Doug Brunk

TOPLINE:

Nearly half of the US Food and Drug Administration (FDA) approvals for dermatologic drugs between 2012 and 2022 were considered first in class or first in indication.

METHODOLOGY:

• Only five new drugs for diseases treated mostly by dermatologists were approved by the FDA between 1999 and 2009.
• In a cross-sectional analysis to characterize the frequency and degree of innovation of dermatologic drugs approved more recently, researchers identified new and supplemental dermatologic drugs approved between January 1, 2012, and December 31, 2022, from FDA lists, Centers for Medicare & Medicaid Services CenterWatch, and peer-reviewed articles.
• They used five proxy measures to estimate each drug’s degree of innovation: FDA designation (first in class, advance in class, or addition to class), independent clinical usefulness ratings, and benefit ratings by health technology assessment organizations.

TAKEAWAY:

• The study authors identified 52 new drug applications and 26 supplemental new indications approved by the FDA for dermatologic indications between 2012 and 2022.
• Of the 52 new drugs, the researchers categorized 11 (21%) as first in class and 13 (25%) as first in indication.
• An analysis of benefit ratings available for 38 of the drugs showed that 15 (39%) were rated as being clinically useful or having high added therapeutic benefit.
• Of the 10 supplemental new indications with ratings by any organization, 3 (30%) were rated as clinically useful or having high added therapeutic benefit.

IN PRACTICE:

While innovative drug development in dermatology may have increased, “these findings also highlight opportunities to develop more truly innovative dermatologic agents, particularly for diseases with unmet therapeutic need,” the authors wrote.

[embed:render:related:node:219314]

SOURCE:

First author Samir Kamat, MD, of the Medical Education Department at Icahn School of Medicine at Mount Sinai, New York City, and corresponding author Ravi Gupta, MD, MSHP, of the Internal Medicine Division at Johns Hopkins University, Baltimore, Maryland, led the research. The study was published online as a research letter on December 20, 2023, in JAMA Dermatology.

LIMITATIONS:

They include the use of individual indications to assess clinical usefulness and benefit ratings. Many drugs, particularly supplemental indications, lacked such ratings. Reformulations of already marketed drugs or indications were not included.

DISCLOSURES:

Dr. Kamat and Dr. Gupta had no relevant disclosures. Three coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly half of the US Food and Drug Administration (FDA) approvals for dermatologic drugs between 2012 and 2022 were considered first in class or first in indication.

METHODOLOGY:

• Only five new drugs for diseases treated mostly by dermatologists were approved by the FDA between 1999 and 2009.
• In a cross-sectional analysis to characterize the frequency and degree of innovation of dermatologic drugs approved more recently, researchers identified new and supplemental dermatologic drugs approved between January 1, 2012, and December 31, 2022, from FDA lists, Centers for Medicare & Medicaid Services CenterWatch, and peer-reviewed articles.
• They used five proxy measures to estimate each drug’s degree of innovation: FDA designation (first in class, advance in class, or addition to class), independent clinical usefulness ratings, and benefit ratings by health technology assessment organizations.

TAKEAWAY:

• The study authors identified 52 new drug applications and 26 supplemental new indications approved by the FDA for dermatologic indications between 2012 and 2022.
• Of the 52 new drugs, the researchers categorized 11 (21%) as first in class and 13 (25%) as first in indication.
• An analysis of benefit ratings available for 38 of the drugs showed that 15 (39%) were rated as being clinically useful or having high added therapeutic benefit.
• Of the 10 supplemental new indications with ratings by any organization, 3 (30%) were rated as clinically useful or having high added therapeutic benefit.

IN PRACTICE:

While innovative drug development in dermatology may have increased, “these findings also highlight opportunities to develop more truly innovative dermatologic agents, particularly for diseases with unmet therapeutic need,” the authors wrote.

[embed:render:related:node:219314]

SOURCE:

First author Samir Kamat, MD, of the Medical Education Department at Icahn School of Medicine at Mount Sinai, New York City, and corresponding author Ravi Gupta, MD, MSHP, of the Internal Medicine Division at Johns Hopkins University, Baltimore, Maryland, led the research. The study was published online as a research letter on December 20, 2023, in JAMA Dermatology.

LIMITATIONS:

They include the use of individual indications to assess clinical usefulness and benefit ratings. Many drugs, particularly supplemental indications, lacked such ratings. Reformulations of already marketed drugs or indications were not included.

DISCLOSURES:

Dr. Kamat and Dr. Gupta had no relevant disclosures. Three coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly half of the US Food and Drug Administration (FDA) approvals for dermatologic drugs between 2012 and 2022 were considered first in class or first in indication.

METHODOLOGY:

• Only five new drugs for diseases treated mostly by dermatologists were approved by the FDA between 1999 and 2009.
• In a cross-sectional analysis to characterize the frequency and degree of innovation of dermatologic drugs approved more recently, researchers identified new and supplemental dermatologic drugs approved between January 1, 2012, and December 31, 2022, from FDA lists, Centers for Medicare & Medicaid Services CenterWatch, and peer-reviewed articles.
• They used five proxy measures to estimate each drug’s degree of innovation: FDA designation (first in class, advance in class, or addition to class), independent clinical usefulness ratings, and benefit ratings by health technology assessment organizations.

TAKEAWAY:

• The study authors identified 52 new drug applications and 26 supplemental new indications approved by the FDA for dermatologic indications between 2012 and 2022.
• Of the 52 new drugs, the researchers categorized 11 (21%) as first in class and 13 (25%) as first in indication.
• An analysis of benefit ratings available for 38 of the drugs showed that 15 (39%) were rated as being clinically useful or having high added therapeutic benefit.
• Of the 10 supplemental new indications with ratings by any organization, 3 (30%) were rated as clinically useful or having high added therapeutic benefit.

IN PRACTICE:

While innovative drug development in dermatology may have increased, “these findings also highlight opportunities to develop more truly innovative dermatologic agents, particularly for diseases with unmet therapeutic need,” the authors wrote.

[embed:render:related:node:219314]

SOURCE:

First author Samir Kamat, MD, of the Medical Education Department at Icahn School of Medicine at Mount Sinai, New York City, and corresponding author Ravi Gupta, MD, MSHP, of the Internal Medicine Division at Johns Hopkins University, Baltimore, Maryland, led the research. The study was published online as a research letter on December 20, 2023, in JAMA Dermatology.

LIMITATIONS:

They include the use of individual indications to assess clinical usefulness and benefit ratings. Many drugs, particularly supplemental indications, lacked such ratings. Reformulations of already marketed drugs or indications were not included.

DISCLOSURES:

Dr. Kamat and Dr. Gupta had no relevant disclosures. Three coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

The myriad of clinical tools available for assessing patients with atopic dermatitis may leave clinicians wondering how to best incorporate the tools into the daily clinical workflow.

“It can be overwhelming because there are many choices but so little time,” Jonathan I. Silverberg, MD, PhD, MPH, associate professor and director of clinical research in the dermatology department at George Washington University, Washington, DC, said at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Assessment tools such as the Eczema Area and Severity Index (EASI), the Numeric Rating scale for itch (NRS-itch), and the Dermatology Life Quality Index (DLQI) “all correlate, but they’re all different, and there is value in all of them,” said Dr. Silverberg. “Of course, you’re not going to use all of them, but which ones should you use?”

He favors a structured approach that considers signs, symptoms, and quality of life, a framework that he and Shanthi Narla, MD, proposed in an article published online in Dermatitis. In the United States, he said, the Investigator’s Global Assessment scale (IGA) and BSA are the preferred tools for assessing the clinical severity of AD.

“If you go to Australia and New Zealand, they love EASI, while in Western Europe, they love the SCORAD [SCORing Atopic Dermatitis] tool because they’ve been using it since the 1990s,” Dr. Silverberg said. “So whatever works for you, pick it. But just use something that’s going to work within your practice setting. The IGA and the BSA are the easiest to do and the fastest to do in clinical practice. You’re going to have to document disease severity anyway if you’re going to get systemic therapies approved,” he said, referring to approval for coverage by the patient’s health insurance drug formulary.
 

Several Recommendations

Based on his clinical experience, Dr. Silverberg recommended certain assessment tools as “feasible” to use in daily practice. In the domain of clinical signs, “the IGA and the BSA are the most useful,” he said. “If the patient is gowned up, it probably takes about 30 seconds to do an IGA scale, and a BSA can be done in under a minute, easily.”

In the domain of symptoms, he recommends having the patient or caregiver complete at least one of the following patient-reported outcome measures (PROMs): the NRS-itch, the NRS-pain, the NRS-Sleep Disturbance, the Patient Health Questionnaire-2 (PHQ-2), and either the Patient Global Assessment (PtGA) or the Patient-Reported Global AD Severity (PrtGA).

“Pick one or two that reflect what you can do in clinical practice,” Dr. Silverberg advised. “The NRS-itch is clinically meaningful and takes 10 seconds to do. Or you can just ask the patient, ‘How do you rate your itch? Clear, mild, moderate, or severe?’ A verbal rating scale, like a Likert scale, would also work. Again, this takes 10 seconds to assess. This is not slowing you down in practice; it will speed you up in the long run.”

He favors the NRS scale assessments, “because the 2023 AAD guidelines for AD advocate for open-ended questions,” he said. “I can tell you from personal experience that when you go down that rabbit hole of open-ended questions, you’re never getting out of that exam room. If you ask a patient how AD affects their life, you might as well just plan on a 30- to 40-minute visit. But if you use structured questions, you can get the information you need so dearly to make the right assessments, but you can keep the visit moving efficiently.”

He noted that the NRS-itch or the PtGA and PrtGA tools “each take about 10 seconds to complete. I would argue that you could probably have the patient [complete all of these PROMs], and you’re still in under a minute, and you get incredibly rich information.”

In the quality-of-life domain, Dr. Silverberg recommends that the patient or caregiver complete the DLQI. If there is additional time, he also suggests the Atopic Dermatitis Control Tool (ADCT) to gain further insight on symptomatology.

“The DLQI takes about a minute or minute-and-a-half to complete, while the ADCT takes about a minute,” he said. “It measures overall disease control, and there are some interesting individual questions there, such as how AD bothers them, how it impacts their sleep, how it impacts them emotionally.”

To optimize efficiency, Dr. Silverberg recommends that patients or caregivers complete PROMs prior to the patient encounter by e-mail or on the patient’s online portal the night before. Freely available smart phone applications designed for AD patients can help them track their disease symptoms, such as EczemaWise from the National Eczema Association.

“[The PROMs] can even be completed in the waiting area; a lot of times we’re running behind anyway,” he said. “Even if we’re not, it can be done in a minute or two while they’re filling out their insurance paperwork or whatever. Patient-reported outcomes can also be collected by the medical assistant or nursing while rooming the patient.”

Administering such structured assessments prior to the actual patient encounter “seems counterintuitive because you’re asking seemingly more information, but that doesn’t matter, because you are asking it in an efficient, structured manner, and you are getting the information you need,” he noted. “These tools can also help fill in the gaps of telehealth encounters.”

Dr. Silverberg reported being a consultant and/or an adviser for many pharmaceutical companies. He has also received grant or research support from Galderma and Pfizer.

The myriad of clinical tools available for assessing patients with atopic dermatitis may leave clinicians wondering how to best incorporate the tools into the daily clinical workflow.

“It can be overwhelming because there are many choices but so little time,” Jonathan I. Silverberg, MD, PhD, MPH, associate professor and director of clinical research in the dermatology department at George Washington University, Washington, DC, said at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Assessment tools such as the Eczema Area and Severity Index (EASI), the Numeric Rating scale for itch (NRS-itch), and the Dermatology Life Quality Index (DLQI) “all correlate, but they’re all different, and there is value in all of them,” said Dr. Silverberg. “Of course, you’re not going to use all of them, but which ones should you use?”

He favors a structured approach that considers signs, symptoms, and quality of life, a framework that he and Shanthi Narla, MD, proposed in an article published online in Dermatitis. In the United States, he said, the Investigator’s Global Assessment scale (IGA) and BSA are the preferred tools for assessing the clinical severity of AD.

