Conference Coverage

SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.

“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”

LucaLorenzelli/Thinkstock

Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:

Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.

As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”

Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”

He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.


 

Courtesy University of California, San Diego

Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”

Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.

Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”

Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”

Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.

SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.

“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”

LucaLorenzelli/Thinkstock

Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:

Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.

As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”

Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”

He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.


 

Courtesy University of California, San Diego

Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”

Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.

Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”

Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”

Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.

SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.

“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”

LucaLorenzelli/Thinkstock

Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:

Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.

As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”

Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”

He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.


 

Courtesy University of California, San Diego

Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”

Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.

Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”

Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”

Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.

SAN DIEGO — Compared with the use of topical minoxidil for hair loss, the used of low-dose oral minoxidil (LDOM) can be considered when topical minoxidil is more expensive or logistically challenging, has plateaued in efficacy, leaves unwanted product residue, causes skin irritation, or exacerbates the inflammatory process.

Those are among the key recommendations that resulted from a modified eDelphi consensus of experts who convened to develop guidelines for LDOM prescribing and monitoring.

“Topical minoxidil is safe, effective, over-the-counter, and FDA-approved to treat the most common form of hair loss, androgenetic alopecia,” one of the study authors, Jennifer Fu, MD, a dermatologist who directs the Hair Disorders Clinic at the University of California, San Francisco, told this news organization following the annual meeting of the American Academy of Dermatology. The results of the expert consensus were presented during a poster session at the meeting. “It is often used off label for other types of hair loss, yet clinicians who treat hair loss know that patient compliance with topical minoxidil can be poor for a variety of reasons,” she said. “Patients report that it can be difficult to apply and complicate hair styling. For many patients, topical minoxidil can be drying or cause irritant or allergic contact reactions.”

Dr. Fu

LDOM has become a popular alternative for patients for whom topical minoxidil is logistically challenging, irritating, or ineffective, she continued. Although oral minoxidil is no longer a first-line antihypertensive agent given the risk of cardiovascular adverse effects at higher antihypertensive dosing (10-40 mg daily), a growing number of small studies have documented the use of LDOM at doses ranging from 0.25 mg to 5 mg daily as a safe, effective option for various types of hair loss.

“Given the current absence of larger trials on this topic, our research group identified a need for expert-based guidelines for prescribing and monitoring LDOM use in hair loss patients,” Dr. Fu said. “Our goal was to provide clinicians who treat hair loss patients a road map for using LDOM effectively, maximizing hair growth, and minimizing potential cardiovascular adverse effects.”


 

Arriving at a Consensus

The process involved 43 hair loss specialists from 12 countries with an average of 6.29 years of experience with LDOM for hair loss, who participated in a multi-round modified Delphi process. They considered questions that addressed LDOM safety, efficacy, dosing, and monitoring for hair loss, and consensus was reached if at least 70% of participants indicated “agree” or “strongly agree” on a five-point Likert scale. Round 1 consisted of 180 open-ended, multiple-choice, or Likert-scale questions, while round 2 involved 121 Likert-scale questions, round 3 consisted of 16 Likert-scale questions, and round 4 included 11 Likert-scale questions. In all, 94 items achieved Likert-scale consensus.

Specifically, experts on the panel found a direct benefit of LDOM for androgenetic alopecia, age-related patterned thinning, alopecia areata, telogen effluvium, traction alopecia, persistent chemotherapy-induced alopecia, and endocrine therapy-induced alopecia. They found a supportive benefit of LDOM for lichen planopilaris, frontal fibrosing alopecia, central centrifugal alopecia, and fibrosing alopecia in a patterned distribution.

“LDOM can be considered when topical minoxidil is more expensive, logistically challenging, has plateaued in efficacy, results in undesirable product residue/skin irritation,” or exacerbates inflammatory processes (ie eczema, psoriasis), they added.

Contraindications to LDOM listed in the consensus recommendations include hypersensitivity to minoxidil, significant drug-drug interactions with LDOM, a history of pericardial effusion/tamponade, pericarditis, heart failure, pulmonary hypertension associated with mitral stenosis, pheochromocytoma, and pregnancy/breastfeeding. Cited precautions of LDOM use include a history of tachycardia or arrhythmia, hypotension, renal impairment, and being on dialysis.

Dr. Fu and colleagues noted that the earliest time point at which LDOM should be expected to demonstrate efficacy is 3-6 months. “Baseline testing is not routine but may be considered in case of identified precautions,” they wrote. They also noted that LDOM can possibly be co-administered with beta-blockers with a specialty consultation, and with spironolactone in biologic female or transgender female patients with hirsutism, acne, polycystic ovary syndrome (PCOS), and with lower extremity and facial edema.

According to the consensus statement, the most frequently prescribed LDOM dosing regimen in adult females aged 18 years and older includes a starting dose of 1.25 mg daily, with a dosing range between 0.625 mg and 5 mg daily. For adult males, the most frequently prescribed dosing regimen is a starting dose of 2.5 daily, with a dosing range between 1.25 mg and 5 mg daily. The most frequently prescribed LDOM dosing regimen in adolescent females aged 12-17 years is a starting dose of 0.625 mg daily, with a dosing range of 0.625 to 2.5 mg daily. For adolescent males, the recommended regimen is a starting dose of 1.25 mg daily, with a dosing range of 1.25 mg to 5 mg daily.

“We hope that this consensus statement will guide our colleagues who would like to use LDOM to treat hair loss in their adult and adolescent patients,” Dr. Fu told this news organization. “These recommendations may be used to inform clinical practice until additional evidence-based data becomes available.”

She acknowledged certain limitations of the effort, including the fact that the expert panel was underrepresented in treating hair loss in pediatric patients, “and therefore failed to reach consensus on LDOM pediatric use and dosing,” she said. “We encourage our pediatric dermatology colleagues to further research LDOM in pediatric patients.”

In an interview, Shari Lipner, MD, PhD, associate professor of clinical dermatology, Weill Cornell Medicine, New York, who was asked to comment, but was not involved with the work, characterized the consensus as a “helpful, concise reference guide for dermatologists.”

Dr. Lipner

The advantages of the study are the standardized methods used, “and the experience of the panel,” she said. “Study limitations include the response rate, which was less than 60%, and the risk of potential side effects are not stratified by age, sex, or comorbidities,” she added.

Dr. Fu disclosed that she is a consultant to Pfizer. Dr. Lipner reported having no relevant disclosures.

SAN DIEGO — Compared with the use of topical minoxidil for hair loss, the used of low-dose oral minoxidil (LDOM) can be considered when topical minoxidil is more expensive or logistically challenging, has plateaued in efficacy, leaves unwanted product residue, causes skin irritation, or exacerbates the inflammatory process.

Those are among the key recommendations that resulted from a modified eDelphi consensus of experts who convened to develop guidelines for LDOM prescribing and monitoring.

“Topical minoxidil is safe, effective, over-the-counter, and FDA-approved to treat the most common form of hair loss, androgenetic alopecia,” one of the study authors, Jennifer Fu, MD, a dermatologist who directs the Hair Disorders Clinic at the University of California, San Francisco, told this news organization following the annual meeting of the American Academy of Dermatology. The results of the expert consensus were presented during a poster session at the meeting. “It is often used off label for other types of hair loss, yet clinicians who treat hair loss know that patient compliance with topical minoxidil can be poor for a variety of reasons,” she said. “Patients report that it can be difficult to apply and complicate hair styling. For many patients, topical minoxidil can be drying or cause irritant or allergic contact reactions.”

Dr. Fu

LDOM has become a popular alternative for patients for whom topical minoxidil is logistically challenging, irritating, or ineffective, she continued. Although oral minoxidil is no longer a first-line antihypertensive agent given the risk of cardiovascular adverse effects at higher antihypertensive dosing (10-40 mg daily), a growing number of small studies have documented the use of LDOM at doses ranging from 0.25 mg to 5 mg daily as a safe, effective option for various types of hair loss.

“Given the current absence of larger trials on this topic, our research group identified a need for expert-based guidelines for prescribing and monitoring LDOM use in hair loss patients,” Dr. Fu said. “Our goal was to provide clinicians who treat hair loss patients a road map for using LDOM effectively, maximizing hair growth, and minimizing potential cardiovascular adverse effects.”


 

Arriving at a Consensus

The process involved 43 hair loss specialists from 12 countries with an average of 6.29 years of experience with LDOM for hair loss, who participated in a multi-round modified Delphi process. They considered questions that addressed LDOM safety, efficacy, dosing, and monitoring for hair loss, and consensus was reached if at least 70% of participants indicated “agree” or “strongly agree” on a five-point Likert scale. Round 1 consisted of 180 open-ended, multiple-choice, or Likert-scale questions, while round 2 involved 121 Likert-scale questions, round 3 consisted of 16 Likert-scale questions, and round 4 included 11 Likert-scale questions. In all, 94 items achieved Likert-scale consensus.

Specifically, experts on the panel found a direct benefit of LDOM for androgenetic alopecia, age-related patterned thinning, alopecia areata, telogen effluvium, traction alopecia, persistent chemotherapy-induced alopecia, and endocrine therapy-induced alopecia. They found a supportive benefit of LDOM for lichen planopilaris, frontal fibrosing alopecia, central centrifugal alopecia, and fibrosing alopecia in a patterned distribution.

“LDOM can be considered when topical minoxidil is more expensive, logistically challenging, has plateaued in efficacy, results in undesirable product residue/skin irritation,” or exacerbates inflammatory processes (ie eczema, psoriasis), they added.

Contraindications to LDOM listed in the consensus recommendations include hypersensitivity to minoxidil, significant drug-drug interactions with LDOM, a history of pericardial effusion/tamponade, pericarditis, heart failure, pulmonary hypertension associated with mitral stenosis, pheochromocytoma, and pregnancy/breastfeeding. Cited precautions of LDOM use include a history of tachycardia or arrhythmia, hypotension, renal impairment, and being on dialysis.

