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Roflumilast foam effectively eases seborrheic dermatitis
.
More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
Common condition led to rapid recruitment
“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.
“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”
While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”
Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.
It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”
Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.
For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years.
Multiple improvements seen in ‘happy trial’
The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).
Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.
“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.
A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.
“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.
“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.
The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
Lesson for practice: Advise patients to moisturize?
“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.
It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.
“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”
The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.
A version of this article first appeared on Medscape.com.
.
More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
Common condition led to rapid recruitment
“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.
“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”
While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”
Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.
It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”
Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.
For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years.
Multiple improvements seen in ‘happy trial’
The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).
Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.
“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.
A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.
“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.
“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.
The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
Lesson for practice: Advise patients to moisturize?
“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.
It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.
“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”
The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.
A version of this article first appeared on Medscape.com.
.
More than half experienced clearance of their symptoms, and three out of five achieved a significant improvement in pruritus, it was revealed during a late-breaking session at the annual congress of the European Academy of Dermatology and Venereology.
Common condition led to rapid recruitment
“Seborrheic dermatitis is a disease that’s very common, yet in my opinion, undertreated in dermatology,” said Andrew Blauvelt, MD, MBA, who presented the findings.
“It’s so common that when we did this trial, I was very surprised to see how easy it was to recruit,” said Dr. Blauvelt, a dermatologist who is president of the Oregon Medical Research Center, Portland. “Patients came in rapidly, out of the woodwork – they were desperate.”
While there are several tried and tested treatments for the condition, such as topical steroids and antifungal agents, he noted that they have their limitations: “Sometimes efficacy, sometimes the ability to be used on hair-bearing areas.”
Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor that is available for topical use in a 0.3% cream formulation (Zoryve). This formulation gained FDA approval for plaque psoriasis for patients ages 12 and older this summer and is also under investigation as a treatment for atopic dermatitis.
It’s the same product in both preparations, Dr. Blauvelt said during the discussion period. “The only major difference between the cream and the foam is the propellant used to make it into a foam. Otherwise, they have the exact same list of ingredients.”
Dr. Blauvelt reported that just over 450 patients had been recruited at 53 U.S. centers into the 8-week, double-blind, placebo-controlled trial.
For inclusion, patients had to have moderate seborrheic dermatitis, defined as an Investigator’s Global Assessment (IGA) score of three or more. Dr. Blauvelt noted that patients as young as 9 years old could be recruited, and there was no upper age limit. The average age of participating patients, however, was around 42 years.
Multiple improvements seen in ‘happy trial’
The primary endpoint was an IGA score of 0 or 1 with at least a 2-grade improvement (IGA success) after 8 weeks of treatment. This was achieved by 80% of patients who were treated with roflumilast 0.3% foam, compared with 60% of those who were treated with the vehicle (P less than .0001).
Dr. Blauvelt pointed out that significant improvements had also been seen after 2 weeks (about 42% vs. about 26%; P = .0003) and 4 weeks (about 72% vs. about 49%; P less than .0001) of treatment.
“Now if we raise the bar a little higher” and ask how many patients were completely clear of their seborrheic dermatitis, Dr. Blauvelt said, it was 50% at 8 weeks, more than a third at 4 weeks, over 15% at 2 weeks with the foam, and significantly lower at just under 30%, 15%, and 7% in the vehicle group.
A 4-point or more improvement in the Worst Itch Numeric Rating Scale (WI-NRS) – accepted as the minimally clinically important difference – was achieved by more than 60% of patients treated with the foam at week 8, just under 50% at week 4, and just over 30% at week 2. Corresponding rates in the vehicle group were around 40%, 30%, and 15%.
“Many patients responded in this trial. So much so that when I was doing it, I called it the ‘happy trial.’ Every time I saw patients in this trial, they seemed to be happy,” Dr. Blauvelt said anecdotally.
“In terms of adverse events, the drug turned out to be very safe, and there didn’t seem to be any issues with any things that we see with, for example, oral phosphodiesterase inhibitors,” he added.
The tolerability findings suggest that the foam vehicle “was an excellent vehicle to be used for this particular drug,” with no signs of skin irritation, as rated by patients or investigators.
Lesson for practice: Advise patients to moisturize?
“It seems like the vehicle would be a good skincare product for patients,” observed the session’s cochair, Jo Lambert, MD, PhD, professor and academic head of the department of dermatology at Ghent University Hospital, Belgium.
It was “a pretty dramatic vehicle response, right?” Dr. Blauvelt responded. “We normally don’t think of telling seborrheic dermatitis patients to moisturize,” he added.
“I think one of the interesting findings is perhaps we should be telling them to moisturize their scalp or moisturize their face, or it could be something unique to this particular foam.”
The study was funded by Arcutis Biotherapeutics. Dr. Blauvelt disclosed that he was an investigator for the trial and acted as consultant to the company, receiving grants/research funding and/or honoraria. Several of the study’s co-investigators are employees of Arcutis. Dr. Lambert was not involved in the study and cochaired the late-breaking session during which the STRATUM trial findings were reported.