“If you go to Australia and New Zealand, they love EASI, while in Western Europe, they love the SCORAD [SCORing Atopic Dermatitis] tool because they’ve been using it since the 1990s,” Dr. Silverberg said. “So whatever works for you, pick it. But just use something that’s going to work within your practice setting. The IGA and the BSA are the easiest to do and the fastest to do in clinical practice. You’re going to have to document disease severity anyway if you’re going to get systemic therapies approved,” he said, referring to approval for coverage by the patient’s health insurance drug formulary.
 

Several Recommendations

Based on his clinical experience, Dr. Silverberg recommended certain assessment tools as “feasible” to use in daily practice. In the domain of clinical signs, “the IGA and the BSA are the most useful,” he said. “If the patient is gowned up, it probably takes about 30 seconds to do an IGA scale, and a BSA can be done in under a minute, easily.”

In the domain of symptoms, he recommends having the patient or caregiver complete at least one of the following patient-reported outcome measures (PROMs): the NRS-itch, the NRS-pain, the NRS-Sleep Disturbance, the Patient Health Questionnaire-2 (PHQ-2), and either the Patient Global Assessment (PtGA) or the Patient-Reported Global AD Severity (PrtGA).

“Pick one or two that reflect what you can do in clinical practice,” Dr. Silverberg advised. “The NRS-itch is clinically meaningful and takes 10 seconds to do. Or you can just ask the patient, ‘How do you rate your itch? Clear, mild, moderate, or severe?’ A verbal rating scale, like a Likert scale, would also work. Again, this takes 10 seconds to assess. This is not slowing you down in practice; it will speed you up in the long run.”

He favors the NRS scale assessments, “because the 2023 AAD guidelines for AD advocate for open-ended questions,” he said. “I can tell you from personal experience that when you go down that rabbit hole of open-ended questions, you’re never getting out of that exam room. If you ask a patient how AD affects their life, you might as well just plan on a 30- to 40-minute visit. But if you use structured questions, you can get the information you need so dearly to make the right assessments, but you can keep the visit moving efficiently.”

He noted that the NRS-itch or the PtGA and PrtGA tools “each take about 10 seconds to complete. I would argue that you could probably have the patient [complete all of these PROMs], and you’re still in under a minute, and you get incredibly rich information.”

In the quality-of-life domain, Dr. Silverberg recommends that the patient or caregiver complete the DLQI. If there is additional time, he also suggests the Atopic Dermatitis Control Tool (ADCT) to gain further insight on symptomatology.

“The DLQI takes about a minute or minute-and-a-half to complete, while the ADCT takes about a minute,” he said. “It measures overall disease control, and there are some interesting individual questions there, such as how AD bothers them, how it impacts their sleep, how it impacts them emotionally.”

To optimize efficiency, Dr. Silverberg recommends that patients or caregivers complete PROMs prior to the patient encounter by e-mail or on the patient’s online portal the night before. Freely available smart phone applications designed for AD patients can help them track their disease symptoms, such as EczemaWise from the National Eczema Association.

“[The PROMs] can even be completed in the waiting area; a lot of times we’re running behind anyway,” he said. “Even if we’re not, it can be done in a minute or two while they’re filling out their insurance paperwork or whatever. Patient-reported outcomes can also be collected by the medical assistant or nursing while rooming the patient.”

Administering such structured assessments prior to the actual patient encounter “seems counterintuitive because you’re asking seemingly more information, but that doesn’t matter, because you are asking it in an efficient, structured manner, and you are getting the information you need,” he noted. “These tools can also help fill in the gaps of telehealth encounters.”

Dr. Silverberg reported being a consultant and/or an adviser for many pharmaceutical companies. He has also received grant or research support from Galderma and Pfizer.

The myriad of clinical tools available for assessing patients with atopic dermatitis may leave clinicians wondering how to best incorporate the tools into the daily clinical workflow.

“It can be overwhelming because there are many choices but so little time,” Jonathan I. Silverberg, MD, PhD, MPH, associate professor and director of clinical research in the dermatology department at George Washington University, Washington, DC, said at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Assessment tools such as the Eczema Area and Severity Index (EASI), the Numeric Rating scale for itch (NRS-itch), and the Dermatology Life Quality Index (DLQI) “all correlate, but they’re all different, and there is value in all of them,” said Dr. Silverberg. “Of course, you’re not going to use all of them, but which ones should you use?”

He favors a structured approach that considers signs, symptoms, and quality of life, a framework that he and Shanthi Narla, MD, proposed in an article published online in Dermatitis. In the United States, he said, the Investigator’s Global Assessment scale (IGA) and BSA are the preferred tools for assessing the clinical severity of AD.

“If you go to Australia and New Zealand, they love EASI, while in Western Europe, they love the SCORAD [SCORing Atopic Dermatitis] tool because they’ve been using it since the 1990s,” Dr. Silverberg said. “So whatever works for you, pick it. But just use something that’s going to work within your practice setting. The IGA and the BSA are the easiest to do and the fastest to do in clinical practice. You’re going to have to document disease severity anyway if you’re going to get systemic therapies approved,” he said, referring to approval for coverage by the patient’s health insurance drug formulary.
 

Several Recommendations

Based on his clinical experience, Dr. Silverberg recommended certain assessment tools as “feasible” to use in daily practice. In the domain of clinical signs, “the IGA and the BSA are the most useful,” he said. “If the patient is gowned up, it probably takes about 30 seconds to do an IGA scale, and a BSA can be done in under a minute, easily.”

In the domain of symptoms, he recommends having the patient or caregiver complete at least one of the following patient-reported outcome measures (PROMs): the NRS-itch, the NRS-pain, the NRS-Sleep Disturbance, the Patient Health Questionnaire-2 (PHQ-2), and either the Patient Global Assessment (PtGA) or the Patient-Reported Global AD Severity (PrtGA).

“Pick one or two that reflect what you can do in clinical practice,” Dr. Silverberg advised. “The NRS-itch is clinically meaningful and takes 10 seconds to do. Or you can just ask the patient, ‘How do you rate your itch? Clear, mild, moderate, or severe?’ A verbal rating scale, like a Likert scale, would also work. Again, this takes 10 seconds to assess. This is not slowing you down in practice; it will speed you up in the long run.”

He favors the NRS scale assessments, “because the 2023 AAD guidelines for AD advocate for open-ended questions,” he said. “I can tell you from personal experience that when you go down that rabbit hole of open-ended questions, you’re never getting out of that exam room. If you ask a patient how AD affects their life, you might as well just plan on a 30- to 40-minute visit. But if you use structured questions, you can get the information you need so dearly to make the right assessments, but you can keep the visit moving efficiently.”

He noted that the NRS-itch or the PtGA and PrtGA tools “each take about 10 seconds to complete. I would argue that you could probably have the patient [complete all of these PROMs], and you’re still in under a minute, and you get incredibly rich information.”

In the quality-of-life domain, Dr. Silverberg recommends that the patient or caregiver complete the DLQI. If there is additional time, he also suggests the Atopic Dermatitis Control Tool (ADCT) to gain further insight on symptomatology.

“The DLQI takes about a minute or minute-and-a-half to complete, while the ADCT takes about a minute,” he said. “It measures overall disease control, and there are some interesting individual questions there, such as how AD bothers them, how it impacts their sleep, how it impacts them emotionally.”

To optimize efficiency, Dr. Silverberg recommends that patients or caregivers complete PROMs prior to the patient encounter by e-mail or on the patient’s online portal the night before. Freely available smart phone applications designed for AD patients can help them track their disease symptoms, such as EczemaWise from the National Eczema Association.

“[The PROMs] can even be completed in the waiting area; a lot of times we’re running behind anyway,” he said. “Even if we’re not, it can be done in a minute or two while they’re filling out their insurance paperwork or whatever. Patient-reported outcomes can also be collected by the medical assistant or nursing while rooming the patient.”

Administering such structured assessments prior to the actual patient encounter “seems counterintuitive because you’re asking seemingly more information, but that doesn’t matter, because you are asking it in an efficient, structured manner, and you are getting the information you need,” he noted. “These tools can also help fill in the gaps of telehealth encounters.”

Dr. Silverberg reported being a consultant and/or an adviser for many pharmaceutical companies. He has also received grant or research support from Galderma and Pfizer.

An experimental topical phosphodiesterase 4 (PDE4) inhibitor showed superior efficacy to vehicle in patients with mild to moderate atopic dermatitis (AD) and plaque psoriasis, results from a phase 2a study showed.

Eichenfield_Lawrence_CA_web.jpg

PDE4 inhibitors are a promising therapeutic target for inflammatory diseases because “they can increase cyclic adenosine monophosphate levels and subsequently reduce the production of proinflammatory cytokines,” lead study author Lawrence F. Eichenfield, MD, of the dermatology department at the University of California, San Diego, and colleagues wrote. The paper was published online in JAMA Dermatology.

Currently Available Treatments

For plaque psoriasis, the FDA approved the topical PDE4 inhibitor roflumilast in 2022. The oral PDE4 inhibitor apremilast has shown to be effective for plaque psoriasis and is well tolerated, and “it has been associated with gastrointestinal adverse events (AEs) such as nausea and diarrhea,” the researchers wrote.

For AD, crisaborole is the only approved topical PDE4 treatment, and it is associated with application site burning and stinging, they wrote.

An Experimental Alternative

The new study tested a topical PDE4 inhibitor known as PF-07038124, which is being developed by Pfizer. It is designed to be “a potent, oxaborole-based PDE4 inhibitor [that shows] immunomodulatory activity in T-cell–based assays, contributing to inhibition of [interleukin]-4 and IL-13; thus, it could provide therapeutic benefit in the treatment of AD and plaque psoriasis,” the authors wrote.

The phase 2a study was conducted from December 21, 2020, to August 18, 2021. Researchers at 34 sites in four countries randomized 104 patients with mild to moderate AD (70) or plaque psoriasis (34) to receive PF-07038124 as a 0.001% topical ointment or a vehicle only once daily for 6 weeks.

The primary end point was the percent change from baseline in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures of interest included treatment-emergent adverse events.

Overall, the mean age of the 104 patients was 43 years, 52.9%, were women, 3.8% were Asian, 12.5% were Black, and 83.7% were White. Most had moderate disease.

At week 6 in patients with AD, the PF-07038124 group showed statistically significantly greater improvement in the EASI total score, compared with vehicle group (−74.9% vs −35.5% respectively; least squares mean [LSM] difference, −39.4%; 90% CI, −58.8% to−20.1%]; P < .001).

Similarly, at week 6 in patients with plaque psoriasis, the PF-07038124 group demonstrated a significantly greater improvement in the PASI total score, compared with the vehicle group (LSM, −4.8; 90% CI, −6.2 to −3.4] vs 0.1; 90% CI, −1.5 to 1.7), for a difference of −4.9; 90% CI, −7.0 to −2.8; P < .001.

In safety outcomes, treatment-emergent adverse events were reported in 16 people receiving PF-07038124 and 26 people receiving a vehicle. The treatment-related adverse events were reported only in the vehicle groups across all indications, while no patients in the PF-07038124 groups experienced pain or skin reactions at the application sites.

The researchers acknowledged certain limitations of the trial, including its small size and the 6-week treatment period. “Unlike crisaborole, topical PF-07038124 was not associated with application site burning and stinging,” they noted. “To confirm persistence of efficacy and the safety profile of PF-07038124, long-term data should be collected in larger studies.”

Pfizer supported the study. Dr. Eichenfield reported receiving personal fees from Pfizer during the conduct of the study. He also has received grant support from, is consultant to, and/or is a member of the advisory board for many other pharmaceutical companies. Several other study authors reported similar disclosures.

An experimental topical phosphodiesterase 4 (PDE4) inhibitor showed superior efficacy to vehicle in patients with mild to moderate atopic dermatitis (AD) and plaque psoriasis, results from a phase 2a study showed.

Eichenfield_Lawrence_CA_web.jpg

PDE4 inhibitors are a promising therapeutic target for inflammatory diseases because “they can increase cyclic adenosine monophosphate levels and subsequently reduce the production of proinflammatory cytokines,” lead study author Lawrence F. Eichenfield, MD, of the dermatology department at the University of California, San Diego, and colleagues wrote. The paper was published online in JAMA Dermatology.