Dr. Fu and colleagues noted that the earliest time point at which LDOM should be expected to demonstrate efficacy is 3-6 months. “Baseline testing is not routine but may be considered in case of identified precautions,” they wrote. They also noted that LDOM can possibly be co-administered with beta-blockers with a specialty consultation, and with spironolactone in biologic female or transgender female patients with hirsutism, acne, polycystic ovary syndrome (PCOS), and with lower extremity and facial edema.

According to the consensus statement, the most frequently prescribed LDOM dosing regimen in adult females aged 18 years and older includes a starting dose of 1.25 mg daily, with a dosing range between 0.625 mg and 5 mg daily. For adult males, the most frequently prescribed dosing regimen is a starting dose of 2.5 daily, with a dosing range between 1.25 mg and 5 mg daily. The most frequently prescribed LDOM dosing regimen in adolescent females aged 12-17 years is a starting dose of 0.625 mg daily, with a dosing range of 0.625 to 2.5 mg daily. For adolescent males, the recommended regimen is a starting dose of 1.25 mg daily, with a dosing range of 1.25 mg to 5 mg daily.

“We hope that this consensus statement will guide our colleagues who would like to use LDOM to treat hair loss in their adult and adolescent patients,” Dr. Fu told this news organization. “These recommendations may be used to inform clinical practice until additional evidence-based data becomes available.”

She acknowledged certain limitations of the effort, including the fact that the expert panel was underrepresented in treating hair loss in pediatric patients, “and therefore failed to reach consensus on LDOM pediatric use and dosing,” she said. “We encourage our pediatric dermatology colleagues to further research LDOM in pediatric patients.”

In an interview, Shari Lipner, MD, PhD, associate professor of clinical dermatology, Weill Cornell Medicine, New York, who was asked to comment, but was not involved with the work, characterized the consensus as a “helpful, concise reference guide for dermatologists.”

Dr. Lipner

The advantages of the study are the standardized methods used, “and the experience of the panel,” she said. “Study limitations include the response rate, which was less than 60%, and the risk of potential side effects are not stratified by age, sex, or comorbidities,” she added.

Dr. Fu disclosed that she is a consultant to Pfizer. Dr. Lipner reported having no relevant disclosures.

SAN DIEGO — Compared with the use of topical minoxidil for hair loss, the used of low-dose oral minoxidil (LDOM) can be considered when topical minoxidil is more expensive or logistically challenging, has plateaued in efficacy, leaves unwanted product residue, causes skin irritation, or exacerbates the inflammatory process.

Those are among the key recommendations that resulted from a modified eDelphi consensus of experts who convened to develop guidelines for LDOM prescribing and monitoring.

“Topical minoxidil is safe, effective, over-the-counter, and FDA-approved to treat the most common form of hair loss, androgenetic alopecia,” one of the study authors, Jennifer Fu, MD, a dermatologist who directs the Hair Disorders Clinic at the University of California, San Francisco, told this news organization following the annual meeting of the American Academy of Dermatology. The results of the expert consensus were presented during a poster session at the meeting. “It is often used off label for other types of hair loss, yet clinicians who treat hair loss know that patient compliance with topical minoxidil can be poor for a variety of reasons,” she said. “Patients report that it can be difficult to apply and complicate hair styling. For many patients, topical minoxidil can be drying or cause irritant or allergic contact reactions.”

Dr. Fu

LDOM has become a popular alternative for patients for whom topical minoxidil is logistically challenging, irritating, or ineffective, she continued. Although oral minoxidil is no longer a first-line antihypertensive agent given the risk of cardiovascular adverse effects at higher antihypertensive dosing (10-40 mg daily), a growing number of small studies have documented the use of LDOM at doses ranging from 0.25 mg to 5 mg daily as a safe, effective option for various types of hair loss.

“Given the current absence of larger trials on this topic, our research group identified a need for expert-based guidelines for prescribing and monitoring LDOM use in hair loss patients,” Dr. Fu said. “Our goal was to provide clinicians who treat hair loss patients a road map for using LDOM effectively, maximizing hair growth, and minimizing potential cardiovascular adverse effects.”


 

Arriving at a Consensus

The process involved 43 hair loss specialists from 12 countries with an average of 6.29 years of experience with LDOM for hair loss, who participated in a multi-round modified Delphi process. They considered questions that addressed LDOM safety, efficacy, dosing, and monitoring for hair loss, and consensus was reached if at least 70% of participants indicated “agree” or “strongly agree” on a five-point Likert scale. Round 1 consisted of 180 open-ended, multiple-choice, or Likert-scale questions, while round 2 involved 121 Likert-scale questions, round 3 consisted of 16 Likert-scale questions, and round 4 included 11 Likert-scale questions. In all, 94 items achieved Likert-scale consensus.

Specifically, experts on the panel found a direct benefit of LDOM for androgenetic alopecia, age-related patterned thinning, alopecia areata, telogen effluvium, traction alopecia, persistent chemotherapy-induced alopecia, and endocrine therapy-induced alopecia. They found a supportive benefit of LDOM for lichen planopilaris, frontal fibrosing alopecia, central centrifugal alopecia, and fibrosing alopecia in a patterned distribution.

“LDOM can be considered when topical minoxidil is more expensive, logistically challenging, has plateaued in efficacy, results in undesirable product residue/skin irritation,” or exacerbates inflammatory processes (ie eczema, psoriasis), they added.

Contraindications to LDOM listed in the consensus recommendations include hypersensitivity to minoxidil, significant drug-drug interactions with LDOM, a history of pericardial effusion/tamponade, pericarditis, heart failure, pulmonary hypertension associated with mitral stenosis, pheochromocytoma, and pregnancy/breastfeeding. Cited precautions of LDOM use include a history of tachycardia or arrhythmia, hypotension, renal impairment, and being on dialysis.

Dr. Fu and colleagues noted that the earliest time point at which LDOM should be expected to demonstrate efficacy is 3-6 months. “Baseline testing is not routine but may be considered in case of identified precautions,” they wrote. They also noted that LDOM can possibly be co-administered with beta-blockers with a specialty consultation, and with spironolactone in biologic female or transgender female patients with hirsutism, acne, polycystic ovary syndrome (PCOS), and with lower extremity and facial edema.

According to the consensus statement, the most frequently prescribed LDOM dosing regimen in adult females aged 18 years and older includes a starting dose of 1.25 mg daily, with a dosing range between 0.625 mg and 5 mg daily. For adult males, the most frequently prescribed dosing regimen is a starting dose of 2.5 daily, with a dosing range between 1.25 mg and 5 mg daily. The most frequently prescribed LDOM dosing regimen in adolescent females aged 12-17 years is a starting dose of 0.625 mg daily, with a dosing range of 0.625 to 2.5 mg daily. For adolescent males, the recommended regimen is a starting dose of 1.25 mg daily, with a dosing range of 1.25 mg to 5 mg daily.

“We hope that this consensus statement will guide our colleagues who would like to use LDOM to treat hair loss in their adult and adolescent patients,” Dr. Fu told this news organization. “These recommendations may be used to inform clinical practice until additional evidence-based data becomes available.”

She acknowledged certain limitations of the effort, including the fact that the expert panel was underrepresented in treating hair loss in pediatric patients, “and therefore failed to reach consensus on LDOM pediatric use and dosing,” she said. “We encourage our pediatric dermatology colleagues to further research LDOM in pediatric patients.”

In an interview, Shari Lipner, MD, PhD, associate professor of clinical dermatology, Weill Cornell Medicine, New York, who was asked to comment, but was not involved with the work, characterized the consensus as a “helpful, concise reference guide for dermatologists.”

Dr. Lipner

The advantages of the study are the standardized methods used, “and the experience of the panel,” she said. “Study limitations include the response rate, which was less than 60%, and the risk of potential side effects are not stratified by age, sex, or comorbidities,” she added.

Dr. Fu disclosed that she is a consultant to Pfizer. Dr. Lipner reported having no relevant disclosures.

Even in large urban areas there aren’t enough rheumatologists to go around, and as a 2015 American College of Rheumatology workforce study projected, the number of rheumatology providers is expected to drop by 25% by the year 2030, while the demand for patient care in rheumatology is expected to increase by more than 100%.

The shortage of rheumatology care is even more acute in rural areas, but as a pilot project supported by the Arthritis Foundation shows, linking rheumatologists to health centers in remote and underserved locations via telehealth can help community providers improve care for patients with rheumatic diseases.

The novel collaborative model was described by Alfredo Rivadeneira, MD, professor of medicine in the division of rheumatology, allergy, and immunology at the University of North Carolina (UNC) School of Medicine in Chapel Hill, North Carolina.

UNC School of Medicine

“We found that this pilot, a unique partnership in North Carolina, improves access to rheumatology care to a rural population with high satisfaction scores. It underlines the importance of seeking collaboration with community providers when implementing these programs. It also allows timely specialty care and alleviates the barriers relating to transportation, insurance coverage, and telecommunication challenges,” he said at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City. 
 

Too Many Patients, Too Few Rheumatologists

Access to health is challenging for people from traditionally underserved racial and ethnic backgrounds, especially in states such as North Carolina, where 40% of the population lives in rural counties, which have higher age-adjusted mortality than more densely populated areas of the state, Dr. Rivadeneira said. 

In addition, 42% of the North Carolina residents seen at the state’s 42 Federally Qualified Health Centers (FQHCs) don’t have health insurance, which is higher than the average of 23% uninsured seen at FQHCs in other states.