A version of this article first appeared on Medscape.com.
FROM THE EADV CONGRESS
Dupilumab offers ‘clinically meaningful’ improvements in prurigo nodularis
(Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.
The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.
More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.
The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.
Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”
In the discussion after the presentation, Dr. Yosipovitch was asked whether the presence or absence of atopy had any bearing on the results.
He replied that although there were too few patients with atopy in the current study to answer that question, other data indicate that there is no overall difference between patients with atopy and those without atopy.
Asked whether dupilumab should be used for only 24 weeks, Dr. Yosipovitch said his that “impression” is that there can be a “honeymoon period” during which the medication is stopped and the treating clinician sees “what happens.”
“It would be interesting in the future” to find out, he added, but he noted that whatever the result, patients would need treatment “for the rest of their life.”
Dr. Yosipovitch, director of the Miami Itch Center and the study’s principal investigator, began his presentation by noting that currently, no systemic therapies have been approved by the FDA or the European Medicines Agency for PN.
Although treatments such as topical medications, ultraviolet light therapy, immunosuppressive agents, and systemic neuromodulators are used off label, for many patients with moderate to severe PN, disease control is inadequate, and the patients are “miserable.”
Recently, the phase 3 LIBERTY-PN PRIME2 trial showed that dupilumab significantly reduced itch and skin lesions for patients with PN, and the safety profile was consistent with that seen in approved indications for the drug.
Dr. Yosipovitch explained that LIBERTY-PN PRIME was a phase 2 study in which, after a screening period, patients with PN were randomly assigned in a 1:1 ratio to receive dupilumab as a 600-mg loading dose followed by 300 mg twice weekly or a matched placebo. Treatment was given for 24 weeks, after which there was a post treatment 12-week follow-up period.
Participants were aged 18-80 years and had been diagnosed with PN for a period of at least 3 months. To be included in the trial, patients had to have an average Worst Itch Numerical Rating Scale (WI-NRS) score of at least 7 and at least 20 lesions, among other criteria. (Patients were allowed to continue treatment with mid- to low-potency topical steroids or topical calcineurin inhibitors if they had been taking them at baseline.)
Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.
The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.
Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.
He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).
Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).
With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.
Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.
Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.
The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.
A version of this article first appeared on Medscape.com.
(Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.
The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.
More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.
The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.
Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”
In the discussion after the presentation, Dr. Yosipovitch was asked whether the presence or absence of atopy had any bearing on the results.
He replied that although there were too few patients with atopy in the current study to answer that question, other data indicate that there is no overall difference between patients with atopy and those without atopy.
Asked whether dupilumab should be used for only 24 weeks, Dr. Yosipovitch said his that “impression” is that there can be a “honeymoon period” during which the medication is stopped and the treating clinician sees “what happens.”
“It would be interesting in the future” to find out, he added, but he noted that whatever the result, patients would need treatment “for the rest of their life.”
Dr. Yosipovitch, director of the Miami Itch Center and the study’s principal investigator, began his presentation by noting that currently, no systemic therapies have been approved by the FDA or the European Medicines Agency for PN.
Although treatments such as topical medications, ultraviolet light therapy, immunosuppressive agents, and systemic neuromodulators are used off label, for many patients with moderate to severe PN, disease control is inadequate, and the patients are “miserable.”
Recently, the phase 3 LIBERTY-PN PRIME2 trial showed that dupilumab significantly reduced itch and skin lesions for patients with PN, and the safety profile was consistent with that seen in approved indications for the drug.
Dr. Yosipovitch explained that LIBERTY-PN PRIME was a phase 2 study in which, after a screening period, patients with PN were randomly assigned in a 1:1 ratio to receive dupilumab as a 600-mg loading dose followed by 300 mg twice weekly or a matched placebo. Treatment was given for 24 weeks, after which there was a post treatment 12-week follow-up period.
Participants were aged 18-80 years and had been diagnosed with PN for a period of at least 3 months. To be included in the trial, patients had to have an average Worst Itch Numerical Rating Scale (WI-NRS) score of at least 7 and at least 20 lesions, among other criteria. (Patients were allowed to continue treatment with mid- to low-potency topical steroids or topical calcineurin inhibitors if they had been taking them at baseline.)
Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.
The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.
Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.
He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).
Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).
With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.
Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.
Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.
The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.
A version of this article first appeared on Medscape.com.
(Dupixent), indicate results from the phase 2 LIBERTY-PN PRIME trial.
The research was presented at the annual Congress of the European Academy of Dermatology and Venereology.
More than 150 patients with severe PN whose quality of life was impaired were randomly assigned to receive dupilumab (Dupixent) or placebo for 24 weeks. Use of the monoclonal antibody was associated with significant improvements in itch scores.
The researchers also found that the percentage of patients who had no or few PN lesions increased substantially with use of dupilumab, and there were no new safety signals, confirming results from previous studies. Dupilumab, an interleukin-4 receptor alpha antagonist administered by injection, was initially approved by the U.S. Food and Drug Administration for treating atopic dermatitis in 2022.
