Atopic Dermatitis

On April 23, the Committee for Medicinal Products for Human Use of the European Medicines Agency issued a positive opinion for the IL-13 inhibitor tralokinumab (Adtralza) for the treatment of adults with moderate to severe atopic dermatitis (AD) who are eligible for systemic therapy.

The new opinion represents the final stages before the European Commission decides whether tralokinumab will be authorized for use throughout the European Union. The final decision should be made in the next few months.

If ultimately authorized, tralokinumab would become the first approved fully human monoclonal antibody targeting the interleukin-13 cytokine, a key factor that drives the signs and symptoms of AD. Tralokinumab has previously shown to target IL-13 with high affinity and subsequently improve symptoms associated with the inflammatory skin disease.

The EMA accepted the marketing application for tralokinumab back in June 2020. Submitted alongside the marketing application were data from the ECZTRA 1, 2, and 3 pivotal randomized, placebo-controlled trials.

In the ECZTRA trials, treatment with tralokinumab, either alone or with topical corticosteroids, was associated with significant improvements in the Investigator Global Assessment score of clear or almost clear skin and at least a 75% improvement in the Eczema Area and Severity Index score. Safety of tralokinumab in these trials was comparable with that reported with placebo.

Interim data from the open-label extension trial, ECZTEND, also showed that treatment with tralokinumab was associated with durable efficacy in adult patients with moderate to severe AD. Patients in this study were previously enrolled in the ECZTRA 1 and 2 parent trials and had received the IL-13 inhibitor for up to 2 years. Data from this trial were presented at the 2021 American Academy of Dermatology Virtual Meeting Experience.

Pending the European Commission’s final decision, the Marketing Authorization Application for use of tralokinumab in adults with moderate to severe AD will be valid in across all European Union member states in addition to Iceland, Norway, and Liechtenstein. Other regulatory filings for the drug are currently underway with health authorities from various countries worldwide.

Back in July 2020, the Food and Drug Administration accepted a Biologics License Application for tralokinumab for the treatment of moderate to severe AD in adults. Data from the pivotal ECZTRA 1, 2, and ECZTRA 3 trials were submitted to the FDA.

The FDA expects to make a final decision in the second quarter of this year on whether to approve tralokinumab in the United States for the adult AD indication.

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

On April 23, the Committee for Medicinal Products for Human Use of the European Medicines Agency issued a positive opinion for the IL-13 inhibitor tralokinumab (Adtralza) for the treatment of adults with moderate to severe atopic dermatitis (AD) who are eligible for systemic therapy.

The new opinion represents the final stages before the European Commission decides whether tralokinumab will be authorized for use throughout the European Union. The final decision should be made in the next few months.

If ultimately authorized, tralokinumab would become the first approved fully human monoclonal antibody targeting the interleukin-13 cytokine, a key factor that drives the signs and symptoms of AD. Tralokinumab has previously shown to target IL-13 with high affinity and subsequently improve symptoms associated with the inflammatory skin disease.

The EMA accepted the marketing application for tralokinumab back in June 2020. Submitted alongside the marketing application were data from the ECZTRA 1, 2, and 3 pivotal randomized, placebo-controlled trials.

In the ECZTRA trials, treatment with tralokinumab, either alone or with topical corticosteroids, was associated with significant improvements in the Investigator Global Assessment score of clear or almost clear skin and at least a 75% improvement in the Eczema Area and Severity Index score. Safety of tralokinumab in these trials was comparable with that reported with placebo.

Interim data from the open-label extension trial, ECZTEND, also showed that treatment with tralokinumab was associated with durable efficacy in adult patients with moderate to severe AD. Patients in this study were previously enrolled in the ECZTRA 1 and 2 parent trials and had received the IL-13 inhibitor for up to 2 years. Data from this trial were presented at the 2021 American Academy of Dermatology Virtual Meeting Experience.

Pending the European Commission’s final decision, the Marketing Authorization Application for use of tralokinumab in adults with moderate to severe AD will be valid in across all European Union member states in addition to Iceland, Norway, and Liechtenstein. Other regulatory filings for the drug are currently underway with health authorities from various countries worldwide.

Back in July 2020, the Food and Drug Administration accepted a Biologics License Application for tralokinumab for the treatment of moderate to severe AD in adults. Data from the pivotal ECZTRA 1, 2, and ECZTRA 3 trials were submitted to the FDA.

The FDA expects to make a final decision in the second quarter of this year on whether to approve tralokinumab in the United States for the adult AD indication.

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

On April 23, the Committee for Medicinal Products for Human Use of the European Medicines Agency issued a positive opinion for the IL-13 inhibitor tralokinumab (Adtralza) for the treatment of adults with moderate to severe atopic dermatitis (AD) who are eligible for systemic therapy.

The new opinion represents the final stages before the European Commission decides whether tralokinumab will be authorized for use throughout the European Union. The final decision should be made in the next few months.

If ultimately authorized, tralokinumab would become the first approved fully human monoclonal antibody targeting the interleukin-13 cytokine, a key factor that drives the signs and symptoms of AD. Tralokinumab has previously shown to target IL-13 with high affinity and subsequently improve symptoms associated with the inflammatory skin disease.

The EMA accepted the marketing application for tralokinumab back in June 2020. Submitted alongside the marketing application were data from the ECZTRA 1, 2, and 3 pivotal randomized, placebo-controlled trials.

In the ECZTRA trials, treatment with tralokinumab, either alone or with topical corticosteroids, was associated with significant improvements in the Investigator Global Assessment score of clear or almost clear skin and at least a 75% improvement in the Eczema Area and Severity Index score. Safety of tralokinumab in these trials was comparable with that reported with placebo.

Interim data from the open-label extension trial, ECZTEND, also showed that treatment with tralokinumab was associated with durable efficacy in adult patients with moderate to severe AD. Patients in this study were previously enrolled in the ECZTRA 1 and 2 parent trials and had received the IL-13 inhibitor for up to 2 years. Data from this trial were presented at the 2021 American Academy of Dermatology Virtual Meeting Experience.

Pending the European Commission’s final decision, the Marketing Authorization Application for use of tralokinumab in adults with moderate to severe AD will be valid in across all European Union member states in addition to Iceland, Norway, and Liechtenstein. Other regulatory filings for the drug are currently underway with health authorities from various countries worldwide.

Back in July 2020, the Food and Drug Administration accepted a Biologics License Application for tralokinumab for the treatment of moderate to severe AD in adults. Data from the pivotal ECZTRA 1, 2, and ECZTRA 3 trials were submitted to the FDA.

The FDA expects to make a final decision in the second quarter of this year on whether to approve tralokinumab in the United States for the adult AD indication.

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

A novel, highly selective oral sphingosine 1-phosphate (S1P)–receptor modulator showed promise as a treatment for atopic dermatitis (AD) in a 12-week phase 2b trial, according to researchers who released their findings at the American Academy of Dermatology Virtual Meeting Experience.

Courtesy Mount Sinai Health System

The drug, called etrasimod, did not meet the primary endpoint for improvement in the Eczema Area and Severity Index. However, nearly a third (29.8%) of those treated with a 2-mg dose daily reached “clear” or “almost clear” skin at 12 weeks vs. 13% for placebo as measured with clinician-reported Validated Investigator Global Assessment (vIGA) scores of 0 or 1 (P = .0450), study presenter Emma Guttman-Yassky, MD, PhD, professor and chair, department of dermatology, Icahn School of Medicine at Mount Sinai, New York, noted in an interview.

“This was a short proof-of-concept study to show this mechanism is valid. The results are promising,” Dr. Guttman-Yassky said. “They tell us that this can be a valid treatment for atopic dermatitis, a completely new mechanism of action that has potential in improving and even modifying the disease.”

Arena Pharmaceuticals, which developed the drug, hopes to launch a phase 3 study of the medication.

The ADVISE study enrolled 140 people in the United States, Australia, and Canada with chronic, moderate to severe eczema lasting for at least a year. (Their average age was 43, 61% were female, and 60% were White). They were randomly assigned to cohorts who took 1 mg or 2 mg daily of etrasimod or placebo for 12 weeks.

Those in the 2-mg cohort saw their scores on the peak pruritus numeric rating scale (PP-NRS) fall by 15.3% at week 4, compared with 1% for placebo (P = .0380); at week 12, the scores fell by 34.1% among those on 2 mg vs. 23.9% for placebo (P = .15 49). At 12 weeks, patients on the 2-mg dose also had more improvement in the Dermatology Life Quality Index or DLQI (a 7.6-point decline in degree of impairment vs. 4.2 points for placebo, P = .0122) and in the Patient-Oriented Eczema Measure or POEM (8.4-point reduction versus 4 points for placebo, P = .0045).

“Basically, there was a dose response. It doesn’t show a plateau,” Dr. Guttman-Yassky said. “ I think the data will be even better in a longer study.”

In regards to adverse events, participants who took etrasimod reported nausea, constipation, back pain, and dizziness at levels above 5% and above the levels for the placebo.

The drug appears to work by preventing immune cells from entering the skin, Dr. Guttman-Yassky said, and may be able to treat existing lesions and prevent new ones from appearing. Etrasimod is also being explored as a treatment for ulcerative colitis, alopecia areata, and multiple sclerosis, she said.

Dr. Guttman-Yassky noted that 12 weeks is a short time in AD, and she said some participants left the study because it took place during the coronavirus pandemic.

“There’s a huge unmet need in atopic dermatitis,” she said. “We need more drugs and different classes of drugs to treat the disease in all patients.” While biologics are often helpful, she said, they don’t work in many cases. And “some patients just don’t want a biologic, no matter how much we tell them it’s safe, and they may want an oral medication,” she said.

Dr. Guttman-Yassky is a paid consultant and researcher for Arena.

A novel, highly selective oral sphingosine 1-phosphate (S1P)–receptor modulator showed promise as a treatment for atopic dermatitis (AD) in a 12-week phase 2b trial, according to researchers who released their findings at the American Academy of Dermatology Virtual Meeting Experience.

Courtesy Mount Sinai Health System

The drug, called etrasimod, did not meet the primary endpoint for improvement in the Eczema Area and Severity Index. However, nearly a third (29.8%) of those treated with a 2-mg dose daily reached “clear” or “almost clear” skin at 12 weeks vs. 13% for placebo as measured with clinician-reported Validated Investigator Global Assessment (vIGA) scores of 0 or 1 (P = .0450), study presenter Emma Guttman-Yassky, MD, PhD, professor and chair, department of dermatology, Icahn School of Medicine at Mount Sinai, New York, noted in an interview.

“This was a short proof-of-concept study to show this mechanism is valid. The results are promising,” Dr. Guttman-Yassky said. “They tell us that this can be a valid treatment for atopic dermatitis, a completely new mechanism of action that has potential in improving and even modifying the disease.”

Arena Pharmaceuticals, which developed the drug, hopes to launch a phase 3 study of the medication.

The ADVISE study enrolled 140 people in the United States, Australia, and Canada with chronic, moderate to severe eczema lasting for at least a year. (Their average age was 43, 61% were female, and 60% were White). They were randomly assigned to cohorts who took 1 mg or 2 mg daily of etrasimod or placebo for 12 weeks.

Those in the 2-mg cohort saw their scores on the peak pruritus numeric rating scale (PP-NRS) fall by 15.3% at week 4, compared with 1% for placebo (P = .0380); at week 12, the scores fell by 34.1% among those on 2 mg vs. 23.9% for placebo (P = .15 49). At 12 weeks, patients on the 2-mg dose also had more improvement in the Dermatology Life Quality Index or DLQI (a 7.6-point decline in degree of impairment vs. 4.2 points for placebo, P = .0122) and in the Patient-Oriented Eczema Measure or POEM (8.4-point reduction versus 4 points for placebo, P = .0045).

“Basically, there was a dose response. It doesn’t show a plateau,” Dr. Guttman-Yassky said. “ I think the data will be even better in a longer study.”

In regards to adverse events, participants who took etrasimod reported nausea, constipation, back pain, and dizziness at levels above 5% and above the levels for the placebo.