There are currently approximately 250 rheumatology providers in North Carolina, the majority of whom work in the states’ three academic medical centers. Currently, North Carolina has an estimated population of 10 million people, which is projected to increase to 11.7 million by 2030. And by 2030, 20% of North Carolinians will be aged ≥ 65 years, Dr. Rivadeneira said, highlighting the need for expanded rheumatology care. 

Although telehealth services could be an option for expanding services to underserved communities, only 14 of the 42 FQHCs in the state use telehealth and only on a limited basis because it is not sufficiently reimbursed. 

Rivadeneira pointed to a 2022 study that showed how patients with rheumatic and musculoskeletal disease patients in North Carolina were less likely to use online patient portals if they lived in rural areas; came from racial or ethnic minority backgrounds; were older, men, had lower economic status (Medicaid enrollment or uninsured); or spoke a language other than English as their primary tongue. 
 

Pilot Project

To help smooth out some of the above-mentioned disparities, Dr. Rivadeneira and colleagues, in collaboration with the Arthritis Foundation, started a pilot project in 2022 designed to enhance access to rheumatology specialty care for rural residents through a shared telehealth model between the UNC rheumatology clinic and two separate Piedmont Health Services clinics in rural areas.

The project includes tailored educational sessions designed to empower Piedmont Health Services providers for evaluating and managing patients with rheumatic diseases.

Patients with prior diagnoses of rheumatologic diseases who were lost to rheumatology specialty care follow-up and those with new rheumatic symptoms who had transportation and/or financial barriers to receiving specialty care are triaged to the shared telemedicine visits.

Providers conduct monthly clinic sessions via shared visits between the on-site Piedmont Health Services provider and patients, with off-site UNC rheumatology fellows and attending physicians connected virtually. 

The educational component of the project includes monthly didactic sessions offered to all Piedmont Health Services providers across 12 locations. 

The topics that were chosen cover the most common rheumatologic conditions seen by community providers, including evaluating pain from a rheumatology perspective; using antinuclear antibodies and other serologies; evaluating and managing rheumatoid arthritis, lupus, gout, giant cell arteritis, polymyalgia rheumatica, and osteoarthritis; and methotrexate management and complications. 

“One of the aspects of this pilot that I want to emphasize is the importance of having the generalists with the patient, relaying the objective data, especially the physical exam, and that’s one of the great features of this model. It also provides a stable platform for telehealth to the individual patients, as many of these patients don’t have access to health technology,” Dr. Rivadeneira said. 
 

Thumbs Up

Both patients and general practitioners in the Piedmont Health system expressed high degrees of satisfaction with the shared telehealth program. Patients especially liked the time they saved not having to travel to see a specialist, and a large majority agreed that the visits were “as good as” in-person visits, felt that their concerns were addressed appropriately during the virtual visit, expressed overall satisfaction, and said they would like to continue virtual visits.

Physicians expressed a high degree of satisfaction with the rheumatology didactic sessions and said that the sessions enhanced their knowledge of evaluating and managing or co-managing rheumatologic diseases, as well as helping them to feel comfortable about applying this knowledge to patient care.

Dr. Rivadeneira noted that the pilot study was limited by low levels of Piedmont Health Services physician participation (two out of 45 total participated in shared visits), and only three or four providers typically took part in each didactic session. 
 

How to Improve?

In a follow-up study, the investigators asked Piedmont Health Services providers about barriers to rheumatology care, the most common and challenging diseases they encountered, how to improve the didactic components, and their perspectives on the pilot and how it may have affected referral patterns to rheumatology care.

The providers identified the cost of diagnostic evaluations and medications, transportation, long wait times, and language as the main barriers to patient access of rheumatology care.

“Additionally, over a third of them encountered patients on a weekly basis that were overdue for a visit with a rheumatologist,” Dr. Rivadeneira said. 

“Direct participation in the physical exam by the primary care provider enhances greatly, in my opinion, these telehealth visits. Focused didactic sessions, electronic handouts and/or quick access guides could empower more rural community providers to manage rheumatic diseases,” he concluded.

In the Q&A following the presentation, Laura Cappelli, MD, MHS, MS, associate professor of medicine in the division of rheumatology at Johns Hopkins School of Medicine in Baltimore, asked Dr. Rivadeneira how rheumatologists involved felt about the program and whether his team did any surveying or qualitative work with them.

“Just so you know, the rheumatologist was me,” he replied.

“I’m very picky about telemedicine,” he continued. “I don’t like it, I prefer, as most of us do, to have the patient there. But having the provider there, doing the exam, and you guiding them — I can ask, ‘Did you check their joints? Did you check their strength?’ — makes a huge difference and makes me feel comfortable with the sessions.”

Dr. Rivadeneira added that if a particular case was too complex or too vague to adequately assess via telehealth, he would arrange to see the patient in person.

The project was supported by the Arthritis Foundation. Dr. Rivadeneira and Dr. Cappelli reported no conflicts of interest.
 

A version of this article appeared on Medscape.com.

Even in large urban areas there aren’t enough rheumatologists to go around, and as a 2015 American College of Rheumatology workforce study projected, the number of rheumatology providers is expected to drop by 25% by the year 2030, while the demand for patient care in rheumatology is expected to increase by more than 100%.

The shortage of rheumatology care is even more acute in rural areas, but as a pilot project supported by the Arthritis Foundation shows, linking rheumatologists to health centers in remote and underserved locations via telehealth can help community providers improve care for patients with rheumatic diseases.

The novel collaborative model was described by Alfredo Rivadeneira, MD, professor of medicine in the division of rheumatology, allergy, and immunology at the University of North Carolina (UNC) School of Medicine in Chapel Hill, North Carolina.

UNC School of Medicine

“We found that this pilot, a unique partnership in North Carolina, improves access to rheumatology care to a rural population with high satisfaction scores. It underlines the importance of seeking collaboration with community providers when implementing these programs. It also allows timely specialty care and alleviates the barriers relating to transportation, insurance coverage, and telecommunication challenges,” he said at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City. 
 

Too Many Patients, Too Few Rheumatologists

Access to health is challenging for people from traditionally underserved racial and ethnic backgrounds, especially in states such as North Carolina, where 40% of the population lives in rural counties, which have higher age-adjusted mortality than more densely populated areas of the state, Dr. Rivadeneira said. 

In addition, 42% of the North Carolina residents seen at the state’s 42 Federally Qualified Health Centers (FQHCs) don’t have health insurance, which is higher than the average of 23% uninsured seen at FQHCs in other states.

There are currently approximately 250 rheumatology providers in North Carolina, the majority of whom work in the states’ three academic medical centers. Currently, North Carolina has an estimated population of 10 million people, which is projected to increase to 11.7 million by 2030. And by 2030, 20% of North Carolinians will be aged ≥ 65 years, Dr. Rivadeneira said, highlighting the need for expanded rheumatology care. 

Although telehealth services could be an option for expanding services to underserved communities, only 14 of the 42 FQHCs in the state use telehealth and only on a limited basis because it is not sufficiently reimbursed. 

Rivadeneira pointed to a 2022 study that showed how patients with rheumatic and musculoskeletal disease patients in North Carolina were less likely to use online patient portals if they lived in rural areas; came from racial or ethnic minority backgrounds; were older, men, had lower economic status (Medicaid enrollment or uninsured); or spoke a language other than English as their primary tongue. 
 

Pilot Project

To help smooth out some of the above-mentioned disparities, Dr. Rivadeneira and colleagues, in collaboration with the Arthritis Foundation, started a pilot project in 2022 designed to enhance access to rheumatology specialty care for rural residents through a shared telehealth model between the UNC rheumatology clinic and two separate Piedmont Health Services clinics in rural areas.

The project includes tailored educational sessions designed to empower Piedmont Health Services providers for evaluating and managing patients with rheumatic diseases.

Patients with prior diagnoses of rheumatologic diseases who were lost to rheumatology specialty care follow-up and those with new rheumatic symptoms who had transportation and/or financial barriers to receiving specialty care are triaged to the shared telemedicine visits.

Providers conduct monthly clinic sessions via shared visits between the on-site Piedmont Health Services provider and patients, with off-site UNC rheumatology fellows and attending physicians connected virtually. 

The educational component of the project includes monthly didactic sessions offered to all Piedmont Health Services providers across 12 locations. 

The topics that were chosen cover the most common rheumatologic conditions seen by community providers, including evaluating pain from a rheumatology perspective; using antinuclear antibodies and other serologies; evaluating and managing rheumatoid arthritis, lupus, gout, giant cell arteritis, polymyalgia rheumatica, and osteoarthritis; and methotrexate management and complications. 

“One of the aspects of this pilot that I want to emphasize is the importance of having the generalists with the patient, relaying the objective data, especially the physical exam, and that’s one of the great features of this model. It also provides a stable platform for telehealth to the individual patients, as many of these patients don’t have access to health technology,” Dr. Rivadeneira said. 
 

Thumbs Up

Both patients and general practitioners in the Piedmont Health system expressed high degrees of satisfaction with the shared telehealth program. Patients especially liked the time they saved not having to travel to see a specialist, and a large majority agreed that the visits were “as good as” in-person visits, felt that their concerns were addressed appropriately during the virtual visit, expressed overall satisfaction, and said they would like to continue virtual visits.

Physicians expressed a high degree of satisfaction with the rheumatology didactic sessions and said that the sessions enhanced their knowledge of evaluating and managing or co-managing rheumatologic diseases, as well as helping them to feel comfortable about applying this knowledge to patient care.

Dr. Rivadeneira noted that the pilot study was limited by low levels of Piedmont Health Services physician participation (two out of 45 total participated in shared visits), and only three or four providers typically took part in each didactic session. 
 

How to Improve?