Currently Available Treatments

For plaque psoriasis, the FDA approved the topical PDE4 inhibitor roflumilast in 2022. The oral PDE4 inhibitor apremilast has shown to be effective for plaque psoriasis and is well tolerated, and “it has been associated with gastrointestinal adverse events (AEs) such as nausea and diarrhea,” the researchers wrote.

For AD, crisaborole is the only approved topical PDE4 treatment, and it is associated with application site burning and stinging, they wrote.

An Experimental Alternative

The new study tested a topical PDE4 inhibitor known as PF-07038124, which is being developed by Pfizer. It is designed to be “a potent, oxaborole-based PDE4 inhibitor [that shows] immunomodulatory activity in T-cell–based assays, contributing to inhibition of [interleukin]-4 and IL-13; thus, it could provide therapeutic benefit in the treatment of AD and plaque psoriasis,” the authors wrote.

The phase 2a study was conducted from December 21, 2020, to August 18, 2021. Researchers at 34 sites in four countries randomized 104 patients with mild to moderate AD (70) or plaque psoriasis (34) to receive PF-07038124 as a 0.001% topical ointment or a vehicle only once daily for 6 weeks.

The primary end point was the percent change from baseline in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures of interest included treatment-emergent adverse events.

Overall, the mean age of the 104 patients was 43 years, 52.9%, were women, 3.8% were Asian, 12.5% were Black, and 83.7% were White. Most had moderate disease.

At week 6 in patients with AD, the PF-07038124 group showed statistically significantly greater improvement in the EASI total score, compared with vehicle group (−74.9% vs −35.5% respectively; least squares mean [LSM] difference, −39.4%; 90% CI, −58.8% to−20.1%]; P < .001).

Similarly, at week 6 in patients with plaque psoriasis, the PF-07038124 group demonstrated a significantly greater improvement in the PASI total score, compared with the vehicle group (LSM, −4.8; 90% CI, −6.2 to −3.4] vs 0.1; 90% CI, −1.5 to 1.7), for a difference of −4.9; 90% CI, −7.0 to −2.8; P < .001.

In safety outcomes, treatment-emergent adverse events were reported in 16 people receiving PF-07038124 and 26 people receiving a vehicle. The treatment-related adverse events were reported only in the vehicle groups across all indications, while no patients in the PF-07038124 groups experienced pain or skin reactions at the application sites.

The researchers acknowledged certain limitations of the trial, including its small size and the 6-week treatment period. “Unlike crisaborole, topical PF-07038124 was not associated with application site burning and stinging,” they noted. “To confirm persistence of efficacy and the safety profile of PF-07038124, long-term data should be collected in larger studies.”

Pfizer supported the study. Dr. Eichenfield reported receiving personal fees from Pfizer during the conduct of the study. He also has received grant support from, is consultant to, and/or is a member of the advisory board for many other pharmaceutical companies. Several other study authors reported similar disclosures.

An experimental topical phosphodiesterase 4 (PDE4) inhibitor showed superior efficacy to vehicle in patients with mild to moderate atopic dermatitis (AD) and plaque psoriasis, results from a phase 2a study showed.

Eichenfield_Lawrence_CA_web.jpg

PDE4 inhibitors are a promising therapeutic target for inflammatory diseases because “they can increase cyclic adenosine monophosphate levels and subsequently reduce the production of proinflammatory cytokines,” lead study author Lawrence F. Eichenfield, MD, of the dermatology department at the University of California, San Diego, and colleagues wrote. The paper was published online in JAMA Dermatology.

Currently Available Treatments

For plaque psoriasis, the FDA approved the topical PDE4 inhibitor roflumilast in 2022. The oral PDE4 inhibitor apremilast has shown to be effective for plaque psoriasis and is well tolerated, and “it has been associated with gastrointestinal adverse events (AEs) such as nausea and diarrhea,” the researchers wrote.

For AD, crisaborole is the only approved topical PDE4 treatment, and it is associated with application site burning and stinging, they wrote.

An Experimental Alternative

The new study tested a topical PDE4 inhibitor known as PF-07038124, which is being developed by Pfizer. It is designed to be “a potent, oxaborole-based PDE4 inhibitor [that shows] immunomodulatory activity in T-cell–based assays, contributing to inhibition of [interleukin]-4 and IL-13; thus, it could provide therapeutic benefit in the treatment of AD and plaque psoriasis,” the authors wrote.

The phase 2a study was conducted from December 21, 2020, to August 18, 2021. Researchers at 34 sites in four countries randomized 104 patients with mild to moderate AD (70) or plaque psoriasis (34) to receive PF-07038124 as a 0.001% topical ointment or a vehicle only once daily for 6 weeks.

The primary end point was the percent change from baseline in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures of interest included treatment-emergent adverse events.

Overall, the mean age of the 104 patients was 43 years, 52.9%, were women, 3.8% were Asian, 12.5% were Black, and 83.7% were White. Most had moderate disease.

At week 6 in patients with AD, the PF-07038124 group showed statistically significantly greater improvement in the EASI total score, compared with vehicle group (−74.9% vs −35.5% respectively; least squares mean [LSM] difference, −39.4%; 90% CI, −58.8% to−20.1%]; P < .001).

Similarly, at week 6 in patients with plaque psoriasis, the PF-07038124 group demonstrated a significantly greater improvement in the PASI total score, compared with the vehicle group (LSM, −4.8; 90% CI, −6.2 to −3.4] vs 0.1; 90% CI, −1.5 to 1.7), for a difference of −4.9; 90% CI, −7.0 to −2.8; P < .001.

In safety outcomes, treatment-emergent adverse events were reported in 16 people receiving PF-07038124 and 26 people receiving a vehicle. The treatment-related adverse events were reported only in the vehicle groups across all indications, while no patients in the PF-07038124 groups experienced pain or skin reactions at the application sites.

The researchers acknowledged certain limitations of the trial, including its small size and the 6-week treatment period. “Unlike crisaborole, topical PF-07038124 was not associated with application site burning and stinging,” they noted. “To confirm persistence of efficacy and the safety profile of PF-07038124, long-term data should be collected in larger studies.”

Pfizer supported the study. Dr. Eichenfield reported receiving personal fees from Pfizer during the conduct of the study. He also has received grant support from, is consultant to, and/or is a member of the advisory board for many other pharmaceutical companies. Several other study authors reported similar disclosures.

With so many treatment options available for atopic dermatitis (AD) and more in the pipeline, one common question Raj Chovatiya, MD, PhD, hears from his fellow dermatologists is: How do I choose the right therapy for my patients?

“There isn’t going to be a one-size-fits-all approach, and it may be impossible to differentiate, given that these agents are not likely to be studied head-to-head,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Chovatiya_Ray_ILL_web.jpg

He shared a list of factors to consider when engaged in shared decision-making with patients about their AD treatment options. These include:

• Severity of disease (mild vs moderate vs severe).
• Extent of disease (low vs high body surface area).
• Rapidity of drug onset (hours vs days vs weeks).
• Depth of response based on different endpoints such as itch and number of lesions.
• Long-term efficacy (durability on treatment vs off treatment).
• Adverse events (cutaneous vs systemic).
• Black box warnings (present vs absent).
• Tolerance (selective areas vs the entire skin).
• Vehicle (ointment vs cream).
• Patient preference. “This may be the biggest driver; what do patients want?” Dr. Chovatiya said.
• Access to the drug. Is it easily obtainable for the patient?

He concluded his remarks by posing a question to attendees: “Are we closer to living in a topical steroid–free world for AD? Is that what we want?” he asked. “I wholeheartedly say that’s what we’ve been working toward all these years, and we should keep up the good fight. We have more data for targeted therapy to treat very specific disease with very specific outcomes and endpoints, because I think that’s [what] we all dream about in dermatology.”

Dr. Chovatiya disclosed that he is speaker for and/or a consultant and advisory board member to many pharmaceutical companies.

With so many treatment options available for atopic dermatitis (AD) and more in the pipeline, one common question Raj Chovatiya, MD, PhD, hears from his fellow dermatologists is: How do I choose the right therapy for my patients?

“There isn’t going to be a one-size-fits-all approach, and it may be impossible to differentiate, given that these agents are not likely to be studied head-to-head,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Chovatiya_Ray_ILL_web.jpg

He shared a list of factors to consider when engaged in shared decision-making with patients about their AD treatment options. These include:

• Severity of disease (mild vs moderate vs severe).
• Extent of disease (low vs high body surface area).
• Rapidity of drug onset (hours vs days vs weeks).
• Depth of response based on different endpoints such as itch and number of lesions.
• Long-term efficacy (durability on treatment vs off treatment).
• Adverse events (cutaneous vs systemic).
• Black box warnings (present vs absent).
• Tolerance (selective areas vs the entire skin).
• Vehicle (ointment vs cream).
• Patient preference. “This may be the biggest driver; what do patients want?” Dr. Chovatiya said.
• Access to the drug. Is it easily obtainable for the patient?

He concluded his remarks by posing a question to attendees: “Are we closer to living in a topical steroid–free world for AD? Is that what we want?” he asked. “I wholeheartedly say that’s what we’ve been working toward all these years, and we should keep up the good fight. We have more data for targeted therapy to treat very specific disease with very specific outcomes and endpoints, because I think that’s [what] we all dream about in dermatology.”

Dr. Chovatiya disclosed that he is speaker for and/or a consultant and advisory board member to many pharmaceutical companies.

With so many treatment options available for atopic dermatitis (AD) and more in the pipeline, one common question Raj Chovatiya, MD, PhD, hears from his fellow dermatologists is: How do I choose the right therapy for my patients?

“There isn’t going to be a one-size-fits-all approach, and it may be impossible to differentiate, given that these agents are not likely to be studied head-to-head,” Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Chovatiya_Ray_ILL_web.jpg

He shared a list of factors to consider when engaged in shared decision-making with patients about their AD treatment options. These include:

• Severity of disease (mild vs moderate vs severe).
• Extent of disease (low vs high body surface area).
• Rapidity of drug onset (hours vs days vs weeks).
• Depth of response based on different endpoints such as itch and number of lesions.
• Long-term efficacy (durability on treatment vs off treatment).
• Adverse events (cutaneous vs systemic).
• Black box warnings (present vs absent).
• Tolerance (selective areas vs the entire skin).
• Vehicle (ointment vs cream).
• Patient preference. “This may be the biggest driver; what do patients want?” Dr. Chovatiya said.
• Access to the drug. Is it easily obtainable for the patient?

He concluded his remarks by posing a question to attendees: “Are we closer to living in a topical steroid–free world for AD? Is that what we want?” he asked. “I wholeheartedly say that’s what we’ve been working toward all these years, and we should keep up the good fight. We have more data for targeted therapy to treat very specific disease with very specific outcomes and endpoints, because I think that’s [what] we all dream about in dermatology.”

Dr. Chovatiya disclosed that he is speaker for and/or a consultant and advisory board member to many pharmaceutical companies.

Safety data spanning up to 5 years from clinical trials of adolescents and adults using 15 mg or 30 mg of upadacitinib to treat moderate to severe atopic dermatitis (AD) indicates that rates of treatment-emergent adverse events remained low and consistent, with no new safety risks identified, underscoring the medication’s stable safety profile over an extended duration.

Those are among the key findings from an integrated analysis of long-term upadacitinib use presented by Christopher G. Bunick, MD, PhD, during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis Virtual Conference. Upadacitinib (Rinvoq) is an oral Janus kinase (JAK) inhibitor, approved by the Food and Drug Administration for adults and pediatric patients aged 12 years of age and older with refractory, moderate to severe AD in January 2022.

“What makes this study special is that these patients are followed for 260 weeks, or 5 years, and it encompasses over 7,000 patient-years of exposure,” said Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut. “This is a milestone because it’s the longest safety study ever published for any systemic drug for AD.”

Bunick_Christopher_CONN_web.jpg

He and his colleagues evaluated the safety data for up to 5 years of upadacitinib 15 mg and 30 mg use in adolescents and adults with moderate to severe AD, based on the results of integrated data from three ongoing global multicenter phase 3 trials: Measure Up 1, Measure Up 2, and AD Up. Patients in the trials were randomized 1:1:1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily alone (Measure Up 1 and 2) or with concomitant topical corticosteroids (AD Up). At week 16, patients receiving 15 mg or 30 mg upadacitinib during the double-blind period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were randomized 1:1 to receive either 15 mg or 30 mg upadacitinib in the BE period. The integrated analysis included 2683 patients (529 adolescents and 2154 adults) who received at least one dose of upadacitinib. Of these, 1337 received the 15-mg dose, while 1346 received the 30-mg dose. The researchers analyzed treatment-emergent events of special interest as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different follow-up durations.

