Psoriasis

More than 3 months after the Dobbs decision by the U.S. Supreme Court overturned Roe v. Wade and revoked the constitutional right to an abortion, dermatologists who prescribe isotretinoin, a teratogenic drug used to treat severe nodular acne, say they worry even more than in the past about their patients and the risk of accidental pregnancies. Some have beefed up their already stringent instructions and lengthy conversations about avoiding pregnancy while on the medication.

The major fear is that a patient who is taking contraceptive precautions, in accordance with the isotretinoin risk-management program, iPLEDGE, but still becomes pregnant while on isotretinoin may find out about the pregnancy too late to undergo an abortion in her own state and may not be able to travel to another state – or the patient may live in a state where abortions are entirely prohibited and is unable to travel to another state.

Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane; its former brand name was Accutane.

As of Oct. 7, a total of 14 states have banned most abortions, while 4 others have bans at 6, 15, 18, or 20 weeks. Attempts to restrict abortion on several other states are underway.

“To date, we don’t know of any specific effects of the Dobbs decision on isotretinoin prescribing, but with abortion access banned in many states, we anticipate that this could be a very real issue for individuals who accidentally become pregnant while taking isotretinoin,” said Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and chair of the American Academy of Dermatology Association’s iPLEDGE Workgroup.

The iPLEDGE REMS (Risk Evaluation and Mitigation Strategy) is the Food and Drug Administration–required safety program that is in place to manage the risk of isotretinoin teratogenicity and minimize fetal exposure. The work group meets with the FDA and isotretinoin manufacturers to keep the program safe and operating smoothly. The iPLEDGE workgroup has not yet issued any specific statements on the implications of the Dobbs decision on prescribing isotretinoin.

But work on the issue is ongoing by the American Academy of Dermatology. In a statement issued in September, Mark D. Kaufmann, MD, president of the AAD, said that the academy “is continuing to work with its Patient Guidance for State Regulations Regarding Reproductive Health Task Force to help dermatologists best navigate state laws about how care should be implemented for patients who are or might become pregnant, and have been exposed to teratogenic medications.”

The task force, working with the academy, is “in the process of developing resources to help members better assist patients and have a productive and caring dialogue with them,” according to the statement. No specific timeline was given for when those resources might be available.
 

Methotrexate prescriptions

Also of concern are prescriptions for methotrexate, which is prescribed for psoriasis, atopic dermatitis, and other skin diseases. Soon after the Dobbs decision was announced on June 24, pharmacies began to require pharmacists in states that banned abortions to verify that a prescription for methotrexate was not intended for an abortion, since methotrexate is used in combination with misoprostol for termination of an early pregnancy.

The action was taken, spokespersons for several major pharmacies said, to comply with state laws. According to Kara Page, a CVS spokesperson: “Pharmacists are caught in the middle on this issue.” Laws in some states, she told this news organization, “restrict the dispensing of medications for the purpose of inducing an abortion. These laws, some of which include criminal penalties, have forced us to require pharmacists in these states to validate that the intended indication is not to terminate a pregnancy before they can fill a prescription for methotrexate.”

“New laws in various states require additional steps for dispensing certain prescriptions and apply to all pharmacies, including Walgreens,” Fraser Engerman, a spokesperson for Walgreens, told this news organization. “In these states, our pharmacists work closely with prescribers as needed, to fill lawful, clinically appropriate prescriptions. We provide ongoing training and information to help our pharmacists understand the latest requirements in their area, and with these supports, the expectation is they are empowered to fill these prescriptions.”

The iPLEDGE program has numerous requirements before a patient can begin isotretinoin treatment. Patients capable of becoming pregnant must agree to use two effective forms of birth control during the entire treatment period, which typically lasts 4 or 5 months, as well as 1 month before and 1 month after treatment, or commit to total abstinence during that time.

Perspective: A Georgia dermatologist

Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, who sees patients regularly, practices in Georgia, where abortion is now banned at about 6 weeks of pregnancy. Dr. Yeung worries that some dermatologists in Georgia and elsewhere may not even want to take the risk of prescribing isotretinoin, although the results in treating resistant acne are well documented.

That isn’t his only concern. “Some may not want to prescribe it to a patient who reports they are abstinent and instead require them to go on two forms [of contraception].” Or some women who are not sexually active with anyone who can get them pregnant may also be asked to go on contraception, he said. Abstinence is an alternative option in iPLEDGE.

In the past, he said, well before the Dobbs decision, some doctors have argued that iPLEDGE should not include abstinence as an option. That 2020 report was challenged by others who pointed out that removing the abstinence option would pose ethical issues and may disproportionately affect minorities and others.

Before the Dobbs decision, Dr. Yeung noted, dermatologists prescribing isotretinoin focused on pregnancy prevention but knew that if pregnancy accidentally occurred, abortion was available as an option. “The reality after the decision is, it may or may not be available to all our patients.”

Of the 14 states banning most abortions, 10 are clustered within the South and Southeast. A woman living in Arkansas, which bans most abortions, for example, is surrounded by 6 other states that do the same.
 

Perspective: An Arizona dermatologist

Christina Kranc, MD, is a general dermatologist in Phoenix and Scottsdale. Arizona now bans most abortions. However, this has not changed her practice much when prescribing isotretinoin, she told this news organization, because when selecting appropriate candidates for the medication, she is strict on the contraceptive requirement, and only very rarely agrees to a patient relying on abstinence.

And if a patient capable of becoming pregnant was only having sex with another patient capable of becoming pregnant? Dr. Kranc said she would still require contraception unless it was impossible for pregnancy to occur.

Among the many scenarios a dermatologist might have to consider are a lesbian cisgender woman who is having, or has only had, sexual activity with another cisgender women.
 

Perspective: A Connecticut dermatologist

The concern is not only about isotretinoin but all teratogenic drugs, according to Jane M. Grant-Kels, MD, vice chair of dermatology and professor of dermatology, pathology, and pediatrics at the University of Connecticut, Farmington. She often prescribes methotrexate, which is also teratogenic.

Her advice for colleagues: “Whether you believe in abortion or not is irrelevant; it’s something you discuss with your patients.” She, too, fears that doctors in states banning abortions will stop prescribing these medications, “and that is very sad.”

For those practicing in states limiting or banning abortions, Dr. Grant-Kels said, “They need to have an even longer discussion with their patients about how serious this is.” Those doctors need to talk about not only two or three types of birth control, but also discuss with the patient about the potential need for travel, should pregnancy occur and abortion be the chosen option.

Although the newer biologics are an option for psoriasis, they are expensive. And, she said, many insurers require a step-therapy approach, and “want you to start with cheaper medications,” such as methotrexate. As a result, “in some states you won’t have access to the targeted therapies unless a patient fails something like methotrexate.”

Dr. Grant-Kels worries in particular about low-income women who may not have the means to travel to get an abortion.
 

Need for EC education

In a recent survey of 57 pediatric dermatologists who prescribe isotretinoin, only a third said they felt confident in their understanding of emergency contraception.

The authors of the study noted that the most common reasons for pregnancies during isotretinoin therapy reported to the FDA from 2011 to 2017 “included ineffective or inconsistent use” of contraceptives and “unsuccessful abstinence,” and recommended that physicians who prescribe isotretinoin update and increase their understanding of emergency contraception.

Dr. Yeung, Dr. Kranc, Dr. Grant-Kels, and Dr. Frieden reported no relevant financial relationships.

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

More than 3 months after the Dobbs decision by the U.S. Supreme Court overturned Roe v. Wade and revoked the constitutional right to an abortion, dermatologists who prescribe isotretinoin, a teratogenic drug used to treat severe nodular acne, say they worry even more than in the past about their patients and the risk of accidental pregnancies. Some have beefed up their already stringent instructions and lengthy conversations about avoiding pregnancy while on the medication.

The major fear is that a patient who is taking contraceptive precautions, in accordance with the isotretinoin risk-management program, iPLEDGE, but still becomes pregnant while on isotretinoin may find out about the pregnancy too late to undergo an abortion in her own state and may not be able to travel to another state – or the patient may live in a state where abortions are entirely prohibited and is unable to travel to another state.

Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane; its former brand name was Accutane.

As of Oct. 7, a total of 14 states have banned most abortions, while 4 others have bans at 6, 15, 18, or 20 weeks. Attempts to restrict abortion on several other states are underway.

“To date, we don’t know of any specific effects of the Dobbs decision on isotretinoin prescribing, but with abortion access banned in many states, we anticipate that this could be a very real issue for individuals who accidentally become pregnant while taking isotretinoin,” said Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and chair of the American Academy of Dermatology Association’s iPLEDGE Workgroup.

The iPLEDGE REMS (Risk Evaluation and Mitigation Strategy) is the Food and Drug Administration–required safety program that is in place to manage the risk of isotretinoin teratogenicity and minimize fetal exposure. The work group meets with the FDA and isotretinoin manufacturers to keep the program safe and operating smoothly. The iPLEDGE workgroup has not yet issued any specific statements on the implications of the Dobbs decision on prescribing isotretinoin.

But work on the issue is ongoing by the American Academy of Dermatology. In a statement issued in September, Mark D. Kaufmann, MD, president of the AAD, said that the academy “is continuing to work with its Patient Guidance for State Regulations Regarding Reproductive Health Task Force to help dermatologists best navigate state laws about how care should be implemented for patients who are or might become pregnant, and have been exposed to teratogenic medications.”

The task force, working with the academy, is “in the process of developing resources to help members better assist patients and have a productive and caring dialogue with them,” according to the statement. No specific timeline was given for when those resources might be available.
 

Methotrexate prescriptions

Also of concern are prescriptions for methotrexate, which is prescribed for psoriasis, atopic dermatitis, and other skin diseases. Soon after the Dobbs decision was announced on June 24, pharmacies began to require pharmacists in states that banned abortions to verify that a prescription for methotrexate was not intended for an abortion, since methotrexate is used in combination with misoprostol for termination of an early pregnancy.

The action was taken, spokespersons for several major pharmacies said, to comply with state laws. According to Kara Page, a CVS spokesperson: “Pharmacists are caught in the middle on this issue.” Laws in some states, she told this news organization, “restrict the dispensing of medications for the purpose of inducing an abortion. These laws, some of which include criminal penalties, have forced us to require pharmacists in these states to validate that the intended indication is not to terminate a pregnancy before they can fill a prescription for methotrexate.”

“New laws in various states require additional steps for dispensing certain prescriptions and apply to all pharmacies, including Walgreens,” Fraser Engerman, a spokesperson for Walgreens, told this news organization. “In these states, our pharmacists work closely with prescribers as needed, to fill lawful, clinically appropriate prescriptions. We provide ongoing training and information to help our pharmacists understand the latest requirements in their area, and with these supports, the expectation is they are empowered to fill these prescriptions.”

The iPLEDGE program has numerous requirements before a patient can begin isotretinoin treatment. Patients capable of becoming pregnant must agree to use two effective forms of birth control during the entire treatment period, which typically lasts 4 or 5 months, as well as 1 month before and 1 month after treatment, or commit to total abstinence during that time.

Perspective: A Georgia dermatologist

Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, who sees patients regularly, practices in Georgia, where abortion is now banned at about 6 weeks of pregnancy. Dr. Yeung worries that some dermatologists in Georgia and elsewhere may not even want to take the risk of prescribing isotretinoin, although the results in treating resistant acne are well documented.

That isn’t his only concern. “Some may not want to prescribe it to a patient who reports they are abstinent and instead require them to go on two forms [of contraception].” Or some women who are not sexually active with anyone who can get them pregnant may also be asked to go on contraception, he said. Abstinence is an alternative option in iPLEDGE.

In the past, he said, well before the Dobbs decision, some doctors have argued that iPLEDGE should not include abstinence as an option. That 2020 report was challenged by others who pointed out that removing the abstinence option would pose ethical issues and may disproportionately affect minorities and others.

Before the Dobbs decision, Dr. Yeung noted, dermatologists prescribing isotretinoin focused on pregnancy prevention but knew that if pregnancy accidentally occurred, abortion was available as an option. “The reality after the decision is, it may or may not be available to all our patients.”

Of the 14 states banning most abortions, 10 are clustered within the South and Southeast. A woman living in Arkansas, which bans most abortions, for example, is surrounded by 6 other states that do the same.
 

Perspective: An Arizona dermatologist

Christina Kranc, MD, is a general dermatologist in Phoenix and Scottsdale. Arizona now bans most abortions. However, this has not changed her practice much when prescribing isotretinoin, she told this news organization, because when selecting appropriate candidates for the medication, she is strict on the contraceptive requirement, and only very rarely agrees to a patient relying on abstinence.

And if a patient capable of becoming pregnant was only having sex with another patient capable of becoming pregnant? Dr. Kranc said she would still require contraception unless it was impossible for pregnancy to occur.

Among the many scenarios a dermatologist might have to consider are a lesbian cisgender woman who is having, or has only had, sexual activity with another cisgender women.
 

Perspective: A Connecticut dermatologist

The concern is not only about isotretinoin but all teratogenic drugs, according to Jane M. Grant-Kels, MD, vice chair of dermatology and professor of dermatology, pathology, and pediatrics at the University of Connecticut, Farmington. She often prescribes methotrexate, which is also teratogenic.

Her advice for colleagues: “Whether you believe in abortion or not is irrelevant; it’s something you discuss with your patients.” She, too, fears that doctors in states banning abortions will stop prescribing these medications, “and that is very sad.”

For those practicing in states limiting or banning abortions, Dr. Grant-Kels said, “They need to have an even longer discussion with their patients about how serious this is.” Those doctors need to talk about not only two or three types of birth control, but also discuss with the patient about the potential need for travel, should pregnancy occur and abortion be the chosen option.

Although the newer biologics are an option for psoriasis, they are expensive. And, she said, many insurers require a step-therapy approach, and “want you to start with cheaper medications,” such as methotrexate. As a result, “in some states you won’t have access to the targeted therapies unless a patient fails something like methotrexate.”

Dr. Grant-Kels worries in particular about low-income women who may not have the means to travel to get an abortion.
 

Need for EC education

In a recent survey of 57 pediatric dermatologists who prescribe isotretinoin, only a third said they felt confident in their understanding of emergency contraception.

The authors of the study noted that the most common reasons for pregnancies during isotretinoin therapy reported to the FDA from 2011 to 2017 “included ineffective or inconsistent use” of contraceptives and “unsuccessful abstinence,” and recommended that physicians who prescribe isotretinoin update and increase their understanding of emergency contraception.

Dr. Yeung, Dr. Kranc, Dr. Grant-Kels, and Dr. Frieden reported no relevant financial relationships.

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

More than 3 months after the Dobbs decision by the U.S. Supreme Court overturned Roe v. Wade and revoked the constitutional right to an abortion, dermatologists who prescribe isotretinoin, a teratogenic drug used to treat severe nodular acne, say they worry even more than in the past about their patients and the risk of accidental pregnancies. Some have beefed up their already stringent instructions and lengthy conversations about avoiding pregnancy while on the medication.

The major fear is that a patient who is taking contraceptive precautions, in accordance with the isotretinoin risk-management program, iPLEDGE, but still becomes pregnant while on isotretinoin may find out about the pregnancy too late to undergo an abortion in her own state and may not be able to travel to another state – or the patient may live in a state where abortions are entirely prohibited and is unable to travel to another state.