The drug appears to work by preventing immune cells from entering the skin, Dr. Guttman-Yassky said, and may be able to treat existing lesions and prevent new ones from appearing. Etrasimod is also being explored as a treatment for ulcerative colitis, alopecia areata, and multiple sclerosis, she said.

Dr. Guttman-Yassky noted that 12 weeks is a short time in AD, and she said some participants left the study because it took place during the coronavirus pandemic.

“There’s a huge unmet need in atopic dermatitis,” she said. “We need more drugs and different classes of drugs to treat the disease in all patients.” While biologics are often helpful, she said, they don’t work in many cases. And “some patients just don’t want a biologic, no matter how much we tell them it’s safe, and they may want an oral medication,” she said.

Dr. Guttman-Yassky is a paid consultant and researcher for Arena.

A novel, highly selective oral sphingosine 1-phosphate (S1P)–receptor modulator showed promise as a treatment for atopic dermatitis (AD) in a 12-week phase 2b trial, according to researchers who released their findings at the American Academy of Dermatology Virtual Meeting Experience.

Courtesy Mount Sinai Health System

The drug, called etrasimod, did not meet the primary endpoint for improvement in the Eczema Area and Severity Index. However, nearly a third (29.8%) of those treated with a 2-mg dose daily reached “clear” or “almost clear” skin at 12 weeks vs. 13% for placebo as measured with clinician-reported Validated Investigator Global Assessment (vIGA) scores of 0 or 1 (P = .0450), study presenter Emma Guttman-Yassky, MD, PhD, professor and chair, department of dermatology, Icahn School of Medicine at Mount Sinai, New York, noted in an interview.

“This was a short proof-of-concept study to show this mechanism is valid. The results are promising,” Dr. Guttman-Yassky said. “They tell us that this can be a valid treatment for atopic dermatitis, a completely new mechanism of action that has potential in improving and even modifying the disease.”

Arena Pharmaceuticals, which developed the drug, hopes to launch a phase 3 study of the medication.

The ADVISE study enrolled 140 people in the United States, Australia, and Canada with chronic, moderate to severe eczema lasting for at least a year. (Their average age was 43, 61% were female, and 60% were White). They were randomly assigned to cohorts who took 1 mg or 2 mg daily of etrasimod or placebo for 12 weeks.

Those in the 2-mg cohort saw their scores on the peak pruritus numeric rating scale (PP-NRS) fall by 15.3% at week 4, compared with 1% for placebo (P = .0380); at week 12, the scores fell by 34.1% among those on 2 mg vs. 23.9% for placebo (P = .15 49). At 12 weeks, patients on the 2-mg dose also had more improvement in the Dermatology Life Quality Index or DLQI (a 7.6-point decline in degree of impairment vs. 4.2 points for placebo, P = .0122) and in the Patient-Oriented Eczema Measure or POEM (8.4-point reduction versus 4 points for placebo, P = .0045).

“Basically, there was a dose response. It doesn’t show a plateau,” Dr. Guttman-Yassky said. “ I think the data will be even better in a longer study.”

In regards to adverse events, participants who took etrasimod reported nausea, constipation, back pain, and dizziness at levels above 5% and above the levels for the placebo.

The drug appears to work by preventing immune cells from entering the skin, Dr. Guttman-Yassky said, and may be able to treat existing lesions and prevent new ones from appearing. Etrasimod is also being explored as a treatment for ulcerative colitis, alopecia areata, and multiple sclerosis, she said.

Dr. Guttman-Yassky noted that 12 weeks is a short time in AD, and she said some participants left the study because it took place during the coronavirus pandemic.

“There’s a huge unmet need in atopic dermatitis,” she said. “We need more drugs and different classes of drugs to treat the disease in all patients.” While biologics are often helpful, she said, they don’t work in many cases. And “some patients just don’t want a biologic, no matter how much we tell them it’s safe, and they may want an oral medication,” she said.

Dr. Guttman-Yassky is a paid consultant and researcher for Arena.

Patients with prurigo nodularis tend to make a greater number of visits to health care specialists and are burdened by a greater number of medical comorbidities, compared with age-matched controls, as well those with atopic dermatitis and psoriasis.

Those are key findings from a retrospective analysis of claims data that was published online April 3, 2021, in the Journal of Investigative Dermatology.

“Prurigo nodularis is a tremendously understudied inflammatory skin disease,” one of the study’s cosenior authors, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said in an interview. “Prurigo nodularis patients have uncontrolled itch, which leads to reduced quality of life, and the association with many disease comorbidities. We focused on better understanding in this work the unique comorbidities of prurigo nodularis, compared to other inflammatory skin diseases.”

For the study, Dr. Kwatra, cosenior author Yevgeniy R. Semenov, MD, of the department of dermatology, Massachusetts General Hospital, Boston, and colleagues evaluated nationally representative, private insurance claims data from October 2015 to December 2019 to identify prurigo nodularis (PN) patients, who were defined as individuals with two or more medical claims for PN using ICD-10-CM codes. For comparison with patients with inflammatory skin diseases, they used the same claims data to identify patients with atopic dermatitis (AD) and psoriasis as well as to select controls who were age and gender matched to PN patients. Next, they quantified the overall comorbidity burden with the Charlson Comorbidity Index (CCI).

In 2016, the claims database included 2,658 patients with PN, 21,482 patients with AD, 21,073 patients with psoriasis, and 13,290 controls. The number of patients in each category rose each subsequent year, so that by the end of 2019 there were 9,426 patients with PN, 70,298 patients with AD, 59,509 patients with psoriasis, and 47,130 controls. Between 2016 and 2019 the mean age of PN patients increased from 57.5 to 59.8 years and the percent of male patients rose from 44.5% to 46.5%.

Between 2016 and 2019, the overall PN prevalence rates rose from 18 per 100,000 to 58 per 100,000, while the PN prevalence rates among adults increased from 22 per 100,000 to 70 per 100,000, and the rates among children rose grew from 2 per 100,000 to 7 per 100,000. “Our report shows an estimated disease prevalence of around 335,000 cases of PN in the United States,” said Dr. Kwatra, who was among a group of researchers to recently report on systemic Th22-polarized inflammation in PN patients.

The researchers also found that patients with PN had the highest mean CCI in both 2016 and 2019. In 2016, their mean CCI was 1.53, compared with 0.98 among controls, 0.53 among those with AD, and 1.16 among those with psoriasis. In 2019, the mean CCI had increased in all groups of patients, to 2.32 among those with PN, 1.57 among controls, 0.75 among those with AD patients, and 1.71 among those with psoriasis.

The top five medical specialties who cared for PN patients, defined as the estimated number of visits per year per patient, were internal medicine (2.01 visits), dermatology (1.87 visits), family practice (1.60 visits), cardiology or cardiovascular disease (0.85 visits), and orthopedics or orthopedic surgery (0.49 visits).

“If you encounter a patient with prurigo nodularis, it’s important to perform a screening for chronic kidney disease, diabetes, and liver disease,” Dr. Kwatra said. “These comorbidities along with emerging studies on circulating blood biomarkers suggest prurigo nodularis is a systemic inflammatory disorder; thus systemic agents are needed for most patients as part of multimodal therapy in prurigo nodularis.”

The researchers acknowledged certain limitations of the study, including its retrospective design and the identification of patients with PN with the ICD-10-CM code, which require further validation. “Furthermore, the increase in annual prevalence estimates for PN, AD, and psoriasis observed in the study could also be a result of increasing coding of these diagnoses in the claims data along with rising awareness by the medical profession,” they wrote.

Dr. Kwatra disclosed that he is an advisory board member/consultant for AbbVie, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals, and has received grant funding from Galderma, Pfizer, and Kiniksa. He has also received a Dermatology Foundation Medical Dermatology Career Development Award, a research grant from the Skin of Color Society, and is supported by the National Institutes of Health. One coauthor has been funded by NIH grants.

dbrunk@mdedge.com

Patients with prurigo nodularis tend to make a greater number of visits to health care specialists and are burdened by a greater number of medical comorbidities, compared with age-matched controls, as well those with atopic dermatitis and psoriasis.

Those are key findings from a retrospective analysis of claims data that was published online April 3, 2021, in the Journal of Investigative Dermatology.

“Prurigo nodularis is a tremendously understudied inflammatory skin disease,” one of the study’s cosenior authors, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said in an interview. “Prurigo nodularis patients have uncontrolled itch, which leads to reduced quality of life, and the association with many disease comorbidities. We focused on better understanding in this work the unique comorbidities of prurigo nodularis, compared to other inflammatory skin diseases.”

For the study, Dr. Kwatra, cosenior author Yevgeniy R. Semenov, MD, of the department of dermatology, Massachusetts General Hospital, Boston, and colleagues evaluated nationally representative, private insurance claims data from October 2015 to December 2019 to identify prurigo nodularis (PN) patients, who were defined as individuals with two or more medical claims for PN using ICD-10-CM codes. For comparison with patients with inflammatory skin diseases, they used the same claims data to identify patients with atopic dermatitis (AD) and psoriasis as well as to select controls who were age and gender matched to PN patients. Next, they quantified the overall comorbidity burden with the Charlson Comorbidity Index (CCI).

In 2016, the claims database included 2,658 patients with PN, 21,482 patients with AD, 21,073 patients with psoriasis, and 13,290 controls. The number of patients in each category rose each subsequent year, so that by the end of 2019 there were 9,426 patients with PN, 70,298 patients with AD, 59,509 patients with psoriasis, and 47,130 controls. Between 2016 and 2019 the mean age of PN patients increased from 57.5 to 59.8 years and the percent of male patients rose from 44.5% to 46.5%.

Between 2016 and 2019, the overall PN prevalence rates rose from 18 per 100,000 to 58 per 100,000, while the PN prevalence rates among adults increased from 22 per 100,000 to 70 per 100,000, and the rates among children rose grew from 2 per 100,000 to 7 per 100,000. “Our report shows an estimated disease prevalence of around 335,000 cases of PN in the United States,” said Dr. Kwatra, who was among a group of researchers to recently report on systemic Th22-polarized inflammation in PN patients.

The researchers also found that patients with PN had the highest mean CCI in both 2016 and 2019. In 2016, their mean CCI was 1.53, compared with 0.98 among controls, 0.53 among those with AD, and 1.16 among those with psoriasis. In 2019, the mean CCI had increased in all groups of patients, to 2.32 among those with PN, 1.57 among controls, 0.75 among those with AD patients, and 1.71 among those with psoriasis.

The top five medical specialties who cared for PN patients, defined as the estimated number of visits per year per patient, were internal medicine (2.01 visits), dermatology (1.87 visits), family practice (1.60 visits), cardiology or cardiovascular disease (0.85 visits), and orthopedics or orthopedic surgery (0.49 visits).

“If you encounter a patient with prurigo nodularis, it’s important to perform a screening for chronic kidney disease, diabetes, and liver disease,” Dr. Kwatra said. “These comorbidities along with emerging studies on circulating blood biomarkers suggest prurigo nodularis is a systemic inflammatory disorder; thus systemic agents are needed for most patients as part of multimodal therapy in prurigo nodularis.”

The researchers acknowledged certain limitations of the study, including its retrospective design and the identification of patients with PN with the ICD-10-CM code, which require further validation. “Furthermore, the increase in annual prevalence estimates for PN, AD, and psoriasis observed in the study could also be a result of increasing coding of these diagnoses in the claims data along with rising awareness by the medical profession,” they wrote.

Dr. Kwatra disclosed that he is an advisory board member/consultant for AbbVie, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals, and has received grant funding from Galderma, Pfizer, and Kiniksa. He has also received a Dermatology Foundation Medical Dermatology Career Development Award, a research grant from the Skin of Color Society, and is supported by the National Institutes of Health. One coauthor has been funded by NIH grants.

dbrunk@mdedge.com

Patients with prurigo nodularis tend to make a greater number of visits to health care specialists and are burdened by a greater number of medical comorbidities, compared with age-matched controls, as well those with atopic dermatitis and psoriasis.

Those are key findings from a retrospective analysis of claims data that was published online April 3, 2021, in the Journal of Investigative Dermatology.

