Dermatology

CARLSBAD, CALIF. – According to Delphine J. Lee, MD, PhD, some patients report that their dermatologists tell them there are no effective treatments for vitiligo.

However, this is not supported by the ongoing level of research on vitiligo, with more than 100 randomized controlled trials published over the last 5 years, Dr. Lee, chief of dermatology at Harbor-UCLA Medical Center, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. And, in 2022, ruxolitinib cream became the first FDA-approved treatment for vitiligo. “There’s a lot of research happening now, and I’m pleased to say that despite the fact that some of these medications are not all brand new and exciting, they’re still new in that we have new evidence for them,” she said. “Of the 100 randomized, controlled trials, UV therapy remains a strong part of our armamentarium.”
 

Stabilizing disease

Dr. Lee underscored the importance of stabilizing existing vitiligo and arresting progressive disease, which may be indicated by four key signs: koebnerization; trichrome lesions; inflammation, which can appear as erythema, scaling, and pruritus; and confetti-like macules that are typically 1 mm to 5 mm in size. Key principles of vitiligo treatment are to stop immune destruction and to stimulate melanocyte differentiation, migration, and melanin production, which is “probably why phototherapy is so important and helpful,” she said.

Managing patients’ expectations is also important, added Dr. Lee, who shows patients photos from published clinical trials “so they can see what excellent repigmentation really means.”
 

Dexamethasone vs. mycophenolate

In a randomized, controlled trial published in 2021, researchers compared dexamethasone oral mini-pulse (OMP), 2.5 mg, on two successive days a week, with oral mycophenolate mofetil, 500 mg b.i.d., up to 2 g every day, for 180 days as a stabilizing treatment for patients with progressive, nonsegmental vitiligo, with 90 days of treatment-free follow-up. Assessments included the vitiligo disease activity (VIDA) score, the number of new lesions in the past 30 days, and the Vitiligo Area Scoring Index (VASI). Arrest of disease progression was defined as the absence of any new lesions in the previous 30 days.

Over the treatment and follow-up period, both groups showed a significant trend for reduction in VIDA and in the number of new lesions in the previous 30 days, compared with baseline (P < .001). The difference between VASI at baseline and VASI at 180 and at 270 days was not significant in both groups.

Adverse side effects reported with dexamethasone included acne, weight gain, headache, insomnia, and menstrual irregularity. “The misconception is that because we only give patients a tiny dose of steroids – 2.5 mg two days per week – that they aren’t going to have any side effects,” Dr. Lee commented. “But in fact, they do.” The most common side effects with mycophenolate were nausea and diarrhea. Two patients on mycophenolate discontinued treatment: one for leukopenia and one for transaminitis, but both conditions resolved after treatment was stopped.

The researchers concluded that both dexamethasone OMP and mycophenolate mofetil halt actively spreading vitiligo. “Relapse occurred earlier with mycophenolate, and the relapse rate was higher than with dexamethasone OMP, but this was not statistically significant,” said Dr. Lee, who also leads an immunology research team at The Lundquist Institute at Harbor-UCLA Medical Center.

Other vitiligo treatment options she discussed included the following:

Betamethasone OMP and oral azathioprine. In a comparative study, researchers compared betamethasone OMP with oral azathioprine in arresting disease progression and inducing repigmentation in adults with vitiligo. Significantly more patients in the betamethasone OMP group achieved arrest of progression at 2 months than those in the azathioprine group, but at 6 months the difference was not significant. At 6 months, of the 19 patients who completed 6 months of betamethasone OMP, 2, 2, and 9 patients had more than 20%, 10%-20%, and 5%-10% repigmentation, respectively; and of the 18 patients who completed 6 months of azathioprine, 2 patients had 10%-20% repigmentation, with the remaining patients having no repigmentation or less than 5% repigmentation.

One patient in the azathioprine group developed acute pancreatitis but none developed transaminitis or leukopenia. “Azathioprine is another agent to add to our toolbox,” Dr. Lee said of the study findings. “Both betamethasone OMP and daily azathioprine are effective” in halting disease progression.

Low-dose cyclosporine. In a comparative study, 50 patients with active vitiligo were randomized into two groups: 25 to dexamethasone OMP 2.5 mg on two consecutive days/week for 4 months, and 25 to cyclosporine 3 mg/kg per day for 4 months, stopped treatment, and were then followed up for another 2 months. After 6 months, 84% of patients in the dexamethasone OMP group and 88% of patients in the cyclosporine group achieved arrest of disease progression (P = 1.00), but the mean time to achieve that endpoint was shorter for those in the cyclosporine group, compared with those in the dexamethasone OMP group (a mean of 3.92 weeks vs. 4.12 weeks, respectively; P = .01).