According to Dr. Bunick, researchers often refer to “100 patient-years” in safety analyses to measure how common certain events are. “It is a straightforward way to convey the collective experience of the study’s participants over time,” he told this news organization. “For instance, if 100 patients are each monitored for 1 year, or 50 patients for 2 years each, both scenarios amount to 100 patient-years. This metric allows clinicians to understand how often certain adverse events occur across a diverse group over a specific time frame, providing a clear picture of long-term safety.”

Upadacitinib trials in atopic dermatitis have included diverse patient groups with varying risk factors. “Patients were not cherry-picked,” he said. “What I mean by that is that about 50% of patients enrolled in these trials had, at baseline, at least one cardiovascular risk factor: about 30% used tobacco; 10% had hypertension, and 5% had a history of a cardiovascular event.” In addition, about 15% were over age 50 with one cardiovascular risk factor and about 20% had a body mass index (BMI) greater than 30 kg/m². Among women in the study, about 20% were on oral contraceptives, yet none developed a venous thromboembolism (VTE).

In the integrated analysis, the rate of treatment-emergent adverse events that led to discontinuation of upadacitinib was about 4.2 events per 100 PY, “meaning that this medicine shows durability,” Dr. Bunick said. “Very few people are discontinuing due to adverse events.”

Serious and opportunistic infections ranged from 1.6 to 2.8 events per 100 PY, but these were stable across the 1- to 5-year time points. The rates of active TB were less than 0.1 per 100 PY, while the rates of herpes zoster ranged from 3.5 to 5.5 events per 100 PY. “The key take-home point here is that 5% or less of the patients at baseline had received the shingles vaccine, so it’s very important to talk to patients about receiving the shingles vaccine before they go on upadacitinib,” Dr. Bunick advised, because “this could reduce risk of herpes zoster occurring in upadacitinib-treated patients substantially.”

In other findings, incidence rates of nonmelanoma skin cancer (NMSC) ranged between 0.3 and 0.4 per 100 PY, while the rate of malignancy excluding NMSC ranged between 0.3 and 0.4 per 100 PY. Meanwhile, the rates of gastrointestinal perforations and VTE stood at 0.1 per 100 PY or lower, and MACE incidence rates ranged from 0.1 to 0.2 per 100 PY.

During his presentation, Dr. Bunick compared findings related to malignancy (excluding NMSC), MACE, and VTE to other published real-world background rates observed in moderate to severe AD populations. He noted that, while the malignancy rate in the current trial ranged from 0.3 to 0.4 per 100 PY, an observational study of more than 66,000 AD patients in the United Kingdom reported a malignancy (excluding NMSC) background incidence rate of 0.33 per 100 PY, and SEER data estimate that the malignancy incidence rate in the US general population is 0.45 per 100 PY. “Therefore, patients on upadacitinib at the 5-year mark are right at the AD population baseline risk,” he said.

And while the incidence rate of MACE in the current trial ranged from less than 0.1 to 0.2 per 100 PY, the background incidence rate of MACE in a Danish observational study of more than 2,500 patients with moderate to severe AD was 0.63 per 100 PY. “This suggests that there may be an anti-inflammatory and even a cardiovascular protective effect for patients on upadacitinib,” Dr. Bunick said.

As for VTE, the incidence rate in the current trial was 0.1 per 100 PY, but VTE background incidence rate observed in a moderate to severe AD population in the United States is 0.31 per 100 PY. “Again, this suggests anti-inflammatory and cardiovascular protective effects of upadacitinib in AD patients at the 5-year mark,” he said. “Reporting of MACE, VTE, and malignancy (excluding NMSC) in upadacitinib phase 3 clinical trials for AD generally reflects the background observations of these events in the AD population.”

He acknowledged certain limitations of the study, including the fact that observational data may overestimate the risk of adverse events.

Discussing the incidence rates for MACE, VTE, and malignancy in upadacitinib AD trials, Dr. Bunick remarked, “these are rock-bottom rates that have been low through 5 years of treatment.”

Dr. Bunick disclosed that he has received grant or research support from AbbVie (the manufacturer of upadacitinib), Almirall, Ortho Dermatologics, Timber, and Palvella. He is also a consultant and/or an adviser to AbbVie, Almirall, Apogee, Connect Bropharma, Arcutis, Eli Lilly, Novartis, Pfizer, Sanofi-Regeneron, Ortho Dermatologics, Leo Pharma, and UCB.

Safety data spanning up to 5 years from clinical trials of adolescents and adults using 15 mg or 30 mg of upadacitinib to treat moderate to severe atopic dermatitis (AD) indicates that rates of treatment-emergent adverse events remained low and consistent, with no new safety risks identified, underscoring the medication’s stable safety profile over an extended duration.

Those are among the key findings from an integrated analysis of long-term upadacitinib use presented by Christopher G. Bunick, MD, PhD, during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis Virtual Conference. Upadacitinib (Rinvoq) is an oral Janus kinase (JAK) inhibitor, approved by the Food and Drug Administration for adults and pediatric patients aged 12 years of age and older with refractory, moderate to severe AD in January 2022.

“What makes this study special is that these patients are followed for 260 weeks, or 5 years, and it encompasses over 7,000 patient-years of exposure,” said Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut. “This is a milestone because it’s the longest safety study ever published for any systemic drug for AD.”

Bunick_Christopher_CONN_web.jpg

He and his colleagues evaluated the safety data for up to 5 years of upadacitinib 15 mg and 30 mg use in adolescents and adults with moderate to severe AD, based on the results of integrated data from three ongoing global multicenter phase 3 trials: Measure Up 1, Measure Up 2, and AD Up. Patients in the trials were randomized 1:1:1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily alone (Measure Up 1 and 2) or with concomitant topical corticosteroids (AD Up). At week 16, patients receiving 15 mg or 30 mg upadacitinib during the double-blind period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were randomized 1:1 to receive either 15 mg or 30 mg upadacitinib in the BE period. The integrated analysis included 2683 patients (529 adolescents and 2154 adults) who received at least one dose of upadacitinib. Of these, 1337 received the 15-mg dose, while 1346 received the 30-mg dose. The researchers analyzed treatment-emergent events of special interest as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different follow-up durations.

According to Dr. Bunick, researchers often refer to “100 patient-years” in safety analyses to measure how common certain events are. “It is a straightforward way to convey the collective experience of the study’s participants over time,” he told this news organization. “For instance, if 100 patients are each monitored for 1 year, or 50 patients for 2 years each, both scenarios amount to 100 patient-years. This metric allows clinicians to understand how often certain adverse events occur across a diverse group over a specific time frame, providing a clear picture of long-term safety.”

Upadacitinib trials in atopic dermatitis have included diverse patient groups with varying risk factors. “Patients were not cherry-picked,” he said. “What I mean by that is that about 50% of patients enrolled in these trials had, at baseline, at least one cardiovascular risk factor: about 30% used tobacco; 10% had hypertension, and 5% had a history of a cardiovascular event.” In addition, about 15% were over age 50 with one cardiovascular risk factor and about 20% had a body mass index (BMI) greater than 30 kg/m². Among women in the study, about 20% were on oral contraceptives, yet none developed a venous thromboembolism (VTE).

In the integrated analysis, the rate of treatment-emergent adverse events that led to discontinuation of upadacitinib was about 4.2 events per 100 PY, “meaning that this medicine shows durability,” Dr. Bunick said. “Very few people are discontinuing due to adverse events.”

Serious and opportunistic infections ranged from 1.6 to 2.8 events per 100 PY, but these were stable across the 1- to 5-year time points. The rates of active TB were less than 0.1 per 100 PY, while the rates of herpes zoster ranged from 3.5 to 5.5 events per 100 PY. “The key take-home point here is that 5% or less of the patients at baseline had received the shingles vaccine, so it’s very important to talk to patients about receiving the shingles vaccine before they go on upadacitinib,” Dr. Bunick advised, because “this could reduce risk of herpes zoster occurring in upadacitinib-treated patients substantially.”

In other findings, incidence rates of nonmelanoma skin cancer (NMSC) ranged between 0.3 and 0.4 per 100 PY, while the rate of malignancy excluding NMSC ranged between 0.3 and 0.4 per 100 PY. Meanwhile, the rates of gastrointestinal perforations and VTE stood at 0.1 per 100 PY or lower, and MACE incidence rates ranged from 0.1 to 0.2 per 100 PY.

During his presentation, Dr. Bunick compared findings related to malignancy (excluding NMSC), MACE, and VTE to other published real-world background rates observed in moderate to severe AD populations. He noted that, while the malignancy rate in the current trial ranged from 0.3 to 0.4 per 100 PY, an observational study of more than 66,000 AD patients in the United Kingdom reported a malignancy (excluding NMSC) background incidence rate of 0.33 per 100 PY, and SEER data estimate that the malignancy incidence rate in the US general population is 0.45 per 100 PY. “Therefore, patients on upadacitinib at the 5-year mark are right at the AD population baseline risk,” he said.

And while the incidence rate of MACE in the current trial ranged from less than 0.1 to 0.2 per 100 PY, the background incidence rate of MACE in a Danish observational study of more than 2,500 patients with moderate to severe AD was 0.63 per 100 PY. “This suggests that there may be an anti-inflammatory and even a cardiovascular protective effect for patients on upadacitinib,” Dr. Bunick said.

As for VTE, the incidence rate in the current trial was 0.1 per 100 PY, but VTE background incidence rate observed in a moderate to severe AD population in the United States is 0.31 per 100 PY. “Again, this suggests anti-inflammatory and cardiovascular protective effects of upadacitinib in AD patients at the 5-year mark,” he said. “Reporting of MACE, VTE, and malignancy (excluding NMSC) in upadacitinib phase 3 clinical trials for AD generally reflects the background observations of these events in the AD population.”

He acknowledged certain limitations of the study, including the fact that observational data may overestimate the risk of adverse events.

Discussing the incidence rates for MACE, VTE, and malignancy in upadacitinib AD trials, Dr. Bunick remarked, “these are rock-bottom rates that have been low through 5 years of treatment.”

Dr. Bunick disclosed that he has received grant or research support from AbbVie (the manufacturer of upadacitinib), Almirall, Ortho Dermatologics, Timber, and Palvella. He is also a consultant and/or an adviser to AbbVie, Almirall, Apogee, Connect Bropharma, Arcutis, Eli Lilly, Novartis, Pfizer, Sanofi-Regeneron, Ortho Dermatologics, Leo Pharma, and UCB.

Safety data spanning up to 5 years from clinical trials of adolescents and adults using 15 mg or 30 mg of upadacitinib to treat moderate to severe atopic dermatitis (AD) indicates that rates of treatment-emergent adverse events remained low and consistent, with no new safety risks identified, underscoring the medication’s stable safety profile over an extended duration.

Those are among the key findings from an integrated analysis of long-term upadacitinib use presented by Christopher G. Bunick, MD, PhD, during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis Virtual Conference. Upadacitinib (Rinvoq) is an oral Janus kinase (JAK) inhibitor, approved by the Food and Drug Administration for adults and pediatric patients aged 12 years of age and older with refractory, moderate to severe AD in January 2022.

“What makes this study special is that these patients are followed for 260 weeks, or 5 years, and it encompasses over 7,000 patient-years of exposure,” said Dr. Bunick, associate professor of dermatology at Yale University, New Haven, Connecticut. “This is a milestone because it’s the longest safety study ever published for any systemic drug for AD.”

Bunick_Christopher_CONN_web.jpg

He and his colleagues evaluated the safety data for up to 5 years of upadacitinib 15 mg and 30 mg use in adolescents and adults with moderate to severe AD, based on the results of integrated data from three ongoing global multicenter phase 3 trials: Measure Up 1, Measure Up 2, and AD Up. Patients in the trials were randomized 1:1:1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily alone (Measure Up 1 and 2) or with concomitant topical corticosteroids (AD Up). At week 16, patients receiving 15 mg or 30 mg upadacitinib during the double-blind period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were randomized 1:1 to receive either 15 mg or 30 mg upadacitinib in the BE period. The integrated analysis included 2683 patients (529 adolescents and 2154 adults) who received at least one dose of upadacitinib. Of these, 1337 received the 15-mg dose, while 1346 received the 30-mg dose. The researchers analyzed treatment-emergent events of special interest as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different follow-up durations.

