Starting this month, I will be joining Dr. Leslie S. Baumann as a cocontributor to the Cosmeceutical Critique column, and since this is my first column, I would like to formally introduce myself. I am a cosmetic and general dermatologist in private practice in Miami and a longtime skin care enthusiast. My path toward becoming a dermatologist began when I was working in New York City, my hometown, as a scientific researcher, fulfilling my passion for scientific inquiry. After realizing that I most enjoyed applying discoveries made in the lab directly to patient care, I decided to pursue medical school at New York University before completing a dermatology residency at the University of Miami, serving as Chief Resident during my final year. Although I was born and raised in New York, staying in Miami was an obvious decision for me. In addition to the tropical weather and amazing lifestyle, the medical community in Miami supports adventure, creativity, and innovation, which are key aspects that drew me to the University of Miami and continue to drive my personal evolution in private practice.

I now practice at Baumann Cosmetic & Research Institute alongside my mentor, Dr. Baumann. I truly have my dream job – I get to talk skin care and do a wide array of cosmetics procedures, perform skin surgeries, and solve complex medical dermatology cases all in a day’s work. My career sits at the intersection of my passions for science, critical thinking, beauty, aesthetics, and most importantly, engaging with patients.

For my first column, I want to provide a newly minted dermatologist’s perspective on cosmeceuticals. I will focus this discussion on the limited training in cosmeceuticals during residency and the importance of learning about cosmeceuticals, and I will provide a simple framework to approach the design of skin care regimens and utilization of cosmeceuticals in practice.

The focus of a dermatology residency is on medical and surgical skills. We become experts in diagnosing and treating conditions ranging from life-threatening drug reactions like Stevens-Johnson Syndrome to complex diseases like dermatomyositis, utilizing medications and treatments ranging from cyclosporine and methotrexate to biologics and intravenous immunoglobulin, and performing advanced skin surgeries utilizing flaps and grafts to repair defects.

The discipline of cosmetic dermatology, let alone cosmeceuticals, accounts for a fraction of our didactic and hands-on training. I completed a top dermatology residency program that prepared me to treat any dermatologic condition; however, I honestly felt like I didn’t have a strong understanding of cosmeceuticals and skin care and how to integrate them with prescription therapies when I completed residency, which is a sentiment shared by residents across the country. I remember a study break while preparing for my final board exam when I went into a tailspin for an entire day trying to decode an ingredient list of a new “antiaging serum” and researching its mechanisms of action and the clinical data supporting the active ingredients in the serum, which included bakuchiol and a blend of peptides. As a dermatologist who likes to treat and provide recommendations based on scientific rationale and data to deliver the highest level of care, I admit that I felt insecure not being as knowledgeable about cosmeceuticals as I was about more complex dermatology treatments. As both a cosmetic and general dermatologist, discussing skin care and cosmeceuticals independent of or in conjunction with medical management occurs daily, and I recognized that becoming an expert in this area is essential to becoming a top, well-rounded dermatologist.
 

A gap in cosmeceutical education in dermatology residency

Multiple studies have established that the field of cosmetic dermatology comprises a fraction of dermatology residency training. In 2013, Kirby et al. published a survey of dermatology instructors and chief residents across the country and found that only 67% of responders reported having received formal lectures on cosmetic dermatology.¹ In 2014, Bauer et al. published a survey of dermatology program directors assessing attitudes toward cosmetic dermatology and reported that only 38% of program directors believed that cosmetic dermatology should be a necessary aspect of residency training.² A survey sent to dermatology residents published in 2012 found that among respondents, more than 58% of residency programs have an “encouraging or somewhat encouraging” attitude toward teaching cosmetic dermatology, yet 22% of programs had a “somewhat discouraging” or “discouraging” attitude.³ While these noted studies have focused on procedural aspects of cosmetic dermatology training, Feetham et al. surveyed dermatology residents and faculty to assess attitudes toward and training on skin care and cosmeceuticals specifically. Among resident respondents, most (74.5%) reported their education on skin care and cosmeceuticals has been “too little or nonexistent” during residency and 76.5% “agree or strongly agree” that it should be part of their education.4 In contrast, 60% of faculty reported resident education on skin care and cosmeceuticals is “just the right amount or too much” (P < .001).

In my personal experience as a resident, discussing skin care was emphasized when treating patients with eczema, contact dermatitis, acne, and hair disorders, but otherwise, the majority of skin care discussions relied on having a stock list of recommended cleansers, moisturizers, and sunscreens. In regards to cosmeceuticals for facial skin specifically, there were only a handful of instances in which alternative ingredients, such as vitamin C for hyperpigmentation, were discussed and specific brands were mentioned. Upon reflection, I wish I had more opportunity to see the clinical benefits of cosmeceuticals first hand, just like when I observe dupilumab clear patients with severe atopic dermatitis, rather than reading about it in textbooks and journals.

While one hypothesis for programs’ limited attention given to cosmetic training may be that it detracts from medical training, the survey by Bauer et al. found that residents did not feel less prepared (94.9%) or less interested (97.4%) in medical dermatology as a result of their cosmetic training.² In addition, providers in an academic dermatology residency may limit discussions of skin care because of the high patient volume and because extensive skin care discussions will not impact insurance billings. Academic dermatology programs often service patients with more financial constraints, which further limits OTC cosmeceutical discussions. In my residency experience, I had the opportunity to regularly treat more severe and rare dermatologic cases than those I encounter in private practice; therefore, I spent more time focusing on systemic therapies, with fewer opportunities to dedicate time to cosmeceuticals.
 

Why skin care and cosmeceuticals should be an essential aspect of residency training

Discussing skin care and cosmeceuticals is a valuable aspect of medical and general dermatology, not just aesthetic dermatology. When treating general dermatologic conditions, guidance on proper skin care can improve both adherence and efficacy of medical treatments. For example, an acne study by de Lucas et al. demonstrated that adherence to adjuvant treatment of acne (such as the use of moisturizers) was associated not only with a 2.4-fold increase in the probability of adherence to pharmacological treatment, but also with a significant reduction in acne severity.⁵ Aside from skin care, cosmeceuticals themselves have efficacy in treating general dermatologic conditions. In the treatment of acne, topical niacinamide, a popular cosmeceutical ingredient, has been shown to have sebosuppressive and anti-inflammatory effects, addressing key aspects of acne pathogenesis.⁶ A double-blind study by Draelos et al. reported topical 2% niacinamide was effective in reducing the rate of sebum excretion in 50 Japanese patients over 4 weeks.⁶ In several double-blind studies that have compared twice daily application of 4% nicotinamide gel with the same application of 1% clindamycin gel in moderate inflammatory acne over 8 weeks, nicotinamide gel reduced the number of inflammatory papules and acne lesions to a level comparable with clindamycin gel.6 These studies support the use of niacinamide cosmeceutical products as an adjunctive treatment for acne.

With increased clinical data supporting cosmeceuticals, it can be expected that some cosmeceuticals will substitute traditional prescription medications in the dermatologists’ arsenal. For example, hydroquinone – both prescription strength and OTC 2% – is a workhorse in treating melasma; however, there is increasing interest in hydroquinone-free treatments, especially since OTC cosmeceuticals containing 2% hydroquinone were banned in 2020 because of safety concerns. Dermatologists will therefore need to provide guidance about hydroquinone alternatives for skin lightening, including soy, licorice extracts, kojic acid, arbutin, niacinamide, N-acetylglucosamine, and vitamin C, among others.⁷ Utilizing knowledge of a cosmeceutical’s mechanisms of action and clinical data, the dermatologist is in the best position to guide patients toward optimal ingredients and dispel cosmeceutical myths. Given that cosmeceuticals are not regulated by the Food and Drug Administration, it is even more important that the dermatologist serves as an authority on cosmeceuticals.
 

How to become a master skin care and cosmeceutical prescriber

A common pitfall I have observed among practitioners less experienced with aesthetic-focused skin care and cosmeceuticals is adapting a one-size-fits-all approach. In the one-size-fits-all approach, every patient concerned about aging gets the same vitamin C serum and retinoid, and every patient with hyperpigmentation gets the same hydroquinone prescription, for example. This approach, however, does not take into account unique differences in patients’ skin. Below

is the basic skin care framework that I follow, taught to me by Dr. Baumann. It utilizes an individualized approach based on the patient’s skin qualities to achieve optimal results.

Determine the patient’s skin type (dry vs. oily; sensitive vs. not sensitive; pigmentation issues vs. no hyperpigmentation; wrinkled and mature vs. nonwrinkled) and identify concerns (e.g., dark spots, redness, acne, dehydration).

Separate products into categories of cleansers, eye creams, moisturizers, sun protection, and treatments. Treatments refers to any additional products in a skin care regimen intended to ameliorate a particular condition (e.g., vitamin C for hyperpigmentation, retinoids for fine lines).

Choose products for each category in step 2 (cleansers, eye creams, moisturizers, sun protection, treatments) that are complementary to the patient’s skin type (determined in step 1) and aid the patient in meeting their particular skin goals. For example, a salicylic acid cleanser would be beneficial for a patient with oily skin and acne, but this same cleanser may be too drying and irritating for an acne patient with dry skin.

Ensure that chosen ingredients and products work together harmoniously. For example, while the acne patient may benefit from a salicylic acid cleanser and retinoid cream, using them in succession initially may be overly drying for some patients.

Spend the time to make sure patients understand the appropriate order of application and recognize when efficacy of a product is impacted by another product in the regimen. For example, a low pH cleanser can increase penetration of an ascorbic acid product that follows it in the regimen.

After establishing a basic skin care framework, the next step for beginners is learning about ingredients and their mechanisms of action and familiarizing themselves with scientific and clinical studies. Until cosmeceuticals become an integral part of the training curriculum, dermatologists can gain knowledge independently by reading literature and studies on cosmeceutical active ingredients and experimenting with consumer products. I look forward to regularly contributing to this column to further our awareness and understanding of the mechanisms of and data supporting cosmeceuticals so that we can better guide our patients.

Please feel free to email me at chloe@derm.net or message me on Instagram @DrChloeGoldman with ideas that you would like me to address in this column.
 

Dr. Goldman is a dermatologist in private practice in Miami, and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a new general dermatology practice. Dr. Goldman receives compensation to create social media content for Replenix, a skin care company. She has no other relevant disclosures.

References

1. Kirby JS et al. J Am Acad Dermatol. 2013;68(2):e23-8.

2. Bauer et al. JAMA Dermatol. 2014;150(2):125-9.

3. Group A et al. Dermatol Surg. 2012;38(12):1975-80.

4. Feetham HJ et al. J Cosmet Dermatol. 2018;17(2):220-6.

5. de Lucas R et al. BMC Dermatol. 2015;15:17.

6. Araviiskaia E and Dreno BJ. Eur Acad Dermatol Venereol. 2016;30(6):926-35.

7. Leyden JJ et al. J Eur Acad Dermatol Venereol. 2011;25(10):1140-5.

Starting this month, I will be joining Dr. Leslie S. Baumann as a cocontributor to the Cosmeceutical Critique column, and since this is my first column, I would like to formally introduce myself. I am a cosmetic and general dermatologist in private practice in Miami and a longtime skin care enthusiast. My path toward becoming a dermatologist began when I was working in New York City, my hometown, as a scientific researcher, fulfilling my passion for scientific inquiry. After realizing that I most enjoyed applying discoveries made in the lab directly to patient care, I decided to pursue medical school at New York University before completing a dermatology residency at the University of Miami, serving as Chief Resident during my final year. Although I was born and raised in New York, staying in Miami was an obvious decision for me. In addition to the tropical weather and amazing lifestyle, the medical community in Miami supports adventure, creativity, and innovation, which are key aspects that drew me to the University of Miami and continue to drive my personal evolution in private practice.

I now practice at Baumann Cosmetic & Research Institute alongside my mentor, Dr. Baumann. I truly have my dream job – I get to talk skin care and do a wide array of cosmetics procedures, perform skin surgeries, and solve complex medical dermatology cases all in a day’s work. My career sits at the intersection of my passions for science, critical thinking, beauty, aesthetics, and most importantly, engaging with patients.

For my first column, I want to provide a newly minted dermatologist’s perspective on cosmeceuticals. I will focus this discussion on the limited training in cosmeceuticals during residency and the importance of learning about cosmeceuticals, and I will provide a simple framework to approach the design of skin care regimens and utilization of cosmeceuticals in practice.

The focus of a dermatology residency is on medical and surgical skills. We become experts in diagnosing and treating conditions ranging from life-threatening drug reactions like Stevens-Johnson Syndrome to complex diseases like dermatomyositis, utilizing medications and treatments ranging from cyclosporine and methotrexate to biologics and intravenous immunoglobulin, and performing advanced skin surgeries utilizing flaps and grafts to repair defects.

The discipline of cosmetic dermatology, let alone cosmeceuticals, accounts for a fraction of our didactic and hands-on training. I completed a top dermatology residency program that prepared me to treat any dermatologic condition; however, I honestly felt like I didn’t have a strong understanding of cosmeceuticals and skin care and how to integrate them with prescription therapies when I completed residency, which is a sentiment shared by residents across the country. I remember a study break while preparing for my final board exam when I went into a tailspin for an entire day trying to decode an ingredient list of a new “antiaging serum” and researching its mechanisms of action and the clinical data supporting the active ingredients in the serum, which included bakuchiol and a blend of peptides. As a dermatologist who likes to treat and provide recommendations based on scientific rationale and data to deliver the highest level of care, I admit that I felt insecure not being as knowledgeable about cosmeceuticals as I was about more complex dermatology treatments. As both a cosmetic and general dermatologist, discussing skin care and cosmeceuticals independent of or in conjunction with medical management occurs daily, and I recognized that becoming an expert in this area is essential to becoming a top, well-rounded dermatologist.
 

A gap in cosmeceutical education in dermatology residency

Multiple studies have established that the field of cosmetic dermatology comprises a fraction of dermatology residency training. In 2013, Kirby et al. published a survey of dermatology instructors and chief residents across the country and found that only 67% of responders reported having received formal lectures on cosmetic dermatology.¹ In 2014, Bauer et al. published a survey of dermatology program directors assessing attitudes toward cosmetic dermatology and reported that only 38% of program directors believed that cosmetic dermatology should be a necessary aspect of residency training.² A survey sent to dermatology residents published in 2012 found that among respondents, more than 58% of residency programs have an “encouraging or somewhat encouraging” attitude toward teaching cosmetic dermatology, yet 22% of programs had a “somewhat discouraging” or “discouraging” attitude.³ While these noted studies have focused on procedural aspects of cosmetic dermatology training, Feetham et al. surveyed dermatology residents and faculty to assess attitudes toward and training on skin care and cosmeceuticals specifically. Among resident respondents, most (74.5%) reported their education on skin care and cosmeceuticals has been “too little or nonexistent” during residency and 76.5% “agree or strongly agree” that it should be part of their education.4 In contrast, 60% of faculty reported resident education on skin care and cosmeceuticals is “just the right amount or too much” (P < .001).

In my personal experience as a resident, discussing skin care was emphasized when treating patients with eczema, contact dermatitis, acne, and hair disorders, but otherwise, the majority of skin care discussions relied on having a stock list of recommended cleansers, moisturizers, and sunscreens. In regards to cosmeceuticals for facial skin specifically, there were only a handful of instances in which alternative ingredients, such as vitamin C for hyperpigmentation, were discussed and specific brands were mentioned. Upon reflection, I wish I had more opportunity to see the clinical benefits of cosmeceuticals first hand, just like when I observe dupilumab clear patients with severe atopic dermatitis, rather than reading about it in textbooks and journals.