The list of adverse side effects for cyclosporine was “quite lengthy compared to the usual you would expect for dexamethasone,” said Dr. Lee, who was not involved with the study. “This is something we want to take seriously and discuss with our patients. Still, I would say that low-dose cyclosporine is another possibility to add to our toolbox.”

Phototherapy combined with polypodium leucotomos. Dr. Lee highlighted a randomized, controlled trial in which 21 patients with generalized vitiligo received narrow band (NB)-UVB phototherapy plus polypodium leucotomos extract (480 mg b.i.d.) and 21 patients received NB-UVB phototherapy plus placebo. After 6 months of treatment, patients in the NB-UVB plus oral polypodium leucotomos extract group had a better response rate, compared with those in the NB-UVB plus placebo group (47.8% vs. 22%). “We know from studies of polypodium leucotomos that it seems to have an impact on adaptive immunity as well as helps to decrease oxidative stress, so that may help with melanocyte stability in vitiligo,” said Dr. Lee, who was not affiliated with the study. “As with all treatments, the head and neck is very responsive to this combination treatment. The next most responsive area would be the trunk, followed by the extremities, and hands, and feet.”
 

Topical treatments

What about topical options for vitiligo? In a randomized, double-blind, comparative study, researchers evaluated the efficacy and safety of combination treatment with 308-nm excimer light and topical calcipotriol or topical clobetasol ointment for acral vitiligo. Combination treatment (excimer light and topical medication) was applied in the first 12 weeks, followed by topical medication alone for 12 weeks. Calcipotriol 0.005% ointment was applied on one hand vs. clobetasol propionate 0.05% ointment on the other for 24 weeks.

Of the hands treated with excimer light and calcipotriol, 7.7% achieved excellent repigmentation at the end of the combination treatment period and 23% achieved good to excellent improvement after 12 weeks of calcipotriol monotherapy. More than 85% and 77% of the hands treated with calcipotriol-based and clobetasol-based regimens showed some repigmentation at the end of the study, respectively (P < .05). However, no significant difference was found between the two treatments. “The evaluation from study participants was similar in that they felt that there was clearly a difference from baseline, but there was no difference across the two-hand therapy,” Dr. Lee said.

Adverse side effects included the development of blisters in some of patients who received clobetasol. “The take-home here is that you get excellent repigmentation with calcipotriol, though it’s a small percentage, 7.7%,” Dr. Lee said. “No excellent repigmentation was observed with excimer light and topical clobetasol. These data support two possible topical regimens that could be added to phototherapy or excimer light therapy to improve results.”

In another study of 42 patients, researchers compared twice-daily tacrolimus 0.1% ointment with vehicle for facial vitiligo through 24 weeks of intervention and 24 weeks of follow-up. The researchers defined treatment success as a change of 75% or greater in repigmentation of the target lesion between baseline and week 24, as measured by computer imaging software.

They found that 65% of tacrolimus-treated patients achieved therapeutic success, compared with none of the vehicle-treated patients at week 24 (P < .0001). “Tacrolimus is thought to be an old drug, but it does deserve to have continued proper study based on much anecdotal evidence I hear,” Dr. Lee said. “There was also efficacy over vehicle during the 24 weeks of follow-up. I find that tacrolimus works very well on the face. I’ve had very good results in children.”

Another topical option is the cream formulation of the JAK inhibitor ruxolitinib (Opzelura), approved in 2022 for the treatment of nonsegmental vitiligo in patients ages 12 and older, the first FDA-approved treatment for vitiligo. “As with the tacrolimus study, there are patients who achieve 100% repigmentation [with ruxolitinib], but others who may not,” Dr. Lee said. In addition, she noted that the combination of JAK inhibitors with phototherapy is emerging as another possible treatment choice, referring to a recently published systematic review suggesting that concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.

Dr. Lee reported having no relevant financial disclosures.

CARLSBAD, CALIF. – According to Delphine J. Lee, MD, PhD, some patients report that their dermatologists tell them there are no effective treatments for vitiligo.