Study presenter Gil Yosipovitch, MD, professor of dermatology at the University of Miami, emphasized that the improvements in itch and skin lesions seen in these patients were “clinically meaningful.”
In the discussion after the presentation, Dr. Yosipovitch was asked whether the presence or absence of atopy had any bearing on the results.
He replied that although there were too few patients with atopy in the current study to answer that question, other data indicate that there is no overall difference between patients with atopy and those without atopy.
Asked whether dupilumab should be used for only 24 weeks, Dr. Yosipovitch said his that “impression” is that there can be a “honeymoon period” during which the medication is stopped and the treating clinician sees “what happens.”
“It would be interesting in the future” to find out, he added, but he noted that whatever the result, patients would need treatment “for the rest of their life.”
Dr. Yosipovitch, director of the Miami Itch Center and the study’s principal investigator, began his presentation by noting that currently, no systemic therapies have been approved by the FDA or the European Medicines Agency for PN.
Although treatments such as topical medications, ultraviolet light therapy, immunosuppressive agents, and systemic neuromodulators are used off label, for many patients with moderate to severe PN, disease control is inadequate, and the patients are “miserable.”
Recently, the phase 3 LIBERTY-PN PRIME2 trial showed that dupilumab significantly reduced itch and skin lesions for patients with PN, and the safety profile was consistent with that seen in approved indications for the drug.
Dr. Yosipovitch explained that LIBERTY-PN PRIME was a phase 2 study in which, after a screening period, patients with PN were randomly assigned in a 1:1 ratio to receive dupilumab as a 600-mg loading dose followed by 300 mg twice weekly or a matched placebo. Treatment was given for 24 weeks, after which there was a post treatment 12-week follow-up period.
Participants were aged 18-80 years and had been diagnosed with PN for a period of at least 3 months. To be included in the trial, patients had to have an average Worst Itch Numerical Rating Scale (WI-NRS) score of at least 7 and at least 20 lesions, among other criteria. (Patients were allowed to continue treatment with mid- to low-potency topical steroids or topical calcineurin inhibitors if they had been taking them at baseline.)
Among 151 patients in the study, the mean age was 50.1 years, and 66.2% were women. The majority (53.0%) were White; 7.3% were Black; and 35.8% were Asian; 40.4% of patients had a history of atopy. The mean WI-NRS was 8.5, and the mean skin pain score on a 10-point scale was 7.2.
The Investigator’s Global Assessment for PN stage of disease (IGA PN-S) was also employed in the trial. That measure uses a 5-point scale to assess disease severity, with 0 indicating no lesions and 4 indicating more than 100 lesions. At baseline, 28.7% of patients had a score of 4, and the remainder had a score of 3, indicating the presence of 20-100 PN lesions.
Dr. Yosipovitch said that quality of life for these patients was “low” and that scores on the Hospital Anxiety and Depression scale indicated that the participants, many of whom had previously received topical and systemic medications for their PN, indicated they were depressed.
He showed that at week 24, the proportion of patients who had experienced an improvement in the WI-NRS score of greater than or equal to 4 (the study’s primary endpoint) was significantly greater with dupilumab, at 60.0% versus 18.4% among patients given placebo (P < .0001).
Moreover, the proportion of patients at week 24 with an IGA PN-S score of 0 or 1 (the secondary endpoint) was 48.0% in the active treatment group, versus 18.4% with placebo (P =.0004).
With regard to safety, rates of any treatment-emergent adverse events were similar between the groups, at 70.7% for dupilumab and 62.7% for placebo, as were rates for severe treatment-emergent adverse events, at 6.7% and 10.7%, respectively.
Rates of treatment-emergent adverse events of interest, such as skin infections, conjunctivitis, herpes viral infections, and injection site reactions, also suggested that there was no increased risk with active treatment.
Dupilumab is currently under review at the FDA and in Europe for the treatment of PN, according to dupilumab manufacturers Regeneron and Sanofi.
The study was sponsored by Sanofi in collaboration with Regeneron Pharmaceuticals. Dr. Yosipovitch has relationships with Arcutis Biotherapeutics, Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics.
A version of this article first appeared on Medscape.com.
FROM THE EADV CONGRESS
Overall survival dips with vitamin D deficiency in melanoma
, according to research presented at the annual congress of the European Academy of Dermatology and Venereology.
Whereas the 5-year overall survival was 90% when vitamin D serum levels were above a 10 ng/mL threshold, it was 84% when levels fell below it. Notably, the gap in overall survival between those above and below the threshold appeared to widen as time went on.
The research adds to existing evidence that “vitamin D levels can play an important and independent role in patients’ survival outcomes,” study investigator Inés Gracia-Darder, MD, told this news organization. “The important application in clinical practice would be to know if vitamin D supplementation influences the survival of melanoma patients,” said Dr. Gracia-Darder, a clinical specialist in dermatology at the Hospital Universitari Son Espases, Mallorca, Spain.
Known association, but not much data
“It is not a new finding,” but there are limited data, especially in melanoma, said Julie De Smedt, MD, of KU Leuven, Belgium, who was asked to comment on the results. Other groups have shown, certainly for cancer in general, that vitamin D can have an effect on overall survival.