“Prurigo nodularis is a tremendously understudied inflammatory skin disease,” one of the study’s cosenior authors, Shawn G. Kwatra, MD, of the department of dermatology, Johns Hopkins University, Baltimore, said in an interview. “Prurigo nodularis patients have uncontrolled itch, which leads to reduced quality of life, and the association with many disease comorbidities. We focused on better understanding in this work the unique comorbidities of prurigo nodularis, compared to other inflammatory skin diseases.”

For the study, Dr. Kwatra, cosenior author Yevgeniy R. Semenov, MD, of the department of dermatology, Massachusetts General Hospital, Boston, and colleagues evaluated nationally representative, private insurance claims data from October 2015 to December 2019 to identify prurigo nodularis (PN) patients, who were defined as individuals with two or more medical claims for PN using ICD-10-CM codes. For comparison with patients with inflammatory skin diseases, they used the same claims data to identify patients with atopic dermatitis (AD) and psoriasis as well as to select controls who were age and gender matched to PN patients. Next, they quantified the overall comorbidity burden with the Charlson Comorbidity Index (CCI).

In 2016, the claims database included 2,658 patients with PN, 21,482 patients with AD, 21,073 patients with psoriasis, and 13,290 controls. The number of patients in each category rose each subsequent year, so that by the end of 2019 there were 9,426 patients with PN, 70,298 patients with AD, 59,509 patients with psoriasis, and 47,130 controls. Between 2016 and 2019 the mean age of PN patients increased from 57.5 to 59.8 years and the percent of male patients rose from 44.5% to 46.5%.

Between 2016 and 2019, the overall PN prevalence rates rose from 18 per 100,000 to 58 per 100,000, while the PN prevalence rates among adults increased from 22 per 100,000 to 70 per 100,000, and the rates among children rose grew from 2 per 100,000 to 7 per 100,000. “Our report shows an estimated disease prevalence of around 335,000 cases of PN in the United States,” said Dr. Kwatra, who was among a group of researchers to recently report on systemic Th22-polarized inflammation in PN patients.

The researchers also found that patients with PN had the highest mean CCI in both 2016 and 2019. In 2016, their mean CCI was 1.53, compared with 0.98 among controls, 0.53 among those with AD, and 1.16 among those with psoriasis. In 2019, the mean CCI had increased in all groups of patients, to 2.32 among those with PN, 1.57 among controls, 0.75 among those with AD patients, and 1.71 among those with psoriasis.

The top five medical specialties who cared for PN patients, defined as the estimated number of visits per year per patient, were internal medicine (2.01 visits), dermatology (1.87 visits), family practice (1.60 visits), cardiology or cardiovascular disease (0.85 visits), and orthopedics or orthopedic surgery (0.49 visits).

“If you encounter a patient with prurigo nodularis, it’s important to perform a screening for chronic kidney disease, diabetes, and liver disease,” Dr. Kwatra said. “These comorbidities along with emerging studies on circulating blood biomarkers suggest prurigo nodularis is a systemic inflammatory disorder; thus systemic agents are needed for most patients as part of multimodal therapy in prurigo nodularis.”

The researchers acknowledged certain limitations of the study, including its retrospective design and the identification of patients with PN with the ICD-10-CM code, which require further validation. “Furthermore, the increase in annual prevalence estimates for PN, AD, and psoriasis observed in the study could also be a result of increasing coding of these diagnoses in the claims data along with rising awareness by the medical profession,” they wrote.

Dr. Kwatra disclosed that he is an advisory board member/consultant for AbbVie, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals, and has received grant funding from Galderma, Pfizer, and Kiniksa. He has also received a Dermatology Foundation Medical Dermatology Career Development Award, a research grant from the Skin of Color Society, and is supported by the National Institutes of Health. One coauthor has been funded by NIH grants.

dbrunk@mdedge.com

Marine algae are relatively common raw sources for cosmeceutical products.¹ The photoprotective compounds identified among marine algae range from mycosporinelike amino acids, sulfated polysaccharides, and carotenoids to polyphenols, all of which are noted for absorbing UV and conferring antioxidant, matrix metalloproteinase–suppressing, anti-aging, and immunomodulatory effects.² Such biologic activities understandably account for the interest in harnessing their potential in the skin care realm. Indeed, marine ingredients have been steadily flowing into the market for skin care, and research has proliferated – so much so, in fact, that I’ll take two columns to cover some of the most recent research on various marine species and some of the indications or potential uses for these products in skin care.

ph2212/Getty Images

Key activities and potential uses

Kim and associates note that carbohydrates are the primary components of marine algae, with copious amounts delivering a moisturizing and thickening effect when incorporated into cosmetic products. They add that marine carbohydrates are also known to impart antioxidant, antimelanogenic, and anti-aging activities.³

In 2017, Colantonio and Rivers reviewed the evidence supporting the use of seaweed, among other plants, for dermatologic purposes. The researchers considered four plants and algae (seaweed, witch hazel, bearberry, and mayapple) used in traditional First Nations approaches to skin disease. They found that seaweed shows promise for clinical use in treating acne and wrinkles and could deliver healthy benefits when included in biofunctional textiles.⁴

Atopic dermatitis

Found in the seaweed Fucus vesiculosus, fucoidan is known to impart anti-inflammatory, antioxidant, and antitumor activity.⁵ In a 2019 BALB/c mouse study, Tian and associates showed that fucoidan, which is rich in polysaccharides, significantly improved ear swelling and skin lesions and reduced inflammatory cell infiltration. Given the resolution of the 2,4-dinitrofluorobenzene–induced atopic dermatitis symptoms, the investigators suggested that fucoidan may have potential as an anti-AD agent.⁵

Also that year, Gil and associates studied the effects of Seaweed fulvescens, a chlorophyll-rich green alga (also called Maesaengi) known to have antioxidant properties, in a mouse model of Dermatophagoides farinae body-induced AD and in tumor necrosis factor–alpha and interferon-gamma–stimulated HaCaT keratinocytes. They observed that 200-mg/mouse treatment hindered AD symptom development, compared with controls, with enhanced dorsal skin lesions, diminished thickness and infiltration of inflammation, and decreased proinflammatory cytokines. In addition, the investigators reported the dose-dependent inhibition of proinflammatory cytokine synthesis in HaCaT keratinocytes. They concluded that Seaweed fulvescens shows promise as a therapeutic option for AD treatment.⁶

Alopecia

In 2017, Kang and associates studied the impact and mechanism of Undariopsis peterseniana, an edible brown alga, and determined that the extract promotes hair growth by activating the Wnt/beta-catenin and ERK pathways. Specifically, they found that U. peterseniana significantly enhanced hair-fiber length ex vivo and in vivo. They also concluded that the brown alga has potential to treat alopecia as it accelerated anagen initiation.⁷

Skin protection potential of Ishige okamurae

In 2015, Piao and associates demonstrated that diphlorethohydroxycarmalol (DPHC), a phlorotannin isolated from Ishige okamurae, protected human keratinocytes from UVB-induced matrix metalloproteinase (MMP) expression by inactivating ERK and JNK. MMPs are known to contribute to photoaging and tumor promotion.⁸

Early in 2020, Wang and associates demonstrated that DPHC, isolated from the marine brown alga I. okamurae, exerted protective effects against UVB-induced photodamage in vitro in human dermal fibroblasts and in vivo in zebrafish by suppressing collagenase and elastase production and the expression of matrix metalloproteinases. In vivo, the brown alga extract lowered cell death by decreasing lipid peroxidation and inflammatory response. The investigators concluded that DPHC warrants consideration as an ingredient in cosmeceutical formulations intended to protect against the effects of UVB radiation.⁹

The same team also reported on their study of the protective effects of DPHC against skin damage in human dermal fibroblasts caused by particulate matter. They found that DPHC dose-dependently exerted significant decreases in intracellular synthesis of reactive oxygen species. The seaweed product also stimulated collagen production and suppressed collagenase activity, as well as matrix metalloproteinases. The researchers concluded that DPHC may be an effective skin-protective ingredient against particulate matter for use in cosmeceutical products.¹⁰

Skin protection mouse studies using various marine species

The last 3 years alone have featured several studies in mice that may have significant implications in accelerating our understanding of how to harness the bioactive properties of multiple marine species.

In 2018, Wiraguna and associates studied the protective effects of 0.2% and 0.4% Caulerpa sp. (a genus of seaweed native to the Indo-Pacific region) extract gels on photoaging in the UVB-irradiated skin of Wistar mice, finding that topical applications of both concentrations of the seaweed extract protected mouse skin from UVB-induced photoaging, with treated mice revealed to have higher collagen expression and preserved collagen structure and decreased MMP-1 levels, compared with vehicle controls.¹¹

The next year, Prasedya and associates showed that the brown macroalgae Sargassum cristafolium exerted photoprotective activity against UVA in mice. Mice pretreated with the seaweed before exposure displayed intact collagen formation and no increases in epidermal thickness, compared with controls.¹²

At the same time, Santos and associates demonstrated that mice fed a diet supplemented with the red seaweed Porphyra umbilicalis experienced significant decreases in the incidence of human papillomavirus type 16–induced premalignant dysplastic skin lesions.¹³

Also that year, Zhen and associates evaluated the protective effects of eckol, a phlorotannin isolated from brown seaweed, on human HaCaT keratinocytes against PM2.5-induced cell damage. They showed that eckol (30 mcm) reduced reactive oxygen species production and protected cells from apoptosis by hampering the MAPK signaling pathway.¹⁴Earlier that year, Kim and associates studied the viability of the microalga Nannochloropsis oceanica, considered most often as a possible biofuel, for potential photoprotective activity against UVB-irradiated human dermal fibroblasts. They determined that pigment extracts (violaxanthin was identified as the main pigment) were not cytotoxic to the fibroblasts and that treatment with the pigment extract upregulated collagen expression and significantly inhibited UVB-induced damage. Further study revealed that violaxanthin significantly mitigated UVB-induced G1 phase arrest, senescence-associated beta-galactosidase activation, and p16 and p21 up-regulation, among other functions, suggesting its consideration, according to the authors, as a possible antiphotoaging agent.¹⁵

Finally, early in 2020, Bellan and associates evaluated the antitumor characteristics of the sulfated heterorhamnan derived from the green seaweed Gayralia brasiliensis as seen on the biological activities in the B16-F10 murine melanoma cell line. The polysaccharidic fraction was found to be effective in reducing melanoma cell migration and invasion capacity.¹⁶

Conclusion

Marine ingredients have been ripe for exploration, extraction, and usage in the cosmetic realm for several years. Evidence suggests widespread potential across several species for dermatologic purposes. Indeed, data indicate that some species appear to be suited for treating AD, alopecia, and wrinkles and may possibly render effective photoprotection. More research is necessary, of course, to ascertain the extent to which such ingredients can adequately address cutaneous health and how truly effective the marine ingredients are in currently marketed products.

