liver toxicity can be prevented, “but if that can be resolved then patients could have a significant delay in accumulating disability.”
 

GEMINI Trials Also Show Slowed Disability 

Two other phase 3 trials of tolebrutinib were presented during the same ECTRIMS session — GEMINI 1 and 2 — which compared the new drug with teriflunomide, a standard of care treatment, in participants with relapsing MS. Neither study met the primary endpoint of an improvement in annualized relapse rates, compared with teriflunomide. 

However, with respect to the key secondary endpoint, in a pooled analysis of data from GEMINI 1 and 2, tolebrutinib delayed the time to onset of 6-month confirmed disability worsening by 29%, a finding in line with the main results of the HERCULES trial. 

“The significant impact of tolebrutinib on disability accumulation versus teriflunomide, in the absence of a statistically superior impact on relapses, also suggests that tolebrutinib may address smoldering neuroinflammation, which manifests as progression independent of relapses” Dr. Fox said. 

The HERCULES trial was sponsored by Sanofi. Dr. Fox is a paid adviser to Sanofi. Dr. Kappos led the EXPAND trial of siponimod in SPMS.

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

TOPLINE:

The long-term use of muscle relaxants may benefit patients with painful spasms or cramps and neck pain, according to a systematic review of clinical studies, but they do not appear to be beneficial for low back pain, fibromyalgia, or headaches and can have adverse effects such as sedation and dry mouth.

METHODOLOGY:

• Researchers conducted a systematic review to evaluate the effectiveness of long-term use (≥ 4 weeks) of muscle relaxants for chronic pain lasting ≥ 3 months.
• They identified 30 randomized clinical trials involving 1314 patients and 14 cohort studies involving 1168 patients, grouped according to the categories of low back pain, fibromyalgia, painful cramps or spasticity, headaches, and other syndromes.
• Baclofen, tizanidine, cyclobenzaprine, eperisone, quinine, carisoprodol, orphenadrine, chlormezanone, and methocarbamol were the muscle relaxants assessed in comparison with placebo, other treatments, or untreated individuals.

TAKEAWAY:

• The long-term use of muscle relaxants reduced pain intensity in those with painful spasms or cramps and neck pain. Baclofen, orphenadrine, carisoprodol, and methocarbamol improved cramp frequency, while the use of eperisone and chlormezanone improved neck pain and enhanced the quality of sleep, respectively, in those with neck osteoarthritis.
• While some studies suggested that muscle relaxants reduced pain intensity in those with back pain and fibromyalgia, between-group differences were not observed. The benefits seen with some medications diminished after their discontinuation.
• Despite tizanidine improving pain severity in headaches, 25% participants dropped out owing to adverse effects. Although certain muscle relaxants demonstrated pain relief, others did not.
• The most common adverse effects of muscle relaxants were somnolence and dry mouth. Other adverse events included vomiting, diarrhea, nausea, weakness, and constipation.

IN PRACTICE:

“For patients already prescribed long-term SMRs [skeletal muscle relaxants], interventions are needed to assist clinicians to engage in shared decision-making with patients about deprescribing SMRs. This may be particularly true for older patients for whom risks of adverse events may be greater,” the authors wrote. “Clinicians should be vigilant for adverse effects and consider deprescribing if pain-related goals are not met.”

SOURCE:

The study, led by Benjamin J. Oldfield, MD, MHS, Yale School of Medicine, New Haven, Connecticut, was published online on September 19, 2024, in JAMA Network Open

LIMITATIONS:

This systematic review was limited to publications written in English, Spanish, and Italian language, potentially excluding studies from other regions. Variations in clinical sites, definitions of pain syndromes, medications, and durations of therapy prevented the possibility of conducting meta-analyses. Only quantitative studies were included, excluding valuable insights into patient experiences offered by qualitative studies. 

DISCLOSURES:

The study was supported by the National Institute on Drug Abuse. The authors declared no conflicts of interest.

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

TOPLINE:

The long-term use of muscle relaxants may benefit patients with painful spasms or cramps and neck pain, according to a systematic review of clinical studies, but they do not appear to be beneficial for low back pain, fibromyalgia, or headaches and can have adverse effects such as sedation and dry mouth.

METHODOLOGY:

• Researchers conducted a systematic review to evaluate the effectiveness of long-term use (≥ 4 weeks) of muscle relaxants for chronic pain lasting ≥ 3 months.
• They identified 30 randomized clinical trials involving 1314 patients and 14 cohort studies involving 1168 patients, grouped according to the categories of low back pain, fibromyalgia, painful cramps or spasticity, headaches, and other syndromes.
• Baclofen, tizanidine, cyclobenzaprine, eperisone, quinine, carisoprodol, orphenadrine, chlormezanone, and methocarbamol were the muscle relaxants assessed in comparison with placebo, other treatments, or untreated individuals.

TAKEAWAY:

• The long-term use of muscle relaxants reduced pain intensity in those with painful spasms or cramps and neck pain. Baclofen, orphenadrine, carisoprodol, and methocarbamol improved cramp frequency, while the use of eperisone and chlormezanone improved neck pain and enhanced the quality of sleep, respectively, in those with neck osteoarthritis.
• While some studies suggested that muscle relaxants reduced pain intensity in those with back pain and fibromyalgia, between-group differences were not observed. The benefits seen with some medications diminished after their discontinuation.
• Despite tizanidine improving pain severity in headaches, 25% participants dropped out owing to adverse effects. Although certain muscle relaxants demonstrated pain relief, others did not.
• The most common adverse effects of muscle relaxants were somnolence and dry mouth. Other adverse events included vomiting, diarrhea, nausea, weakness, and constipation.

IN PRACTICE:

“For patients already prescribed long-term SMRs [skeletal muscle relaxants], interventions are needed to assist clinicians to engage in shared decision-making with patients about deprescribing SMRs. This may be particularly true for older patients for whom risks of adverse events may be greater,” the authors wrote. “Clinicians should be vigilant for adverse effects and consider deprescribing if pain-related goals are not met.”

SOURCE:

The study, led by Benjamin J. Oldfield, MD, MHS, Yale School of Medicine, New Haven, Connecticut, was published online on September 19, 2024, in JAMA Network Open

LIMITATIONS:

This systematic review was limited to publications written in English, Spanish, and Italian language, potentially excluding studies from other regions. Variations in clinical sites, definitions of pain syndromes, medications, and durations of therapy prevented the possibility of conducting meta-analyses. Only quantitative studies were included, excluding valuable insights into patient experiences offered by qualitative studies. 

DISCLOSURES:

The study was supported by the National Institute on Drug Abuse. The authors declared no conflicts of interest.

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

TOPLINE:

The long-term use of muscle relaxants may benefit patients with painful spasms or cramps and neck pain, according to a systematic review of clinical studies, but they do not appear to be beneficial for low back pain, fibromyalgia, or headaches and can have adverse effects such as sedation and dry mouth.

METHODOLOGY:

• Researchers conducted a systematic review to evaluate the effectiveness of long-term use (≥ 4 weeks) of muscle relaxants for chronic pain lasting ≥ 3 months.
• They identified 30 randomized clinical trials involving 1314 patients and 14 cohort studies involving 1168 patients, grouped according to the categories of low back pain, fibromyalgia, painful cramps or spasticity, headaches, and other syndromes.
• Baclofen, tizanidine, cyclobenzaprine, eperisone, quinine, carisoprodol, orphenadrine, chlormezanone, and methocarbamol were the muscle relaxants assessed in comparison with placebo, other treatments, or untreated individuals.

TAKEAWAY:

• The long-term use of muscle relaxants reduced pain intensity in those with painful spasms or cramps and neck pain. Baclofen, orphenadrine, carisoprodol, and methocarbamol improved cramp frequency, while the use of eperisone and chlormezanone improved neck pain and enhanced the quality of sleep, respectively, in those with neck osteoarthritis.
• While some studies suggested that muscle relaxants reduced pain intensity in those with back pain and fibromyalgia, between-group differences were not observed. The benefits seen with some medications diminished after their discontinuation.
• Despite tizanidine improving pain severity in headaches, 25% participants dropped out owing to adverse effects. Although certain muscle relaxants demonstrated pain relief, others did not.
• The most common adverse effects of muscle relaxants were somnolence and dry mouth. Other adverse events included vomiting, diarrhea, nausea, weakness, and constipation.

IN PRACTICE:

“For patients already prescribed long-term SMRs [skeletal muscle relaxants], interventions are needed to assist clinicians to engage in shared decision-making with patients about deprescribing SMRs. This may be particularly true for older patients for whom risks of adverse events may be greater,” the authors wrote. “Clinicians should be vigilant for adverse effects and consider deprescribing if pain-related goals are not met.”

SOURCE:

The study, led by Benjamin J. Oldfield, MD, MHS, Yale School of Medicine, New Haven, Connecticut, was published online on September 19, 2024, in JAMA Network Open

LIMITATIONS:

This systematic review was limited to publications written in English, Spanish, and Italian language, potentially excluding studies from other regions. Variations in clinical sites, definitions of pain syndromes, medications, and durations of therapy prevented the possibility of conducting meta-analyses. Only quantitative studies were included, excluding valuable insights into patient experiences offered by qualitative studies. 

DISCLOSURES:

The study was supported by the National Institute on Drug Abuse. The authors declared no conflicts of interest.

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

When a large rheumatology clinic in Richmond, Virginia, heard that Medicare would be reimbursing patient navigators, they decided to launch their own virtual navigator program. 

“We read about it and felt like it was the perfect representation of what we were already trying to do,” said Blake Wehman, founder and CEO of Remission Medical, which offers virtual diagnosis and longitudinal care in rheumatology.

Mr. Wehman has plans to start submitting for these principal illness navigation (PIN) codes in 2025. 

The Centers for Medicare & Medicaid Services (CMS) in 2024 began paying navigators who assist Medicare patients with high-risk conditions, which could include rheumatologic diseases. “The codes are not limited to a specific set of diagnoses; rather, the definition of a serious, high-risk condition is dependent on clinical judgment,” the agency clarified. 

CMS established this provision in the CY 2024 Physician Fee Schedule final rule. 

Reimbursing patient navigators is long overdue, noted Edith Williams, PhD, MS, director of the Center for Community Health and Prevention and founding director of the Office of Health Equity Research at the University of Rochester in New York. “It’s something our patients need. It’s something that the science is telling us can impact outcomes as an adjunct to clinical care,” she said. 

John Schlia

Dr. Williams said the new CMS codes “got our departments talking about what this policy is and how it would translate into patient care.”

The codes apply when navigators are assigned to support patients with high-risk conditions who need assistance connecting with clinical and other resources, including any unmet social determinants of health needs, or in diagnosis or treatment of their medical problems.

“Having a navigator by their side to help get through all the clinical and administrative challenges gives people an advocate and a partner who is with them and their families every step of the way to help make the journey easier,” said a CMS spokesperson. 

Not all navigator programs may qualify for the new codes. Some are supported by grants and don’t bill patient insurance. However, they all share a common goal: to guide patients through the healthcare continuum and assist with appointments and medication adherence. 
 

Identifying ‘Root Causes’ of Barriers

Navigators represent a wide variety of backgrounds, ranging from healthcare professionals to students or even patients themselves. They generally don’t provide medical advice. “However, we are responsible for making sure our patients and their families are educated and aware, then assist with guidance on their path,” said Katie Costillo, BSW, CPPN, patient navigator and program manager with the Lupus Foundation of America, Heartland Region.

“Training and experience in engaging and building rapport is essential to assisting patients overcome obstacles that limit their access to healthcare,” she said. Narrowing down with patients the root causes of their barriers and then identifying appropriate and available community resources is key. 

Studies have demonstrated the effectiveness of adding a navigator to a rheumatology patient’s care plan. In one study, a group of Boston researchers determined that navigators played a useful role in reducing adherence barriers to oral disease-modifying antirheumatic drugs. The navigators uncovered several concerns among 107 rheumatology patients, including fear of adverse events and medication effectiveness. 

They also helped to facilitate patient-physician communication, developed strategies to improve medication adherence, and provided medication and diagnosis education. Patients reported satisfaction with the navigator experience.

A study Dr. Williams coauthored that examined behavioral interventions to support African American women with systemic lupus erythematosus found that patient navigator participants had superior coping scores, compared with those engaged in peer-to-peer methodology and patient support groups.

“We had a lot of success with the mentorship program, too,” Dr. Williams said. Navigator services, however, offer more one-on-one attention, “and it’s more tailored to what the person needs rather than the set curriculum that the mentors delivered to their mentees.”
 

Supporting Patients With Lupus

Ideally, navigators should be able to relate to patients and know what they’re going through, Dr. Williams said. This is someone whom the patient can trust and depend on. “That’s where the benefit of having someone who is also a patient lies because they’re ultimately relatable to other patients. But different institutions have taken different approaches to this.” 

Some programs focus on specific rheumatologic conditions. The Lupus Foundation of America, for example, established patient navigator programs to assist patients with lupus in four markets across the country. 