However, this is not supported by the ongoing level of research on vitiligo, with more than 100 randomized controlled trials published over the last 5 years, Dr. Lee, chief of dermatology at Harbor-UCLA Medical Center, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. And, in 2022, ruxolitinib cream became the first FDA-approved treatment for vitiligo. “There’s a lot of research happening now, and I’m pleased to say that despite the fact that some of these medications are not all brand new and exciting, they’re still new in that we have new evidence for them,” she said. “Of the 100 randomized, controlled trials, UV therapy remains a strong part of our armamentarium.”
 

Stabilizing disease

Dr. Lee underscored the importance of stabilizing existing vitiligo and arresting progressive disease, which may be indicated by four key signs: koebnerization; trichrome lesions; inflammation, which can appear as erythema, scaling, and pruritus; and confetti-like macules that are typically 1 mm to 5 mm in size. Key principles of vitiligo treatment are to stop immune destruction and to stimulate melanocyte differentiation, migration, and melanin production, which is “probably why phototherapy is so important and helpful,” she said.

Managing patients’ expectations is also important, added Dr. Lee, who shows patients photos from published clinical trials “so they can see what excellent repigmentation really means.”
 

Dexamethasone vs. mycophenolate

In a randomized, controlled trial published in 2021, researchers compared dexamethasone oral mini-pulse (OMP), 2.5 mg, on two successive days a week, with oral mycophenolate mofetil, 500 mg b.i.d., up to 2 g every day, for 180 days as a stabilizing treatment for patients with progressive, nonsegmental vitiligo, with 90 days of treatment-free follow-up. Assessments included the vitiligo disease activity (VIDA) score, the number of new lesions in the past 30 days, and the Vitiligo Area Scoring Index (VASI). Arrest of disease progression was defined as the absence of any new lesions in the previous 30 days.

Over the treatment and follow-up period, both groups showed a significant trend for reduction in VIDA and in the number of new lesions in the previous 30 days, compared with baseline (P < .001). The difference between VASI at baseline and VASI at 180 and at 270 days was not significant in both groups.

Adverse side effects reported with dexamethasone included acne, weight gain, headache, insomnia, and menstrual irregularity. “The misconception is that because we only give patients a tiny dose of steroids – 2.5 mg two days per week – that they aren’t going to have any side effects,” Dr. Lee commented. “But in fact, they do.” The most common side effects with mycophenolate were nausea and diarrhea. Two patients on mycophenolate discontinued treatment: one for leukopenia and one for transaminitis, but both conditions resolved after treatment was stopped.

The researchers concluded that both dexamethasone OMP and mycophenolate mofetil halt actively spreading vitiligo. “Relapse occurred earlier with mycophenolate, and the relapse rate was higher than with dexamethasone OMP, but this was not statistically significant,” said Dr. Lee, who also leads an immunology research team at The Lundquist Institute at Harbor-UCLA Medical Center.

Other vitiligo treatment options she discussed included the following:

Betamethasone OMP and oral azathioprine. In a comparative study, researchers compared betamethasone OMP with oral azathioprine in arresting disease progression and inducing repigmentation in adults with vitiligo. Significantly more patients in the betamethasone OMP group achieved arrest of progression at 2 months than those in the azathioprine group, but at 6 months the difference was not significant. At 6 months, of the 19 patients who completed 6 months of betamethasone OMP, 2, 2, and 9 patients had more than 20%, 10%-20%, and 5%-10% repigmentation, respectively; and of the 18 patients who completed 6 months of azathioprine, 2 patients had 10%-20% repigmentation, with the remaining patients having no repigmentation or less than 5% repigmentation.

One patient in the azathioprine group developed acute pancreatitis but none developed transaminitis or leukopenia. “Azathioprine is another agent to add to our toolbox,” Dr. Lee said of the study findings. “Both betamethasone OMP and daily azathioprine are effective” in halting disease progression.

Low-dose cyclosporine. In a comparative study, 50 patients with active vitiligo were randomized into two groups: 25 to dexamethasone OMP 2.5 mg on two consecutive days/week for 4 months, and 25 to cyclosporine 3 mg/kg per day for 4 months, stopped treatment, and were then followed up for another 2 months. After 6 months, 84% of patients in the dexamethasone OMP group and 88% of patients in the cyclosporine group achieved arrest of disease progression (P = 1.00), but the mean time to achieve that endpoint was shorter for those in the cyclosporine group, compared with those in the dexamethasone OMP group (a mean of 3.92 weeks vs. 4.12 weeks, respectively; P = .01).

The list of adverse side effects for cyclosporine was “quite lengthy compared to the usual you would expect for dexamethasone,” said Dr. Lee, who was not involved with the study. “This is something we want to take seriously and discuss with our patients. Still, I would say that low-dose cyclosporine is another possibility to add to our toolbox.”