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

References

1. Fabrowska J et al. Acta Pol Pharm. 2017 Mar;74(2):633-41.

2. Pangestuti R et al. Mar Drugs. 2018 Oct 23;16(11):399.

3. Kim JH et al. Mar Drugs. 2018 Nov 21;16(11):459.

4. Colantonio S & Rivers JK. J Cutan Med Surg. Jul/Aug 2017;21(4):299-307.

5. Tian T et al. Int Immunopharmacol. 2019 Oct;75:105823.

6. Gil TY et al. Mediators Inflamm. 2019 Mar 17;2019:3760934.

7. Kang JI et al. Mar Drugs. 2017 May 5;15(5):130.

8. Piao MJ et al. Biomol Ther (Seoul). 2015 Nov;23(6):557-63.

9. Wang L et al. Food Chem Toxicol. 2020 Feb;136:110963.

10. Wang L et al. Molecules. 2020 Feb 26;25(5):1055.

11. Wiraguna AAGP et al. Dermatol Reports. 2018 Oct 1;10(2):7597.

12. Prasedya ES et al. Biomedicines. 2019 Sep 27;7(4):77.

13. Santos S et al. Mar Drugs. 2019 Oct 29;17(11):615.

14. Zhen AX et al. Mar Drugs. 2019 Jul 27;17(8):444.

15. Kim HM et al. Photochem Photobiol. 2019 Mar;95(2):595-604.

16. Bellan DL et al. Mar Biotechnol. 2020 Apr;22(2):194-206.

Marine algae are relatively common raw sources for cosmeceutical products.¹ The photoprotective compounds identified among marine algae range from mycosporinelike amino acids, sulfated polysaccharides, and carotenoids to polyphenols, all of which are noted for absorbing UV and conferring antioxidant, matrix metalloproteinase–suppressing, anti-aging, and immunomodulatory effects.² Such biologic activities understandably account for the interest in harnessing their potential in the skin care realm. Indeed, marine ingredients have been steadily flowing into the market for skin care, and research has proliferated – so much so, in fact, that I’ll take two columns to cover some of the most recent research on various marine species and some of the indications or potential uses for these products in skin care.

ph2212/Getty Images

Key activities and potential uses

Kim and associates note that carbohydrates are the primary components of marine algae, with copious amounts delivering a moisturizing and thickening effect when incorporated into cosmetic products. They add that marine carbohydrates are also known to impart antioxidant, antimelanogenic, and anti-aging activities.³

In 2017, Colantonio and Rivers reviewed the evidence supporting the use of seaweed, among other plants, for dermatologic purposes. The researchers considered four plants and algae (seaweed, witch hazel, bearberry, and mayapple) used in traditional First Nations approaches to skin disease. They found that seaweed shows promise for clinical use in treating acne and wrinkles and could deliver healthy benefits when included in biofunctional textiles.⁴

Atopic dermatitis

Found in the seaweed Fucus vesiculosus, fucoidan is known to impart anti-inflammatory, antioxidant, and antitumor activity.⁵ In a 2019 BALB/c mouse study, Tian and associates showed that fucoidan, which is rich in polysaccharides, significantly improved ear swelling and skin lesions and reduced inflammatory cell infiltration. Given the resolution of the 2,4-dinitrofluorobenzene–induced atopic dermatitis symptoms, the investigators suggested that fucoidan may have potential as an anti-AD agent.⁵

Also that year, Gil and associates studied the effects of Seaweed fulvescens, a chlorophyll-rich green alga (also called Maesaengi) known to have antioxidant properties, in a mouse model of Dermatophagoides farinae body-induced AD and in tumor necrosis factor–alpha and interferon-gamma–stimulated HaCaT keratinocytes. They observed that 200-mg/mouse treatment hindered AD symptom development, compared with controls, with enhanced dorsal skin lesions, diminished thickness and infiltration of inflammation, and decreased proinflammatory cytokines. In addition, the investigators reported the dose-dependent inhibition of proinflammatory cytokine synthesis in HaCaT keratinocytes. They concluded that Seaweed fulvescens shows promise as a therapeutic option for AD treatment.⁶

Alopecia

In 2017, Kang and associates studied the impact and mechanism of Undariopsis peterseniana, an edible brown alga, and determined that the extract promotes hair growth by activating the Wnt/beta-catenin and ERK pathways. Specifically, they found that U. peterseniana significantly enhanced hair-fiber length ex vivo and in vivo. They also concluded that the brown alga has potential to treat alopecia as it accelerated anagen initiation.⁷

Skin protection potential of Ishige okamurae

In 2015, Piao and associates demonstrated that diphlorethohydroxycarmalol (DPHC), a phlorotannin isolated from Ishige okamurae, protected human keratinocytes from UVB-induced matrix metalloproteinase (MMP) expression by inactivating ERK and JNK. MMPs are known to contribute to photoaging and tumor promotion.⁸

Early in 2020, Wang and associates demonstrated that DPHC, isolated from the marine brown alga I. okamurae, exerted protective effects against UVB-induced photodamage in vitro in human dermal fibroblasts and in vivo in zebrafish by suppressing collagenase and elastase production and the expression of matrix metalloproteinases. In vivo, the brown alga extract lowered cell death by decreasing lipid peroxidation and inflammatory response. The investigators concluded that DPHC warrants consideration as an ingredient in cosmeceutical formulations intended to protect against the effects of UVB radiation.⁹

The same team also reported on their study of the protective effects of DPHC against skin damage in human dermal fibroblasts caused by particulate matter. They found that DPHC dose-dependently exerted significant decreases in intracellular synthesis of reactive oxygen species. The seaweed product also stimulated collagen production and suppressed collagenase activity, as well as matrix metalloproteinases. The researchers concluded that DPHC may be an effective skin-protective ingredient against particulate matter for use in cosmeceutical products.¹⁰

Skin protection mouse studies using various marine species

The last 3 years alone have featured several studies in mice that may have significant implications in accelerating our understanding of how to harness the bioactive properties of multiple marine species.

In 2018, Wiraguna and associates studied the protective effects of 0.2% and 0.4% Caulerpa sp. (a genus of seaweed native to the Indo-Pacific region) extract gels on photoaging in the UVB-irradiated skin of Wistar mice, finding that topical applications of both concentrations of the seaweed extract protected mouse skin from UVB-induced photoaging, with treated mice revealed to have higher collagen expression and preserved collagen structure and decreased MMP-1 levels, compared with vehicle controls.¹¹

The next year, Prasedya and associates showed that the brown macroalgae Sargassum cristafolium exerted photoprotective activity against UVA in mice. Mice pretreated with the seaweed before exposure displayed intact collagen formation and no increases in epidermal thickness, compared with controls.¹²

At the same time, Santos and associates demonstrated that mice fed a diet supplemented with the red seaweed Porphyra umbilicalis experienced significant decreases in the incidence of human papillomavirus type 16–induced premalignant dysplastic skin lesions.¹³

Also that year, Zhen and associates evaluated the protective effects of eckol, a phlorotannin isolated from brown seaweed, on human HaCaT keratinocytes against PM2.5-induced cell damage. They showed that eckol (30 mcm) reduced reactive oxygen species production and protected cells from apoptosis by hampering the MAPK signaling pathway.¹⁴Earlier that year, Kim and associates studied the viability of the microalga Nannochloropsis oceanica, considered most often as a possible biofuel, for potential photoprotective activity against UVB-irradiated human dermal fibroblasts. They determined that pigment extracts (violaxanthin was identified as the main pigment) were not cytotoxic to the fibroblasts and that treatment with the pigment extract upregulated collagen expression and significantly inhibited UVB-induced damage. Further study revealed that violaxanthin significantly mitigated UVB-induced G1 phase arrest, senescence-associated beta-galactosidase activation, and p16 and p21 up-regulation, among other functions, suggesting its consideration, according to the authors, as a possible antiphotoaging agent.¹⁵

Finally, early in 2020, Bellan and associates evaluated the antitumor characteristics of the sulfated heterorhamnan derived from the green seaweed Gayralia brasiliensis as seen on the biological activities in the B16-F10 murine melanoma cell line. The polysaccharidic fraction was found to be effective in reducing melanoma cell migration and invasion capacity.¹⁶

Conclusion

Marine ingredients have been ripe for exploration, extraction, and usage in the cosmetic realm for several years. Evidence suggests widespread potential across several species for dermatologic purposes. Indeed, data indicate that some species appear to be suited for treating AD, alopecia, and wrinkles and may possibly render effective photoprotection. More research is necessary, of course, to ascertain the extent to which such ingredients can adequately address cutaneous health and how truly effective the marine ingredients are in currently marketed products.

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

References

1. Fabrowska J et al. Acta Pol Pharm. 2017 Mar;74(2):633-41.

2. Pangestuti R et al. Mar Drugs. 2018 Oct 23;16(11):399.

3. Kim JH et al. Mar Drugs. 2018 Nov 21;16(11):459.

4. Colantonio S & Rivers JK. J Cutan Med Surg. Jul/Aug 2017;21(4):299-307.

5. Tian T et al. Int Immunopharmacol. 2019 Oct;75:105823.

6. Gil TY et al. Mediators Inflamm. 2019 Mar 17;2019:3760934.

7. Kang JI et al. Mar Drugs. 2017 May 5;15(5):130.

8. Piao MJ et al. Biomol Ther (Seoul). 2015 Nov;23(6):557-63.

9. Wang L et al. Food Chem Toxicol. 2020 Feb;136:110963.

10. Wang L et al. Molecules. 2020 Feb 26;25(5):1055.

11. Wiraguna AAGP et al. Dermatol Reports. 2018 Oct 1;10(2):7597.

12. Prasedya ES et al. Biomedicines. 2019 Sep 27;7(4):77.

13. Santos S et al. Mar Drugs. 2019 Oct 29;17(11):615.

14. Zhen AX et al. Mar Drugs. 2019 Jul 27;17(8):444.

15. Kim HM et al. Photochem Photobiol. 2019 Mar;95(2):595-604.

16. Bellan DL et al. Mar Biotechnol. 2020 Apr;22(2):194-206.

Marine algae are relatively common raw sources for cosmeceutical products.¹ The photoprotective compounds identified among marine algae range from mycosporinelike amino acids, sulfated polysaccharides, and carotenoids to polyphenols, all of which are noted for absorbing UV and conferring antioxidant, matrix metalloproteinase–suppressing, anti-aging, and immunomodulatory effects.² Such biologic activities understandably account for the interest in harnessing their potential in the skin care realm. Indeed, marine ingredients have been steadily flowing into the market for skin care, and research has proliferated – so much so, in fact, that I’ll take two columns to cover some of the most recent research on various marine species and some of the indications or potential uses for these products in skin care.

ph2212/Getty Images

Key activities and potential uses

Kim and associates note that carbohydrates are the primary components of marine algae, with copious amounts delivering a moisturizing and thickening effect when incorporated into cosmetic products. They add that marine carbohydrates are also known to impart antioxidant, antimelanogenic, and anti-aging activities.³

In 2017, Colantonio and Rivers reviewed the evidence supporting the use of seaweed, among other plants, for dermatologic purposes. The researchers considered four plants and algae (seaweed, witch hazel, bearberry, and mayapple) used in traditional First Nations approaches to skin disease. They found that seaweed shows promise for clinical use in treating acne and wrinkles and could deliver healthy benefits when included in biofunctional textiles.⁴

Atopic dermatitis

Found in the seaweed Fucus vesiculosus, fucoidan is known to impart anti-inflammatory, antioxidant, and antitumor activity.⁵ In a 2019 BALB/c mouse study, Tian and associates showed that fucoidan, which is rich in polysaccharides, significantly improved ear swelling and skin lesions and reduced inflammatory cell infiltration. Given the resolution of the 2,4-dinitrofluorobenzene–induced atopic dermatitis symptoms, the investigators suggested that fucoidan may have potential as an anti-AD agent.⁵

Also that year, Gil and associates studied the effects of Seaweed fulvescens, a chlorophyll-rich green alga (also called Maesaengi) known to have antioxidant properties, in a mouse model of Dermatophagoides farinae body-induced AD and in tumor necrosis factor–alpha and interferon-gamma–stimulated HaCaT keratinocytes. They observed that 200-mg/mouse treatment hindered AD symptom development, compared with controls, with enhanced dorsal skin lesions, diminished thickness and infiltration of inflammation, and decreased proinflammatory cytokines. In addition, the investigators reported the dose-dependent inhibition of proinflammatory cytokine synthesis in HaCaT keratinocytes. They concluded that Seaweed fulvescens shows promise as a therapeutic option for AD treatment.⁶

Alopecia

In 2017, Kang and associates studied the impact and mechanism of Undariopsis peterseniana, an edible brown alga, and determined that the extract promotes hair growth by activating the Wnt/beta-catenin and ERK pathways. Specifically, they found that U. peterseniana significantly enhanced hair-fiber length ex vivo and in vivo. They also concluded that the brown alga has potential to treat alopecia as it accelerated anagen initiation.⁷

Skin protection potential of Ishige okamurae

In 2015, Piao and associates demonstrated that diphlorethohydroxycarmalol (DPHC), a phlorotannin isolated from Ishige okamurae, protected human keratinocytes from UVB-induced matrix metalloproteinase (MMP) expression by inactivating ERK and JNK. MMPs are known to contribute to photoaging and tumor promotion.⁸

Early in 2020, Wang and associates demonstrated that DPHC, isolated from the marine brown alga I. okamurae, exerted protective effects against UVB-induced photodamage in vitro in human dermal fibroblasts and in vivo in zebrafish by suppressing collagenase and elastase production and the expression of matrix metalloproteinases. In vivo, the brown alga extract lowered cell death by decreasing lipid peroxidation and inflammatory response. The investigators concluded that DPHC warrants consideration as an ingredient in cosmeceutical formulations intended to protect against the effects of UVB radiation.⁹

The same team also reported on their study of the protective effects of DPHC against skin damage in human dermal fibroblasts caused by particulate matter. They found that DPHC dose-dependently exerted significant decreases in intracellular synthesis of reactive oxygen species. The seaweed product also stimulated collagen production and suppressed collagenase activity, as well as matrix metalloproteinases. The researchers concluded that DPHC may be an effective skin-protective ingredient against particulate matter for use in cosmeceutical products.¹⁰

Skin protection mouse studies using various marine species

The last 3 years alone have featured several studies in mice that may have significant implications in accelerating our understanding of how to harness the bioactive properties of multiple marine species.

