Internal Medicine News

HUNTINGTON BEACH, CALIF. — The Food and Drug Administration (FDA) approvals of tapinarof 1% cream and roflumilast 0.3% cream as treatment options for patients with plaque psoriasis came more than 1 year after the American Academy of Dermatology/National Psoriasis Foundation Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures were published in 2021, leaving some clinicians to wonder how these two newcomer drugs fit into their clinical practice.

At the annual meeting of the Pacific Dermatologic Association, Jashin J. Wu, MD, one of the authors of the guidelines and a voluntary associate professor of dermatology at the University of Miami, Coral Gables, Florida, proposed that tapinarof 1% cream and roflumilast 0.3% cream be considered first-line treatments for mild psoriasis. “The reason is because they’re very fast-acting, effective,” and result in a large improvement over steroids, Dr. Wu said. “You don’t have to worry about steroid atrophy, and it eliminates the need to use many different agents for different parts of the body necessarily, such as a weaker steroid for the face and sensitive areas. It also eliminates the need for patients to switch out steroids, such as 2 weeks on and 2 weeks off.”

courtesy Doug Brunk

Tapinarof 1% cream (Vtama) was approved in May 2022, for the topical treatment of plaque psoriasis in adults, and is under FDA review for treating atopic dermatitis (AD). “It’s once a day application, which is nice,” Dr. Wu said. “It is a first-in-class topical aryl hydrocarbon receptor agonist that can be used for the intertriginous areas. That’s where I find it helpful.”

Roflumilast 0.3% cream (Zoryve), a phosphodiesterase-4 inhibitor, was approved in July 2022 for the treatment of plaque psoriasis, including intertriginous areas, in patients aged 12 years and older. It was subsequently approved for treating plaque psoriasis in patients 6 years and older. (Roflumilast 0.15% cream is approved for mild to moderate AD in people aged 6 years or older, and roflumilast 0.3% topical foam is approved for seborrheic dermatitis in adults and children 9 years of age and older.)

The drug is contraindicated for use in patients with certain liver problems. “Patients are not going to be eating tubes of this drug, so I wouldn’t worry about that too much, but be aware if the pharmacist raises a concern about this,” Dr. Wu said.

Dr. Wu disclosed that he is or has been a consultant, investigator, or speaker for AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Codex Labs, Dermavant, DermTech, Dr. Reddy’s Laboratories, Eli Lilly, EPI Health, Galderma, Incyte, Janssen, LEO Pharma, Mindera, Novartis, Pfizer, Regeneron, Samsung Bioepis, Sanofi Genzyme, Solius, Sun Pharmaceuticals, UCB, and Zerigo Health.

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

HUNTINGTON BEACH, CALIF. — The Food and Drug Administration (FDA) approvals of tapinarof 1% cream and roflumilast 0.3% cream as treatment options for patients with plaque psoriasis came more than 1 year after the American Academy of Dermatology/National Psoriasis Foundation Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures were published in 2021, leaving some clinicians to wonder how these two newcomer drugs fit into their clinical practice.

At the annual meeting of the Pacific Dermatologic Association, Jashin J. Wu, MD, one of the authors of the guidelines and a voluntary associate professor of dermatology at the University of Miami, Coral Gables, Florida, proposed that tapinarof 1% cream and roflumilast 0.3% cream be considered first-line treatments for mild psoriasis. “The reason is because they’re very fast-acting, effective,” and result in a large improvement over steroids, Dr. Wu said. “You don’t have to worry about steroid atrophy, and it eliminates the need to use many different agents for different parts of the body necessarily, such as a weaker steroid for the face and sensitive areas. It also eliminates the need for patients to switch out steroids, such as 2 weeks on and 2 weeks off.”

courtesy Doug Brunk

Tapinarof 1% cream (Vtama) was approved in May 2022, for the topical treatment of plaque psoriasis in adults, and is under FDA review for treating atopic dermatitis (AD). “It’s once a day application, which is nice,” Dr. Wu said. “It is a first-in-class topical aryl hydrocarbon receptor agonist that can be used for the intertriginous areas. That’s where I find it helpful.”

Roflumilast 0.3% cream (Zoryve), a phosphodiesterase-4 inhibitor, was approved in July 2022 for the treatment of plaque psoriasis, including intertriginous areas, in patients aged 12 years and older. It was subsequently approved for treating plaque psoriasis in patients 6 years and older. (Roflumilast 0.15% cream is approved for mild to moderate AD in people aged 6 years or older, and roflumilast 0.3% topical foam is approved for seborrheic dermatitis in adults and children 9 years of age and older.)

The drug is contraindicated for use in patients with certain liver problems. “Patients are not going to be eating tubes of this drug, so I wouldn’t worry about that too much, but be aware if the pharmacist raises a concern about this,” Dr. Wu said.

Dr. Wu disclosed that he is or has been a consultant, investigator, or speaker for AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Codex Labs, Dermavant, DermTech, Dr. Reddy’s Laboratories, Eli Lilly, EPI Health, Galderma, Incyte, Janssen, LEO Pharma, Mindera, Novartis, Pfizer, Regeneron, Samsung Bioepis, Sanofi Genzyme, Solius, Sun Pharmaceuticals, UCB, and Zerigo Health.

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

HUNTINGTON BEACH, CALIF. — The Food and Drug Administration (FDA) approvals of tapinarof 1% cream and roflumilast 0.3% cream as treatment options for patients with plaque psoriasis came more than 1 year after the American Academy of Dermatology/National Psoriasis Foundation Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures were published in 2021, leaving some clinicians to wonder how these two newcomer drugs fit into their clinical practice.

At the annual meeting of the Pacific Dermatologic Association, Jashin J. Wu, MD, one of the authors of the guidelines and a voluntary associate professor of dermatology at the University of Miami, Coral Gables, Florida, proposed that tapinarof 1% cream and roflumilast 0.3% cream be considered first-line treatments for mild psoriasis. “The reason is because they’re very fast-acting, effective,” and result in a large improvement over steroids, Dr. Wu said. “You don’t have to worry about steroid atrophy, and it eliminates the need to use many different agents for different parts of the body necessarily, such as a weaker steroid for the face and sensitive areas. It also eliminates the need for patients to switch out steroids, such as 2 weeks on and 2 weeks off.”

courtesy Doug Brunk

Tapinarof 1% cream (Vtama) was approved in May 2022, for the topical treatment of plaque psoriasis in adults, and is under FDA review for treating atopic dermatitis (AD). “It’s once a day application, which is nice,” Dr. Wu said. “It is a first-in-class topical aryl hydrocarbon receptor agonist that can be used for the intertriginous areas. That’s where I find it helpful.”

Roflumilast 0.3% cream (Zoryve), a phosphodiesterase-4 inhibitor, was approved in July 2022 for the treatment of plaque psoriasis, including intertriginous areas, in patients aged 12 years and older. It was subsequently approved for treating plaque psoriasis in patients 6 years and older. (Roflumilast 0.15% cream is approved for mild to moderate AD in people aged 6 years or older, and roflumilast 0.3% topical foam is approved for seborrheic dermatitis in adults and children 9 years of age and older.)

The drug is contraindicated for use in patients with certain liver problems. “Patients are not going to be eating tubes of this drug, so I wouldn’t worry about that too much, but be aware if the pharmacist raises a concern about this,” Dr. Wu said.

Dr. Wu disclosed that he is or has been a consultant, investigator, or speaker for AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Codex Labs, Dermavant, DermTech, Dr. Reddy’s Laboratories, Eli Lilly, EPI Health, Galderma, Incyte, Janssen, LEO Pharma, Mindera, Novartis, Pfizer, Regeneron, Samsung Bioepis, Sanofi Genzyme, Solius, Sun Pharmaceuticals, UCB, and Zerigo Health.

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

Tirzepatide (Zepbound) is not in shortage for now, but the weight loss drug has remained inaccessible to people without insurance coverage who can’t afford to pay out of pocket. Now, its manufacturer, Eli Lilly, has introduced a new formulation it says will “significantly expand” the supply. But not all endocrinologists are enthusiastic.

As of August 27, LillyDirect made 2.5-mg and 5-mg single-dose vials of tirzepatide available to self-pay patients with an on-label electronic prescription. Lilly’s announcement said the single-dose vials “are priced at a 50% or greater discount compared to the list price of all other incretin (glucagon-like peptide 1 receptor agonists or GLP-1) medicines for obesity.”

For a 4-week supply of the weekly injections, the discount at LillyDirect translates to $399 for a 2.5-mg single-dose vial ($99.75 per vial) and $549 for the 5-mg dose ($137.25 per vial), which the company noted was “in line with the Zepbound savings program for noncovered individuals.” (The new direct single-dose prescriptions cannot be filled at community or retail pharmacies.)

“In a clinical study, the 5-mg maintenance dose helped patients achieve an average of 15% weight loss after 72 weeks of treatment and has been a powerful tool for millions of people with obesity looking to lose weight and keep it off,” according to the announcement.