The Heartland patient navigator program is available for all patients with lupus within its region, which includes Kansas, Missouri, and central and southern Illinois. As a navigator, Ms. Costillo has been assisting patients since 2022. In 2023, she began meeting with patients at the Washington University Lupus Clinic (WULC) in St. Louis, Missouri. 

Navigators work directly with patients before and after their appointment to ensure follow-up and reduce missed appointments. “They help lupus patients connect with community services and overcoming barriers to access and care. The goal of this position is to improve overall disease management, which results in better health outcomes,” Ms. Costillo said. 

Since its inception, the patient navigator program at WULC has shown a decrease in patient no-call no-shows and an increase in requests to reschedule as opposed to not showing up for their scheduled appointment, based on history. 

Patients have reported fewer barriers to transportation and improvement in access to resources, support, and disease education. “Our patients have also stated [that] meeting with the navigator during their appointments has helped them to feel heard, understood, and supported,” Ms. Costillo said.
 

Navigator Work Is Not Without Challenges

A total of 90% of patients with lupus are women, and women of color are two to three times more likely to develop lupus in their lifetime. 

“Based on socioeconomic statistics, lupus patients are in a demographic that is commonly underserved, underfunded, and often overlooked. Finding appropriate local community resources for a patient who must choose between feeding her family or paying for transportation to multiple physician appointments is a common problem,” Ms. Costillo said.

Much of the assistance that became available during the COVID pandemic is starting to disappear. “With the rising costs of daily living, we are having to find creative and alternative ways to break down barriers and find support to fill those gaps,” she continued.

Getting insurance coverage of patients is another challenge. Many patients with lupus will be prescribed a treatment that insurance refuses to cover even after the physician disputes it.

Additionally, many patients with lupus are unable to work to support their family. A majority who apply for Social Security Disability Insurance are denied on their first and second attempts, “requiring multiple hearings and pages of documentation from their physicians,” Ms. Costillo said. 
 

Students Serve as Navigators

One inner-city program is seeking to increase access to healthcare services to patients with lupus and lupus nephritis in underserved communities. In 2021, SUNY Downstate Health Sciences University in New York City, in partnership with the Brooklyn Free Clinic and Brooklyn Health Disparities Center, launched a program to teach navigator skills to second-year medical students. 

The students assist patients at the Arthritis Clinic at University Hospital at Downstate. “Many of our patients have either low medical literacy or difficulty with English. Many of them are immigrants,” said Ellen M. Ginzler, MD, MPH, SUNY Downstate’s professor emerita and former vice-chair for research and rheumatology division chief. 

Dr. Ginzler sought out navigator candidates who showed a strong interest in working with underserved patients with complicated, severe disease who struggled with keeping appointments or adhering to medication regimens. The program also gave preference to students fluent in other languages such as Spanish. 

All these efforts have generated improvements in care.

Assessing the program’s effectiveness in a cross-sectional study, Dr. Ginzler and colleagues reported that 94% of navigators were able to schedule appointments and 87% assisted with prescriptions. Navigators also had high success rates in answering medical questions, getting in touch with a patient’s doctor, and reminding patients of medical appointments. 

Medical student Jeremy Wilson, a coauthor of the study, served as a navigator for a woman with lupus and scleroderma for many years, along with other comorbidities.

Mr. Wilson went above and beyond for this patient, helping to secure social services supports that included accompanying her to clinic visits and serving as her advocate. “She found an enormous difference in how she was treated when she went to these clinics because the doctors in those clinics took her much more seriously,” Dr. Ginzler said. Mr. Wilson ran interference to secure clinic appointments and worked with the patient’s rheumatology fellow in the clinic to get approval for medications. 

Mr. Wilson and the patient formed a great bond. “It not only helped the patient, but it helped Jeremy tremendously in terms of how he felt about his medical career,” Dr. Ginzler said. 

The program has since expanded to include patients with other rheumatic diseases, such as rheumatoid arthritis and psoriatic arthritis, and also offers navigator services in dermatology. 

A total of 21 students to date have completed the second year of the program. “We’ve just selected eight more,” Dr. Ginzler said. Some of the students continue to do the program in their third or even fourth year as they’re applying for residencies. 

A student-run, unpublished survey of nine students in the SUNY program found that all nine reported high confidence in identifying social factors that impact patient health and well-being, compared with four who reported high confidence prior to starting the program. “Additionally, students reported increased confidence in providing comprehensive care in rheumatology and dermatology, and interdisciplinary collaboration,” study author Alejandra K. Moncayo, MPH, and colleagues wrote. 
 

When Navigators Go Virtual

Remission Medical offers its navigator service through its own standalone virtual clinic. 

Pain associated with rheumatologic conditions increases the urgency to see a doctor. The goal of the virtual RemissionNavigator program is to meet rheumatology patients where they live, to bridge care gaps and reduce wait times, said Mr. Wehman.

RemissionNavigator accomplishes this through video visits and unlimited texting to its network of board-certified rheumatologists or rheumatology-focused advanced practice providers. Experts can answer questions about why labs are ordered, why a patient may have received a certain diagnosis, or provide detailed explanations of a rheumatic condition. 

“There are instances where improvement for the patient means waiting a couple days for us versus 45 days for their brick-and-mortar choice,” Mr. Wehman said. 

The program currently has 36 subscribers to Remission’s services, which include navigation. “We have 15 providers in a blend of employed and contracted relationships with Remission,” Mr. Wehman said. 

Even in its infancy, the navigator program has produced some success stories. “We had a patient tell us that thanks to us, he was seen faster, found relief immediately through our diagnosis and prescription of methotrexate, felt better at work, lost weight, and was happier in general,” Mr. Wehman said. 

Another patient was making monthly, 90-minute trips to Richmond for infusion services. Through the virtual program’s assistance, she is now receiving care from home and can get her monthly infusions at a local clinic. 

Ultimately, the goal is to help rheumatology move into an era of value-based care where the transition from fee-for-service to per patient will enable optimized care models and better accessibility, Mr. Wehman said. “It will not happen overnight, but every day we work toward this future.”
 

VA Targets Rheumatology Care

The Department of Veterans Affairs (VA) has also explored the use of navigator services in rheumatology, including virtual services. 

VA uses an integrated, interdisciplinary model that manages each veteran’s individual healthcare needs through a coordinated effort among providers, nurses, social workers, pharmacists, and other health professionals, according to VA press secretary Terrence Hayes.

Care coordination may include supporting scheduling appointments, managing chronic conditions, and coordinating care across different medical departments. “This coordination is particularly important in managing complex rheumatologic conditions, where multiple providers may be involved,” Mr. Hayes said.

Additionally, VA has launched a national telerheumatology initiative to improve access to rheumatology providers in rural areas. The initiative will assist veterans in understanding the telehealth system, navigating appointments, and ensuring they have the necessary technology for virtual consultations. 

“It will also facilitate communication between rheumatologists, primary care providers, and other specialists, ensuring that all team members are aligned in their approach to the veteran’s care,” Mr. Hayes said.
 

Who Will Take Advantage of New Codes? 

Currently, Remission Medical operates on a cash-pay model, but the company intends to transition to insurance-based coverage in 2025. 

Remission Medical also partners directly with preexisting healthcare systems and clinics such as Sentara Health and OrthoVirginia, where a PIN program, powered by Remission Medical’s virtual rheumatology network, may be explored as well. 

The company offers its partners synchronous virtual visits and e-consults. It’s likely that these larger organizations will explore coverage for navigator services for Medicare and private insurance. “We can be there to support them as they decide to implement this,” Mr. Wehman said.

Taking advantage of CMS’s navigator PIN codes is an eventual goal. Remission Medical has not submitted the codes yet, “but we do intend to as we continue to grow our membership count,” Mr. Wehman said. “We hope to provide coverage for most of the US and submit the codes to reimbursement by early to mid-2025.” 

In terms of reimbursement, the VA operates under a different payment model than Medicare or private insurance, focusing on providing integrated care within the VA system rather than reimbursing for specific services such as patient navigation.

While the SUNY clinic takes care of Medicare patients, it’s unlikely that the new CMS codes for navigators would apply to medical students. Students get paid a monthly stipend for doing navigator work. “There’s a policy about what students can get paid, and how many hours they can work,” Dr. Ginzler clarified. 

The SUNY Downstate and Lupus Foundation navigator programs rely on grants to sustain their services. Aurinia Pharmaceuticals has funded both programs, and the SUNY program received an additional grant from Janssen to expand its offerings. 

Because it’s grant funded, the navigator position at the Lupus Foundation does not bill patient insurance, Ms. Costillo explained. 
 

Navigator Work Requires Training

Before they start working with patients, navigators often go through a vetting or training process. At Remission Medical, a clinical leadership team does a synchronous interview, background check, and CV review of its potential navigators. 

Even before she became a navigator, Ms. Costillo had a strong baseline education in this work. She has a bachelor’s degree in social work and 15 years of experience in social services working with disabled, vulnerable, and underserved populations. Some of her fellow navigators at the Lupus Foundation of America also have degrees in social work. 

Ms. Costillo underwent training with the Patient-Centered Education & Research Institute to become a certified professional patient navigator. Her name is on the national registry. The curriculum covered various aspects of medical care such as patient and care team interactions and communications, health and clinical knowledge, patient care coordination and resources, and using evidence-based approaches. 

“For our lupus patients, it is essential that navigators understand the disease and the impact on patients and families, treatments available and those in the pipelines, and also the ins and outs of various insurance options,” Ms. Costillo said.

Mr. Wehman, Dr. Williams, and Ms. Costillo reported no disclosures. Dr. Ginzler has been a consultant for Aurinia Pharmaceuticals.

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

When a large rheumatology clinic in Richmond, Virginia, heard that Medicare would be reimbursing patient navigators, they decided to launch their own virtual navigator program. 

“We read about it and felt like it was the perfect representation of what we were already trying to do,” said Blake Wehman, founder and CEO of Remission Medical, which offers virtual diagnosis and longitudinal care in rheumatology.

Mr. Wehman has plans to start submitting for these principal illness navigation (PIN) codes in 2025. 

The Centers for Medicare & Medicaid Services (CMS) in 2024 began paying navigators who assist Medicare patients with high-risk conditions, which could include rheumatologic diseases. “The codes are not limited to a specific set of diagnoses; rather, the definition of a serious, high-risk condition is dependent on clinical judgment,” the agency clarified. 

CMS established this provision in the CY 2024 Physician Fee Schedule final rule. 

Reimbursing patient navigators is long overdue, noted Edith Williams, PhD, MS, director of the Center for Community Health and Prevention and founding director of the Office of Health Equity Research at the University of Rochester in New York. “It’s something our patients need. It’s something that the science is telling us can impact outcomes as an adjunct to clinical care,” she said. 

John Schlia

Dr. Williams said the new CMS codes “got our departments talking about what this policy is and how it would translate into patient care.”

The codes apply when navigators are assigned to support patients with high-risk conditions who need assistance connecting with clinical and other resources, including any unmet social determinants of health needs, or in diagnosis or treatment of their medical problems.

“Having a navigator by their side to help get through all the clinical and administrative challenges gives people an advocate and a partner who is with them and their families every step of the way to help make the journey easier,” said a CMS spokesperson. 

Not all navigator programs may qualify for the new codes. Some are supported by grants and don’t bill patient insurance. However, they all share a common goal: to guide patients through the healthcare continuum and assist with appointments and medication adherence. 
 

Identifying ‘Root Causes’ of Barriers

Navigators represent a wide variety of backgrounds, ranging from healthcare professionals to students or even patients themselves. They generally don’t provide medical advice. “However, we are responsible for making sure our patients and their families are educated and aware, then assist with guidance on their path,” said Katie Costillo, BSW, CPPN, patient navigator and program manager with the Lupus Foundation of America, Heartland Region.

“Training and experience in engaging and building rapport is essential to assisting patients overcome obstacles that limit their access to healthcare,” she said. Narrowing down with patients the root causes of their barriers and then identifying appropriate and available community resources is key. 

Studies have demonstrated the effectiveness of adding a navigator to a rheumatology patient’s care plan. In one study, a group of Boston researchers determined that navigators played a useful role in reducing adherence barriers to oral disease-modifying antirheumatic drugs. The navigators uncovered several concerns among 107 rheumatology patients, including fear of adverse events and medication effectiveness. 

They also helped to facilitate patient-physician communication, developed strategies to improve medication adherence, and provided medication and diagnosis education. Patients reported satisfaction with the navigator experience.

A study Dr. Williams coauthored that examined behavioral interventions to support African American women with systemic lupus erythematosus found that patient navigator participants had superior coping scores, compared with those engaged in peer-to-peer methodology and patient support groups.

“We had a lot of success with the mentorship program, too,” Dr. Williams said. Navigator services, however, offer more one-on-one attention, “and it’s more tailored to what the person needs rather than the set curriculum that the mentors delivered to their mentees.”
 

Supporting Patients With Lupus

Ideally, navigators should be able to relate to patients and know what they’re going through, Dr. Williams said. This is someone whom the patient can trust and depend on. “That’s where the benefit of having someone who is also a patient lies because they’re ultimately relatable to other patients. But different institutions have taken different approaches to this.” 