While one hypothesis for programs’ limited attention given to cosmetic training may be that it detracts from medical training, the survey by Bauer et al. found that residents did not feel less prepared (94.9%) or less interested (97.4%) in medical dermatology as a result of their cosmetic training.² In addition, providers in an academic dermatology residency may limit discussions of skin care because of the high patient volume and because extensive skin care discussions will not impact insurance billings. Academic dermatology programs often service patients with more financial constraints, which further limits OTC cosmeceutical discussions. In my residency experience, I had the opportunity to regularly treat more severe and rare dermatologic cases than those I encounter in private practice; therefore, I spent more time focusing on systemic therapies, with fewer opportunities to dedicate time to cosmeceuticals.
 

Why skin care and cosmeceuticals should be an essential aspect of residency training

Discussing skin care and cosmeceuticals is a valuable aspect of medical and general dermatology, not just aesthetic dermatology. When treating general dermatologic conditions, guidance on proper skin care can improve both adherence and efficacy of medical treatments. For example, an acne study by de Lucas et al. demonstrated that adherence to adjuvant treatment of acne (such as the use of moisturizers) was associated not only with a 2.4-fold increase in the probability of adherence to pharmacological treatment, but also with a significant reduction in acne severity.⁵ Aside from skin care, cosmeceuticals themselves have efficacy in treating general dermatologic conditions. In the treatment of acne, topical niacinamide, a popular cosmeceutical ingredient, has been shown to have sebosuppressive and anti-inflammatory effects, addressing key aspects of acne pathogenesis.⁶ A double-blind study by Draelos et al. reported topical 2% niacinamide was effective in reducing the rate of sebum excretion in 50 Japanese patients over 4 weeks.⁶ In several double-blind studies that have compared twice daily application of 4% nicotinamide gel with the same application of 1% clindamycin gel in moderate inflammatory acne over 8 weeks, nicotinamide gel reduced the number of inflammatory papules and acne lesions to a level comparable with clindamycin gel.6 These studies support the use of niacinamide cosmeceutical products as an adjunctive treatment for acne.

With increased clinical data supporting cosmeceuticals, it can be expected that some cosmeceuticals will substitute traditional prescription medications in the dermatologists’ arsenal. For example, hydroquinone – both prescription strength and OTC 2% – is a workhorse in treating melasma; however, there is increasing interest in hydroquinone-free treatments, especially since OTC cosmeceuticals containing 2% hydroquinone were banned in 2020 because of safety concerns. Dermatologists will therefore need to provide guidance about hydroquinone alternatives for skin lightening, including soy, licorice extracts, kojic acid, arbutin, niacinamide, N-acetylglucosamine, and vitamin C, among others.⁷ Utilizing knowledge of a cosmeceutical’s mechanisms of action and clinical data, the dermatologist is in the best position to guide patients toward optimal ingredients and dispel cosmeceutical myths. Given that cosmeceuticals are not regulated by the Food and Drug Administration, it is even more important that the dermatologist serves as an authority on cosmeceuticals.
 

How to become a master skin care and cosmeceutical prescriber

A common pitfall I have observed among practitioners less experienced with aesthetic-focused skin care and cosmeceuticals is adapting a one-size-fits-all approach. In the one-size-fits-all approach, every patient concerned about aging gets the same vitamin C serum and retinoid, and every patient with hyperpigmentation gets the same hydroquinone prescription, for example. This approach, however, does not take into account unique differences in patients’ skin. Below

is the basic skin care framework that I follow, taught to me by Dr. Baumann. It utilizes an individualized approach based on the patient’s skin qualities to achieve optimal results.

Determine the patient’s skin type (dry vs. oily; sensitive vs. not sensitive; pigmentation issues vs. no hyperpigmentation; wrinkled and mature vs. nonwrinkled) and identify concerns (e.g., dark spots, redness, acne, dehydration).

Separate products into categories of cleansers, eye creams, moisturizers, sun protection, and treatments. Treatments refers to any additional products in a skin care regimen intended to ameliorate a particular condition (e.g., vitamin C for hyperpigmentation, retinoids for fine lines).

Choose products for each category in step 2 (cleansers, eye creams, moisturizers, sun protection, treatments) that are complementary to the patient’s skin type (determined in step 1) and aid the patient in meeting their particular skin goals. For example, a salicylic acid cleanser would be beneficial for a patient with oily skin and acne, but this same cleanser may be too drying and irritating for an acne patient with dry skin.

Ensure that chosen ingredients and products work together harmoniously. For example, while the acne patient may benefit from a salicylic acid cleanser and retinoid cream, using them in succession initially may be overly drying for some patients.

Spend the time to make sure patients understand the appropriate order of application and recognize when efficacy of a product is impacted by another product in the regimen. For example, a low pH cleanser can increase penetration of an ascorbic acid product that follows it in the regimen.

After establishing a basic skin care framework, the next step for beginners is learning about ingredients and their mechanisms of action and familiarizing themselves with scientific and clinical studies. Until cosmeceuticals become an integral part of the training curriculum, dermatologists can gain knowledge independently by reading literature and studies on cosmeceutical active ingredients and experimenting with consumer products. I look forward to regularly contributing to this column to further our awareness and understanding of the mechanisms of and data supporting cosmeceuticals so that we can better guide our patients.

Please feel free to email me at chloe@derm.net or message me on Instagram @DrChloeGoldman with ideas that you would like me to address in this column.
 

Dr. Goldman is a dermatologist in private practice in Miami, and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a new general dermatology practice. Dr. Goldman receives compensation to create social media content for Replenix, a skin care company. She has no other relevant disclosures.

References

1. Kirby JS et al. J Am Acad Dermatol. 2013;68(2):e23-8.

2. Bauer et al. JAMA Dermatol. 2014;150(2):125-9.

3. Group A et al. Dermatol Surg. 2012;38(12):1975-80.

4. Feetham HJ et al. J Cosmet Dermatol. 2018;17(2):220-6.

5. de Lucas R et al. BMC Dermatol. 2015;15:17.

6. Araviiskaia E and Dreno BJ. Eur Acad Dermatol Venereol. 2016;30(6):926-35.

7. Leyden JJ et al. J Eur Acad Dermatol Venereol. 2011;25(10):1140-5.

Starting this month, I will be joining Dr. Leslie S. Baumann as a cocontributor to the Cosmeceutical Critique column, and since this is my first column, I would like to formally introduce myself. I am a cosmetic and general dermatologist in private practice in Miami and a longtime skin care enthusiast. My path toward becoming a dermatologist began when I was working in New York City, my hometown, as a scientific researcher, fulfilling my passion for scientific inquiry. After realizing that I most enjoyed applying discoveries made in the lab directly to patient care, I decided to pursue medical school at New York University before completing a dermatology residency at the University of Miami, serving as Chief Resident during my final year. Although I was born and raised in New York, staying in Miami was an obvious decision for me. In addition to the tropical weather and amazing lifestyle, the medical community in Miami supports adventure, creativity, and innovation, which are key aspects that drew me to the University of Miami and continue to drive my personal evolution in private practice.

I now practice at Baumann Cosmetic & Research Institute alongside my mentor, Dr. Baumann. I truly have my dream job – I get to talk skin care and do a wide array of cosmetics procedures, perform skin surgeries, and solve complex medical dermatology cases all in a day’s work. My career sits at the intersection of my passions for science, critical thinking, beauty, aesthetics, and most importantly, engaging with patients.

For my first column, I want to provide a newly minted dermatologist’s perspective on cosmeceuticals. I will focus this discussion on the limited training in cosmeceuticals during residency and the importance of learning about cosmeceuticals, and I will provide a simple framework to approach the design of skin care regimens and utilization of cosmeceuticals in practice.

The focus of a dermatology residency is on medical and surgical skills. We become experts in diagnosing and treating conditions ranging from life-threatening drug reactions like Stevens-Johnson Syndrome to complex diseases like dermatomyositis, utilizing medications and treatments ranging from cyclosporine and methotrexate to biologics and intravenous immunoglobulin, and performing advanced skin surgeries utilizing flaps and grafts to repair defects.

The discipline of cosmetic dermatology, let alone cosmeceuticals, accounts for a fraction of our didactic and hands-on training. I completed a top dermatology residency program that prepared me to treat any dermatologic condition; however, I honestly felt like I didn’t have a strong understanding of cosmeceuticals and skin care and how to integrate them with prescription therapies when I completed residency, which is a sentiment shared by residents across the country. I remember a study break while preparing for my final board exam when I went into a tailspin for an entire day trying to decode an ingredient list of a new “antiaging serum” and researching its mechanisms of action and the clinical data supporting the active ingredients in the serum, which included bakuchiol and a blend of peptides. As a dermatologist who likes to treat and provide recommendations based on scientific rationale and data to deliver the highest level of care, I admit that I felt insecure not being as knowledgeable about cosmeceuticals as I was about more complex dermatology treatments. As both a cosmetic and general dermatologist, discussing skin care and cosmeceuticals independent of or in conjunction with medical management occurs daily, and I recognized that becoming an expert in this area is essential to becoming a top, well-rounded dermatologist.
 

A gap in cosmeceutical education in dermatology residency

Multiple studies have established that the field of cosmetic dermatology comprises a fraction of dermatology residency training. In 2013, Kirby et al. published a survey of dermatology instructors and chief residents across the country and found that only 67% of responders reported having received formal lectures on cosmetic dermatology.¹ In 2014, Bauer et al. published a survey of dermatology program directors assessing attitudes toward cosmetic dermatology and reported that only 38% of program directors believed that cosmetic dermatology should be a necessary aspect of residency training.² A survey sent to dermatology residents published in 2012 found that among respondents, more than 58% of residency programs have an “encouraging or somewhat encouraging” attitude toward teaching cosmetic dermatology, yet 22% of programs had a “somewhat discouraging” or “discouraging” attitude.³ While these noted studies have focused on procedural aspects of cosmetic dermatology training, Feetham et al. surveyed dermatology residents and faculty to assess attitudes toward and training on skin care and cosmeceuticals specifically. Among resident respondents, most (74.5%) reported their education on skin care and cosmeceuticals has been “too little or nonexistent” during residency and 76.5% “agree or strongly agree” that it should be part of their education.4 In contrast, 60% of faculty reported resident education on skin care and cosmeceuticals is “just the right amount or too much” (P < .001).

In my personal experience as a resident, discussing skin care was emphasized when treating patients with eczema, contact dermatitis, acne, and hair disorders, but otherwise, the majority of skin care discussions relied on having a stock list of recommended cleansers, moisturizers, and sunscreens. In regards to cosmeceuticals for facial skin specifically, there were only a handful of instances in which alternative ingredients, such as vitamin C for hyperpigmentation, were discussed and specific brands were mentioned. Upon reflection, I wish I had more opportunity to see the clinical benefits of cosmeceuticals first hand, just like when I observe dupilumab clear patients with severe atopic dermatitis, rather than reading about it in textbooks and journals.

While one hypothesis for programs’ limited attention given to cosmetic training may be that it detracts from medical training, the survey by Bauer et al. found that residents did not feel less prepared (94.9%) or less interested (97.4%) in medical dermatology as a result of their cosmetic training.² In addition, providers in an academic dermatology residency may limit discussions of skin care because of the high patient volume and because extensive skin care discussions will not impact insurance billings. Academic dermatology programs often service patients with more financial constraints, which further limits OTC cosmeceutical discussions. In my residency experience, I had the opportunity to regularly treat more severe and rare dermatologic cases than those I encounter in private practice; therefore, I spent more time focusing on systemic therapies, with fewer opportunities to dedicate time to cosmeceuticals.
 

Why skin care and cosmeceuticals should be an essential aspect of residency training

Discussing skin care and cosmeceuticals is a valuable aspect of medical and general dermatology, not just aesthetic dermatology. When treating general dermatologic conditions, guidance on proper skin care can improve both adherence and efficacy of medical treatments. For example, an acne study by de Lucas et al. demonstrated that adherence to adjuvant treatment of acne (such as the use of moisturizers) was associated not only with a 2.4-fold increase in the probability of adherence to pharmacological treatment, but also with a significant reduction in acne severity.⁵ Aside from skin care, cosmeceuticals themselves have efficacy in treating general dermatologic conditions. In the treatment of acne, topical niacinamide, a popular cosmeceutical ingredient, has been shown to have sebosuppressive and anti-inflammatory effects, addressing key aspects of acne pathogenesis.⁶ A double-blind study by Draelos et al. reported topical 2% niacinamide was effective in reducing the rate of sebum excretion in 50 Japanese patients over 4 weeks.⁶ In several double-blind studies that have compared twice daily application of 4% nicotinamide gel with the same application of 1% clindamycin gel in moderate inflammatory acne over 8 weeks, nicotinamide gel reduced the number of inflammatory papules and acne lesions to a level comparable with clindamycin gel.6 These studies support the use of niacinamide cosmeceutical products as an adjunctive treatment for acne.

With increased clinical data supporting cosmeceuticals, it can be expected that some cosmeceuticals will substitute traditional prescription medications in the dermatologists’ arsenal. For example, hydroquinone – both prescription strength and OTC 2% – is a workhorse in treating melasma; however, there is increasing interest in hydroquinone-free treatments, especially since OTC cosmeceuticals containing 2% hydroquinone were banned in 2020 because of safety concerns. Dermatologists will therefore need to provide guidance about hydroquinone alternatives for skin lightening, including soy, licorice extracts, kojic acid, arbutin, niacinamide, N-acetylglucosamine, and vitamin C, among others.⁷ Utilizing knowledge of a cosmeceutical’s mechanisms of action and clinical data, the dermatologist is in the best position to guide patients toward optimal ingredients and dispel cosmeceutical myths. Given that cosmeceuticals are not regulated by the Food and Drug Administration, it is even more important that the dermatologist serves as an authority on cosmeceuticals.
 

How to become a master skin care and cosmeceutical prescriber

A common pitfall I have observed among practitioners less experienced with aesthetic-focused skin care and cosmeceuticals is adapting a one-size-fits-all approach. In the one-size-fits-all approach, every patient concerned about aging gets the same vitamin C serum and retinoid, and every patient with hyperpigmentation gets the same hydroquinone prescription, for example. This approach, however, does not take into account unique differences in patients’ skin. Below

is the basic skin care framework that I follow, taught to me by Dr. Baumann. It utilizes an individualized approach based on the patient’s skin qualities to achieve optimal results.

Determine the patient’s skin type (dry vs. oily; sensitive vs. not sensitive; pigmentation issues vs. no hyperpigmentation; wrinkled and mature vs. nonwrinkled) and identify concerns (e.g., dark spots, redness, acne, dehydration).

Separate products into categories of cleansers, eye creams, moisturizers, sun protection, and treatments. Treatments refers to any additional products in a skin care regimen intended to ameliorate a particular condition (e.g., vitamin C for hyperpigmentation, retinoids for fine lines).

Choose products for each category in step 2 (cleansers, eye creams, moisturizers, sun protection, treatments) that are complementary to the patient’s skin type (determined in step 1) and aid the patient in meeting their particular skin goals. For example, a salicylic acid cleanser would be beneficial for a patient with oily skin and acne, but this same cleanser may be too drying and irritating for an acne patient with dry skin.

Ensure that chosen ingredients and products work together harmoniously. For example, while the acne patient may benefit from a salicylic acid cleanser and retinoid cream, using them in succession initially may be overly drying for some patients.