The clinical study, which is not named or referenced in the announcement, is SURMOUNT-1, a Lilly spokesperson said in an interview. Yet, that study also found that patients achieved an average weight loss of 19.5% with 10-mg doses and 20.9% with 15-mg doses of tirzepatide. Furthermore, the percentage of participants achieving body weight reductions of ≥ 5% was 85% (5 mg), 89% (10 mg), and 91% (15 mg), showing the benefits of higher doses.

And there’s the rub.
 

‘Only Two Different Doses’

Anne Peters, MD, a professor of clinical medicine and a clinical scholar at the University of Southern California, Los Angeles, said in an interview: “My concern is, they’re only providing two different doses, 2.5 mg and 5 mg. You get somebody on it, and then they still have to go back to the traditional pens. I’m very opposed to getting patients connected to a medication they can’t then continue to take.

“Now we have starter doses that are easy to come by,” she said. “But the problem isn’t starting. The problem for all of these patients is chronic continuation of the right dose of the drug, and out-of-pocket costs become exorbitantly higher when they have to self-purchase the pens for the higher doses.

“Yes, the 5-mg dose has benefits, but not the same as higher doses,” she continued. “I have nobody for whom 5 mg is the right dose. They have to take more, sometimes within a month or 2 of starting, in order to achieve the kind of weight loss they need.”

If their insurance doesn’t cover the drug, “what are they going to do to stay on 5 mg? Or pay a crapload of money to buy three of the 5-mg doses to reach a higher dose?”

Michael Weintraub, MD, clinical assistant professor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism at New York University Grossman School of Medicine in New York City, said that, “for many, this lower monthly cost is attainable and is a significant advancement in increasing access. For others, however, an out-of-pocket monthly cost of $349-549 for a chronic medication is still unaffordable.”

And like Dr. Peters, he said, “some patients do not lose a clinically significant amount of weight with 2.5 mg or 5 mg and require higher doses. There is no way of prescribing a higher dose of Zepbound vials, so patients would have to resort to the higher-dose auto-injector pens that are still double the price.”

A Lilly spokesperson countered in a comment: “Offering Zepbound single-dose vials in higher dosage strengths could increase the potential for dose splitting, which is not contemplated by the FDA [Food and Drug Adminstration]–approved label and may pose patient safety risks.”

But Dr. Peters wondered: “Wouldn’t dose splitting of a known-to-be-pure compound be better than getting it at a compounding pharmacy that lacks purity/safety? The one message from all of this is that patients need to know what they’re getting into. They’re starting a drug that can help with weight loss, but they’re going to be on a sub-max dose. And a higher dose is going to be double the price.”

In addition, said Robert F. Kushner, MD, a professor at Northwestern University Feinberg School of Medicine in Chicago, Illinois, “for the lower-dose vials, instead of administering the drug with a self-auto-injection pen, patients will need to use a needle and syringe and draw up the dose from a vial. This will take a higher skill level and health literacy that may be challenging for some patients. Patients may need additional training on how to use this new formulation. That will take additional time and resources, such as a demonstration in the office or referral to video.”

The Lilly news release noted that “patients can also purchase ancillary supplies, like syringes and needles, and will have access to important patient-friendly instructional materials on correctly administering the medicine via needle and syringe.”
 

Protection From Compounders?

According to the Lilly spokesperson, the launch of Zepbound vials “furthers our commitment to helping patients avoid the risks associated with compounded products by providing patients another option for access to genuine Lilly medicine.”

Indeed, said Jaime Almandoz, MD, medical director of the Weight Wellness Program and associate professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, “The introduction of Zepbound/tirzepatide in single-dose vials should improve access to evidence-based obesity treatments, reducing potential risks associated with compounded additives and eliminating the need for patients to calculate correct medication doses,” which have led to accidental overdoses of compounded semaglutide.

Lilly’s spokesperson added: “We have taken multiple steps — including publishing an open letter and launching lilly.com/real-medicine — to warn the public about the risks posed by the proliferation of counterfeit, fake, unsafe, or untested knockoffs of Lilly’s genuine medicines.”

But whether these steps are strong enough to overcome the realities of cost and the need for affordable higher doses remains to be seen.

Scott Brunner, CEO of the Alliance for Pharmacy Compounding, said in a statement that the new version of Zepbound “is great news for patients. It’s a much more rational and care-focused response to the remarkable demand for their drug than the lawsuits and cease-and-desist letters Lilly has been raining down on compounding pharmacies.”

“For 20 months now,” he continued, “compounders have been a lifeline for many patients, filling prescriptions for compounded tirzepatide injection at a time when the FDA-approved drug has been in shortage. We’ll be eager to see whether Lilly’s direct-to-patient approach actually works.”

Dr. Almandoz affirmed: “Everyone wants to see improved access to evidence-based obesity care. It’s crucial to ensure patients receive the most appropriate interventions, whether it is lifestyle changes, medications, or bariatric surgery,” he said. “There are resources available, [including his recent paper], for nutrition and lifestyle modifications specifically for patients taking obesity medications, which can help clinicians guide their patients toward better health.”

Dr. Almandoz is a member of advisory boards and consults for: Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr. Kushner is an adviser to Eli Lilly and Novo Nordisk. Dr. Peters and Dr. Weintraub declared no competing interests.

A version of this article appeared on Medscape.com.

Tirzepatide (Zepbound) is not in shortage for now, but the weight loss drug has remained inaccessible to people without insurance coverage who can’t afford to pay out of pocket. Now, its manufacturer, Eli Lilly, has introduced a new formulation it says will “significantly expand” the supply. But not all endocrinologists are enthusiastic.

As of August 27, LillyDirect made 2.5-mg and 5-mg single-dose vials of tirzepatide available to self-pay patients with an on-label electronic prescription. Lilly’s announcement said the single-dose vials “are priced at a 50% or greater discount compared to the list price of all other incretin (glucagon-like peptide 1 receptor agonists or GLP-1) medicines for obesity.”

For a 4-week supply of the weekly injections, the discount at LillyDirect translates to $399 for a 2.5-mg single-dose vial ($99.75 per vial) and $549 for the 5-mg dose ($137.25 per vial), which the company noted was “in line with the Zepbound savings program for noncovered individuals.” (The new direct single-dose prescriptions cannot be filled at community or retail pharmacies.)

“In a clinical study, the 5-mg maintenance dose helped patients achieve an average of 15% weight loss after 72 weeks of treatment and has been a powerful tool for millions of people with obesity looking to lose weight and keep it off,” according to the announcement.

The clinical study, which is not named or referenced in the announcement, is SURMOUNT-1, a Lilly spokesperson said in an interview. Yet, that study also found that patients achieved an average weight loss of 19.5% with 10-mg doses and 20.9% with 15-mg doses of tirzepatide. Furthermore, the percentage of participants achieving body weight reductions of ≥ 5% was 85% (5 mg), 89% (10 mg), and 91% (15 mg), showing the benefits of higher doses.

And there’s the rub.
 

‘Only Two Different Doses’

Anne Peters, MD, a professor of clinical medicine and a clinical scholar at the University of Southern California, Los Angeles, said in an interview: “My concern is, they’re only providing two different doses, 2.5 mg and 5 mg. You get somebody on it, and then they still have to go back to the traditional pens. I’m very opposed to getting patients connected to a medication they can’t then continue to take.

“Now we have starter doses that are easy to come by,” she said. “But the problem isn’t starting. The problem for all of these patients is chronic continuation of the right dose of the drug, and out-of-pocket costs become exorbitantly higher when they have to self-purchase the pens for the higher doses.

“Yes, the 5-mg dose has benefits, but not the same as higher doses,” she continued. “I have nobody for whom 5 mg is the right dose. They have to take more, sometimes within a month or 2 of starting, in order to achieve the kind of weight loss they need.”

If their insurance doesn’t cover the drug, “what are they going to do to stay on 5 mg? Or pay a crapload of money to buy three of the 5-mg doses to reach a higher dose?”

Michael Weintraub, MD, clinical assistant professor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism at New York University Grossman School of Medicine in New York City, said that, “for many, this lower monthly cost is attainable and is a significant advancement in increasing access. For others, however, an out-of-pocket monthly cost of $349-549 for a chronic medication is still unaffordable.”

And like Dr. Peters, he said, “some patients do not lose a clinically significant amount of weight with 2.5 mg or 5 mg and require higher doses. There is no way of prescribing a higher dose of Zepbound vials, so patients would have to resort to the higher-dose auto-injector pens that are still double the price.”

A Lilly spokesperson countered in a comment: “Offering Zepbound single-dose vials in higher dosage strengths could increase the potential for dose splitting, which is not contemplated by the FDA [Food and Drug Adminstration]–approved label and may pose patient safety risks.”

But Dr. Peters wondered: “Wouldn’t dose splitting of a known-to-be-pure compound be better than getting it at a compounding pharmacy that lacks purity/safety? The one message from all of this is that patients need to know what they’re getting into. They’re starting a drug that can help with weight loss, but they’re going to be on a sub-max dose. And a higher dose is going to be double the price.”