Some programs focus on specific rheumatologic conditions. The Lupus Foundation of America, for example, established patient navigator programs to assist patients with lupus in four markets across the country. 

The Heartland patient navigator program is available for all patients with lupus within its region, which includes Kansas, Missouri, and central and southern Illinois. As a navigator, Ms. Costillo has been assisting patients since 2022. In 2023, she began meeting with patients at the Washington University Lupus Clinic (WULC) in St. Louis, Missouri. 

Navigators work directly with patients before and after their appointment to ensure follow-up and reduce missed appointments. “They help lupus patients connect with community services and overcoming barriers to access and care. The goal of this position is to improve overall disease management, which results in better health outcomes,” Ms. Costillo said. 

Since its inception, the patient navigator program at WULC has shown a decrease in patient no-call no-shows and an increase in requests to reschedule as opposed to not showing up for their scheduled appointment, based on history. 

Patients have reported fewer barriers to transportation and improvement in access to resources, support, and disease education. “Our patients have also stated [that] meeting with the navigator during their appointments has helped them to feel heard, understood, and supported,” Ms. Costillo said.
 

Navigator Work Is Not Without Challenges

A total of 90% of patients with lupus are women, and women of color are two to three times more likely to develop lupus in their lifetime. 

“Based on socioeconomic statistics, lupus patients are in a demographic that is commonly underserved, underfunded, and often overlooked. Finding appropriate local community resources for a patient who must choose between feeding her family or paying for transportation to multiple physician appointments is a common problem,” Ms. Costillo said.

Much of the assistance that became available during the COVID pandemic is starting to disappear. “With the rising costs of daily living, we are having to find creative and alternative ways to break down barriers and find support to fill those gaps,” she continued.

Getting insurance coverage of patients is another challenge. Many patients with lupus will be prescribed a treatment that insurance refuses to cover even after the physician disputes it.

Additionally, many patients with lupus are unable to work to support their family. A majority who apply for Social Security Disability Insurance are denied on their first and second attempts, “requiring multiple hearings and pages of documentation from their physicians,” Ms. Costillo said. 
 

Students Serve as Navigators

One inner-city program is seeking to increase access to healthcare services to patients with lupus and lupus nephritis in underserved communities. In 2021, SUNY Downstate Health Sciences University in New York City, in partnership with the Brooklyn Free Clinic and Brooklyn Health Disparities Center, launched a program to teach navigator skills to second-year medical students. 

The students assist patients at the Arthritis Clinic at University Hospital at Downstate. “Many of our patients have either low medical literacy or difficulty with English. Many of them are immigrants,” said Ellen M. Ginzler, MD, MPH, SUNY Downstate’s professor emerita and former vice-chair for research and rheumatology division chief. 

Dr. Ginzler sought out navigator candidates who showed a strong interest in working with underserved patients with complicated, severe disease who struggled with keeping appointments or adhering to medication regimens. The program also gave preference to students fluent in other languages such as Spanish. 

All these efforts have generated improvements in care.

Assessing the program’s effectiveness in a cross-sectional study, Dr. Ginzler and colleagues reported that 94% of navigators were able to schedule appointments and 87% assisted with prescriptions. Navigators also had high success rates in answering medical questions, getting in touch with a patient’s doctor, and reminding patients of medical appointments. 

Medical student Jeremy Wilson, a coauthor of the study, served as a navigator for a woman with lupus and scleroderma for many years, along with other comorbidities.

Mr. Wilson went above and beyond for this patient, helping to secure social services supports that included accompanying her to clinic visits and serving as her advocate. “She found an enormous difference in how she was treated when she went to these clinics because the doctors in those clinics took her much more seriously,” Dr. Ginzler said. Mr. Wilson ran interference to secure clinic appointments and worked with the patient’s rheumatology fellow in the clinic to get approval for medications. 

Mr. Wilson and the patient formed a great bond. “It not only helped the patient, but it helped Jeremy tremendously in terms of how he felt about his medical career,” Dr. Ginzler said. 

The program has since expanded to include patients with other rheumatic diseases, such as rheumatoid arthritis and psoriatic arthritis, and also offers navigator services in dermatology. 

A total of 21 students to date have completed the second year of the program. “We’ve just selected eight more,” Dr. Ginzler said. Some of the students continue to do the program in their third or even fourth year as they’re applying for residencies. 

A student-run, unpublished survey of nine students in the SUNY program found that all nine reported high confidence in identifying social factors that impact patient health and well-being, compared with four who reported high confidence prior to starting the program. “Additionally, students reported increased confidence in providing comprehensive care in rheumatology and dermatology, and interdisciplinary collaboration,” study author Alejandra K. Moncayo, MPH, and colleagues wrote. 
 

When Navigators Go Virtual

Remission Medical offers its navigator service through its own standalone virtual clinic. 

Pain associated with rheumatologic conditions increases the urgency to see a doctor. The goal of the virtual RemissionNavigator program is to meet rheumatology patients where they live, to bridge care gaps and reduce wait times, said Mr. Wehman.

RemissionNavigator accomplishes this through video visits and unlimited texting to its network of board-certified rheumatologists or rheumatology-focused advanced practice providers. Experts can answer questions about why labs are ordered, why a patient may have received a certain diagnosis, or provide detailed explanations of a rheumatic condition. 

“There are instances where improvement for the patient means waiting a couple days for us versus 45 days for their brick-and-mortar choice,” Mr. Wehman said. 

The program currently has 36 subscribers to Remission’s services, which include navigation. “We have 15 providers in a blend of employed and contracted relationships with Remission,” Mr. Wehman said. 

Even in its infancy, the navigator program has produced some success stories. “We had a patient tell us that thanks to us, he was seen faster, found relief immediately through our diagnosis and prescription of methotrexate, felt better at work, lost weight, and was happier in general,” Mr. Wehman said. 

Another patient was making monthly, 90-minute trips to Richmond for infusion services. Through the virtual program’s assistance, she is now receiving care from home and can get her monthly infusions at a local clinic. 

Ultimately, the goal is to help rheumatology move into an era of value-based care where the transition from fee-for-service to per patient will enable optimized care models and better accessibility, Mr. Wehman said. “It will not happen overnight, but every day we work toward this future.”
 

VA Targets Rheumatology Care

The Department of Veterans Affairs (VA) has also explored the use of navigator services in rheumatology, including virtual services. 

VA uses an integrated, interdisciplinary model that manages each veteran’s individual healthcare needs through a coordinated effort among providers, nurses, social workers, pharmacists, and other health professionals, according to VA press secretary Terrence Hayes.

Care coordination may include supporting scheduling appointments, managing chronic conditions, and coordinating care across different medical departments. “This coordination is particularly important in managing complex rheumatologic conditions, where multiple providers may be involved,” Mr. Hayes said.

Additionally, VA has launched a national telerheumatology initiative to improve access to rheumatology providers in rural areas. The initiative will assist veterans in understanding the telehealth system, navigating appointments, and ensuring they have the necessary technology for virtual consultations. 

“It will also facilitate communication between rheumatologists, primary care providers, and other specialists, ensuring that all team members are aligned in their approach to the veteran’s care,” Mr. Hayes said.
 

Who Will Take Advantage of New Codes? 

Currently, Remission Medical operates on a cash-pay model, but the company intends to transition to insurance-based coverage in 2025. 

Remission Medical also partners directly with preexisting healthcare systems and clinics such as Sentara Health and OrthoVirginia, where a PIN program, powered by Remission Medical’s virtual rheumatology network, may be explored as well. 

The company offers its partners synchronous virtual visits and e-consults. It’s likely that these larger organizations will explore coverage for navigator services for Medicare and private insurance. “We can be there to support them as they decide to implement this,” Mr. Wehman said.

Taking advantage of CMS’s navigator PIN codes is an eventual goal. Remission Medical has not submitted the codes yet, “but we do intend to as we continue to grow our membership count,” Mr. Wehman said. “We hope to provide coverage for most of the US and submit the codes to reimbursement by early to mid-2025.” 

In terms of reimbursement, the VA operates under a different payment model than Medicare or private insurance, focusing on providing integrated care within the VA system rather than reimbursing for specific services such as patient navigation.

While the SUNY clinic takes care of Medicare patients, it’s unlikely that the new CMS codes for navigators would apply to medical students. Students get paid a monthly stipend for doing navigator work. “There’s a policy about what students can get paid, and how many hours they can work,” Dr. Ginzler clarified. 

The SUNY Downstate and Lupus Foundation navigator programs rely on grants to sustain their services. Aurinia Pharmaceuticals has funded both programs, and the SUNY program received an additional grant from Janssen to expand its offerings. 

Because it’s grant funded, the navigator position at the Lupus Foundation does not bill patient insurance, Ms. Costillo explained. 
 

Navigator Work Requires Training

Before they start working with patients, navigators often go through a vetting or training process. At Remission Medical, a clinical leadership team does a synchronous interview, background check, and CV review of its potential navigators. 

Even before she became a navigator, Ms. Costillo had a strong baseline education in this work. She has a bachelor’s degree in social work and 15 years of experience in social services working with disabled, vulnerable, and underserved populations. Some of her fellow navigators at the Lupus Foundation of America also have degrees in social work. 

Ms. Costillo underwent training with the Patient-Centered Education & Research Institute to become a certified professional patient navigator. Her name is on the national registry. The curriculum covered various aspects of medical care such as patient and care team interactions and communications, health and clinical knowledge, patient care coordination and resources, and using evidence-based approaches. 

“For our lupus patients, it is essential that navigators understand the disease and the impact on patients and families, treatments available and those in the pipelines, and also the ins and outs of various insurance options,” Ms. Costillo said.

Mr. Wehman, Dr. Williams, and Ms. Costillo reported no disclosures. Dr. Ginzler has been a consultant for Aurinia Pharmaceuticals.

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

When a large rheumatology clinic in Richmond, Virginia, heard that Medicare would be reimbursing patient navigators, they decided to launch their own virtual navigator program. 

“We read about it and felt like it was the perfect representation of what we were already trying to do,” said Blake Wehman, founder and CEO of Remission Medical, which offers virtual diagnosis and longitudinal care in rheumatology.

Mr. Wehman has plans to start submitting for these principal illness navigation (PIN) codes in 2025. 

The Centers for Medicare & Medicaid Services (CMS) in 2024 began paying navigators who assist Medicare patients with high-risk conditions, which could include rheumatologic diseases. “The codes are not limited to a specific set of diagnoses; rather, the definition of a serious, high-risk condition is dependent on clinical judgment,” the agency clarified. 

CMS established this provision in the CY 2024 Physician Fee Schedule final rule. 

Reimbursing patient navigators is long overdue, noted Edith Williams, PhD, MS, director of the Center for Community Health and Prevention and founding director of the Office of Health Equity Research at the University of Rochester in New York. “It’s something our patients need. It’s something that the science is telling us can impact outcomes as an adjunct to clinical care,” she said. 

John Schlia

Dr. Williams said the new CMS codes “got our departments talking about what this policy is and how it would translate into patient care.”

The codes apply when navigators are assigned to support patients with high-risk conditions who need assistance connecting with clinical and other resources, including any unmet social determinants of health needs, or in diagnosis or treatment of their medical problems.

“Having a navigator by their side to help get through all the clinical and administrative challenges gives people an advocate and a partner who is with them and their families every step of the way to help make the journey easier,” said a CMS spokesperson. 

Not all navigator programs may qualify for the new codes. Some are supported by grants and don’t bill patient insurance. However, they all share a common goal: to guide patients through the healthcare continuum and assist with appointments and medication adherence. 
 

Identifying ‘Root Causes’ of Barriers

Navigators represent a wide variety of backgrounds, ranging from healthcare professionals to students or even patients themselves. They generally don’t provide medical advice. “However, we are responsible for making sure our patients and their families are educated and aware, then assist with guidance on their path,” said Katie Costillo, BSW, CPPN, patient navigator and program manager with the Lupus Foundation of America, Heartland Region.

“Training and experience in engaging and building rapport is essential to assisting patients overcome obstacles that limit their access to healthcare,” she said. Narrowing down with patients the root causes of their barriers and then identifying appropriate and available community resources is key. 

Studies have demonstrated the effectiveness of adding a navigator to a rheumatology patient’s care plan. In one study, a group of Boston researchers determined that navigators played a useful role in reducing adherence barriers to oral disease-modifying antirheumatic drugs. The navigators uncovered several concerns among 107 rheumatology patients, including fear of adverse events and medication effectiveness. 

They also helped to facilitate patient-physician communication, developed strategies to improve medication adherence, and provided medication and diagnosis education. Patients reported satisfaction with the navigator experience.

A study Dr. Williams coauthored that examined behavioral interventions to support African American women with systemic lupus erythematosus found that patient navigator participants had superior coping scores, compared with those engaged in peer-to-peer methodology and patient support groups.

“We had a lot of success with the mentorship program, too,” Dr. Williams said. Navigator services, however, offer more one-on-one attention, “and it’s more tailored to what the person needs rather than the set curriculum that the mentors delivered to their mentees.”
 