“Low levels of vitamin D are associated with the pathological parameters of the melanoma, such as the thickness of the tumor,” Dr. De Smedt said in an interview, indicating that it’s not just overall survival that might be affected.
“So we assume that also has an effect on melanoma-specific survival,” she added.
That assumption, however, is not supported by the data Dr. Gracia-Darder presented, as there was no difference in melanoma-specific survival among the two groups of patients that had been studied.
Retrospective cohort analysis
Vitamin D levels had been studied in 264 patients who were included in the retrospective cohort analysis. All had invasive melanomas, and all had been seen at the Hospital Clinic of Barcelona between January 1998 and June 2021. Their mean age was 57 years, and the median follow-up was 6.7 years.
For inclusion, all patients had to have had their vitamin D levels measured after being diagnosed with melanoma; those with a 25-hydroxyvitamin D3 serum level of less than 10 ng/mL were deemed to be vitamin D deficient, whereas those with levels of 10 ng/mL and above were deemed normal or insufficient.
A measurement less than 10 ng/mL is considered vitamin D deficiency, Dr. De Smedt said. “But there is a difference between countries, and there’s also a difference between societies,” noting the cut-off used in the lab where she works is 20 ng/mL. This makes it difficult to compare studies, she said.
Independent association with overall survival
Seasonal variation in vitamin D levels were considered as a possible confounding factor, but Dr. Gracia-Darder noted that there was a similar distribution of measurements taken between October to March and April to September.
Univariate and multivariate analyses established vitamin D deficiency as being independently associated with overall survival with hazard ratios of 2.34 and 2.45, respectively.
Other predictive factors were having a higher Breslow index, as well as older age and gender.
Time to recommend vitamin D supplementation?
So should patients with melanoma have their vitamin D levels routinely checked? And what about advising them to take vitamin D supplements?
“In our practice, we analyze the vitamin D levels of our patients,” Dr. Gracia-Darder said. Patients are told to limit their exposure to the sun because of their skin cancer, so they are very likely to become vitamin D deficient.
While dietary changes or supplements might be suggested, there’s no real evidence to support upping vitamin D levels to date, so “future prospective studies are needed,” Dr. Gracia-Darder added.
Such studies have already started, including one in Italy, one in Australia, and another study that Dr. De Smedt has been involved with for the past few years.
Called the ViDMe study, it’s a multicenter, randomized, double-blind trial in which patients are being given a high-dose oral vitamin D supplement or placebo once a month for at least 1 year. About 430 patients with a first cutaneous malignant melanoma have been included in the trial, which started in December 2012.
It is hoped that the results will show that the supplementation will have had a protective effect on the risk of relapse and that there will be a correlation between vitamin D levels in the blood and vitamin D receptor immunoreactivity in the tumor.
“The study is still blinded,” Dr. De Smedt said. “We will unblind in the coming months and then at the end of the year, maybe next year, we will have the results.”
The study reported by Dr. Gracia-Darder did not receive any specific funding. Dr. Gracia-Darder disclosed that the melanoma unit where the study was performed receives many grants and funds to carry out research. She reported no other relevant financial relationships. Dr. De Smedt had no relevant financial relationships. The ViDMe study is sponsored by the Universitaire Ziekenhuizen Leuven.
A version of this article first appeared on Medscape.com.
, according to research presented at the annual congress of the European Academy of Dermatology and Venereology.
Whereas the 5-year overall survival was 90% when vitamin D serum levels were above a 10 ng/mL threshold, it was 84% when levels fell below it. Notably, the gap in overall survival between those above and below the threshold appeared to widen as time went on.
The research adds to existing evidence that “vitamin D levels can play an important and independent role in patients’ survival outcomes,” study investigator Inés Gracia-Darder, MD, told this news organization. “The important application in clinical practice would be to know if vitamin D supplementation influences the survival of melanoma patients,” said Dr. Gracia-Darder, a clinical specialist in dermatology at the Hospital Universitari Son Espases, Mallorca, Spain.
Known association, but not much data
“It is not a new finding,” but there are limited data, especially in melanoma, said Julie De Smedt, MD, of KU Leuven, Belgium, who was asked to comment on the results. Other groups have shown, certainly for cancer in general, that vitamin D can have an effect on overall survival.
“Low levels of vitamin D are associated with the pathological parameters of the melanoma, such as the thickness of the tumor,” Dr. De Smedt said in an interview, indicating that it’s not just overall survival that might be affected.
“So we assume that also has an effect on melanoma-specific survival,” she added.
That assumption, however, is not supported by the data Dr. Gracia-Darder presented, as there was no difference in melanoma-specific survival among the two groups of patients that had been studied.
Retrospective cohort analysis
Vitamin D levels had been studied in 264 patients who were included in the retrospective cohort analysis. All had invasive melanomas, and all had been seen at the Hospital Clinic of Barcelona between January 1998 and June 2021. Their mean age was 57 years, and the median follow-up was 6.7 years.