In addition, said Robert F. Kushner, MD, a professor at Northwestern University Feinberg School of Medicine in Chicago, Illinois, “for the lower-dose vials, instead of administering the drug with a self-auto-injection pen, patients will need to use a needle and syringe and draw up the dose from a vial. This will take a higher skill level and health literacy that may be challenging for some patients. Patients may need additional training on how to use this new formulation. That will take additional time and resources, such as a demonstration in the office or referral to video.”

The Lilly news release noted that “patients can also purchase ancillary supplies, like syringes and needles, and will have access to important patient-friendly instructional materials on correctly administering the medicine via needle and syringe.”
 

Protection From Compounders?

According to the Lilly spokesperson, the launch of Zepbound vials “furthers our commitment to helping patients avoid the risks associated with compounded products by providing patients another option for access to genuine Lilly medicine.”

Indeed, said Jaime Almandoz, MD, medical director of the Weight Wellness Program and associate professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, “The introduction of Zepbound/tirzepatide in single-dose vials should improve access to evidence-based obesity treatments, reducing potential risks associated with compounded additives and eliminating the need for patients to calculate correct medication doses,” which have led to accidental overdoses of compounded semaglutide.

Lilly’s spokesperson added: “We have taken multiple steps — including publishing an open letter and launching lilly.com/real-medicine — to warn the public about the risks posed by the proliferation of counterfeit, fake, unsafe, or untested knockoffs of Lilly’s genuine medicines.”

But whether these steps are strong enough to overcome the realities of cost and the need for affordable higher doses remains to be seen.

Scott Brunner, CEO of the Alliance for Pharmacy Compounding, said in a statement that the new version of Zepbound “is great news for patients. It’s a much more rational and care-focused response to the remarkable demand for their drug than the lawsuits and cease-and-desist letters Lilly has been raining down on compounding pharmacies.”

“For 20 months now,” he continued, “compounders have been a lifeline for many patients, filling prescriptions for compounded tirzepatide injection at a time when the FDA-approved drug has been in shortage. We’ll be eager to see whether Lilly’s direct-to-patient approach actually works.”

Dr. Almandoz affirmed: “Everyone wants to see improved access to evidence-based obesity care. It’s crucial to ensure patients receive the most appropriate interventions, whether it is lifestyle changes, medications, or bariatric surgery,” he said. “There are resources available, [including his recent paper], for nutrition and lifestyle modifications specifically for patients taking obesity medications, which can help clinicians guide their patients toward better health.”

Dr. Almandoz is a member of advisory boards and consults for: Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr. Kushner is an adviser to Eli Lilly and Novo Nordisk. Dr. Peters and Dr. Weintraub declared no competing interests.

A version of this article appeared on Medscape.com.

Tirzepatide (Zepbound) is not in shortage for now, but the weight loss drug has remained inaccessible to people without insurance coverage who can’t afford to pay out of pocket. Now, its manufacturer, Eli Lilly, has introduced a new formulation it says will “significantly expand” the supply. But not all endocrinologists are enthusiastic.

As of August 27, LillyDirect made 2.5-mg and 5-mg single-dose vials of tirzepatide available to self-pay patients with an on-label electronic prescription. Lilly’s announcement said the single-dose vials “are priced at a 50% or greater discount compared to the list price of all other incretin (glucagon-like peptide 1 receptor agonists or GLP-1) medicines for obesity.”

For a 4-week supply of the weekly injections, the discount at LillyDirect translates to $399 for a 2.5-mg single-dose vial ($99.75 per vial) and $549 for the 5-mg dose ($137.25 per vial), which the company noted was “in line with the Zepbound savings program for noncovered individuals.” (The new direct single-dose prescriptions cannot be filled at community or retail pharmacies.)

“In a clinical study, the 5-mg maintenance dose helped patients achieve an average of 15% weight loss after 72 weeks of treatment and has been a powerful tool for millions of people with obesity looking to lose weight and keep it off,” according to the announcement.

The clinical study, which is not named or referenced in the announcement, is SURMOUNT-1, a Lilly spokesperson said in an interview. Yet, that study also found that patients achieved an average weight loss of 19.5% with 10-mg doses and 20.9% with 15-mg doses of tirzepatide. Furthermore, the percentage of participants achieving body weight reductions of ≥ 5% was 85% (5 mg), 89% (10 mg), and 91% (15 mg), showing the benefits of higher doses.

And there’s the rub.
 

‘Only Two Different Doses’

Anne Peters, MD, a professor of clinical medicine and a clinical scholar at the University of Southern California, Los Angeles, said in an interview: “My concern is, they’re only providing two different doses, 2.5 mg and 5 mg. You get somebody on it, and then they still have to go back to the traditional pens. I’m very opposed to getting patients connected to a medication they can’t then continue to take.

“Now we have starter doses that are easy to come by,” she said. “But the problem isn’t starting. The problem for all of these patients is chronic continuation of the right dose of the drug, and out-of-pocket costs become exorbitantly higher when they have to self-purchase the pens for the higher doses.

“Yes, the 5-mg dose has benefits, but not the same as higher doses,” she continued. “I have nobody for whom 5 mg is the right dose. They have to take more, sometimes within a month or 2 of starting, in order to achieve the kind of weight loss they need.”

If their insurance doesn’t cover the drug, “what are they going to do to stay on 5 mg? Or pay a crapload of money to buy three of the 5-mg doses to reach a higher dose?”

Michael Weintraub, MD, clinical assistant professor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism at New York University Grossman School of Medicine in New York City, said that, “for many, this lower monthly cost is attainable and is a significant advancement in increasing access. For others, however, an out-of-pocket monthly cost of $349-549 for a chronic medication is still unaffordable.”

And like Dr. Peters, he said, “some patients do not lose a clinically significant amount of weight with 2.5 mg or 5 mg and require higher doses. There is no way of prescribing a higher dose of Zepbound vials, so patients would have to resort to the higher-dose auto-injector pens that are still double the price.”

A Lilly spokesperson countered in a comment: “Offering Zepbound single-dose vials in higher dosage strengths could increase the potential for dose splitting, which is not contemplated by the FDA [Food and Drug Adminstration]–approved label and may pose patient safety risks.”

But Dr. Peters wondered: “Wouldn’t dose splitting of a known-to-be-pure compound be better than getting it at a compounding pharmacy that lacks purity/safety? The one message from all of this is that patients need to know what they’re getting into. They’re starting a drug that can help with weight loss, but they’re going to be on a sub-max dose. And a higher dose is going to be double the price.”

In addition, said Robert F. Kushner, MD, a professor at Northwestern University Feinberg School of Medicine in Chicago, Illinois, “for the lower-dose vials, instead of administering the drug with a self-auto-injection pen, patients will need to use a needle and syringe and draw up the dose from a vial. This will take a higher skill level and health literacy that may be challenging for some patients. Patients may need additional training on how to use this new formulation. That will take additional time and resources, such as a demonstration in the office or referral to video.”

The Lilly news release noted that “patients can also purchase ancillary supplies, like syringes and needles, and will have access to important patient-friendly instructional materials on correctly administering the medicine via needle and syringe.”
 

Protection From Compounders?

According to the Lilly spokesperson, the launch of Zepbound vials “furthers our commitment to helping patients avoid the risks associated with compounded products by providing patients another option for access to genuine Lilly medicine.”

Indeed, said Jaime Almandoz, MD, medical director of the Weight Wellness Program and associate professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, “The introduction of Zepbound/tirzepatide in single-dose vials should improve access to evidence-based obesity treatments, reducing potential risks associated with compounded additives and eliminating the need for patients to calculate correct medication doses,” which have led to accidental overdoses of compounded semaglutide.

Lilly’s spokesperson added: “We have taken multiple steps — including publishing an open letter and launching lilly.com/real-medicine — to warn the public about the risks posed by the proliferation of counterfeit, fake, unsafe, or untested knockoffs of Lilly’s genuine medicines.”

But whether these steps are strong enough to overcome the realities of cost and the need for affordable higher doses remains to be seen.

Scott Brunner, CEO of the Alliance for Pharmacy Compounding, said in a statement that the new version of Zepbound “is great news for patients. It’s a much more rational and care-focused response to the remarkable demand for their drug than the lawsuits and cease-and-desist letters Lilly has been raining down on compounding pharmacies.”

“For 20 months now,” he continued, “compounders have been a lifeline for many patients, filling prescriptions for compounded tirzepatide injection at a time when the FDA-approved drug has been in shortage. We’ll be eager to see whether Lilly’s direct-to-patient approach actually works.”

Dr. Almandoz affirmed: “Everyone wants to see improved access to evidence-based obesity care. It’s crucial to ensure patients receive the most appropriate interventions, whether it is lifestyle changes, medications, or bariatric surgery,” he said. “There are resources available, [including his recent paper], for nutrition and lifestyle modifications specifically for patients taking obesity medications, which can help clinicians guide their patients toward better health.”

Dr. Almandoz is a member of advisory boards and consults for: Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr. Kushner is an adviser to Eli Lilly and Novo Nordisk. Dr. Peters and Dr. Weintraub declared no competing interests.

A version of this article appeared on Medscape.com.