Spend the time to make sure patients understand the appropriate order of application and recognize when efficacy of a product is impacted by another product in the regimen. For example, a low pH cleanser can increase penetration of an ascorbic acid product that follows it in the regimen.

After establishing a basic skin care framework, the next step for beginners is learning about ingredients and their mechanisms of action and familiarizing themselves with scientific and clinical studies. Until cosmeceuticals become an integral part of the training curriculum, dermatologists can gain knowledge independently by reading literature and studies on cosmeceutical active ingredients and experimenting with consumer products. I look forward to regularly contributing to this column to further our awareness and understanding of the mechanisms of and data supporting cosmeceuticals so that we can better guide our patients.

Please feel free to email me at chloe@derm.net or message me on Instagram @DrChloeGoldman with ideas that you would like me to address in this column.
 

Dr. Goldman is a dermatologist in private practice in Miami, and specializes in cosmetic and general dermatology. She practices at Baumann Cosmetic & Research Institute and is also opening a new general dermatology practice. Dr. Goldman receives compensation to create social media content for Replenix, a skin care company. She has no other relevant disclosures.

References

1. Kirby JS et al. J Am Acad Dermatol. 2013;68(2):e23-8.

2. Bauer et al. JAMA Dermatol. 2014;150(2):125-9.

3. Group A et al. Dermatol Surg. 2012;38(12):1975-80.

4. Feetham HJ et al. J Cosmet Dermatol. 2018;17(2):220-6.

5. de Lucas R et al. BMC Dermatol. 2015;15:17.

6. Araviiskaia E and Dreno BJ. Eur Acad Dermatol Venereol. 2016;30(6):926-35.

7. Leyden JJ et al. J Eur Acad Dermatol Venereol. 2011;25(10):1140-5.

Oral tofacitinib (Xeljanz), a Janus kinase inhibitor, helped regrow hair in three-quarters of pediatric patients with alopecia areata (AA) in a small study conducted at the University of Colorado and published in Pediatric Dermatology.

The 11 pediatric patients, ages 8-18 years, all with a diagnosis of AA, were treated with tofacitinib. Eight patients, or nearly 73%, experienced hair regrowth, while the other three (27.3%) did not, as the investigators reported in the retrospective chart review.

“A success rate of 73% is very good,” said lead author Cory A. Dunnick, MD, professor of dermatology and director of clinical trials at the University of Colorado at Denver, Aurora. No serious adverse events occurred, and adverse events of any kind were limited, the researchers found.

“It is important to get information into the literature about potential treatments for severe alopecia areata because there is no [Food and Drug Administration]–approved therapy at the present time,” Dr. Dunnick told this news organization. Patients’ insurance plans often deny non–FDA-approved therapies unless there are data to support their use.

The researchers found no correlation between the dose, duration of treatment, or the presence of comorbidities and clinical response.

Oral tofacitinib has been shown to be effective and well tolerated for AA in adults, the researchers said. They referred to recent studies that have used JAK inhibitors, including tofacitinib, “in an effort to inhibit T-cell activation and halt disease progression in adult and pediatric patients” with AA.
 

Study details

Of the 11 patients evaluated, 6 had alopecia universalis, 1 had alopecia totalis, and 4 had patchy AA. Concomitant medical conditions known to be associated with AA affected four patients. These included atopic dermatitis, autoimmune hypothyroidism, and asthma. One patient reported having two brothers with AA.

The median disease duration was 6 years. “In my experience, JAK inhibitors are less effective for patients with longstanding – more than 10 years – alopecia totalis or alopecia universalis,” Dr. Dunnick said.

Previously, patients had been given methotrexate, oral prednisone, intralesional triamcinolone, topical corticosteroids, and topical diphenylcyclopropenone. During treatment with tofacitinib, 5 of the 11 patients also received topical steroid treatment.

The study was a retrospective chart review, so dosing was not standardized, the researchers said. Most took 5-10 mg twice daily. Median treatment time was 32 months, with a range of 5-39 months.

Patients with a complete or near complete clinical response were categorized as responders; subjectively, these were the patients who had persistent hair regrowth over more than 50% of affected areas. Five patients had complete regrowth of hair on the scalp, eyebrows, and body during treatment. Others had incomplete responses. For instance, one patient had improved growth of eyelashes and eyebrows but not on the scalp. Once the medication was increased to 15 mg daily, the patient had complete regrowth of body hair, eyelashes, and eyebrows but slow regrowth on the scalp after 1 year of treatment.

“Patients are very happy with regrowth of their hair,” Dr. Dunnick said, noting that severe AA affects self-esteem and quality of life.
 

Other research

In a retrospective study that looked at the effects of oral tofacitinib given to 14 preadolescent patients with AA, 9 experienced “clinically significant improvement” in their Severity of Alopecia Tool score. Three had complete remission, and seven (63.6%) had more than a 50% improvement in the score.

Mechanisms, concerns

The researchers of the current study explained that interferon signaling activity through the JAK pathways is a key mediator of the inflammation and cytotoxic T-cell response in AA. That modulation of the signaling may decrease disease progression, as the results of the current chart review suggest.

A main concern, the researchers wrote, is the potential for significant adverse events. Although this chart review did not find any, the researchers did see some transient lab abnormalities. One study found lab abnormalities in such measures as triglycerides and cholesterol.

Asked to comment on the study results, Brett King, MD, PHD, associate professor of dermatology at Yale University, New Haven, Conn., said that the study “is an important addition to a series of articles dating back to 2017 showing efficacy of tofacitinib in the pediatric age group.” The results are similar to those of previous studies, “showing that severe AA can be treated effectively with tofacitinib. Cumulatively, there is significant data to support treatment of this age group with JAK inhibitors,” he said.

At the 2021 European Academy of Dermatology and Venereology meeting, Dr. King presented the results of two phase 3 studies, which found that treatment with the oral JAK inhibitor baricitinib resulted in substantial hair growth in adults with AA. He and colleagues have also reported positive results of tofacitinib in treating AA in four children ages 8-10, with alopecia totalis and alopecia universalis, and in adolescents with AA.

Currently, three large, randomized, phase 3 clinical trials of other JAK inhibitors for AA are underway – ritlecitinib, baricitinib, and ruxolitinib – and the ritlecitinib trial includes adolescents (ages 12 years and older). “It is the results of these trials that we eagerly await, because FDA approval will bring greater access to these treatments,” Dr. King said.

Dr. Dunnick has disclosed no relevant financial relationships. Dr. King has served on advisory boards and/or is a consultant and/or a clinical trial investigator for AbbVie, Bristol-Myers Squibb, Concert Pharmaceuticals, Eli Lilly, Incyte, Pfizer, and others. He is on speaker bureaus for AbbVie, Incyte, Pfizer, and others.

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

Oral tofacitinib (Xeljanz), a Janus kinase inhibitor, helped regrow hair in three-quarters of pediatric patients with alopecia areata (AA) in a small study conducted at the University of Colorado and published in Pediatric Dermatology.

The 11 pediatric patients, ages 8-18 years, all with a diagnosis of AA, were treated with tofacitinib. Eight patients, or nearly 73%, experienced hair regrowth, while the other three (27.3%) did not, as the investigators reported in the retrospective chart review.

“A success rate of 73% is very good,” said lead author Cory A. Dunnick, MD, professor of dermatology and director of clinical trials at the University of Colorado at Denver, Aurora. No serious adverse events occurred, and adverse events of any kind were limited, the researchers found.

“It is important to get information into the literature about potential treatments for severe alopecia areata because there is no [Food and Drug Administration]–approved therapy at the present time,” Dr. Dunnick told this news organization. Patients’ insurance plans often deny non–FDA-approved therapies unless there are data to support their use.

The researchers found no correlation between the dose, duration of treatment, or the presence of comorbidities and clinical response.

Oral tofacitinib has been shown to be effective and well tolerated for AA in adults, the researchers said. They referred to recent studies that have used JAK inhibitors, including tofacitinib, “in an effort to inhibit T-cell activation and halt disease progression in adult and pediatric patients” with AA.
 

Study details

Of the 11 patients evaluated, 6 had alopecia universalis, 1 had alopecia totalis, and 4 had patchy AA. Concomitant medical conditions known to be associated with AA affected four patients. These included atopic dermatitis, autoimmune hypothyroidism, and asthma. One patient reported having two brothers with AA.

The median disease duration was 6 years. “In my experience, JAK inhibitors are less effective for patients with longstanding – more than 10 years – alopecia totalis or alopecia universalis,” Dr. Dunnick said.

Previously, patients had been given methotrexate, oral prednisone, intralesional triamcinolone, topical corticosteroids, and topical diphenylcyclopropenone. During treatment with tofacitinib, 5 of the 11 patients also received topical steroid treatment.

The study was a retrospective chart review, so dosing was not standardized, the researchers said. Most took 5-10 mg twice daily. Median treatment time was 32 months, with a range of 5-39 months.

Patients with a complete or near complete clinical response were categorized as responders; subjectively, these were the patients who had persistent hair regrowth over more than 50% of affected areas. Five patients had complete regrowth of hair on the scalp, eyebrows, and body during treatment. Others had incomplete responses. For instance, one patient had improved growth of eyelashes and eyebrows but not on the scalp. Once the medication was increased to 15 mg daily, the patient had complete regrowth of body hair, eyelashes, and eyebrows but slow regrowth on the scalp after 1 year of treatment.

“Patients are very happy with regrowth of their hair,” Dr. Dunnick said, noting that severe AA affects self-esteem and quality of life.
 

Other research

In a retrospective study that looked at the effects of oral tofacitinib given to 14 preadolescent patients with AA, 9 experienced “clinically significant improvement” in their Severity of Alopecia Tool score. Three had complete remission, and seven (63.6%) had more than a 50% improvement in the score.

Mechanisms, concerns

The researchers of the current study explained that interferon signaling activity through the JAK pathways is a key mediator of the inflammation and cytotoxic T-cell response in AA. That modulation of the signaling may decrease disease progression, as the results of the current chart review suggest.

A main concern, the researchers wrote, is the potential for significant adverse events. Although this chart review did not find any, the researchers did see some transient lab abnormalities. One study found lab abnormalities in such measures as triglycerides and cholesterol.

Asked to comment on the study results, Brett King, MD, PHD, associate professor of dermatology at Yale University, New Haven, Conn., said that the study “is an important addition to a series of articles dating back to 2017 showing efficacy of tofacitinib in the pediatric age group.” The results are similar to those of previous studies, “showing that severe AA can be treated effectively with tofacitinib. Cumulatively, there is significant data to support treatment of this age group with JAK inhibitors,” he said.

At the 2021 European Academy of Dermatology and Venereology meeting, Dr. King presented the results of two phase 3 studies, which found that treatment with the oral JAK inhibitor baricitinib resulted in substantial hair growth in adults with AA. He and colleagues have also reported positive results of tofacitinib in treating AA in four children ages 8-10, with alopecia totalis and alopecia universalis, and in adolescents with AA.

Currently, three large, randomized, phase 3 clinical trials of other JAK inhibitors for AA are underway – ritlecitinib, baricitinib, and ruxolitinib – and the ritlecitinib trial includes adolescents (ages 12 years and older). “It is the results of these trials that we eagerly await, because FDA approval will bring greater access to these treatments,” Dr. King said.

Dr. Dunnick has disclosed no relevant financial relationships. Dr. King has served on advisory boards and/or is a consultant and/or a clinical trial investigator for AbbVie, Bristol-Myers Squibb, Concert Pharmaceuticals, Eli Lilly, Incyte, Pfizer, and others. He is on speaker bureaus for AbbVie, Incyte, Pfizer, and others.

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

Oral tofacitinib (Xeljanz), a Janus kinase inhibitor, helped regrow hair in three-quarters of pediatric patients with alopecia areata (AA) in a small study conducted at the University of Colorado and published in Pediatric Dermatology.

The 11 pediatric patients, ages 8-18 years, all with a diagnosis of AA, were treated with tofacitinib. Eight patients, or nearly 73%, experienced hair regrowth, while the other three (27.3%) did not, as the investigators reported in the retrospective chart review.

“A success rate of 73% is very good,” said lead author Cory A. Dunnick, MD, professor of dermatology and director of clinical trials at the University of Colorado at Denver, Aurora. No serious adverse events occurred, and adverse events of any kind were limited, the researchers found.

“It is important to get information into the literature about potential treatments for severe alopecia areata because there is no [Food and Drug Administration]–approved therapy at the present time,” Dr. Dunnick told this news organization. Patients’ insurance plans often deny non–FDA-approved therapies unless there are data to support their use.

The researchers found no correlation between the dose, duration of treatment, or the presence of comorbidities and clinical response.

Oral tofacitinib has been shown to be effective and well tolerated for AA in adults, the researchers said. They referred to recent studies that have used JAK inhibitors, including tofacitinib, “in an effort to inhibit T-cell activation and halt disease progression in adult and pediatric patients” with AA.
 

Study details

Of the 11 patients evaluated, 6 had alopecia universalis, 1 had alopecia totalis, and 4 had patchy AA. Concomitant medical conditions known to be associated with AA affected four patients. These included atopic dermatitis, autoimmune hypothyroidism, and asthma. One patient reported having two brothers with AA.

The median disease duration was 6 years. “In my experience, JAK inhibitors are less effective for patients with longstanding – more than 10 years – alopecia totalis or alopecia universalis,” Dr. Dunnick said.

Previously, patients had been given methotrexate, oral prednisone, intralesional triamcinolone, topical corticosteroids, and topical diphenylcyclopropenone. During treatment with tofacitinib, 5 of the 11 patients also received topical steroid treatment.

The study was a retrospective chart review, so dosing was not standardized, the researchers said. Most took 5-10 mg twice daily. Median treatment time was 32 months, with a range of 5-39 months.

Patients with a complete or near complete clinical response were categorized as responders; subjectively, these were the patients who had persistent hair regrowth over more than 50% of affected areas. Five patients had complete regrowth of hair on the scalp, eyebrows, and body during treatment. Others had incomplete responses. For instance, one patient had improved growth of eyelashes and eyebrows but not on the scalp. Once the medication was increased to 15 mg daily, the patient had complete regrowth of body hair, eyelashes, and eyebrows but slow regrowth on the scalp after 1 year of treatment.

“Patients are very happy with regrowth of their hair,” Dr. Dunnick said, noting that severe AA affects self-esteem and quality of life.
 

Other research

In a retrospective study that looked at the effects of oral tofacitinib given to 14 preadolescent patients with AA, 9 experienced “clinically significant improvement” in their Severity of Alopecia Tool score. Three had complete remission, and seven (63.6%) had more than a 50% improvement in the score.

Mechanisms, concerns

The researchers of the current study explained that interferon signaling activity through the JAK pathways is a key mediator of the inflammation and cytotoxic T-cell response in AA. That modulation of the signaling may decrease disease progression, as the results of the current chart review suggest.

A main concern, the researchers wrote, is the potential for significant adverse events. Although this chart review did not find any, the researchers did see some transient lab abnormalities. One study found lab abnormalities in such measures as triglycerides and cholesterol.

Asked to comment on the study results, Brett King, MD, PHD, associate professor of dermatology at Yale University, New Haven, Conn., said that the study “is an important addition to a series of articles dating back to 2017 showing efficacy of tofacitinib in the pediatric age group.” The results are similar to those of previous studies, “showing that severe AA can be treated effectively with tofacitinib. Cumulatively, there is significant data to support treatment of this age group with JAK inhibitors,” he said.