According to Dr. Bunick, researchers often refer to “100 patient-years” in safety analyses to measure how common certain events are. “It is a straightforward way to convey the collective experience of the study’s participants over time,” he told this news organization. “For instance, if 100 patients are each monitored for 1 year, or 50 patients for 2 years each, both scenarios amount to 100 patient-years. This metric allows clinicians to understand how often certain adverse events occur across a diverse group over a specific time frame, providing a clear picture of long-term safety.”

Upadacitinib trials in atopic dermatitis have included diverse patient groups with varying risk factors. “Patients were not cherry-picked,” he said. “What I mean by that is that about 50% of patients enrolled in these trials had, at baseline, at least one cardiovascular risk factor: about 30% used tobacco; 10% had hypertension, and 5% had a history of a cardiovascular event.” In addition, about 15% were over age 50 with one cardiovascular risk factor and about 20% had a body mass index (BMI) greater than 30 kg/m². Among women in the study, about 20% were on oral contraceptives, yet none developed a venous thromboembolism (VTE).

In the integrated analysis, the rate of treatment-emergent adverse events that led to discontinuation of upadacitinib was about 4.2 events per 100 PY, “meaning that this medicine shows durability,” Dr. Bunick said. “Very few people are discontinuing due to adverse events.”

Serious and opportunistic infections ranged from 1.6 to 2.8 events per 100 PY, but these were stable across the 1- to 5-year time points. The rates of active TB were less than 0.1 per 100 PY, while the rates of herpes zoster ranged from 3.5 to 5.5 events per 100 PY. “The key take-home point here is that 5% or less of the patients at baseline had received the shingles vaccine, so it’s very important to talk to patients about receiving the shingles vaccine before they go on upadacitinib,” Dr. Bunick advised, because “this could reduce risk of herpes zoster occurring in upadacitinib-treated patients substantially.”

In other findings, incidence rates of nonmelanoma skin cancer (NMSC) ranged between 0.3 and 0.4 per 100 PY, while the rate of malignancy excluding NMSC ranged between 0.3 and 0.4 per 100 PY. Meanwhile, the rates of gastrointestinal perforations and VTE stood at 0.1 per 100 PY or lower, and MACE incidence rates ranged from 0.1 to 0.2 per 100 PY.

During his presentation, Dr. Bunick compared findings related to malignancy (excluding NMSC), MACE, and VTE to other published real-world background rates observed in moderate to severe AD populations. He noted that, while the malignancy rate in the current trial ranged from 0.3 to 0.4 per 100 PY, an observational study of more than 66,000 AD patients in the United Kingdom reported a malignancy (excluding NMSC) background incidence rate of 0.33 per 100 PY, and SEER data estimate that the malignancy incidence rate in the US general population is 0.45 per 100 PY. “Therefore, patients on upadacitinib at the 5-year mark are right at the AD population baseline risk,” he said.

And while the incidence rate of MACE in the current trial ranged from less than 0.1 to 0.2 per 100 PY, the background incidence rate of MACE in a Danish observational study of more than 2,500 patients with moderate to severe AD was 0.63 per 100 PY. “This suggests that there may be an anti-inflammatory and even a cardiovascular protective effect for patients on upadacitinib,” Dr. Bunick said.

As for VTE, the incidence rate in the current trial was 0.1 per 100 PY, but VTE background incidence rate observed in a moderate to severe AD population in the United States is 0.31 per 100 PY. “Again, this suggests anti-inflammatory and cardiovascular protective effects of upadacitinib in AD patients at the 5-year mark,” he said. “Reporting of MACE, VTE, and malignancy (excluding NMSC) in upadacitinib phase 3 clinical trials for AD generally reflects the background observations of these events in the AD population.”

He acknowledged certain limitations of the study, including the fact that observational data may overestimate the risk of adverse events.

Discussing the incidence rates for MACE, VTE, and malignancy in upadacitinib AD trials, Dr. Bunick remarked, “these are rock-bottom rates that have been low through 5 years of treatment.”

Dr. Bunick disclosed that he has received grant or research support from AbbVie (the manufacturer of upadacitinib), Almirall, Ortho Dermatologics, Timber, and Palvella. He is also a consultant and/or an adviser to AbbVie, Almirall, Apogee, Connect Bropharma, Arcutis, Eli Lilly, Novartis, Pfizer, Sanofi-Regeneron, Ortho Dermatologics, Leo Pharma, and UCB.

The prevalence of clinically meaningful conjunctivitis in patients taking dupilumab for atopic dermatitis (AD) is likely about 2%, and it most often occurs in the first 16 weeks of therapy.

Those are key findings from an analysis of published trials of dupilumab for AD and other conditions that study author Matthew Zirwas, MD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Adults with AD have a significant and disease severity–dependent increased risk of developing ocular surface diseases, including conjunctivitis and keratitis, compared with the general population and independent of any drug effect, according to Dr. Zirwas, a dermatologist with Probity Medical Research of Columbus, Ohio.

Zirwas_Matthew_OHIO_web.jpg

Dupilumab inhibits signaling of interleukin (IL)-4 and IL-13, which drive type 2 inflammatory diseases such as AD, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), prurigo nodularis (PN), and chronic spontaneous urticaria (CSU).

In randomized, placebo-controlled trials of dupilumab in patients with moderate to severe AD, conjunctivitis was reported in more patients who received dupilumab treatment than in placebo-treated patients.

“When it comes to dupilumab-induced conjunctivitis, we have a good idea of the etiology, but the question of how frequently it occurs versus how frequently the conjunctivitis is unrelated to dupilumab is an interesting one,” he said. “How often is it clinically meaningful? What is it that is so unique about AD patients? We’ve all heard that it is a unique adverse event that only happens to people with AD and not to people using dupilumab for other indications. Where it gets interesting to me is how do we differentiate the cases that are dupilumab induced versus the cases that are just part of the underlying AD process?”

For their analysis, Dr. Zirwas and co-authors reviewed the incidence of conjunctivitis adverse events in patients from 15 completed, randomized, double-blind placebo-controlled trials evaluating dupilumab in AD, asthma, CRSwNP, EoE, PN, and CSU, along with the severity and resolution of conjunctivitis events in adults with AD.

Of the 15 trials, 7 were conducted in patients with AD: 4 in adults, 1 in adolescents, 1 in school-aged children, and 1 in preschoolers. One of the AD trials, LIBERTY AD CHRONOS, extends 52 weeks. The remaining eight trials of patients with asthma, CRSwNP, EoE, PN, and CSU lasted 24-52 weeks.

In the non-AD trials, the researchers observed that conjunctivitis rates were generally in the 1%-3% range, with less pronounced or no differences between the dupilumab and placebo groups. In the AD trials, conjunctivitis rates were higher in patients receiving dupilumab, compared with those receiving placebo across age groups.

In the 16-week SOLO 1 & 2 and AD-1021 monotherapy trials, 12 conjunctivitis events occurred in 517 patients who received placebo (2%), compared with 103 of 1047 patients (9.84%) who received dupilumab. Of the dupilumab-associated conjunctivitis cases, 80 (78%) patients recovered by the end of the trials. Of the 23 cases of conjunctivitis that did not recover or dropped out of the trial, 15 were among the 529 patients who received 300 mg dupilumab once every 2 weeks (q2w) (3%) and eight were among the 518 who received 300 mg dupilumab once weekly (qw) (2%).

In the 52-week LIBERTY AD CHRONOS trial, 29 conjunctivitis events occurred in 315 patients who received placebo plus topical corticosteroid (TCS) (9%), compared with 113 of 425 patients (27%) who received dupilumab plus TCS. Of these, 103 (91%) recovered by the end of the trial. Of the 11 patients with conjunctivitis who did not recover or dropped out of the trial, 3 were among the 110 patients who received 300 mg dupilumab q2w plus TCS (3%), and 8 were among the 315 who received 300 mg dupilumab qw plus TCS (3%).

“When I look at all of this data, I think that about 2% of people treated with dupilumab are going to get clinically very meaningful conjunctivitis that may be therapy limiting,” Dr. Zirwas concluded. “The vast majority of those cases appear to happen in the first 16 weeks. This is just not something we see in cases of patients treated with dupilumab treated for other reasons.”

Following his presentation, a meeting attendee asked Dr. Zirwas if conjunctivitis occurs more often in patients with facial dermatitis. “My perception is that it happens more often in people who have facial or eyelid dermatitis, but I’ve seen it in plenty of people who didn’t have any facial or eyelid dermatitis,” he said. “I have seen more conjunctivitis in people with more severe AD and more severe atopic comorbidities. That is anecdotal. The data that I have seen has been back and forth on this topic.”

Dr. Zirwas disclosed that he is a speaker and consultant for Sanofi, Regeneron, Leo, Lilly, Galderma, Pfizer, and AbbVie. Several of his co-authors work for Regeneron Pharmaceuticals.

The prevalence of clinically meaningful conjunctivitis in patients taking dupilumab for atopic dermatitis (AD) is likely about 2%, and it most often occurs in the first 16 weeks of therapy.

Those are key findings from an analysis of published trials of dupilumab for AD and other conditions that study author Matthew Zirwas, MD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Adults with AD have a significant and disease severity–dependent increased risk of developing ocular surface diseases, including conjunctivitis and keratitis, compared with the general population and independent of any drug effect, according to Dr. Zirwas, a dermatologist with Probity Medical Research of Columbus, Ohio.

Zirwas_Matthew_OHIO_web.jpg

Dupilumab inhibits signaling of interleukin (IL)-4 and IL-13, which drive type 2 inflammatory diseases such as AD, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), prurigo nodularis (PN), and chronic spontaneous urticaria (CSU).

In randomized, placebo-controlled trials of dupilumab in patients with moderate to severe AD, conjunctivitis was reported in more patients who received dupilumab treatment than in placebo-treated patients.

“When it comes to dupilumab-induced conjunctivitis, we have a good idea of the etiology, but the question of how frequently it occurs versus how frequently the conjunctivitis is unrelated to dupilumab is an interesting one,” he said. “How often is it clinically meaningful? What is it that is so unique about AD patients? We’ve all heard that it is a unique adverse event that only happens to people with AD and not to people using dupilumab for other indications. Where it gets interesting to me is how do we differentiate the cases that are dupilumab induced versus the cases that are just part of the underlying AD process?”

For their analysis, Dr. Zirwas and co-authors reviewed the incidence of conjunctivitis adverse events in patients from 15 completed, randomized, double-blind placebo-controlled trials evaluating dupilumab in AD, asthma, CRSwNP, EoE, PN, and CSU, along with the severity and resolution of conjunctivitis events in adults with AD.

Of the 15 trials, 7 were conducted in patients with AD: 4 in adults, 1 in adolescents, 1 in school-aged children, and 1 in preschoolers. One of the AD trials, LIBERTY AD CHRONOS, extends 52 weeks. The remaining eight trials of patients with asthma, CRSwNP, EoE, PN, and CSU lasted 24-52 weeks.

In the non-AD trials, the researchers observed that conjunctivitis rates were generally in the 1%-3% range, with less pronounced or no differences between the dupilumab and placebo groups. In the AD trials, conjunctivitis rates were higher in patients receiving dupilumab, compared with those receiving placebo across age groups.

In the 16-week SOLO 1 & 2 and AD-1021 monotherapy trials, 12 conjunctivitis events occurred in 517 patients who received placebo (2%), compared with 103 of 1047 patients (9.84%) who received dupilumab. Of the dupilumab-associated conjunctivitis cases, 80 (78%) patients recovered by the end of the trials. Of the 23 cases of conjunctivitis that did not recover or dropped out of the trial, 15 were among the 529 patients who received 300 mg dupilumab once every 2 weeks (q2w) (3%) and eight were among the 518 who received 300 mg dupilumab once weekly (qw) (2%).