In the setting of isocaloric eating, time-restricted eating (TRE) did not reduce weight or improve glucose homeostasis relative to a usual eating pattern (UEP), a small randomized controlled trial found.

The results suggested that any effects of TRE on weight observed in prior studies may be due to reductions in caloric intake and not timing, according to Nisa M. Maruthur, MD, MHS, of the Division of General Internal Medicine at the Johns Hopkins School of Medicine in Baltimore, and colleagues.

Published in Annals of Internal Medicine, the 12-week trial randomly assigned 41 adults aged 18-69 years with obesity and prediabetes or diet-controlled diabetes 1:1 as follows: To TRE, involving a 10-hour eating window with 80% of calories consumed before 1 PM, or to UEP, involving a ≤ 16-hour window, with at least 50% of calories consumed after 5 PM. The regimen in each group was based on the OmniHeart unsaturated fat diet and the SPICE study.

“The diet was similar to the DASH [Dietary Approaches to Stop Hypertension] diet for hypertension and maybe a bit higher in unsaturated fat and micronutrients,” said study co-author Scott J. Pilla, MD, MHS, an assistant professor of medicine at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an interview. For each participant, macro- and micronutrient content remained constant throughout the study period, with total calories individually determined at baseline and ranging from 1600 to 3500 kcal/d. “That differs from some TRE studies in which calories were adjusted according to whether participants lost or gained weight,” he said. “This was a purely mechanistic study to determine the impact of time of eating alone with no change in calories.”

The Cohort

The mean age was 59 years, 93% of patients were women, and 93% were Black. The mean body mass index was 36, and the mean baseline weight was 96.2 kg — 95.6 kg in the TRE group and 103.7 kg in the UEP group.

At 12 weeks, weight decreased comparably by 2.3 kg (95% CI, 1.0-3.5) in the TRE group and by 2.6 kg (95% CI, 1.5-3.7) in the UEP group. Change in glycemic measures did not differ between the two groups.

Interestingly, self-reporting questionnaires revealed a slight reduction in physical activity in the TRE group, an effect that requires further study. “We don’t know why but anecdotally, some TRE participants said they tended to go to bed earlier,” Dr. Pilla said. Earlier bedtimes may put an end sooner to the daily eating pattern.

Subanalyses of the data are ongoing and will be published later.

“In the context of several clinical trials that suggest a benefit of TRE, our findings suggest that if or when TRE interventions induce weight loss, it is likely in part due to a reduction in energy intake, and therefore, clinicians can counsel patients that TRE may help them lose weight by decreasing their caloric intake,” the authors wrote.

In an accompanying editorial, Krista A. Varady, PhD, and Vanessa M. Oddo, PhD, of the Department of Kinesiology and Nutrition at the University of Illinois–Chicago, said the study results have important clinical implications. “Many patients stop following standard-care diets (such as daily calorie restriction) because they become frustrated with having to monitor food intake vigilantly each day,” they wrote.

Gastroenterologists and Obesity

Of late, support has grown for gastroenterologists to become actively involved in obesity treatment — even to “take ownership” of this field.

In a 2023 article in Gut, Michael Camilleri, MD, AGAF, a gastroenterologist at the Mayo Clinic in Rochester, Minnesota, made the case for the natural fit between gastrointestinal (GI) specialists and obesity management. He noted that obesity is a significant risk factor for GI, pancreatic, and liver diseases. It can even affect inflammatory bowel disease.

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

In the setting of isocaloric eating, time-restricted eating (TRE) did not reduce weight or improve glucose homeostasis relative to a usual eating pattern (UEP), a small randomized controlled trial found.

The results suggested that any effects of TRE on weight observed in prior studies may be due to reductions in caloric intake and not timing, according to Nisa M. Maruthur, MD, MHS, of the Division of General Internal Medicine at the Johns Hopkins School of Medicine in Baltimore, and colleagues.

Published in Annals of Internal Medicine, the 12-week trial randomly assigned 41 adults aged 18-69 years with obesity and prediabetes or diet-controlled diabetes 1:1 as follows: To TRE, involving a 10-hour eating window with 80% of calories consumed before 1 PM, or to UEP, involving a ≤ 16-hour window, with at least 50% of calories consumed after 5 PM. The regimen in each group was based on the OmniHeart unsaturated fat diet and the SPICE study.

“The diet was similar to the DASH [Dietary Approaches to Stop Hypertension] diet for hypertension and maybe a bit higher in unsaturated fat and micronutrients,” said study co-author Scott J. Pilla, MD, MHS, an assistant professor of medicine at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an interview. For each participant, macro- and micronutrient content remained constant throughout the study period, with total calories individually determined at baseline and ranging from 1600 to 3500 kcal/d. “That differs from some TRE studies in which calories were adjusted according to whether participants lost or gained weight,” he said. “This was a purely mechanistic study to determine the impact of time of eating alone with no change in calories.”

The Cohort

The mean age was 59 years, 93% of patients were women, and 93% were Black. The mean body mass index was 36, and the mean baseline weight was 96.2 kg — 95.6 kg in the TRE group and 103.7 kg in the UEP group.

At 12 weeks, weight decreased comparably by 2.3 kg (95% CI, 1.0-3.5) in the TRE group and by 2.6 kg (95% CI, 1.5-3.7) in the UEP group. Change in glycemic measures did not differ between the two groups.

Interestingly, self-reporting questionnaires revealed a slight reduction in physical activity in the TRE group, an effect that requires further study. “We don’t know why but anecdotally, some TRE participants said they tended to go to bed earlier,” Dr. Pilla said. Earlier bedtimes may put an end sooner to the daily eating pattern.

Subanalyses of the data are ongoing and will be published later.

“In the context of several clinical trials that suggest a benefit of TRE, our findings suggest that if or when TRE interventions induce weight loss, it is likely in part due to a reduction in energy intake, and therefore, clinicians can counsel patients that TRE may help them lose weight by decreasing their caloric intake,” the authors wrote.

In an accompanying editorial, Krista A. Varady, PhD, and Vanessa M. Oddo, PhD, of the Department of Kinesiology and Nutrition at the University of Illinois–Chicago, said the study results have important clinical implications. “Many patients stop following standard-care diets (such as daily calorie restriction) because they become frustrated with having to monitor food intake vigilantly each day,” they wrote.

Gastroenterologists and Obesity

Of late, support has grown for gastroenterologists to become actively involved in obesity treatment — even to “take ownership” of this field.

In a 2023 article in Gut, Michael Camilleri, MD, AGAF, a gastroenterologist at the Mayo Clinic in Rochester, Minnesota, made the case for the natural fit between gastrointestinal (GI) specialists and obesity management. He noted that obesity is a significant risk factor for GI, pancreatic, and liver diseases. It can even affect inflammatory bowel disease.

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

In the setting of isocaloric eating, time-restricted eating (TRE) did not reduce weight or improve glucose homeostasis relative to a usual eating pattern (UEP), a small randomized controlled trial found.

The results suggested that any effects of TRE on weight observed in prior studies may be due to reductions in caloric intake and not timing, according to Nisa M. Maruthur, MD, MHS, of the Division of General Internal Medicine at the Johns Hopkins School of Medicine in Baltimore, and colleagues.

Published in Annals of Internal Medicine, the 12-week trial randomly assigned 41 adults aged 18-69 years with obesity and prediabetes or diet-controlled diabetes 1:1 as follows: To TRE, involving a 10-hour eating window with 80% of calories consumed before 1 PM, or to UEP, involving a ≤ 16-hour window, with at least 50% of calories consumed after 5 PM. The regimen in each group was based on the OmniHeart unsaturated fat diet and the SPICE study.

“The diet was similar to the DASH [Dietary Approaches to Stop Hypertension] diet for hypertension and maybe a bit higher in unsaturated fat and micronutrients,” said study co-author Scott J. Pilla, MD, MHS, an assistant professor of medicine at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an interview. For each participant, macro- and micronutrient content remained constant throughout the study period, with total calories individually determined at baseline and ranging from 1600 to 3500 kcal/d. “That differs from some TRE studies in which calories were adjusted according to whether participants lost or gained weight,” he said. “This was a purely mechanistic study to determine the impact of time of eating alone with no change in calories.”

The Cohort

The mean age was 59 years, 93% of patients were women, and 93% were Black. The mean body mass index was 36, and the mean baseline weight was 96.2 kg — 95.6 kg in the TRE group and 103.7 kg in the UEP group.

At 12 weeks, weight decreased comparably by 2.3 kg (95% CI, 1.0-3.5) in the TRE group and by 2.6 kg (95% CI, 1.5-3.7) in the UEP group. Change in glycemic measures did not differ between the two groups.

Interestingly, self-reporting questionnaires revealed a slight reduction in physical activity in the TRE group, an effect that requires further study. “We don’t know why but anecdotally, some TRE participants said they tended to go to bed earlier,” Dr. Pilla said. Earlier bedtimes may put an end sooner to the daily eating pattern.

Subanalyses of the data are ongoing and will be published later.