At the 2021 European Academy of Dermatology and Venereology meeting, Dr. King presented the results of two phase 3 studies, which found that treatment with the oral JAK inhibitor baricitinib resulted in substantial hair growth in adults with AA. He and colleagues have also reported positive results of tofacitinib in treating AA in four children ages 8-10, with alopecia totalis and alopecia universalis, and in adolescents with AA.

Currently, three large, randomized, phase 3 clinical trials of other JAK inhibitors for AA are underway – ritlecitinib, baricitinib, and ruxolitinib – and the ritlecitinib trial includes adolescents (ages 12 years and older). “It is the results of these trials that we eagerly await, because FDA approval will bring greater access to these treatments,” Dr. King said.

Dr. Dunnick has disclosed no relevant financial relationships. Dr. King has served on advisory boards and/or is a consultant and/or a clinical trial investigator for AbbVie, Bristol-Myers Squibb, Concert Pharmaceuticals, Eli Lilly, Incyte, Pfizer, and others. He is on speaker bureaus for AbbVie, Incyte, Pfizer, and others.

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

One year into treatment with an every-6-month dose of the investigational drug lenacapavir (LEN, Gilead Sciences) in a dual-treatment combination, 88% of treatment-naive people living with HIV had undetectable viral loads.

The findings, presented at the Conference on Retroviruses and Opportunistic Infections, also showed the drug was well tolerated, with 2 of 182 people developing drug-resistant mutations to lenacapavir and one person developing a nodule at the injection site.

Laura Waters, MD, consulting physician in HIV and sexual health at Central and Northwest London NHS Trust, who was not involved in the trial, called the findings “hugely exciting,” especially given its unique mode of administration. Right now it’s formulated as a subcutaneous injection, not an intramuscular injection like cabotegravir and rilpivirine (Cabenuva, ViiV Healthcare).

“Clearly it’s incredibly exciting to have the option for a subcutaneous drug that could be given at home every 6 months,” Dr. Waters said in an interview. With phase 3 trials and long-term follow-up still to come, she said she’s looking forward to how the treatment evolves.

CALIBRATE is a phase 2, four-arm, open-label, active-control study. Of the 182 participants, 25 were randomized to the active control arm, in which participants took daily oral bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy, Gilead Sciences) as standard of care. The rest of the 182 participants were divided evenly between three arms. In one of those, treatment group three, participants took a daily oral version of 50-mg LEN with emtricitabine and tenofovir alafenamide (F/TAF, Descovy, Gilead Sciences).

The other two arms, treatment groups one and two, were the arms in which Samir K. Gupta, MD, of Indiana University, Indianapolis, and colleagues tried the twice-yearly subcutaneous shots of LEN (LEN SC). Participants in those arms underwent a 2-week lead-in period in which they took 600 mg of LEN orally on days 1 and 2 and then a 300-mg pill on day 8 before starting the shots on day 15. As currently formulated, LEN SC shots can be given into the stomach and are designed to be simple enough to administer at home.

“It’s like doing an insulin shot,” Dr. Gupta said in an interview.

In addition to LEN SC, participants in treatment group one took a daily Descovy lead-in and then engaged in dual therapy of LEN plus TAF. In group two, they took a daily Descovy lead-in and then switched to LEN SC plus bictegravir (BIC) daily at 28 weeks.

Study results presented at the meeting were the results at 54 weeks. Researchers had previously presented 28-week results for CALIBRATE at the International AIDS Society Conference on HIV Science 2021.

Of the participants, 7% were cisgender women, 52% were Black, and 45% were Latinx. A total of 15% of participants had baseline viral loads of more than 100,000 copies, and median CD4 counts were 437. None of the participants in either the active-control arm or the LEN SC plus Descovy group had a history of AIDS, defined as fewer than 200 cells/mcL. In the LEN SC plus Biktarvy group, two did, and there were six people with a history of AIDS in the oral LEN plus Descovy group.

At 54 weeks, 88% of participants in groups one and two – the LEN SC arms – had undetectable viral loads (viral loads below 50 copies/mL). Specifically, 90% of those in the LEN SC plus TAF arm had viral loads below 50 copies. Those taking LEN SC plus BIC had an 85% viral suppression rate. The best performing of all was the control arm, in which 92% had undetectable viral loads. The protocol didn’t allow for analysis of statistical significance between the arms, so it’s unclear if any of the treatments really surpassed the others, Dr. Gupta said.

When they looked only at people whose viral loads became undetectable early, by week 28, the results were slightly better, with 93% of people between the two subcutaneous arms having undetectable viral loads at week 54. Again, the results were slightly higher in the LEN SC plus TAF arm (94%) than the LEN SC plus BIC (92%). People taking daily oral LEN plus Descovy had the lowest rate of viral suppression, but it was still at 90% if they were virally suppressed early. Again, it’s unclear whether those differences were statistically significant.
 

Well tolerated, with a chance of a nodule

Regarding safety, LEN was well tolerated across treatment arms, though the oral LEN group had as many people develop resistance mutations as the other three groups combined. Still, that was only three people, with one each in the two subcutaneous arms and one in the control arm.

Two people developed resistance to LEN – one in the LEN SC plus BIC arm and one in the oral LEN plus Descovy arm. In the LEN SC plus BIC arm, the mutations Q67H and K70R emerged at week 10, following a mutation that’s common when people don’t take integrase inhibitors as they’re supposed to (M184M/I). This led Dr. Gupta to conclude that lack of adherence to the oral part of the regimen may have contributed to the development of resistance, rather than an issue with LEN SC itself.

In the oral LEN plus Descovy arm, mutation Q67H didn’t emerge until week 54, when pill counts and drug levels revealed that that participant hadn’t been taking his Descovy as prescribed. In both cases, viral loads in those participants returned to undetectable after switching to an integrase inhibitor–based three-drug regimen.

Most safety concerns were mild and included nausea, diarrhea, and vomiting. But that was for non–injection-site reactions. There were more side effects of that sort, with most of them being pain, hardening of the site, and swelling. But 11% of participants developed more serious side effects, including nodules. Only one nodule was considered a grade 3 reaction; that person didn’t leave the trial because of it.

“These phase 2 data from the ongoing CALIBRATE trial support the further evaluation of lenacapavir for treatment and prevention of HIV-1,” he said.
 

Finding the right partner

In short, the findings are promising, Dr. Gupta told this news organization . But the question now, as Gilead prepares to begin a phase 3 efficacy trial, is what would be a good combination with LEN SC?

“Lenacapavir in a two-drug regimen should work,” he said. “The question now, though, is you have to find a suitable, potent, second agent to pair it with.”

Indeed, the long-acting HIV treatment pipeline sustained a blow in December 2021 when the U.S. Food and Drug Administration halted all trials for Merck’s investigational, long-acting drug islatravir. This led Dr. Waters to tweet: “Is it just me or are the islatravir abstracts at #CROI2022 quite sad to read?” She ended the tweet with, “I just hope it recovers!”

Indeed, Merck and Gilead have entered into an agreement to codevelop lenacapavir and islatravir as a weekly oral tablet. Islatravir seemed like the obvious choice as a partner to lenacapavir if phase 3 trials are successful, said Dr. Gupta. But now, it’s anyone’s guess as to what will happen. And while it’s too soon to say that lenacapavir is a success, it does leave the field wondering about how to use LEN SC without another, equally long-acting agent.

“When I talk about LEN, I show a picture of a man standing solo at a party, leaning against the wall looking a bit lonely, with ‘lenacapavir’ written over his head,” she said in an interview. “Right now, lenacapavir is the only drug at the 6-monthly party. It’s going to need some other guests if that party is going to rock.”

The study was funded by Gilead Sciences. Dr. Gupta has received research funding from ViiV Healthcare and advisory board fees from Gilead Sciences and ViiV Healthcare. Dr. Waters has received speaker or advisory fees from Gilead Sciences, ViiV Healthcare, Merck, Janssen, Theratech, Sipla, and Mylan.

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

One year into treatment with an every-6-month dose of the investigational drug lenacapavir (LEN, Gilead Sciences) in a dual-treatment combination, 88% of treatment-naive people living with HIV had undetectable viral loads.

The findings, presented at the Conference on Retroviruses and Opportunistic Infections, also showed the drug was well tolerated, with 2 of 182 people developing drug-resistant mutations to lenacapavir and one person developing a nodule at the injection site.

Laura Waters, MD, consulting physician in HIV and sexual health at Central and Northwest London NHS Trust, who was not involved in the trial, called the findings “hugely exciting,” especially given its unique mode of administration. Right now it’s formulated as a subcutaneous injection, not an intramuscular injection like cabotegravir and rilpivirine (Cabenuva, ViiV Healthcare).

“Clearly it’s incredibly exciting to have the option for a subcutaneous drug that could be given at home every 6 months,” Dr. Waters said in an interview. With phase 3 trials and long-term follow-up still to come, she said she’s looking forward to how the treatment evolves.

CALIBRATE is a phase 2, four-arm, open-label, active-control study. Of the 182 participants, 25 were randomized to the active control arm, in which participants took daily oral bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy, Gilead Sciences) as standard of care. The rest of the 182 participants were divided evenly between three arms. In one of those, treatment group three, participants took a daily oral version of 50-mg LEN with emtricitabine and tenofovir alafenamide (F/TAF, Descovy, Gilead Sciences).

The other two arms, treatment groups one and two, were the arms in which Samir K. Gupta, MD, of Indiana University, Indianapolis, and colleagues tried the twice-yearly subcutaneous shots of LEN (LEN SC). Participants in those arms underwent a 2-week lead-in period in which they took 600 mg of LEN orally on days 1 and 2 and then a 300-mg pill on day 8 before starting the shots on day 15. As currently formulated, LEN SC shots can be given into the stomach and are designed to be simple enough to administer at home.

“It’s like doing an insulin shot,” Dr. Gupta said in an interview.

In addition to LEN SC, participants in treatment group one took a daily Descovy lead-in and then engaged in dual therapy of LEN plus TAF. In group two, they took a daily Descovy lead-in and then switched to LEN SC plus bictegravir (BIC) daily at 28 weeks.

Study results presented at the meeting were the results at 54 weeks. Researchers had previously presented 28-week results for CALIBRATE at the International AIDS Society Conference on HIV Science 2021.

Of the participants, 7% were cisgender women, 52% were Black, and 45% were Latinx. A total of 15% of participants had baseline viral loads of more than 100,000 copies, and median CD4 counts were 437. None of the participants in either the active-control arm or the LEN SC plus Descovy group had a history of AIDS, defined as fewer than 200 cells/mcL. In the LEN SC plus Biktarvy group, two did, and there were six people with a history of AIDS in the oral LEN plus Descovy group.

At 54 weeks, 88% of participants in groups one and two – the LEN SC arms – had undetectable viral loads (viral loads below 50 copies/mL). Specifically, 90% of those in the LEN SC plus TAF arm had viral loads below 50 copies. Those taking LEN SC plus BIC had an 85% viral suppression rate. The best performing of all was the control arm, in which 92% had undetectable viral loads. The protocol didn’t allow for analysis of statistical significance between the arms, so it’s unclear if any of the treatments really surpassed the others, Dr. Gupta said.

When they looked only at people whose viral loads became undetectable early, by week 28, the results were slightly better, with 93% of people between the two subcutaneous arms having undetectable viral loads at week 54. Again, the results were slightly higher in the LEN SC plus TAF arm (94%) than the LEN SC plus BIC (92%). People taking daily oral LEN plus Descovy had the lowest rate of viral suppression, but it was still at 90% if they were virally suppressed early. Again, it’s unclear whether those differences were statistically significant.
 

Well tolerated, with a chance of a nodule

Regarding safety, LEN was well tolerated across treatment arms, though the oral LEN group had as many people develop resistance mutations as the other three groups combined. Still, that was only three people, with one each in the two subcutaneous arms and one in the control arm.

Two people developed resistance to LEN – one in the LEN SC plus BIC arm and one in the oral LEN plus Descovy arm. In the LEN SC plus BIC arm, the mutations Q67H and K70R emerged at week 10, following a mutation that’s common when people don’t take integrase inhibitors as they’re supposed to (M184M/I). This led Dr. Gupta to conclude that lack of adherence to the oral part of the regimen may have contributed to the development of resistance, rather than an issue with LEN SC itself.

In the oral LEN plus Descovy arm, mutation Q67H didn’t emerge until week 54, when pill counts and drug levels revealed that that participant hadn’t been taking his Descovy as prescribed. In both cases, viral loads in those participants returned to undetectable after switching to an integrase inhibitor–based three-drug regimen.

Most safety concerns were mild and included nausea, diarrhea, and vomiting. But that was for non–injection-site reactions. There were more side effects of that sort, with most of them being pain, hardening of the site, and swelling. But 11% of participants developed more serious side effects, including nodules. Only one nodule was considered a grade 3 reaction; that person didn’t leave the trial because of it.

“These phase 2 data from the ongoing CALIBRATE trial support the further evaluation of lenacapavir for treatment and prevention of HIV-1,” he said.
 

Finding the right partner

In short, the findings are promising, Dr. Gupta told this news organization . But the question now, as Gilead prepares to begin a phase 3 efficacy trial, is what would be a good combination with LEN SC?

“Lenacapavir in a two-drug regimen should work,” he said. “The question now, though, is you have to find a suitable, potent, second agent to pair it with.”

Indeed, the long-acting HIV treatment pipeline sustained a blow in December 2021 when the U.S. Food and Drug Administration halted all trials for Merck’s investigational, long-acting drug islatravir. This led Dr. Waters to tweet: “Is it just me or are the islatravir abstracts at #CROI2022 quite sad to read?” She ended the tweet with, “I just hope it recovers!”

Indeed, Merck and Gilead have entered into an agreement to codevelop lenacapavir and islatravir as a weekly oral tablet. Islatravir seemed like the obvious choice as a partner to lenacapavir if phase 3 trials are successful, said Dr. Gupta. But now, it’s anyone’s guess as to what will happen. And while it’s too soon to say that lenacapavir is a success, it does leave the field wondering about how to use LEN SC without another, equally long-acting agent.

“When I talk about LEN, I show a picture of a man standing solo at a party, leaning against the wall looking a bit lonely, with ‘lenacapavir’ written over his head,” she said in an interview. “Right now, lenacapavir is the only drug at the 6-monthly party. It’s going to need some other guests if that party is going to rock.”

The study was funded by Gilead Sciences. Dr. Gupta has received research funding from ViiV Healthcare and advisory board fees from Gilead Sciences and ViiV Healthcare. Dr. Waters has received speaker or advisory fees from Gilead Sciences, ViiV Healthcare, Merck, Janssen, Theratech, Sipla, and Mylan.

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

One year into treatment with an every-6-month dose of the investigational drug lenacapavir (LEN, Gilead Sciences) in a dual-treatment combination, 88% of treatment-naive people living with HIV had undetectable viral loads.

The findings, presented at the Conference on Retroviruses and Opportunistic Infections, also showed the drug was well tolerated, with 2 of 182 people developing drug-resistant mutations to lenacapavir and one person developing a nodule at the injection site.

Laura Waters, MD, consulting physician in HIV and sexual health at Central and Northwest London NHS Trust, who was not involved in the trial, called the findings “hugely exciting,” especially given its unique mode of administration. Right now it’s formulated as a subcutaneous injection, not an intramuscular injection like cabotegravir and rilpivirine (Cabenuva, ViiV Healthcare).