In the 52-week LIBERTY AD CHRONOS trial, 29 conjunctivitis events occurred in 315 patients who received placebo plus topical corticosteroid (TCS) (9%), compared with 113 of 425 patients (27%) who received dupilumab plus TCS. Of these, 103 (91%) recovered by the end of the trial. Of the 11 patients with conjunctivitis who did not recover or dropped out of the trial, 3 were among the 110 patients who received 300 mg dupilumab q2w plus TCS (3%), and 8 were among the 315 who received 300 mg dupilumab qw plus TCS (3%).

“When I look at all of this data, I think that about 2% of people treated with dupilumab are going to get clinically very meaningful conjunctivitis that may be therapy limiting,” Dr. Zirwas concluded. “The vast majority of those cases appear to happen in the first 16 weeks. This is just not something we see in cases of patients treated with dupilumab treated for other reasons.”

Following his presentation, a meeting attendee asked Dr. Zirwas if conjunctivitis occurs more often in patients with facial dermatitis. “My perception is that it happens more often in people who have facial or eyelid dermatitis, but I’ve seen it in plenty of people who didn’t have any facial or eyelid dermatitis,” he said. “I have seen more conjunctivitis in people with more severe AD and more severe atopic comorbidities. That is anecdotal. The data that I have seen has been back and forth on this topic.”

Dr. Zirwas disclosed that he is a speaker and consultant for Sanofi, Regeneron, Leo, Lilly, Galderma, Pfizer, and AbbVie. Several of his co-authors work for Regeneron Pharmaceuticals.

The prevalence of clinically meaningful conjunctivitis in patients taking dupilumab for atopic dermatitis (AD) is likely about 2%, and it most often occurs in the first 16 weeks of therapy.

Those are key findings from an analysis of published trials of dupilumab for AD and other conditions that study author Matthew Zirwas, MD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Adults with AD have a significant and disease severity–dependent increased risk of developing ocular surface diseases, including conjunctivitis and keratitis, compared with the general population and independent of any drug effect, according to Dr. Zirwas, a dermatologist with Probity Medical Research of Columbus, Ohio.

Zirwas_Matthew_OHIO_web.jpg

Dupilumab inhibits signaling of interleukin (IL)-4 and IL-13, which drive type 2 inflammatory diseases such as AD, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), prurigo nodularis (PN), and chronic spontaneous urticaria (CSU).

In randomized, placebo-controlled trials of dupilumab in patients with moderate to severe AD, conjunctivitis was reported in more patients who received dupilumab treatment than in placebo-treated patients.

“When it comes to dupilumab-induced conjunctivitis, we have a good idea of the etiology, but the question of how frequently it occurs versus how frequently the conjunctivitis is unrelated to dupilumab is an interesting one,” he said. “How often is it clinically meaningful? What is it that is so unique about AD patients? We’ve all heard that it is a unique adverse event that only happens to people with AD and not to people using dupilumab for other indications. Where it gets interesting to me is how do we differentiate the cases that are dupilumab induced versus the cases that are just part of the underlying AD process?”

For their analysis, Dr. Zirwas and co-authors reviewed the incidence of conjunctivitis adverse events in patients from 15 completed, randomized, double-blind placebo-controlled trials evaluating dupilumab in AD, asthma, CRSwNP, EoE, PN, and CSU, along with the severity and resolution of conjunctivitis events in adults with AD.

Of the 15 trials, 7 were conducted in patients with AD: 4 in adults, 1 in adolescents, 1 in school-aged children, and 1 in preschoolers. One of the AD trials, LIBERTY AD CHRONOS, extends 52 weeks. The remaining eight trials of patients with asthma, CRSwNP, EoE, PN, and CSU lasted 24-52 weeks.

In the non-AD trials, the researchers observed that conjunctivitis rates were generally in the 1%-3% range, with less pronounced or no differences between the dupilumab and placebo groups. In the AD trials, conjunctivitis rates were higher in patients receiving dupilumab, compared with those receiving placebo across age groups.

In the 16-week SOLO 1 & 2 and AD-1021 monotherapy trials, 12 conjunctivitis events occurred in 517 patients who received placebo (2%), compared with 103 of 1047 patients (9.84%) who received dupilumab. Of the dupilumab-associated conjunctivitis cases, 80 (78%) patients recovered by the end of the trials. Of the 23 cases of conjunctivitis that did not recover or dropped out of the trial, 15 were among the 529 patients who received 300 mg dupilumab once every 2 weeks (q2w) (3%) and eight were among the 518 who received 300 mg dupilumab once weekly (qw) (2%).

In the 52-week LIBERTY AD CHRONOS trial, 29 conjunctivitis events occurred in 315 patients who received placebo plus topical corticosteroid (TCS) (9%), compared with 113 of 425 patients (27%) who received dupilumab plus TCS. Of these, 103 (91%) recovered by the end of the trial. Of the 11 patients with conjunctivitis who did not recover or dropped out of the trial, 3 were among the 110 patients who received 300 mg dupilumab q2w plus TCS (3%), and 8 were among the 315 who received 300 mg dupilumab qw plus TCS (3%).

“When I look at all of this data, I think that about 2% of people treated with dupilumab are going to get clinically very meaningful conjunctivitis that may be therapy limiting,” Dr. Zirwas concluded. “The vast majority of those cases appear to happen in the first 16 weeks. This is just not something we see in cases of patients treated with dupilumab treated for other reasons.”

Following his presentation, a meeting attendee asked Dr. Zirwas if conjunctivitis occurs more often in patients with facial dermatitis. “My perception is that it happens more often in people who have facial or eyelid dermatitis, but I’ve seen it in plenty of people who didn’t have any facial or eyelid dermatitis,” he said. “I have seen more conjunctivitis in people with more severe AD and more severe atopic comorbidities. That is anecdotal. The data that I have seen has been back and forth on this topic.”

Dr. Zirwas disclosed that he is a speaker and consultant for Sanofi, Regeneron, Leo, Lilly, Galderma, Pfizer, and AbbVie. Several of his co-authors work for Regeneron Pharmaceuticals.

Among patients with moderate-to-severe atopic dermatitis (AD) treated with the oral Janus kinase inhibitor upadacitinib for 4 or more weeks, more than half achieved clear or almost clear skin and 45% or more reported no or minimal itch, results from an analysis of registry data showed.

“We know from clinical trials that upadacitinib is effective, but we have very little real-world experience on its effectiveness,” presenting study author Melinda Gooderham, MD, medical director of the Skin Center for Dermatology in Peterborough, Ontario, Canada, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Gooderham_Melinda_CANADA_web.jpg

For the analysis, she and her coauthors evaluated the real-world clinical and patient-reported outcomes of 335 adults enrolled in the CorEvitas AD Registry from July 21, 2020, through Aug. 7, 2023. They included patients who were on upadacitinib for at least 4 weeks and persisted on the drug until the time of evaluation.

The CorEvitas AD Registry is a prospective, non-interventional registry of adults diagnosed with AD by a dermatologist or qualified dermatology practitioner. Outcomes measures included the proportion of patients who achieved skin clearance as defined by a Validated Investigators Global Assessment Scale for Atopic Dermatitis (vIGA) score of 0 or 1, an Eczema Area and Severity Index (EASI) score of 3 or less, a Peak Pruritus Numeric Rating Scale (PP-NRS) score of 0 or 1, Patient-Oriented Eczema Measure (POEM) scores of 0-2, Dermatology Life Quality Index (DLQI) scores of 0 or 1, or an Atopic Dermatitis Control Tool (ADCT) score of <7.

The researchers evaluated cross-sectional data from three different cohorts: data from the last registry visit (the overall cohort), data from a visit within 1 month to less than 5 months of upadacitinib initiation (the 1-5 months cohort), and data from a visit within 5-9 months following upadacitinib initiation (the 5-9 months cohort). They also conducted subgroup analyses of patients with prior use of biologics for AD (bio-experience) and those with no such history (bio-naive). Safety events were not assessed in this analysis.

The mean age of the 335 patients was 45.6 years, 51.6% were female, 64.2% were White, 64.2% were based in the United States and the rest were based in Canada. Most patients (70.8%) were treated with the 15-mg dose of upadacitinib. The median duration of treatment was 6.9 months. Slightly more than one-quarter of patients (28.1%) reported concomitant use of topical corticosteroids for AD, while 45.4% reported prior use of dupilumab and 6% reported prior use of tralokinumab.

[embed:render:related:node:250777]

Dr. Gooderham reported that 57.5% of patients in the total cohort total cohort achieved clear or almost clear skin (a vIGA-AD score of 0 or 1), with slight differences between the bio-naive (60.6%) and bio-experienced (54.1%) subgroups.

The other outcomes were similarly close between the 176 bio-naive and 159 bio-experienced patients. Specifically, 74.8% in the total cohort, 79.4% in the bio-naive subgroup, and 69.6% in the bio-experienced subgroup achieved an EASI score of 3 or less. In the measure of the worst itch in the past 24 hours, 45.3%, 47.7%, and 42.8% respectively achieved a PP-NRS of 0 or 1. In the patient-reported disease burden, 36.4%, 41%, and 31.4% achieved a POEM score of 0-2. In the quality of life measure, 39.8%, 42.8%, and 36.5% achieved a DLQI score of 0 or 1. In the measure of disease control, 69.3%, 70.5%, and 67.9% achieved an ADCT score of <7. In a combination of skin clearance and itch control, 40.9%, 43.2%, and 38.4% of the total cohort, bio-naive, and bio-experienced respectively achieved both an EASI score of 3 or less and a PP-NRS of 0 or 1.

The study outcomes were similar between the 1-5 months cohort and the 5-9 months cohort, but there was a trend toward more clearance the longer patients were on therapy.

“The findings suggest that low levels of disease severity are observed in patients on upadacitinib in a real-world setting,” Dr. Gooderham concluded. “This confirms what we see in the clinical trials.”

She disclosed that she is a consultant to, a speaker for, and/or a member of the advisory board for many pharmaceutical companies, including AbbVie.

Among patients with moderate-to-severe atopic dermatitis (AD) treated with the oral Janus kinase inhibitor upadacitinib for 4 or more weeks, more than half achieved clear or almost clear skin and 45% or more reported no or minimal itch, results from an analysis of registry data showed.

“We know from clinical trials that upadacitinib is effective, but we have very little real-world experience on its effectiveness,” presenting study author Melinda Gooderham, MD, medical director of the Skin Center for Dermatology in Peterborough, Ontario, Canada, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Gooderham_Melinda_CANADA_web.jpg

For the analysis, she and her coauthors evaluated the real-world clinical and patient-reported outcomes of 335 adults enrolled in the CorEvitas AD Registry from July 21, 2020, through Aug. 7, 2023. They included patients who were on upadacitinib for at least 4 weeks and persisted on the drug until the time of evaluation.

The CorEvitas AD Registry is a prospective, non-interventional registry of adults diagnosed with AD by a dermatologist or qualified dermatology practitioner. Outcomes measures included the proportion of patients who achieved skin clearance as defined by a Validated Investigators Global Assessment Scale for Atopic Dermatitis (vIGA) score of 0 or 1, an Eczema Area and Severity Index (EASI) score of 3 or less, a Peak Pruritus Numeric Rating Scale (PP-NRS) score of 0 or 1, Patient-Oriented Eczema Measure (POEM) scores of 0-2, Dermatology Life Quality Index (DLQI) scores of 0 or 1, or an Atopic Dermatitis Control Tool (ADCT) score of <7.

The researchers evaluated cross-sectional data from three different cohorts: data from the last registry visit (the overall cohort), data from a visit within 1 month to less than 5 months of upadacitinib initiation (the 1-5 months cohort), and data from a visit within 5-9 months following upadacitinib initiation (the 5-9 months cohort). They also conducted subgroup analyses of patients with prior use of biologics for AD (bio-experience) and those with no such history (bio-naive). Safety events were not assessed in this analysis.

The mean age of the 335 patients was 45.6 years, 51.6% were female, 64.2% were White, 64.2% were based in the United States and the rest were based in Canada. Most patients (70.8%) were treated with the 15-mg dose of upadacitinib. The median duration of treatment was 6.9 months. Slightly more than one-quarter of patients (28.1%) reported concomitant use of topical corticosteroids for AD, while 45.4% reported prior use of dupilumab and 6% reported prior use of tralokinumab.