Isotretinoin is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane; its former brand name was Accutane.

As of Oct. 7, a total of 14 states have banned most abortions, while 4 others have bans at 6, 15, 18, or 20 weeks. Attempts to restrict abortion on several other states are underway.

“To date, we don’t know of any specific effects of the Dobbs decision on isotretinoin prescribing, but with abortion access banned in many states, we anticipate that this could be a very real issue for individuals who accidentally become pregnant while taking isotretinoin,” said Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, and chair of the American Academy of Dermatology Association’s iPLEDGE Workgroup.

The iPLEDGE REMS (Risk Evaluation and Mitigation Strategy) is the Food and Drug Administration–required safety program that is in place to manage the risk of isotretinoin teratogenicity and minimize fetal exposure. The work group meets with the FDA and isotretinoin manufacturers to keep the program safe and operating smoothly. The iPLEDGE workgroup has not yet issued any specific statements on the implications of the Dobbs decision on prescribing isotretinoin.

But work on the issue is ongoing by the American Academy of Dermatology. In a statement issued in September, Mark D. Kaufmann, MD, president of the AAD, said that the academy “is continuing to work with its Patient Guidance for State Regulations Regarding Reproductive Health Task Force to help dermatologists best navigate state laws about how care should be implemented for patients who are or might become pregnant, and have been exposed to teratogenic medications.”

The task force, working with the academy, is “in the process of developing resources to help members better assist patients and have a productive and caring dialogue with them,” according to the statement. No specific timeline was given for when those resources might be available.
 

Methotrexate prescriptions

Also of concern are prescriptions for methotrexate, which is prescribed for psoriasis, atopic dermatitis, and other skin diseases. Soon after the Dobbs decision was announced on June 24, pharmacies began to require pharmacists in states that banned abortions to verify that a prescription for methotrexate was not intended for an abortion, since methotrexate is used in combination with misoprostol for termination of an early pregnancy.

The action was taken, spokespersons for several major pharmacies said, to comply with state laws. According to Kara Page, a CVS spokesperson: “Pharmacists are caught in the middle on this issue.” Laws in some states, she told this news organization, “restrict the dispensing of medications for the purpose of inducing an abortion. These laws, some of which include criminal penalties, have forced us to require pharmacists in these states to validate that the intended indication is not to terminate a pregnancy before they can fill a prescription for methotrexate.”

“New laws in various states require additional steps for dispensing certain prescriptions and apply to all pharmacies, including Walgreens,” Fraser Engerman, a spokesperson for Walgreens, told this news organization. “In these states, our pharmacists work closely with prescribers as needed, to fill lawful, clinically appropriate prescriptions. We provide ongoing training and information to help our pharmacists understand the latest requirements in their area, and with these supports, the expectation is they are empowered to fill these prescriptions.”

The iPLEDGE program has numerous requirements before a patient can begin isotretinoin treatment. Patients capable of becoming pregnant must agree to use two effective forms of birth control during the entire treatment period, which typically lasts 4 or 5 months, as well as 1 month before and 1 month after treatment, or commit to total abstinence during that time.

Perspective: A Georgia dermatologist

Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, who sees patients regularly, practices in Georgia, where abortion is now banned at about 6 weeks of pregnancy. Dr. Yeung worries that some dermatologists in Georgia and elsewhere may not even want to take the risk of prescribing isotretinoin, although the results in treating resistant acne are well documented.

That isn’t his only concern. “Some may not want to prescribe it to a patient who reports they are abstinent and instead require them to go on two forms [of contraception].” Or some women who are not sexually active with anyone who can get them pregnant may also be asked to go on contraception, he said. Abstinence is an alternative option in iPLEDGE.

In the past, he said, well before the Dobbs decision, some doctors have argued that iPLEDGE should not include abstinence as an option. That 2020 report was challenged by others who pointed out that removing the abstinence option would pose ethical issues and may disproportionately affect minorities and others.

Before the Dobbs decision, Dr. Yeung noted, dermatologists prescribing isotretinoin focused on pregnancy prevention but knew that if pregnancy accidentally occurred, abortion was available as an option. “The reality after the decision is, it may or may not be available to all our patients.”

Of the 14 states banning most abortions, 10 are clustered within the South and Southeast. A woman living in Arkansas, which bans most abortions, for example, is surrounded by 6 other states that do the same.
 

Perspective: An Arizona dermatologist

Christina Kranc, MD, is a general dermatologist in Phoenix and Scottsdale. Arizona now bans most abortions. However, this has not changed her practice much when prescribing isotretinoin, she told this news organization, because when selecting appropriate candidates for the medication, she is strict on the contraceptive requirement, and only very rarely agrees to a patient relying on abstinence.

And if a patient capable of becoming pregnant was only having sex with another patient capable of becoming pregnant? Dr. Kranc said she would still require contraception unless it was impossible for pregnancy to occur.

Among the many scenarios a dermatologist might have to consider are a lesbian cisgender woman who is having, or has only had, sexual activity with another cisgender women.
 

Perspective: A Connecticut dermatologist

The concern is not only about isotretinoin but all teratogenic drugs, according to Jane M. Grant-Kels, MD, vice chair of dermatology and professor of dermatology, pathology, and pediatrics at the University of Connecticut, Farmington. She often prescribes methotrexate, which is also teratogenic.

Her advice for colleagues: “Whether you believe in abortion or not is irrelevant; it’s something you discuss with your patients.” She, too, fears that doctors in states banning abortions will stop prescribing these medications, “and that is very sad.”

For those practicing in states limiting or banning abortions, Dr. Grant-Kels said, “They need to have an even longer discussion with their patients about how serious this is.” Those doctors need to talk about not only two or three types of birth control, but also discuss with the patient about the potential need for travel, should pregnancy occur and abortion be the chosen option.

Although the newer biologics are an option for psoriasis, they are expensive. And, she said, many insurers require a step-therapy approach, and “want you to start with cheaper medications,” such as methotrexate. As a result, “in some states you won’t have access to the targeted therapies unless a patient fails something like methotrexate.”

Dr. Grant-Kels worries in particular about low-income women who may not have the means to travel to get an abortion.
 

Need for EC education

In a recent survey of 57 pediatric dermatologists who prescribe isotretinoin, only a third said they felt confident in their understanding of emergency contraception.

The authors of the study noted that the most common reasons for pregnancies during isotretinoin therapy reported to the FDA from 2011 to 2017 “included ineffective or inconsistent use” of contraceptives and “unsuccessful abstinence,” and recommended that physicians who prescribe isotretinoin update and increase their understanding of emergency contraception.

Dr. Yeung, Dr. Kranc, Dr. Grant-Kels, and Dr. Frieden reported no relevant financial relationships.

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

Psoriasis is an immune-mediated chronic inflammatory disease characterized by well-demarcated, scaly, erythematous plaques. Those who present with the condition often have a family history, which supports recent research uncovering various genes implicated in its pathogenesis. The disease is also associated with other systemic complications, most notably cardiovascular disease.

Palmoplantar psoriasis is a unique manifestation of psoriasis appearing in an acral distribution, but can coexist with plaque psoriasis, which is commonly found on extensor surfaces. This condition is found in a small percentage of patients with psoriasis and presentation varies from hyperkeratotic plaques to pustular lesions. The pustular form is known as palmoplantar pustulosis and is within the spectrum of palmoplantar psoriasis.

Psoriasis is typically a clinical diagnosis and its severity can be measured using the Psoriasis Area and Severity Index. If biopsy is performed, the histology demonstrates parakeratosis, orthokeratosis, loss of the stratum granulosum, and dilated vasculature with an inflammatory cell infiltrate. The keratinocytes present with abnormal differentiation and hyperplasia, and the presence of foci of neutrophils known as “Munro’s microabscesses” in the stratum corneum serve as the hallmark of histological diagnosis. However, it is important to note that appearance can vary based on the stage of the lesion and the subtype of psoriasis present.

Palmoplantar psoriasis can be especially limiting and difficult to treat because of its distribution. Topical steroids, topical vitamin D analogues, and narrow band ultraviolet light therapy can be effective for less severe cases. Methotrexate, biologic treatments, and apremilast can be used for more extensive disease.

This patient is HLA-B27 positive and has uveitis. The presence of the HLA-B27 allele has been associated with inflammatory bowel disease, uveitis, psoriatic arthritis, and reactive arthritis. It has also been reported to be associated with pustular psoriasis. She responded well to topical steroids and vitamin D analogues.

This case and photo were submitted by Mr. Shapiro at Nova Southeastern University College of Osteopathic Medicine, Davie, Fla., and Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Psoriasis: Overview and Diagnosis, in “Evidence-Based Psoriasis. Updates in Clinical Dermatology.” (Cham, Switzerland: Springer International, 2018).

2. Merola JF et al. Dermatol Ther. 2018 May;31(3):e12589.

3. Chung J et al. J Am Acad Dermatol. 2014 Oct;71(4):623-32.

Psoriasis is an immune-mediated chronic inflammatory disease characterized by well-demarcated, scaly, erythematous plaques. Those who present with the condition often have a family history, which supports recent research uncovering various genes implicated in its pathogenesis. The disease is also associated with other systemic complications, most notably cardiovascular disease.

Palmoplantar psoriasis is a unique manifestation of psoriasis appearing in an acral distribution, but can coexist with plaque psoriasis, which is commonly found on extensor surfaces. This condition is found in a small percentage of patients with psoriasis and presentation varies from hyperkeratotic plaques to pustular lesions. The pustular form is known as palmoplantar pustulosis and is within the spectrum of palmoplantar psoriasis.

Psoriasis is typically a clinical diagnosis and its severity can be measured using the Psoriasis Area and Severity Index. If biopsy is performed, the histology demonstrates parakeratosis, orthokeratosis, loss of the stratum granulosum, and dilated vasculature with an inflammatory cell infiltrate. The keratinocytes present with abnormal differentiation and hyperplasia, and the presence of foci of neutrophils known as “Munro’s microabscesses” in the stratum corneum serve as the hallmark of histological diagnosis. However, it is important to note that appearance can vary based on the stage of the lesion and the subtype of psoriasis present.

Palmoplantar psoriasis can be especially limiting and difficult to treat because of its distribution. Topical steroids, topical vitamin D analogues, and narrow band ultraviolet light therapy can be effective for less severe cases. Methotrexate, biologic treatments, and apremilast can be used for more extensive disease.

This patient is HLA-B27 positive and has uveitis. The presence of the HLA-B27 allele has been associated with inflammatory bowel disease, uveitis, psoriatic arthritis, and reactive arthritis. It has also been reported to be associated with pustular psoriasis. She responded well to topical steroids and vitamin D analogues.

This case and photo were submitted by Mr. Shapiro at Nova Southeastern University College of Osteopathic Medicine, Davie, Fla., and Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Psoriasis: Overview and Diagnosis, in “Evidence-Based Psoriasis. Updates in Clinical Dermatology.” (Cham, Switzerland: Springer International, 2018).

2. Merola JF et al. Dermatol Ther. 2018 May;31(3):e12589.

3. Chung J et al. J Am Acad Dermatol. 2014 Oct;71(4):623-32.

Psoriasis is an immune-mediated chronic inflammatory disease characterized by well-demarcated, scaly, erythematous plaques. Those who present with the condition often have a family history, which supports recent research uncovering various genes implicated in its pathogenesis. The disease is also associated with other systemic complications, most notably cardiovascular disease.

Palmoplantar psoriasis is a unique manifestation of psoriasis appearing in an acral distribution, but can coexist with plaque psoriasis, which is commonly found on extensor surfaces. This condition is found in a small percentage of patients with psoriasis and presentation varies from hyperkeratotic plaques to pustular lesions. The pustular form is known as palmoplantar pustulosis and is within the spectrum of palmoplantar psoriasis.

Psoriasis is typically a clinical diagnosis and its severity can be measured using the Psoriasis Area and Severity Index. If biopsy is performed, the histology demonstrates parakeratosis, orthokeratosis, loss of the stratum granulosum, and dilated vasculature with an inflammatory cell infiltrate. The keratinocytes present with abnormal differentiation and hyperplasia, and the presence of foci of neutrophils known as “Munro’s microabscesses” in the stratum corneum serve as the hallmark of histological diagnosis. However, it is important to note that appearance can vary based on the stage of the lesion and the subtype of psoriasis present.

Palmoplantar psoriasis can be especially limiting and difficult to treat because of its distribution. Topical steroids, topical vitamin D analogues, and narrow band ultraviolet light therapy can be effective for less severe cases. Methotrexate, biologic treatments, and apremilast can be used for more extensive disease.

This patient is HLA-B27 positive and has uveitis. The presence of the HLA-B27 allele has been associated with inflammatory bowel disease, uveitis, psoriatic arthritis, and reactive arthritis. It has also been reported to be associated with pustular psoriasis. She responded well to topical steroids and vitamin D analogues.

This case and photo were submitted by Mr. Shapiro at Nova Southeastern University College of Osteopathic Medicine, Davie, Fla., and Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Psoriasis: Overview and Diagnosis, in “Evidence-Based Psoriasis. Updates in Clinical Dermatology.” (Cham, Switzerland: Springer International, 2018).

2. Merola JF et al. Dermatol Ther. 2018 May;31(3):e12589.

3. Chung J et al. J Am Acad Dermatol. 2014 Oct;71(4):623-32.

To the Editor:

Brodalumab, a monoclonal antibody targeting IL-17RA, was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of moderate to severe chronic plaque psoriasis. The drug is the only biologic agent available for the treatment of psoriasis for which a psoriasis area severity index score of 100 is a primary end point.^1,2 Brodalumab is associated with an FDA boxed warning due to an increased risk for suicidal ideation and behavior (SIB), including completed suicides, during clinical trials.

We sought to characterize national utilization of this effective yet underutilized drug among Medicare beneficiaries by surveying the Medicare Part D Prescriber dataset.³ We tabulated brodalumab utilization statistics and characteristics of high-volume prescribers who had 11 or more annual claims for brodalumab.

Despite its associated boxed warning, the number of Medicare D claims for brodalumab increased by 1756 from 2017 to 2019, surpassing $7 million in costs by 2019. The number of beneficiaries also increased from 11 to 292—a 415.2% annual increase in beneficiaries for whom brodalumab was prescribed (Table 1).

In addition, states in the West and South had the highest utilization rates of brodalumab in 2019. There also was an increasing trend toward high-volume prescribers of brodalumab, with private practice clinicians constituting the majority (Table 2).

There was a substantial increase in advanced practice providers including nurse practitioners and physician assistants who were brodalumab prescribers. Although this trend might promote greater access to brodalumab, it is vital to ensure that advanced practice providers receive targeted training to properly understand the complexities of treatment with brodalumab.