Phototherapy combined with polypodium leucotomos. Dr. Lee highlighted a randomized, controlled trial in which 21 patients with generalized vitiligo received narrow band (NB)-UVB phototherapy plus polypodium leucotomos extract (480 mg b.i.d.) and 21 patients received NB-UVB phototherapy plus placebo. After 6 months of treatment, patients in the NB-UVB plus oral polypodium leucotomos extract group had a better response rate, compared with those in the NB-UVB plus placebo group (47.8% vs. 22%). “We know from studies of polypodium leucotomos that it seems to have an impact on adaptive immunity as well as helps to decrease oxidative stress, so that may help with melanocyte stability in vitiligo,” said Dr. Lee, who was not affiliated with the study. “As with all treatments, the head and neck is very responsive to this combination treatment. The next most responsive area would be the trunk, followed by the extremities, and hands, and feet.”
 

Topical treatments

What about topical options for vitiligo? In a randomized, double-blind, comparative study, researchers evaluated the efficacy and safety of combination treatment with 308-nm excimer light and topical calcipotriol or topical clobetasol ointment for acral vitiligo. Combination treatment (excimer light and topical medication) was applied in the first 12 weeks, followed by topical medication alone for 12 weeks. Calcipotriol 0.005% ointment was applied on one hand vs. clobetasol propionate 0.05% ointment on the other for 24 weeks.

Of the hands treated with excimer light and calcipotriol, 7.7% achieved excellent repigmentation at the end of the combination treatment period and 23% achieved good to excellent improvement after 12 weeks of calcipotriol monotherapy. More than 85% and 77% of the hands treated with calcipotriol-based and clobetasol-based regimens showed some repigmentation at the end of the study, respectively (P < .05). However, no significant difference was found between the two treatments. “The evaluation from study participants was similar in that they felt that there was clearly a difference from baseline, but there was no difference across the two-hand therapy,” Dr. Lee said.

Adverse side effects included the development of blisters in some of patients who received clobetasol. “The take-home here is that you get excellent repigmentation with calcipotriol, though it’s a small percentage, 7.7%,” Dr. Lee said. “No excellent repigmentation was observed with excimer light and topical clobetasol. These data support two possible topical regimens that could be added to phototherapy or excimer light therapy to improve results.”

In another study of 42 patients, researchers compared twice-daily tacrolimus 0.1% ointment with vehicle for facial vitiligo through 24 weeks of intervention and 24 weeks of follow-up. The researchers defined treatment success as a change of 75% or greater in repigmentation of the target lesion between baseline and week 24, as measured by computer imaging software.

They found that 65% of tacrolimus-treated patients achieved therapeutic success, compared with none of the vehicle-treated patients at week 24 (P < .0001). “Tacrolimus is thought to be an old drug, but it does deserve to have continued proper study based on much anecdotal evidence I hear,” Dr. Lee said. “There was also efficacy over vehicle during the 24 weeks of follow-up. I find that tacrolimus works very well on the face. I’ve had very good results in children.”

Another topical option is the cream formulation of the JAK inhibitor ruxolitinib (Opzelura), approved in 2022 for the treatment of nonsegmental vitiligo in patients ages 12 and older, the first FDA-approved treatment for vitiligo. “As with the tacrolimus study, there are patients who achieve 100% repigmentation [with ruxolitinib], but others who may not,” Dr. Lee said. In addition, she noted that the combination of JAK inhibitors with phototherapy is emerging as another possible treatment choice, referring to a recently published systematic review suggesting that concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.

Dr. Lee reported having no relevant financial disclosures.

CARLSBAD, CALIF. – According to Delphine J. Lee, MD, PhD, some patients report that their dermatologists tell them there are no effective treatments for vitiligo.

However, this is not supported by the ongoing level of research on vitiligo, with more than 100 randomized controlled trials published over the last 5 years, Dr. Lee, chief of dermatology at Harbor-UCLA Medical Center, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery. And, in 2022, ruxolitinib cream became the first FDA-approved treatment for vitiligo. “There’s a lot of research happening now, and I’m pleased to say that despite the fact that some of these medications are not all brand new and exciting, they’re still new in that we have new evidence for them,” she said. “Of the 100 randomized, controlled trials, UV therapy remains a strong part of our armamentarium.”
 