In 2018, Wiraguna and associates studied the protective effects of 0.2% and 0.4% Caulerpa sp. (a genus of seaweed native to the Indo-Pacific region) extract gels on photoaging in the UVB-irradiated skin of Wistar mice, finding that topical applications of both concentrations of the seaweed extract protected mouse skin from UVB-induced photoaging, with treated mice revealed to have higher collagen expression and preserved collagen structure and decreased MMP-1 levels, compared with vehicle controls.¹¹

The next year, Prasedya and associates showed that the brown macroalgae Sargassum cristafolium exerted photoprotective activity against UVA in mice. Mice pretreated with the seaweed before exposure displayed intact collagen formation and no increases in epidermal thickness, compared with controls.¹²

At the same time, Santos and associates demonstrated that mice fed a diet supplemented with the red seaweed Porphyra umbilicalis experienced significant decreases in the incidence of human papillomavirus type 16–induced premalignant dysplastic skin lesions.¹³

Also that year, Zhen and associates evaluated the protective effects of eckol, a phlorotannin isolated from brown seaweed, on human HaCaT keratinocytes against PM2.5-induced cell damage. They showed that eckol (30 mcm) reduced reactive oxygen species production and protected cells from apoptosis by hampering the MAPK signaling pathway.¹⁴Earlier that year, Kim and associates studied the viability of the microalga Nannochloropsis oceanica, considered most often as a possible biofuel, for potential photoprotective activity against UVB-irradiated human dermal fibroblasts. They determined that pigment extracts (violaxanthin was identified as the main pigment) were not cytotoxic to the fibroblasts and that treatment with the pigment extract upregulated collagen expression and significantly inhibited UVB-induced damage. Further study revealed that violaxanthin significantly mitigated UVB-induced G1 phase arrest, senescence-associated beta-galactosidase activation, and p16 and p21 up-regulation, among other functions, suggesting its consideration, according to the authors, as a possible antiphotoaging agent.¹⁵

Finally, early in 2020, Bellan and associates evaluated the antitumor characteristics of the sulfated heterorhamnan derived from the green seaweed Gayralia brasiliensis as seen on the biological activities in the B16-F10 murine melanoma cell line. The polysaccharidic fraction was found to be effective in reducing melanoma cell migration and invasion capacity.¹⁶

Conclusion

Marine ingredients have been ripe for exploration, extraction, and usage in the cosmetic realm for several years. Evidence suggests widespread potential across several species for dermatologic purposes. Indeed, data indicate that some species appear to be suited for treating AD, alopecia, and wrinkles and may possibly render effective photoprotection. More research is necessary, of course, to ascertain the extent to which such ingredients can adequately address cutaneous health and how truly effective the marine ingredients are in currently marketed products.

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

References

1. Fabrowska J et al. Acta Pol Pharm. 2017 Mar;74(2):633-41.

2. Pangestuti R et al. Mar Drugs. 2018 Oct 23;16(11):399.

3. Kim JH et al. Mar Drugs. 2018 Nov 21;16(11):459.

4. Colantonio S & Rivers JK. J Cutan Med Surg. Jul/Aug 2017;21(4):299-307.

5. Tian T et al. Int Immunopharmacol. 2019 Oct;75:105823.

6. Gil TY et al. Mediators Inflamm. 2019 Mar 17;2019:3760934.

7. Kang JI et al. Mar Drugs. 2017 May 5;15(5):130.

8. Piao MJ et al. Biomol Ther (Seoul). 2015 Nov;23(6):557-63.

9. Wang L et al. Food Chem Toxicol. 2020 Feb;136:110963.

10. Wang L et al. Molecules. 2020 Feb 26;25(5):1055.

11. Wiraguna AAGP et al. Dermatol Reports. 2018 Oct 1;10(2):7597.

12. Prasedya ES et al. Biomedicines. 2019 Sep 27;7(4):77.

13. Santos S et al. Mar Drugs. 2019 Oct 29;17(11):615.

14. Zhen AX et al. Mar Drugs. 2019 Jul 27;17(8):444.

15. Kim HM et al. Photochem Photobiol. 2019 Mar;95(2):595-604.

16. Bellan DL et al. Mar Biotechnol. 2020 Apr;22(2):194-206.

Itch is one of the most protean manifestations of skin disease and can take a substantial physical and emotional toll on patients. For physicians, it is a frequent—if often dreaded—patient concern with a rising incidence. Lack of specific itch therapies as well as associations with multiple dermatologic conditions, including xerosis, psoriasis, atopic dermatitis, cutaneous lymphoma, contact dermatitis, and internal malignancies, make management of these itchy patients challenging and deserving of our attention. Studies evaluating patients with chronic pruritus identified a considerable impact on health-related quality of life, including development of depression, inability to perform activities of daily living, and sleep difficulties. ¹

How to Classify Itching

Itch, or pruritus, originally was defined as an unpleasant sensation that provokes the desire to scratch,² but this definition likely limits our ability to assess itch. The urge to scratch the skin to relieve the itch is sometimes a reflex of the muscles triggered by the spinal cord that can be either conscious or unconscious. If 2 patients present with itch, does the patient with more excoriated skin experience more severe itch? Conversely, does the patient who scratches less have an equivalent decrease in itch severity? Although it is tempting to quantify itch through physical signs such as excoriations, it ultimately is a subjective symptom that is difficult to assess.

Pain is another complex subjective symptom but is one that has been better studied. A previous intensity theory postulated that itch is a form of pain: low-intensity noxious stimuli are perceived as itch, while high-intensity stimuli are perceived as pain. Over time, our understanding of itch evolved, and it became clear that a specific neuronal pathway for itch also exists.³ However, the pathophysiology of itch and pain remain intertwined. Scratching may elicit pain, providing a change in sensation that replaces the itch, whereas opioid analgesics suppress pain but may worsen the itch.

We are gaining a better understanding of the biology and classification of itch, which will hopefully enable the development of new measures to accurately assess itch. Four main categories of itch currently exist: neurogenic, psychogenic, neuropathic, and pruritoceptive.⁴ Patients may have one or multiple types of itch, which can be differentiated clinically and biochemically. Neurogenic (also known as systemic) itch is transmitted via the central nervous system with possible involvement of itch-specific neurons in the spinal cord and encompasses itch associated with pruritus from other organ systems. As the term implies, psychogenic itch is associated with psychiatric disorders. Neuropathic itch is generated from the inappropriate firing of peripheral or central sensory neurons in the absence of pruritogenic stimuli, which can be seen in notalgia paresthetica, brachioradial pruritus, and postherpetic neuralgia. Pruritoceptive itch most commonly is encountered in dermatology and is associated with skin inflammation or other dermatoses.⁴

How to Assess Itch Quantitatively

There currently are 2 major questions about quantitative assessments of itch. First, how do we measure itch in studies that are designed to relieve a different skin disease that is associated with itch? Most clinical trials investigating therapeutic options for atopic dermatitis and psoriasis now include itch assessment and improvement as a secondary outcome. Second, how do we measure itch in studies that are designed with relief of itch as the primary end point? Both of these scenarios require a fundamental set of decisions. Itch clearly is a subjective experience, but it also is one that can be local, regional, generalized, or transitory. Just as with pain, an individual can be distracted from their itch to some extent and consequently experience it more acutely when there are fewer stimuli in their environment. Classically, patients will report that itching is worse at night, preventing them from sleeping. Sleep disruption previously has been demonstrated.⁵ Of course, the environment also can exacerbate itch, as dry air and in some cases humidity can flare the sensation.

Fundamentally, therefore, the questions that are asked to assess itch are incredibly relevant, and there is a matrix of possible avenues of inquiry. Should you measure the peak itch in one area or the peak itch overall? Is the duration, the frequency, or the persistence of the itching most relevant? What is the correct time frame in which to do an assessment: the last 24 hours, the last 48 hours, or the last week? Because these parameters have been so challenging, most investigators have used a visual analog scale, similar to what is used to assess pain, at a 24-hour interval to decrease recall bias. The most commonly employed tool is the itch numeric rating scale (NRS), which asks patients to rate their symptoms on a scale of 0 (no itch) to 10 (worst imaginable itch). Although the psychometric properties of the itch NRS have been validated, debate still exists as to whether the itch NRS is best administered at a specific time of day or if it should be updated to evaluate peak pruritus scores explicitly. Regardless, implementing these scales often is time consuming and burdensome in the clinical trial setting, as participants are asked to complete daily diaries at the same time each day using either paper forms or electronic tablets.

Once scores are collected, we then need to quantitate a meaningful difference in itch. For pain, there has been some acceptance of a 30% difference, or a 2-point reduction, as being clinically meaningful; however, there was substantial debate at the time of the approval of ixekizumab as to whether that was a similarly appropriate threshold for itch. Using data from ixekizumab phase 2 and phase 3 trials, a 4-point reduction in itch NRS was found to be optimal for evaluating clinically significant changes in moderate to severe psoriasis.⁶ A more recent study of the validity of the itch NRS in prurigo nodularis suggested a 1-point change was correlated with minimal clinical improvement.⁷ Thus, the interesting question of how assessment of itch varies across clinical trials and disease states needs to be raised. Psoriasis classically has been thought of as not particularly itchy, and atopic dermatitis and prurigo nodularis have been regarded as extraordinarily itchy, yet one study comparing baseline itch scores in psoriasis and atopic dermatitis suggested that the experience actually is somewhat similar.⁸

Final Thoughts

The subjective nature of itch makes NRSs our best option at this time, but the best disease severity assessment tools are objective, sensitive, and generalizable. Unfortunately, we do not have such tools available to us yet, but technology—smart devices to monitor nocturnal scratching and machine learning algorithms that use electromagnetic impact to capture motion associated with itching and scratching⁹—may offer new objective measures for itch that can be used to further validate the current itch NRS. Even if these technology-based approaches become the standard of measurement, they will certainly help us understand what we are measuring. And even better, the focus on how to develop meaningful end points around the improvement of itch will likely lead us to measure it more and drive the development of therapeutics that address the effect and consequences of this pernicious problem.

Itch is one of the most protean manifestations of skin disease and can take a substantial physical and emotional toll on patients. For physicians, it is a frequent—if often dreaded—patient concern with a rising incidence. Lack of specific itch therapies as well as associations with multiple dermatologic conditions, including xerosis, psoriasis, atopic dermatitis, cutaneous lymphoma, contact dermatitis, and internal malignancies, make management of these itchy patients challenging and deserving of our attention. Studies evaluating patients with chronic pruritus identified a considerable impact on health-related quality of life, including development of depression, inability to perform activities of daily living, and sleep difficulties. ¹

How to Classify Itching

Itch, or pruritus, originally was defined as an unpleasant sensation that provokes the desire to scratch,² but this definition likely limits our ability to assess itch. The urge to scratch the skin to relieve the itch is sometimes a reflex of the muscles triggered by the spinal cord that can be either conscious or unconscious. If 2 patients present with itch, does the patient with more excoriated skin experience more severe itch? Conversely, does the patient who scratches less have an equivalent decrease in itch severity? Although it is tempting to quantify itch through physical signs such as excoriations, it ultimately is a subjective symptom that is difficult to assess.