Although the utilization of brodalumab has increased since 2017 (P<.001), it is still underutilized compared to the other IL-17 inhibitors secukinumab and ixekizumab. Secukinumab was FDA approved for the treatment of moderate to severe plaque psoriasis in 2015, followed by ixekizumab in 2016.⁴

According to the Medicare Part D database, both secukinumab and ixekizumab had a higher number of total claims and prescribers compared to brodalumab in the years of their debut.³ In 2015, there were 3593 claims for and 862 prescribers of secukinumab; in 2016, there were 1731 claims for and 681 prescribers of ixekizumab. In contrast, there were only 29 claims for and 11 prescribers of brodalumab in 2017, the year that the drug was approved by the FDA. During the same 3-year period, secukinumab and ixekizumab had a substantially greater number of claims—totals of 176,823 and 55,289, respectively—than brodalumab. The higher number of claims for secukinumab and ixekizumab compared to brodalumab may reflect clinicians’ increasing confidence in prescribing those drugs, given their long-term safety and efficacy. In addition, secukinumab and ixekizumab do not require completion of a Risk Evaluation and Mitigation Strategy (REMS) program, which makes them more readily prescribable.³

Overall, most experts agree that there is no increase in the risk for suicide associated with brodalumab compared to the general population. A 2-year pharmacovigilance report on brodalumab supports the safety of this drug.⁵ All participants who completed suicide during the clinical trials harbored an underlying psychiatric disorder or stressor(s).⁶

Although causation between brodalumab and SIB has not been demonstrated, it remains imperative that prescribers diligently assess patients’ risk of SIB and subsequently their access to appropriate psychiatric services as a precaution, if necessary. This is particularly important for private practice prescribers, who constitute the majority of Medicare D brodalumab claims, because they must ensure collaboration with a multidisciplinary team involving mental health providers. Lastly, considering that the highest number of brodalumab Medicare D claims were in western and southern states, it is critical to note that those 2 regions also harbor comparatively fewer mental health facilities that accept Medicare than other regions of the country.⁷ Prescribers in western and southern states must be mindful of mental health coverage limitations when treating psoriasis patients with brodalumab.

The increase in the number of claims, beneficiaries, and prescribers of brodalumab during its first 3 years of availability might be attributed to its efficacy and safety. On the other hand, the boxed warning and REMS associated with brodalumab might have led to underutilization of this drug compared to other IL-17 inhibitors.

Our analysis is limited by its representative restriction to Medicare patients. There also are limited data on brodalumab given its novelty. Individual attributes of prescribers with fewer than 11 annual claims for brodalumab could not be obtained because of dataset regulations; however, aggregated utilization statistics provide an indication of brodalumab prescribing patterns among all providers. Furthermore, during this analysis, data on the Medicare D database were limited to 2013 through 2020. Studies are needed to determine prescribing patterns of brodalumab since this study period.

To the Editor:

Brodalumab, a monoclonal antibody targeting IL-17RA, was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of moderate to severe chronic plaque psoriasis. The drug is the only biologic agent available for the treatment of psoriasis for which a psoriasis area severity index score of 100 is a primary end point.^1,2 Brodalumab is associated with an FDA boxed warning due to an increased risk for suicidal ideation and behavior (SIB), including completed suicides, during clinical trials.

We sought to characterize national utilization of this effective yet underutilized drug among Medicare beneficiaries by surveying the Medicare Part D Prescriber dataset.³ We tabulated brodalumab utilization statistics and characteristics of high-volume prescribers who had 11 or more annual claims for brodalumab.

Despite its associated boxed warning, the number of Medicare D claims for brodalumab increased by 1756 from 2017 to 2019, surpassing $7 million in costs by 2019. The number of beneficiaries also increased from 11 to 292—a 415.2% annual increase in beneficiaries for whom brodalumab was prescribed (Table 1).

In addition, states in the West and South had the highest utilization rates of brodalumab in 2019. There also was an increasing trend toward high-volume prescribers of brodalumab, with private practice clinicians constituting the majority (Table 2).

There was a substantial increase in advanced practice providers including nurse practitioners and physician assistants who were brodalumab prescribers. Although this trend might promote greater access to brodalumab, it is vital to ensure that advanced practice providers receive targeted training to properly understand the complexities of treatment with brodalumab.

Although the utilization of brodalumab has increased since 2017 (P<.001), it is still underutilized compared to the other IL-17 inhibitors secukinumab and ixekizumab. Secukinumab was FDA approved for the treatment of moderate to severe plaque psoriasis in 2015, followed by ixekizumab in 2016.⁴

According to the Medicare Part D database, both secukinumab and ixekizumab had a higher number of total claims and prescribers compared to brodalumab in the years of their debut.³ In 2015, there were 3593 claims for and 862 prescribers of secukinumab; in 2016, there were 1731 claims for and 681 prescribers of ixekizumab. In contrast, there were only 29 claims for and 11 prescribers of brodalumab in 2017, the year that the drug was approved by the FDA. During the same 3-year period, secukinumab and ixekizumab had a substantially greater number of claims—totals of 176,823 and 55,289, respectively—than brodalumab. The higher number of claims for secukinumab and ixekizumab compared to brodalumab may reflect clinicians’ increasing confidence in prescribing those drugs, given their long-term safety and efficacy. In addition, secukinumab and ixekizumab do not require completion of a Risk Evaluation and Mitigation Strategy (REMS) program, which makes them more readily prescribable.³

Overall, most experts agree that there is no increase in the risk for suicide associated with brodalumab compared to the general population. A 2-year pharmacovigilance report on brodalumab supports the safety of this drug.⁵ All participants who completed suicide during the clinical trials harbored an underlying psychiatric disorder or stressor(s).⁶

Although causation between brodalumab and SIB has not been demonstrated, it remains imperative that prescribers diligently assess patients’ risk of SIB and subsequently their access to appropriate psychiatric services as a precaution, if necessary. This is particularly important for private practice prescribers, who constitute the majority of Medicare D brodalumab claims, because they must ensure collaboration with a multidisciplinary team involving mental health providers. Lastly, considering that the highest number of brodalumab Medicare D claims were in western and southern states, it is critical to note that those 2 regions also harbor comparatively fewer mental health facilities that accept Medicare than other regions of the country.⁷ Prescribers in western and southern states must be mindful of mental health coverage limitations when treating psoriasis patients with brodalumab.

The increase in the number of claims, beneficiaries, and prescribers of brodalumab during its first 3 years of availability might be attributed to its efficacy and safety. On the other hand, the boxed warning and REMS associated with brodalumab might have led to underutilization of this drug compared to other IL-17 inhibitors.

Our analysis is limited by its representative restriction to Medicare patients. There also are limited data on brodalumab given its novelty. Individual attributes of prescribers with fewer than 11 annual claims for brodalumab could not be obtained because of dataset regulations; however, aggregated utilization statistics provide an indication of brodalumab prescribing patterns among all providers. Furthermore, during this analysis, data on the Medicare D database were limited to 2013 through 2020. Studies are needed to determine prescribing patterns of brodalumab since this study period.

To the Editor:

Brodalumab, a monoclonal antibody targeting IL-17RA, was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of moderate to severe chronic plaque psoriasis. The drug is the only biologic agent available for the treatment of psoriasis for which a psoriasis area severity index score of 100 is a primary end point.^1,2 Brodalumab is associated with an FDA boxed warning due to an increased risk for suicidal ideation and behavior (SIB), including completed suicides, during clinical trials.

We sought to characterize national utilization of this effective yet underutilized drug among Medicare beneficiaries by surveying the Medicare Part D Prescriber dataset.³ We tabulated brodalumab utilization statistics and characteristics of high-volume prescribers who had 11 or more annual claims for brodalumab.

Despite its associated boxed warning, the number of Medicare D claims for brodalumab increased by 1756 from 2017 to 2019, surpassing $7 million in costs by 2019. The number of beneficiaries also increased from 11 to 292—a 415.2% annual increase in beneficiaries for whom brodalumab was prescribed (Table 1).

In addition, states in the West and South had the highest utilization rates of brodalumab in 2019. There also was an increasing trend toward high-volume prescribers of brodalumab, with private practice clinicians constituting the majority (Table 2).

There was a substantial increase in advanced practice providers including nurse practitioners and physician assistants who were brodalumab prescribers. Although this trend might promote greater access to brodalumab, it is vital to ensure that advanced practice providers receive targeted training to properly understand the complexities of treatment with brodalumab.

Although the utilization of brodalumab has increased since 2017 (P<.001), it is still underutilized compared to the other IL-17 inhibitors secukinumab and ixekizumab. Secukinumab was FDA approved for the treatment of moderate to severe plaque psoriasis in 2015, followed by ixekizumab in 2016.⁴

According to the Medicare Part D database, both secukinumab and ixekizumab had a higher number of total claims and prescribers compared to brodalumab in the years of their debut.³ In 2015, there were 3593 claims for and 862 prescribers of secukinumab; in 2016, there were 1731 claims for and 681 prescribers of ixekizumab. In contrast, there were only 29 claims for and 11 prescribers of brodalumab in 2017, the year that the drug was approved by the FDA. During the same 3-year period, secukinumab and ixekizumab had a substantially greater number of claims—totals of 176,823 and 55,289, respectively—than brodalumab. The higher number of claims for secukinumab and ixekizumab compared to brodalumab may reflect clinicians’ increasing confidence in prescribing those drugs, given their long-term safety and efficacy. In addition, secukinumab and ixekizumab do not require completion of a Risk Evaluation and Mitigation Strategy (REMS) program, which makes them more readily prescribable.³

Overall, most experts agree that there is no increase in the risk for suicide associated with brodalumab compared to the general population. A 2-year pharmacovigilance report on brodalumab supports the safety of this drug.⁵ All participants who completed suicide during the clinical trials harbored an underlying psychiatric disorder or stressor(s).⁶

Although causation between brodalumab and SIB has not been demonstrated, it remains imperative that prescribers diligently assess patients’ risk of SIB and subsequently their access to appropriate psychiatric services as a precaution, if necessary. This is particularly important for private practice prescribers, who constitute the majority of Medicare D brodalumab claims, because they must ensure collaboration with a multidisciplinary team involving mental health providers. Lastly, considering that the highest number of brodalumab Medicare D claims were in western and southern states, it is critical to note that those 2 regions also harbor comparatively fewer mental health facilities that accept Medicare than other regions of the country.⁷ Prescribers in western and southern states must be mindful of mental health coverage limitations when treating psoriasis patients with brodalumab.

The increase in the number of claims, beneficiaries, and prescribers of brodalumab during its first 3 years of availability might be attributed to its efficacy and safety. On the other hand, the boxed warning and REMS associated with brodalumab might have led to underutilization of this drug compared to other IL-17 inhibitors.

Our analysis is limited by its representative restriction to Medicare patients. There also are limited data on brodalumab given its novelty. Individual attributes of prescribers with fewer than 11 annual claims for brodalumab could not be obtained because of dataset regulations; however, aggregated utilization statistics provide an indication of brodalumab prescribing patterns among all providers. Furthermore, during this analysis, data on the Medicare D database were limited to 2013 through 2020. Studies are needed to determine prescribing patterns of brodalumab since this study period.

Apremilast may have an overall benefit for patients with cardiometabolic disease and psoriasis, new results from a nonrandomized clinical trial suggest.

The trial, led by Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania, Philadelphia, found that apremilast (Otezla) has a neutral effect on aortic vascular inflammation in patients with moderate to severe psoriasis.

It also had variable, but generally favorable, associations with 68 cardiometabolic biomarkers tested and associations with reductions in both visceral and subcutaneous fat. Findings of the study were published online in JAMA Dermatology.

Fat reductions maintained at 1-year mark

The researchers found a 5%-6% reduction in subcutaneous and visceral fat at week 16 of the study that was maintained at the 1-year mark. “The fact that it was rock stable a year later is pretty encouraging,” Dr. Gelfand told this news organization.

Courtesy Dr. Joel M. Gelfand

As for effects on vascular inflammation, Dr. Gelfand said, “The good news is we didn’t find any adverse effects on aortic vascular inflammation, but we didn’t find any beneficial effects either. That was a little disappointing.

“The most surprising thing was really the effects on visceral adiposity,” he added. “I’m not aware of any other drug having demonstrated that effect.”

Michael S. Garshick, MD, a cardiologist with NYU Langone Health in New York, who was not involved with the trial, told this news organization that despite seemingly good epidemiologic evidence in observational studies that by treating psoriasis surrogates of cardiovascular risk can be reduced, this trial, like others before it, failed to reduce aortic vascular inflammation.

Courtesy NYU Langone

Seventy patients enrolled

In total, 70 patients with moderate to severe psoriasis were enrolled, 60 completed week 16, and 39 completed week 52 of the single-arm, open-label trial conducted between April 2017 and August 2021 at seven dermatology sites in the United States.

Participants took 30 mg of apremilast, an oral phosphodiesterase-4 (PDE-4) inhibitor approved for treating psoriasis and psoriatic arthritis, twice daily. Participants’ average age was 47.5 years; most were male (77.1%) and White (82.9%); almost 6% were Black. Average body mass index was 30 kg/m². Patients could not have received biologics within 90 days of study baseline (or 180 days for ustekinumab [Stelara]).

There was no change in aortic vascular inflammation at week 16 (target to background ratio, −0.02; 95% confidence interval [CI], −0.08 to 0.05; P = .61) or week 52 (target to background ratio, −0.07; 95% CI, −0.15 to 0.01; P = .09) compared with baseline.

“At week 16, there were reductions in levels of interleukin-1b, fetuin A, valine, leucine, and isoleucine,” the authors wrote, adding that at week 52, compared with baseline, “there were reductions in levels of ferritin, cholesterol efflux capacity, beta-hydroxybutyrate, acetone, and ketone bodies, and an increase in levels of apolipoprotein A-1.”

This study highlights the importance of screening, Dr. Garshick said.

He and Dr. Gelfand said people with psoriatic disease tend to be vastly underscreened for cardiovascular risk factors.

Dr. Gelfand said, “If we did what we knew worked – meaning we screened them for diabetes, we screen their cholesterol, we check their blood pressure, and we adequately treated those traditional cardiovascular risk factors, we probably could narrow the gap quite a bit” in terms of the lower life expectancy people face when they have more significant psoriasis.

Celgene was the initial funding sponsor; sponsorship was then transferred to Amgen. The authors designed, executed, analyzed, and reported the study. Celgene provided nonbinding input into study design, and Amgen provided nonbinding input into the reporting of results. Dr. Gelfand reported numerous disclosures with various pharmaceutical companies and organizations. Dr. Garshick reported no relevant financial relationships.

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

Apremilast may have an overall benefit for patients with cardiometabolic disease and psoriasis, new results from a nonrandomized clinical trial suggest.

The trial, led by Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania, Philadelphia, found that apremilast (Otezla) has a neutral effect on aortic vascular inflammation in patients with moderate to severe psoriasis.

It also had variable, but generally favorable, associations with 68 cardiometabolic biomarkers tested and associations with reductions in both visceral and subcutaneous fat. Findings of the study were published online in JAMA Dermatology.

Fat reductions maintained at 1-year mark

The researchers found a 5%-6% reduction in subcutaneous and visceral fat at week 16 of the study that was maintained at the 1-year mark. “The fact that it was rock stable a year later is pretty encouraging,” Dr. Gelfand told this news organization.