[embed:render:related:node:250777]

Dr. Gooderham reported that 57.5% of patients in the total cohort total cohort achieved clear or almost clear skin (a vIGA-AD score of 0 or 1), with slight differences between the bio-naive (60.6%) and bio-experienced (54.1%) subgroups.

The other outcomes were similarly close between the 176 bio-naive and 159 bio-experienced patients. Specifically, 74.8% in the total cohort, 79.4% in the bio-naive subgroup, and 69.6% in the bio-experienced subgroup achieved an EASI score of 3 or less. In the measure of the worst itch in the past 24 hours, 45.3%, 47.7%, and 42.8% respectively achieved a PP-NRS of 0 or 1. In the patient-reported disease burden, 36.4%, 41%, and 31.4% achieved a POEM score of 0-2. In the quality of life measure, 39.8%, 42.8%, and 36.5% achieved a DLQI score of 0 or 1. In the measure of disease control, 69.3%, 70.5%, and 67.9% achieved an ADCT score of <7. In a combination of skin clearance and itch control, 40.9%, 43.2%, and 38.4% of the total cohort, bio-naive, and bio-experienced respectively achieved both an EASI score of 3 or less and a PP-NRS of 0 or 1.

The study outcomes were similar between the 1-5 months cohort and the 5-9 months cohort, but there was a trend toward more clearance the longer patients were on therapy.

“The findings suggest that low levels of disease severity are observed in patients on upadacitinib in a real-world setting,” Dr. Gooderham concluded. “This confirms what we see in the clinical trials.”

She disclosed that she is a consultant to, a speaker for, and/or a member of the advisory board for many pharmaceutical companies, including AbbVie.

Among patients with moderate-to-severe atopic dermatitis (AD) treated with the oral Janus kinase inhibitor upadacitinib for 4 or more weeks, more than half achieved clear or almost clear skin and 45% or more reported no or minimal itch, results from an analysis of registry data showed.

“We know from clinical trials that upadacitinib is effective, but we have very little real-world experience on its effectiveness,” presenting study author Melinda Gooderham, MD, medical director of the Skin Center for Dermatology in Peterborough, Ontario, Canada, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Gooderham_Melinda_CANADA_web.jpg

For the analysis, she and her coauthors evaluated the real-world clinical and patient-reported outcomes of 335 adults enrolled in the CorEvitas AD Registry from July 21, 2020, through Aug. 7, 2023. They included patients who were on upadacitinib for at least 4 weeks and persisted on the drug until the time of evaluation.

The CorEvitas AD Registry is a prospective, non-interventional registry of adults diagnosed with AD by a dermatologist or qualified dermatology practitioner. Outcomes measures included the proportion of patients who achieved skin clearance as defined by a Validated Investigators Global Assessment Scale for Atopic Dermatitis (vIGA) score of 0 or 1, an Eczema Area and Severity Index (EASI) score of 3 or less, a Peak Pruritus Numeric Rating Scale (PP-NRS) score of 0 or 1, Patient-Oriented Eczema Measure (POEM) scores of 0-2, Dermatology Life Quality Index (DLQI) scores of 0 or 1, or an Atopic Dermatitis Control Tool (ADCT) score of <7.

The researchers evaluated cross-sectional data from three different cohorts: data from the last registry visit (the overall cohort), data from a visit within 1 month to less than 5 months of upadacitinib initiation (the 1-5 months cohort), and data from a visit within 5-9 months following upadacitinib initiation (the 5-9 months cohort). They also conducted subgroup analyses of patients with prior use of biologics for AD (bio-experience) and those with no such history (bio-naive). Safety events were not assessed in this analysis.

The mean age of the 335 patients was 45.6 years, 51.6% were female, 64.2% were White, 64.2% were based in the United States and the rest were based in Canada. Most patients (70.8%) were treated with the 15-mg dose of upadacitinib. The median duration of treatment was 6.9 months. Slightly more than one-quarter of patients (28.1%) reported concomitant use of topical corticosteroids for AD, while 45.4% reported prior use of dupilumab and 6% reported prior use of tralokinumab.

[embed:render:related:node:250777]

Dr. Gooderham reported that 57.5% of patients in the total cohort total cohort achieved clear or almost clear skin (a vIGA-AD score of 0 or 1), with slight differences between the bio-naive (60.6%) and bio-experienced (54.1%) subgroups.

The other outcomes were similarly close between the 176 bio-naive and 159 bio-experienced patients. Specifically, 74.8% in the total cohort, 79.4% in the bio-naive subgroup, and 69.6% in the bio-experienced subgroup achieved an EASI score of 3 or less. In the measure of the worst itch in the past 24 hours, 45.3%, 47.7%, and 42.8% respectively achieved a PP-NRS of 0 or 1. In the patient-reported disease burden, 36.4%, 41%, and 31.4% achieved a POEM score of 0-2. In the quality of life measure, 39.8%, 42.8%, and 36.5% achieved a DLQI score of 0 or 1. In the measure of disease control, 69.3%, 70.5%, and 67.9% achieved an ADCT score of <7. In a combination of skin clearance and itch control, 40.9%, 43.2%, and 38.4% of the total cohort, bio-naive, and bio-experienced respectively achieved both an EASI score of 3 or less and a PP-NRS of 0 or 1.

The study outcomes were similar between the 1-5 months cohort and the 5-9 months cohort, but there was a trend toward more clearance the longer patients were on therapy.

“The findings suggest that low levels of disease severity are observed in patients on upadacitinib in a real-world setting,” Dr. Gooderham concluded. “This confirms what we see in the clinical trials.”

She disclosed that she is a consultant to, a speaker for, and/or a member of the advisory board for many pharmaceutical companies, including AbbVie.

Delusions of parasitosis is linked to female gender, older age, polypharmacy with more than five drugs, and certain types of drugs (attention-deficit/hyperactivity disorder drugs, selective serotonin reuptake inhibitors, gabapentin, and opioids), reported researchers in a small retrospective case-control study.

Delusions of parasitosis (DOP) affects mostly middle-aged women and has associations with renal failure and some medications, wrote corresponding author Colleen Reisz, MD, a dermatologist with the department of internal medicine at the University of Missouri–Kansas City School of Medicine, and her coauthors. The study was published online December 15, 2023, in the Journal of the American Academy of Dermatology.

“We hypothesize that vulnerability to DOP emerges when multiple factors combine, such as age, sex, medications, and changes in [drug] clearance capacity,” Dr. Reisz and her coauthors wrote. “Changes in health care, such as the dramatic increase in stimulant prescriptions and alternatives to opioids in pain management, may be contributing to off target drug effects on the brain.”

[embed:render:related:node:235540]

To test their hypothesis, the researchers conducted a case-control study of biometric and pharmaceutical data from 34 patients with DOP which they compared to an age-matched control group of 53 women presenting with a dermatitis above the clavicle from a general dermatology practice between 2012 and 2020. They de-identified the data and performed statistical analysis on variables that included biometric data and intake of pharmaceuticals and nutraceuticals. Polypharmacy was defined as five or more drugs.

Of the 34 patients with DOP, 27 were women with a mean age of 58 years and 7 were men with a mean age of 60 years. Dr. Reisz and her colleagues observed statistical significance between cases and controls in terms of polypharmacy (P = .011), attention-deficit/hyperactivity disorder medications (P < .001), selective serotonin reuptake inhibitors (P = .005), opioids (P = .003), and gabapentin (P = .003).

In other findings, half of DOP cases presented with samples of perceived parasitic material, and four associated the perceived infestation with a single emotion-laden event. This prompted the researchers “to consider that DOP may share mechanisms with fear conditioning and extinction,” they wrote. “Fear conditioning refers to the process of memory acquisition and extinction. This process is essential for survival and has been studied in posttraumatic stress disorder.”

They acknowledged certain limitations of the study, including its retrospective single-center design and the lack of control for factors such as socioeconomic background and level of education.

“Patients with DOP should undergo detailed drug histories and examination of clearance profiles, especially renal function,” the researchers concluded.

Evan A. Rieder, MD, a New York City–based dermatologist and psychiatrist who was asked to comment on the study, said that delusional infestation is one of the most difficult medical conditions to treat and study.

Rieder_Evan_NY_web.JPG

“Though the numbers of cases in this research letter are small, they are instructive in demonstrating a high burden of polypharmacy including psychostimulants, opioids, and SSRIs in such patients,” he told this news organization. “Dermatologists should be performing detailed drug histories, obtaining comprehensive lab work, and considering the effects of medications — both illicit and prescribed — on clinical presentations. While in many cases, delusional patients refuse to consent to psychopharmacologic medications (or treatment in general), the elimination or decrease in dose of certain problematic medications may be helpful in and of themselves.”

The researchers reported having no financial disclosures. Dr. Rieder disclosed that he is a consultant for AbbVie, L’Oréal, Pierre Fabre, Procter & Gamble, and Unilever.

Delusions of parasitosis is linked to female gender, older age, polypharmacy with more than five drugs, and certain types of drugs (attention-deficit/hyperactivity disorder drugs, selective serotonin reuptake inhibitors, gabapentin, and opioids), reported researchers in a small retrospective case-control study.

Delusions of parasitosis (DOP) affects mostly middle-aged women and has associations with renal failure and some medications, wrote corresponding author Colleen Reisz, MD, a dermatologist with the department of internal medicine at the University of Missouri–Kansas City School of Medicine, and her coauthors. The study was published online December 15, 2023, in the Journal of the American Academy of Dermatology.

“We hypothesize that vulnerability to DOP emerges when multiple factors combine, such as age, sex, medications, and changes in [drug] clearance capacity,” Dr. Reisz and her coauthors wrote. “Changes in health care, such as the dramatic increase in stimulant prescriptions and alternatives to opioids in pain management, may be contributing to off target drug effects on the brain.”

[embed:render:related:node:235540]

To test their hypothesis, the researchers conducted a case-control study of biometric and pharmaceutical data from 34 patients with DOP which they compared to an age-matched control group of 53 women presenting with a dermatitis above the clavicle from a general dermatology practice between 2012 and 2020. They de-identified the data and performed statistical analysis on variables that included biometric data and intake of pharmaceuticals and nutraceuticals. Polypharmacy was defined as five or more drugs.

Of the 34 patients with DOP, 27 were women with a mean age of 58 years and 7 were men with a mean age of 60 years. Dr. Reisz and her colleagues observed statistical significance between cases and controls in terms of polypharmacy (P = .011), attention-deficit/hyperactivity disorder medications (P < .001), selective serotonin reuptake inhibitors (P = .005), opioids (P = .003), and gabapentin (P = .003).

In other findings, half of DOP cases presented with samples of perceived parasitic material, and four associated the perceived infestation with a single emotion-laden event. This prompted the researchers “to consider that DOP may share mechanisms with fear conditioning and extinction,” they wrote. “Fear conditioning refers to the process of memory acquisition and extinction. This process is essential for survival and has been studied in posttraumatic stress disorder.”

They acknowledged certain limitations of the study, including its retrospective single-center design and the lack of control for factors such as socioeconomic background and level of education.

“Patients with DOP should undergo detailed drug histories and examination of clearance profiles, especially renal function,” the researchers concluded.

Evan A. Rieder, MD, a New York City–based dermatologist and psychiatrist who was asked to comment on the study, said that delusional infestation is one of the most difficult medical conditions to treat and study.

Rieder_Evan_NY_web.JPG

“Though the numbers of cases in this research letter are small, they are instructive in demonstrating a high burden of polypharmacy including psychostimulants, opioids, and SSRIs in such patients,” he told this news organization. “Dermatologists should be performing detailed drug histories, obtaining comprehensive lab work, and considering the effects of medications — both illicit and prescribed — on clinical presentations. While in many cases, delusional patients refuse to consent to psychopharmacologic medications (or treatment in general), the elimination or decrease in dose of certain problematic medications may be helpful in and of themselves.”

The researchers reported having no financial disclosures. Dr. Rieder disclosed that he is a consultant for AbbVie, L’Oréal, Pierre Fabre, Procter & Gamble, and Unilever.

Delusions of parasitosis is linked to female gender, older age, polypharmacy with more than five drugs, and certain types of drugs (attention-deficit/hyperactivity disorder drugs, selective serotonin reuptake inhibitors, gabapentin, and opioids), reported researchers in a small retrospective case-control study.