“In the context of several clinical trials that suggest a benefit of TRE, our findings suggest that if or when TRE interventions induce weight loss, it is likely in part due to a reduction in energy intake, and therefore, clinicians can counsel patients that TRE may help them lose weight by decreasing their caloric intake,” the authors wrote.

In an accompanying editorial, Krista A. Varady, PhD, and Vanessa M. Oddo, PhD, of the Department of Kinesiology and Nutrition at the University of Illinois–Chicago, said the study results have important clinical implications. “Many patients stop following standard-care diets (such as daily calorie restriction) because they become frustrated with having to monitor food intake vigilantly each day,” they wrote.

Gastroenterologists and Obesity

Of late, support has grown for gastroenterologists to become actively involved in obesity treatment — even to “take ownership” of this field.

In a 2023 article in Gut, Michael Camilleri, MD, AGAF, a gastroenterologist at the Mayo Clinic in Rochester, Minnesota, made the case for the natural fit between gastrointestinal (GI) specialists and obesity management. He noted that obesity is a significant risk factor for GI, pancreatic, and liver diseases. It can even affect inflammatory bowel disease.

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

HUNTINGTON BEACH, CALIFORNIA — When patients with vitiligo see Jessica Shiu, MD, PhD, for the first time, some mention that prior healthcare providers have told them that vitiligo is merely a cosmetic issue — much to her dismay.

“Vitiligo is not a cosmetic disease,” Dr. Shiu, assistant professor of dermatology at the University of California, Irvine, said at the annual meeting of the Pacific Dermatologic Association. “It is associated with significant depression, stigmatization, and low self-esteem. I have patients who say that vitiligo has affected their marriage ... In certain cultures, it also affects their job prospects.”

As the most common pigmentary disorder, vitiligo is an autoimmune condition that often results in the recruitment of CD8+ T cells into the skin. These cells destroy melanocytes, depleting melanocytes in the epidermis. “Over time, this results in milky white patches of skin that we often see in our patients,” Dr. Shiu said.

Dr. Shiu

“Another sign of active disease is when patients tell you that their vitiligo is expanding rapidly,” Dr. Shiu added. “Stable vitiligo is more difficult to define. Many patients think their lesions don’t change, but we’re now appreciating that there can be some sites in those patients such as the hands and feet that are more susceptible to change in activity.” In general, she noted, vitiligo is considered stable when there is no change in activity for at least 12 months, and “lesions are usually completely depigmented with sharp borders.”

The level of vitiligo disease activity drives medical management. For patients with nonsegmental vitiligo who have clinical signs of active disease, the first goal is to stabilize the active disease and stop further spread of depigmentation. “This is key because losing pigment can occur very quickly, but gaining pigment back is a very slow process,” she said. Stabilization involves suppressing immune responses with topical steroids, topical calcineurin inhibitors, or 1.5% ruxolitinib cream, a JAK inhibitor that became the first Food and Drug Administration (FDA)–approved pharmacologic treatment for nonsegmental vitiligo, in 2022, for patients aged 12 years or older.

“The choice here depends somewhat on insurance coverage and shared decision-making with the patient,” Dr. Shiu said. Meanwhile, clinical trials evaluating the effect of the oral JAK inhibitors ritlecitinib, upadacitinib, povorcitinib, and baricitinib on vitiligo are underway.

Combining Phototherapy With Topical Treatment

A mainstay therapy for nonsegmental vitiligo is phototherapy, which can induce the migration of melanocyte stem cells from hair follicles. “There’s good data to show that combining topical treatment with phototherapy can augment the repigmentation that you see,” she said. “So if it’s possible, try to add phototherapy for your vitiligo patients, but sometimes, logistics for that are a challenge.”

Discussing treatment expectations with patients is key because it can take up to 1 year to see a significant response with topical immunosuppressants and narrowband ultraviolet B treatment. The head and neck areas are often the first sites to repigment, she said, followed by the extremities or the trunk. “The hands and feet are generally last; they are usually the most stubborn areas,” Dr. Shiu said. “Even when you do see repigmentation, it usually happens on the dorsal surfaces. The tips of the fingers and toes are difficult to repigment. Luckily, the face is one of the top responders, so that helps a lot.”

While some treatment efforts result in “complete and beautiful” repigmentation, she added, many yield uneven and incomplete results. “We don’t understand why repigmentation occurs in some areas but not in others,” she said. “We don’t have any biomarkers for treatment response. That is something we are looking into.”

For a patient with rapidly progressing active disease, consider an oral steroid mini-pulse 2 consecutive days per week for a maximum of 3-6 months. “I usually recommend that patients do this on Saturday and Sunday,” Dr. Shiu said. “Studies have shown this strategy can halt progression in 85%-91% of cases if patients are on it for at least 3 months.”

Relapse after successful repigmentation occurs in about 40% of cases following discontinuation of treatment, so she recommends biweekly application of 0.1% tacrolimus ointment as maintenance therapy. “Studies have shown this is enough to decrease the relapse rate to around 9%,” she said.
 

Tissue, Cellular Grafts

Surgical repigmentation strategies rely on transplanting normal skin to areas affected by vitiligo. In general, more than 50% of patients achieve more than 80% repigmentation. Options are divided into tissue grafts vs cellular grafts. “The old methods are tissue grafting such as punch grafting, tissue blister grafting, and spit thickness grafting, which can treat limited areas of skin,” Dr. Shiu said. Newer approaches include cellular grafting using the melanocyte-keratinocyte transplantation procedure, which can treat larger areas of skin.

The main drawback of this approach is that it is expensive and there is no insurance code for it, “but I hope that this becomes an option for our patients in the future because data indicate that repigmentation is maintained for up to 72 months after treatment,” she said.

In June 2023, an autologous cell harvesting device known as RECELL received FDA approval for repigmentation of stable vitiligo lesions. According to a press release from the manufacturer, AVITA Medical, a clinician “prepares and delivers autologous skin cells from pigmented skin to stable depigmented areas, offering a safe and effective treatment for vitiligo.”

Dr. Shiu disclosed that she received research support from AbbVie.
 

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

HUNTINGTON BEACH, CALIFORNIA — When patients with vitiligo see Jessica Shiu, MD, PhD, for the first time, some mention that prior healthcare providers have told them that vitiligo is merely a cosmetic issue — much to her dismay.

“Vitiligo is not a cosmetic disease,” Dr. Shiu, assistant professor of dermatology at the University of California, Irvine, said at the annual meeting of the Pacific Dermatologic Association. “It is associated with significant depression, stigmatization, and low self-esteem. I have patients who say that vitiligo has affected their marriage ... In certain cultures, it also affects their job prospects.”

As the most common pigmentary disorder, vitiligo is an autoimmune condition that often results in the recruitment of CD8+ T cells into the skin. These cells destroy melanocytes, depleting melanocytes in the epidermis. “Over time, this results in milky white patches of skin that we often see in our patients,” Dr. Shiu said.

Dr. Shiu

“Another sign of active disease is when patients tell you that their vitiligo is expanding rapidly,” Dr. Shiu added. “Stable vitiligo is more difficult to define. Many patients think their lesions don’t change, but we’re now appreciating that there can be some sites in those patients such as the hands and feet that are more susceptible to change in activity.” In general, she noted, vitiligo is considered stable when there is no change in activity for at least 12 months, and “lesions are usually completely depigmented with sharp borders.”

The level of vitiligo disease activity drives medical management. For patients with nonsegmental vitiligo who have clinical signs of active disease, the first goal is to stabilize the active disease and stop further spread of depigmentation. “This is key because losing pigment can occur very quickly, but gaining pigment back is a very slow process,” she said. Stabilization involves suppressing immune responses with topical steroids, topical calcineurin inhibitors, or 1.5% ruxolitinib cream, a JAK inhibitor that became the first Food and Drug Administration (FDA)–approved pharmacologic treatment for nonsegmental vitiligo, in 2022, for patients aged 12 years or older.

“The choice here depends somewhat on insurance coverage and shared decision-making with the patient,” Dr. Shiu said. Meanwhile, clinical trials evaluating the effect of the oral JAK inhibitors ritlecitinib, upadacitinib, povorcitinib, and baricitinib on vitiligo are underway.

Combining Phototherapy With Topical Treatment

A mainstay therapy for nonsegmental vitiligo is phototherapy, which can induce the migration of melanocyte stem cells from hair follicles. “There’s good data to show that combining topical treatment with phototherapy can augment the repigmentation that you see,” she said. “So if it’s possible, try to add phototherapy for your vitiligo patients, but sometimes, logistics for that are a challenge.”

Discussing treatment expectations with patients is key because it can take up to 1 year to see a significant response with topical immunosuppressants and narrowband ultraviolet B treatment. The head and neck areas are often the first sites to repigment, she said, followed by the extremities or the trunk. “The hands and feet are generally last; they are usually the most stubborn areas,” Dr. Shiu said. “Even when you do see repigmentation, it usually happens on the dorsal surfaces. The tips of the fingers and toes are difficult to repigment. Luckily, the face is one of the top responders, so that helps a lot.”