For inclusion, all patients had to have had their vitamin D levels measured after being diagnosed with melanoma; those with a 25-hydroxyvitamin D3 serum level of less than 10 ng/mL were deemed to be vitamin D deficient, whereas those with levels of 10 ng/mL and above were deemed normal or insufficient.
A measurement less than 10 ng/mL is considered vitamin D deficiency, Dr. De Smedt said. “But there is a difference between countries, and there’s also a difference between societies,” noting the cut-off used in the lab where she works is 20 ng/mL. This makes it difficult to compare studies, she said.
Independent association with overall survival
Seasonal variation in vitamin D levels were considered as a possible confounding factor, but Dr. Gracia-Darder noted that there was a similar distribution of measurements taken between October to March and April to September.
Univariate and multivariate analyses established vitamin D deficiency as being independently associated with overall survival with hazard ratios of 2.34 and 2.45, respectively.
Other predictive factors were having a higher Breslow index, as well as older age and gender.
Time to recommend vitamin D supplementation?
So should patients with melanoma have their vitamin D levels routinely checked? And what about advising them to take vitamin D supplements?
“In our practice, we analyze the vitamin D levels of our patients,” Dr. Gracia-Darder said. Patients are told to limit their exposure to the sun because of their skin cancer, so they are very likely to become vitamin D deficient.
While dietary changes or supplements might be suggested, there’s no real evidence to support upping vitamin D levels to date, so “future prospective studies are needed,” Dr. Gracia-Darder added.
Such studies have already started, including one in Italy, one in Australia, and another study that Dr. De Smedt has been involved with for the past few years.
Called the ViDMe study, it’s a multicenter, randomized, double-blind trial in which patients are being given a high-dose oral vitamin D supplement or placebo once a month for at least 1 year. About 430 patients with a first cutaneous malignant melanoma have been included in the trial, which started in December 2012.
It is hoped that the results will show that the supplementation will have had a protective effect on the risk of relapse and that there will be a correlation between vitamin D levels in the blood and vitamin D receptor immunoreactivity in the tumor.
“The study is still blinded,” Dr. De Smedt said. “We will unblind in the coming months and then at the end of the year, maybe next year, we will have the results.”
The study reported by Dr. Gracia-Darder did not receive any specific funding. Dr. Gracia-Darder disclosed that the melanoma unit where the study was performed receives many grants and funds to carry out research. She reported no other relevant financial relationships. Dr. De Smedt had no relevant financial relationships. The ViDMe study is sponsored by the Universitaire Ziekenhuizen Leuven.
A version of this article first appeared on Medscape.com.
, according to research presented at the annual congress of the European Academy of Dermatology and Venereology.
Whereas the 5-year overall survival was 90% when vitamin D serum levels were above a 10 ng/mL threshold, it was 84% when levels fell below it. Notably, the gap in overall survival between those above and below the threshold appeared to widen as time went on.
The research adds to existing evidence that “vitamin D levels can play an important and independent role in patients’ survival outcomes,” study investigator Inés Gracia-Darder, MD, told this news organization. “The important application in clinical practice would be to know if vitamin D supplementation influences the survival of melanoma patients,” said Dr. Gracia-Darder, a clinical specialist in dermatology at the Hospital Universitari Son Espases, Mallorca, Spain.
Known association, but not much data
“It is not a new finding,” but there are limited data, especially in melanoma, said Julie De Smedt, MD, of KU Leuven, Belgium, who was asked to comment on the results. Other groups have shown, certainly for cancer in general, that vitamin D can have an effect on overall survival.
“Low levels of vitamin D are associated with the pathological parameters of the melanoma, such as the thickness of the tumor,” Dr. De Smedt said in an interview, indicating that it’s not just overall survival that might be affected.
“So we assume that also has an effect on melanoma-specific survival,” she added.
That assumption, however, is not supported by the data Dr. Gracia-Darder presented, as there was no difference in melanoma-specific survival among the two groups of patients that had been studied.
Retrospective cohort analysis
Vitamin D levels had been studied in 264 patients who were included in the retrospective cohort analysis. All had invasive melanomas, and all had been seen at the Hospital Clinic of Barcelona between January 1998 and June 2021. Their mean age was 57 years, and the median follow-up was 6.7 years.
For inclusion, all patients had to have had their vitamin D levels measured after being diagnosed with melanoma; those with a 25-hydroxyvitamin D3 serum level of less than 10 ng/mL were deemed to be vitamin D deficient, whereas those with levels of 10 ng/mL and above were deemed normal or insufficient.
A measurement less than 10 ng/mL is considered vitamin D deficiency, Dr. De Smedt said. “But there is a difference between countries, and there’s also a difference between societies,” noting the cut-off used in the lab where she works is 20 ng/mL. This makes it difficult to compare studies, she said.
Independent association with overall survival
Seasonal variation in vitamin D levels were considered as a possible confounding factor, but Dr. Gracia-Darder noted that there was a similar distribution of measurements taken between October to March and April to September.
Univariate and multivariate analyses established vitamin D deficiency as being independently associated with overall survival with hazard ratios of 2.34 and 2.45, respectively.