Pain is another complex subjective symptom but is one that has been better studied. A previous intensity theory postulated that itch is a form of pain: low-intensity noxious stimuli are perceived as itch, while high-intensity stimuli are perceived as pain. Over time, our understanding of itch evolved, and it became clear that a specific neuronal pathway for itch also exists.³ However, the pathophysiology of itch and pain remain intertwined. Scratching may elicit pain, providing a change in sensation that replaces the itch, whereas opioid analgesics suppress pain but may worsen the itch.

We are gaining a better understanding of the biology and classification of itch, which will hopefully enable the development of new measures to accurately assess itch. Four main categories of itch currently exist: neurogenic, psychogenic, neuropathic, and pruritoceptive.⁴ Patients may have one or multiple types of itch, which can be differentiated clinically and biochemically. Neurogenic (also known as systemic) itch is transmitted via the central nervous system with possible involvement of itch-specific neurons in the spinal cord and encompasses itch associated with pruritus from other organ systems. As the term implies, psychogenic itch is associated with psychiatric disorders. Neuropathic itch is generated from the inappropriate firing of peripheral or central sensory neurons in the absence of pruritogenic stimuli, which can be seen in notalgia paresthetica, brachioradial pruritus, and postherpetic neuralgia. Pruritoceptive itch most commonly is encountered in dermatology and is associated with skin inflammation or other dermatoses.⁴

How to Assess Itch Quantitatively

There currently are 2 major questions about quantitative assessments of itch. First, how do we measure itch in studies that are designed to relieve a different skin disease that is associated with itch? Most clinical trials investigating therapeutic options for atopic dermatitis and psoriasis now include itch assessment and improvement as a secondary outcome. Second, how do we measure itch in studies that are designed with relief of itch as the primary end point? Both of these scenarios require a fundamental set of decisions. Itch clearly is a subjective experience, but it also is one that can be local, regional, generalized, or transitory. Just as with pain, an individual can be distracted from their itch to some extent and consequently experience it more acutely when there are fewer stimuli in their environment. Classically, patients will report that itching is worse at night, preventing them from sleeping. Sleep disruption previously has been demonstrated.⁵ Of course, the environment also can exacerbate itch, as dry air and in some cases humidity can flare the sensation.

Fundamentally, therefore, the questions that are asked to assess itch are incredibly relevant, and there is a matrix of possible avenues of inquiry. Should you measure the peak itch in one area or the peak itch overall? Is the duration, the frequency, or the persistence of the itching most relevant? What is the correct time frame in which to do an assessment: the last 24 hours, the last 48 hours, or the last week? Because these parameters have been so challenging, most investigators have used a visual analog scale, similar to what is used to assess pain, at a 24-hour interval to decrease recall bias. The most commonly employed tool is the itch numeric rating scale (NRS), which asks patients to rate their symptoms on a scale of 0 (no itch) to 10 (worst imaginable itch). Although the psychometric properties of the itch NRS have been validated, debate still exists as to whether the itch NRS is best administered at a specific time of day or if it should be updated to evaluate peak pruritus scores explicitly. Regardless, implementing these scales often is time consuming and burdensome in the clinical trial setting, as participants are asked to complete daily diaries at the same time each day using either paper forms or electronic tablets.

Once scores are collected, we then need to quantitate a meaningful difference in itch. For pain, there has been some acceptance of a 30% difference, or a 2-point reduction, as being clinically meaningful; however, there was substantial debate at the time of the approval of ixekizumab as to whether that was a similarly appropriate threshold for itch. Using data from ixekizumab phase 2 and phase 3 trials, a 4-point reduction in itch NRS was found to be optimal for evaluating clinically significant changes in moderate to severe psoriasis.⁶ A more recent study of the validity of the itch NRS in prurigo nodularis suggested a 1-point change was correlated with minimal clinical improvement.⁷ Thus, the interesting question of how assessment of itch varies across clinical trials and disease states needs to be raised. Psoriasis classically has been thought of as not particularly itchy, and atopic dermatitis and prurigo nodularis have been regarded as extraordinarily itchy, yet one study comparing baseline itch scores in psoriasis and atopic dermatitis suggested that the experience actually is somewhat similar.⁸

Final Thoughts

The subjective nature of itch makes NRSs our best option at this time, but the best disease severity assessment tools are objective, sensitive, and generalizable. Unfortunately, we do not have such tools available to us yet, but technology—smart devices to monitor nocturnal scratching and machine learning algorithms that use electromagnetic impact to capture motion associated with itching and scratching⁹—may offer new objective measures for itch that can be used to further validate the current itch NRS. Even if these technology-based approaches become the standard of measurement, they will certainly help us understand what we are measuring. And even better, the focus on how to develop meaningful end points around the improvement of itch will likely lead us to measure it more and drive the development of therapeutics that address the effect and consequences of this pernicious problem.

Itch is one of the most protean manifestations of skin disease and can take a substantial physical and emotional toll on patients. For physicians, it is a frequent—if often dreaded—patient concern with a rising incidence. Lack of specific itch therapies as well as associations with multiple dermatologic conditions, including xerosis, psoriasis, atopic dermatitis, cutaneous lymphoma, contact dermatitis, and internal malignancies, make management of these itchy patients challenging and deserving of our attention. Studies evaluating patients with chronic pruritus identified a considerable impact on health-related quality of life, including development of depression, inability to perform activities of daily living, and sleep difficulties. ¹

How to Classify Itching

Itch, or pruritus, originally was defined as an unpleasant sensation that provokes the desire to scratch,² but this definition likely limits our ability to assess itch. The urge to scratch the skin to relieve the itch is sometimes a reflex of the muscles triggered by the spinal cord that can be either conscious or unconscious. If 2 patients present with itch, does the patient with more excoriated skin experience more severe itch? Conversely, does the patient who scratches less have an equivalent decrease in itch severity? Although it is tempting to quantify itch through physical signs such as excoriations, it ultimately is a subjective symptom that is difficult to assess.

Pain is another complex subjective symptom but is one that has been better studied. A previous intensity theory postulated that itch is a form of pain: low-intensity noxious stimuli are perceived as itch, while high-intensity stimuli are perceived as pain. Over time, our understanding of itch evolved, and it became clear that a specific neuronal pathway for itch also exists.³ However, the pathophysiology of itch and pain remain intertwined. Scratching may elicit pain, providing a change in sensation that replaces the itch, whereas opioid analgesics suppress pain but may worsen the itch.

We are gaining a better understanding of the biology and classification of itch, which will hopefully enable the development of new measures to accurately assess itch. Four main categories of itch currently exist: neurogenic, psychogenic, neuropathic, and pruritoceptive.⁴ Patients may have one or multiple types of itch, which can be differentiated clinically and biochemically. Neurogenic (also known as systemic) itch is transmitted via the central nervous system with possible involvement of itch-specific neurons in the spinal cord and encompasses itch associated with pruritus from other organ systems. As the term implies, psychogenic itch is associated with psychiatric disorders. Neuropathic itch is generated from the inappropriate firing of peripheral or central sensory neurons in the absence of pruritogenic stimuli, which can be seen in notalgia paresthetica, brachioradial pruritus, and postherpetic neuralgia. Pruritoceptive itch most commonly is encountered in dermatology and is associated with skin inflammation or other dermatoses.⁴

How to Assess Itch Quantitatively

There currently are 2 major questions about quantitative assessments of itch. First, how do we measure itch in studies that are designed to relieve a different skin disease that is associated with itch? Most clinical trials investigating therapeutic options for atopic dermatitis and psoriasis now include itch assessment and improvement as a secondary outcome. Second, how do we measure itch in studies that are designed with relief of itch as the primary end point? Both of these scenarios require a fundamental set of decisions. Itch clearly is a subjective experience, but it also is one that can be local, regional, generalized, or transitory. Just as with pain, an individual can be distracted from their itch to some extent and consequently experience it more acutely when there are fewer stimuli in their environment. Classically, patients will report that itching is worse at night, preventing them from sleeping. Sleep disruption previously has been demonstrated.⁵ Of course, the environment also can exacerbate itch, as dry air and in some cases humidity can flare the sensation.

Fundamentally, therefore, the questions that are asked to assess itch are incredibly relevant, and there is a matrix of possible avenues of inquiry. Should you measure the peak itch in one area or the peak itch overall? Is the duration, the frequency, or the persistence of the itching most relevant? What is the correct time frame in which to do an assessment: the last 24 hours, the last 48 hours, or the last week? Because these parameters have been so challenging, most investigators have used a visual analog scale, similar to what is used to assess pain, at a 24-hour interval to decrease recall bias. The most commonly employed tool is the itch numeric rating scale (NRS), which asks patients to rate their symptoms on a scale of 0 (no itch) to 10 (worst imaginable itch). Although the psychometric properties of the itch NRS have been validated, debate still exists as to whether the itch NRS is best administered at a specific time of day or if it should be updated to evaluate peak pruritus scores explicitly. Regardless, implementing these scales often is time consuming and burdensome in the clinical trial setting, as participants are asked to complete daily diaries at the same time each day using either paper forms or electronic tablets.

Once scores are collected, we then need to quantitate a meaningful difference in itch. For pain, there has been some acceptance of a 30% difference, or a 2-point reduction, as being clinically meaningful; however, there was substantial debate at the time of the approval of ixekizumab as to whether that was a similarly appropriate threshold for itch. Using data from ixekizumab phase 2 and phase 3 trials, a 4-point reduction in itch NRS was found to be optimal for evaluating clinically significant changes in moderate to severe psoriasis.⁶ A more recent study of the validity of the itch NRS in prurigo nodularis suggested a 1-point change was correlated with minimal clinical improvement.⁷ Thus, the interesting question of how assessment of itch varies across clinical trials and disease states needs to be raised. Psoriasis classically has been thought of as not particularly itchy, and atopic dermatitis and prurigo nodularis have been regarded as extraordinarily itchy, yet one study comparing baseline itch scores in psoriasis and atopic dermatitis suggested that the experience actually is somewhat similar.⁸

Final Thoughts

The subjective nature of itch makes NRSs our best option at this time, but the best disease severity assessment tools are objective, sensitive, and generalizable. Unfortunately, we do not have such tools available to us yet, but technology—smart devices to monitor nocturnal scratching and machine learning algorithms that use electromagnetic impact to capture motion associated with itching and scratching⁹—may offer new objective measures for itch that can be used to further validate the current itch NRS. Even if these technology-based approaches become the standard of measurement, they will certainly help us understand what we are measuring. And even better, the focus on how to develop meaningful end points around the improvement of itch will likely lead us to measure it more and drive the development of therapeutics that address the effect and consequences of this pernicious problem.

An experimental oral Janus kinase 1 (JAK1) inhibitor, abrocitinib, showed greater itch reduction after 2 weeks of treatment than dupilumab in patients with moderate to severe atopic dermatitis (AD), in a multicenter, randomized trial.

In addition, in the study, those on 200-mg and 100-mg daily doses of abrocitinib experienced significantly greater reductions in signs and symptoms of AD at 12 and 16 weeks, than those on placebo, the authors reported.

The findings from the JADE COMPARE trial, published on March 25 in the New England Journal of Medicine, suggest abrocitinib will provide clinicians with another treatment option for patients who don’t get adequate relief from either topical medications or dupilumab. Abrocitinib is associated with a different set of adverse reactions than dupilumab, according to investigators.

In 2017, dupilumab (Dupixent) became the first systemic drug approved by the Food and Drug Administration specifically for AD, though systemic steroids and other immunosuppressant drugs are sometimes prescribed. A monoclonal antibody delivered by subcutaneous injection, dupilumab binds to interleukin-4 receptors to block signaling pathways involved in AD; it is now approved for treatment of patients with moderate to severe AD down to age 6 years.