Supporting Patients With Lupus

Ideally, navigators should be able to relate to patients and know what they’re going through, Dr. Williams said. This is someone whom the patient can trust and depend on. “That’s where the benefit of having someone who is also a patient lies because they’re ultimately relatable to other patients. But different institutions have taken different approaches to this.” 

Some programs focus on specific rheumatologic conditions. The Lupus Foundation of America, for example, established patient navigator programs to assist patients with lupus in four markets across the country. 

The Heartland patient navigator program is available for all patients with lupus within its region, which includes Kansas, Missouri, and central and southern Illinois. As a navigator, Ms. Costillo has been assisting patients since 2022. In 2023, she began meeting with patients at the Washington University Lupus Clinic (WULC) in St. Louis, Missouri. 

Navigators work directly with patients before and after their appointment to ensure follow-up and reduce missed appointments. “They help lupus patients connect with community services and overcoming barriers to access and care. The goal of this position is to improve overall disease management, which results in better health outcomes,” Ms. Costillo said. 

Since its inception, the patient navigator program at WULC has shown a decrease in patient no-call no-shows and an increase in requests to reschedule as opposed to not showing up for their scheduled appointment, based on history. 

Patients have reported fewer barriers to transportation and improvement in access to resources, support, and disease education. “Our patients have also stated [that] meeting with the navigator during their appointments has helped them to feel heard, understood, and supported,” Ms. Costillo said.
 

Navigator Work Is Not Without Challenges

A total of 90% of patients with lupus are women, and women of color are two to three times more likely to develop lupus in their lifetime. 

“Based on socioeconomic statistics, lupus patients are in a demographic that is commonly underserved, underfunded, and often overlooked. Finding appropriate local community resources for a patient who must choose between feeding her family or paying for transportation to multiple physician appointments is a common problem,” Ms. Costillo said.

Much of the assistance that became available during the COVID pandemic is starting to disappear. “With the rising costs of daily living, we are having to find creative and alternative ways to break down barriers and find support to fill those gaps,” she continued.

Getting insurance coverage of patients is another challenge. Many patients with lupus will be prescribed a treatment that insurance refuses to cover even after the physician disputes it.

Additionally, many patients with lupus are unable to work to support their family. A majority who apply for Social Security Disability Insurance are denied on their first and second attempts, “requiring multiple hearings and pages of documentation from their physicians,” Ms. Costillo said. 
 

Students Serve as Navigators

One inner-city program is seeking to increase access to healthcare services to patients with lupus and lupus nephritis in underserved communities. In 2021, SUNY Downstate Health Sciences University in New York City, in partnership with the Brooklyn Free Clinic and Brooklyn Health Disparities Center, launched a program to teach navigator skills to second-year medical students. 

The students assist patients at the Arthritis Clinic at University Hospital at Downstate. “Many of our patients have either low medical literacy or difficulty with English. Many of them are immigrants,” said Ellen M. Ginzler, MD, MPH, SUNY Downstate’s professor emerita and former vice-chair for research and rheumatology division chief. 

Dr. Ginzler sought out navigator candidates who showed a strong interest in working with underserved patients with complicated, severe disease who struggled with keeping appointments or adhering to medication regimens. The program also gave preference to students fluent in other languages such as Spanish. 

All these efforts have generated improvements in care.

Assessing the program’s effectiveness in a cross-sectional study, Dr. Ginzler and colleagues reported that 94% of navigators were able to schedule appointments and 87% assisted with prescriptions. Navigators also had high success rates in answering medical questions, getting in touch with a patient’s doctor, and reminding patients of medical appointments. 

Medical student Jeremy Wilson, a coauthor of the study, served as a navigator for a woman with lupus and scleroderma for many years, along with other comorbidities.

Mr. Wilson went above and beyond for this patient, helping to secure social services supports that included accompanying her to clinic visits and serving as her advocate. “She found an enormous difference in how she was treated when she went to these clinics because the doctors in those clinics took her much more seriously,” Dr. Ginzler said. Mr. Wilson ran interference to secure clinic appointments and worked with the patient’s rheumatology fellow in the clinic to get approval for medications. 

Mr. Wilson and the patient formed a great bond. “It not only helped the patient, but it helped Jeremy tremendously in terms of how he felt about his medical career,” Dr. Ginzler said. 

The program has since expanded to include patients with other rheumatic diseases, such as rheumatoid arthritis and psoriatic arthritis, and also offers navigator services in dermatology. 

A total of 21 students to date have completed the second year of the program. “We’ve just selected eight more,” Dr. Ginzler said. Some of the students continue to do the program in their third or even fourth year as they’re applying for residencies. 

A student-run, unpublished survey of nine students in the SUNY program found that all nine reported high confidence in identifying social factors that impact patient health and well-being, compared with four who reported high confidence prior to starting the program. “Additionally, students reported increased confidence in providing comprehensive care in rheumatology and dermatology, and interdisciplinary collaboration,” study author Alejandra K. Moncayo, MPH, and colleagues wrote. 
 

When Navigators Go Virtual

Remission Medical offers its navigator service through its own standalone virtual clinic. 

Pain associated with rheumatologic conditions increases the urgency to see a doctor. The goal of the virtual RemissionNavigator program is to meet rheumatology patients where they live, to bridge care gaps and reduce wait times, said Mr. Wehman.

RemissionNavigator accomplishes this through video visits and unlimited texting to its network of board-certified rheumatologists or rheumatology-focused advanced practice providers. Experts can answer questions about why labs are ordered, why a patient may have received a certain diagnosis, or provide detailed explanations of a rheumatic condition. 

“There are instances where improvement for the patient means waiting a couple days for us versus 45 days for their brick-and-mortar choice,” Mr. Wehman said. 

The program currently has 36 subscribers to Remission’s services, which include navigation. “We have 15 providers in a blend of employed and contracted relationships with Remission,” Mr. Wehman said. 

Even in its infancy, the navigator program has produced some success stories. “We had a patient tell us that thanks to us, he was seen faster, found relief immediately through our diagnosis and prescription of methotrexate, felt better at work, lost weight, and was happier in general,” Mr. Wehman said. 

Another patient was making monthly, 90-minute trips to Richmond for infusion services. Through the virtual program’s assistance, she is now receiving care from home and can get her monthly infusions at a local clinic. 

Ultimately, the goal is to help rheumatology move into an era of value-based care where the transition from fee-for-service to per patient will enable optimized care models and better accessibility, Mr. Wehman said. “It will not happen overnight, but every day we work toward this future.”
 

VA Targets Rheumatology Care

The Department of Veterans Affairs (VA) has also explored the use of navigator services in rheumatology, including virtual services. 

VA uses an integrated, interdisciplinary model that manages each veteran’s individual healthcare needs through a coordinated effort among providers, nurses, social workers, pharmacists, and other health professionals, according to VA press secretary Terrence Hayes.

Care coordination may include supporting scheduling appointments, managing chronic conditions, and coordinating care across different medical departments. “This coordination is particularly important in managing complex rheumatologic conditions, where multiple providers may be involved,” Mr. Hayes said.

Additionally, VA has launched a national telerheumatology initiative to improve access to rheumatology providers in rural areas. The initiative will assist veterans in understanding the telehealth system, navigating appointments, and ensuring they have the necessary technology for virtual consultations. 

“It will also facilitate communication between rheumatologists, primary care providers, and other specialists, ensuring that all team members are aligned in their approach to the veteran’s care,” Mr. Hayes said.
 

Who Will Take Advantage of New Codes? 

Currently, Remission Medical operates on a cash-pay model, but the company intends to transition to insurance-based coverage in 2025. 

Remission Medical also partners directly with preexisting healthcare systems and clinics such as Sentara Health and OrthoVirginia, where a PIN program, powered by Remission Medical’s virtual rheumatology network, may be explored as well. 

The company offers its partners synchronous virtual visits and e-consults. It’s likely that these larger organizations will explore coverage for navigator services for Medicare and private insurance. “We can be there to support them as they decide to implement this,” Mr. Wehman said.

Taking advantage of CMS’s navigator PIN codes is an eventual goal. Remission Medical has not submitted the codes yet, “but we do intend to as we continue to grow our membership count,” Mr. Wehman said. “We hope to provide coverage for most of the US and submit the codes to reimbursement by early to mid-2025.” 

In terms of reimbursement, the VA operates under a different payment model than Medicare or private insurance, focusing on providing integrated care within the VA system rather than reimbursing for specific services such as patient navigation.

While the SUNY clinic takes care of Medicare patients, it’s unlikely that the new CMS codes for navigators would apply to medical students. Students get paid a monthly stipend for doing navigator work. “There’s a policy about what students can get paid, and how many hours they can work,” Dr. Ginzler clarified. 

The SUNY Downstate and Lupus Foundation navigator programs rely on grants to sustain their services. Aurinia Pharmaceuticals has funded both programs, and the SUNY program received an additional grant from Janssen to expand its offerings. 

Because it’s grant funded, the navigator position at the Lupus Foundation does not bill patient insurance, Ms. Costillo explained. 
 

Navigator Work Requires Training

Before they start working with patients, navigators often go through a vetting or training process. At Remission Medical, a clinical leadership team does a synchronous interview, background check, and CV review of its potential navigators. 

Even before she became a navigator, Ms. Costillo had a strong baseline education in this work. She has a bachelor’s degree in social work and 15 years of experience in social services working with disabled, vulnerable, and underserved populations. Some of her fellow navigators at the Lupus Foundation of America also have degrees in social work. 

Ms. Costillo underwent training with the Patient-Centered Education & Research Institute to become a certified professional patient navigator. Her name is on the national registry. The curriculum covered various aspects of medical care such as patient and care team interactions and communications, health and clinical knowledge, patient care coordination and resources, and using evidence-based approaches. 

“For our lupus patients, it is essential that navigators understand the disease and the impact on patients and families, treatments available and those in the pipelines, and also the ins and outs of various insurance options,” Ms. Costillo said.

Mr. Wehman, Dr. Williams, and Ms. Costillo reported no disclosures. Dr. Ginzler has been a consultant for Aurinia Pharmaceuticals.

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

The US Food and Drug Administration (FDA) has granted a second-line indication to amivantamab-vmjw (Rybrevant, Janssen Biotech) in non–small-cell lung cancer (NSCLC). 

Amivantamab with carboplatin and pemetrexed is now indicated for adults with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI).

The FDA has already approved first-line use of amivantamab in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as reported by Medscape Medical News. 

The second-line approval for amivantamab plus chemotherapy “may address the most common mechanisms of treatment resistance to third-generation EGFR TKIs, such as osimertinib, in the first line,” Martin Dietrich, MD, PhD, oncologist, Cancer Care Centers of Brevard in Florida, said in a company news release.

“This multitargeted combination extended progression-free survival (PFS) and improved overall response compared to chemotherapy alone, offering an important and effective new second-line option for patients,” Dr. Dietrich added. 

The second-line indication is supported by the phase 3 MARIPOSA-2 study, which included 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and disease progression on or after receiving osimertinib.

The study demonstrated a 52% reduced risk of disease progression or death when amivantamab was added to carboplatin and pemetrexed (hazard ratio, 0.48). 

Median PFS was 6.3 months with amivantamab vs 4.2 months with chemotherapy alone. The confirmed objective response rate was 53% in the amivantamab plus chemotherapy group vs 29% in the chemotherapy only group. 

The most common adverse reactions, occurring in at least 20% of patients, were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.

The company noted that amivantamab in combination with chemotherapy is the only category 1 treatment option in National Comprehensive Cancer Network clinical practice guidelines for patients with EGFR-mutated NSCLC who have progressed on osimertinib and who are symptomatic with multiple lesions.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted a second-line indication to amivantamab-vmjw (Rybrevant, Janssen Biotech) in non–small-cell lung cancer (NSCLC). 

Amivantamab with carboplatin and pemetrexed is now indicated for adults with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI).

The FDA has already approved first-line use of amivantamab in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as reported by Medscape Medical News. 

The second-line approval for amivantamab plus chemotherapy “may address the most common mechanisms of treatment resistance to third-generation EGFR TKIs, such as osimertinib, in the first line,” Martin Dietrich, MD, PhD, oncologist, Cancer Care Centers of Brevard in Florida, said in a company news release.

“This multitargeted combination extended progression-free survival (PFS) and improved overall response compared to chemotherapy alone, offering an important and effective new second-line option for patients,” Dr. Dietrich added. 

The second-line indication is supported by the phase 3 MARIPOSA-2 study, which included 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and disease progression on or after receiving osimertinib.

The study demonstrated a 52% reduced risk of disease progression or death when amivantamab was added to carboplatin and pemetrexed (hazard ratio, 0.48). 

Median PFS was 6.3 months with amivantamab vs 4.2 months with chemotherapy alone. The confirmed objective response rate was 53% in the amivantamab plus chemotherapy group vs 29% in the chemotherapy only group. 

The most common adverse reactions, occurring in at least 20% of patients, were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.