Stabilizing disease

Dr. Lee underscored the importance of stabilizing existing vitiligo and arresting progressive disease, which may be indicated by four key signs: koebnerization; trichrome lesions; inflammation, which can appear as erythema, scaling, and pruritus; and confetti-like macules that are typically 1 mm to 5 mm in size. Key principles of vitiligo treatment are to stop immune destruction and to stimulate melanocyte differentiation, migration, and melanin production, which is “probably why phototherapy is so important and helpful,” she said.

Managing patients’ expectations is also important, added Dr. Lee, who shows patients photos from published clinical trials “so they can see what excellent repigmentation really means.”
 

Dexamethasone vs. mycophenolate

In a randomized, controlled trial published in 2021, researchers compared dexamethasone oral mini-pulse (OMP), 2.5 mg, on two successive days a week, with oral mycophenolate mofetil, 500 mg b.i.d., up to 2 g every day, for 180 days as a stabilizing treatment for patients with progressive, nonsegmental vitiligo, with 90 days of treatment-free follow-up. Assessments included the vitiligo disease activity (VIDA) score, the number of new lesions in the past 30 days, and the Vitiligo Area Scoring Index (VASI). Arrest of disease progression was defined as the absence of any new lesions in the previous 30 days.

Over the treatment and follow-up period, both groups showed a significant trend for reduction in VIDA and in the number of new lesions in the previous 30 days, compared with baseline (P < .001). The difference between VASI at baseline and VASI at 180 and at 270 days was not significant in both groups.

Adverse side effects reported with dexamethasone included acne, weight gain, headache, insomnia, and menstrual irregularity. “The misconception is that because we only give patients a tiny dose of steroids – 2.5 mg two days per week – that they aren’t going to have any side effects,” Dr. Lee commented. “But in fact, they do.” The most common side effects with mycophenolate were nausea and diarrhea. Two patients on mycophenolate discontinued treatment: one for leukopenia and one for transaminitis, but both conditions resolved after treatment was stopped.

The researchers concluded that both dexamethasone OMP and mycophenolate mofetil halt actively spreading vitiligo. “Relapse occurred earlier with mycophenolate, and the relapse rate was higher than with dexamethasone OMP, but this was not statistically significant,” said Dr. Lee, who also leads an immunology research team at The Lundquist Institute at Harbor-UCLA Medical Center.

Other vitiligo treatment options she discussed included the following:

Betamethasone OMP and oral azathioprine. In a comparative study, researchers compared betamethasone OMP with oral azathioprine in arresting disease progression and inducing repigmentation in adults with vitiligo. Significantly more patients in the betamethasone OMP group achieved arrest of progression at 2 months than those in the azathioprine group, but at 6 months the difference was not significant. At 6 months, of the 19 patients who completed 6 months of betamethasone OMP, 2, 2, and 9 patients had more than 20%, 10%-20%, and 5%-10% repigmentation, respectively; and of the 18 patients who completed 6 months of azathioprine, 2 patients had 10%-20% repigmentation, with the remaining patients having no repigmentation or less than 5% repigmentation.

One patient in the azathioprine group developed acute pancreatitis but none developed transaminitis or leukopenia. “Azathioprine is another agent to add to our toolbox,” Dr. Lee said of the study findings. “Both betamethasone OMP and daily azathioprine are effective” in halting disease progression.

Low-dose cyclosporine. In a comparative study, 50 patients with active vitiligo were randomized into two groups: 25 to dexamethasone OMP 2.5 mg on two consecutive days/week for 4 months, and 25 to cyclosporine 3 mg/kg per day for 4 months, stopped treatment, and were then followed up for another 2 months. After 6 months, 84% of patients in the dexamethasone OMP group and 88% of patients in the cyclosporine group achieved arrest of disease progression (P = 1.00), but the mean time to achieve that endpoint was shorter for those in the cyclosporine group, compared with those in the dexamethasone OMP group (a mean of 3.92 weeks vs. 4.12 weeks, respectively; P = .01).

The list of adverse side effects for cyclosporine was “quite lengthy compared to the usual you would expect for dexamethasone,” said Dr. Lee, who was not involved with the study. “This is something we want to take seriously and discuss with our patients. Still, I would say that low-dose cyclosporine is another possibility to add to our toolbox.”