In a follow-up study, the investigators asked Piedmont Health Services providers about barriers to rheumatology care, the most common and challenging diseases they encountered, how to improve the didactic components, and their perspectives on the pilot and how it may have affected referral patterns to rheumatology care.

The providers identified the cost of diagnostic evaluations and medications, transportation, long wait times, and language as the main barriers to patient access of rheumatology care.

“Additionally, over a third of them encountered patients on a weekly basis that were overdue for a visit with a rheumatologist,” Dr. Rivadeneira said. 

“Direct participation in the physical exam by the primary care provider enhances greatly, in my opinion, these telehealth visits. Focused didactic sessions, electronic handouts and/or quick access guides could empower more rural community providers to manage rheumatic diseases,” he concluded.

In the Q&A following the presentation, Laura Cappelli, MD, MHS, MS, associate professor of medicine in the division of rheumatology at Johns Hopkins School of Medicine in Baltimore, asked Dr. Rivadeneira how rheumatologists involved felt about the program and whether his team did any surveying or qualitative work with them.

“Just so you know, the rheumatologist was me,” he replied.

“I’m very picky about telemedicine,” he continued. “I don’t like it, I prefer, as most of us do, to have the patient there. But having the provider there, doing the exam, and you guiding them — I can ask, ‘Did you check their joints? Did you check their strength?’ — makes a huge difference and makes me feel comfortable with the sessions.”

Dr. Rivadeneira added that if a particular case was too complex or too vague to adequately assess via telehealth, he would arrange to see the patient in person.

The project was supported by the Arthritis Foundation. Dr. Rivadeneira and Dr. Cappelli reported no conflicts of interest.
 

A version of this article appeared on Medscape.com.

Even in large urban areas there aren’t enough rheumatologists to go around, and as a 2015 American College of Rheumatology workforce study projected, the number of rheumatology providers is expected to drop by 25% by the year 2030, while the demand for patient care in rheumatology is expected to increase by more than 100%.

The shortage of rheumatology care is even more acute in rural areas, but as a pilot project supported by the Arthritis Foundation shows, linking rheumatologists to health centers in remote and underserved locations via telehealth can help community providers improve care for patients with rheumatic diseases.

The novel collaborative model was described by Alfredo Rivadeneira, MD, professor of medicine in the division of rheumatology, allergy, and immunology at the University of North Carolina (UNC) School of Medicine in Chapel Hill, North Carolina.

UNC School of Medicine

“We found that this pilot, a unique partnership in North Carolina, improves access to rheumatology care to a rural population with high satisfaction scores. It underlines the importance of seeking collaboration with community providers when implementing these programs. It also allows timely specialty care and alleviates the barriers relating to transportation, insurance coverage, and telecommunication challenges,” he said at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City. 
 

Too Many Patients, Too Few Rheumatologists

Access to health is challenging for people from traditionally underserved racial and ethnic backgrounds, especially in states such as North Carolina, where 40% of the population lives in rural counties, which have higher age-adjusted mortality than more densely populated areas of the state, Dr. Rivadeneira said. 

In addition, 42% of the North Carolina residents seen at the state’s 42 Federally Qualified Health Centers (FQHCs) don’t have health insurance, which is higher than the average of 23% uninsured seen at FQHCs in other states.

There are currently approximately 250 rheumatology providers in North Carolina, the majority of whom work in the states’ three academic medical centers. Currently, North Carolina has an estimated population of 10 million people, which is projected to increase to 11.7 million by 2030. And by 2030, 20% of North Carolinians will be aged ≥ 65 years, Dr. Rivadeneira said, highlighting the need for expanded rheumatology care. 

Although telehealth services could be an option for expanding services to underserved communities, only 14 of the 42 FQHCs in the state use telehealth and only on a limited basis because it is not sufficiently reimbursed. 

Rivadeneira pointed to a 2022 study that showed how patients with rheumatic and musculoskeletal disease patients in North Carolina were less likely to use online patient portals if they lived in rural areas; came from racial or ethnic minority backgrounds; were older, men, had lower economic status (Medicaid enrollment or uninsured); or spoke a language other than English as their primary tongue. 
 

Pilot Project

To help smooth out some of the above-mentioned disparities, Dr. Rivadeneira and colleagues, in collaboration with the Arthritis Foundation, started a pilot project in 2022 designed to enhance access to rheumatology specialty care for rural residents through a shared telehealth model between the UNC rheumatology clinic and two separate Piedmont Health Services clinics in rural areas.

The project includes tailored educational sessions designed to empower Piedmont Health Services providers for evaluating and managing patients with rheumatic diseases.

Patients with prior diagnoses of rheumatologic diseases who were lost to rheumatology specialty care follow-up and those with new rheumatic symptoms who had transportation and/or financial barriers to receiving specialty care are triaged to the shared telemedicine visits.

Providers conduct monthly clinic sessions via shared visits between the on-site Piedmont Health Services provider and patients, with off-site UNC rheumatology fellows and attending physicians connected virtually. 

The educational component of the project includes monthly didactic sessions offered to all Piedmont Health Services providers across 12 locations. 

The topics that were chosen cover the most common rheumatologic conditions seen by community providers, including evaluating pain from a rheumatology perspective; using antinuclear antibodies and other serologies; evaluating and managing rheumatoid arthritis, lupus, gout, giant cell arteritis, polymyalgia rheumatica, and osteoarthritis; and methotrexate management and complications. 

“One of the aspects of this pilot that I want to emphasize is the importance of having the generalists with the patient, relaying the objective data, especially the physical exam, and that’s one of the great features of this model. It also provides a stable platform for telehealth to the individual patients, as many of these patients don’t have access to health technology,” Dr. Rivadeneira said. 
 

Thumbs Up

Both patients and general practitioners in the Piedmont Health system expressed high degrees of satisfaction with the shared telehealth program. Patients especially liked the time they saved not having to travel to see a specialist, and a large majority agreed that the visits were “as good as” in-person visits, felt that their concerns were addressed appropriately during the virtual visit, expressed overall satisfaction, and said they would like to continue virtual visits.

Physicians expressed a high degree of satisfaction with the rheumatology didactic sessions and said that the sessions enhanced their knowledge of evaluating and managing or co-managing rheumatologic diseases, as well as helping them to feel comfortable about applying this knowledge to patient care.

Dr. Rivadeneira noted that the pilot study was limited by low levels of Piedmont Health Services physician participation (two out of 45 total participated in shared visits), and only three or four providers typically took part in each didactic session. 
 

How to Improve?

In a follow-up study, the investigators asked Piedmont Health Services providers about barriers to rheumatology care, the most common and challenging diseases they encountered, how to improve the didactic components, and their perspectives on the pilot and how it may have affected referral patterns to rheumatology care.

The providers identified the cost of diagnostic evaluations and medications, transportation, long wait times, and language as the main barriers to patient access of rheumatology care.

“Additionally, over a third of them encountered patients on a weekly basis that were overdue for a visit with a rheumatologist,” Dr. Rivadeneira said. 

“Direct participation in the physical exam by the primary care provider enhances greatly, in my opinion, these telehealth visits. Focused didactic sessions, electronic handouts and/or quick access guides could empower more rural community providers to manage rheumatic diseases,” he concluded.

In the Q&A following the presentation, Laura Cappelli, MD, MHS, MS, associate professor of medicine in the division of rheumatology at Johns Hopkins School of Medicine in Baltimore, asked Dr. Rivadeneira how rheumatologists involved felt about the program and whether his team did any surveying or qualitative work with them.

“Just so you know, the rheumatologist was me,” he replied.

“I’m very picky about telemedicine,” he continued. “I don’t like it, I prefer, as most of us do, to have the patient there. But having the provider there, doing the exam, and you guiding them — I can ask, ‘Did you check their joints? Did you check their strength?’ — makes a huge difference and makes me feel comfortable with the sessions.”

Dr. Rivadeneira added that if a particular case was too complex or too vague to adequately assess via telehealth, he would arrange to see the patient in person.

The project was supported by the Arthritis Foundation. Dr. Rivadeneira and Dr. Cappelli reported no conflicts of interest.
 

A version of this article appeared on Medscape.com.

For patients with relapsed/refractory follicular lymphoma (R/R FL), chimeric antigen responder (CAR) T-cell therapy offers the best chance of survival, despite its high rate of serious side effects and the need to travel to infusion centers. Alternatively, updated chemo+immunotherapy regimens and bispecific antibodies provide less rigorous but effective treatment options for low-risk patients who cannot tolerate or access CAR T.

“CAR T-cells offer patients with relapsed or refractory follicular lymphoma the most durable responses and improved chance of survival beyond all other available therapies. This holds true for a broad range of high-risk disease features in patients with relapsed or refractory FL. Furthermore, it accomplishes this with a single infusion, and a discrete toxicity that is predictable, reversible and manageable,” said Caron Jacobson, MD, MMSc, of the Dana-Farber Cancer Institute in Boston.

Presenting at the Great Debates & Updates Hematologic Malignancies conference, held April 5-6 in New York City, Dr. Jacobson argued that more patients with R/R FL should be treated with CAR T.

Dana-Farber Cancer Institute

NY Presbyterian Hospital, Weill Cornell Medicine

For patients with relapsed/refractory follicular lymphoma (R/R FL), chimeric antigen responder (CAR) T-cell therapy offers the best chance of survival, despite its high rate of serious side effects and the need to travel to infusion centers. Alternatively, updated chemo+immunotherapy regimens and bispecific antibodies provide less rigorous but effective treatment options for low-risk patients who cannot tolerate or access CAR T.

“CAR T-cells offer patients with relapsed or refractory follicular lymphoma the most durable responses and improved chance of survival beyond all other available therapies. This holds true for a broad range of high-risk disease features in patients with relapsed or refractory FL. Furthermore, it accomplishes this with a single infusion, and a discrete toxicity that is predictable, reversible and manageable,” said Caron Jacobson, MD, MMSc, of the Dana-Farber Cancer Institute in Boston.