Courtesy Dr. Joel M. Gelfand

As for effects on vascular inflammation, Dr. Gelfand said, “The good news is we didn’t find any adverse effects on aortic vascular inflammation, but we didn’t find any beneficial effects either. That was a little disappointing.

“The most surprising thing was really the effects on visceral adiposity,” he added. “I’m not aware of any other drug having demonstrated that effect.”

Michael S. Garshick, MD, a cardiologist with NYU Langone Health in New York, who was not involved with the trial, told this news organization that despite seemingly good epidemiologic evidence in observational studies that by treating psoriasis surrogates of cardiovascular risk can be reduced, this trial, like others before it, failed to reduce aortic vascular inflammation.

Courtesy NYU Langone

Seventy patients enrolled

In total, 70 patients with moderate to severe psoriasis were enrolled, 60 completed week 16, and 39 completed week 52 of the single-arm, open-label trial conducted between April 2017 and August 2021 at seven dermatology sites in the United States.

Participants took 30 mg of apremilast, an oral phosphodiesterase-4 (PDE-4) inhibitor approved for treating psoriasis and psoriatic arthritis, twice daily. Participants’ average age was 47.5 years; most were male (77.1%) and White (82.9%); almost 6% were Black. Average body mass index was 30 kg/m². Patients could not have received biologics within 90 days of study baseline (or 180 days for ustekinumab [Stelara]).

There was no change in aortic vascular inflammation at week 16 (target to background ratio, −0.02; 95% confidence interval [CI], −0.08 to 0.05; P = .61) or week 52 (target to background ratio, −0.07; 95% CI, −0.15 to 0.01; P = .09) compared with baseline.

“At week 16, there were reductions in levels of interleukin-1b, fetuin A, valine, leucine, and isoleucine,” the authors wrote, adding that at week 52, compared with baseline, “there were reductions in levels of ferritin, cholesterol efflux capacity, beta-hydroxybutyrate, acetone, and ketone bodies, and an increase in levels of apolipoprotein A-1.”

This study highlights the importance of screening, Dr. Garshick said.

He and Dr. Gelfand said people with psoriatic disease tend to be vastly underscreened for cardiovascular risk factors.

Dr. Gelfand said, “If we did what we knew worked – meaning we screened them for diabetes, we screen their cholesterol, we check their blood pressure, and we adequately treated those traditional cardiovascular risk factors, we probably could narrow the gap quite a bit” in terms of the lower life expectancy people face when they have more significant psoriasis.

Celgene was the initial funding sponsor; sponsorship was then transferred to Amgen. The authors designed, executed, analyzed, and reported the study. Celgene provided nonbinding input into study design, and Amgen provided nonbinding input into the reporting of results. Dr. Gelfand reported numerous disclosures with various pharmaceutical companies and organizations. Dr. Garshick reported no relevant financial relationships.

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

Apremilast may have an overall benefit for patients with cardiometabolic disease and psoriasis, new results from a nonrandomized clinical trial suggest.

The trial, led by Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania, Philadelphia, found that apremilast (Otezla) has a neutral effect on aortic vascular inflammation in patients with moderate to severe psoriasis.

It also had variable, but generally favorable, associations with 68 cardiometabolic biomarkers tested and associations with reductions in both visceral and subcutaneous fat. Findings of the study were published online in JAMA Dermatology.

Fat reductions maintained at 1-year mark

The researchers found a 5%-6% reduction in subcutaneous and visceral fat at week 16 of the study that was maintained at the 1-year mark. “The fact that it was rock stable a year later is pretty encouraging,” Dr. Gelfand told this news organization.

Courtesy Dr. Joel M. Gelfand

As for effects on vascular inflammation, Dr. Gelfand said, “The good news is we didn’t find any adverse effects on aortic vascular inflammation, but we didn’t find any beneficial effects either. That was a little disappointing.

“The most surprising thing was really the effects on visceral adiposity,” he added. “I’m not aware of any other drug having demonstrated that effect.”

Michael S. Garshick, MD, a cardiologist with NYU Langone Health in New York, who was not involved with the trial, told this news organization that despite seemingly good epidemiologic evidence in observational studies that by treating psoriasis surrogates of cardiovascular risk can be reduced, this trial, like others before it, failed to reduce aortic vascular inflammation.

Courtesy NYU Langone

Seventy patients enrolled

In total, 70 patients with moderate to severe psoriasis were enrolled, 60 completed week 16, and 39 completed week 52 of the single-arm, open-label trial conducted between April 2017 and August 2021 at seven dermatology sites in the United States.

Participants took 30 mg of apremilast, an oral phosphodiesterase-4 (PDE-4) inhibitor approved for treating psoriasis and psoriatic arthritis, twice daily. Participants’ average age was 47.5 years; most were male (77.1%) and White (82.9%); almost 6% were Black. Average body mass index was 30 kg/m². Patients could not have received biologics within 90 days of study baseline (or 180 days for ustekinumab [Stelara]).

There was no change in aortic vascular inflammation at week 16 (target to background ratio, −0.02; 95% confidence interval [CI], −0.08 to 0.05; P = .61) or week 52 (target to background ratio, −0.07; 95% CI, −0.15 to 0.01; P = .09) compared with baseline.

“At week 16, there were reductions in levels of interleukin-1b, fetuin A, valine, leucine, and isoleucine,” the authors wrote, adding that at week 52, compared with baseline, “there were reductions in levels of ferritin, cholesterol efflux capacity, beta-hydroxybutyrate, acetone, and ketone bodies, and an increase in levels of apolipoprotein A-1.”

This study highlights the importance of screening, Dr. Garshick said.

He and Dr. Gelfand said people with psoriatic disease tend to be vastly underscreened for cardiovascular risk factors.

Dr. Gelfand said, “If we did what we knew worked – meaning we screened them for diabetes, we screen their cholesterol, we check their blood pressure, and we adequately treated those traditional cardiovascular risk factors, we probably could narrow the gap quite a bit” in terms of the lower life expectancy people face when they have more significant psoriasis.

Celgene was the initial funding sponsor; sponsorship was then transferred to Amgen. The authors designed, executed, analyzed, and reported the study. Celgene provided nonbinding input into study design, and Amgen provided nonbinding input into the reporting of results. Dr. Gelfand reported numerous disclosures with various pharmaceutical companies and organizations. Dr. Garshick reported no relevant financial relationships.

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

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

Catalin205/Thinkstock

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

Catalin205/Thinkstock

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.

Insurance coverage for specialty drugs to treat psoriasis and psoriatic arthritis varies extensively among insurance companies and often restricts coverage beyond the drug labels, according to a review of data from commercial health plans in the United States.

Although specialty medications have demonstrated effectiveness for psoriasis and psoriatic arthritis, data on insurance coverage for these indications are limited and costs are often a barrier to treatment, Christine Learned, of Tufts Medical Center, Boston, and colleagues wrote.

Catalin205/Thinkstock

In a study published in the Journal of Psoriasis and Psoriatic Arthritis, the researchers used the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes information on 158 specialty drugs covered by 17 U.S. commercial health plans, to review data on a total of 11 medications indicated for psoriasis (etanercept, adalimumab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, and apremilast) and 11 indicated for psoriatic arthritis (etanercept, adalimumab, certolizumab pegol, golimumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tofacitinib, apremilast, and abatacept) at the time of the study.

Overall, an average of 78.6% and 66.8% of insurance plans were more restrictive than the Food and Drug Association label in coverage of specialty medications for psoriasis and psoriatic arthritis, respectively.

Disease severity affected insurance coverage for psoriasis. The percentage of plans with a body surface area requirement for specialty medications ranged from 11% for apremilast to 39% for tildrakizumab, adalimumab, and certolizumab pegol. The percentage of plans with exceptions for special body locations affected by psoriasis ranged from 6% for risankizumab and brodalumab to 39% for certolizumab pegol. In addition, 6% of plans had Psoriasis Area and Severity Index requirements for etanercept and ixekizumab, and 11% had PASI requirements for adalimumab, certolizumab pegol, and tildrakizumab.

The percentage of plans with prescriber restrictions for both psoriasis and psoriatic arthritis ranged from 33% to 50%.

All 11 medications for psoriatic arthritis were approved as first-line treatments by at least one plan, compared with 3 the 11 medications with indications for psoriasis. However, medications for both psoriasis and psoriatic arthritis were approved mainly as second-line therapies.

Study designs may impact insurance coverage, as randomized, controlled trials are often used as the basis for coverage decisions for psoriasis, while coverage for psoriatic arthritis is more often based on clinical guidelines, the researchers explained.

“Our analysis confirms that variability exists for the indications of psoriasis and psoriatic arthritis,” they wrote.

The comorbidities associated with psoriasis are not always considered in insurance coverage, and coverage complications may contribute to the persistent undertreatment of many patients with psoriasis, the researchers added.

“Insurance restrictions may blunt provider and patient autonomy in selection of specialty medications and have the potential to diminish a provider’s ability to tailor regimens so as to optimize outcomes while minimizing risks,” they emphasized.

The study findings were limited by the inclusion only of publicly available policy information; therefore, some plans’ restrictions may have been missed in the analysis, the researchers said.

The results suggest that patients should review their insurance coverage of specialty drugs when choosing a health plan, and clinicians should factor in a patient’s plan a likely drug access when considering treatment options, they concluded.

The study received no outside funding. Ms. Learned had no relevant financial conflicts to disclose, but two coauthors reported financial relationships with pharmaceutical companies that manufacturer drugs for psoriasis and psoriatic arthritis.

Apremilast (Otezla), an oral drug approved for adult psoriasis, appears to reduce psoriasis severity in some children with moderate to severe psoriasis not controlled by topical therapy, according to the results of a phase 3 trial.

“Unfortunately, there are limited treatment options for pediatric patients with moderate to severe plaque psoriasis” who do not respond to or cannot use topical therapy, said study investigator Anna Belloni Fortina, MD, speaking at the annual meeting of the European Academy of Dermatology and Venereology.

“In this randomized, placebo-controlled trial, oral apremilast demonstrated effectiveness and was well tolerated,” added Dr. Belloni Fortina, of Azienda Ospedale Università Padova (Italy). “I underline oral because for children, oral administration is better than the injection treatment.”
 

Key findings

Dubbed the SPROUT study, the trial set a primary endpoint of the percentage of children with a Physician’s Global Assessment (sPGA) response after 16 weeks of treatment or placebo. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe). The study enrolled children with an sPGA greater than or equal to 3. Response was defined as a sPGA score of 0 or 1, indicating clear or almost clear skin, with at least a 2-point reduction from baseline values.

At week 16, the primary endpoint was met by 33% of 163 children treated with apremilast versus 11% of 82 children who had been given a placebo, a treatment difference of 21.7% (95% confidence interval, 11.2%-32.1%).

A greater proportion of children treated with apremilast also achieved a major secondary endpoint, a 75% or greater reduction in the Psoriasis Area and Severity Index (PASI-75) (45.4% vs. 16.1%), a treatment difference of 29.4% (95% CI, 17.8%-40.9%).
 

Results unaffected by weight and age

Regarding apremilast, “it’s important to underline that patients were dosed according to their weight,” Dr. Belloni Fortina said.

A dose of 20 mg twice daily was given to children who weighed between 20 kg and less than 50 kg, and a 30-mg twice-daily dose was given to those who weighed greater than or equal to 50 kg.

When the data were analyzed according to weight, proportionately more children on apremilast saw a sPGA response: 47.4% versus 21.8% in the lower weight and dose range and 19.2% versus 1.6% in the higher weight and dose range.

As for PASI-75, a greater proportion of children on apremilast also responded in both the lower and upper weight ranges, a respective 52.4% and 38.7% of patients, compared with 21.4% and 11% of those treated with placebo.

Data were also evaluated according to age, with a younger (aged 6-11 years) and older (age 12-17 years) group. The mean age of children was 12 years overall. Results showed a similar pattern for weight: The psoriasis of more children treated with apremilast was reduced by both measures, sPGA response, and PASI-75.
 

Safety of apremilast in children

“The overall safety profile during the placebo-controlled phase was comparable with the known safety profile of apremilast,” Dr. Belloni Fontina reported. “No new safety signals were identified.”

The rate of any adverse event was substantially higher in children given the active treatment, however, at 65% versus 41.3% for placebo.

Rates of severe and serious adverse events were low, at around 1.3%, and similar between the groups.

There was also a low rate of withdrawal because of side effects, although this was higher in the apremilast group (3.1% vs. 1.3%).

The primary reason for withdrawal of apremilast treatment were the most commonly reported adverse events: gastrointestinal disorders, including diarrhea, nausea, upper and lower abdominal pain, and vomiting. Headache, pyrexia, and nasopharyngitis were also reported.

Despite being common, most treatment-related adverse effects resolved within 3 days, Dr. Belloni Fontina said.
 

Expect further data

Further data from the trial are to be expected, because only the 16-week primary endpoint results have been released so far. The trial also included a 36-week extension phase, during which all children who had originally been randomly assigned to placebo were now eligible to be treated with apremilast, and all those who were originally given the active treatment were able to continue. This extension treatment period means that data will be available for a full year of treatment, and there will also be a further 2-week observational follow-up at the end of the trial.

The study was funded by Amgen. Dr. Belloni Fontina reported acting as an investigator and advisory board member for and receiving honoraria from Amgen, Galderma, Leo Pharma, and Pfizer. She also reported speaking on behalf of Pierre-Fabre and Galderma.

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

Apremilast (Otezla), an oral drug approved for adult psoriasis, appears to reduce psoriasis severity in some children with moderate to severe psoriasis not controlled by topical therapy, according to the results of a phase 3 trial.

“Unfortunately, there are limited treatment options for pediatric patients with moderate to severe plaque psoriasis” who do not respond to or cannot use topical therapy, said study investigator Anna Belloni Fortina, MD, speaking at the annual meeting of the European Academy of Dermatology and Venereology.

“In this randomized, placebo-controlled trial, oral apremilast demonstrated effectiveness and was well tolerated,” added Dr. Belloni Fortina, of Azienda Ospedale Università Padova (Italy). “I underline oral because for children, oral administration is better than the injection treatment.”
 

Key findings

Dubbed the SPROUT study, the trial set a primary endpoint of the percentage of children with a Physician’s Global Assessment (sPGA) response after 16 weeks of treatment or placebo. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe). The study enrolled children with an sPGA greater than or equal to 3. Response was defined as a sPGA score of 0 or 1, indicating clear or almost clear skin, with at least a 2-point reduction from baseline values.

At week 16, the primary endpoint was met by 33% of 163 children treated with apremilast versus 11% of 82 children who had been given a placebo, a treatment difference of 21.7% (95% confidence interval, 11.2%-32.1%).

A greater proportion of children treated with apremilast also achieved a major secondary endpoint, a 75% or greater reduction in the Psoriasis Area and Severity Index (PASI-75) (45.4% vs. 16.1%), a treatment difference of 29.4% (95% CI, 17.8%-40.9%).
 

Results unaffected by weight and age

Regarding apremilast, “it’s important to underline that patients were dosed according to their weight,” Dr. Belloni Fortina said.

A dose of 20 mg twice daily was given to children who weighed between 20 kg and less than 50 kg, and a 30-mg twice-daily dose was given to those who weighed greater than or equal to 50 kg.