Other predictive factors were having a higher Breslow index, as well as older age and gender.
Time to recommend vitamin D supplementation?
So should patients with melanoma have their vitamin D levels routinely checked? And what about advising them to take vitamin D supplements?
“In our practice, we analyze the vitamin D levels of our patients,” Dr. Gracia-Darder said. Patients are told to limit their exposure to the sun because of their skin cancer, so they are very likely to become vitamin D deficient.
While dietary changes or supplements might be suggested, there’s no real evidence to support upping vitamin D levels to date, so “future prospective studies are needed,” Dr. Gracia-Darder added.
Such studies have already started, including one in Italy, one in Australia, and another study that Dr. De Smedt has been involved with for the past few years.
Called the ViDMe study, it’s a multicenter, randomized, double-blind trial in which patients are being given a high-dose oral vitamin D supplement or placebo once a month for at least 1 year. About 430 patients with a first cutaneous malignant melanoma have been included in the trial, which started in December 2012.
It is hoped that the results will show that the supplementation will have had a protective effect on the risk of relapse and that there will be a correlation between vitamin D levels in the blood and vitamin D receptor immunoreactivity in the tumor.
“The study is still blinded,” Dr. De Smedt said. “We will unblind in the coming months and then at the end of the year, maybe next year, we will have the results.”
The study reported by Dr. Gracia-Darder did not receive any specific funding. Dr. Gracia-Darder disclosed that the melanoma unit where the study was performed receives many grants and funds to carry out research. She reported no other relevant financial relationships. Dr. De Smedt had no relevant financial relationships. The ViDMe study is sponsored by the Universitaire Ziekenhuizen Leuven.
A version of this article first appeared on Medscape.com.
FROM THE EADV CONGRESS
Polypodium leucotomos found to reverse AK skin damage
MILAN – Application of topical or both treated over 12 months, in a randomized, blinded study presented at the annual congress of the European Academy of Dermatology and Venereology.
At 12 months, the percentage of patients with a normal or almost normal honeycomb pattern when evaluated blindly with reflectance confocal microscopy (RCM) was about twice as great in either of the two groups that received PLE relative to those treated with topical photoprotection alone, according to Giovanni Pellacani, MD, PhD, chair of dermatology, University of Sapienza, Rome.
“In patients with severe actinic keratosis, the 12-month use of a PLE-based topical or oral photoprotection is associated with positive clinical and anatomical outcomes,” Dr. Pellacani said.
PLE, which is already commonly used in sun protection products, is derived from a South American species of fern and has been proposed for a broad array of dermatologic diseases. According to Dr. Pellacani, in vivo studies associating PLE with immune photoprotection make this agent particularly promising for severe AKs.
In this study involving two clinical research centers in Italy, 131 patients with photoaging and at least three AKs were randomized to one of three treatment arms. The control arm received topical photoprotection with an SPF of 100 or higher applied twice daily to all sun-exposed areas. The two treatment arms received the same topical photoprotection plus either a PLE-containing topical cream alone or a PLE-containing topical cream plus PLE in an oral form (240 mg) once daily
Patients were evaluated at 3 months, 6 months, and 1 year with several measures, including the Actinic Keratosis Area Score Index (AKASI) and the AK Field Assessment Scale Area (AK-FAS). They were also assessed with RCM. All clinical assessments and RCM evaluations, which assessed seven different parameters, such as honeycomb pattern, mottled pigmentation, and reticulated collagen, were performed by dermatologists blinded to the treatment assignment.
Complete data were available for 116 patients who completed all three evaluations over the 12 months of follow-up. On RCM, 50% of those receiving the oral and topical forms of PLE and 45% of those receiving topical PLE had normalization of the honeycomb pattern. These responses were significantly greater (P = .04 for both) than the 26% with normalization in the control group.
Although there were no significant differences in any of the other parameters evaluated by RCM, the improvement in the honeycomb pattern was accompanied by a 7% improvement in the AKASI score in patients taking PLE, either topically or orally and topically, while there was a 6% worsening (P < .001) among controls.
The AK-FAS score improved at 12 months by 26% in the group on oral/topical PLE and by 4% in the group on topical PLE. The score worsened by 13% among controls.
Over the course of the study, patients were permitted to take an appropriate therapy, such as imiquimod, cryotherapy, or 5-flourouracil if there was worsening of the AK-FAS score or if new lesions appeared.
On this measure, 38% of controls and 11% of those randomized to topical PLE had progressive disease versus only 2% of those randomized to take both topical and oral PLE, Dr. Pellacani reported.
The lower rate of new lesions or a start of a new drug over the course of the study in the group receiving both the topical and the oral formulations of PLE relative to those receiving topical PLE alone did not reach statistical significance, but Dr. Pellacani concluded that the addition of PLE to topical photoprotection without PLE seemed to provide a potentially clinically meaningful advantage.
Larger studies and longer term studies are needed, according to Dr. Pellacani, who noted that the substantial body of clinical studies associating PLE with benefit in a variety of dermatologic disorders has been weakened by the absence of well-designed studies that are adequately powered to guide clinical use.