Presenting at the Great Debates & Updates Hematologic Malignancies conference, held April 5-6 in New York City, Dr. Jacobson argued that more patients with R/R FL should be treated with CAR T.

Dana-Farber Cancer Institute

NY Presbyterian Hospital, Weill Cornell Medicine

For patients with relapsed/refractory follicular lymphoma (R/R FL), chimeric antigen responder (CAR) T-cell therapy offers the best chance of survival, despite its high rate of serious side effects and the need to travel to infusion centers. Alternatively, updated chemo+immunotherapy regimens and bispecific antibodies provide less rigorous but effective treatment options for low-risk patients who cannot tolerate or access CAR T.

“CAR T-cells offer patients with relapsed or refractory follicular lymphoma the most durable responses and improved chance of survival beyond all other available therapies. This holds true for a broad range of high-risk disease features in patients with relapsed or refractory FL. Furthermore, it accomplishes this with a single infusion, and a discrete toxicity that is predictable, reversible and manageable,” said Caron Jacobson, MD, MMSc, of the Dana-Farber Cancer Institute in Boston.

Presenting at the Great Debates & Updates Hematologic Malignancies conference, held April 5-6 in New York City, Dr. Jacobson argued that more patients with R/R FL should be treated with CAR T.

Dana-Farber Cancer Institute

NY Presbyterian Hospital, Weill Cornell Medicine

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — An interim analysis of an ongoing extension study supports the long-term safety and efficacy of the oral calcitonin gene-related peptide (CGRP) receptor antagonist atogepant (Qulipta, AbbVie) to prevent chronic and episodic migraine.

The data show that 70% of patients treated with atogepant 60 mg daily achieved at least a 50% reduction in monthly migraine days at weeks 13-16 and this was maintained over 48 weeks of treatment. 

“This is the first long-term study for assessing the safety and efficacy of a drug belonging to the gepant class, atogepant, used in the prevention of migraine in persons with episodic migraine who did not benefit from several previous preventive treatments or with chronic migraine,” said study investigator Cristina Tassorelli, MD, professor and chair of neurology, University of Pavia, Italy. 

“It shows consistency of efficacy over 48 weeks and confirms the known safety profile of atogepant reported in randomized controlled trials, without detecting any new signal with the open-label use over 1 year,” Dr. Tassorelli said.

The results were reported at the 2024 annual meeting of the American Academy of Neurology by Sait Ashina, MD, with the Comprehensive Headache Center at Beth Israel Deaconess Medical Center in Boston.
 

Novel Longer-Term Data

The extension study includes more than 500 patients who completed the phase 3 PROGRESS or ELEVATE randomized placebo-controlled trials of atogepant 60 mg once daily for prevention of episodic or chronic migraine. It will run for 156 weeks. 

Dr. Ashina reported safety and tolerability data at 52 weeks of treatment and efficacy data between 13 and 48 weeks of treatment. The mean duration of atogepant exposure was 496.5 days, and the mean number of migraine days at baseline was 14.5. 

With atogepant, monthly migraine days improved on average by 8.5 days at weeks 13-16, and this was consistent over 48 weeks, Dr. Ashina reported. Similar improvements were observed for monthly headache days and monthly acute medication use days.

In addition, 70% of patients achieved a 50% or greater reduction in monthly migraine days at weeks 13-16, and this was consistent during the 48 weeks of open-label treatment.

Overall safety results were consistent with the known safety profile of atogepant. “A small percentage of subjects (< 6%) discontinue the treatment because of side effects,” Dr. Tassorelli said. 

The most common treatment-emergent adverse events (≥ 5% of participants) were COVID-19 (28.7%), nasopharyngitis (10.9%), and constipation (8.2%).

As the first report of 1-year atogepant data, the results are “very encouraging” for patients and clinicians, Dr. Ashina said in wrapping up his presentation. 
 

Important Advance, but Not Transformative

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, noted that “[w]hile the anti-CGRP medications represent an important advancement in migraine treatment, the data suggests they have not necessarily transformed the landscape as dramatically as some may have expected. 

“The efficacy of the anti-CGRP drugs appears to be generally similar to previous preventive and mostly genericized treatments, offering modest but meaningful improvements in migraine frequency and severity for many patients,” Dr. Lakhan said.

“In terms of safety, the anti-CGRPs do seem to have a somewhat cleaner profile compared to earlier migraine preventives, which is certainly a positive. However, the long-term data is still emerging, so the full safety picture is not yet clear,” Dr. Lakhan added. 

“These medications are also associated with significantly higher overall healthcare costs compared to other treatment approaches. The substantial cost implications, both for patients and the healthcare system, deserve careful consideration as we assess their overall value and role in migraine care going forward,” Dr. Lakhan said.

Funding was provided by AbbVie. Several investigators have disclosed financial relationships with the company. Dr. Lakhan has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — An interim analysis of an ongoing extension study supports the long-term safety and efficacy of the oral calcitonin gene-related peptide (CGRP) receptor antagonist atogepant (Qulipta, AbbVie) to prevent chronic and episodic migraine.

The data show that 70% of patients treated with atogepant 60 mg daily achieved at least a 50% reduction in monthly migraine days at weeks 13-16 and this was maintained over 48 weeks of treatment. 

“This is the first long-term study for assessing the safety and efficacy of a drug belonging to the gepant class, atogepant, used in the prevention of migraine in persons with episodic migraine who did not benefit from several previous preventive treatments or with chronic migraine,” said study investigator Cristina Tassorelli, MD, professor and chair of neurology, University of Pavia, Italy. 

“It shows consistency of efficacy over 48 weeks and confirms the known safety profile of atogepant reported in randomized controlled trials, without detecting any new signal with the open-label use over 1 year,” Dr. Tassorelli said.

The results were reported at the 2024 annual meeting of the American Academy of Neurology by Sait Ashina, MD, with the Comprehensive Headache Center at Beth Israel Deaconess Medical Center in Boston.
 

Novel Longer-Term Data

The extension study includes more than 500 patients who completed the phase 3 PROGRESS or ELEVATE randomized placebo-controlled trials of atogepant 60 mg once daily for prevention of episodic or chronic migraine. It will run for 156 weeks. 

Dr. Ashina reported safety and tolerability data at 52 weeks of treatment and efficacy data between 13 and 48 weeks of treatment. The mean duration of atogepant exposure was 496.5 days, and the mean number of migraine days at baseline was 14.5. 

With atogepant, monthly migraine days improved on average by 8.5 days at weeks 13-16, and this was consistent over 48 weeks, Dr. Ashina reported. Similar improvements were observed for monthly headache days and monthly acute medication use days.

In addition, 70% of patients achieved a 50% or greater reduction in monthly migraine days at weeks 13-16, and this was consistent during the 48 weeks of open-label treatment.

Overall safety results were consistent with the known safety profile of atogepant. “A small percentage of subjects (< 6%) discontinue the treatment because of side effects,” Dr. Tassorelli said. 

The most common treatment-emergent adverse events (≥ 5% of participants) were COVID-19 (28.7%), nasopharyngitis (10.9%), and constipation (8.2%).

As the first report of 1-year atogepant data, the results are “very encouraging” for patients and clinicians, Dr. Ashina said in wrapping up his presentation. 
 

Important Advance, but Not Transformative

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, noted that “[w]hile the anti-CGRP medications represent an important advancement in migraine treatment, the data suggests they have not necessarily transformed the landscape as dramatically as some may have expected. 

“The efficacy of the anti-CGRP drugs appears to be generally similar to previous preventive and mostly genericized treatments, offering modest but meaningful improvements in migraine frequency and severity for many patients,” Dr. Lakhan said.

“In terms of safety, the anti-CGRPs do seem to have a somewhat cleaner profile compared to earlier migraine preventives, which is certainly a positive. However, the long-term data is still emerging, so the full safety picture is not yet clear,” Dr. Lakhan added. 

“These medications are also associated with significantly higher overall healthcare costs compared to other treatment approaches. The substantial cost implications, both for patients and the healthcare system, deserve careful consideration as we assess their overall value and role in migraine care going forward,” Dr. Lakhan said.

Funding was provided by AbbVie. Several investigators have disclosed financial relationships with the company. Dr. Lakhan has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — An interim analysis of an ongoing extension study supports the long-term safety and efficacy of the oral calcitonin gene-related peptide (CGRP) receptor antagonist atogepant (Qulipta, AbbVie) to prevent chronic and episodic migraine.

The data show that 70% of patients treated with atogepant 60 mg daily achieved at least a 50% reduction in monthly migraine days at weeks 13-16 and this was maintained over 48 weeks of treatment. 

“This is the first long-term study for assessing the safety and efficacy of a drug belonging to the gepant class, atogepant, used in the prevention of migraine in persons with episodic migraine who did not benefit from several previous preventive treatments or with chronic migraine,” said study investigator Cristina Tassorelli, MD, professor and chair of neurology, University of Pavia, Italy. 

“It shows consistency of efficacy over 48 weeks and confirms the known safety profile of atogepant reported in randomized controlled trials, without detecting any new signal with the open-label use over 1 year,” Dr. Tassorelli said.

The results were reported at the 2024 annual meeting of the American Academy of Neurology by Sait Ashina, MD, with the Comprehensive Headache Center at Beth Israel Deaconess Medical Center in Boston.
 

Novel Longer-Term Data

The extension study includes more than 500 patients who completed the phase 3 PROGRESS or ELEVATE randomized placebo-controlled trials of atogepant 60 mg once daily for prevention of episodic or chronic migraine. It will run for 156 weeks. 