While some treatment efforts result in “complete and beautiful” repigmentation, she added, many yield uneven and incomplete results. “We don’t understand why repigmentation occurs in some areas but not in others,” she said. “We don’t have any biomarkers for treatment response. That is something we are looking into.”

For a patient with rapidly progressing active disease, consider an oral steroid mini-pulse 2 consecutive days per week for a maximum of 3-6 months. “I usually recommend that patients do this on Saturday and Sunday,” Dr. Shiu said. “Studies have shown this strategy can halt progression in 85%-91% of cases if patients are on it for at least 3 months.”

Relapse after successful repigmentation occurs in about 40% of cases following discontinuation of treatment, so she recommends biweekly application of 0.1% tacrolimus ointment as maintenance therapy. “Studies have shown this is enough to decrease the relapse rate to around 9%,” she said.
 

Tissue, Cellular Grafts

Surgical repigmentation strategies rely on transplanting normal skin to areas affected by vitiligo. In general, more than 50% of patients achieve more than 80% repigmentation. Options are divided into tissue grafts vs cellular grafts. “The old methods are tissue grafting such as punch grafting, tissue blister grafting, and spit thickness grafting, which can treat limited areas of skin,” Dr. Shiu said. Newer approaches include cellular grafting using the melanocyte-keratinocyte transplantation procedure, which can treat larger areas of skin.

The main drawback of this approach is that it is expensive and there is no insurance code for it, “but I hope that this becomes an option for our patients in the future because data indicate that repigmentation is maintained for up to 72 months after treatment,” she said.

In June 2023, an autologous cell harvesting device known as RECELL received FDA approval for repigmentation of stable vitiligo lesions. According to a press release from the manufacturer, AVITA Medical, a clinician “prepares and delivers autologous skin cells from pigmented skin to stable depigmented areas, offering a safe and effective treatment for vitiligo.”

Dr. Shiu disclosed that she received research support from AbbVie.
 

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

HUNTINGTON BEACH, CALIFORNIA — When patients with vitiligo see Jessica Shiu, MD, PhD, for the first time, some mention that prior healthcare providers have told them that vitiligo is merely a cosmetic issue — much to her dismay.

“Vitiligo is not a cosmetic disease,” Dr. Shiu, assistant professor of dermatology at the University of California, Irvine, said at the annual meeting of the Pacific Dermatologic Association. “It is associated with significant depression, stigmatization, and low self-esteem. I have patients who say that vitiligo has affected their marriage ... In certain cultures, it also affects their job prospects.”

As the most common pigmentary disorder, vitiligo is an autoimmune condition that often results in the recruitment of CD8+ T cells into the skin. These cells destroy melanocytes, depleting melanocytes in the epidermis. “Over time, this results in milky white patches of skin that we often see in our patients,” Dr. Shiu said.

Dr. Shiu

“Another sign of active disease is when patients tell you that their vitiligo is expanding rapidly,” Dr. Shiu added. “Stable vitiligo is more difficult to define. Many patients think their lesions don’t change, but we’re now appreciating that there can be some sites in those patients such as the hands and feet that are more susceptible to change in activity.” In general, she noted, vitiligo is considered stable when there is no change in activity for at least 12 months, and “lesions are usually completely depigmented with sharp borders.”

The level of vitiligo disease activity drives medical management. For patients with nonsegmental vitiligo who have clinical signs of active disease, the first goal is to stabilize the active disease and stop further spread of depigmentation. “This is key because losing pigment can occur very quickly, but gaining pigment back is a very slow process,” she said. Stabilization involves suppressing immune responses with topical steroids, topical calcineurin inhibitors, or 1.5% ruxolitinib cream, a JAK inhibitor that became the first Food and Drug Administration (FDA)–approved pharmacologic treatment for nonsegmental vitiligo, in 2022, for patients aged 12 years or older.

“The choice here depends somewhat on insurance coverage and shared decision-making with the patient,” Dr. Shiu said. Meanwhile, clinical trials evaluating the effect of the oral JAK inhibitors ritlecitinib, upadacitinib, povorcitinib, and baricitinib on vitiligo are underway.

Combining Phototherapy With Topical Treatment

A mainstay therapy for nonsegmental vitiligo is phototherapy, which can induce the migration of melanocyte stem cells from hair follicles. “There’s good data to show that combining topical treatment with phototherapy can augment the repigmentation that you see,” she said. “So if it’s possible, try to add phototherapy for your vitiligo patients, but sometimes, logistics for that are a challenge.”

Discussing treatment expectations with patients is key because it can take up to 1 year to see a significant response with topical immunosuppressants and narrowband ultraviolet B treatment. The head and neck areas are often the first sites to repigment, she said, followed by the extremities or the trunk. “The hands and feet are generally last; they are usually the most stubborn areas,” Dr. Shiu said. “Even when you do see repigmentation, it usually happens on the dorsal surfaces. The tips of the fingers and toes are difficult to repigment. Luckily, the face is one of the top responders, so that helps a lot.”

While some treatment efforts result in “complete and beautiful” repigmentation, she added, many yield uneven and incomplete results. “We don’t understand why repigmentation occurs in some areas but not in others,” she said. “We don’t have any biomarkers for treatment response. That is something we are looking into.”

For a patient with rapidly progressing active disease, consider an oral steroid mini-pulse 2 consecutive days per week for a maximum of 3-6 months. “I usually recommend that patients do this on Saturday and Sunday,” Dr. Shiu said. “Studies have shown this strategy can halt progression in 85%-91% of cases if patients are on it for at least 3 months.”

Relapse after successful repigmentation occurs in about 40% of cases following discontinuation of treatment, so she recommends biweekly application of 0.1% tacrolimus ointment as maintenance therapy. “Studies have shown this is enough to decrease the relapse rate to around 9%,” she said.
 

Tissue, Cellular Grafts

Surgical repigmentation strategies rely on transplanting normal skin to areas affected by vitiligo. In general, more than 50% of patients achieve more than 80% repigmentation. Options are divided into tissue grafts vs cellular grafts. “The old methods are tissue grafting such as punch grafting, tissue blister grafting, and spit thickness grafting, which can treat limited areas of skin,” Dr. Shiu said. Newer approaches include cellular grafting using the melanocyte-keratinocyte transplantation procedure, which can treat larger areas of skin.

The main drawback of this approach is that it is expensive and there is no insurance code for it, “but I hope that this becomes an option for our patients in the future because data indicate that repigmentation is maintained for up to 72 months after treatment,” she said.

In June 2023, an autologous cell harvesting device known as RECELL received FDA approval for repigmentation of stable vitiligo lesions. According to a press release from the manufacturer, AVITA Medical, a clinician “prepares and delivers autologous skin cells from pigmented skin to stable depigmented areas, offering a safe and effective treatment for vitiligo.”

Dr. Shiu disclosed that she received research support from AbbVie.
 

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

The Food and Drug Administration’s (FDA) decision not to approve midomafetamine-assisted therapy (MDMA-AT) for posttraumatic stress disorder (PTSD) puts the therapy’s near-term future in doubt, but officials say the rejection may not knock it out of contention as an eventual therapeutic tool for a variety of conditions.

In August the agency declined to approve the drug with currently available study data and requested that the company conduct an additional phase 3 trial. The agency’s action had potentially devastating consequences for MDMA-AT’s sponsor, Lykos Therapeutics, and was a huge disappointment for researchers, clinicians, and patients who were optimistic that it would be a new option for a condition that affects 13-17 million Americans.

For now, no other company is poised to imminently seek FDA approval for MDMA.

Despite the setback, research into MDMA that combines different psychotherapeutic approaches continues. Currently, there are seven US studies actively recruiting participants, and another 13 are registered with an eye toward starting recruitment, as reported on ClinicalTrials.gov.

The lack of FDA approval “actually increases the opportunity now for us to do trials,” said Michael Ostacher, MD, professor of psychiatry and behavioral sciences at Stanford Medicine in California. Researchers won’t have to be sponsored by Lykos to get access to MDMA.

“There’s a lot of energy and interest in doing these studies,” he said in an interview, adding that philanthropic organizations and Veterans Affairs (VA) are contributing funds to support such studies.

The VA provided a statement saying that it “intends to gather rigorous scientific evidence on the potential efficacy and safety of psychedelic compounds when used in conjunction with psychotherapy.” It also noted that “these studies will be conducted under stringent safety protocols and will mark the first time since the 1960’s that VA is funding research on such compounds.”

Rachel Yehuda, PhD, director of the Center for Psychedelic Therapy Research at Icahn School of Medicine at Mount Sinai in New York City, said in an interview that the FDA rejection “raises questions about how to keep the work going.”

Without the FDA’s imprimatur, MDMA remains a schedule 1 drug, which means it has no valid medical use.

“It’s a lot more complicated and expensive to work with a scheduled compound than to work with a compound that has been approved,” Dr. Yehuda said.

Also, without Lykos or another drug company sponsor, investigators have to find an acceptable MDMA source on their own, said Dr. Yehuda, who was an investigator on a study in which Lykos provided MDMA but was not involved in study design, data collection, analysis, or manuscript preparation.
 