Salvador González, MD, PhD, a dermatology specialist at Alcalá University, Madrid, also believes that PLE deserves further evaluation not just for photoprotection but for reinvigorating damaged skin due to its antioxidant and anti-inflammatory properties. He was the senior author of a 2020 paper in Photochemical and Photobiological Sciences that summarized the potential benefits of PLE in preventing damage related to sun exposure.
Among its mechanism, PLE generates reactive oxygen species (ROS) and prevents depletion of Langerhans cells induced by ultraviolet (UV) light, Dr. González explained in an interview. “At the cellular level, PLE activates tumor suppression p53, inhibits UV-induced COX-2 expression, reduces inflammation, and preventions immunosuppression,” he continued. In addition, he said PLE also prevents UV-A-induced common deletions related to mitochondrial damage and MMP1 expression induced by various UV wavelengths.
“These molecular and cellular effects may translate into long-term inhibition of carcinogenesis including actinic keratosis,” he said, noting that all of these findings “justify the work by Pellacani and collaborators.”
Dr. Pellacani reports no potential conflicts of interest. Dr. González has a financial relationship with Cantabria Laboratories.
MILAN – Application of topical or both treated over 12 months, in a randomized, blinded study presented at the annual congress of the European Academy of Dermatology and Venereology.
At 12 months, the percentage of patients with a normal or almost normal honeycomb pattern when evaluated blindly with reflectance confocal microscopy (RCM) was about twice as great in either of the two groups that received PLE relative to those treated with topical photoprotection alone, according to Giovanni Pellacani, MD, PhD, chair of dermatology, University of Sapienza, Rome.
“In patients with severe actinic keratosis, the 12-month use of a PLE-based topical or oral photoprotection is associated with positive clinical and anatomical outcomes,” Dr. Pellacani said.
PLE, which is already commonly used in sun protection products, is derived from a South American species of fern and has been proposed for a broad array of dermatologic diseases. According to Dr. Pellacani, in vivo studies associating PLE with immune photoprotection make this agent particularly promising for severe AKs.
In this study involving two clinical research centers in Italy, 131 patients with photoaging and at least three AKs were randomized to one of three treatment arms. The control arm received topical photoprotection with an SPF of 100 or higher applied twice daily to all sun-exposed areas. The two treatment arms received the same topical photoprotection plus either a PLE-containing topical cream alone or a PLE-containing topical cream plus PLE in an oral form (240 mg) once daily
Patients were evaluated at 3 months, 6 months, and 1 year with several measures, including the Actinic Keratosis Area Score Index (AKASI) and the AK Field Assessment Scale Area (AK-FAS). They were also assessed with RCM. All clinical assessments and RCM evaluations, which assessed seven different parameters, such as honeycomb pattern, mottled pigmentation, and reticulated collagen, were performed by dermatologists blinded to the treatment assignment.
Complete data were available for 116 patients who completed all three evaluations over the 12 months of follow-up. On RCM, 50% of those receiving the oral and topical forms of PLE and 45% of those receiving topical PLE had normalization of the honeycomb pattern. These responses were significantly greater (P = .04 for both) than the 26% with normalization in the control group.
Although there were no significant differences in any of the other parameters evaluated by RCM, the improvement in the honeycomb pattern was accompanied by a 7% improvement in the AKASI score in patients taking PLE, either topically or orally and topically, while there was a 6% worsening (P < .001) among controls.
The AK-FAS score improved at 12 months by 26% in the group on oral/topical PLE and by 4% in the group on topical PLE. The score worsened by 13% among controls.
Over the course of the study, patients were permitted to take an appropriate therapy, such as imiquimod, cryotherapy, or 5-flourouracil if there was worsening of the AK-FAS score or if new lesions appeared.
On this measure, 38% of controls and 11% of those randomized to topical PLE had progressive disease versus only 2% of those randomized to take both topical and oral PLE, Dr. Pellacani reported.
The lower rate of new lesions or a start of a new drug over the course of the study in the group receiving both the topical and the oral formulations of PLE relative to those receiving topical PLE alone did not reach statistical significance, but Dr. Pellacani concluded that the addition of PLE to topical photoprotection without PLE seemed to provide a potentially clinically meaningful advantage.
Larger studies and longer term studies are needed, according to Dr. Pellacani, who noted that the substantial body of clinical studies associating PLE with benefit in a variety of dermatologic disorders has been weakened by the absence of well-designed studies that are adequately powered to guide clinical use.
Salvador González, MD, PhD, a dermatology specialist at Alcalá University, Madrid, also believes that PLE deserves further evaluation not just for photoprotection but for reinvigorating damaged skin due to its antioxidant and anti-inflammatory properties. He was the senior author of a 2020 paper in Photochemical and Photobiological Sciences that summarized the potential benefits of PLE in preventing damage related to sun exposure.