Dr. Ashina reported safety and tolerability data at 52 weeks of treatment and efficacy data between 13 and 48 weeks of treatment. The mean duration of atogepant exposure was 496.5 days, and the mean number of migraine days at baseline was 14.5. 

With atogepant, monthly migraine days improved on average by 8.5 days at weeks 13-16, and this was consistent over 48 weeks, Dr. Ashina reported. Similar improvements were observed for monthly headache days and monthly acute medication use days.

In addition, 70% of patients achieved a 50% or greater reduction in monthly migraine days at weeks 13-16, and this was consistent during the 48 weeks of open-label treatment.

Overall safety results were consistent with the known safety profile of atogepant. “A small percentage of subjects (< 6%) discontinue the treatment because of side effects,” Dr. Tassorelli said. 

The most common treatment-emergent adverse events (≥ 5% of participants) were COVID-19 (28.7%), nasopharyngitis (10.9%), and constipation (8.2%).

As the first report of 1-year atogepant data, the results are “very encouraging” for patients and clinicians, Dr. Ashina said in wrapping up his presentation. 
 

Important Advance, but Not Transformative

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, noted that “[w]hile the anti-CGRP medications represent an important advancement in migraine treatment, the data suggests they have not necessarily transformed the landscape as dramatically as some may have expected. 

“The efficacy of the anti-CGRP drugs appears to be generally similar to previous preventive and mostly genericized treatments, offering modest but meaningful improvements in migraine frequency and severity for many patients,” Dr. Lakhan said.

“In terms of safety, the anti-CGRPs do seem to have a somewhat cleaner profile compared to earlier migraine preventives, which is certainly a positive. However, the long-term data is still emerging, so the full safety picture is not yet clear,” Dr. Lakhan added. 

“These medications are also associated with significantly higher overall healthcare costs compared to other treatment approaches. The substantial cost implications, both for patients and the healthcare system, deserve careful consideration as we assess their overall value and role in migraine care going forward,” Dr. Lakhan said.

Funding was provided by AbbVie. Several investigators have disclosed financial relationships with the company. Dr. Lakhan has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER – Headaches, including tension-type, migraine, and posttraumatic, are robustly associated with both attempted and completed suicide, results of a large study suggest. 

The risk for suicide attempt was four times higher in people with trigeminal and autonomic cephalalgias (TAC), and the risk for completed suicide was double among those with posttraumatic headache compared with individuals with no headache.

The retrospective analysis included data on more than 100,000 headache patients from a Danish registry. 

“The results suggest there’s a unique risk among headache patients for attempted and completed suicide,” lead investigator Holly Elser, MD, MPH, PhD, resident, Department of Neurology, University of Pennsylvania, Philadelphia, said at the 2024 annual meeting of the American Academy of Neurology, where the findings were presented. “This really underscores the potential importance of complementary psychiatric evaluation and treatment for individuals diagnosed with headache.”
 

Underestimated Problem

Headache disorders affect about half of working-age adults and are among the leading causes of productivity loss, absence from work, and disability. 

Prior research suggests headache disorders often co-occur with psychiatric illness including depression, anxiety, posttraumatic stress disorder, and even attempted suicide.

However, previous studies that showed an increased risk for attempted suicide in patients with headache relied heavily on survey data and mostly focused on patients with migraine. There was little information on other headache types and on the risk for completed suicide.

Researchers used Danish registries to identify 64,057 patients with migraine, 40,160 with tension-type headache (TTH), 5743 with TAC, and 4253 with posttraumatic headache, all diagnosed from 1995 to 2019.

Some 5.8% of those with migraine, 6.3% with TAC, 7.2% with TTH, and 7.2% with posttraumatic headache, had a mood disorder (depression and anxiety combined) at baseline.

Those without a headache diagnosis were matched 5:1 to those with a headache diagnosis by sex and birth year.

Across all headache disorders, baseline prevalence of mood disorder was higher among those with headache versus population-matched controls. Dr. Elser emphasized that these are people diagnosed with a mood disorder in the inpatient, emergency department, or outpatient specialist clinic setting, “which means we are almost certainly underestimating the true burden of mood symptoms in our cohort,” she said.

Researchers identified attempted suicides using diagnostic codes. For completed suicide, they determined whether those who attempted suicide died within 30 days of the attempt.

For each headache type, investigators examined both the absolute and relative risk for attempted and completed suicides and estimated the risk at intervals of 5, 10, and 20 years after initial headache diagnosis.
 

Robust Link

The “power of this study is that we asked a simple, but important question, and answered it with simple, but appropriate, methodologic techniques,” Dr. Elser said.

The estimated risk differences (RDs) for attempted suicide were strongest for TAC and posttraumatic headache and for longer follow-ups. The RDs for completed suicide were largely the same but of a smaller magnitude and were “relatively less precise,” reflecting the “rarity of this outcome,” said Dr. Elser.

After adjusting for sex, age, education, income, comorbidities, and baseline medical and psychiatric diagnoses, researchers found the strongest association or attempted suicide was among those with TAC (adjusted hazard ratio [aHR], 4.25; 95% CI, 2.85-6.33).

“A hazard ratio of 4 is enormous” for this type of comparison, Dr. Elser noted.

For completed suicide, the strongest association was with posttraumatic headache (aHR, 2.19; 95% CI, 0.78-6.16).

The study revealed a robust association with attempted and completed suicide across all headache types, including TTH, noted Dr. Elser. The link between tension headaches and suicide “was the most striking finding to me because I think of that as sort of a benign and common headache disorder,” she said.

The was an observational study, so “it’s not clear whether headache is playing an etiological role in the relationship with suicide,” she said. “It’s possible there are common shared risk factors or confounders that explain the relationship in full or in part that aren’t accounted for in this study.”
 

Ask About Mood

The results underscore the need for psychiatric evaluations in patients with a headache disorder. “For me, this is just going to make me that much more likely to ask my patients about their mood when I see them in clinic,” Dr. Elser said.

After asking patients with headache about their mood and stress at home and at work, physicians should have a “low threshold to refer to a behavioral health provider,” she added.

Future research should aim to better understand the link between headache and suicide risk, with a focus on the mechanisms behind low- and high-risk subgroups, said Dr. Elser.

A limitation of the study was that headache diagnoses were based on inpatient, emergency department, and outpatient specialist visits but not on visits to primary care practitioners. The study didn’t include information on headache severity or frequency and included only people who sought treatment for their headaches.

Though it’s unlikely the results “are perfectly generalizable” with respect to other geographical or cultural contexts, “I don’t think this relationship is unique to Denmark based on the literature to date,” Dr. Elser said.

Commenting on the study, session co-chair Todd J. Schwedt, MD, professor of neurology, Mayo Clinic Arizona, Phoenix, and president-elect of the American Headache Society, noted that the study offers important findings “that demonstrate the enormous negative impact that headaches can exert.”

It’s “a strong reminder” that clinicians should assess the mental health of their patients with headaches and offer treatment when appropriate, he said.

The study received support from Aarhus University. No relevant conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

DENVER – Headaches, including tension-type, migraine, and posttraumatic, are robustly associated with both attempted and completed suicide, results of a large study suggest. 

The risk for suicide attempt was four times higher in people with trigeminal and autonomic cephalalgias (TAC), and the risk for completed suicide was double among those with posttraumatic headache compared with individuals with no headache.

The retrospective analysis included data on more than 100,000 headache patients from a Danish registry. 

“The results suggest there’s a unique risk among headache patients for attempted and completed suicide,” lead investigator Holly Elser, MD, MPH, PhD, resident, Department of Neurology, University of Pennsylvania, Philadelphia, said at the 2024 annual meeting of the American Academy of Neurology, where the findings were presented. “This really underscores the potential importance of complementary psychiatric evaluation and treatment for individuals diagnosed with headache.”
 

Underestimated Problem

Headache disorders affect about half of working-age adults and are among the leading causes of productivity loss, absence from work, and disability. 

Prior research suggests headache disorders often co-occur with psychiatric illness including depression, anxiety, posttraumatic stress disorder, and even attempted suicide.

However, previous studies that showed an increased risk for attempted suicide in patients with headache relied heavily on survey data and mostly focused on patients with migraine. There was little information on other headache types and on the risk for completed suicide.

Researchers used Danish registries to identify 64,057 patients with migraine, 40,160 with tension-type headache (TTH), 5743 with TAC, and 4253 with posttraumatic headache, all diagnosed from 1995 to 2019.

Some 5.8% of those with migraine, 6.3% with TAC, 7.2% with TTH, and 7.2% with posttraumatic headache, had a mood disorder (depression and anxiety combined) at baseline.

Those without a headache diagnosis were matched 5:1 to those with a headache diagnosis by sex and birth year.

Across all headache disorders, baseline prevalence of mood disorder was higher among those with headache versus population-matched controls. Dr. Elser emphasized that these are people diagnosed with a mood disorder in the inpatient, emergency department, or outpatient specialist clinic setting, “which means we are almost certainly underestimating the true burden of mood symptoms in our cohort,” she said.

Researchers identified attempted suicides using diagnostic codes. For completed suicide, they determined whether those who attempted suicide died within 30 days of the attempt.

For each headache type, investigators examined both the absolute and relative risk for attempted and completed suicides and estimated the risk at intervals of 5, 10, and 20 years after initial headache diagnosis.
 

Robust Link

The “power of this study is that we asked a simple, but important question, and answered it with simple, but appropriate, methodologic techniques,” Dr. Elser said.

The estimated risk differences (RDs) for attempted suicide were strongest for TAC and posttraumatic headache and for longer follow-ups. The RDs for completed suicide were largely the same but of a smaller magnitude and were “relatively less precise,” reflecting the “rarity of this outcome,” said Dr. Elser.