When the data were analyzed according to weight, proportionately more children on apremilast saw a sPGA response: 47.4% versus 21.8% in the lower weight and dose range and 19.2% versus 1.6% in the higher weight and dose range.

As for PASI-75, a greater proportion of children on apremilast also responded in both the lower and upper weight ranges, a respective 52.4% and 38.7% of patients, compared with 21.4% and 11% of those treated with placebo.

Data were also evaluated according to age, with a younger (aged 6-11 years) and older (age 12-17 years) group. The mean age of children was 12 years overall. Results showed a similar pattern for weight: The psoriasis of more children treated with apremilast was reduced by both measures, sPGA response, and PASI-75.
 

Safety of apremilast in children

“The overall safety profile during the placebo-controlled phase was comparable with the known safety profile of apremilast,” Dr. Belloni Fontina reported. “No new safety signals were identified.”

The rate of any adverse event was substantially higher in children given the active treatment, however, at 65% versus 41.3% for placebo.

Rates of severe and serious adverse events were low, at around 1.3%, and similar between the groups.

There was also a low rate of withdrawal because of side effects, although this was higher in the apremilast group (3.1% vs. 1.3%).

The primary reason for withdrawal of apremilast treatment were the most commonly reported adverse events: gastrointestinal disorders, including diarrhea, nausea, upper and lower abdominal pain, and vomiting. Headache, pyrexia, and nasopharyngitis were also reported.

Despite being common, most treatment-related adverse effects resolved within 3 days, Dr. Belloni Fontina said.
 

Expect further data

Further data from the trial are to be expected, because only the 16-week primary endpoint results have been released so far. The trial also included a 36-week extension phase, during which all children who had originally been randomly assigned to placebo were now eligible to be treated with apremilast, and all those who were originally given the active treatment were able to continue. This extension treatment period means that data will be available for a full year of treatment, and there will also be a further 2-week observational follow-up at the end of the trial.

The study was funded by Amgen. Dr. Belloni Fontina reported acting as an investigator and advisory board member for and receiving honoraria from Amgen, Galderma, Leo Pharma, and Pfizer. She also reported speaking on behalf of Pierre-Fabre and Galderma.

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

Apremilast (Otezla), an oral drug approved for adult psoriasis, appears to reduce psoriasis severity in some children with moderate to severe psoriasis not controlled by topical therapy, according to the results of a phase 3 trial.

“Unfortunately, there are limited treatment options for pediatric patients with moderate to severe plaque psoriasis” who do not respond to or cannot use topical therapy, said study investigator Anna Belloni Fortina, MD, speaking at the annual meeting of the European Academy of Dermatology and Venereology.

“In this randomized, placebo-controlled trial, oral apremilast demonstrated effectiveness and was well tolerated,” added Dr. Belloni Fortina, of Azienda Ospedale Università Padova (Italy). “I underline oral because for children, oral administration is better than the injection treatment.”
 

Key findings

Dubbed the SPROUT study, the trial set a primary endpoint of the percentage of children with a Physician’s Global Assessment (sPGA) response after 16 weeks of treatment or placebo. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe). The study enrolled children with an sPGA greater than or equal to 3. Response was defined as a sPGA score of 0 or 1, indicating clear or almost clear skin, with at least a 2-point reduction from baseline values.

At week 16, the primary endpoint was met by 33% of 163 children treated with apremilast versus 11% of 82 children who had been given a placebo, a treatment difference of 21.7% (95% confidence interval, 11.2%-32.1%).

A greater proportion of children treated with apremilast also achieved a major secondary endpoint, a 75% or greater reduction in the Psoriasis Area and Severity Index (PASI-75) (45.4% vs. 16.1%), a treatment difference of 29.4% (95% CI, 17.8%-40.9%).
 

Results unaffected by weight and age

Regarding apremilast, “it’s important to underline that patients were dosed according to their weight,” Dr. Belloni Fortina said.

A dose of 20 mg twice daily was given to children who weighed between 20 kg and less than 50 kg, and a 30-mg twice-daily dose was given to those who weighed greater than or equal to 50 kg.

When the data were analyzed according to weight, proportionately more children on apremilast saw a sPGA response: 47.4% versus 21.8% in the lower weight and dose range and 19.2% versus 1.6% in the higher weight and dose range.

As for PASI-75, a greater proportion of children on apremilast also responded in both the lower and upper weight ranges, a respective 52.4% and 38.7% of patients, compared with 21.4% and 11% of those treated with placebo.

Data were also evaluated according to age, with a younger (aged 6-11 years) and older (age 12-17 years) group. The mean age of children was 12 years overall. Results showed a similar pattern for weight: The psoriasis of more children treated with apremilast was reduced by both measures, sPGA response, and PASI-75.
 

Safety of apremilast in children

“The overall safety profile during the placebo-controlled phase was comparable with the known safety profile of apremilast,” Dr. Belloni Fontina reported. “No new safety signals were identified.”

The rate of any adverse event was substantially higher in children given the active treatment, however, at 65% versus 41.3% for placebo.

Rates of severe and serious adverse events were low, at around 1.3%, and similar between the groups.

There was also a low rate of withdrawal because of side effects, although this was higher in the apremilast group (3.1% vs. 1.3%).

The primary reason for withdrawal of apremilast treatment were the most commonly reported adverse events: gastrointestinal disorders, including diarrhea, nausea, upper and lower abdominal pain, and vomiting. Headache, pyrexia, and nasopharyngitis were also reported.

Despite being common, most treatment-related adverse effects resolved within 3 days, Dr. Belloni Fontina said.
 

Expect further data

Further data from the trial are to be expected, because only the 16-week primary endpoint results have been released so far. The trial also included a 36-week extension phase, during which all children who had originally been randomly assigned to placebo were now eligible to be treated with apremilast, and all those who were originally given the active treatment were able to continue. This extension treatment period means that data will be available for a full year of treatment, and there will also be a further 2-week observational follow-up at the end of the trial.

The study was funded by Amgen. Dr. Belloni Fontina reported acting as an investigator and advisory board member for and receiving honoraria from Amgen, Galderma, Leo Pharma, and Pfizer. She also reported speaking on behalf of Pierre-Fabre and Galderma.

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

The psoriasis clinical trials listed below are all phase 3 and recruiting participants as of July 19, 2022. For additional information on the study design, eligibility criteria, and contacts/locations, visit ClinicalTrials.gov.

GENERALIZED PUSTULAR PSORIASIS

Long-Term Safety and Efficacy of Imsidolimab (ANB019) in Subjects With Generalized Pustular Psoriasis (GEMINI2)

ClinicalTrials.gov Identifier: NCT05366855

An Expanded Access Trial in Japan to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have no Other Treatment Options

ClinicalTrials.gov Identifier: NCT05200247

An Expanded Access Program in China to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have No Other Treatment Options

ClinicalTrials.gov Identifier: NCT05239039

Study to Evaluate the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Subjects With GPP (GEMINI1)

ClinicalTrials.gov Identifier: NCT05352893

NAIL PSORIASIS

Efficacy and Safety Study of Tildrakizumab in the Treatment of Nail Psoriasis

ClinicalTrials.gov Identifier: NCT03897075

PALMOPLANTAR PUSTULOSIS

Phase 3, Randomized Study of Apremilast in Japanese Participants With Palmoplantar Pustulosis (PPP)

ClinicalTrials.gov Identifier: NCT05174065

PLAQUE PSORIASIS

A Long-term Extension Study of Apremilast (CC-10004) in Pediatric Subjects From 6 Through 17 Years of Age With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04175613

A Phase III Efficacy and Safety Study of Hemay005 in Subjects With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04839328

A Study of Subcutaneous Risankizumab Injection for Pediatric Participants With Moderate to Severe Plaque Psoriasis to Assess Change in Disease Symptoms

ClinicalTrials.gov Identifier: NCT04435600

A Study to Evaluate the Drug Levels, Efficacy and Safety of Deucravacitinib in Adolescent Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04772079

Investigator Initiated Trial to Study Duobrii® Lotion in the Treatment of Mild Plaque Psoriasis in Adults

ClinicalTrials.gov Identifier: NCT05203315

Comparative Study of BAT2206 With Stelara® in Patients With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04728360

A Study to Evaluate the Efficacy and Safety of Bimekizumab in Adult Korean Study Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT05020249

Comparing Efficacy and Safety of Bmab 1200 and Stelara in Patients With Moderate to Severe Chronic Plaque Psoriasis (STELLAR-2)

ClinicalTrials.gov Identifier: NCT05335356

A Study to Evaluate the Efficacy, Safety, and Drug Concentration of Certolizumab Pegol (CZP) in Children and Adolescent Study Participants With Moderate to Severe Chronic Plaque Psoriasis (PSO)(CIMcare)

ClinicalTrials.gov Identifier: NCT04123795

A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT03997786

Tapinarof for the Treatment of Plaque Psoriasis in Pediatric Subjects

ClinicalTrials.gov Identifier: NCT05172726

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Guselkumab for the Treatment of Chronic Plaque Psoriasis in Pediatric Participants (PROTOSTAR)

ClinicalTrials.gov Identifier: NCT03451851

PSORIATIC ARTHRITIS

Efficacy of Secukinumab Compared to Ustekinumab in Adults With Active Psoriatic Arthritis and Failure of TNFα-Inhibitor Treatment (AgAIN)

ClinicalTrials.gov Identifier: NCT04632927

A Long-term Extension Study of Ustekinumab in Pediatric Participants (UNITED)

ClinicalTrials.gov Identifier: NCT05092269

A Study of Ustekinumab or Guselkumab in Pediatric Participants With Active Juvenile Psoriatic Arthritis (PSUMMIT-Jr)

ClinicalTrials.gov Identifier: NCT05083182

Comparative Study of BAT2506 With Simponi® in Participants With Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT05046431

Long Term Evaluation of Safety and Efficacy of Tildrakizumab in Patients With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04991116

To Evaluate the Efficacy and Safety of SHR0302 Tablet in Subjects of Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04957550

PSORIATIC ARTHRITIS (continued)

Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent (SOLSTICE)

ClinicalTrials.gov Identifier: NCT04936308

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease-modifying Anti-rheumatic Drugs

ClinicalTrials.gov Identifier: NCT04908202

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease Modifying Anti-rheumatic Drugs or Had Previously Received TNFα Inhibitor Treatment

ClinicalTrials.gov Identifier: NCT04908189

A Study of Guselkumab in Participants With Active Psoriatic Arthritis (APEX) ClinicalTrials.gov Identifier: NCT04882098 Apremilast Pediatric Study in Children With Active Juvenile Psoriatic Arthritis (PEAPOD)

ClinicalTrials.gov Identifier: NCT04804553

Impact of Tapering Immunosuppressants on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04610476

A Study of Ixekizumab (LY2439821) in Children With Juvenile Idiopathic Arthritis Categories of Enthesitis-related Arthritis (Including Juvenile Onset Ankylosing Spondylitis) and Juvenile Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04527380

Efficacy and Safety of Tildrakizumab Compared to Placebo in Subjects With Active Psoriatic Arthritis I (INSPIRE 1)

ClinicalTrials.gov Identifier: NCT04314544

Efficacy and Safety of Tildrakizumab Compared to Placebo in Anti- TNF naïve Subjects With Active Psoriatic Arthritis II (INSPIRE 2)

ClinicalTrials.gov Identifier: NCT04314531

The psoriasis clinical trials listed below are all phase 3 and recruiting participants as of July 19, 2022. For additional information on the study design, eligibility criteria, and contacts/locations, visit ClinicalTrials.gov.

GENERALIZED PUSTULAR PSORIASIS

Long-Term Safety and Efficacy of Imsidolimab (ANB019) in Subjects With Generalized Pustular Psoriasis (GEMINI2)

ClinicalTrials.gov Identifier: NCT05366855

An Expanded Access Trial in Japan to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have no Other Treatment Options

ClinicalTrials.gov Identifier: NCT05200247

An Expanded Access Program in China to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have No Other Treatment Options

ClinicalTrials.gov Identifier: NCT05239039

Study to Evaluate the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Subjects With GPP (GEMINI1)

ClinicalTrials.gov Identifier: NCT05352893

NAIL PSORIASIS

Efficacy and Safety Study of Tildrakizumab in the Treatment of Nail Psoriasis

ClinicalTrials.gov Identifier: NCT03897075

PALMOPLANTAR PUSTULOSIS

Phase 3, Randomized Study of Apremilast in Japanese Participants With Palmoplantar Pustulosis (PPP)

ClinicalTrials.gov Identifier: NCT05174065

PLAQUE PSORIASIS

A Long-term Extension Study of Apremilast (CC-10004) in Pediatric Subjects From 6 Through 17 Years of Age With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04175613

A Phase III Efficacy and Safety Study of Hemay005 in Subjects With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04839328

A Study of Subcutaneous Risankizumab Injection for Pediatric Participants With Moderate to Severe Plaque Psoriasis to Assess Change in Disease Symptoms

ClinicalTrials.gov Identifier: NCT04435600

A Study to Evaluate the Drug Levels, Efficacy and Safety of Deucravacitinib in Adolescent Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04772079

Investigator Initiated Trial to Study Duobrii® Lotion in the Treatment of Mild Plaque Psoriasis in Adults

ClinicalTrials.gov Identifier: NCT05203315

Comparative Study of BAT2206 With Stelara® in Patients With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04728360

A Study to Evaluate the Efficacy and Safety of Bimekizumab in Adult Korean Study Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT05020249

Comparing Efficacy and Safety of Bmab 1200 and Stelara in Patients With Moderate to Severe Chronic Plaque Psoriasis (STELLAR-2)

ClinicalTrials.gov Identifier: NCT05335356

A Study to Evaluate the Efficacy, Safety, and Drug Concentration of Certolizumab Pegol (CZP) in Children and Adolescent Study Participants With Moderate to Severe Chronic Plaque Psoriasis (PSO)(CIMcare)

ClinicalTrials.gov Identifier: NCT04123795

A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT03997786

Tapinarof for the Treatment of Plaque Psoriasis in Pediatric Subjects

ClinicalTrials.gov Identifier: NCT05172726

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Guselkumab for the Treatment of Chronic Plaque Psoriasis in Pediatric Participants (PROTOSTAR)

ClinicalTrials.gov Identifier: NCT03451851

PSORIATIC ARTHRITIS

Efficacy of Secukinumab Compared to Ustekinumab in Adults With Active Psoriatic Arthritis and Failure of TNFα-Inhibitor Treatment (AgAIN)

ClinicalTrials.gov Identifier: NCT04632927

A Long-term Extension Study of Ustekinumab in Pediatric Participants (UNITED)

ClinicalTrials.gov Identifier: NCT05092269

A Study of Ustekinumab or Guselkumab in Pediatric Participants With Active Juvenile Psoriatic Arthritis (PSUMMIT-Jr)

ClinicalTrials.gov Identifier: NCT05083182

Comparative Study of BAT2506 With Simponi® in Participants With Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT05046431

Long Term Evaluation of Safety and Efficacy of Tildrakizumab in Patients With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04991116

To Evaluate the Efficacy and Safety of SHR0302 Tablet in Subjects of Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04957550

PSORIATIC ARTHRITIS (continued)

Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent (SOLSTICE)

ClinicalTrials.gov Identifier: NCT04936308

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease-modifying Anti-rheumatic Drugs

ClinicalTrials.gov Identifier: NCT04908202

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease Modifying Anti-rheumatic Drugs or Had Previously Received TNFα Inhibitor Treatment

ClinicalTrials.gov Identifier: NCT04908189

A Study of Guselkumab in Participants With Active Psoriatic Arthritis (APEX) ClinicalTrials.gov Identifier: NCT04882098 Apremilast Pediatric Study in Children With Active Juvenile Psoriatic Arthritis (PEAPOD)

ClinicalTrials.gov Identifier: NCT04804553

Impact of Tapering Immunosuppressants on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04610476

A Study of Ixekizumab (LY2439821) in Children With Juvenile Idiopathic Arthritis Categories of Enthesitis-related Arthritis (Including Juvenile Onset Ankylosing Spondylitis) and Juvenile Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04527380

Efficacy and Safety of Tildrakizumab Compared to Placebo in Subjects With Active Psoriatic Arthritis I (INSPIRE 1)

ClinicalTrials.gov Identifier: NCT04314544

Efficacy and Safety of Tildrakizumab Compared to Placebo in Anti- TNF naïve Subjects With Active Psoriatic Arthritis II (INSPIRE 2)

ClinicalTrials.gov Identifier: NCT04314531

The psoriasis clinical trials listed below are all phase 3 and recruiting participants as of July 19, 2022. For additional information on the study design, eligibility criteria, and contacts/locations, visit ClinicalTrials.gov.