“It is sort of the bar for efficacy and for safety in those patients, because that’s what we have right now,” said one of the JADE Compare investigators and study author, Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology and director of clinical research and contact dermatitis at George Washington University, Washington, said in an interview. “For any new therapy coming to market, we really do want to understand how it compares to what’s out there.”

Abrocitinib is a small molecule that inhibits JAK1, which is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin. Two other JAK1 inhibitors, baricitinib and upadacitinib, are also being investigated as systemic treatments for AD.

In JADE COMPARE, people with moderate to severe AD from 18 countries on four continents, entered a 28-day screening period during which they discontinued treatments. They began using emollients twice a day at least 7 days before being randomly assigned to a treatment group, and continued on topical medication once daily. Topical treatments included low- or medium-potency topical glucocorticoids, calcineurin inhibitors, and phosphodiesterase-4 inhibitors.

The researchers randomly assigned 838 to trial groups: 226 received 200 mg of abrocitinib orally once a day, 238 received 100 mg of abrocitinib once a day, 243 received a 300-mg dupilumab injection every other week, and 131 received placebo versions of both medications, for 16 weeks. The mean age of the patients overall was about 38 years; about two-thirds were White.

At 2 weeks, half of the patients on 200 mg of abrocitinib and 31.8% of those on the 100-mg dose had an itch response, defined as at least a 4-point improvement from baseline in the 0-10 Peak Pruritus Numerical Rating Scale. This was compared with 26.4% of those on dupilumab and 13.8% of those on placebo.

And at 12 weeks, more of the patients in the 200-mg abrocitinib group than in the other groups had an Investigator’s Global Assessment (IGA) response (defined as clear or almost clear) and more had an Eczema Area and Severity Index (EASI-75) response (defined as an improvement of at least 75%). (See Table) EASI-75 and IGA responses at week 12 were the primary outcomes of the study.

The overall incidence of adverse events was higher in the 200-mg abrocitinib arm than in the other groups, but the incidence of serious or severe adverse events, and the incidence of adverse events that resulted in discontinuing the medication, were similar across the trial groups.

However, nausea affected 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group. Acne was also reported in these groups (6.6% and 2.9%, among those on 200 mg and 100 mg, respectively, compared with 1.2% of those on dupilumab and none of those on placebo). In a few of those on abrocitinib, herpes zoster flared up. And median platelet counts decreased among the patients taking abrocitinib, although none dropped below 75,000/mm³. Serious infections were reported in two patients on abrocitinib, but resolved.

By contrast, only 2.9% of the patients on dupilumab had nausea. But 6.2% in the dupilumab group had conjunctivitis, compared with 1.3% of patients in the 200-mg abrocitinib group and 0.8 in the 100-mg abrocitinib group.

As an oral medication, abrocitinib will appeal to patients who want to avoid injections, and dosing will be easier to adjust, Dr. Silverberg said. On the other hand, he added, dupilumab will have an advantage for patients who don’t want to take a daily medication, or who are concerned about the adverse events associated with abrocitinib, particularly those with blood-clotting disorders.

On the basis of two previous JADE phase 3 trials, Pfizer has submitted a new drug application for abrocitinib for treating moderate to severe AD in patients aged 12 and older to the FDA; a decision is expected in April, according to the company. The company has also applied to market the drug in Europe and the United Kingdom.

The study was funded by Pfizer. Dr. Silverberg’s disclosures included serving as a consultant to companies including AbbVie, Pfizer, and Regeneron. Several authors are Pfizer employees; other authors had disclosures related to Pfizer and other pharmaceutical companies.

 

An experimental oral Janus kinase 1 (JAK1) inhibitor, abrocitinib, showed greater itch reduction after 2 weeks of treatment than dupilumab in patients with moderate to severe atopic dermatitis (AD), in a multicenter, randomized trial.

In addition, in the study, those on 200-mg and 100-mg daily doses of abrocitinib experienced significantly greater reductions in signs and symptoms of AD at 12 and 16 weeks, than those on placebo, the authors reported.

The findings from the JADE COMPARE trial, published on March 25 in the New England Journal of Medicine, suggest abrocitinib will provide clinicians with another treatment option for patients who don’t get adequate relief from either topical medications or dupilumab. Abrocitinib is associated with a different set of adverse reactions than dupilumab, according to investigators.

In 2017, dupilumab (Dupixent) became the first systemic drug approved by the Food and Drug Administration specifically for AD, though systemic steroids and other immunosuppressant drugs are sometimes prescribed. A monoclonal antibody delivered by subcutaneous injection, dupilumab binds to interleukin-4 receptors to block signaling pathways involved in AD; it is now approved for treatment of patients with moderate to severe AD down to age 6 years.

“It is sort of the bar for efficacy and for safety in those patients, because that’s what we have right now,” said one of the JADE Compare investigators and study author, Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology and director of clinical research and contact dermatitis at George Washington University, Washington, said in an interview. “For any new therapy coming to market, we really do want to understand how it compares to what’s out there.”

Abrocitinib is a small molecule that inhibits JAK1, which is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin. Two other JAK1 inhibitors, baricitinib and upadacitinib, are also being investigated as systemic treatments for AD.

In JADE COMPARE, people with moderate to severe AD from 18 countries on four continents, entered a 28-day screening period during which they discontinued treatments. They began using emollients twice a day at least 7 days before being randomly assigned to a treatment group, and continued on topical medication once daily. Topical treatments included low- or medium-potency topical glucocorticoids, calcineurin inhibitors, and phosphodiesterase-4 inhibitors.

The researchers randomly assigned 838 to trial groups: 226 received 200 mg of abrocitinib orally once a day, 238 received 100 mg of abrocitinib once a day, 243 received a 300-mg dupilumab injection every other week, and 131 received placebo versions of both medications, for 16 weeks. The mean age of the patients overall was about 38 years; about two-thirds were White.

At 2 weeks, half of the patients on 200 mg of abrocitinib and 31.8% of those on the 100-mg dose had an itch response, defined as at least a 4-point improvement from baseline in the 0-10 Peak Pruritus Numerical Rating Scale. This was compared with 26.4% of those on dupilumab and 13.8% of those on placebo.

And at 12 weeks, more of the patients in the 200-mg abrocitinib group than in the other groups had an Investigator’s Global Assessment (IGA) response (defined as clear or almost clear) and more had an Eczema Area and Severity Index (EASI-75) response (defined as an improvement of at least 75%). (See Table) EASI-75 and IGA responses at week 12 were the primary outcomes of the study.

The overall incidence of adverse events was higher in the 200-mg abrocitinib arm than in the other groups, but the incidence of serious or severe adverse events, and the incidence of adverse events that resulted in discontinuing the medication, were similar across the trial groups.

However, nausea affected 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group. Acne was also reported in these groups (6.6% and 2.9%, among those on 200 mg and 100 mg, respectively, compared with 1.2% of those on dupilumab and none of those on placebo). In a few of those on abrocitinib, herpes zoster flared up. And median platelet counts decreased among the patients taking abrocitinib, although none dropped below 75,000/mm³. Serious infections were reported in two patients on abrocitinib, but resolved.

By contrast, only 2.9% of the patients on dupilumab had nausea. But 6.2% in the dupilumab group had conjunctivitis, compared with 1.3% of patients in the 200-mg abrocitinib group and 0.8 in the 100-mg abrocitinib group.

As an oral medication, abrocitinib will appeal to patients who want to avoid injections, and dosing will be easier to adjust, Dr. Silverberg said. On the other hand, he added, dupilumab will have an advantage for patients who don’t want to take a daily medication, or who are concerned about the adverse events associated with abrocitinib, particularly those with blood-clotting disorders.

On the basis of two previous JADE phase 3 trials, Pfizer has submitted a new drug application for abrocitinib for treating moderate to severe AD in patients aged 12 and older to the FDA; a decision is expected in April, according to the company. The company has also applied to market the drug in Europe and the United Kingdom.

The study was funded by Pfizer. Dr. Silverberg’s disclosures included serving as a consultant to companies including AbbVie, Pfizer, and Regeneron. Several authors are Pfizer employees; other authors had disclosures related to Pfizer and other pharmaceutical companies.

 

An experimental oral Janus kinase 1 (JAK1) inhibitor, abrocitinib, showed greater itch reduction after 2 weeks of treatment than dupilumab in patients with moderate to severe atopic dermatitis (AD), in a multicenter, randomized trial.

In addition, in the study, those on 200-mg and 100-mg daily doses of abrocitinib experienced significantly greater reductions in signs and symptoms of AD at 12 and 16 weeks, than those on placebo, the authors reported.

The findings from the JADE COMPARE trial, published on March 25 in the New England Journal of Medicine, suggest abrocitinib will provide clinicians with another treatment option for patients who don’t get adequate relief from either topical medications or dupilumab. Abrocitinib is associated with a different set of adverse reactions than dupilumab, according to investigators.

In 2017, dupilumab (Dupixent) became the first systemic drug approved by the Food and Drug Administration specifically for AD, though systemic steroids and other immunosuppressant drugs are sometimes prescribed. A monoclonal antibody delivered by subcutaneous injection, dupilumab binds to interleukin-4 receptors to block signaling pathways involved in AD; it is now approved for treatment of patients with moderate to severe AD down to age 6 years.

“It is sort of the bar for efficacy and for safety in those patients, because that’s what we have right now,” said one of the JADE Compare investigators and study author, Jonathan I. Silverberg, MD, PhD, MPH, associate professor of dermatology and director of clinical research and contact dermatitis at George Washington University, Washington, said in an interview. “For any new therapy coming to market, we really do want to understand how it compares to what’s out there.”

Abrocitinib is a small molecule that inhibits JAK1, which is thought to modulate multiple cytokines involved in AD, including interleukin (IL)–4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin. Two other JAK1 inhibitors, baricitinib and upadacitinib, are also being investigated as systemic treatments for AD.

In JADE COMPARE, people with moderate to severe AD from 18 countries on four continents, entered a 28-day screening period during which they discontinued treatments. They began using emollients twice a day at least 7 days before being randomly assigned to a treatment group, and continued on topical medication once daily. Topical treatments included low- or medium-potency topical glucocorticoids, calcineurin inhibitors, and phosphodiesterase-4 inhibitors.

The researchers randomly assigned 838 to trial groups: 226 received 200 mg of abrocitinib orally once a day, 238 received 100 mg of abrocitinib once a day, 243 received a 300-mg dupilumab injection every other week, and 131 received placebo versions of both medications, for 16 weeks. The mean age of the patients overall was about 38 years; about two-thirds were White.

At 2 weeks, half of the patients on 200 mg of abrocitinib and 31.8% of those on the 100-mg dose had an itch response, defined as at least a 4-point improvement from baseline in the 0-10 Peak Pruritus Numerical Rating Scale. This was compared with 26.4% of those on dupilumab and 13.8% of those on placebo.

And at 12 weeks, more of the patients in the 200-mg abrocitinib group than in the other groups had an Investigator’s Global Assessment (IGA) response (defined as clear or almost clear) and more had an Eczema Area and Severity Index (EASI-75) response (defined as an improvement of at least 75%). (See Table) EASI-75 and IGA responses at week 12 were the primary outcomes of the study.

The overall incidence of adverse events was higher in the 200-mg abrocitinib arm than in the other groups, but the incidence of serious or severe adverse events, and the incidence of adverse events that resulted in discontinuing the medication, were similar across the trial groups.

However, nausea affected 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group. Acne was also reported in these groups (6.6% and 2.9%, among those on 200 mg and 100 mg, respectively, compared with 1.2% of those on dupilumab and none of those on placebo). In a few of those on abrocitinib, herpes zoster flared up. And median platelet counts decreased among the patients taking abrocitinib, although none dropped below 75,000/mm³. Serious infections were reported in two patients on abrocitinib, but resolved.

By contrast, only 2.9% of the patients on dupilumab had nausea. But 6.2% in the dupilumab group had conjunctivitis, compared with 1.3% of patients in the 200-mg abrocitinib group and 0.8 in the 100-mg abrocitinib group.