“Clearly it’s incredibly exciting to have the option for a subcutaneous drug that could be given at home every 6 months,” Dr. Waters said in an interview. With phase 3 trials and long-term follow-up still to come, she said she’s looking forward to how the treatment evolves.

CALIBRATE is a phase 2, four-arm, open-label, active-control study. Of the 182 participants, 25 were randomized to the active control arm, in which participants took daily oral bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy, Gilead Sciences) as standard of care. The rest of the 182 participants were divided evenly between three arms. In one of those, treatment group three, participants took a daily oral version of 50-mg LEN with emtricitabine and tenofovir alafenamide (F/TAF, Descovy, Gilead Sciences).

The other two arms, treatment groups one and two, were the arms in which Samir K. Gupta, MD, of Indiana University, Indianapolis, and colleagues tried the twice-yearly subcutaneous shots of LEN (LEN SC). Participants in those arms underwent a 2-week lead-in period in which they took 600 mg of LEN orally on days 1 and 2 and then a 300-mg pill on day 8 before starting the shots on day 15. As currently formulated, LEN SC shots can be given into the stomach and are designed to be simple enough to administer at home.

“It’s like doing an insulin shot,” Dr. Gupta said in an interview.

In addition to LEN SC, participants in treatment group one took a daily Descovy lead-in and then engaged in dual therapy of LEN plus TAF. In group two, they took a daily Descovy lead-in and then switched to LEN SC plus bictegravir (BIC) daily at 28 weeks.

Study results presented at the meeting were the results at 54 weeks. Researchers had previously presented 28-week results for CALIBRATE at the International AIDS Society Conference on HIV Science 2021.

Of the participants, 7% were cisgender women, 52% were Black, and 45% were Latinx. A total of 15% of participants had baseline viral loads of more than 100,000 copies, and median CD4 counts were 437. None of the participants in either the active-control arm or the LEN SC plus Descovy group had a history of AIDS, defined as fewer than 200 cells/mcL. In the LEN SC plus Biktarvy group, two did, and there were six people with a history of AIDS in the oral LEN plus Descovy group.

At 54 weeks, 88% of participants in groups one and two – the LEN SC arms – had undetectable viral loads (viral loads below 50 copies/mL). Specifically, 90% of those in the LEN SC plus TAF arm had viral loads below 50 copies. Those taking LEN SC plus BIC had an 85% viral suppression rate. The best performing of all was the control arm, in which 92% had undetectable viral loads. The protocol didn’t allow for analysis of statistical significance between the arms, so it’s unclear if any of the treatments really surpassed the others, Dr. Gupta said.

When they looked only at people whose viral loads became undetectable early, by week 28, the results were slightly better, with 93% of people between the two subcutaneous arms having undetectable viral loads at week 54. Again, the results were slightly higher in the LEN SC plus TAF arm (94%) than the LEN SC plus BIC (92%). People taking daily oral LEN plus Descovy had the lowest rate of viral suppression, but it was still at 90% if they were virally suppressed early. Again, it’s unclear whether those differences were statistically significant.
 

Well tolerated, with a chance of a nodule

Regarding safety, LEN was well tolerated across treatment arms, though the oral LEN group had as many people develop resistance mutations as the other three groups combined. Still, that was only three people, with one each in the two subcutaneous arms and one in the control arm.

Two people developed resistance to LEN – one in the LEN SC plus BIC arm and one in the oral LEN plus Descovy arm. In the LEN SC plus BIC arm, the mutations Q67H and K70R emerged at week 10, following a mutation that’s common when people don’t take integrase inhibitors as they’re supposed to (M184M/I). This led Dr. Gupta to conclude that lack of adherence to the oral part of the regimen may have contributed to the development of resistance, rather than an issue with LEN SC itself.

In the oral LEN plus Descovy arm, mutation Q67H didn’t emerge until week 54, when pill counts and drug levels revealed that that participant hadn’t been taking his Descovy as prescribed. In both cases, viral loads in those participants returned to undetectable after switching to an integrase inhibitor–based three-drug regimen.

Most safety concerns were mild and included nausea, diarrhea, and vomiting. But that was for non–injection-site reactions. There were more side effects of that sort, with most of them being pain, hardening of the site, and swelling. But 11% of participants developed more serious side effects, including nodules. Only one nodule was considered a grade 3 reaction; that person didn’t leave the trial because of it.

“These phase 2 data from the ongoing CALIBRATE trial support the further evaluation of lenacapavir for treatment and prevention of HIV-1,” he said.
 

Finding the right partner

In short, the findings are promising, Dr. Gupta told this news organization . But the question now, as Gilead prepares to begin a phase 3 efficacy trial, is what would be a good combination with LEN SC?

“Lenacapavir in a two-drug regimen should work,” he said. “The question now, though, is you have to find a suitable, potent, second agent to pair it with.”

Indeed, the long-acting HIV treatment pipeline sustained a blow in December 2021 when the U.S. Food and Drug Administration halted all trials for Merck’s investigational, long-acting drug islatravir. This led Dr. Waters to tweet: “Is it just me or are the islatravir abstracts at #CROI2022 quite sad to read?” She ended the tweet with, “I just hope it recovers!”

Indeed, Merck and Gilead have entered into an agreement to codevelop lenacapavir and islatravir as a weekly oral tablet. Islatravir seemed like the obvious choice as a partner to lenacapavir if phase 3 trials are successful, said Dr. Gupta. But now, it’s anyone’s guess as to what will happen. And while it’s too soon to say that lenacapavir is a success, it does leave the field wondering about how to use LEN SC without another, equally long-acting agent.

“When I talk about LEN, I show a picture of a man standing solo at a party, leaning against the wall looking a bit lonely, with ‘lenacapavir’ written over his head,” she said in an interview. “Right now, lenacapavir is the only drug at the 6-monthly party. It’s going to need some other guests if that party is going to rock.”

The study was funded by Gilead Sciences. Dr. Gupta has received research funding from ViiV Healthcare and advisory board fees from Gilead Sciences and ViiV Healthcare. Dr. Waters has received speaker or advisory fees from Gilead Sciences, ViiV Healthcare, Merck, Janssen, Theratech, Sipla, and Mylan.

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

New prescriptions of hydroxychloroquine (HCQ) and ivermectin increased in 2020, driven particularly by rates in counties with the highest proportion of Republican votes in the 2020 U.S. presidential election, according to a cross-sectional study published in JAMA Internal Medicine.

“Our findings are consistent with the hypothesis that U.S. prescribing of hydroxychloroquine and ivermectin during the COVID-19 pandemic may have been influenced by political affiliation,” wrote Michael L. Barnett, MD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.
 

The researchers used data from the OptumLabs Data Warehouse to analyze commercial and Medicare Advantage medical claims from January 2019 through December 2020 for more than 18.5 million adults living in counties with at least 50 enrollees.

Marc Bruxelle/Getty Images

The Food and Drug Administration issued an emergency use authorization (EUA) for HCQ as a COVID-19 treatment on March 28, 2020, but the agency revoked the EUA 3 months later on June 15. Ivermectin never received an EUA for COVID treatment, but an in vitro study published April 3, 2020 claimed it had an antiviral effect.

The National Institutes of Health recommended against using ivermectin as a COVID-19 treatment on Aug. 1, 2020, but a few months later, on Nov. 13, a flawed clinical trial – later retracted – claimed ivermectin was 90% effective in treating COVID-19. Despite the lack of evidence for ivermectin’s efficacy, a Senate committee meeting on Dec. 8, 2020, included testimony from a physician who promoted its use.

Mario Olaya/Pixabay

In comparing ivermectin and HCQ prescription rates with counties’ political composition, the researchers adjusted their findings to account for differences in the counties’ racial composition and COVID-19 incidence as well as enrollees’ age, sex, insurance type, income, comorbidity burden, and home in a rural or urban area.

The results showed an average of 20 new HCQ prescriptions per 100,000 enrollees in 2019, but 2020 saw a sharp increase and drop in new HCQ prescriptions in March-April 2020, independent of counties’ breakdown of political affiliation.

“However, after June 2020, coinciding with the revocation of the U.S. Food and Drug Administration’s emergency use authorization for hydroxychloroquine, prescribing volume was significantly higher in the highest vs. lowest Republican vote share counties,” the authors report. The gradual increase from June through December 2020 averaged to 42 new prescriptions per 100,000, a 146% increase over 2019 rates that was driven largely by the 25% of counties with the highest proportion of Republican voters.

Similarly, rates of new ivermectin prescriptions in December 2020 were more than nine times higher in counties with the highest Republican vote share, compared with new prescriptions throughout 2019. The researchers found no differences in new prescriptions for methotrexate or albendazole in 2020 based on counties’ proportion of Republican votes.

Since the study is an ecological, observational one, it cannot show causation or shed light on what role patients, physicians, or other factors might have played in prescribing patterns. Nevertheless, the authors noted the potentially negative implications of their findings.

“Because political affiliation should not be a factor in clinical treatment decisions, our findings raise concerns for public trust in a nonpartisan health care system,” the authors write.

Coauthor Ateev Mehrotra, MD, MPH, reported personal fees from Sanofi-Aventis, and coauthor Anupam B. Jena, MD, PhD, reported personal fees from Bioverativ, Merck, Janssen, Edwards Lifesciences, Novartis, Amgen, Eisai, Otsuka, Vertex, Celgene, Sanofi-Aventis, Precision Health Economics (now PRECISIONheor), Analysis Group, and Doubleday and hosting the podcast Freakonomics, M.D. The other coauthors have disclosed no relevant financial relationships. No external funding source was noted.

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

New prescriptions of hydroxychloroquine (HCQ) and ivermectin increased in 2020, driven particularly by rates in counties with the highest proportion of Republican votes in the 2020 U.S. presidential election, according to a cross-sectional study published in JAMA Internal Medicine.

“Our findings are consistent with the hypothesis that U.S. prescribing of hydroxychloroquine and ivermectin during the COVID-19 pandemic may have been influenced by political affiliation,” wrote Michael L. Barnett, MD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.
 

The researchers used data from the OptumLabs Data Warehouse to analyze commercial and Medicare Advantage medical claims from January 2019 through December 2020 for more than 18.5 million adults living in counties with at least 50 enrollees.

Marc Bruxelle/Getty Images

The Food and Drug Administration issued an emergency use authorization (EUA) for HCQ as a COVID-19 treatment on March 28, 2020, but the agency revoked the EUA 3 months later on June 15. Ivermectin never received an EUA for COVID treatment, but an in vitro study published April 3, 2020 claimed it had an antiviral effect.

The National Institutes of Health recommended against using ivermectin as a COVID-19 treatment on Aug. 1, 2020, but a few months later, on Nov. 13, a flawed clinical trial – later retracted – claimed ivermectin was 90% effective in treating COVID-19. Despite the lack of evidence for ivermectin’s efficacy, a Senate committee meeting on Dec. 8, 2020, included testimony from a physician who promoted its use.

Mario Olaya/Pixabay

In comparing ivermectin and HCQ prescription rates with counties’ political composition, the researchers adjusted their findings to account for differences in the counties’ racial composition and COVID-19 incidence as well as enrollees’ age, sex, insurance type, income, comorbidity burden, and home in a rural or urban area.

The results showed an average of 20 new HCQ prescriptions per 100,000 enrollees in 2019, but 2020 saw a sharp increase and drop in new HCQ prescriptions in March-April 2020, independent of counties’ breakdown of political affiliation.

“However, after June 2020, coinciding with the revocation of the U.S. Food and Drug Administration’s emergency use authorization for hydroxychloroquine, prescribing volume was significantly higher in the highest vs. lowest Republican vote share counties,” the authors report. The gradual increase from June through December 2020 averaged to 42 new prescriptions per 100,000, a 146% increase over 2019 rates that was driven largely by the 25% of counties with the highest proportion of Republican voters.

Similarly, rates of new ivermectin prescriptions in December 2020 were more than nine times higher in counties with the highest Republican vote share, compared with new prescriptions throughout 2019. The researchers found no differences in new prescriptions for methotrexate or albendazole in 2020 based on counties’ proportion of Republican votes.

Since the study is an ecological, observational one, it cannot show causation or shed light on what role patients, physicians, or other factors might have played in prescribing patterns. Nevertheless, the authors noted the potentially negative implications of their findings.

“Because political affiliation should not be a factor in clinical treatment decisions, our findings raise concerns for public trust in a nonpartisan health care system,” the authors write.

Coauthor Ateev Mehrotra, MD, MPH, reported personal fees from Sanofi-Aventis, and coauthor Anupam B. Jena, MD, PhD, reported personal fees from Bioverativ, Merck, Janssen, Edwards Lifesciences, Novartis, Amgen, Eisai, Otsuka, Vertex, Celgene, Sanofi-Aventis, Precision Health Economics (now PRECISIONheor), Analysis Group, and Doubleday and hosting the podcast Freakonomics, M.D. The other coauthors have disclosed no relevant financial relationships. No external funding source was noted.

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

New prescriptions of hydroxychloroquine (HCQ) and ivermectin increased in 2020, driven particularly by rates in counties with the highest proportion of Republican votes in the 2020 U.S. presidential election, according to a cross-sectional study published in JAMA Internal Medicine.

“Our findings are consistent with the hypothesis that U.S. prescribing of hydroxychloroquine and ivermectin during the COVID-19 pandemic may have been influenced by political affiliation,” wrote Michael L. Barnett, MD, of the Harvard T.H. Chan School of Public Health in Boston and colleagues.
 

The researchers used data from the OptumLabs Data Warehouse to analyze commercial and Medicare Advantage medical claims from January 2019 through December 2020 for more than 18.5 million adults living in counties with at least 50 enrollees.

Marc Bruxelle/Getty Images

The Food and Drug Administration issued an emergency use authorization (EUA) for HCQ as a COVID-19 treatment on March 28, 2020, but the agency revoked the EUA 3 months later on June 15. Ivermectin never received an EUA for COVID treatment, but an in vitro study published April 3, 2020 claimed it had an antiviral effect.

The National Institutes of Health recommended against using ivermectin as a COVID-19 treatment on Aug. 1, 2020, but a few months later, on Nov. 13, a flawed clinical trial – later retracted – claimed ivermectin was 90% effective in treating COVID-19. Despite the lack of evidence for ivermectin’s efficacy, a Senate committee meeting on Dec. 8, 2020, included testimony from a physician who promoted its use.

Mario Olaya/Pixabay

In comparing ivermectin and HCQ prescription rates with counties’ political composition, the researchers adjusted their findings to account for differences in the counties’ racial composition and COVID-19 incidence as well as enrollees’ age, sex, insurance type, income, comorbidity burden, and home in a rural or urban area.

The results showed an average of 20 new HCQ prescriptions per 100,000 enrollees in 2019, but 2020 saw a sharp increase and drop in new HCQ prescriptions in March-April 2020, independent of counties’ breakdown of political affiliation.

“However, after June 2020, coinciding with the revocation of the U.S. Food and Drug Administration’s emergency use authorization for hydroxychloroquine, prescribing volume was significantly higher in the highest vs. lowest Republican vote share counties,” the authors report. The gradual increase from June through December 2020 averaged to 42 new prescriptions per 100,000, a 146% increase over 2019 rates that was driven largely by the 25% of counties with the highest proportion of Republican voters.

Similarly, rates of new ivermectin prescriptions in December 2020 were more than nine times higher in counties with the highest Republican vote share, compared with new prescriptions throughout 2019. The researchers found no differences in new prescriptions for methotrexate or albendazole in 2020 based on counties’ proportion of Republican votes.