GENERALIZED PUSTULAR PSORIASIS

Long-Term Safety and Efficacy of Imsidolimab (ANB019) in Subjects With Generalized Pustular Psoriasis (GEMINI2)

ClinicalTrials.gov Identifier: NCT05366855

An Expanded Access Trial in Japan to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have no Other Treatment Options

ClinicalTrials.gov Identifier: NCT05200247

An Expanded Access Program in China to Provide Spesolimab to People With a Flare-up in Generalized Pustular Psoriasis Who Have No Other Treatment Options

ClinicalTrials.gov Identifier: NCT05239039

Study to Evaluate the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Subjects With GPP (GEMINI1)

ClinicalTrials.gov Identifier: NCT05352893

NAIL PSORIASIS

Efficacy and Safety Study of Tildrakizumab in the Treatment of Nail Psoriasis

ClinicalTrials.gov Identifier: NCT03897075

PALMOPLANTAR PUSTULOSIS

Phase 3, Randomized Study of Apremilast in Japanese Participants With Palmoplantar Pustulosis (PPP)

ClinicalTrials.gov Identifier: NCT05174065

PLAQUE PSORIASIS

A Long-term Extension Study of Apremilast (CC-10004) in Pediatric Subjects From 6 Through 17 Years of Age With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04175613

A Phase III Efficacy and Safety Study of Hemay005 in Subjects With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04839328

A Study of Subcutaneous Risankizumab Injection for Pediatric Participants With Moderate to Severe Plaque Psoriasis to Assess Change in Disease Symptoms

ClinicalTrials.gov Identifier: NCT04435600

A Study to Evaluate the Drug Levels, Efficacy and Safety of Deucravacitinib in Adolescent Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04772079

Investigator Initiated Trial to Study Duobrii® Lotion in the Treatment of Mild Plaque Psoriasis in Adults

ClinicalTrials.gov Identifier: NCT05203315

Comparative Study of BAT2206 With Stelara® in Patients With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT04728360

A Study to Evaluate the Efficacy and Safety of Bimekizumab in Adult Korean Study Participants With Moderate to Severe Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT05020249

Comparing Efficacy and Safety of Bmab 1200 and Stelara in Patients With Moderate to Severe Chronic Plaque Psoriasis (STELLAR-2)

ClinicalTrials.gov Identifier: NCT05335356

A Study to Evaluate the Efficacy, Safety, and Drug Concentration of Certolizumab Pegol (CZP) in Children and Adolescent Study Participants With Moderate to Severe Chronic Plaque Psoriasis (PSO)(CIMcare)

ClinicalTrials.gov Identifier: NCT04123795

A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis

ClinicalTrials.gov Identifier: NCT03997786

Tapinarof for the Treatment of Plaque Psoriasis in Pediatric Subjects

ClinicalTrials.gov Identifier: NCT05172726

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Guselkumab for the Treatment of Chronic Plaque Psoriasis in Pediatric Participants (PROTOSTAR)

ClinicalTrials.gov Identifier: NCT03451851

PSORIATIC ARTHRITIS

Efficacy of Secukinumab Compared to Ustekinumab in Adults With Active Psoriatic Arthritis and Failure of TNFα-Inhibitor Treatment (AgAIN)

ClinicalTrials.gov Identifier: NCT04632927

A Long-term Extension Study of Ustekinumab in Pediatric Participants (UNITED)

ClinicalTrials.gov Identifier: NCT05092269

A Study of Ustekinumab or Guselkumab in Pediatric Participants With Active Juvenile Psoriatic Arthritis (PSUMMIT-Jr)

ClinicalTrials.gov Identifier: NCT05083182

Comparative Study of BAT2506 With Simponi® in Participants With Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT05046431

Long Term Evaluation of Safety and Efficacy of Tildrakizumab in Patients With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04991116

To Evaluate the Efficacy and Safety of SHR0302 Tablet in Subjects of Active Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04957550

PSORIATIC ARTHRITIS (continued)

Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent (SOLSTICE)

ClinicalTrials.gov Identifier: NCT04936308

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease-modifying Anti-rheumatic Drugs

ClinicalTrials.gov Identifier: NCT04908202

A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease Modifying Anti-rheumatic Drugs or Had Previously Received TNFα Inhibitor Treatment

ClinicalTrials.gov Identifier: NCT04908189

A Study of Guselkumab in Participants With Active Psoriatic Arthritis (APEX) ClinicalTrials.gov Identifier: NCT04882098 Apremilast Pediatric Study in Children With Active Juvenile Psoriatic Arthritis (PEAPOD)

ClinicalTrials.gov Identifier: NCT04804553

Impact of Tapering Immunosuppressants on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04610476

A Study of Ixekizumab (LY2439821) in Children With Juvenile Idiopathic Arthritis Categories of Enthesitis-related Arthritis (Including Juvenile Onset Ankylosing Spondylitis) and Juvenile Psoriatic Arthritis

ClinicalTrials.gov Identifier: NCT04527380

Efficacy and Safety of Tildrakizumab Compared to Placebo in Subjects With Active Psoriatic Arthritis I (INSPIRE 1)

ClinicalTrials.gov Identifier: NCT04314544

Efficacy and Safety of Tildrakizumab Compared to Placebo in Anti- TNF naïve Subjects With Active Psoriatic Arthritis II (INSPIRE 2)

ClinicalTrials.gov Identifier: NCT04314531

An analysis of postmarketing suicide data shows that the risk of suicide associated with brodalumab use is similar to that of other biologics prescribed for psoriasis.

The Food and Drug Administration approved brodalumab (Siliq) in 2017 for treatment of moderate to severe plaque psoriasis with a boxed warning for suicidal ideation and behavior and an associated Risk Evaluation and Mitigation Strategies (REMS) program indicating an increased risk of suicidality.

Half a decade later, “the available worldwide data do not support the notion that brodalumab has a unique risk of increased suicides,” senior investigator John Koo, MD, and coinvestigators at the University of California, San Francisco, wrote in a preproof article in JAAD International, noting that postmarketing data are “often considered a better reflection of real-world outcomes than clinical trials.”

The researchers extracted data through the end of 2021 on the number of completed suicides for brodalumab and ten other biologics approved for psoriasis from the FDA’s Adverse Events Reporting System (FAERS), an international publicly available database. The researchers included suicide data on the biologics for all indications.

The authors contacted pharmaceutical companies to determine the total number of patients prescribed each drug, securing mostly “best estimates” data on 5 of the 11 biologics available for psoriasis. The researchers then calculated the number of completed suicides per total number of prescribed patients.

For brodalumab, across 20,871 total prescriptions, there was only one verifiable suicide. It occurred in a Japanese man with terminal cancer and no nearby relatives 36 days after his first dose. The suicide rate for brodalumab was similar to that of ixekizumab, secukinumab, infliximab, and adalimumab.

“Brodalumab is a very efficacious agent and may have the fastest onset of action, yet its usage is minimal compared to the other agents because of this ‘black box’ warning ... despite the fact that it’s the least expensive of any biologic,” Dr. Koo, professor of dermatology and director of the Psoriasis and Skin Treatment Center, University of California, San Francisco, said in an interview.

Dr. Koo, who is board-certified in both dermatology and psychiatry, said he believes the boxed warning was never warranted. All three of the verified completed suicides that occurred during clinical trials of brodalumab for psoriasis were in people who had underlying psychiatric disorders or significant stressors, such as going to jail in one case, and depression and significant isolation in another, he said.

(An analysis of psychiatric adverse events during the psoriasis clinical trials, involving more than 4,000 patients, was published online Oct. 4, 2017, in the Journal of the American Academy of Dermatology.

George Han, MD, PhD, associate professor and director of research and teledermatology at the Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, N.Y., who was not involved in the research, said the new data is reassuring.

“We sometimes put it into context [in thinking and counseling about risk] that in the trials for brodalumab, the number of suicide attempts [versus completed suicides] was not an outlier,” he said. “But it’s hard to know what to make of that, so this piece of knowledge that the postmarketing data show there’s no safety signal should give people a lot of reassurance.”

Dr. Han said he has used the medication, a fully human anti-interleukin 17 receptor A monoclonal antibody, in many patients who “have not done so well on other biologics and it’s been a lifesaver ... a couple who have switched over have maintained the longest level of clearance they’ve had with anything. It’s quite striking.”

The efficacy stems at least partly from its mechanism of blocking all cytokines in the IL-17 family – including those involved in the “feedback loops that perpetuate psoriasis” – rather than just one as other biologics do, Dr. Han said.

Usage of the drug has been hindered by the black box warning and REMS program, not only because of the extra steps required and hesitation potentially evoked, but because samples are not available, and because the “formulary access is not what it could have been otherwise,” he noted.

The Siliq REMS patient enrollment form requires patients to pledge awareness of the fact that suicidal thoughts and behaviors have occurred in treated patients and that they should seek medical attention if they experience suicidal thoughts or new or worsening depression, anxiety, or other mood changes. Prescribers must be certified with the program and must pledge on each enrollment form that they have counseled their patients.

The box warning states that there is no established causal association between treatment with brodalumab and increased risk for suicidal ideation and behaviors (SIB).

Individuals with psoriasis are an “already vulnerable population” who have been shown in reviews and meta-analyses to have a higher prevalence of depression and a higher risk of SIB than those without the disease, Dr. Koo and colleagues wrote in a narrative review published in Cutis .

Regardless of therapy, they wrote in the review, dermatologists should assess for any history of depression and SIB, and evaluate for signs and symptoms of current depression and SIB, referring patients as necessary to primary care or mental health care.

In the psoriasis trials, brodalumab treatment appeared to improve symptoms of depression and anxiety – a finding consistent with the effects reported for other biologic therapies, they wrote.

The first author on the newly published preproof is Samuel Yeroushalmi, BS, a fourth-year medical student at George Washington University, Washington.

Siliq is marketed by Valeant Pharmaceuticals.

Dr. Koo disclosed that he is an adviser/consultant/speaker for numerous pharmaceutical companies, but not those that were involved in the development of brodalumab. Dr. Han said he has relationships with numerous companies, including those that have developed brodalumab and other biologic agents used for psoriasis. The authors declared funding sources as none.

An analysis of postmarketing suicide data shows that the risk of suicide associated with brodalumab use is similar to that of other biologics prescribed for psoriasis.

The Food and Drug Administration approved brodalumab (Siliq) in 2017 for treatment of moderate to severe plaque psoriasis with a boxed warning for suicidal ideation and behavior and an associated Risk Evaluation and Mitigation Strategies (REMS) program indicating an increased risk of suicidality.

Half a decade later, “the available worldwide data do not support the notion that brodalumab has a unique risk of increased suicides,” senior investigator John Koo, MD, and coinvestigators at the University of California, San Francisco, wrote in a preproof article in JAAD International, noting that postmarketing data are “often considered a better reflection of real-world outcomes than clinical trials.”

The researchers extracted data through the end of 2021 on the number of completed suicides for brodalumab and ten other biologics approved for psoriasis from the FDA’s Adverse Events Reporting System (FAERS), an international publicly available database. The researchers included suicide data on the biologics for all indications.

The authors contacted pharmaceutical companies to determine the total number of patients prescribed each drug, securing mostly “best estimates” data on 5 of the 11 biologics available for psoriasis. The researchers then calculated the number of completed suicides per total number of prescribed patients.

For brodalumab, across 20,871 total prescriptions, there was only one verifiable suicide. It occurred in a Japanese man with terminal cancer and no nearby relatives 36 days after his first dose. The suicide rate for brodalumab was similar to that of ixekizumab, secukinumab, infliximab, and adalimumab.

“Brodalumab is a very efficacious agent and may have the fastest onset of action, yet its usage is minimal compared to the other agents because of this ‘black box’ warning ... despite the fact that it’s the least expensive of any biologic,” Dr. Koo, professor of dermatology and director of the Psoriasis and Skin Treatment Center, University of California, San Francisco, said in an interview.

Dr. Koo, who is board-certified in both dermatology and psychiatry, said he believes the boxed warning was never warranted. All three of the verified completed suicides that occurred during clinical trials of brodalumab for psoriasis were in people who had underlying psychiatric disorders or significant stressors, such as going to jail in one case, and depression and significant isolation in another, he said.

(An analysis of psychiatric adverse events during the psoriasis clinical trials, involving more than 4,000 patients, was published online Oct. 4, 2017, in the Journal of the American Academy of Dermatology.

George Han, MD, PhD, associate professor and director of research and teledermatology at the Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, N.Y., who was not involved in the research, said the new data is reassuring.

“We sometimes put it into context [in thinking and counseling about risk] that in the trials for brodalumab, the number of suicide attempts [versus completed suicides] was not an outlier,” he said. “But it’s hard to know what to make of that, so this piece of knowledge that the postmarketing data show there’s no safety signal should give people a lot of reassurance.”

Dr. Han said he has used the medication, a fully human anti-interleukin 17 receptor A monoclonal antibody, in many patients who “have not done so well on other biologics and it’s been a lifesaver ... a couple who have switched over have maintained the longest level of clearance they’ve had with anything. It’s quite striking.”

The efficacy stems at least partly from its mechanism of blocking all cytokines in the IL-17 family – including those involved in the “feedback loops that perpetuate psoriasis” – rather than just one as other biologics do, Dr. Han said.

Usage of the drug has been hindered by the black box warning and REMS program, not only because of the extra steps required and hesitation potentially evoked, but because samples are not available, and because the “formulary access is not what it could have been otherwise,” he noted.