Among its mechanism, PLE generates reactive oxygen species (ROS) and prevents depletion of Langerhans cells induced by ultraviolet (UV) light, Dr. González explained in an interview. “At the cellular level, PLE activates tumor suppression p53, inhibits UV-induced COX-2 expression, reduces inflammation, and preventions immunosuppression,” he continued. In addition, he said PLE also prevents UV-A-induced common deletions related to mitochondrial damage and MMP1 expression induced by various UV wavelengths.
“These molecular and cellular effects may translate into long-term inhibition of carcinogenesis including actinic keratosis,” he said, noting that all of these findings “justify the work by Pellacani and collaborators.”
Dr. Pellacani reports no potential conflicts of interest. Dr. González has a financial relationship with Cantabria Laboratories.
MILAN – Application of topical or both treated over 12 months, in a randomized, blinded study presented at the annual congress of the European Academy of Dermatology and Venereology.
At 12 months, the percentage of patients with a normal or almost normal honeycomb pattern when evaluated blindly with reflectance confocal microscopy (RCM) was about twice as great in either of the two groups that received PLE relative to those treated with topical photoprotection alone, according to Giovanni Pellacani, MD, PhD, chair of dermatology, University of Sapienza, Rome.
“In patients with severe actinic keratosis, the 12-month use of a PLE-based topical or oral photoprotection is associated with positive clinical and anatomical outcomes,” Dr. Pellacani said.
PLE, which is already commonly used in sun protection products, is derived from a South American species of fern and has been proposed for a broad array of dermatologic diseases. According to Dr. Pellacani, in vivo studies associating PLE with immune photoprotection make this agent particularly promising for severe AKs.
In this study involving two clinical research centers in Italy, 131 patients with photoaging and at least three AKs were randomized to one of three treatment arms. The control arm received topical photoprotection with an SPF of 100 or higher applied twice daily to all sun-exposed areas. The two treatment arms received the same topical photoprotection plus either a PLE-containing topical cream alone or a PLE-containing topical cream plus PLE in an oral form (240 mg) once daily
Patients were evaluated at 3 months, 6 months, and 1 year with several measures, including the Actinic Keratosis Area Score Index (AKASI) and the AK Field Assessment Scale Area (AK-FAS). They were also assessed with RCM. All clinical assessments and RCM evaluations, which assessed seven different parameters, such as honeycomb pattern, mottled pigmentation, and reticulated collagen, were performed by dermatologists blinded to the treatment assignment.
Complete data were available for 116 patients who completed all three evaluations over the 12 months of follow-up. On RCM, 50% of those receiving the oral and topical forms of PLE and 45% of those receiving topical PLE had normalization of the honeycomb pattern. These responses were significantly greater (P = .04 for both) than the 26% with normalization in the control group.
Although there were no significant differences in any of the other parameters evaluated by RCM, the improvement in the honeycomb pattern was accompanied by a 7% improvement in the AKASI score in patients taking PLE, either topically or orally and topically, while there was a 6% worsening (P < .001) among controls.
The AK-FAS score improved at 12 months by 26% in the group on oral/topical PLE and by 4% in the group on topical PLE. The score worsened by 13% among controls.
Over the course of the study, patients were permitted to take an appropriate therapy, such as imiquimod, cryotherapy, or 5-flourouracil if there was worsening of the AK-FAS score or if new lesions appeared.
On this measure, 38% of controls and 11% of those randomized to topical PLE had progressive disease versus only 2% of those randomized to take both topical and oral PLE, Dr. Pellacani reported.
The lower rate of new lesions or a start of a new drug over the course of the study in the group receiving both the topical and the oral formulations of PLE relative to those receiving topical PLE alone did not reach statistical significance, but Dr. Pellacani concluded that the addition of PLE to topical photoprotection without PLE seemed to provide a potentially clinically meaningful advantage.
Larger studies and longer term studies are needed, according to Dr. Pellacani, who noted that the substantial body of clinical studies associating PLE with benefit in a variety of dermatologic disorders has been weakened by the absence of well-designed studies that are adequately powered to guide clinical use.
Salvador González, MD, PhD, a dermatology specialist at Alcalá University, Madrid, also believes that PLE deserves further evaluation not just for photoprotection but for reinvigorating damaged skin due to its antioxidant and anti-inflammatory properties. He was the senior author of a 2020 paper in Photochemical and Photobiological Sciences that summarized the potential benefits of PLE in preventing damage related to sun exposure.
Among its mechanism, PLE generates reactive oxygen species (ROS) and prevents depletion of Langerhans cells induced by ultraviolet (UV) light, Dr. González explained in an interview. “At the cellular level, PLE activates tumor suppression p53, inhibits UV-induced COX-2 expression, reduces inflammation, and preventions immunosuppression,” he continued. In addition, he said PLE also prevents UV-A-induced common deletions related to mitochondrial damage and MMP1 expression induced by various UV wavelengths.
“These molecular and cellular effects may translate into long-term inhibition of carcinogenesis including actinic keratosis,” he said, noting that all of these findings “justify the work by Pellacani and collaborators.”
Dr. Pellacani reports no potential conflicts of interest. Dr. González has a financial relationship with Cantabria Laboratories.
AT THE EADV CONGRESS