Since the study is an ecological, observational one, it cannot show causation or shed light on what role patients, physicians, or other factors might have played in prescribing patterns. Nevertheless, the authors noted the potentially negative implications of their findings.

“Because political affiliation should not be a factor in clinical treatment decisions, our findings raise concerns for public trust in a nonpartisan health care system,” the authors write.

Coauthor Ateev Mehrotra, MD, MPH, reported personal fees from Sanofi-Aventis, and coauthor Anupam B. Jena, MD, PhD, reported personal fees from Bioverativ, Merck, Janssen, Edwards Lifesciences, Novartis, Amgen, Eisai, Otsuka, Vertex, Celgene, Sanofi-Aventis, Precision Health Economics (now PRECISIONheor), Analysis Group, and Doubleday and hosting the podcast Freakonomics, M.D. The other coauthors have disclosed no relevant financial relationships. No external funding source was noted.

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

The thrombolytic tenecteplase may have a role in reestablishing blood flow in patients with large-vessel acute ischemic stroke up to 24 hours after stroke onset selected by perfusion imaging, a new trial from China suggests.

The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.

“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.

Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.

Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.

For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.

The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.

Recanalization at 4-6 hours occurred in 44% of both groups.

In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.

Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.

In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).

“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”

The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.

Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”

He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.

“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”

Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”

The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.

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

The thrombolytic tenecteplase may have a role in reestablishing blood flow in patients with large-vessel acute ischemic stroke up to 24 hours after stroke onset selected by perfusion imaging, a new trial from China suggests.

The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.

“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.

Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.

Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.

For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.

The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.

Recanalization at 4-6 hours occurred in 44% of both groups.

In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.

Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.

In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).

“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”

The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.

Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”

He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.

“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”

Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”

The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.

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

The thrombolytic tenecteplase may have a role in reestablishing blood flow in patients with large-vessel acute ischemic stroke up to 24 hours after stroke onset selected by perfusion imaging, a new trial from China suggests.

The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.

“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.

Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.

Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.

For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.

The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.

Recanalization at 4-6 hours occurred in 44% of both groups.

In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.

Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.

In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).

“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”

The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.

Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”

He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.

“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”

Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”

The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.

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

Adjunctive treatment with intravenous tirofiban does not improve clinical outcomes in patients with large-vessel occlusion stroke who undergo endovascular treatment within 24 hours of symptom onset, new data suggest.

In a randomized, phase 3 trial of more than 900 patients with acute ischemic stroke who underwent endovascular treatment, the median Modified Rankin Scale (mRS) score at 90 days was 3 both in patients who received tirofiban and those who received placebo.

“There was treatment-effect modification by stroke etiology, where patients with large-artery atherosclerosis [LAA] seemed to benefit from the treatment,” said investigator Raul Nogueira, MD, director of the University of Pittsburgh Medical Center Stroke Institute, during his presentation. “Tirofiban may improve endovascular treatment outcomes in LAA strokes. This obviously requires further investigation in future trials to confirm these findings.”

Results of the RESCUE BT trial were presented at the hybrid International Stroke Conference (ISC) 2022, which was held in New Orleans, Louisiana, and online.
 

Multicenter trial

Endovascular treatment greatly increases the rate of reperfusion and improves functional outcomes in patients with large-vessel occlusion stroke, the researchers note. But mechanical thrombectomy devices may injure the vessel wall, which can lead to clot formation and vessel reocclusion.

Platelet inhibition is a potential tactic for improving outcomes in this setting. Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is a reversible antiplatelet drug with a rapid onset of action and a short half-life. The drug’s safety and efficacy in acute coronary syndrome are well established. There has been little evidence to date, however, on whether tirofiban improves outcomes among patients with large-vessel occlusion stroke.

The investigators conducted the Endovascular Treatment With Versus Without Tirofiban for Stroke Patients With Large Vessel Occlusion (RESCUE BT) trial to evaluate the safety and efficacy of IV tirofiban therapy before endovascular treatment in patients with large-vessel occlusion stroke. They recruited consecutive patients at 55 thrombectomy-capable hospitals in China.

Eligible patients were aged 18 years or older and presented within 24 hours of the time they were last seen when well. Baseline National Institutes of Health Stroke Scale (NIHSS) score was required to be 30 or lower, and all patients were required to have plans to undergo endovascular treatment. Eligible patients also had a baseline Alberta Stroke Program Early CT Score of 6 or greater.

Patients were randomized in groups of equal size to placebo or tirofiban and stratified by NIHSS score and occlusion site. Tirofiban was administered in a 10-mcg/kg bolus followed by continuous infusion (0.15 mcg/kg per min) for 24 hours. All patients underwent rapid endovascular treatment.

At the 20th hour after treatment initiation, antiplatelets were administered orally. IV study drug was stopped at the 24th hour.

The study’s primary endpoint was disability level, as measured by overall distribution of the 90-day mRS score. The primary safety endpoints were symptomatic intracranial hemorrhage (ICH) at 48 hours and mortality at 90 days.
 

Increased ICH risk

The investigators screened 1,970 patients and enrolled 950 into their study. The population’s median age was 67 years, and 58.8% of participants were men. In all, 463 participants were randomly assigned to tirofiban, and 485 to placebo. Two patients withdrew consent, and none were lost to follow-up.

Baseline characteristics were well balanced in both groups. One difference, however, was that large-vessel occlusion was less prevalent in the tirofiban group (42.6%) than in the control group (49.1%).

The primary endpoint did not differ between treatment groups. The adjusted common odds ratio was 1.09 (P = .46). “There is perhaps a sign that there is maybe a favorable effect of tirofiban,” said Dr. Nogueira. “However, this did not reach statistical significance.”

The rates of symptomatic ICH and mortality at 90 days did not differ significantly between groups. There was a trend toward a higher rate of symptomatic ICH in the tirofiban group, however. Moreover, the rate of any ICH was 34.9% in the tirofiban group and 28.0% in the control group (P = .02).

In prespecified subgroup analysis, the researchers found that, among patients with large-vessel occlusion, the adjusted common odds ratio was 1.43 favoring tirofiban treatment. No other subgroups showed significant differences.

“In the intention-to-treat analysis, tirofiban did not improve clinical outcomes in the overall study population,” said Dr. Nogueira. “It did increase the rate of any ICH and potentially increased the rate of symptomatic ICH as well.”

The ongoing RESCUE BT2 trial is examining the safety and efficacy of tirofiban in patients with acute ischemic stroke with non–large-vessel occlusion. As of Jan. 20, 781 patients had been assigned randomly to treatment, said Dr. Nogueira.
 

Patient selection crucial

Louise McCullough, MD, PhD, professor and chair of neurology at the University of Texas Health Science Center at Houston, said that the study was well designed.

“The concern with any kind of platelet therapy or adjunctive therapy is hemorrhage,” said Dr. McCullough, who was not involved in the research. The results in the overall population support this concern.

The location of the trial sites may have influenced the results. “It was a multicenter trial, but it was predominantly done in Asia, and we know that there are higher levels of intracranial atherosclerosis in that population,” said Dr. McCullough.

The results indicate a potential benefit of tirofiban in patients with large-vessel occlusion, yet this finding raises practical questions. “It’s often difficult to know if these patients have atherosclerosis until you’re actually in the vessel,” said Dr. McCullough.

The findings may not have immediate practical implications. “I don’t think that in routine clinical practice it’s something that we would offer until we can decide how safe it is,” said Dr. McCullough. The question will be how to select the populations in whom the drug will have the most efficacy.

The study was funded by the National Natural Science Foundation of China, Army Medical University, and Lunan Pharmaceutical Group, the manufacturer of tirofiban. Dr. Nogueira reported holding stock in Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Viz-AI, and Ceretrieve. He has received research support from Corindus Vascular Robotics. Dr. Nogueira reported other financial relationships related to Stryker Neurovascular, Medtronic, Cerenovus, and Phenox. Dr. McCullough has disclosed no relevant financial relationships.

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

Adjunctive treatment with intravenous tirofiban does not improve clinical outcomes in patients with large-vessel occlusion stroke who undergo endovascular treatment within 24 hours of symptom onset, new data suggest.

In a randomized, phase 3 trial of more than 900 patients with acute ischemic stroke who underwent endovascular treatment, the median Modified Rankin Scale (mRS) score at 90 days was 3 both in patients who received tirofiban and those who received placebo.

“There was treatment-effect modification by stroke etiology, where patients with large-artery atherosclerosis [LAA] seemed to benefit from the treatment,” said investigator Raul Nogueira, MD, director of the University of Pittsburgh Medical Center Stroke Institute, during his presentation. “Tirofiban may improve endovascular treatment outcomes in LAA strokes. This obviously requires further investigation in future trials to confirm these findings.”

Results of the RESCUE BT trial were presented at the hybrid International Stroke Conference (ISC) 2022, which was held in New Orleans, Louisiana, and online.
 

Multicenter trial

Endovascular treatment greatly increases the rate of reperfusion and improves functional outcomes in patients with large-vessel occlusion stroke, the researchers note. But mechanical thrombectomy devices may injure the vessel wall, which can lead to clot formation and vessel reocclusion.

Platelet inhibition is a potential tactic for improving outcomes in this setting. Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is a reversible antiplatelet drug with a rapid onset of action and a short half-life. The drug’s safety and efficacy in acute coronary syndrome are well established. There has been little evidence to date, however, on whether tirofiban improves outcomes among patients with large-vessel occlusion stroke.

The investigators conducted the Endovascular Treatment With Versus Without Tirofiban for Stroke Patients With Large Vessel Occlusion (RESCUE BT) trial to evaluate the safety and efficacy of IV tirofiban therapy before endovascular treatment in patients with large-vessel occlusion stroke. They recruited consecutive patients at 55 thrombectomy-capable hospitals in China.

Eligible patients were aged 18 years or older and presented within 24 hours of the time they were last seen when well. Baseline National Institutes of Health Stroke Scale (NIHSS) score was required to be 30 or lower, and all patients were required to have plans to undergo endovascular treatment. Eligible patients also had a baseline Alberta Stroke Program Early CT Score of 6 or greater.

Patients were randomized in groups of equal size to placebo or tirofiban and stratified by NIHSS score and occlusion site. Tirofiban was administered in a 10-mcg/kg bolus followed by continuous infusion (0.15 mcg/kg per min) for 24 hours. All patients underwent rapid endovascular treatment.

At the 20th hour after treatment initiation, antiplatelets were administered orally. IV study drug was stopped at the 24th hour.

The study’s primary endpoint was disability level, as measured by overall distribution of the 90-day mRS score. The primary safety endpoints were symptomatic intracranial hemorrhage (ICH) at 48 hours and mortality at 90 days.
 

Increased ICH risk

The investigators screened 1,970 patients and enrolled 950 into their study. The population’s median age was 67 years, and 58.8% of participants were men. In all, 463 participants were randomly assigned to tirofiban, and 485 to placebo. Two patients withdrew consent, and none were lost to follow-up.

Baseline characteristics were well balanced in both groups. One difference, however, was that large-vessel occlusion was less prevalent in the tirofiban group (42.6%) than in the control group (49.1%).

The primary endpoint did not differ between treatment groups. The adjusted common odds ratio was 1.09 (P = .46). “There is perhaps a sign that there is maybe a favorable effect of tirofiban,” said Dr. Nogueira. “However, this did not reach statistical significance.”

The rates of symptomatic ICH and mortality at 90 days did not differ significantly between groups. There was a trend toward a higher rate of symptomatic ICH in the tirofiban group, however. Moreover, the rate of any ICH was 34.9% in the tirofiban group and 28.0% in the control group (P = .02).

In prespecified subgroup analysis, the researchers found that, among patients with large-vessel occlusion, the adjusted common odds ratio was 1.43 favoring tirofiban treatment. No other subgroups showed significant differences.

“In the intention-to-treat analysis, tirofiban did not improve clinical outcomes in the overall study population,” said Dr. Nogueira. “It did increase the rate of any ICH and potentially increased the rate of symptomatic ICH as well.”

The ongoing RESCUE BT2 trial is examining the safety and efficacy of tirofiban in patients with acute ischemic stroke with non–large-vessel occlusion. As of Jan. 20, 781 patients had been assigned randomly to treatment, said Dr. Nogueira.
 

Patient selection crucial

Louise McCullough, MD, PhD, professor and chair of neurology at the University of Texas Health Science Center at Houston, said that the study was well designed.

“The concern with any kind of platelet therapy or adjunctive therapy is hemorrhage,” said Dr. McCullough, who was not involved in the research. The results in the overall population support this concern.

The location of the trial sites may have influenced the results. “It was a multicenter trial, but it was predominantly done in Asia, and we know that there are higher levels of intracranial atherosclerosis in that population,” said Dr. McCullough.

The results indicate a potential benefit of tirofiban in patients with large-vessel occlusion, yet this finding raises practical questions. “It’s often difficult to know if these patients have atherosclerosis until you’re actually in the vessel,” said Dr. McCullough.

The findings may not have immediate practical implications. “I don’t think that in routine clinical practice it’s something that we would offer until we can decide how safe it is,” said Dr. McCullough. The question will be how to select the populations in whom the drug will have the most efficacy.

The study was funded by the National Natural Science Foundation of China, Army Medical University, and Lunan Pharmaceutical Group, the manufacturer of tirofiban. Dr. Nogueira reported holding stock in Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Viz-AI, and Ceretrieve. He has received research support from Corindus Vascular Robotics. Dr. Nogueira reported other financial relationships related to Stryker Neurovascular, Medtronic, Cerenovus, and Phenox. Dr. McCullough has disclosed no relevant financial relationships.

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

Adjunctive treatment with intravenous tirofiban does not improve clinical outcomes in patients with large-vessel occlusion stroke who undergo endovascular treatment within 24 hours of symptom onset, new data suggest.

In a randomized, phase 3 trial of more than 900 patients with acute ischemic stroke who underwent endovascular treatment, the median Modified Rankin Scale (mRS) score at 90 days was 3 both in patients who received tirofiban and those who received placebo.

“There was treatment-effect modification by stroke etiology, where patients with large-artery atherosclerosis [LAA] seemed to benefit from the treatment,” said investigator Raul Nogueira, MD, director of the University of Pittsburgh Medical Center Stroke Institute, during his presentation. “Tirofiban may improve endovascular treatment outcomes in LAA strokes. This obviously requires further investigation in future trials to confirm these findings.”

Results of the RESCUE BT trial were presented at the hybrid International Stroke Conference (ISC) 2022, which was held in New Orleans, Louisiana, and online.
 

Multicenter trial

Endovascular treatment greatly increases the rate of reperfusion and improves functional outcomes in patients with large-vessel occlusion stroke, the researchers note. But mechanical thrombectomy devices may injure the vessel wall, which can lead to clot formation and vessel reocclusion.

Platelet inhibition is a potential tactic for improving outcomes in this setting. Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is a reversible antiplatelet drug with a rapid onset of action and a short half-life. The drug’s safety and efficacy in acute coronary syndrome are well established. There has been little evidence to date, however, on whether tirofiban improves outcomes among patients with large-vessel occlusion stroke.

The investigators conducted the Endovascular Treatment With Versus Without Tirofiban for Stroke Patients With Large Vessel Occlusion (RESCUE BT) trial to evaluate the safety and efficacy of IV tirofiban therapy before endovascular treatment in patients with large-vessel occlusion stroke. They recruited consecutive patients at 55 thrombectomy-capable hospitals in China.