The Siliq REMS patient enrollment form requires patients to pledge awareness of the fact that suicidal thoughts and behaviors have occurred in treated patients and that they should seek medical attention if they experience suicidal thoughts or new or worsening depression, anxiety, or other mood changes. Prescribers must be certified with the program and must pledge on each enrollment form that they have counseled their patients.

The box warning states that there is no established causal association between treatment with brodalumab and increased risk for suicidal ideation and behaviors (SIB).

Individuals with psoriasis are an “already vulnerable population” who have been shown in reviews and meta-analyses to have a higher prevalence of depression and a higher risk of SIB than those without the disease, Dr. Koo and colleagues wrote in a narrative review published in Cutis .

Regardless of therapy, they wrote in the review, dermatologists should assess for any history of depression and SIB, and evaluate for signs and symptoms of current depression and SIB, referring patients as necessary to primary care or mental health care.

In the psoriasis trials, brodalumab treatment appeared to improve symptoms of depression and anxiety – a finding consistent with the effects reported for other biologic therapies, they wrote.

The first author on the newly published preproof is Samuel Yeroushalmi, BS, a fourth-year medical student at George Washington University, Washington.

Siliq is marketed by Valeant Pharmaceuticals.

Dr. Koo disclosed that he is an adviser/consultant/speaker for numerous pharmaceutical companies, but not those that were involved in the development of brodalumab. Dr. Han said he has relationships with numerous companies, including those that have developed brodalumab and other biologic agents used for psoriasis. The authors declared funding sources as none.

An analysis of postmarketing suicide data shows that the risk of suicide associated with brodalumab use is similar to that of other biologics prescribed for psoriasis.

The Food and Drug Administration approved brodalumab (Siliq) in 2017 for treatment of moderate to severe plaque psoriasis with a boxed warning for suicidal ideation and behavior and an associated Risk Evaluation and Mitigation Strategies (REMS) program indicating an increased risk of suicidality.

Half a decade later, “the available worldwide data do not support the notion that brodalumab has a unique risk of increased suicides,” senior investigator John Koo, MD, and coinvestigators at the University of California, San Francisco, wrote in a preproof article in JAAD International, noting that postmarketing data are “often considered a better reflection of real-world outcomes than clinical trials.”

The researchers extracted data through the end of 2021 on the number of completed suicides for brodalumab and ten other biologics approved for psoriasis from the FDA’s Adverse Events Reporting System (FAERS), an international publicly available database. The researchers included suicide data on the biologics for all indications.

The authors contacted pharmaceutical companies to determine the total number of patients prescribed each drug, securing mostly “best estimates” data on 5 of the 11 biologics available for psoriasis. The researchers then calculated the number of completed suicides per total number of prescribed patients.

For brodalumab, across 20,871 total prescriptions, there was only one verifiable suicide. It occurred in a Japanese man with terminal cancer and no nearby relatives 36 days after his first dose. The suicide rate for brodalumab was similar to that of ixekizumab, secukinumab, infliximab, and adalimumab.

“Brodalumab is a very efficacious agent and may have the fastest onset of action, yet its usage is minimal compared to the other agents because of this ‘black box’ warning ... despite the fact that it’s the least expensive of any biologic,” Dr. Koo, professor of dermatology and director of the Psoriasis and Skin Treatment Center, University of California, San Francisco, said in an interview.

Dr. Koo, who is board-certified in both dermatology and psychiatry, said he believes the boxed warning was never warranted. All three of the verified completed suicides that occurred during clinical trials of brodalumab for psoriasis were in people who had underlying psychiatric disorders or significant stressors, such as going to jail in one case, and depression and significant isolation in another, he said.

(An analysis of psychiatric adverse events during the psoriasis clinical trials, involving more than 4,000 patients, was published online Oct. 4, 2017, in the Journal of the American Academy of Dermatology.

George Han, MD, PhD, associate professor and director of research and teledermatology at the Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, N.Y., who was not involved in the research, said the new data is reassuring.

“We sometimes put it into context [in thinking and counseling about risk] that in the trials for brodalumab, the number of suicide attempts [versus completed suicides] was not an outlier,” he said. “But it’s hard to know what to make of that, so this piece of knowledge that the postmarketing data show there’s no safety signal should give people a lot of reassurance.”

Dr. Han said he has used the medication, a fully human anti-interleukin 17 receptor A monoclonal antibody, in many patients who “have not done so well on other biologics and it’s been a lifesaver ... a couple who have switched over have maintained the longest level of clearance they’ve had with anything. It’s quite striking.”

The efficacy stems at least partly from its mechanism of blocking all cytokines in the IL-17 family – including those involved in the “feedback loops that perpetuate psoriasis” – rather than just one as other biologics do, Dr. Han said.

Usage of the drug has been hindered by the black box warning and REMS program, not only because of the extra steps required and hesitation potentially evoked, but because samples are not available, and because the “formulary access is not what it could have been otherwise,” he noted.

The Siliq REMS patient enrollment form requires patients to pledge awareness of the fact that suicidal thoughts and behaviors have occurred in treated patients and that they should seek medical attention if they experience suicidal thoughts or new or worsening depression, anxiety, or other mood changes. Prescribers must be certified with the program and must pledge on each enrollment form that they have counseled their patients.

The box warning states that there is no established causal association between treatment with brodalumab and increased risk for suicidal ideation and behaviors (SIB).

Individuals with psoriasis are an “already vulnerable population” who have been shown in reviews and meta-analyses to have a higher prevalence of depression and a higher risk of SIB than those without the disease, Dr. Koo and colleagues wrote in a narrative review published in Cutis .

Regardless of therapy, they wrote in the review, dermatologists should assess for any history of depression and SIB, and evaluate for signs and symptoms of current depression and SIB, referring patients as necessary to primary care or mental health care.

In the psoriasis trials, brodalumab treatment appeared to improve symptoms of depression and anxiety – a finding consistent with the effects reported for other biologic therapies, they wrote.

The first author on the newly published preproof is Samuel Yeroushalmi, BS, a fourth-year medical student at George Washington University, Washington.

Siliq is marketed by Valeant Pharmaceuticals.

Dr. Koo disclosed that he is an adviser/consultant/speaker for numerous pharmaceutical companies, but not those that were involved in the development of brodalumab. Dr. Han said he has relationships with numerous companies, including those that have developed brodalumab and other biologic agents used for psoriasis. The authors declared funding sources as none.

Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia. Artemisia capillaris is a natural botanical ingredient already used in skin care products in Asia.

There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.¹ Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.^2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,³ and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.^4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
 

Chemical constituents

In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.⁶

moxumbic/iStock/Getty Images Plus

The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.³

Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation

Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.⁴ TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.

Effects on melanin synthesis

A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.

Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H₂O₂ activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.⁷

Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.⁸
 

Anti-inflammatory activity

Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.

In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.⁹ Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.¹⁰

Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.⁵

In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.²

Atopic dermatitis and A. capillaris

In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.¹¹

Summary

Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.

References

1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.

2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.

3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.

4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.

5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.

6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.

7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.

8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.

9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.

10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.

11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.

Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia. Artemisia capillaris is a natural botanical ingredient already used in skin care products in Asia.

There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.¹ Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.^2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,³ and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.^4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
 

Chemical constituents

In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.⁶

moxumbic/iStock/Getty Images Plus

The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.³

Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation

Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.⁴ TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.

Effects on melanin synthesis

A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.

Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H₂O₂ activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.⁷

Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.⁸
 

Anti-inflammatory activity

Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.

In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.⁹ Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.¹⁰

Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.⁵

In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.²

Atopic dermatitis and A. capillaris

In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.¹¹

Summary

Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.

References

1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.

2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.

3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.

4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.

5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.

6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.

7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.

8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.

9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.

10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.

11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.

Melasma is a difficult disorder to treat. With the removal of hydroquinone from the cosmetic market and the prevalence of dyschromia, new skin lightening ingredients are being sought and many new discoveries are coming from Asia. Artemisia capillaris is a natural botanical ingredient already used in skin care products in Asia.

There are more than 500 species of the genus Artemisia (of the Astraceae or Compositae family) dispersed throughout the temperate areas of Asia, Europe, and North America.¹ Various parts of the shrub Artemisia capillaris, found abundantly in China, Japan, and Korea, have been used in traditional medicine in Asia for hundreds of years. A. capillaris (Yin-Chen in Chinese) has been deployed in traditional Chinese medicine as a diuretic, to protect the liver, and to treat skin inflammation.^2,3 Antioxidant, anti-inflammatory, antisteatotic, antitumor, and antiviral properties have been associated with this plant,³ and hydrating effects have been recently attributed to it. In Korean medicine, A. capillaris (InJin in Korean) has been used for its hepatoprotective, analgesic, and antipyretic activities.^4,5 In this column, the focus will be on recent evidence that suggests possible applications in skin care.
 

Chemical constituents

In 2008, Kim et al. studied the anticarcinogenic activity of A. capillaris, among other medicinal herbs, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis model. The researchers found that A. capillaris exhibited the most effective anticarcinogenic activity compared to the other herbs tested, with such properties ascribed to its constituent camphor, 1-borneol, coumarin, and achillin. Notably, the chloroform fraction of A. capillaris significantly lowered the number of tumors/mouse and tumor incidence compared with the other tested herbs.⁶

moxumbic/iStock/Getty Images Plus

The wide range of biological functions associated with A. capillaris, including anti-inflammatory, antioxidant, antidiabetic, antisteatotic, and antitumor activities have, in various studies, been attributed to the bioactive constituents scoparone, scopoletin, capillarisin, capillin, and chlorogenic acids.³

Tyrosinase-related protein 1 (TYRP-1) and its role in skin pigmentation

Tyrosinase related protein 1 (TYRP-1) is structurally similar to tyrosinase, but its role is still being elucidated. Mutations in TYR-1 results in oculocutaneous albinism. TYRP-1 is involved in eumelanin synthesis, but not in pheomelanin synthesis. Mutations in TYRP-1 affect the quality of melanin synthesized rather than the quantity.⁴ TYRP-1 is being looked at as a target for treatment of hyperpigmentation disorders such as melasma.

Effects on melanin synthesis

A. capillaris reduces the expression of TYRP-1, making it attractive for use in skin lightening products. Although there are not a lot of data, this is a developing area of interest and the following will discuss what is known so far.

Kim et al. investigated the antimelanogenic activity of 10 essential oils, including A. capillaris, utilizing the B16F10 cell line model. A. capillaris was among four extracts found to hinder melanogenesis, and the only one that improved cell proliferation, displayed anti-H₂O₂ activity, and reduced tyrosinase-related protein (TRP)-1 expression. The researchers determined that A. capillaris extract suppressed melanin production through the downregulation of the TRP 1 translational level. They concluded that while investigations using in vivo models are necessary to buttress and validate these results, A. capillaris extract appears to be suitable as a natural therapeutic antimelanogenic agent as well as a skin-whitening ingredient in cosmeceutical products.⁷

Tabassum et al. screened A. capillaris for antipigmentary functions using murine cultured cells (B16-F10 malignant melanocytes). They found that the A. capillaris constituent 4,5-O-dicaffeoylquinic acid significantly and dose-dependently diminished melanin production and tyrosinase activity in the melanocytes. The expression of tyrosinase-related protein-1 was also decreased. Further, the researchers observed antipigmentary activity in a zebrafish model, with no toxicity demonstrated by either A. capillaris or its component 4,5-O-dicaffeoylquinic acid. They concluded that this compound could be included as an active ingredient in products intended to address pigmentation disorders.⁸
 

Anti-inflammatory activity

Inflammation is well known to trigger the production of melanin. This is why anti-inflammatory ingredients are often included in skin lighting products. A. capillaris displays anti-inflammatory activity and has shown some antioxidant activity.

In 2018, Lee et al. confirmed the therapeutic potential of A. capillaris extract to treat psoriasis in HaCaT cells and imiquimod-induced psoriasis-like mouse models. In the murine models, those treated with the ethanol extract of A. capillaris had a significantly lower Psoriasis Area and Severity Index score than that of the mice not given the topical application of the botanical. Epidermal thickness was noted to be significantly lower compared with the mice not treated with A. capillaris.⁹ Further studies in mice by the same team later that year supported the use of a cream formulation containing A. capillaris that they developed to treat psoriasis, warranting new investigations in human skin.¹⁰

Yeo et al. reported, earlier in 2018, on other anti-inflammatory activity of the herb, finding that the aqueous extract from A. capillaris blocked acute gastric mucosal injury by hindering reactive oxygen species and nuclear factor kappa B. They added that A. capillaris maintains oxidant/antioxidant homeostasis and displays potential as a nutraceutical agent for treating gastric ulcers and gastritis.⁵

In 2011, Kwon et al. studied the 5-lipoxygenase inhibitory action of a 70% ethanol extract of aerial parts of A. capillaris. They identified esculetin and quercetin as strong inhibitors of 5-lipoxygenase. The botanical agent, and esculetin in particular, robustly suppressed arachidonic acid-induced ear edema in mice as well as delayed-type hypersensitivity reactions. Further, A. capillaris potently blocked 5-lipoxygenase-catalyzed leukotriene synthesis by ionophore-induced rat basophilic leukemia-1 cells. The researchers concluded that their findings may partially account for the use of A. capillaris as a traditional medical treatment for cutaneous inflammatory conditions.²

Atopic dermatitis and A. capillaris

In 2014, Ha et al. used in vitro and in vivo systems to assess the anti-inflammatory effects of A. capillaris as well as its activity against atopic dermatitis. The in vitro studies revealed that A. capillaris hampered NO and cellular histamine synthesis. In Nc/Nga mice sensitized by Dermatophagoides farinae, dermatitis scores as well as hemorrhage, hypertrophy, and hyperkeratosis of the epidermis in the dorsal skin and ear all declined after the topical application of A. capillaris. Plasma levels of histamine and IgE also significantly decreased after treatment with A. capillaris. The investigators concluded that further study of A. capillaris is warranted as a potential therapeutic option for atopic dermatitis.¹¹

Summary

Many botanical ingredients from Asia are making their way into skin care products in the USA. A. capillaris extract is an example and may have utility in treating hyperpigmentation-associated skin issues such as melasma. Its inhibitory effects on both inflammation and melanin production in addition to possible antioxidant activity make it an interesting compound worthy of more scrutiny.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.

References

1. Bora KS and Sharma A. Pharm Biol. 2011 Jan;49(1):101-9.

2. Kwon OS et al. Arch Pharm Res. 2011 Sep;34(9):1561-9.

3. Hsueh TP et al. Biomedicines. 2021 Oct 8;9(10):1412.

4. Dolinska MB et al. Int J Mol Sci. 2020 Jan 3;21(1):331.

5. Yeo D et al. Biomed Pharmacother. 2018 Mar;99:681-7.

6. Kim YS et al. J Food Sci. 2008 Jan;73(1):T16-20.

7. Kim MJ et al. Mol Med Rep. 2022 Apr;25(4):113.

8. Tabassum N et al. Evid Based Complement Alternat Med. 2016;2016:7823541.

9. Lee SY et al. Phytother Res. 2018 May;32(5):923-2.

10. Lee SY et al. Evid Based Complement Alternat Med. 2018 Aug 19;2018:3610494.

11. Ha H et al. BMC Complement Altern Med. 2014 Mar 14;14:100.

MILAN – The day after deucravacitinib became the first TYK2 inhibitor approved for the treatment of moderate to severe psoriasis, long-term data were presented at the annual congress of the European Academy of Dermatology and Venereology, suggesting that a high degree of benefit persists for at least 2 years, making this oral drug a potential competitor for biologics.