The company noted that amivantamab in combination with chemotherapy is the only category 1 treatment option in National Comprehensive Cancer Network clinical practice guidelines for patients with EGFR-mutated NSCLC who have progressed on osimertinib and who are symptomatic with multiple lesions.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted a second-line indication to amivantamab-vmjw (Rybrevant, Janssen Biotech) in non–small-cell lung cancer (NSCLC). 

Amivantamab with carboplatin and pemetrexed is now indicated for adults with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI).

The FDA has already approved first-line use of amivantamab in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as reported by Medscape Medical News. 

The second-line approval for amivantamab plus chemotherapy “may address the most common mechanisms of treatment resistance to third-generation EGFR TKIs, such as osimertinib, in the first line,” Martin Dietrich, MD, PhD, oncologist, Cancer Care Centers of Brevard in Florida, said in a company news release.

“This multitargeted combination extended progression-free survival (PFS) and improved overall response compared to chemotherapy alone, offering an important and effective new second-line option for patients,” Dr. Dietrich added. 

The second-line indication is supported by the phase 3 MARIPOSA-2 study, which included 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and disease progression on or after receiving osimertinib.

The study demonstrated a 52% reduced risk of disease progression or death when amivantamab was added to carboplatin and pemetrexed (hazard ratio, 0.48). 

Median PFS was 6.3 months with amivantamab vs 4.2 months with chemotherapy alone. The confirmed objective response rate was 53% in the amivantamab plus chemotherapy group vs 29% in the chemotherapy only group. 

The most common adverse reactions, occurring in at least 20% of patients, were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.

The company noted that amivantamab in combination with chemotherapy is the only category 1 treatment option in National Comprehensive Cancer Network clinical practice guidelines for patients with EGFR-mutated NSCLC who have progressed on osimertinib and who are symptomatic with multiple lesions.

A version of this article appeared on Medscape.com.

TOPLINE:

Newborns who go on to develop atopic dermatitis (AD) show higher transepidermal water loss (TEWL) and cord blood serum levels of CCL17/thymus- and activation-regulated chemokine (TARC) and interleukin (IL) 31.

METHODOLOGY:

• Researchers conducted a prospective study to evaluate the predictive role of serologic biomarkers and cutaneous markers and the development of AD in 40 full-term newborns from a university hospital in Italy.
• Cord blood was collected at birth and analyzed for serum biomarkers such as CCL17/TARC and IL-31.
• TEWL and skin hydration rates were measured at 1, 6, and 12 months, and dermatological features such as dryness, cradle cap, and eczematous lesions were also monitored during visits.

TAKEAWAY:

• At 6 months, 16 infants had symptoms of AD, which included dry skin, pruritus, and keratosis pilaris, which persisted at 12 months. Their mean Eczema Area and Severity Index score was 6.6 at 6 months and 2.9 at 12 months.
• Infants with signs of AD had significantly higher TEWL levels at the anterior cubital fossa at 1, 6, and 12 months than those without AD.
• Cord blood levels of CCL17/TARC and IL-31 were significantly higher in infants with AD.
• A correlation was found between TEWL values and CCL17 levels at 1, 6, and 12 months.

IN PRACTICE:

“This study highlights the potential of cord serum/TARC and IL-31 levels as predictive markers for AD onset in infancy, in combination with cutaneous markers,” the authors wrote. “Stratified interventions based on these variables, family history, FLG [filaggrin] variations, and other biomarkers could offer more targeted approaches to AD prevention and management, especially during the first year of life,” they added.

SOURCE:

The study was led by Angelo Massimiliano D’Erme, MD, PhD, of the Dermatology Unit, in the Department of Medical and Oncology, University of Pisa, Pisa, Italy, and was published online in JAMA Dermatology.

LIMITATIONS:

The limitations included the observational design and small sample size, and it was a single-center study.

DISCLOSURES:

The authors did not disclose any funding information. One author disclosed receiving personal fees from various pharmaceutical companies and serving as a founder and chairman of a nonprofit organization.

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

TOPLINE:

Newborns who go on to develop atopic dermatitis (AD) show higher transepidermal water loss (TEWL) and cord blood serum levels of CCL17/thymus- and activation-regulated chemokine (TARC) and interleukin (IL) 31.

METHODOLOGY:

• Researchers conducted a prospective study to evaluate the predictive role of serologic biomarkers and cutaneous markers and the development of AD in 40 full-term newborns from a university hospital in Italy.
• Cord blood was collected at birth and analyzed for serum biomarkers such as CCL17/TARC and IL-31.
• TEWL and skin hydration rates were measured at 1, 6, and 12 months, and dermatological features such as dryness, cradle cap, and eczematous lesions were also monitored during visits.

TAKEAWAY:

• At 6 months, 16 infants had symptoms of AD, which included dry skin, pruritus, and keratosis pilaris, which persisted at 12 months. Their mean Eczema Area and Severity Index score was 6.6 at 6 months and 2.9 at 12 months.
• Infants with signs of AD had significantly higher TEWL levels at the anterior cubital fossa at 1, 6, and 12 months than those without AD.
• Cord blood levels of CCL17/TARC and IL-31 were significantly higher in infants with AD.
• A correlation was found between TEWL values and CCL17 levels at 1, 6, and 12 months.

IN PRACTICE:

“This study highlights the potential of cord serum/TARC and IL-31 levels as predictive markers for AD onset in infancy, in combination with cutaneous markers,” the authors wrote. “Stratified interventions based on these variables, family history, FLG [filaggrin] variations, and other biomarkers could offer more targeted approaches to AD prevention and management, especially during the first year of life,” they added.

SOURCE:

The study was led by Angelo Massimiliano D’Erme, MD, PhD, of the Dermatology Unit, in the Department of Medical and Oncology, University of Pisa, Pisa, Italy, and was published online in JAMA Dermatology.

LIMITATIONS:

The limitations included the observational design and small sample size, and it was a single-center study.

DISCLOSURES:

The authors did not disclose any funding information. One author disclosed receiving personal fees from various pharmaceutical companies and serving as a founder and chairman of a nonprofit organization.

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

TOPLINE:

Newborns who go on to develop atopic dermatitis (AD) show higher transepidermal water loss (TEWL) and cord blood serum levels of CCL17/thymus- and activation-regulated chemokine (TARC) and interleukin (IL) 31.

METHODOLOGY:

• Researchers conducted a prospective study to evaluate the predictive role of serologic biomarkers and cutaneous markers and the development of AD in 40 full-term newborns from a university hospital in Italy.
• Cord blood was collected at birth and analyzed for serum biomarkers such as CCL17/TARC and IL-31.
• TEWL and skin hydration rates were measured at 1, 6, and 12 months, and dermatological features such as dryness, cradle cap, and eczematous lesions were also monitored during visits.

TAKEAWAY:

• At 6 months, 16 infants had symptoms of AD, which included dry skin, pruritus, and keratosis pilaris, which persisted at 12 months. Their mean Eczema Area and Severity Index score was 6.6 at 6 months and 2.9 at 12 months.
• Infants with signs of AD had significantly higher TEWL levels at the anterior cubital fossa at 1, 6, and 12 months than those without AD.
• Cord blood levels of CCL17/TARC and IL-31 were significantly higher in infants with AD.
• A correlation was found between TEWL values and CCL17 levels at 1, 6, and 12 months.

IN PRACTICE:

“This study highlights the potential of cord serum/TARC and IL-31 levels as predictive markers for AD onset in infancy, in combination with cutaneous markers,” the authors wrote. “Stratified interventions based on these variables, family history, FLG [filaggrin] variations, and other biomarkers could offer more targeted approaches to AD prevention and management, especially during the first year of life,” they added.

SOURCE:

The study was led by Angelo Massimiliano D’Erme, MD, PhD, of the Dermatology Unit, in the Department of Medical and Oncology, University of Pisa, Pisa, Italy, and was published online in JAMA Dermatology.

LIMITATIONS:

The limitations included the observational design and small sample size, and it was a single-center study.

DISCLOSURES:

The authors did not disclose any funding information. One author disclosed receiving personal fees from various pharmaceutical companies and serving as a founder and chairman of a nonprofit organization.

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

CHICAGO — The nonhormonal investigational drug elinzanetant led to significant improvement in hot flashes as well as sleep disturbance and quality of life, according to data from three randomized controlled trials presented at The Menopause Society 2024 Annual Meeting in Chicago. Two phase 3 trials, OASIS 1 and 2, were also published in JAMA, and the longer-term OASIS 3 trial was presented as a poster at the conference.

Elinzanetant is a selective neurokinin (NK) receptor antagonist, similar to fezolinetant, the first drug in this class approved by the US Food and Drug Administration (FDA) for vasomotor symptoms in May 2023. This class of medications targets the estrogen-sensitive kisspeptin/NK B/dynorphin (KNDy) neurons thought to play a role in thermoregulation and hot flashes during menopause. While fezolinetant targets only the NK-3 receptor, elinzanetant is a dual NK receptor antagonist that targets both NK-1 and NK-3. Bayer submitted a New Drug Application for elinzanetant to the FDA on August 1.

For those in whom hormone therapy is contraindicated, “it’s always been difficult for women with really severe symptoms to have a safe and effective therapy,” lead author JoAnn Pinkerton, MD, a professor of ob.gyn. at the University of Virginia in Charlottesville, Virginia, told this news organization. “The nonhormonal therapies we’ve used mostly off-label — the antidepressants, gabapentin, clonidine, oxybutynin — do help the hot flashes, but they don’t work nearly as effectively as these new NK receptor antagonists, and having one that looks like it might have a broader use for hot flashes, night sweats, mood, and sleep is just really exciting.”

Dr. Pinkerton said approximately 80% of the women in the OASIS 1 and 2 studies had at least a 50% reduction in hot flashes. “It was a very strong, dramatic positive finding, but the improvements in sleep and mood have really encouraged us to go further,” she said.

Declining estrogen levels during and after menopause can cause hypertrophy and hyperactivity of the KNDy neurons, which has been linked to thermoregulation disruptions that may trigger hot flashes, James Simon, MD, a clinical professor of ob.gyn. at The George Washington University School of Medicine & Health Sciences and medical director of IntimMedicine in Washington, DC, told attendees. He presented pooled data from OASIS 1 and 2. The NK-1 receptor, targeted by elinzanetant but not fezolinetant, is also thought to play a role in insomnia and possibly in mood.

“Oftentimes the focus on a lot of these drugs is hot flashes, hot flashes, hot flashes, but we know hot flashes do not occur in isolation,” Chrisandra Shufelt, MD, professor and chair of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Florida, told this news organization. Elinzanetant is “an interesting compound because it actually works on sleep, and that was critical because sleep disturbance precedes” many other menopausal symptoms, said Dr. Shufelt, who was not involved in the study.

“I think it is an outstanding option for women who don’t have the opportunity to get hormones,” Dr. Shufelt said, and she was particularly pleased to see there were no safety concerns for the liver in the trial data. The FDA issued a warning on September 12 about the risk for rare liver injury with fezolinetant, but the early signals that had been seen in fezolinetant data were not seen in these elinzanetant data.

The OASIS 1 and 2 trials enrolled postmenopausal women, aged 40-65 years, who had at least 50 moderate to severe vasomotor occurrences per week.

“A moderate hot flash is a hot flash that is also associated with sweating, and a severe hot flash is a moderate hot flash that stops a woman in her tracks,” Dr. Simon said. “Namely, it’s severe enough with sweating and central nervous system effects that she is interrupted in whatever it is that she’s doing at the time.”

Exclusion criteria for the trials included a history of arrhythmias, heart block, or QT prolongation; abnormal lab results; history of malignancy within the past 5 years; uncontrolled or treatment-resistant hypertension, hypothyroidism, or hyperthyroidism; unexplained postmenopausal bleeding; clinically relevant abnormal mammogram findings; or disordered proliferative endometrium, endometrial hyperplasia, polyp, or endometrial cancer.

The predominantly White (80%) women were an average 54 years old, with an average body mass index (BMI) of 27.8, and were an average 3.5 years from their last period. For the first 12 weeks of the trials, 399 women were assigned to receive 120 mg once daily of oral elinzanetant and 397 were assigned to once daily placebo. Then the women taking placebo switched to elinzanetant for the final 14 weeks of the study.

The endpoints included mean change in frequency and severity of vasomotor symptoms at weeks 1, 4, and 12 as well as change in sleep disturbance and quality of life at week 12. Sleep was assessed with the Patient-Reported Outcomes Measurement Information System Sleep Disturbance–Short Form score, which ranges from 28.9 to 76.5, with a higher number denoting greater sleep disturbance. The Menopause-Specific Quality-of-Life score ranges from 1 to 8, with a higher score indicating poorer quality of life.

Daily frequency of vasomotor symptoms was 14 per day at baseline in the elinzanetant group, decreasing by 4.8 per day at week 1, 8 per day at week 4, and 9.4 per day at week 12. In the placebo group, women had an average 15.2 occurrences per day at baseline, which decreased by 3.2 at week 1, 5.2 at week 4, and 6.4 at week 12. Comparing the groups at 12 weeks, those receiving elinzanetant had 3.2 fewer daily vasomotor symptoms than those receiving placebo (P < .0001).