As an oral medication, abrocitinib will appeal to patients who want to avoid injections, and dosing will be easier to adjust, Dr. Silverberg said. On the other hand, he added, dupilumab will have an advantage for patients who don’t want to take a daily medication, or who are concerned about the adverse events associated with abrocitinib, particularly those with blood-clotting disorders.

On the basis of two previous JADE phase 3 trials, Pfizer has submitted a new drug application for abrocitinib for treating moderate to severe AD in patients aged 12 and older to the FDA; a decision is expected in April, according to the company. The company has also applied to market the drug in Europe and the United Kingdom.

The study was funded by Pfizer. Dr. Silverberg’s disclosures included serving as a consultant to companies including AbbVie, Pfizer, and Regeneron. Several authors are Pfizer employees; other authors had disclosures related to Pfizer and other pharmaceutical companies.

 

Ruxolitinib cream, an investigational selective Janus kinase 1 and 2 inhibitor now under priority review by the Food and Drug Administration for the treatment of atopic dermatitis (AD) down to age 12 years, demonstrated a dual mechanism of action in two pivotal phase 3 trials: antipruritic and anti-inflammatory, Kim A. Papp, MD, PhD, said at Innovations in Dermatology: Virtual Spring Conference 2021. He presented a pooled analysis of the TRuE-AD1 and TRuE-AD2 trials, in which 1,249 patients with AD affecting 3%-20% of the body surface area were randomized 2:2:1 double-blind to ruxolitinib cream 0.75%, 1.5%, or vehicle twice daily for 8 weeks.

Striking evidence of the drug’s antipruritic effect comes from the finding that patient-reported itch scores separated significantly from the vehicle controls within just 12 hours after the first application. The margin of difference grew over time such that at 4 weeks, 48.5% of patients on ruxolitinib 1.5% experienced a clinically meaningful reduction in itch – defined by at least a 4-point improvement on the itch numeric rating scale – as did 30.1% of those on ruxolitinib 0.75% and 6.1% of controls. By week 8, these figures had further improved to 51.5%, 41.5%, and 15.8%, respectively, noted Dr. Papp, a dermatologist and president of Probity Medical Research in Waterloo, Ont.

Ruxolitinib’s anti-inflammatory mechanism of action was on display in the primary study endpoint, which was the proportion of patients achieving an Investigator Global Assessment score of 0 or 1 with at least a 2-grade improvement from baseline at week 8. The rates were 52.6% with ruxolitinib 1.5% and 44.7% at the lower dose, both significantly better than the 11.5% rate with vehicle.

For the secondary endpoint of at least a 75% improvement in Eczema Area and Severity Index score at week 8, the rates were 62% with ruxolitinib 1.5% and 53.8% at the 0.75% concentration, compared with 19.7% with vehicle.

The topical JAK inhibitor also showed superior efficacy in terms of improvement on the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Score, with a clinically meaningful 6-point or greater improvement in 23.9% and 20.9% of patients in the high- and low-dose ruxolitinib groups, versus 14.2% in controls.

Plasma drug levels remained consistently low and near-flat throughout the study.

Session comoderator Lawrence F. Eichenfield, MD, was struck by what he termed the “incredibly low” rates of irritancy, burning, and stinging in the ruxolitinib-treated patients: 7 cases of application-site burning in 999 treated patients, compared with 11 cases in 250 vehicle-treated patients, and 4 cases of application-site pruritus in nearly 1,000 patients on ruxolitinib, versus 6 cases in one-fourth as many controls.

“If that’s really true in clinical practice, it would be tremendous to have a nonsteroid that doesn’t have stinging and burning and may have that efficacy,” said Dr. Eichenfield, professor of dermatology and pediatrics and vice-chair of dermatology at the University of California, San Diego.

“I think the fast action is an exciting aspect of this,” said comoderator Jonathan I. Silverberg, MD, PhD, MBA, director of clinical research and contact dermatitis in the department of dermatology at George Washington University in Washington.

He noted that in an earlier phase 2 study, ruxolitinib cream was at least as efficacious as 0.1% triamcinolone cream, providing dermatologists with a rough yardstick as to where the topical JAK inhibitor lies on the potency spectrum for AD treatment.

The FDA is expected to issue a decision on the application for approval of ruxolitinib cream in June. Dr. Eichenfield expects the drug to easily win approval. The big unanswered question is whether the regulatory agency will require boxed safety warnings, as it does for the oral JAK inhibitors approved for various indications, even though safety issues haven’t arisen with the topical agent in the clinical trials.

Dr. Papp reported receiving research grants from and serving as a consultant to Incyte Corp., which funded the ruxolitinib studies, as well as numerous other pharmaceutical companies. MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Ruxolitinib cream, an investigational selective Janus kinase 1 and 2 inhibitor now under priority review by the Food and Drug Administration for the treatment of atopic dermatitis (AD) down to age 12 years, demonstrated a dual mechanism of action in two pivotal phase 3 trials: antipruritic and anti-inflammatory, Kim A. Papp, MD, PhD, said at Innovations in Dermatology: Virtual Spring Conference 2021. He presented a pooled analysis of the TRuE-AD1 and TRuE-AD2 trials, in which 1,249 patients with AD affecting 3%-20% of the body surface area were randomized 2:2:1 double-blind to ruxolitinib cream 0.75%, 1.5%, or vehicle twice daily for 8 weeks.

Striking evidence of the drug’s antipruritic effect comes from the finding that patient-reported itch scores separated significantly from the vehicle controls within just 12 hours after the first application. The margin of difference grew over time such that at 4 weeks, 48.5% of patients on ruxolitinib 1.5% experienced a clinically meaningful reduction in itch – defined by at least a 4-point improvement on the itch numeric rating scale – as did 30.1% of those on ruxolitinib 0.75% and 6.1% of controls. By week 8, these figures had further improved to 51.5%, 41.5%, and 15.8%, respectively, noted Dr. Papp, a dermatologist and president of Probity Medical Research in Waterloo, Ont.

Ruxolitinib’s anti-inflammatory mechanism of action was on display in the primary study endpoint, which was the proportion of patients achieving an Investigator Global Assessment score of 0 or 1 with at least a 2-grade improvement from baseline at week 8. The rates were 52.6% with ruxolitinib 1.5% and 44.7% at the lower dose, both significantly better than the 11.5% rate with vehicle.

For the secondary endpoint of at least a 75% improvement in Eczema Area and Severity Index score at week 8, the rates were 62% with ruxolitinib 1.5% and 53.8% at the 0.75% concentration, compared with 19.7% with vehicle.

The topical JAK inhibitor also showed superior efficacy in terms of improvement on the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Score, with a clinically meaningful 6-point or greater improvement in 23.9% and 20.9% of patients in the high- and low-dose ruxolitinib groups, versus 14.2% in controls.

Plasma drug levels remained consistently low and near-flat throughout the study.

Session comoderator Lawrence F. Eichenfield, MD, was struck by what he termed the “incredibly low” rates of irritancy, burning, and stinging in the ruxolitinib-treated patients: 7 cases of application-site burning in 999 treated patients, compared with 11 cases in 250 vehicle-treated patients, and 4 cases of application-site pruritus in nearly 1,000 patients on ruxolitinib, versus 6 cases in one-fourth as many controls.

“If that’s really true in clinical practice, it would be tremendous to have a nonsteroid that doesn’t have stinging and burning and may have that efficacy,” said Dr. Eichenfield, professor of dermatology and pediatrics and vice-chair of dermatology at the University of California, San Diego.

“I think the fast action is an exciting aspect of this,” said comoderator Jonathan I. Silverberg, MD, PhD, MBA, director of clinical research and contact dermatitis in the department of dermatology at George Washington University in Washington.

He noted that in an earlier phase 2 study, ruxolitinib cream was at least as efficacious as 0.1% triamcinolone cream, providing dermatologists with a rough yardstick as to where the topical JAK inhibitor lies on the potency spectrum for AD treatment.

The FDA is expected to issue a decision on the application for approval of ruxolitinib cream in June. Dr. Eichenfield expects the drug to easily win approval. The big unanswered question is whether the regulatory agency will require boxed safety warnings, as it does for the oral JAK inhibitors approved for various indications, even though safety issues haven’t arisen with the topical agent in the clinical trials.

Dr. Papp reported receiving research grants from and serving as a consultant to Incyte Corp., which funded the ruxolitinib studies, as well as numerous other pharmaceutical companies. MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com

Ruxolitinib cream, an investigational selective Janus kinase 1 and 2 inhibitor now under priority review by the Food and Drug Administration for the treatment of atopic dermatitis (AD) down to age 12 years, demonstrated a dual mechanism of action in two pivotal phase 3 trials: antipruritic and anti-inflammatory, Kim A. Papp, MD, PhD, said at Innovations in Dermatology: Virtual Spring Conference 2021. He presented a pooled analysis of the TRuE-AD1 and TRuE-AD2 trials, in which 1,249 patients with AD affecting 3%-20% of the body surface area were randomized 2:2:1 double-blind to ruxolitinib cream 0.75%, 1.5%, or vehicle twice daily for 8 weeks.

Striking evidence of the drug’s antipruritic effect comes from the finding that patient-reported itch scores separated significantly from the vehicle controls within just 12 hours after the first application. The margin of difference grew over time such that at 4 weeks, 48.5% of patients on ruxolitinib 1.5% experienced a clinically meaningful reduction in itch – defined by at least a 4-point improvement on the itch numeric rating scale – as did 30.1% of those on ruxolitinib 0.75% and 6.1% of controls. By week 8, these figures had further improved to 51.5%, 41.5%, and 15.8%, respectively, noted Dr. Papp, a dermatologist and president of Probity Medical Research in Waterloo, Ont.

Ruxolitinib’s anti-inflammatory mechanism of action was on display in the primary study endpoint, which was the proportion of patients achieving an Investigator Global Assessment score of 0 or 1 with at least a 2-grade improvement from baseline at week 8. The rates were 52.6% with ruxolitinib 1.5% and 44.7% at the lower dose, both significantly better than the 11.5% rate with vehicle.

For the secondary endpoint of at least a 75% improvement in Eczema Area and Severity Index score at week 8, the rates were 62% with ruxolitinib 1.5% and 53.8% at the 0.75% concentration, compared with 19.7% with vehicle.

The topical JAK inhibitor also showed superior efficacy in terms of improvement on the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Score, with a clinically meaningful 6-point or greater improvement in 23.9% and 20.9% of patients in the high- and low-dose ruxolitinib groups, versus 14.2% in controls.

Plasma drug levels remained consistently low and near-flat throughout the study.

Session comoderator Lawrence F. Eichenfield, MD, was struck by what he termed the “incredibly low” rates of irritancy, burning, and stinging in the ruxolitinib-treated patients: 7 cases of application-site burning in 999 treated patients, compared with 11 cases in 250 vehicle-treated patients, and 4 cases of application-site pruritus in nearly 1,000 patients on ruxolitinib, versus 6 cases in one-fourth as many controls.

“If that’s really true in clinical practice, it would be tremendous to have a nonsteroid that doesn’t have stinging and burning and may have that efficacy,” said Dr. Eichenfield, professor of dermatology and pediatrics and vice-chair of dermatology at the University of California, San Diego.

“I think the fast action is an exciting aspect of this,” said comoderator Jonathan I. Silverberg, MD, PhD, MBA, director of clinical research and contact dermatitis in the department of dermatology at George Washington University in Washington.

He noted that in an earlier phase 2 study, ruxolitinib cream was at least as efficacious as 0.1% triamcinolone cream, providing dermatologists with a rough yardstick as to where the topical JAK inhibitor lies on the potency spectrum for AD treatment.

The FDA is expected to issue a decision on the application for approval of ruxolitinib cream in June. Dr. Eichenfield expects the drug to easily win approval. The big unanswered question is whether the regulatory agency will require boxed safety warnings, as it does for the oral JAK inhibitors approved for various indications, even though safety issues haven’t arisen with the topical agent in the clinical trials.

Dr. Papp reported receiving research grants from and serving as a consultant to Incyte Corp., which funded the ruxolitinib studies, as well as numerous other pharmaceutical companies. MedscapeLive and this news organization are owned by the same parent company.

bjancin@mdedge.com