Eligible patients were aged 18 years or older and presented within 24 hours of the time they were last seen when well. Baseline National Institutes of Health Stroke Scale (NIHSS) score was required to be 30 or lower, and all patients were required to have plans to undergo endovascular treatment. Eligible patients also had a baseline Alberta Stroke Program Early CT Score of 6 or greater.

Patients were randomized in groups of equal size to placebo or tirofiban and stratified by NIHSS score and occlusion site. Tirofiban was administered in a 10-mcg/kg bolus followed by continuous infusion (0.15 mcg/kg per min) for 24 hours. All patients underwent rapid endovascular treatment.

At the 20th hour after treatment initiation, antiplatelets were administered orally. IV study drug was stopped at the 24th hour.

The study’s primary endpoint was disability level, as measured by overall distribution of the 90-day mRS score. The primary safety endpoints were symptomatic intracranial hemorrhage (ICH) at 48 hours and mortality at 90 days.
 

Increased ICH risk

The investigators screened 1,970 patients and enrolled 950 into their study. The population’s median age was 67 years, and 58.8% of participants were men. In all, 463 participants were randomly assigned to tirofiban, and 485 to placebo. Two patients withdrew consent, and none were lost to follow-up.

Baseline characteristics were well balanced in both groups. One difference, however, was that large-vessel occlusion was less prevalent in the tirofiban group (42.6%) than in the control group (49.1%).

The primary endpoint did not differ between treatment groups. The adjusted common odds ratio was 1.09 (P = .46). “There is perhaps a sign that there is maybe a favorable effect of tirofiban,” said Dr. Nogueira. “However, this did not reach statistical significance.”

The rates of symptomatic ICH and mortality at 90 days did not differ significantly between groups. There was a trend toward a higher rate of symptomatic ICH in the tirofiban group, however. Moreover, the rate of any ICH was 34.9% in the tirofiban group and 28.0% in the control group (P = .02).

In prespecified subgroup analysis, the researchers found that, among patients with large-vessel occlusion, the adjusted common odds ratio was 1.43 favoring tirofiban treatment. No other subgroups showed significant differences.

“In the intention-to-treat analysis, tirofiban did not improve clinical outcomes in the overall study population,” said Dr. Nogueira. “It did increase the rate of any ICH and potentially increased the rate of symptomatic ICH as well.”

The ongoing RESCUE BT2 trial is examining the safety and efficacy of tirofiban in patients with acute ischemic stroke with non–large-vessel occlusion. As of Jan. 20, 781 patients had been assigned randomly to treatment, said Dr. Nogueira.
 

Patient selection crucial

Louise McCullough, MD, PhD, professor and chair of neurology at the University of Texas Health Science Center at Houston, said that the study was well designed.

“The concern with any kind of platelet therapy or adjunctive therapy is hemorrhage,” said Dr. McCullough, who was not involved in the research. The results in the overall population support this concern.

The location of the trial sites may have influenced the results. “It was a multicenter trial, but it was predominantly done in Asia, and we know that there are higher levels of intracranial atherosclerosis in that population,” said Dr. McCullough.

The results indicate a potential benefit of tirofiban in patients with large-vessel occlusion, yet this finding raises practical questions. “It’s often difficult to know if these patients have atherosclerosis until you’re actually in the vessel,” said Dr. McCullough.

The findings may not have immediate practical implications. “I don’t think that in routine clinical practice it’s something that we would offer until we can decide how safe it is,” said Dr. McCullough. The question will be how to select the populations in whom the drug will have the most efficacy.

The study was funded by the National Natural Science Foundation of China, Army Medical University, and Lunan Pharmaceutical Group, the manufacturer of tirofiban. Dr. Nogueira reported holding stock in Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Viz-AI, and Ceretrieve. He has received research support from Corindus Vascular Robotics. Dr. Nogueira reported other financial relationships related to Stryker Neurovascular, Medtronic, Cerenovus, and Phenox. Dr. McCullough has disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved secnidazole for the treatment of bacterial vaginosis (BV) and trichomoniasis in patients aged 12 years and older.

The antimicrobial agent, marketed as Solosec, was first approved in 2017 as a treatment for BV in adult women. In 2021, it was approved for the treatment of trichomoniasis in adult men and women.

Lupin Pharmaceuticals, which manufactures the drug, announced the expanded approval for adolescents in a news release.

The medication is meant to be taken as a single dose. It comes in a packet that should be sprinkled onto applesauce, yogurt, or pudding and consumed without chewing or crunching.

The treatment option may help “address gaps in care related to adherence,” said Tom Merriam, an executive director with Lupin.

Bacterial vaginosis is a common vaginal infection. Trichomoniasis is the most common nonviral, curable STI in the United States. Sexual partners of patients with trichomoniasis can be treated at the same time.

Vulvovaginal candidiasis is one of the possible side effects of secnidazole treatment, the drug’s label notes.

The Food and Drug Administration has approved secnidazole for the treatment of bacterial vaginosis (BV) and trichomoniasis in patients aged 12 years and older.

The antimicrobial agent, marketed as Solosec, was first approved in 2017 as a treatment for BV in adult women. In 2021, it was approved for the treatment of trichomoniasis in adult men and women.

Lupin Pharmaceuticals, which manufactures the drug, announced the expanded approval for adolescents in a news release.

The medication is meant to be taken as a single dose. It comes in a packet that should be sprinkled onto applesauce, yogurt, or pudding and consumed without chewing or crunching.

The treatment option may help “address gaps in care related to adherence,” said Tom Merriam, an executive director with Lupin.

Bacterial vaginosis is a common vaginal infection. Trichomoniasis is the most common nonviral, curable STI in the United States. Sexual partners of patients with trichomoniasis can be treated at the same time.

Vulvovaginal candidiasis is one of the possible side effects of secnidazole treatment, the drug’s label notes.

The Food and Drug Administration has approved secnidazole for the treatment of bacterial vaginosis (BV) and trichomoniasis in patients aged 12 years and older.

The antimicrobial agent, marketed as Solosec, was first approved in 2017 as a treatment for BV in adult women. In 2021, it was approved for the treatment of trichomoniasis in adult men and women.

Lupin Pharmaceuticals, which manufactures the drug, announced the expanded approval for adolescents in a news release.

The medication is meant to be taken as a single dose. It comes in a packet that should be sprinkled onto applesauce, yogurt, or pudding and consumed without chewing or crunching.

The treatment option may help “address gaps in care related to adherence,” said Tom Merriam, an executive director with Lupin.

Bacterial vaginosis is a common vaginal infection. Trichomoniasis is the most common nonviral, curable STI in the United States. Sexual partners of patients with trichomoniasis can be treated at the same time.

Vulvovaginal candidiasis is one of the possible side effects of secnidazole treatment, the drug’s label notes.

The substantial antidepressant effects of psilocybin-assisted therapy may be durable up to at least 1 year in some patients with major depressive disorder (MDD), new research indicates.

Two doses of psilocybin provided in the context of supportive therapy produced “large and stable” antidepressant effects throughout a 12-month follow-up period, report researchers with the Center for Psychedelic and Consciousness Research at Johns Hopkins University School of Medicine, Baltimore.

“We have not yet collected formal data past 1 year in our sample, [but] some participants in our study have stayed in touch and report continued improvements in mood,” study investigator Natalie Gukasyan, MD, told this news organization.

Johns Hopkins University School of Medicine

Enduring benefit

Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with MDD, but the durability of the effects are unclear.

Investigators examined the efficacy and safety of psilocybin through 12 months in 24 adults who met criteria for a moderate to severe episode of MDD as defined by a score of 17 or greater on the GRID-Hamilton Depression Rating Scale (GRID-HAMD) assessed by blinded clinician raters.

Following 6-8 hours of preparatory meetings, participants received two doses of psilocybin at 20 mg/70 kg and 30 mg/70 kg spaced roughly 2 weeks apart. Psilocybin was administered in a comfortable room under supervision following established safety guidelines.

Depression, as measured by GRID-HAMD, decreased substantially after treatment and remained low through 12 months post-treatment, the investigators report.

For most participants, GRID-HAMD scores decreased from 22.8 at baseline to 8.7 at 1 week, 8.9 at 4 weeks, 9.3 at 3 months, 7 at 6 months, and 7.7 at 12 months after treatment.

“The effect size at 12 months was very large (Cohen d = 2.4). Likewise, high and stable rates of response and remission occurred throughout the follow-up period (75% response and 58% remission at 12 months),” the investigators note.

Two patient-rated measures of depression – the Quick Inventory of Depressive Symptoms (QIDS) and the Beck Depression Inventory II (BDI-II) – showed similar “large magnitude and stable” antidepressant effects on mean scores and on response and remission rates, they add.

Response and remission rates at 12 months on the QIDS were 79% and 67%, respectively, and 83% and 75%, respectively, on the BDI-II.

“Psilocybin not only produces significant and immediate effects, it also has a long duration, which suggests that it may be a uniquely useful new treatment for depression,” study investigator Roland Griffiths, PhD, founding director of the Center for Psychedelic and Consciousness Research, says in a statement.

“Compared to standard antidepressants, which must be taken for long stretches of time, psilocybin has the potential to enduringly relieve the symptoms of depression with one or two treatments,” Dr. Griffiths adds.
 

Better than ketamine?

There were no serious adverse events judged to be related to psilocybin during long-term follow-up. Depression symptoms were not significantly exacerbated in any participant, and there was no reported use of psilocybin or other psychedelic drug use during the follow-up period.

The finding that two doses of psilocybin provides antidepressant effects that last through at least 12 months is well beyond the duration of effects reported to date with ketamine, the investigators write.

“In general, treatment with ketamine requires a greater number of drug administrations, and it may be more challenging to get durable therapeutic efficacy without repeated dosing. The longer-term risks of repeated ketamine use are not well characterized,” Dr. Gukasyan told this news organization.

She noted that psilocybin and related compounds are still not available for clinical use under the controlled substances act.

“Some clinics are currently offering ketamine, or ketamine-assisted therapy in a manner that resembles the treatment approach used with psilocybin, but there is less high-quality research to support that practice,” she said.

The study was funded in part by a crowdsourced campaign organized by Tim Ferriss and by grants from the Riverstyx Foundation and Dave Morin. Other support was provided by a grant from the National Institutes of Health and the Center for Psychedelic and Consciousness Research. Dr. Gukasyan is an investigator for a multisite trial of psilocybin-assisted therapy for major depressive disorder sponsored by Usona Institute. A complete list of author disclosures is available with the original article.

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

The substantial antidepressant effects of psilocybin-assisted therapy may be durable up to at least 1 year in some patients with major depressive disorder (MDD), new research indicates.

Two doses of psilocybin provided in the context of supportive therapy produced “large and stable” antidepressant effects throughout a 12-month follow-up period, report researchers with the Center for Psychedelic and Consciousness Research at Johns Hopkins University School of Medicine, Baltimore.

“We have not yet collected formal data past 1 year in our sample, [but] some participants in our study have stayed in touch and report continued improvements in mood,” study investigator Natalie Gukasyan, MD, told this news organization.

Johns Hopkins University School of Medicine

Enduring benefit

Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with MDD, but the durability of the effects are unclear.

Investigators examined the efficacy and safety of psilocybin through 12 months in 24 adults who met criteria for a moderate to severe episode of MDD as defined by a score of 17 or greater on the GRID-Hamilton Depression Rating Scale (GRID-HAMD) assessed by blinded clinician raters.

Following 6-8 hours of preparatory meetings, participants received two doses of psilocybin at 20 mg/70 kg and 30 mg/70 kg spaced roughly 2 weeks apart. Psilocybin was administered in a comfortable room under supervision following established safety guidelines.

Depression, as measured by GRID-HAMD, decreased substantially after treatment and remained low through 12 months post-treatment, the investigators report.

For most participants, GRID-HAMD scores decreased from 22.8 at baseline to 8.7 at 1 week, 8.9 at 4 weeks, 9.3 at 3 months, 7 at 6 months, and 7.7 at 12 months after treatment.

“The effect size at 12 months was very large (Cohen d = 2.4). Likewise, high and stable rates of response and remission occurred throughout the follow-up period (75% response and 58% remission at 12 months),” the investigators note.

Two patient-rated measures of depression – the Quick Inventory of Depressive Symptoms (QIDS) and the Beck Depression Inventory II (BDI-II) – showed similar “large magnitude and stable” antidepressant effects on mean scores and on response and remission rates, they add.

Response and remission rates at 12 months on the QIDS were 79% and 67%, respectively, and 83% and 75%, respectively, on the BDI-II.

“Psilocybin not only produces significant and immediate effects, it also has a long duration, which suggests that it may be a uniquely useful new treatment for depression,” study investigator Roland Griffiths, PhD, founding director of the Center for Psychedelic and Consciousness Research, says in a statement.

“Compared to standard antidepressants, which must be taken for long stretches of time, psilocybin has the potential to enduringly relieve the symptoms of depression with one or two treatments,” Dr. Griffiths adds.
 

Better than ketamine?

There were no serious adverse events judged to be related to psilocybin during long-term follow-up. Depression symptoms were not significantly exacerbated in any participant, and there was no reported use of psilocybin or other psychedelic drug use during the follow-up period.

The finding that two doses of psilocybin provides antidepressant effects that last through at least 12 months is well beyond the duration of effects reported to date with ketamine, the investigators write.

“In general, treatment with ketamine requires a greater number of drug administrations, and it may be more challenging to get durable therapeutic efficacy without repeated dosing. The longer-term risks of repeated ketamine use are not well characterized,” Dr. Gukasyan told this news organization.

She noted that psilocybin and related compounds are still not available for clinical use under the controlled substances act.

“Some clinics are currently offering ketamine, or ketamine-assisted therapy in a manner that resembles the treatment approach used with psilocybin, but there is less high-quality research to support that practice,” she said.

The study was funded in part by a crowdsourced campaign organized by Tim Ferriss and by grants from the Riverstyx Foundation and Dave Morin. Other support was provided by a grant from the National Institutes of Health and the Center for Psychedelic and Consciousness Research. Dr. Gukasyan is an investigator for a multisite trial of psilocybin-assisted therapy for major depressive disorder sponsored by Usona Institute. A complete list of author disclosures is available with the original article.

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

The substantial antidepressant effects of psilocybin-assisted therapy may be durable up to at least 1 year in some patients with major depressive disorder (MDD), new research indicates.

Two doses of psilocybin provided in the context of supportive therapy produced “large and stable” antidepressant effects throughout a 12-month follow-up period, report researchers with the Center for Psychedelic and Consciousness Research at Johns Hopkins University School of Medicine, Baltimore.

“We have not yet collected formal data past 1 year in our sample, [but] some participants in our study have stayed in touch and report continued improvements in mood,” study investigator Natalie Gukasyan, MD, told this news organization.

Johns Hopkins University School of Medicine

Enduring benefit

Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with MDD, but the durability of the effects are unclear.

Investigators examined the efficacy and safety of psilocybin through 12 months in 24 adults who met criteria for a moderate to severe episode of MDD as defined by a score of 17 or greater on the GRID-Hamilton Depression Rating Scale (GRID-HAMD) assessed by blinded clinician raters.

Following 6-8 hours of preparatory meetings, participants received two doses of psilocybin at 20 mg/70 kg and 30 mg/70 kg spaced roughly 2 weeks apart. Psilocybin was administered in a comfortable room under supervision following established safety guidelines.

Depression, as measured by GRID-HAMD, decreased substantially after treatment and remained low through 12 months post-treatment, the investigators report.