After adjusting for sex, age, education, income, comorbidities, and baseline medical and psychiatric diagnoses, researchers found the strongest association or attempted suicide was among those with TAC (adjusted hazard ratio [aHR], 4.25; 95% CI, 2.85-6.33).

“A hazard ratio of 4 is enormous” for this type of comparison, Dr. Elser noted.

For completed suicide, the strongest association was with posttraumatic headache (aHR, 2.19; 95% CI, 0.78-6.16).

The study revealed a robust association with attempted and completed suicide across all headache types, including TTH, noted Dr. Elser. The link between tension headaches and suicide “was the most striking finding to me because I think of that as sort of a benign and common headache disorder,” she said.

The was an observational study, so “it’s not clear whether headache is playing an etiological role in the relationship with suicide,” she said. “It’s possible there are common shared risk factors or confounders that explain the relationship in full or in part that aren’t accounted for in this study.”
 

Ask About Mood

The results underscore the need for psychiatric evaluations in patients with a headache disorder. “For me, this is just going to make me that much more likely to ask my patients about their mood when I see them in clinic,” Dr. Elser said.

After asking patients with headache about their mood and stress at home and at work, physicians should have a “low threshold to refer to a behavioral health provider,” she added.

Future research should aim to better understand the link between headache and suicide risk, with a focus on the mechanisms behind low- and high-risk subgroups, said Dr. Elser.

A limitation of the study was that headache diagnoses were based on inpatient, emergency department, and outpatient specialist visits but not on visits to primary care practitioners. The study didn’t include information on headache severity or frequency and included only people who sought treatment for their headaches.

Though it’s unlikely the results “are perfectly generalizable” with respect to other geographical or cultural contexts, “I don’t think this relationship is unique to Denmark based on the literature to date,” Dr. Elser said.

Commenting on the study, session co-chair Todd J. Schwedt, MD, professor of neurology, Mayo Clinic Arizona, Phoenix, and president-elect of the American Headache Society, noted that the study offers important findings “that demonstrate the enormous negative impact that headaches can exert.”

It’s “a strong reminder” that clinicians should assess the mental health of their patients with headaches and offer treatment when appropriate, he said.

The study received support from Aarhus University. No relevant conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

DENVER – Headaches, including tension-type, migraine, and posttraumatic, are robustly associated with both attempted and completed suicide, results of a large study suggest. 

The risk for suicide attempt was four times higher in people with trigeminal and autonomic cephalalgias (TAC), and the risk for completed suicide was double among those with posttraumatic headache compared with individuals with no headache.

The retrospective analysis included data on more than 100,000 headache patients from a Danish registry. 

“The results suggest there’s a unique risk among headache patients for attempted and completed suicide,” lead investigator Holly Elser, MD, MPH, PhD, resident, Department of Neurology, University of Pennsylvania, Philadelphia, said at the 2024 annual meeting of the American Academy of Neurology, where the findings were presented. “This really underscores the potential importance of complementary psychiatric evaluation and treatment for individuals diagnosed with headache.”
 

Underestimated Problem

Headache disorders affect about half of working-age adults and are among the leading causes of productivity loss, absence from work, and disability. 

Prior research suggests headache disorders often co-occur with psychiatric illness including depression, anxiety, posttraumatic stress disorder, and even attempted suicide.

However, previous studies that showed an increased risk for attempted suicide in patients with headache relied heavily on survey data and mostly focused on patients with migraine. There was little information on other headache types and on the risk for completed suicide.

Researchers used Danish registries to identify 64,057 patients with migraine, 40,160 with tension-type headache (TTH), 5743 with TAC, and 4253 with posttraumatic headache, all diagnosed from 1995 to 2019.

Some 5.8% of those with migraine, 6.3% with TAC, 7.2% with TTH, and 7.2% with posttraumatic headache, had a mood disorder (depression and anxiety combined) at baseline.

Those without a headache diagnosis were matched 5:1 to those with a headache diagnosis by sex and birth year.

Across all headache disorders, baseline prevalence of mood disorder was higher among those with headache versus population-matched controls. Dr. Elser emphasized that these are people diagnosed with a mood disorder in the inpatient, emergency department, or outpatient specialist clinic setting, “which means we are almost certainly underestimating the true burden of mood symptoms in our cohort,” she said.

Researchers identified attempted suicides using diagnostic codes. For completed suicide, they determined whether those who attempted suicide died within 30 days of the attempt.

For each headache type, investigators examined both the absolute and relative risk for attempted and completed suicides and estimated the risk at intervals of 5, 10, and 20 years after initial headache diagnosis.
 

Robust Link

The “power of this study is that we asked a simple, but important question, and answered it with simple, but appropriate, methodologic techniques,” Dr. Elser said.

The estimated risk differences (RDs) for attempted suicide were strongest for TAC and posttraumatic headache and for longer follow-ups. The RDs for completed suicide were largely the same but of a smaller magnitude and were “relatively less precise,” reflecting the “rarity of this outcome,” said Dr. Elser.

After adjusting for sex, age, education, income, comorbidities, and baseline medical and psychiatric diagnoses, researchers found the strongest association or attempted suicide was among those with TAC (adjusted hazard ratio [aHR], 4.25; 95% CI, 2.85-6.33).

“A hazard ratio of 4 is enormous” for this type of comparison, Dr. Elser noted.

For completed suicide, the strongest association was with posttraumatic headache (aHR, 2.19; 95% CI, 0.78-6.16).

The study revealed a robust association with attempted and completed suicide across all headache types, including TTH, noted Dr. Elser. The link between tension headaches and suicide “was the most striking finding to me because I think of that as sort of a benign and common headache disorder,” she said.

The was an observational study, so “it’s not clear whether headache is playing an etiological role in the relationship with suicide,” she said. “It’s possible there are common shared risk factors or confounders that explain the relationship in full or in part that aren’t accounted for in this study.”
 

Ask About Mood

The results underscore the need for psychiatric evaluations in patients with a headache disorder. “For me, this is just going to make me that much more likely to ask my patients about their mood when I see them in clinic,” Dr. Elser said.

After asking patients with headache about their mood and stress at home and at work, physicians should have a “low threshold to refer to a behavioral health provider,” she added.

Future research should aim to better understand the link between headache and suicide risk, with a focus on the mechanisms behind low- and high-risk subgroups, said Dr. Elser.

A limitation of the study was that headache diagnoses were based on inpatient, emergency department, and outpatient specialist visits but not on visits to primary care practitioners. The study didn’t include information on headache severity or frequency and included only people who sought treatment for their headaches.

Though it’s unlikely the results “are perfectly generalizable” with respect to other geographical or cultural contexts, “I don’t think this relationship is unique to Denmark based on the literature to date,” Dr. Elser said.

Commenting on the study, session co-chair Todd J. Schwedt, MD, professor of neurology, Mayo Clinic Arizona, Phoenix, and president-elect of the American Headache Society, noted that the study offers important findings “that demonstrate the enormous negative impact that headaches can exert.”

It’s “a strong reminder” that clinicians should assess the mental health of their patients with headaches and offer treatment when appropriate, he said.

The study received support from Aarhus University. No relevant conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

DENVER — Seizure burden, defined by an artificial intelligence (AI) algorithm applied to point-of-care electroencephalography (POC EEG) recordings, can help predict functional outcomes.

After relevant cofactors were controlled for, higher seizure burden correlated with poorer functional outcomes. All of the patients in the study were being monitored as part of their standard of care owing to suspicion of seizures or because they were at risk for seizures, said study investigator Masoom Desai, MD, with the Department of Neurology, University of New Mexico, Albuquerque. The results were “compelling,” she said.

“Our study addresses the critical need for automation in monitoring epileptic activity and seizure burden,” Dr. Desai added during a press briefing at the 2024 annual meeting of the American Academy of Neurology (AAN).
 

A Pivotal Shift 

“Several decades of research have highlighted the significant correlation between seizure burden and unfavorable outcomes both in adult and pediatric populations,” said Dr. Desai. 

However, the traditional method of manually interpreting EEGs to identify seizures and their associated burden is a “complex and time-consuming process that can be subject to human error and variability,” she noted.

POC EEG is a rapid-access, reduced-montage EEG system that, when paired with an automated machine learning tool called Clarity (Ceribell, Inc; Sunnyvale, CA), can monitor and analyze seizure burden in real time.

The algorithm incorporates a comprehensive list of EEG features that have been associated with outcomes. It analyzes EEG activity every 10 seconds from all EEG channels and calculates a seizure burden in the past 5 minutes for the patient. The higher the seizure burden, the more time the patient has spent in seizure activity. 

Among 344 people with POC EEG (mean age, 62 years, 45% women) in the SAFER-EEG trial, 178 (52%) had seizure burden of zero throughout the recording and 41 (12%) had suspected status epilepticus (maximum seizure burden ≥ 90%). 

Before adjustment for clinical covariates, there was a significant association between high seizure burden and unfavorable outcomes. 

Specifically, 76% of patients with a seizure burden of 50% or greater had an unfavorable modified Rankin Scale score of 4 or greater at discharge and a similar proportion was discharged to long-term care facilities, she noted. 

After adjustment for relevant clinical covariants, patients with a high seizure burden (≥ 50 or > 90%) had a fourfold increase in odds of an unfavorable modified Rankin Scale score compared with those with no seizure burden. 

High seizure burden present in the last quarter of the recording was particularly indicative of unfavorable outcomes (fivefold increased odds), “suggesting the critical timing of seizures and its impact on patient prognosis,” Dr. Desai noted. 
 

‘Profound Implications’

“The implications of our research are profound, indicating a pivotal shift towards integrating AI and machine learning-guided automated EEG interpretation in management of critically ill patients with seizures,” she added. 