Delusions of parasitosis (DOP) affects mostly middle-aged women and has associations with renal failure and some medications, wrote corresponding author Colleen Reisz, MD, a dermatologist with the department of internal medicine at the University of Missouri–Kansas City School of Medicine, and her coauthors. The study was published online December 15, 2023, in the Journal of the American Academy of Dermatology.

“We hypothesize that vulnerability to DOP emerges when multiple factors combine, such as age, sex, medications, and changes in [drug] clearance capacity,” Dr. Reisz and her coauthors wrote. “Changes in health care, such as the dramatic increase in stimulant prescriptions and alternatives to opioids in pain management, may be contributing to off target drug effects on the brain.”

[embed:render:related:node:235540]

To test their hypothesis, the researchers conducted a case-control study of biometric and pharmaceutical data from 34 patients with DOP which they compared to an age-matched control group of 53 women presenting with a dermatitis above the clavicle from a general dermatology practice between 2012 and 2020. They de-identified the data and performed statistical analysis on variables that included biometric data and intake of pharmaceuticals and nutraceuticals. Polypharmacy was defined as five or more drugs.

Of the 34 patients with DOP, 27 were women with a mean age of 58 years and 7 were men with a mean age of 60 years. Dr. Reisz and her colleagues observed statistical significance between cases and controls in terms of polypharmacy (P = .011), attention-deficit/hyperactivity disorder medications (P < .001), selective serotonin reuptake inhibitors (P = .005), opioids (P = .003), and gabapentin (P = .003).

In other findings, half of DOP cases presented with samples of perceived parasitic material, and four associated the perceived infestation with a single emotion-laden event. This prompted the researchers “to consider that DOP may share mechanisms with fear conditioning and extinction,” they wrote. “Fear conditioning refers to the process of memory acquisition and extinction. This process is essential for survival and has been studied in posttraumatic stress disorder.”

They acknowledged certain limitations of the study, including its retrospective single-center design and the lack of control for factors such as socioeconomic background and level of education.

“Patients with DOP should undergo detailed drug histories and examination of clearance profiles, especially renal function,” the researchers concluded.

Evan A. Rieder, MD, a New York City–based dermatologist and psychiatrist who was asked to comment on the study, said that delusional infestation is one of the most difficult medical conditions to treat and study.

Rieder_Evan_NY_web.JPG

“Though the numbers of cases in this research letter are small, they are instructive in demonstrating a high burden of polypharmacy including psychostimulants, opioids, and SSRIs in such patients,” he told this news organization. “Dermatologists should be performing detailed drug histories, obtaining comprehensive lab work, and considering the effects of medications — both illicit and prescribed — on clinical presentations. While in many cases, delusional patients refuse to consent to psychopharmacologic medications (or treatment in general), the elimination or decrease in dose of certain problematic medications may be helpful in and of themselves.”

The researchers reported having no financial disclosures. Dr. Rieder disclosed that he is a consultant for AbbVie, L’Oréal, Pierre Fabre, Procter & Gamble, and Unilever.

The FDA has approved a topical gel containing birch triterpenes for the treatment of partial thickness wounds in patients 6 months and older with junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB).

The gel is marketed under the name Filsuvez. It is the first approved treatment for wounds associated with JEB and the second for patients with DEB, following the approval of Vyjuvek (Krystal Biotech), a topical gene therapy gel, in May 2023.

First developed by Amryt Pharma and intended for home use, Filsuvez is now marketed by Chiesi Global Rare Diseases, which acquired Amryt in January 2023. The gel is applied topically to the wound at each dressing change.

[embed:render:related:node:264410]

The approval of Filsuvez is based on results from the Efficacy and Safety Study of Oleogel-S10 in Epidermolysis Bullosa (EASE), a randomized, placebo-controlled study of 223 people, the largest-ever phase 3 clinical trial for the treatment of EB, according to the Chiesi news release. The gel was well tolerated and met the primary endpoint with statistical significance, with 41.3% of patients achieving first complete target wound closure within 45 days (compared with 28.9% on placebo).

“I am so excited to say that this is another hurdle cleared and milestone achieved for the EB Community,” Brett Kopelan, executive director at debra of America said in a blog post. “We are now on the road to being able to treat EB more effectively, and to make the worst disease you’ve never heard of chronic, but livable, by making use of multiple therapeutic options in conjunction with each other.”

The FDA has approved a topical gel containing birch triterpenes for the treatment of partial thickness wounds in patients 6 months and older with junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB).

The gel is marketed under the name Filsuvez. It is the first approved treatment for wounds associated with JEB and the second for patients with DEB, following the approval of Vyjuvek (Krystal Biotech), a topical gene therapy gel, in May 2023.

First developed by Amryt Pharma and intended for home use, Filsuvez is now marketed by Chiesi Global Rare Diseases, which acquired Amryt in January 2023. The gel is applied topically to the wound at each dressing change.

[embed:render:related:node:264410]

The approval of Filsuvez is based on results from the Efficacy and Safety Study of Oleogel-S10 in Epidermolysis Bullosa (EASE), a randomized, placebo-controlled study of 223 people, the largest-ever phase 3 clinical trial for the treatment of EB, according to the Chiesi news release. The gel was well tolerated and met the primary endpoint with statistical significance, with 41.3% of patients achieving first complete target wound closure within 45 days (compared with 28.9% on placebo).

“I am so excited to say that this is another hurdle cleared and milestone achieved for the EB Community,” Brett Kopelan, executive director at debra of America said in a blog post. “We are now on the road to being able to treat EB more effectively, and to make the worst disease you’ve never heard of chronic, but livable, by making use of multiple therapeutic options in conjunction with each other.”

The FDA has approved a topical gel containing birch triterpenes for the treatment of partial thickness wounds in patients 6 months and older with junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB).

The gel is marketed under the name Filsuvez. It is the first approved treatment for wounds associated with JEB and the second for patients with DEB, following the approval of Vyjuvek (Krystal Biotech), a topical gene therapy gel, in May 2023.

First developed by Amryt Pharma and intended for home use, Filsuvez is now marketed by Chiesi Global Rare Diseases, which acquired Amryt in January 2023. The gel is applied topically to the wound at each dressing change.

[embed:render:related:node:264410]

The approval of Filsuvez is based on results from the Efficacy and Safety Study of Oleogel-S10 in Epidermolysis Bullosa (EASE), a randomized, placebo-controlled study of 223 people, the largest-ever phase 3 clinical trial for the treatment of EB, according to the Chiesi news release. The gel was well tolerated and met the primary endpoint with statistical significance, with 41.3% of patients achieving first complete target wound closure within 45 days (compared with 28.9% on placebo).

“I am so excited to say that this is another hurdle cleared and milestone achieved for the EB Community,” Brett Kopelan, executive director at debra of America said in a blog post. “We are now on the road to being able to treat EB more effectively, and to make the worst disease you’ve never heard of chronic, but livable, by making use of multiple therapeutic options in conjunction with each other.”

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Chovatiya_Ray_ILL_web.jpg

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

[embed:render:related:node:261829]

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Chovatiya_Ray_ILL_web.jpg

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

[embed:render:related:node:261829]

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.

Lebrikizumab, an investigational interleukin-13 inhibitor, showed significant efficacy compared with placebo across racial and ethnic subgroups in patients with moderate-to-severe atopic dermatitis.

The finding comes from an analysis of the 16-week induction periods of the phase 3 ADvocate1 and ADvocate2 trials, which Raj Chovatiya, MD, PhD, presented during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. The efficacy of lebrikizumab monotherapy to treat moderate-to-severe AD has been established in phase 3 studies, “but disease characteristic and efficacy outcomes may vary among racial and ethnic subgroups,” said Dr. Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago. “The goal of the current study is to report the week 16 efficacy of lebrikizumab-treated patients in racial and ethnic subgroups from ADvocate1 and ADvocate2.”

Chovatiya_Ray_ILL_web.jpg

Key eligibility criteria for both trials included adults or adolescents with a diagnosis of AD as defined by the American Academy of Dermatology Consensus Criteria, for at least 1 year prior to screening. They had moderate-to-severe AD, were candidates for systemic therapy, and were dupilumab- and tralokinumab-naive. Outcomes of interest were the Investigator’s Global Assessment 0 or 1, with at least a 2-point improvement; and the proportions of patients who achieved Eczema Area and Severity Index (EASI75) and EASI90 responses, and an improvement of 4 points or more on the Pruritus Numeric Rating Scale (NRS).

For statistical analysis, the researchers pooled data from Advocate1 and Advocate2 and applied imputation methodology to the 16-week induction period. Subsequent data from patients who received topical or systemic rescue medication or discontinued treatment due to lack of efficacy were imputed as nonresponders. Subsequent data from patients who discontinued treatment for other reasons were set to missing, and the researchers handled missing data with multiple imputation. They used logistic regression to test the interaction between the treatment and subgroup and the Cochran-Mantel-Haenszel method to evaluate the treatment effect within each subgroup after adjusting for stratification factors.

Dr. Chovatiya reported findings from the 851 study participants in the combined studies. Of these, 542 were White, 192 were Asian, 84 were Black, and 33 were from other racial subgroups. By ethnic subgroup, 748 were not Hispanic or Latino, 91 were Hispanic or Latino, and ethnicity was unknown or not reported for 12 subjects. At baseline, the mean body mass index was slightly higher among Blacks (30.4 kg/m²) and Hispanics (29.4 kg/m²) compared with other racial and ethnic groups, “which reflects general epidemiologic data among these groups in the United States,” Dr. Chovatiya said. “You can also see a difference in the balance of IGA scores — they were a little bit more severe in the Black or African American and Hispanic groups as well.” The researchers also observed differences in the baseline EASI score across some of these groups, particularly in the Asian individuals, who had higher EASI scores. Prior use of systemic therapy was lower in the Black and “other” subgroups, compared with other racial subgroups.

At week 16, key efficacy endpoints were generally similar between the different racial subgroups. Specifically, 25.1% of Asians in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 4.1% of those in the placebo group (P < .001), while 33.2% of Blacks in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 13.2% of those in the placebo group (no P value was established because this subgroup represented less than 10% of the entire study population). In addition, 43.3% of Whites in the lebrikizumab treatment group achieved an IGA of 0/1, compared with 14.1% of those in the placebo group (P < .001).

[embed:render:related:node:261829]

In other findings, 45.5% of Asians in the lebrikizumab treatment group achieved an EASI75, compared with 8.5% of those in the placebo group (P < .001), while 51.7% of Blacks in the lebrikizumab treatment group achieved an EASI75, compared with 18.8% of those in the placebo group. Among whites in the lebrikizumab treatment group, 59.7% of achieved an EASI75, compared with 20.4% of those in the placebo group (P < .001).

Dr. Chovatiya said that 26.5% of Asians in the lebrikizumab treatment group achieved an EASI90, compared with 4.3% of those in the placebo group (P < .001), while 26.9% of Blacks in the lebrikizumab treatment group achieved an EASI90, compared with 13.2% of those in the placebo group. In addition, 38.3% of Whites in the lebrikizumab treatment group achieved an EASI90, compared with 10.9% of those in the placebo group (P < .001).

Finally, 36.4% of Asians in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 5.7% of those in the placebo group (P <. 001), while 41.7% of Blacks in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 17.4% of those in the placebo group. In addition, 45.9% of Whites in the lebrikizumab treatment group achieved a 4-point or greater improvement on the NRS, compared with 14.8% of those in the placebo group (P < .001). Statistical analyses of efficacy endpoints conducted by ethnic group yielded similar results.

Dr. Chovatiya acknowledged certain limitations of the study, including the fact that differences in baseline demographics and disease characteristics limit direct comparison across racial and ethnic subgroups. “Due to the relatively small sample size of some racial and ethnic subgroups and the post hoc nature of this analysis, additional studies are needed to verify these results,” he concluded. But for now, he said, the data available indicate that “lebrikizumab is effective across racial and ethnic subgroups for the treatment of moderate-to-severe AD after 16 weeks of monotherapy treatment.”

The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Dr. Chovatiya disclosed that he is speaker for and/or a consult and advisory board member to many pharmaceutical companies, including Eli Lilly.