Lykos in Disarray

Within a week of the FDA’s decision, Lykos announced it was cutting its staff by 75% and that Rick Doblin, PhD, the founder and president of the Multidisciplinary Association for Psychedelic Studies (MAPS) that gave rise to Lykos, had resigned from the Lykos board.

A frequently controversial figure, Doblin has been attempting to legitimize MDMA as a therapy since the mid-1980s. He formed a public benefit corporation (PBC) in 2014 with an eye toward FDA approval. The PBC fully separated from MAPS in 2024 and became Lykos.

Although the FDA has left the door open to approval, Lykos has not released the agency’s complete response letter, so it’s not clear exactly what the FDA is seeking. In a statement, the company said it believes the issues “can be addressed with existing data, postapproval requirements, or through reference to the scientific literature.”

Lykos said in an email that it is working on “securing the meeting with the FDA” and that it “will work with the agency to determine what needs to be done to fulfill their requests.”

Soon after the FDA decision, Lykos was hit with another blow. The journal Psychopharmacology retracted an article that pooled six Lykos phase 2 studies, claiming the paper’s authors knew about unethical conduct before submission but did not inform the publisher.

Lykos said the issues could have been addressed through a correction and that it has filed a complaint with the Committee on Publication Ethics. It also noted that the misconduct at issue was reported to the FDA and Health Canada.

“However, we did not disclose the violations to the journal itself, an additional step we should have taken and regret not doing,” the company said. It added that the efficacy data in the paper were not part of the FDA submission.

Author Allison A. Feduccia, PhD, cofounder of Psychedelic Support, agreed with the retraction but disagreed with the wording. In a post on LinkedIn, she said she and other authors were not informed about the misconduct until years after the study’s submission.

Four authors — including Dr. Doblin — disagreed with the retraction.

Dr. Doblin said in a statement that he’d resigned from Lykos to escape the restrictions that came with being a fiduciary. “Now I can advocate and speak freely,” he said, adding that he could also return to his activist roots.

He predicted that Lykos would eventually gain FDA approval. But if Lykos can’t convince the agency, it have the necessary data already in hand; “potential FDA approval is now at least 2 years away, possibly more,” Dr. Doblin said in his statement.
 

Research Continues

Lykos is not the only company hoping to commercialize MDMA. Toronto-based Awakn Life Sciences has an MDMA preclinical development program for addiction. In addition, some companies are offering MDMA therapy through clinics, such as Numinus in Utah and Sunstone Therapies in Rockville, Maryland.

But Lykos was the closest to bringing a product to market. The company is still a sponsor of four MDMA-related clinical trials, three of which appear to be on hold. One study at the VA San Diego Healthcare System, San Diego, that is actively recruiting is an open-label trial to assess MDMA-AT in combination with brief Cognitive-Behavioral Conjoint Therapy for PTSD.

Those studies are among 13 US trials listed in ClinicalTrials.gov that have not yet begun recruiting and 7 that are actively recruiting.

Among them is a study of MDMA plus exposure therapy, funded by and conducted at Emory University in Atlanta. One of the Emory principal investigators, Barbara Rothbaum, MD, has also been named to a Lykos’ panel that would help ensure oversight of MDMA-AT post FDA approval.

Dr. Ostacher is an investigator in a study planned at VA Palo Alto Health Care System in California, that will compare MDMA-AT with cognitive processing therapy in veterans with severe PTSD. He said it will be open label in an effort to minimize expectation bias and issues with blinding — both problems that tripped up the Lykos application. Although placebo-controlled trials are the gold standard, it’s not ideal when “the purpose of the drug is for it to change how you see the world and yourself,” Dr. Ostacher said.

The study aims to see whether MDMA-AT is better than “a much shorter, less onerous, but quite evidence-based psychotherapy for PTSD,” he said.

The FDA’s decision is not the end of the road, said Dr. Ostacher. “Even though I think this makes for an obvious delay, I don’t think that it’s a permanent one,” he said.

Dr. Yehuda also said she is not ready to give up.

“We don’t plan on stopping — we plan on finding a way,” she said.

“In our experience, this is a very powerful approach that helps a lot of people that haven’t found help using other approaches, and when it’s in the hands of really trusted, experienced, ethical clinicians in a trusted environment, this could be a real game changer for people who have not been able to find belief by traditional methods,” she said.

Dr. Ostacher reported no relevant financial relationships. Dr. Yahuda is the principal investigator on clinical trials for the Center for Psychedelic Psychotherapy and Trauma Research that are sponsored by the Multidisciplinary Association for Psychedelic Studies and COMPASS Pathways.

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

The Food and Drug Administration’s (FDA) decision not to approve midomafetamine-assisted therapy (MDMA-AT) for posttraumatic stress disorder (PTSD) puts the therapy’s near-term future in doubt, but officials say the rejection may not knock it out of contention as an eventual therapeutic tool for a variety of conditions.

In August the agency declined to approve the drug with currently available study data and requested that the company conduct an additional phase 3 trial. The agency’s action had potentially devastating consequences for MDMA-AT’s sponsor, Lykos Therapeutics, and was a huge disappointment for researchers, clinicians, and patients who were optimistic that it would be a new option for a condition that affects 13-17 million Americans.

For now, no other company is poised to imminently seek FDA approval for MDMA.

Despite the setback, research into MDMA that combines different psychotherapeutic approaches continues. Currently, there are seven US studies actively recruiting participants, and another 13 are registered with an eye toward starting recruitment, as reported on ClinicalTrials.gov.

The lack of FDA approval “actually increases the opportunity now for us to do trials,” said Michael Ostacher, MD, professor of psychiatry and behavioral sciences at Stanford Medicine in California. Researchers won’t have to be sponsored by Lykos to get access to MDMA.

“There’s a lot of energy and interest in doing these studies,” he said in an interview, adding that philanthropic organizations and Veterans Affairs (VA) are contributing funds to support such studies.

The VA provided a statement saying that it “intends to gather rigorous scientific evidence on the potential efficacy and safety of psychedelic compounds when used in conjunction with psychotherapy.” It also noted that “these studies will be conducted under stringent safety protocols and will mark the first time since the 1960’s that VA is funding research on such compounds.”

Rachel Yehuda, PhD, director of the Center for Psychedelic Therapy Research at Icahn School of Medicine at Mount Sinai in New York City, said in an interview that the FDA rejection “raises questions about how to keep the work going.”

Without the FDA’s imprimatur, MDMA remains a schedule 1 drug, which means it has no valid medical use.

“It’s a lot more complicated and expensive to work with a scheduled compound than to work with a compound that has been approved,” Dr. Yehuda said.

Also, without Lykos or another drug company sponsor, investigators have to find an acceptable MDMA source on their own, said Dr. Yehuda, who was an investigator on a study in which Lykos provided MDMA but was not involved in study design, data collection, analysis, or manuscript preparation.
 

Lykos in Disarray

Within a week of the FDA’s decision, Lykos announced it was cutting its staff by 75% and that Rick Doblin, PhD, the founder and president of the Multidisciplinary Association for Psychedelic Studies (MAPS) that gave rise to Lykos, had resigned from the Lykos board.

A frequently controversial figure, Doblin has been attempting to legitimize MDMA as a therapy since the mid-1980s. He formed a public benefit corporation (PBC) in 2014 with an eye toward FDA approval. The PBC fully separated from MAPS in 2024 and became Lykos.

Although the FDA has left the door open to approval, Lykos has not released the agency’s complete response letter, so it’s not clear exactly what the FDA is seeking. In a statement, the company said it believes the issues “can be addressed with existing data, postapproval requirements, or through reference to the scientific literature.”

Lykos said in an email that it is working on “securing the meeting with the FDA” and that it “will work with the agency to determine what needs to be done to fulfill their requests.”

Soon after the FDA decision, Lykos was hit with another blow. The journal Psychopharmacology retracted an article that pooled six Lykos phase 2 studies, claiming the paper’s authors knew about unethical conduct before submission but did not inform the publisher.

Lykos said the issues could have been addressed through a correction and that it has filed a complaint with the Committee on Publication Ethics. It also noted that the misconduct at issue was reported to the FDA and Health Canada.

“However, we did not disclose the violations to the journal itself, an additional step we should have taken and regret not doing,” the company said. It added that the efficacy data in the paper were not part of the FDA submission.

Author Allison A. Feduccia, PhD, cofounder of Psychedelic Support, agreed with the retraction but disagreed with the wording. In a post on LinkedIn, she said she and other authors were not informed about the misconduct until years after the study’s submission.

Four authors — including Dr. Doblin — disagreed with the retraction.

Dr. Doblin said in a statement that he’d resigned from Lykos to escape the restrictions that came with being a fiduciary. “Now I can advocate and speak freely,” he said, adding that he could also return to his activist roots.

He predicted that Lykos would eventually gain FDA approval. But if Lykos can’t convince the agency, it have the necessary data already in hand; “potential FDA approval is now at least 2 years away, possibly more,” Dr. Doblin said in his statement.
 