“As we move forward, our research will concentrate on applying this advanced tool in clinical decision making in clinical practice, examining how it can steer treatment decisions for patients, with the ultimate goal of enhancing patient care and improving outcomes for those affected by these neurological challenges,” Dr. Desai said. 

Briefing moderator Paul M. George, MD, PhD, chair of the AAN science committee, noted that this abstract was one of three featured at the “top science” press briefing themed “advancing the limits of neurologic care,” because it represents an “innovative method” of using new technology to improve understanding of neurologic conditions.

Dr. George said this technology “could be particularly useful in settings with few clinical specialists. It will be exciting to see as this unfolds, where it can guide maybe the ED doctor or primary care physician to help improve patient care.”

On that note, Dr. George cautioned that it’s still “early in the field” of using AI to guide decision-making and it will be important to gather more information to confirm that “machine learning algorithms can help guide physicians in treating patients with neurologic conditions.”

Funding for the study was provided by the University of Wisconsin-Madison and Ceribell, Inc. Dr. Desai received funding from Ceribell for this project. Dr. George has no relevant disclosures.

A version of this article appeared on Medscape.com.

DENVER — Seizure burden, defined by an artificial intelligence (AI) algorithm applied to point-of-care electroencephalography (POC EEG) recordings, can help predict functional outcomes.

After relevant cofactors were controlled for, higher seizure burden correlated with poorer functional outcomes. All of the patients in the study were being monitored as part of their standard of care owing to suspicion of seizures or because they were at risk for seizures, said study investigator Masoom Desai, MD, with the Department of Neurology, University of New Mexico, Albuquerque. The results were “compelling,” she said.

“Our study addresses the critical need for automation in monitoring epileptic activity and seizure burden,” Dr. Desai added during a press briefing at the 2024 annual meeting of the American Academy of Neurology (AAN).
 

A Pivotal Shift 

“Several decades of research have highlighted the significant correlation between seizure burden and unfavorable outcomes both in adult and pediatric populations,” said Dr. Desai. 

However, the traditional method of manually interpreting EEGs to identify seizures and their associated burden is a “complex and time-consuming process that can be subject to human error and variability,” she noted.

POC EEG is a rapid-access, reduced-montage EEG system that, when paired with an automated machine learning tool called Clarity (Ceribell, Inc; Sunnyvale, CA), can monitor and analyze seizure burden in real time.

The algorithm incorporates a comprehensive list of EEG features that have been associated with outcomes. It analyzes EEG activity every 10 seconds from all EEG channels and calculates a seizure burden in the past 5 minutes for the patient. The higher the seizure burden, the more time the patient has spent in seizure activity. 

Among 344 people with POC EEG (mean age, 62 years, 45% women) in the SAFER-EEG trial, 178 (52%) had seizure burden of zero throughout the recording and 41 (12%) had suspected status epilepticus (maximum seizure burden ≥ 90%). 

Before adjustment for clinical covariates, there was a significant association between high seizure burden and unfavorable outcomes. 

Specifically, 76% of patients with a seizure burden of 50% or greater had an unfavorable modified Rankin Scale score of 4 or greater at discharge and a similar proportion was discharged to long-term care facilities, she noted. 

After adjustment for relevant clinical covariants, patients with a high seizure burden (≥ 50 or > 90%) had a fourfold increase in odds of an unfavorable modified Rankin Scale score compared with those with no seizure burden. 

High seizure burden present in the last quarter of the recording was particularly indicative of unfavorable outcomes (fivefold increased odds), “suggesting the critical timing of seizures and its impact on patient prognosis,” Dr. Desai noted. 
 

‘Profound Implications’

“The implications of our research are profound, indicating a pivotal shift towards integrating AI and machine learning-guided automated EEG interpretation in management of critically ill patients with seizures,” she added. 

“As we move forward, our research will concentrate on applying this advanced tool in clinical decision making in clinical practice, examining how it can steer treatment decisions for patients, with the ultimate goal of enhancing patient care and improving outcomes for those affected by these neurological challenges,” Dr. Desai said. 

Briefing moderator Paul M. George, MD, PhD, chair of the AAN science committee, noted that this abstract was one of three featured at the “top science” press briefing themed “advancing the limits of neurologic care,” because it represents an “innovative method” of using new technology to improve understanding of neurologic conditions.

Dr. George said this technology “could be particularly useful in settings with few clinical specialists. It will be exciting to see as this unfolds, where it can guide maybe the ED doctor or primary care physician to help improve patient care.”

On that note, Dr. George cautioned that it’s still “early in the field” of using AI to guide decision-making and it will be important to gather more information to confirm that “machine learning algorithms can help guide physicians in treating patients with neurologic conditions.”

Funding for the study was provided by the University of Wisconsin-Madison and Ceribell, Inc. Dr. Desai received funding from Ceribell for this project. Dr. George has no relevant disclosures.

A version of this article appeared on Medscape.com.

DENVER — Seizure burden, defined by an artificial intelligence (AI) algorithm applied to point-of-care electroencephalography (POC EEG) recordings, can help predict functional outcomes.

After relevant cofactors were controlled for, higher seizure burden correlated with poorer functional outcomes. All of the patients in the study were being monitored as part of their standard of care owing to suspicion of seizures or because they were at risk for seizures, said study investigator Masoom Desai, MD, with the Department of Neurology, University of New Mexico, Albuquerque. The results were “compelling,” she said.

“Our study addresses the critical need for automation in monitoring epileptic activity and seizure burden,” Dr. Desai added during a press briefing at the 2024 annual meeting of the American Academy of Neurology (AAN).
 

A Pivotal Shift 

“Several decades of research have highlighted the significant correlation between seizure burden and unfavorable outcomes both in adult and pediatric populations,” said Dr. Desai. 

However, the traditional method of manually interpreting EEGs to identify seizures and their associated burden is a “complex and time-consuming process that can be subject to human error and variability,” she noted.

POC EEG is a rapid-access, reduced-montage EEG system that, when paired with an automated machine learning tool called Clarity (Ceribell, Inc; Sunnyvale, CA), can monitor and analyze seizure burden in real time.

The algorithm incorporates a comprehensive list of EEG features that have been associated with outcomes. It analyzes EEG activity every 10 seconds from all EEG channels and calculates a seizure burden in the past 5 minutes for the patient. The higher the seizure burden, the more time the patient has spent in seizure activity. 

Among 344 people with POC EEG (mean age, 62 years, 45% women) in the SAFER-EEG trial, 178 (52%) had seizure burden of zero throughout the recording and 41 (12%) had suspected status epilepticus (maximum seizure burden ≥ 90%). 

Before adjustment for clinical covariates, there was a significant association between high seizure burden and unfavorable outcomes. 

Specifically, 76% of patients with a seizure burden of 50% or greater had an unfavorable modified Rankin Scale score of 4 or greater at discharge and a similar proportion was discharged to long-term care facilities, she noted. 

After adjustment for relevant clinical covariants, patients with a high seizure burden (≥ 50 or > 90%) had a fourfold increase in odds of an unfavorable modified Rankin Scale score compared with those with no seizure burden. 

High seizure burden present in the last quarter of the recording was particularly indicative of unfavorable outcomes (fivefold increased odds), “suggesting the critical timing of seizures and its impact on patient prognosis,” Dr. Desai noted. 
 

‘Profound Implications’

“The implications of our research are profound, indicating a pivotal shift towards integrating AI and machine learning-guided automated EEG interpretation in management of critically ill patients with seizures,” she added. 

“As we move forward, our research will concentrate on applying this advanced tool in clinical decision making in clinical practice, examining how it can steer treatment decisions for patients, with the ultimate goal of enhancing patient care and improving outcomes for those affected by these neurological challenges,” Dr. Desai said. 

Briefing moderator Paul M. George, MD, PhD, chair of the AAN science committee, noted that this abstract was one of three featured at the “top science” press briefing themed “advancing the limits of neurologic care,” because it represents an “innovative method” of using new technology to improve understanding of neurologic conditions.

Dr. George said this technology “could be particularly useful in settings with few clinical specialists. It will be exciting to see as this unfolds, where it can guide maybe the ED doctor or primary care physician to help improve patient care.”

On that note, Dr. George cautioned that it’s still “early in the field” of using AI to guide decision-making and it will be important to gather more information to confirm that “machine learning algorithms can help guide physicians in treating patients with neurologic conditions.”

Funding for the study was provided by the University of Wisconsin-Madison and Ceribell, Inc. Dr. Desai received funding from Ceribell for this project. Dr. George has no relevant disclosures.

A version of this article appeared on Medscape.com.

If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.

That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).

“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.

Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
 

Mucosal Barrier Disruption

There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.

“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.

Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.

“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.

Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
 

DMARD Resistance

To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.

They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.

“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.

They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.

The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.

Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
 

Modulating the Gut

“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.

They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.

Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.

One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.

Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.

Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.

In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.

“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
 

What Are You Measuring?

In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”

Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology

He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.

“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.

He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”

Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.

That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).

“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.

Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
 

Mucosal Barrier Disruption

There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.

“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.

Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.

“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.

Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
 

DMARD Resistance

To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.

They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.

“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.

They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.

The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.

Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
 

Modulating the Gut

“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.

They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.

Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.

One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.

Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.

Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.

In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.

“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
 

What Are You Measuring?

In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”

Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology

He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.

“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.

He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”

Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.

That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).

“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.

Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
 

Mucosal Barrier Disruption

There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.

“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.

Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.

“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.

Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
 

DMARD Resistance

To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.

They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.

“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.

They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.

The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.

Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
 

Modulating the Gut

“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.

They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.

Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.

One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.

Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.

Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.

In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.

“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
 

What Are You Measuring?

In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”

Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology

He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.

“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.

He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”

Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.