For most participants, GRID-HAMD scores decreased from 22.8 at baseline to 8.7 at 1 week, 8.9 at 4 weeks, 9.3 at 3 months, 7 at 6 months, and 7.7 at 12 months after treatment.

“The effect size at 12 months was very large (Cohen d = 2.4). Likewise, high and stable rates of response and remission occurred throughout the follow-up period (75% response and 58% remission at 12 months),” the investigators note.

Two patient-rated measures of depression – the Quick Inventory of Depressive Symptoms (QIDS) and the Beck Depression Inventory II (BDI-II) – showed similar “large magnitude and stable” antidepressant effects on mean scores and on response and remission rates, they add.

Response and remission rates at 12 months on the QIDS were 79% and 67%, respectively, and 83% and 75%, respectively, on the BDI-II.

“Psilocybin not only produces significant and immediate effects, it also has a long duration, which suggests that it may be a uniquely useful new treatment for depression,” study investigator Roland Griffiths, PhD, founding director of the Center for Psychedelic and Consciousness Research, says in a statement.

“Compared to standard antidepressants, which must be taken for long stretches of time, psilocybin has the potential to enduringly relieve the symptoms of depression with one or two treatments,” Dr. Griffiths adds.
 

Better than ketamine?

There were no serious adverse events judged to be related to psilocybin during long-term follow-up. Depression symptoms were not significantly exacerbated in any participant, and there was no reported use of psilocybin or other psychedelic drug use during the follow-up period.

The finding that two doses of psilocybin provides antidepressant effects that last through at least 12 months is well beyond the duration of effects reported to date with ketamine, the investigators write.

“In general, treatment with ketamine requires a greater number of drug administrations, and it may be more challenging to get durable therapeutic efficacy without repeated dosing. The longer-term risks of repeated ketamine use are not well characterized,” Dr. Gukasyan told this news organization.

She noted that psilocybin and related compounds are still not available for clinical use under the controlled substances act.

“Some clinics are currently offering ketamine, or ketamine-assisted therapy in a manner that resembles the treatment approach used with psilocybin, but there is less high-quality research to support that practice,” she said.

The study was funded in part by a crowdsourced campaign organized by Tim Ferriss and by grants from the Riverstyx Foundation and Dave Morin. Other support was provided by a grant from the National Institutes of Health and the Center for Psychedelic and Consciousness Research. Dr. Gukasyan is an investigator for a multisite trial of psilocybin-assisted therapy for major depressive disorder sponsored by Usona Institute. A complete list of author disclosures is available with the original article.

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

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

Childhood-onset insomnia is a chronic problem in 43% of children, based on 15-year follow-up data from approximately 500 individuals.

Difficulty initiating or maintaining sleep (DIMS) is the most frequently reported insomnia symptom in children and teens, but longitudinal data on the trajectory of insomnia symptoms from childhood into adulthood are limited, Julio Fernandez-Mendoza, PhD, of Penn State University, Hershey, and colleagues wrote.

Previous studies have shown varying results, notably on the effect of objective short sleep duration (OSSD), they said. The extent to which the effect of OSSD on insomnia trajectories, and whether OSSD affects the development of insomnia in the transition to adulthood remains uncertain.

In a study published in Pediatrics, the researchers reviewed data from 502 children who enrolled at age 5-12 years between 2000 and 2005. The participants underwent laboratory polysomnography visits at baseline; 421 had a second laboratory visit between 2010 and 2013 (median age, 16 years), and 502 completed a structured self-reported survey between 2018 and 2021 at a median age of 24 years. At the first visit, 118 children met criteria for insomnia, defined as parent reports of often/moderate or very often/severe DIMS and/or use of over-the-counter or prescription sleep medications for DIMS. At the second visit, 120 children met the definition for insomnia.

Among children with insomnia symptoms at baseline, 53.7% had persistence of insomnia symptoms in adolescence and 61.9% had symptoms in young adulthood; 46.3% and 38.1% remitted at these times.

Among children with insomnia symptoms at adolescence, 57.5% and 42.5% had persistence and remittance, respectively, in young adulthood.

In children with insomnia at baseline, therefore, the most frequent developmental trajectory was persistence (43.3%) followed by remission (26.9% since childhood and 11.2% since adolescence) and a waxing and waning pattern (18.6%), the researchers said.

Among children with normal sleep at baseline, 69.7% retained normal sleep patterns in adolescence and 63.3% retained normal sleep in young adulthood; 30.3% and 36.7% developed insomnia in adolescence and young adulthood, respectively.

Overall, adult insomnia was reported by 22.0% and 20.8% of individuals with childhood and adolescent insomnia, respectively. In a multivariate analysis, the odds of adult insomnia were 2.6 times and 5.5 times higher among those with histories of short-sleeping in childhood and adolescence, respectively.

“The most common developmental trajectory for insomnia symptoms was that of persistence from childhood through young adulthood,” the researchers wrote in their discussion of the study.

“These 15-year longitudinal findings across three developmental stages indicate that insomnia symptoms should not be expected to developmentally remit in at least 40% of children and that adolescence is a critical developmental period for the adverse prognosis of the insomnia with short sleep duration phenotype,” they emphasized.

The study findings were limited by several factors including the collection of OSSD and other sleep data via a 1-night, 9-hour polysomnography, which might not be representative of habitual sleep at home, the researchers noted. Other limitations include the lack of polysomnography data to accompany the young adult survey and the inability to validate insomnia in young adults via strict diagnostic criteria.

However, the results reveal that the persistence of childhood insomnia is higher than suggested in previous studies, and that these children and adolescents, especially short sleepers, are at significantly increased risk of adult insomnia, the researchers concluded.

“Early sleep interventions are a priority, as clinicians should not expect insomnia symptoms to developmentally remit in a high proportion of children, although objective sleep measures may be indicated in adolescence to identify those with poorer long-term prognosis,” they said.

Pandemic prompts interest in sleep issues

The current study is important at this time because sleep disruptions in children and adolescents have increased over the course of the COVID-19 pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was especially surprised to see that adolescent insomnia will most likely not remit in young adulthood, as she had considered it a disorder of adolescence.

The study highlights the need for early intervention to manage insomnia in children. However, there are several barriers to such intervention. “Parents [of young children] are overwhelmed and just need sleep themselves, so they don’t always have the energy to work on good sleep habits in their children,” she said. Improving sleep habits in adolescents requires overcoming the barrier of the young patients’ attitudes. “For adolescents, they need to buy into the change.”

However, the take-home message for clinicians is that it is important to work to overcome these barriers and improve sleep in children and teens, because the longitudinal data suggest that the problem is “likely to persist and unlikely to remit,” for many, she said.

As for additional studies, “I would like to see more research done on neurologic and psychological causes of insomnia,” Dr. Kinsella said.

The study was supported in part by grants from the National Heart, Lung, and Blood Institute; National Institute of Mental Health; and the National Center for Advancing Translational Sciences of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Childhood-onset insomnia is a chronic problem in 43% of children, based on 15-year follow-up data from approximately 500 individuals.

Difficulty initiating or maintaining sleep (DIMS) is the most frequently reported insomnia symptom in children and teens, but longitudinal data on the trajectory of insomnia symptoms from childhood into adulthood are limited, Julio Fernandez-Mendoza, PhD, of Penn State University, Hershey, and colleagues wrote.

Previous studies have shown varying results, notably on the effect of objective short sleep duration (OSSD), they said. The extent to which the effect of OSSD on insomnia trajectories, and whether OSSD affects the development of insomnia in the transition to adulthood remains uncertain.

In a study published in Pediatrics, the researchers reviewed data from 502 children who enrolled at age 5-12 years between 2000 and 2005. The participants underwent laboratory polysomnography visits at baseline; 421 had a second laboratory visit between 2010 and 2013 (median age, 16 years), and 502 completed a structured self-reported survey between 2018 and 2021 at a median age of 24 years. At the first visit, 118 children met criteria for insomnia, defined as parent reports of often/moderate or very often/severe DIMS and/or use of over-the-counter or prescription sleep medications for DIMS. At the second visit, 120 children met the definition for insomnia.

Among children with insomnia symptoms at baseline, 53.7% had persistence of insomnia symptoms in adolescence and 61.9% had symptoms in young adulthood; 46.3% and 38.1% remitted at these times.

Among children with insomnia symptoms at adolescence, 57.5% and 42.5% had persistence and remittance, respectively, in young adulthood.

In children with insomnia at baseline, therefore, the most frequent developmental trajectory was persistence (43.3%) followed by remission (26.9% since childhood and 11.2% since adolescence) and a waxing and waning pattern (18.6%), the researchers said.

Among children with normal sleep at baseline, 69.7% retained normal sleep patterns in adolescence and 63.3% retained normal sleep in young adulthood; 30.3% and 36.7% developed insomnia in adolescence and young adulthood, respectively.

Overall, adult insomnia was reported by 22.0% and 20.8% of individuals with childhood and adolescent insomnia, respectively. In a multivariate analysis, the odds of adult insomnia were 2.6 times and 5.5 times higher among those with histories of short-sleeping in childhood and adolescence, respectively.

“The most common developmental trajectory for insomnia symptoms was that of persistence from childhood through young adulthood,” the researchers wrote in their discussion of the study.

“These 15-year longitudinal findings across three developmental stages indicate that insomnia symptoms should not be expected to developmentally remit in at least 40% of children and that adolescence is a critical developmental period for the adverse prognosis of the insomnia with short sleep duration phenotype,” they emphasized.

The study findings were limited by several factors including the collection of OSSD and other sleep data via a 1-night, 9-hour polysomnography, which might not be representative of habitual sleep at home, the researchers noted. Other limitations include the lack of polysomnography data to accompany the young adult survey and the inability to validate insomnia in young adults via strict diagnostic criteria.

However, the results reveal that the persistence of childhood insomnia is higher than suggested in previous studies, and that these children and adolescents, especially short sleepers, are at significantly increased risk of adult insomnia, the researchers concluded.

“Early sleep interventions are a priority, as clinicians should not expect insomnia symptoms to developmentally remit in a high proportion of children, although objective sleep measures may be indicated in adolescence to identify those with poorer long-term prognosis,” they said.

Pandemic prompts interest in sleep issues

The current study is important at this time because sleep disruptions in children and adolescents have increased over the course of the COVID-19 pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was especially surprised to see that adolescent insomnia will most likely not remit in young adulthood, as she had considered it a disorder of adolescence.

The study highlights the need for early intervention to manage insomnia in children. However, there are several barriers to such intervention. “Parents [of young children] are overwhelmed and just need sleep themselves, so they don’t always have the energy to work on good sleep habits in their children,” she said. Improving sleep habits in adolescents requires overcoming the barrier of the young patients’ attitudes. “For adolescents, they need to buy into the change.”

However, the take-home message for clinicians is that it is important to work to overcome these barriers and improve sleep in children and teens, because the longitudinal data suggest that the problem is “likely to persist and unlikely to remit,” for many, she said.

As for additional studies, “I would like to see more research done on neurologic and psychological causes of insomnia,” Dr. Kinsella said.

The study was supported in part by grants from the National Heart, Lung, and Blood Institute; National Institute of Mental Health; and the National Center for Advancing Translational Sciences of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Childhood-onset insomnia is a chronic problem in 43% of children, based on 15-year follow-up data from approximately 500 individuals.

Difficulty initiating or maintaining sleep (DIMS) is the most frequently reported insomnia symptom in children and teens, but longitudinal data on the trajectory of insomnia symptoms from childhood into adulthood are limited, Julio Fernandez-Mendoza, PhD, of Penn State University, Hershey, and colleagues wrote.

Previous studies have shown varying results, notably on the effect of objective short sleep duration (OSSD), they said. The extent to which the effect of OSSD on insomnia trajectories, and whether OSSD affects the development of insomnia in the transition to adulthood remains uncertain.

In a study published in Pediatrics, the researchers reviewed data from 502 children who enrolled at age 5-12 years between 2000 and 2005. The participants underwent laboratory polysomnography visits at baseline; 421 had a second laboratory visit between 2010 and 2013 (median age, 16 years), and 502 completed a structured self-reported survey between 2018 and 2021 at a median age of 24 years. At the first visit, 118 children met criteria for insomnia, defined as parent reports of often/moderate or very often/severe DIMS and/or use of over-the-counter or prescription sleep medications for DIMS. At the second visit, 120 children met the definition for insomnia.

Among children with insomnia symptoms at baseline, 53.7% had persistence of insomnia symptoms in adolescence and 61.9% had symptoms in young adulthood; 46.3% and 38.1% remitted at these times.

Among children with insomnia symptoms at adolescence, 57.5% and 42.5% had persistence and remittance, respectively, in young adulthood.

In children with insomnia at baseline, therefore, the most frequent developmental trajectory was persistence (43.3%) followed by remission (26.9% since childhood and 11.2% since adolescence) and a waxing and waning pattern (18.6%), the researchers said.

Among children with normal sleep at baseline, 69.7% retained normal sleep patterns in adolescence and 63.3% retained normal sleep in young adulthood; 30.3% and 36.7% developed insomnia in adolescence and young adulthood, respectively.

Overall, adult insomnia was reported by 22.0% and 20.8% of individuals with childhood and adolescent insomnia, respectively. In a multivariate analysis, the odds of adult insomnia were 2.6 times and 5.5 times higher among those with histories of short-sleeping in childhood and adolescence, respectively.

“The most common developmental trajectory for insomnia symptoms was that of persistence from childhood through young adulthood,” the researchers wrote in their discussion of the study.

“These 15-year longitudinal findings across three developmental stages indicate that insomnia symptoms should not be expected to developmentally remit in at least 40% of children and that adolescence is a critical developmental period for the adverse prognosis of the insomnia with short sleep duration phenotype,” they emphasized.

The study findings were limited by several factors including the collection of OSSD and other sleep data via a 1-night, 9-hour polysomnography, which might not be representative of habitual sleep at home, the researchers noted. Other limitations include the lack of polysomnography data to accompany the young adult survey and the inability to validate insomnia in young adults via strict diagnostic criteria.

However, the results reveal that the persistence of childhood insomnia is higher than suggested in previous studies, and that these children and adolescents, especially short sleepers, are at significantly increased risk of adult insomnia, the researchers concluded.

“Early sleep interventions are a priority, as clinicians should not expect insomnia symptoms to developmentally remit in a high proportion of children, although objective sleep measures may be indicated in adolescence to identify those with poorer long-term prognosis,” they said.

Pandemic prompts interest in sleep issues

The current study is important at this time because sleep disruptions in children and adolescents have increased over the course of the COVID-19 pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was especially surprised to see that adolescent insomnia will most likely not remit in young adulthood, as she had considered it a disorder of adolescence.

The study highlights the need for early intervention to manage insomnia in children. However, there are several barriers to such intervention. “Parents [of young children] are overwhelmed and just need sleep themselves, so they don’t always have the energy to work on good sleep habits in their children,” she said. Improving sleep habits in adolescents requires overcoming the barrier of the young patients’ attitudes. “For adolescents, they need to buy into the change.”

However, the take-home message for clinicians is that it is important to work to overcome these barriers and improve sleep in children and teens, because the longitudinal data suggest that the problem is “likely to persist and unlikely to remit,” for many, she said.

As for additional studies, “I would like to see more research done on neurologic and psychological causes of insomnia,” Dr. Kinsella said.

The study was supported in part by grants from the National Heart, Lung, and Blood Institute; National Institute of Mental Health; and the National Center for Advancing Translational Sciences of the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.