The severity of vasomotor symptoms also improved more in the elinzanetant group than in the placebo group over 12 weeks, after which severity improved further in those who switched from placebo to elinzanetant (P < .0001).

Sleep disturbance scores, starting at a mean 61.5 in the elinzanetant group and 60.5 in the placebo group, fell 10.7 points in the elinzanetant group and 5.3 points in the placebo group at 12 weeks, for a difference of 4.9 points (P < .0001). Sleep then further improved in those who switched from placebo to elinzanetant. Quality-of-life scores improved 1.37 points (from 4.52 at baseline) in the elinzanetant group and 0.96 points (from 4.49 at baseline) in the placebo group, for a mean difference at 12 weeks of 0.36 (P < .0001).

Though no head-to-head data exist comparing elinzanetant and fezolinetant, Dr. Simon told this news organization the side effects with fezolinetant “tend to be gastrointestinal, whereas the side effects for elinzanetant tend to be central nervous system,” such as drowsiness and lethargy.

The women who are the best candidates for elinzanetant, Dr. Pinkerton told this news organization, include those who have had an estrogen-sensitive cancer, such as breast or endometrial cancer, or who have fear of it, a family history, or are otherwise high risk. Other ideal candidates include those with a history of venous thromboembolism, people who have migraine with aura (due to concerns about increased risk for stroke), and those who have endometriosis or large fibroids.

“Then the last group might be women who took hormone therapy in their 50s and want to continue, but they’re trying to go off, and they have a recurrence of their hot flashes or night sweats or sleep issues,” Dr. Pinkerton said. “This might be a great group to switch over.”

OASIS 3 assessed the drug for 1 year and “supported the results of OASIS 1 and 2, demonstrating efficacy over a longer study duration and in a population with a vasomotor symptom profile representative of that seen in clinical practice,” Nick Panay, BSc, MBBS, director of the Menopause & PMS Centre at Queen Charlotte’s Hospital & Imperial College London, London, England, and his colleague reported.

Among 628 postmenopausal women aged 40-65, the predominantly White (78.5%) women were an average 54 years old, with an average BMI of 27.6, and were an average 5 years past their last period. Half received 120 mg elinzanetant and half received a placebo for 52 weeks.

At 12 weeks, the women receiving elinzanetant reported an average 1.6 moderate to severe vasomotor symptoms per day, down from 6.7 at baseline. Daily average symptoms in the placebo group fell from 6.8 at baseline to 3.4 at 12 weeks, for a difference of 1.6 fewer occurrences per day in the elinzanetant group (P < .0001).

Sleep disturbances also improved, falling 9.4 points from a baseline 57.4 in the elinzanetant group and 5.7 points from a baseline 58 in the placebo group. Quality-of-life scores improved from 4.1 to 2.8 (−1.3 change) in the elinzanetant group and from 4.4 to 3.3 (−1.1 change) in the placebo group.

In addition to looking at treatment-emergent adverse events, the safety assessments also included endometrial biopsies; bone mineral density in the femoral neck, hip, and lumbar spine; weight; and labs. Adverse events related to the study drug occurred in 30.4% of those in the elinzanetant group and 14.6% of those in the placebo group. The most commonly reported adverse events were headache (9.6% elinzanetant vs 7% placebo), fatigue (7% vs 10.2%), and sleepiness (5.1% vs 1.3%). A higher proportion of women taking elinzanetant (12.5%) than those taking placebo (4.1%) discontinued the study.

No serious adverse events deemed to be treatment-related occurred in either group, and no endometrial hyperplasia or malignant neoplasm occurred in either group. Bone mineral density changes in both groups were within the expected range for the women’s age, and their weight remained stable over the 52 weeks.

Six women taking elinzanetant and four taking placebo met predefined criteria for close liver observation, but none showed hepatotoxicity or evidence of possible drug-induced liver injury.

The research was funded by Bayer. Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer. Dr. Shufelt had no disclosures. Dr. Simon had grant/research support, consulting/advisory board participation, and/or speaking disclosures with AbbVie, Bayer Healthcare, Besins Healthcare, California Institute of Integral Studies, Camargo Pharmaceutical Services, Covance, Daré Bioscience, DEKA M.E.L.A S.r.l., Femasys, Ipsen, KaNDy/NeRRe Therapeutics, Khyria, Madorra, Mayne Pharma, Mitsubishi Tanabe Pharma Development America, Mylan/Viatris Inc, Myovant Sciences, ObsEva SA, Pfizer, Pharmavite, QUE Oncology, Scynexis, Sebela Pharmaceuticals, Sprout Pharmaceuticals, TherapeuticsMD, Vella Bioscience, and Viveve Medical, and he is a stockholder in Sermonix Pharmaceuticals.

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

CHICAGO — The nonhormonal investigational drug elinzanetant led to significant improvement in hot flashes as well as sleep disturbance and quality of life, according to data from three randomized controlled trials presented at The Menopause Society 2024 Annual Meeting in Chicago. Two phase 3 trials, OASIS 1 and 2, were also published in JAMA, and the longer-term OASIS 3 trial was presented as a poster at the conference.

Elinzanetant is a selective neurokinin (NK) receptor antagonist, similar to fezolinetant, the first drug in this class approved by the US Food and Drug Administration (FDA) for vasomotor symptoms in May 2023. This class of medications targets the estrogen-sensitive kisspeptin/NK B/dynorphin (KNDy) neurons thought to play a role in thermoregulation and hot flashes during menopause. While fezolinetant targets only the NK-3 receptor, elinzanetant is a dual NK receptor antagonist that targets both NK-1 and NK-3. Bayer submitted a New Drug Application for elinzanetant to the FDA on August 1.

For those in whom hormone therapy is contraindicated, “it’s always been difficult for women with really severe symptoms to have a safe and effective therapy,” lead author JoAnn Pinkerton, MD, a professor of ob.gyn. at the University of Virginia in Charlottesville, Virginia, told this news organization. “The nonhormonal therapies we’ve used mostly off-label — the antidepressants, gabapentin, clonidine, oxybutynin — do help the hot flashes, but they don’t work nearly as effectively as these new NK receptor antagonists, and having one that looks like it might have a broader use for hot flashes, night sweats, mood, and sleep is just really exciting.”

Dr. Pinkerton said approximately 80% of the women in the OASIS 1 and 2 studies had at least a 50% reduction in hot flashes. “It was a very strong, dramatic positive finding, but the improvements in sleep and mood have really encouraged us to go further,” she said.

Declining estrogen levels during and after menopause can cause hypertrophy and hyperactivity of the KNDy neurons, which has been linked to thermoregulation disruptions that may trigger hot flashes, James Simon, MD, a clinical professor of ob.gyn. at The George Washington University School of Medicine & Health Sciences and medical director of IntimMedicine in Washington, DC, told attendees. He presented pooled data from OASIS 1 and 2. The NK-1 receptor, targeted by elinzanetant but not fezolinetant, is also thought to play a role in insomnia and possibly in mood.

“Oftentimes the focus on a lot of these drugs is hot flashes, hot flashes, hot flashes, but we know hot flashes do not occur in isolation,” Chrisandra Shufelt, MD, professor and chair of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Florida, told this news organization. Elinzanetant is “an interesting compound because it actually works on sleep, and that was critical because sleep disturbance precedes” many other menopausal symptoms, said Dr. Shufelt, who was not involved in the study.

“I think it is an outstanding option for women who don’t have the opportunity to get hormones,” Dr. Shufelt said, and she was particularly pleased to see there were no safety concerns for the liver in the trial data. The FDA issued a warning on September 12 about the risk for rare liver injury with fezolinetant, but the early signals that had been seen in fezolinetant data were not seen in these elinzanetant data.

The OASIS 1 and 2 trials enrolled postmenopausal women, aged 40-65 years, who had at least 50 moderate to severe vasomotor occurrences per week.

“A moderate hot flash is a hot flash that is also associated with sweating, and a severe hot flash is a moderate hot flash that stops a woman in her tracks,” Dr. Simon said. “Namely, it’s severe enough with sweating and central nervous system effects that she is interrupted in whatever it is that she’s doing at the time.”

Exclusion criteria for the trials included a history of arrhythmias, heart block, or QT prolongation; abnormal lab results; history of malignancy within the past 5 years; uncontrolled or treatment-resistant hypertension, hypothyroidism, or hyperthyroidism; unexplained postmenopausal bleeding; clinically relevant abnormal mammogram findings; or disordered proliferative endometrium, endometrial hyperplasia, polyp, or endometrial cancer.

The predominantly White (80%) women were an average 54 years old, with an average body mass index (BMI) of 27.8, and were an average 3.5 years from their last period. For the first 12 weeks of the trials, 399 women were assigned to receive 120 mg once daily of oral elinzanetant and 397 were assigned to once daily placebo. Then the women taking placebo switched to elinzanetant for the final 14 weeks of the study.

The endpoints included mean change in frequency and severity of vasomotor symptoms at weeks 1, 4, and 12 as well as change in sleep disturbance and quality of life at week 12. Sleep was assessed with the Patient-Reported Outcomes Measurement Information System Sleep Disturbance–Short Form score, which ranges from 28.9 to 76.5, with a higher number denoting greater sleep disturbance. The Menopause-Specific Quality-of-Life score ranges from 1 to 8, with a higher score indicating poorer quality of life.

Daily frequency of vasomotor symptoms was 14 per day at baseline in the elinzanetant group, decreasing by 4.8 per day at week 1, 8 per day at week 4, and 9.4 per day at week 12. In the placebo group, women had an average 15.2 occurrences per day at baseline, which decreased by 3.2 at week 1, 5.2 at week 4, and 6.4 at week 12. Comparing the groups at 12 weeks, those receiving elinzanetant had 3.2 fewer daily vasomotor symptoms than those receiving placebo (P < .0001).

The severity of vasomotor symptoms also improved more in the elinzanetant group than in the placebo group over 12 weeks, after which severity improved further in those who switched from placebo to elinzanetant (P < .0001).

Sleep disturbance scores, starting at a mean 61.5 in the elinzanetant group and 60.5 in the placebo group, fell 10.7 points in the elinzanetant group and 5.3 points in the placebo group at 12 weeks, for a difference of 4.9 points (P < .0001). Sleep then further improved in those who switched from placebo to elinzanetant. Quality-of-life scores improved 1.37 points (from 4.52 at baseline) in the elinzanetant group and 0.96 points (from 4.49 at baseline) in the placebo group, for a mean difference at 12 weeks of 0.36 (P < .0001).

Though no head-to-head data exist comparing elinzanetant and fezolinetant, Dr. Simon told this news organization the side effects with fezolinetant “tend to be gastrointestinal, whereas the side effects for elinzanetant tend to be central nervous system,” such as drowsiness and lethargy.

The women who are the best candidates for elinzanetant, Dr. Pinkerton told this news organization, include those who have had an estrogen-sensitive cancer, such as breast or endometrial cancer, or who have fear of it, a family history, or are otherwise high risk. Other ideal candidates include those with a history of venous thromboembolism, people who have migraine with aura (due to concerns about increased risk for stroke), and those who have endometriosis or large fibroids.

“Then the last group might be women who took hormone therapy in their 50s and want to continue, but they’re trying to go off, and they have a recurrence of their hot flashes or night sweats or sleep issues,” Dr. Pinkerton said. “This might be a great group to switch over.”

OASIS 3 assessed the drug for 1 year and “supported the results of OASIS 1 and 2, demonstrating efficacy over a longer study duration and in a population with a vasomotor symptom profile representative of that seen in clinical practice,” Nick Panay, BSc, MBBS, director of the Menopause & PMS Centre at Queen Charlotte’s Hospital & Imperial College London, London, England, and his colleague reported.

Among 628 postmenopausal women aged 40-65, the predominantly White (78.5%) women were an average 54 years old, with an average BMI of 27.6, and were an average 5 years past their last period. Half received 120 mg elinzanetant and half received a placebo for 52 weeks.

At 12 weeks, the women receiving elinzanetant reported an average 1.6 moderate to severe vasomotor symptoms per day, down from 6.7 at baseline. Daily average symptoms in the placebo group fell from 6.8 at baseline to 3.4 at 12 weeks, for a difference of 1.6 fewer occurrences per day in the elinzanetant group (P < .0001).

Sleep disturbances also improved, falling 9.4 points from a baseline 57.4 in the elinzanetant group and 5.7 points from a baseline 58 in the placebo group. Quality-of-life scores improved from 4.1 to 2.8 (−1.3 change) in the elinzanetant group and from 4.4 to 3.3 (−1.1 change) in the placebo group.

In addition to looking at treatment-emergent adverse events, the safety assessments also included endometrial biopsies; bone mineral density in the femoral neck, hip, and lumbar spine; weight; and labs. Adverse events related to the study drug occurred in 30.4% of those in the elinzanetant group and 14.6% of those in the placebo group. The most commonly reported adverse events were headache (9.6% elinzanetant vs 7% placebo), fatigue (7% vs 10.2%), and sleepiness (5.1% vs 1.3%). A higher proportion of women taking elinzanetant (12.5%) than those taking placebo (4.1%) discontinued the study.