Research Continues

Lykos is not the only company hoping to commercialize MDMA. Toronto-based Awakn Life Sciences has an MDMA preclinical development program for addiction. In addition, some companies are offering MDMA therapy through clinics, such as Numinus in Utah and Sunstone Therapies in Rockville, Maryland.

But Lykos was the closest to bringing a product to market. The company is still a sponsor of four MDMA-related clinical trials, three of which appear to be on hold. One study at the VA San Diego Healthcare System, San Diego, that is actively recruiting is an open-label trial to assess MDMA-AT in combination with brief Cognitive-Behavioral Conjoint Therapy for PTSD.

Those studies are among 13 US trials listed in ClinicalTrials.gov that have not yet begun recruiting and 7 that are actively recruiting.

Among them is a study of MDMA plus exposure therapy, funded by and conducted at Emory University in Atlanta. One of the Emory principal investigators, Barbara Rothbaum, MD, has also been named to a Lykos’ panel that would help ensure oversight of MDMA-AT post FDA approval.

Dr. Ostacher is an investigator in a study planned at VA Palo Alto Health Care System in California, that will compare MDMA-AT with cognitive processing therapy in veterans with severe PTSD. He said it will be open label in an effort to minimize expectation bias and issues with blinding — both problems that tripped up the Lykos application. Although placebo-controlled trials are the gold standard, it’s not ideal when “the purpose of the drug is for it to change how you see the world and yourself,” Dr. Ostacher said.

The study aims to see whether MDMA-AT is better than “a much shorter, less onerous, but quite evidence-based psychotherapy for PTSD,” he said.

The FDA’s decision is not the end of the road, said Dr. Ostacher. “Even though I think this makes for an obvious delay, I don’t think that it’s a permanent one,” he said.

Dr. Yehuda also said she is not ready to give up.

“We don’t plan on stopping — we plan on finding a way,” she said.

“In our experience, this is a very powerful approach that helps a lot of people that haven’t found help using other approaches, and when it’s in the hands of really trusted, experienced, ethical clinicians in a trusted environment, this could be a real game changer for people who have not been able to find belief by traditional methods,” she said.

Dr. Ostacher reported no relevant financial relationships. Dr. Yahuda is the principal investigator on clinical trials for the Center for Psychedelic Psychotherapy and Trauma Research that are sponsored by the Multidisciplinary Association for Psychedelic Studies and COMPASS Pathways.

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

The Food and Drug Administration’s (FDA) decision not to approve midomafetamine-assisted therapy (MDMA-AT) for posttraumatic stress disorder (PTSD) puts the therapy’s near-term future in doubt, but officials say the rejection may not knock it out of contention as an eventual therapeutic tool for a variety of conditions.

In August the agency declined to approve the drug with currently available study data and requested that the company conduct an additional phase 3 trial. The agency’s action had potentially devastating consequences for MDMA-AT’s sponsor, Lykos Therapeutics, and was a huge disappointment for researchers, clinicians, and patients who were optimistic that it would be a new option for a condition that affects 13-17 million Americans.

For now, no other company is poised to imminently seek FDA approval for MDMA.

Despite the setback, research into MDMA that combines different psychotherapeutic approaches continues. Currently, there are seven US studies actively recruiting participants, and another 13 are registered with an eye toward starting recruitment, as reported on ClinicalTrials.gov.

The lack of FDA approval “actually increases the opportunity now for us to do trials,” said Michael Ostacher, MD, professor of psychiatry and behavioral sciences at Stanford Medicine in California. Researchers won’t have to be sponsored by Lykos to get access to MDMA.

“There’s a lot of energy and interest in doing these studies,” he said in an interview, adding that philanthropic organizations and Veterans Affairs (VA) are contributing funds to support such studies.

The VA provided a statement saying that it “intends to gather rigorous scientific evidence on the potential efficacy and safety of psychedelic compounds when used in conjunction with psychotherapy.” It also noted that “these studies will be conducted under stringent safety protocols and will mark the first time since the 1960’s that VA is funding research on such compounds.”

Rachel Yehuda, PhD, director of the Center for Psychedelic Therapy Research at Icahn School of Medicine at Mount Sinai in New York City, said in an interview that the FDA rejection “raises questions about how to keep the work going.”

Without the FDA’s imprimatur, MDMA remains a schedule 1 drug, which means it has no valid medical use.

“It’s a lot more complicated and expensive to work with a scheduled compound than to work with a compound that has been approved,” Dr. Yehuda said.

Also, without Lykos or another drug company sponsor, investigators have to find an acceptable MDMA source on their own, said Dr. Yehuda, who was an investigator on a study in which Lykos provided MDMA but was not involved in study design, data collection, analysis, or manuscript preparation.
 

Lykos in Disarray

Within a week of the FDA’s decision, Lykos announced it was cutting its staff by 75% and that Rick Doblin, PhD, the founder and president of the Multidisciplinary Association for Psychedelic Studies (MAPS) that gave rise to Lykos, had resigned from the Lykos board.

A frequently controversial figure, Doblin has been attempting to legitimize MDMA as a therapy since the mid-1980s. He formed a public benefit corporation (PBC) in 2014 with an eye toward FDA approval. The PBC fully separated from MAPS in 2024 and became Lykos.

Although the FDA has left the door open to approval, Lykos has not released the agency’s complete response letter, so it’s not clear exactly what the FDA is seeking. In a statement, the company said it believes the issues “can be addressed with existing data, postapproval requirements, or through reference to the scientific literature.”

Lykos said in an email that it is working on “securing the meeting with the FDA” and that it “will work with the agency to determine what needs to be done to fulfill their requests.”

Soon after the FDA decision, Lykos was hit with another blow. The journal Psychopharmacology retracted an article that pooled six Lykos phase 2 studies, claiming the paper’s authors knew about unethical conduct before submission but did not inform the publisher.

Lykos said the issues could have been addressed through a correction and that it has filed a complaint with the Committee on Publication Ethics. It also noted that the misconduct at issue was reported to the FDA and Health Canada.

“However, we did not disclose the violations to the journal itself, an additional step we should have taken and regret not doing,” the company said. It added that the efficacy data in the paper were not part of the FDA submission.

Author Allison A. Feduccia, PhD, cofounder of Psychedelic Support, agreed with the retraction but disagreed with the wording. In a post on LinkedIn, she said she and other authors were not informed about the misconduct until years after the study’s submission.

Four authors — including Dr. Doblin — disagreed with the retraction.

Dr. Doblin said in a statement that he’d resigned from Lykos to escape the restrictions that came with being a fiduciary. “Now I can advocate and speak freely,” he said, adding that he could also return to his activist roots.

He predicted that Lykos would eventually gain FDA approval. But if Lykos can’t convince the agency, it have the necessary data already in hand; “potential FDA approval is now at least 2 years away, possibly more,” Dr. Doblin said in his statement.
 

Research Continues

Lykos is not the only company hoping to commercialize MDMA. Toronto-based Awakn Life Sciences has an MDMA preclinical development program for addiction. In addition, some companies are offering MDMA therapy through clinics, such as Numinus in Utah and Sunstone Therapies in Rockville, Maryland.

But Lykos was the closest to bringing a product to market. The company is still a sponsor of four MDMA-related clinical trials, three of which appear to be on hold. One study at the VA San Diego Healthcare System, San Diego, that is actively recruiting is an open-label trial to assess MDMA-AT in combination with brief Cognitive-Behavioral Conjoint Therapy for PTSD.

Those studies are among 13 US trials listed in ClinicalTrials.gov that have not yet begun recruiting and 7 that are actively recruiting.

Among them is a study of MDMA plus exposure therapy, funded by and conducted at Emory University in Atlanta. One of the Emory principal investigators, Barbara Rothbaum, MD, has also been named to a Lykos’ panel that would help ensure oversight of MDMA-AT post FDA approval.

Dr. Ostacher is an investigator in a study planned at VA Palo Alto Health Care System in California, that will compare MDMA-AT with cognitive processing therapy in veterans with severe PTSD. He said it will be open label in an effort to minimize expectation bias and issues with blinding — both problems that tripped up the Lykos application. Although placebo-controlled trials are the gold standard, it’s not ideal when “the purpose of the drug is for it to change how you see the world and yourself,” Dr. Ostacher said.

The study aims to see whether MDMA-AT is better than “a much shorter, less onerous, but quite evidence-based psychotherapy for PTSD,” he said.

The FDA’s decision is not the end of the road, said Dr. Ostacher. “Even though I think this makes for an obvious delay, I don’t think that it’s a permanent one,” he said.

Dr. Yehuda also said she is not ready to give up.

“We don’t plan on stopping — we plan on finding a way,” she said.

“In our experience, this is a very powerful approach that helps a lot of people that haven’t found help using other approaches, and when it’s in the hands of really trusted, experienced, ethical clinicians in a trusted environment, this could be a real game changer for people who have not been able to find belief by traditional methods,” she said.

Dr. Ostacher reported no relevant financial relationships. Dr. Yahuda is the principal investigator on clinical trials for the Center for Psychedelic Psychotherapy and Trauma Research that are sponsored by the Multidisciplinary Association for Psychedelic Studies and COMPASS Pathways.

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