As a once-daily drug, deucravacitinib has “the potential to be a treatment of choice and a new standard of care for patients who require systemic therapy for their moderate to severe plaque psoriasis,” said Mark G. Lebwohl, MD, professor of dermatology and dean of clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York.

Just 2 months after the 52-week data from the phase 3 POETYK PSO-1 trial were published online in the Journal of the American Academy of Dermatology, a long-term extension study found essentially no loss of benefit at 112 weeks, according to Dr. Lebwohl.

One of the two co-primary endpoints was a 75% clearance on the Psoriasis and Severity Index (PASI75) score. At 52 weeks, 80.2% of patients on deucravacitinib had met this criterion of benefit. At 112 weeks, the proportion was 84.4%.

The other primary endpoint was a static Physician’s Global Assessment (sPGA) score of clear or almost clear skin. The proportion of patients meeting this criterion at weeks 52 and 112 weeks were 65.6% and 67.6%, respectively.

When assessed by Treatment Failure Rule (TFR) or modified nonresponder imputation (mNRI), results were similar. For both, the primary endpoints at every time interval were just one or two percentage points lower but not clinically meaningfully different, according to Dr. Lebwohl.

The same type of sustained response out to 112 weeks was observed in multiple analyses. When the researchers isolated the subgroup of patients who had achieved a PASI 75 response at 16 weeks (100%), there was a modest decline in the PASI 75 rate at week 52 (90.2%) but then no additional decline at week 112 (91.3%).

There were essentially no changes in the PASI 90 rates at week 16 (63%), week 52 (65.3%), and week 112 (63.1%), Dr. Lebwohl reported. PASI 100 rates, once achieved, were sustained long term.

The target, TYK2, is one of four Janus kinase (JAK) inhibitors. Until now, almost all JAK inhibitors have had greater relative specificity for JAK 1, JAK 2, and JAK 3, but several inhibitors of TYK2 inhibitors other than deucravacitinib are in development for inflammatory diseases. Deucravacitinib (Sotyktu), approved by the Food and Drug Administration on Sept. 9, is the only TYK2 inhibitor with regulatory approval for plaque psoriasis.

In the POETYK PSO-1 trial, 666 patients were initially randomized in a 2:1:1 ratio to 6 mg deucravacitinib (now the approved dose), placebo, or the oral phosphodiesterase 4 inhibitor apremilast. At week 16, patients on placebo were switched over to deucravacitinib. At week 24, patients who did not achieve a PASI 50 on apremilast (which had been titrated to 10 mg daily to 30 mg twice a day over the first 5 days of dosing) were switched to deucravacitinib.

In the previously reported data, deucravacitinib was superior for all efficacy endpoints at week 16, including an analysis of quality of life when compared with placebo (P < .0001) or apremilast (P = .0088). At week 52, after having been switched to deucravacitinib at week 16, patients on placebo achieved comparable responses on the efficacy measures in this study, including PASI75.

Relative to JAK inhibitors commonly used in rheumatoid arthritis and other inflammatory diseases, the greater specificity of deucravacitinib for TYK2 appears to have meaningful safety advantages, according to Dr. Lebwohl. Targeted mostly on the TYK2 regulatory domain, deucravacitinib largely avoids inhibition of the JAK 1, 2, and 3 subtypes. Dr. Lebwohl said this explains why deucravacitinib labeling does not share the boxed warnings about off-target effects, such as those on the cardiovascular system, that can be found in the labeling of other JAK inhibitors.

In the published 52-week data, the discontinuation rate for adverse events was lower in the group randomized to deucravacitinib arm than in the placebo arm. In the extended follow-up, there were no new signals for adverse events, including those involving the CV system or immune function.

The key message so far from the long-term follow-up, which is ongoing, is that “continuous treatment with deucravacitinib is associated with durable efficacy,” Dr. Lebwohl said. It is this combination of sustained efficacy and safety that led Dr. Lebwohl to suggest it as a reasonable oral competitor to injectable biologics.

“Patients now have a choice,” he said.

Jashin J. Wu, MD, a board member of the National Psoriasis Foundation and an associate professor in the department of dermatology, University of Miami, has been following the development of deucravacitinib. He said that the recent FDA approval validates the clinical evidence of benefit and safety, while the long-term data presented at the EADV congress support its role in expanding treatment options.

“Deucravacitinib is a very effective oral agent for moderate to severe plaque psoriasis with strong maintenance of effect through week 112,” he said. Differentiating it from other JAK inhibitors, the FDA approval “confirms the safety of this agent as there is no boxed warning,” he added.

Dr. Lebwohl reports financial relationships with more than 30 pharmaceutical companies, including Bristol-Myers Squibb, the manufacturer of deucravacitinib. Dr. Wu has financial relationships with 14 pharmaceutical companies, including Bristol-Myers Squibb, but he was not an investigator for the phase 3 trials of deucravacitinib.

MILAN – The day after deucravacitinib became the first TYK2 inhibitor approved for the treatment of moderate to severe psoriasis, long-term data were presented at the annual congress of the European Academy of Dermatology and Venereology, suggesting that a high degree of benefit persists for at least 2 years, making this oral drug a potential competitor for biologics.

As a once-daily drug, deucravacitinib has “the potential to be a treatment of choice and a new standard of care for patients who require systemic therapy for their moderate to severe plaque psoriasis,” said Mark G. Lebwohl, MD, professor of dermatology and dean of clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York.

Just 2 months after the 52-week data from the phase 3 POETYK PSO-1 trial were published online in the Journal of the American Academy of Dermatology, a long-term extension study found essentially no loss of benefit at 112 weeks, according to Dr. Lebwohl.

One of the two co-primary endpoints was a 75% clearance on the Psoriasis and Severity Index (PASI75) score. At 52 weeks, 80.2% of patients on deucravacitinib had met this criterion of benefit. At 112 weeks, the proportion was 84.4%.

The other primary endpoint was a static Physician’s Global Assessment (sPGA) score of clear or almost clear skin. The proportion of patients meeting this criterion at weeks 52 and 112 weeks were 65.6% and 67.6%, respectively.

When assessed by Treatment Failure Rule (TFR) or modified nonresponder imputation (mNRI), results were similar. For both, the primary endpoints at every time interval were just one or two percentage points lower but not clinically meaningfully different, according to Dr. Lebwohl.

The same type of sustained response out to 112 weeks was observed in multiple analyses. When the researchers isolated the subgroup of patients who had achieved a PASI 75 response at 16 weeks (100%), there was a modest decline in the PASI 75 rate at week 52 (90.2%) but then no additional decline at week 112 (91.3%).

There were essentially no changes in the PASI 90 rates at week 16 (63%), week 52 (65.3%), and week 112 (63.1%), Dr. Lebwohl reported. PASI 100 rates, once achieved, were sustained long term.

The target, TYK2, is one of four Janus kinase (JAK) inhibitors. Until now, almost all JAK inhibitors have had greater relative specificity for JAK 1, JAK 2, and JAK 3, but several inhibitors of TYK2 inhibitors other than deucravacitinib are in development for inflammatory diseases. Deucravacitinib (Sotyktu), approved by the Food and Drug Administration on Sept. 9, is the only TYK2 inhibitor with regulatory approval for plaque psoriasis.

In the POETYK PSO-1 trial, 666 patients were initially randomized in a 2:1:1 ratio to 6 mg deucravacitinib (now the approved dose), placebo, or the oral phosphodiesterase 4 inhibitor apremilast. At week 16, patients on placebo were switched over to deucravacitinib. At week 24, patients who did not achieve a PASI 50 on apremilast (which had been titrated to 10 mg daily to 30 mg twice a day over the first 5 days of dosing) were switched to deucravacitinib.

In the previously reported data, deucravacitinib was superior for all efficacy endpoints at week 16, including an analysis of quality of life when compared with placebo (P < .0001) or apremilast (P = .0088). At week 52, after having been switched to deucravacitinib at week 16, patients on placebo achieved comparable responses on the efficacy measures in this study, including PASI75.

Relative to JAK inhibitors commonly used in rheumatoid arthritis and other inflammatory diseases, the greater specificity of deucravacitinib for TYK2 appears to have meaningful safety advantages, according to Dr. Lebwohl. Targeted mostly on the TYK2 regulatory domain, deucravacitinib largely avoids inhibition of the JAK 1, 2, and 3 subtypes. Dr. Lebwohl said this explains why deucravacitinib labeling does not share the boxed warnings about off-target effects, such as those on the cardiovascular system, that can be found in the labeling of other JAK inhibitors.

In the published 52-week data, the discontinuation rate for adverse events was lower in the group randomized to deucravacitinib arm than in the placebo arm. In the extended follow-up, there were no new signals for adverse events, including those involving the CV system or immune function.

The key message so far from the long-term follow-up, which is ongoing, is that “continuous treatment with deucravacitinib is associated with durable efficacy,” Dr. Lebwohl said. It is this combination of sustained efficacy and safety that led Dr. Lebwohl to suggest it as a reasonable oral competitor to injectable biologics.

“Patients now have a choice,” he said.

Jashin J. Wu, MD, a board member of the National Psoriasis Foundation and an associate professor in the department of dermatology, University of Miami, has been following the development of deucravacitinib. He said that the recent FDA approval validates the clinical evidence of benefit and safety, while the long-term data presented at the EADV congress support its role in expanding treatment options.

“Deucravacitinib is a very effective oral agent for moderate to severe plaque psoriasis with strong maintenance of effect through week 112,” he said. Differentiating it from other JAK inhibitors, the FDA approval “confirms the safety of this agent as there is no boxed warning,” he added.

Dr. Lebwohl reports financial relationships with more than 30 pharmaceutical companies, including Bristol-Myers Squibb, the manufacturer of deucravacitinib. Dr. Wu has financial relationships with 14 pharmaceutical companies, including Bristol-Myers Squibb, but he was not an investigator for the phase 3 trials of deucravacitinib.

MILAN – The day after deucravacitinib became the first TYK2 inhibitor approved for the treatment of moderate to severe psoriasis, long-term data were presented at the annual congress of the European Academy of Dermatology and Venereology, suggesting that a high degree of benefit persists for at least 2 years, making this oral drug a potential competitor for biologics.

As a once-daily drug, deucravacitinib has “the potential to be a treatment of choice and a new standard of care for patients who require systemic therapy for their moderate to severe plaque psoriasis,” said Mark G. Lebwohl, MD, professor of dermatology and dean of clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York.

Just 2 months after the 52-week data from the phase 3 POETYK PSO-1 trial were published online in the Journal of the American Academy of Dermatology, a long-term extension study found essentially no loss of benefit at 112 weeks, according to Dr. Lebwohl.

One of the two co-primary endpoints was a 75% clearance on the Psoriasis and Severity Index (PASI75) score. At 52 weeks, 80.2% of patients on deucravacitinib had met this criterion of benefit. At 112 weeks, the proportion was 84.4%.

The other primary endpoint was a static Physician’s Global Assessment (sPGA) score of clear or almost clear skin. The proportion of patients meeting this criterion at weeks 52 and 112 weeks were 65.6% and 67.6%, respectively.

When assessed by Treatment Failure Rule (TFR) or modified nonresponder imputation (mNRI), results were similar. For both, the primary endpoints at every time interval were just one or two percentage points lower but not clinically meaningfully different, according to Dr. Lebwohl.

The same type of sustained response out to 112 weeks was observed in multiple analyses. When the researchers isolated the subgroup of patients who had achieved a PASI 75 response at 16 weeks (100%), there was a modest decline in the PASI 75 rate at week 52 (90.2%) but then no additional decline at week 112 (91.3%).

There were essentially no changes in the PASI 90 rates at week 16 (63%), week 52 (65.3%), and week 112 (63.1%), Dr. Lebwohl reported. PASI 100 rates, once achieved, were sustained long term.

The target, TYK2, is one of four Janus kinase (JAK) inhibitors. Until now, almost all JAK inhibitors have had greater relative specificity for JAK 1, JAK 2, and JAK 3, but several inhibitors of TYK2 inhibitors other than deucravacitinib are in development for inflammatory diseases. Deucravacitinib (Sotyktu), approved by the Food and Drug Administration on Sept. 9, is the only TYK2 inhibitor with regulatory approval for plaque psoriasis.

In the POETYK PSO-1 trial, 666 patients were initially randomized in a 2:1:1 ratio to 6 mg deucravacitinib (now the approved dose), placebo, or the oral phosphodiesterase 4 inhibitor apremilast. At week 16, patients on placebo were switched over to deucravacitinib. At week 24, patients who did not achieve a PASI 50 on apremilast (which had been titrated to 10 mg daily to 30 mg twice a day over the first 5 days of dosing) were switched to deucravacitinib.

In the previously reported data, deucravacitinib was superior for all efficacy endpoints at week 16, including an analysis of quality of life when compared with placebo (P < .0001) or apremilast (P = .0088). At week 52, after having been switched to deucravacitinib at week 16, patients on placebo achieved comparable responses on the efficacy measures in this study, including PASI75.

Relative to JAK inhibitors commonly used in rheumatoid arthritis and other inflammatory diseases, the greater specificity of deucravacitinib for TYK2 appears to have meaningful safety advantages, according to Dr. Lebwohl. Targeted mostly on the TYK2 regulatory domain, deucravacitinib largely avoids inhibition of the JAK 1, 2, and 3 subtypes. Dr. Lebwohl said this explains why deucravacitinib labeling does not share the boxed warnings about off-target effects, such as those on the cardiovascular system, that can be found in the labeling of other JAK inhibitors.

In the published 52-week data, the discontinuation rate for adverse events was lower in the group randomized to deucravacitinib arm than in the placebo arm. In the extended follow-up, there were no new signals for adverse events, including those involving the CV system or immune function.

The key message so far from the long-term follow-up, which is ongoing, is that “continuous treatment with deucravacitinib is associated with durable efficacy,” Dr. Lebwohl said. It is this combination of sustained efficacy and safety that led Dr. Lebwohl to suggest it as a reasonable oral competitor to injectable biologics.

“Patients now have a choice,” he said.

Jashin J. Wu, MD, a board member of the National Psoriasis Foundation and an associate professor in the department of dermatology, University of Miami, has been following the development of deucravacitinib. He said that the recent FDA approval validates the clinical evidence of benefit and safety, while the long-term data presented at the EADV congress support its role in expanding treatment options.

“Deucravacitinib is a very effective oral agent for moderate to severe plaque psoriasis with strong maintenance of effect through week 112,” he said. Differentiating it from other JAK inhibitors, the FDA approval “confirms the safety of this agent as there is no boxed warning,” he added.

Dr. Lebwohl reports financial relationships with more than 30 pharmaceutical companies, including Bristol-Myers Squibb, the manufacturer of deucravacitinib. Dr. Wu has financial relationships with 14 pharmaceutical companies, including Bristol-Myers Squibb, but he was not an investigator for the phase 3 trials of deucravacitinib.