No serious adverse events deemed to be treatment-related occurred in either group, and no endometrial hyperplasia or malignant neoplasm occurred in either group. Bone mineral density changes in both groups were within the expected range for the women’s age, and their weight remained stable over the 52 weeks.

Six women taking elinzanetant and four taking placebo met predefined criteria for close liver observation, but none showed hepatotoxicity or evidence of possible drug-induced liver injury.

The research was funded by Bayer. Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer. Dr. Shufelt had no disclosures. Dr. Simon had grant/research support, consulting/advisory board participation, and/or speaking disclosures with AbbVie, Bayer Healthcare, Besins Healthcare, California Institute of Integral Studies, Camargo Pharmaceutical Services, Covance, Daré Bioscience, DEKA M.E.L.A S.r.l., Femasys, Ipsen, KaNDy/NeRRe Therapeutics, Khyria, Madorra, Mayne Pharma, Mitsubishi Tanabe Pharma Development America, Mylan/Viatris Inc, Myovant Sciences, ObsEva SA, Pfizer, Pharmavite, QUE Oncology, Scynexis, Sebela Pharmaceuticals, Sprout Pharmaceuticals, TherapeuticsMD, Vella Bioscience, and Viveve Medical, and he is a stockholder in Sermonix Pharmaceuticals.

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

CHICAGO — The nonhormonal investigational drug elinzanetant led to significant improvement in hot flashes as well as sleep disturbance and quality of life, according to data from three randomized controlled trials presented at The Menopause Society 2024 Annual Meeting in Chicago. Two phase 3 trials, OASIS 1 and 2, were also published in JAMA, and the longer-term OASIS 3 trial was presented as a poster at the conference.

Elinzanetant is a selective neurokinin (NK) receptor antagonist, similar to fezolinetant, the first drug in this class approved by the US Food and Drug Administration (FDA) for vasomotor symptoms in May 2023. This class of medications targets the estrogen-sensitive kisspeptin/NK B/dynorphin (KNDy) neurons thought to play a role in thermoregulation and hot flashes during menopause. While fezolinetant targets only the NK-3 receptor, elinzanetant is a dual NK receptor antagonist that targets both NK-1 and NK-3. Bayer submitted a New Drug Application for elinzanetant to the FDA on August 1.

For those in whom hormone therapy is contraindicated, “it’s always been difficult for women with really severe symptoms to have a safe and effective therapy,” lead author JoAnn Pinkerton, MD, a professor of ob.gyn. at the University of Virginia in Charlottesville, Virginia, told this news organization. “The nonhormonal therapies we’ve used mostly off-label — the antidepressants, gabapentin, clonidine, oxybutynin — do help the hot flashes, but they don’t work nearly as effectively as these new NK receptor antagonists, and having one that looks like it might have a broader use for hot flashes, night sweats, mood, and sleep is just really exciting.”

Dr. Pinkerton said approximately 80% of the women in the OASIS 1 and 2 studies had at least a 50% reduction in hot flashes. “It was a very strong, dramatic positive finding, but the improvements in sleep and mood have really encouraged us to go further,” she said.

Declining estrogen levels during and after menopause can cause hypertrophy and hyperactivity of the KNDy neurons, which has been linked to thermoregulation disruptions that may trigger hot flashes, James Simon, MD, a clinical professor of ob.gyn. at The George Washington University School of Medicine & Health Sciences and medical director of IntimMedicine in Washington, DC, told attendees. He presented pooled data from OASIS 1 and 2. The NK-1 receptor, targeted by elinzanetant but not fezolinetant, is also thought to play a role in insomnia and possibly in mood.

“Oftentimes the focus on a lot of these drugs is hot flashes, hot flashes, hot flashes, but we know hot flashes do not occur in isolation,” Chrisandra Shufelt, MD, professor and chair of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Florida, told this news organization. Elinzanetant is “an interesting compound because it actually works on sleep, and that was critical because sleep disturbance precedes” many other menopausal symptoms, said Dr. Shufelt, who was not involved in the study.

“I think it is an outstanding option for women who don’t have the opportunity to get hormones,” Dr. Shufelt said, and she was particularly pleased to see there were no safety concerns for the liver in the trial data. The FDA issued a warning on September 12 about the risk for rare liver injury with fezolinetant, but the early signals that had been seen in fezolinetant data were not seen in these elinzanetant data.

The OASIS 1 and 2 trials enrolled postmenopausal women, aged 40-65 years, who had at least 50 moderate to severe vasomotor occurrences per week.

“A moderate hot flash is a hot flash that is also associated with sweating, and a severe hot flash is a moderate hot flash that stops a woman in her tracks,” Dr. Simon said. “Namely, it’s severe enough with sweating and central nervous system effects that she is interrupted in whatever it is that she’s doing at the time.”

Exclusion criteria for the trials included a history of arrhythmias, heart block, or QT prolongation; abnormal lab results; history of malignancy within the past 5 years; uncontrolled or treatment-resistant hypertension, hypothyroidism, or hyperthyroidism; unexplained postmenopausal bleeding; clinically relevant abnormal mammogram findings; or disordered proliferative endometrium, endometrial hyperplasia, polyp, or endometrial cancer.

The predominantly White (80%) women were an average 54 years old, with an average body mass index (BMI) of 27.8, and were an average 3.5 years from their last period. For the first 12 weeks of the trials, 399 women were assigned to receive 120 mg once daily of oral elinzanetant and 397 were assigned to once daily placebo. Then the women taking placebo switched to elinzanetant for the final 14 weeks of the study.

The endpoints included mean change in frequency and severity of vasomotor symptoms at weeks 1, 4, and 12 as well as change in sleep disturbance and quality of life at week 12. Sleep was assessed with the Patient-Reported Outcomes Measurement Information System Sleep Disturbance–Short Form score, which ranges from 28.9 to 76.5, with a higher number denoting greater sleep disturbance. The Menopause-Specific Quality-of-Life score ranges from 1 to 8, with a higher score indicating poorer quality of life.

Daily frequency of vasomotor symptoms was 14 per day at baseline in the elinzanetant group, decreasing by 4.8 per day at week 1, 8 per day at week 4, and 9.4 per day at week 12. In the placebo group, women had an average 15.2 occurrences per day at baseline, which decreased by 3.2 at week 1, 5.2 at week 4, and 6.4 at week 12. Comparing the groups at 12 weeks, those receiving elinzanetant had 3.2 fewer daily vasomotor symptoms than those receiving placebo (P < .0001).

The severity of vasomotor symptoms also improved more in the elinzanetant group than in the placebo group over 12 weeks, after which severity improved further in those who switched from placebo to elinzanetant (P < .0001).

Sleep disturbance scores, starting at a mean 61.5 in the elinzanetant group and 60.5 in the placebo group, fell 10.7 points in the elinzanetant group and 5.3 points in the placebo group at 12 weeks, for a difference of 4.9 points (P < .0001). Sleep then further improved in those who switched from placebo to elinzanetant. Quality-of-life scores improved 1.37 points (from 4.52 at baseline) in the elinzanetant group and 0.96 points (from 4.49 at baseline) in the placebo group, for a mean difference at 12 weeks of 0.36 (P < .0001).

Though no head-to-head data exist comparing elinzanetant and fezolinetant, Dr. Simon told this news organization the side effects with fezolinetant “tend to be gastrointestinal, whereas the side effects for elinzanetant tend to be central nervous system,” such as drowsiness and lethargy.

The women who are the best candidates for elinzanetant, Dr. Pinkerton told this news organization, include those who have had an estrogen-sensitive cancer, such as breast or endometrial cancer, or who have fear of it, a family history, or are otherwise high risk. Other ideal candidates include those with a history of venous thromboembolism, people who have migraine with aura (due to concerns about increased risk for stroke), and those who have endometriosis or large fibroids.

“Then the last group might be women who took hormone therapy in their 50s and want to continue, but they’re trying to go off, and they have a recurrence of their hot flashes or night sweats or sleep issues,” Dr. Pinkerton said. “This might be a great group to switch over.”

OASIS 3 assessed the drug for 1 year and “supported the results of OASIS 1 and 2, demonstrating efficacy over a longer study duration and in a population with a vasomotor symptom profile representative of that seen in clinical practice,” Nick Panay, BSc, MBBS, director of the Menopause & PMS Centre at Queen Charlotte’s Hospital & Imperial College London, London, England, and his colleague reported.

Among 628 postmenopausal women aged 40-65, the predominantly White (78.5%) women were an average 54 years old, with an average BMI of 27.6, and were an average 5 years past their last period. Half received 120 mg elinzanetant and half received a placebo for 52 weeks.

At 12 weeks, the women receiving elinzanetant reported an average 1.6 moderate to severe vasomotor symptoms per day, down from 6.7 at baseline. Daily average symptoms in the placebo group fell from 6.8 at baseline to 3.4 at 12 weeks, for a difference of 1.6 fewer occurrences per day in the elinzanetant group (P < .0001).

Sleep disturbances also improved, falling 9.4 points from a baseline 57.4 in the elinzanetant group and 5.7 points from a baseline 58 in the placebo group. Quality-of-life scores improved from 4.1 to 2.8 (−1.3 change) in the elinzanetant group and from 4.4 to 3.3 (−1.1 change) in the placebo group.

In addition to looking at treatment-emergent adverse events, the safety assessments also included endometrial biopsies; bone mineral density in the femoral neck, hip, and lumbar spine; weight; and labs. Adverse events related to the study drug occurred in 30.4% of those in the elinzanetant group and 14.6% of those in the placebo group. The most commonly reported adverse events were headache (9.6% elinzanetant vs 7% placebo), fatigue (7% vs 10.2%), and sleepiness (5.1% vs 1.3%). A higher proportion of women taking elinzanetant (12.5%) than those taking placebo (4.1%) discontinued the study.

No serious adverse events deemed to be treatment-related occurred in either group, and no endometrial hyperplasia or malignant neoplasm occurred in either group. Bone mineral density changes in both groups were within the expected range for the women’s age, and their weight remained stable over the 52 weeks.

Six women taking elinzanetant and four taking placebo met predefined criteria for close liver observation, but none showed hepatotoxicity or evidence of possible drug-induced liver injury.

The research was funded by Bayer. Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer. Dr. Shufelt had no disclosures. Dr. Simon had grant/research support, consulting/advisory board participation, and/or speaking disclosures with AbbVie, Bayer Healthcare, Besins Healthcare, California Institute of Integral Studies, Camargo Pharmaceutical Services, Covance, Daré Bioscience, DEKA M.E.L.A S.r.l., Femasys, Ipsen, KaNDy/NeRRe Therapeutics, Khyria, Madorra, Mayne Pharma, Mitsubishi Tanabe Pharma Development America, Mylan/Viatris Inc, Myovant Sciences, ObsEva SA, Pfizer, Pharmavite, QUE Oncology, Scynexis, Sebela Pharmaceuticals, Sprout Pharmaceuticals, TherapeuticsMD, Vella Bioscience, and Viveve Medical, and he is a stockholder in Sermonix Pharmaceuticals.

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

Air pollution, high temperatures, and metabolic risk factors are driving global increases in stroke, contributing to 12 million cases and more than 7 million deaths from stroke each year, new data from the Global Burden of Disease (GBD) study showed.

Between 1990 and 2021, the number of people who experienced a stroke increased to 11.9 million (up by 70% since 1990), while the number of stroke survivors rose to 93.8 million (up by 86%), and stroke-related deaths rose to 7.3 million (up by 44%), making stroke the third leading cause of death worldwide after ischemic heart disease and COVID-19, investigators found.

Stroke is highly preventable, the investigators noted, with 84% of the stroke burden in 2021 attributable to 23 modifiable risk factors, including air pollution, excess body weight, high blood pressure, smoking, and physical inactivity.

This means there are “tremendous opportunities to alter the trajectory of stroke risk for the next generation,” Catherine O. Johnson, MPH, PhD, co-author and lead research scientist at the Institute for Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release.

The study was published online in The Lancet Neurology.
 

Top Risk Factor for Subarachnoid Hemorrhage

Since 1990, the contribution of high temperatures to poor health and early death due to stroke has risen 72%, a trend likely to increase in the future — underscoring the impact of environmental factors on the growing stroke burden, the authors said.

“Given that ambient air pollution is reciprocally linked with ambient temperature and climate change, the importance of urgent climate actions and measures to reduce air pollution cannot be overestimated,” Dr. Johnson said.

Mitchell S.V. Elkind, MD, MS, chief clinical science officer for the American Heart Association, who wasn’t involved in the study, told this news organization that environmental factors such as air pollution, particulate matter from wildfires and other sources, and excessive heat are now recognized as major contributors to the risk for stroke. “This should not be surprising as we have long recognized the risks of stroke associated with toxins in cigarette smoke, which likely share mechanisms for vascular damage with pollutants,” Dr. Elkind said.

The data also reveal for the first time that ambient particulate matter air pollution is a top risk factor for subarachnoid hemorrhage, contributing to 14% of the death and disability caused by this serious stroke subtype, on a par with smoking.

Dr. Elkind noted that smoking is “a major risk factor for subarachnoid hemorrhage. It makes sense that particulate air pollution would therefore similarly be a risk factor for subarachnoid hemorrhage, which similarly damages blood vessels. Prior studies were likely too small or did not assess the role of air pollution in subarachnoid hemorrhage.”

The analysis also showed substantial increases between 1990 and 2021 in the global stroke burden linked to high body mass index (up by 88%), high blood sugar (up 32%), a diet high in sugar-sweetened drinks (up 23%), low physical activity (up 11%), high systolic blood pressure (up 7%), and a diet low in omega-6 polyunsaturated fatty acids (up 5%).

“And with increasing exposure to risk factors such as high blood sugar and diet high in sugar-sweetened drinks, there is a critical need for interventions focused on obesity and metabolic syndromes,” Dr. Johnson said.

“Identifying sustainable ways to work with communities to take action to prevent and control modifiable risk factors for stroke is essential to address this growing crisis,” she added.
 

Prevention Strategies Fall Short

The data also showed that stroke-related disability-adjusted life-years rose from around 121.4 million years of healthy life lost in 1990 to 160.5 million years in 2021, making stroke the fourth leading cause of health loss worldwide after COVID-19, ischemic heart disease, and neonatal disorders.

“The global growth of the number of people who develop stroke and died from or remain disabled by stroke is growing fast, strongly suggesting that currently used stroke prevention strategies are not sufficiently effective,” lead author Valery L. Feigin, MD, PhD, from Auckland University of Technology, Auckland, New Zealand, and affiliate professor at IHME, said in the release.

“New, proven effective population-wide and motivational individual prevention strategies that could be applied to all people at risk of having a stroke, regardless of the level of risk, as recommended in the recent Lancet Neurology Commission on Stroke should be implemented across the globe urgently,” said Dr. Feigin.

Dr. Elkind said the AHA supports research on the effects of air quality on risk for vascular injury and stroke and has “long advocated for policies to mitigate the adverse health impacts of air pollutants, including reduction of vehicle emissions and renewable portfolio standards, taking into account racial, ethnic, and economic disparities.”

“AHA, and the healthcare sector more broadly, must take a leadership role in recommending policies to improve environmental air quality and in working with the private sector and industry to improve air quality,” Dr. Elkind said.

In an accompanying commentary, Ming Liu, MD, and Simiao Wu, MD, PhD, West China Hospital, Sichuan University, Chengdu, China, wrote that “pragmatic solutions to the enormous and increasing stroke burden include surveillance, prevention, acute care, and rehabilitation.”

“Surveillance strategies include establishing a national-level framework for regular monitoring of stroke burden, risk factors, and healthcare services via community-based surveys and health records,” they noted.

“Artificial intelligence and mobile technologies might not only facilitate the dissemination of evidence-based health services but also increase the number of data sources and encourage participation of multidisciplinary collaborators, potentially improving the validity and accuracy of future GBD estimates,” they added.

This study was funded by the Bill & Melinda Gates Foundation. Author disclosures are listed with the original article.

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

Air pollution, high temperatures, and metabolic risk factors are driving global increases in stroke, contributing to 12 million cases and more than 7 million deaths from stroke each year, new data from the Global Burden of Disease (GBD) study showed.

Between 1990 and 2021, the number of people who experienced a stroke increased to 11.9 million (up by 70% since 1990), while the number of stroke survivors rose to 93.8 million (up by 86%), and stroke-related deaths rose to 7.3 million (up by 44%), making stroke the third leading cause of death worldwide after ischemic heart disease and COVID-19, investigators found.

Stroke is highly preventable, the investigators noted, with 84% of the stroke burden in 2021 attributable to 23 modifiable risk factors, including air pollution, excess body weight, high blood pressure, smoking, and physical inactivity.

This means there are “tremendous opportunities to alter the trajectory of stroke risk for the next generation,” Catherine O. Johnson, MPH, PhD, co-author and lead research scientist at the Institute for Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release.

The study was published online in The Lancet Neurology.
 

Top Risk Factor for Subarachnoid Hemorrhage

Since 1990, the contribution of high temperatures to poor health and early death due to stroke has risen 72%, a trend likely to increase in the future — underscoring the impact of environmental factors on the growing stroke burden, the authors said.

“Given that ambient air pollution is reciprocally linked with ambient temperature and climate change, the importance of urgent climate actions and measures to reduce air pollution cannot be overestimated,” Dr. Johnson said.

Mitchell S.V. Elkind, MD, MS, chief clinical science officer for the American Heart Association, who wasn’t involved in the study, told this news organization that environmental factors such as air pollution, particulate matter from wildfires and other sources, and excessive heat are now recognized as major contributors to the risk for stroke. “This should not be surprising as we have long recognized the risks of stroke associated with toxins in cigarette smoke, which likely share mechanisms for vascular damage with pollutants,” Dr. Elkind said.

The data also reveal for the first time that ambient particulate matter air pollution is a top risk factor for subarachnoid hemorrhage, contributing to 14% of the death and disability caused by this serious stroke subtype, on a par with smoking.

Dr. Elkind noted that smoking is “a major risk factor for subarachnoid hemorrhage. It makes sense that particulate air pollution would therefore similarly be a risk factor for subarachnoid hemorrhage, which similarly damages blood vessels. Prior studies were likely too small or did not assess the role of air pollution in subarachnoid hemorrhage.”

The analysis also showed substantial increases between 1990 and 2021 in the global stroke burden linked to high body mass index (up by 88%), high blood sugar (up 32%), a diet high in sugar-sweetened drinks (up 23%), low physical activity (up 11%), high systolic blood pressure (up 7%), and a diet low in omega-6 polyunsaturated fatty acids (up 5%).

“And with increasing exposure to risk factors such as high blood sugar and diet high in sugar-sweetened drinks, there is a critical need for interventions focused on obesity and metabolic syndromes,” Dr. Johnson said.

“Identifying sustainable ways to work with communities to take action to prevent and control modifiable risk factors for stroke is essential to address this growing crisis,” she added.
 

Prevention Strategies Fall Short

The data also showed that stroke-related disability-adjusted life-years rose from around 121.4 million years of healthy life lost in 1990 to 160.5 million years in 2021, making stroke the fourth leading cause of health loss worldwide after COVID-19, ischemic heart disease, and neonatal disorders.

“The global growth of the number of people who develop stroke and died from or remain disabled by stroke is growing fast, strongly suggesting that currently used stroke prevention strategies are not sufficiently effective,” lead author Valery L. Feigin, MD, PhD, from Auckland University of Technology, Auckland, New Zealand, and affiliate professor at IHME, said in the release.

“New, proven effective population-wide and motivational individual prevention strategies that could be applied to all people at risk of having a stroke, regardless of the level of risk, as recommended in the recent Lancet Neurology Commission on Stroke should be implemented across the globe urgently,” said Dr. Feigin.

Dr. Elkind said the AHA supports research on the effects of air quality on risk for vascular injury and stroke and has “long advocated for policies to mitigate the adverse health impacts of air pollutants, including reduction of vehicle emissions and renewable portfolio standards, taking into account racial, ethnic, and economic disparities.”

“AHA, and the healthcare sector more broadly, must take a leadership role in recommending policies to improve environmental air quality and in working with the private sector and industry to improve air quality,” Dr. Elkind said.

In an accompanying commentary, Ming Liu, MD, and Simiao Wu, MD, PhD, West China Hospital, Sichuan University, Chengdu, China, wrote that “pragmatic solutions to the enormous and increasing stroke burden include surveillance, prevention, acute care, and rehabilitation.”

“Surveillance strategies include establishing a national-level framework for regular monitoring of stroke burden, risk factors, and healthcare services via community-based surveys and health records,” they noted.

“Artificial intelligence and mobile technologies might not only facilitate the dissemination of evidence-based health services but also increase the number of data sources and encourage participation of multidisciplinary collaborators, potentially improving the validity and accuracy of future GBD estimates,” they added.

This study was funded by the Bill & Melinda Gates Foundation. Author disclosures are listed with the original article.

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

Air pollution, high temperatures, and metabolic risk factors are driving global increases in stroke, contributing to 12 million cases and more than 7 million deaths from stroke each year, new data from the Global Burden of Disease (GBD) study showed.

Between 1990 and 2021, the number of people who experienced a stroke increased to 11.9 million (up by 70% since 1990), while the number of stroke survivors rose to 93.8 million (up by 86%), and stroke-related deaths rose to 7.3 million (up by 44%), making stroke the third leading cause of death worldwide after ischemic heart disease and COVID-19, investigators found.

Stroke is highly preventable, the investigators noted, with 84% of the stroke burden in 2021 attributable to 23 modifiable risk factors, including air pollution, excess body weight, high blood pressure, smoking, and physical inactivity.

This means there are “tremendous opportunities to alter the trajectory of stroke risk for the next generation,” Catherine O. Johnson, MPH, PhD, co-author and lead research scientist at the Institute for Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release.

The study was published online in The Lancet Neurology.
 

Top Risk Factor for Subarachnoid Hemorrhage

Since 1990, the contribution of high temperatures to poor health and early death due to stroke has risen 72%, a trend likely to increase in the future — underscoring the impact of environmental factors on the growing stroke burden, the authors said.

“Given that ambient air pollution is reciprocally linked with ambient temperature and climate change, the importance of urgent climate actions and measures to reduce air pollution cannot be overestimated,” Dr. Johnson said.

Mitchell S.V. Elkind, MD, MS, chief clinical science officer for the American Heart Association, who wasn’t involved in the study, told this news organization that environmental factors such as air pollution, particulate matter from wildfires and other sources, and excessive heat are now recognized as major contributors to the risk for stroke. “This should not be surprising as we have long recognized the risks of stroke associated with toxins in cigarette smoke, which likely share mechanisms for vascular damage with pollutants,” Dr. Elkind said.

The data also reveal for the first time that ambient particulate matter air pollution is a top risk factor for subarachnoid hemorrhage, contributing to 14% of the death and disability caused by this serious stroke subtype, on a par with smoking.

Dr. Elkind noted that smoking is “a major risk factor for subarachnoid hemorrhage. It makes sense that particulate air pollution would therefore similarly be a risk factor for subarachnoid hemorrhage, which similarly damages blood vessels. Prior studies were likely too small or did not assess the role of air pollution in subarachnoid hemorrhage.”

The analysis also showed substantial increases between 1990 and 2021 in the global stroke burden linked to high body mass index (up by 88%), high blood sugar (up 32%), a diet high in sugar-sweetened drinks (up 23%), low physical activity (up 11%), high systolic blood pressure (up 7%), and a diet low in omega-6 polyunsaturated fatty acids (up 5%).

“And with increasing exposure to risk factors such as high blood sugar and diet high in sugar-sweetened drinks, there is a critical need for interventions focused on obesity and metabolic syndromes,” Dr. Johnson said.

“Identifying sustainable ways to work with communities to take action to prevent and control modifiable risk factors for stroke is essential to address this growing crisis,” she added.
 

Prevention Strategies Fall Short

The data also showed that stroke-related disability-adjusted life-years rose from around 121.4 million years of healthy life lost in 1990 to 160.5 million years in 2021, making stroke the fourth leading cause of health loss worldwide after COVID-19, ischemic heart disease, and neonatal disorders.

“The global growth of the number of people who develop stroke and died from or remain disabled by stroke is growing fast, strongly suggesting that currently used stroke prevention strategies are not sufficiently effective,” lead author Valery L. Feigin, MD, PhD, from Auckland University of Technology, Auckland, New Zealand, and affiliate professor at IHME, said in the release.

“New, proven effective population-wide and motivational individual prevention strategies that could be applied to all people at risk of having a stroke, regardless of the level of risk, as recommended in the recent Lancet Neurology Commission on Stroke should be implemented across the globe urgently,” said Dr. Feigin.

Dr. Elkind said the AHA supports research on the effects of air quality on risk for vascular injury and stroke and has “long advocated for policies to mitigate the adverse health impacts of air pollutants, including reduction of vehicle emissions and renewable portfolio standards, taking into account racial, ethnic, and economic disparities.”

“AHA, and the healthcare sector more broadly, must take a leadership role in recommending policies to improve environmental air quality and in working with the private sector and industry to improve air quality,” Dr. Elkind said.

In an accompanying commentary, Ming Liu, MD, and Simiao Wu, MD, PhD, West China Hospital, Sichuan University, Chengdu, China, wrote that “pragmatic solutions to the enormous and increasing stroke burden include surveillance, prevention, acute care, and rehabilitation.”

“Surveillance strategies include establishing a national-level framework for regular monitoring of stroke burden, risk factors, and healthcare services via community-based surveys and health records,” they noted.

“Artificial intelligence and mobile technologies might not only facilitate the dissemination of evidence-based health services but also increase the number of data sources and encourage participation of multidisciplinary collaborators, potentially improving the validity and accuracy of future GBD estimates,” they added.

This study was funded by the Bill & Melinda Gates Foundation. Author disclosures are listed with the original article.

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