Phototherapy combined with polypodium leucotomos. Dr. Lee highlighted a randomized, controlled trial in which 21 patients with generalized vitiligo received narrow band (NB)-UVB phototherapy plus polypodium leucotomos extract (480 mg b.i.d.) and 21 patients received NB-UVB phototherapy plus placebo. After 6 months of treatment, patients in the NB-UVB plus oral polypodium leucotomos extract group had a better response rate, compared with those in the NB-UVB plus placebo group (47.8% vs. 22%). “We know from studies of polypodium leucotomos that it seems to have an impact on adaptive immunity as well as helps to decrease oxidative stress, so that may help with melanocyte stability in vitiligo,” said Dr. Lee, who was not affiliated with the study. “As with all treatments, the head and neck is very responsive to this combination treatment. The next most responsive area would be the trunk, followed by the extremities, and hands, and feet.”
 

Topical treatments

What about topical options for vitiligo? In a randomized, double-blind, comparative study, researchers evaluated the efficacy and safety of combination treatment with 308-nm excimer light and topical calcipotriol or topical clobetasol ointment for acral vitiligo. Combination treatment (excimer light and topical medication) was applied in the first 12 weeks, followed by topical medication alone for 12 weeks. Calcipotriol 0.005% ointment was applied on one hand vs. clobetasol propionate 0.05% ointment on the other for 24 weeks.

Of the hands treated with excimer light and calcipotriol, 7.7% achieved excellent repigmentation at the end of the combination treatment period and 23% achieved good to excellent improvement after 12 weeks of calcipotriol monotherapy. More than 85% and 77% of the hands treated with calcipotriol-based and clobetasol-based regimens showed some repigmentation at the end of the study, respectively (P < .05). However, no significant difference was found between the two treatments. “The evaluation from study participants was similar in that they felt that there was clearly a difference from baseline, but there was no difference across the two-hand therapy,” Dr. Lee said.

Adverse side effects included the development of blisters in some of patients who received clobetasol. “The take-home here is that you get excellent repigmentation with calcipotriol, though it’s a small percentage, 7.7%,” Dr. Lee said. “No excellent repigmentation was observed with excimer light and topical clobetasol. These data support two possible topical regimens that could be added to phototherapy or excimer light therapy to improve results.”

In another study of 42 patients, researchers compared twice-daily tacrolimus 0.1% ointment with vehicle for facial vitiligo through 24 weeks of intervention and 24 weeks of follow-up. The researchers defined treatment success as a change of 75% or greater in repigmentation of the target lesion between baseline and week 24, as measured by computer imaging software.

They found that 65% of tacrolimus-treated patients achieved therapeutic success, compared with none of the vehicle-treated patients at week 24 (P < .0001). “Tacrolimus is thought to be an old drug, but it does deserve to have continued proper study based on much anecdotal evidence I hear,” Dr. Lee said. “There was also efficacy over vehicle during the 24 weeks of follow-up. I find that tacrolimus works very well on the face. I’ve had very good results in children.”

Another topical option is the cream formulation of the JAK inhibitor ruxolitinib (Opzelura), approved in 2022 for the treatment of nonsegmental vitiligo in patients ages 12 and older, the first FDA-approved treatment for vitiligo. “As with the tacrolimus study, there are patients who achieve 100% repigmentation [with ruxolitinib], but others who may not,” Dr. Lee said. In addition, she noted that the combination of JAK inhibitors with phototherapy is emerging as another possible treatment choice, referring to a recently published systematic review suggesting that concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.

Dr. Lee reported having no relevant financial disclosures.

WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.

“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.

A deep dive into the tissue

Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.

The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.

Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.

“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”

The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.

Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.

Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.

With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”

The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
 

Finding biomarkers, diagnostic signatures

The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”

A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.

Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.

Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.

At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)

Eyes on combination therapy

“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”

Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.

A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.

In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”

It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.

In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”

Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.

WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.

“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.

A deep dive into the tissue

Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.

The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.

Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.

“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”

The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.

Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.

Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.

With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”

The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
 

Finding biomarkers, diagnostic signatures

The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”

A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.

Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.

Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.

At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)

Eyes on combination therapy

“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”

Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.

A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.

In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”

It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.

In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”

Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.

WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.

“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.

A deep dive into the tissue

Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.

The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.

Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.

“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”

The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.

Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.

Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.

With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”

The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
 

Finding biomarkers, diagnostic signatures

The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”

A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.

Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.

Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.

At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)

Eyes on combination therapy

“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”

Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.

A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.

In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”

It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.

In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”

Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.

These tender nodules are classic for cystic acne and are common in women older than 20 years. Instead of outgrowing acne in their teenage years, some people (such as this patient) develop frequent tender cystic acne lesions that often heal with hyperpigmented scars.

Acne is the most prevalent chronic skin condition in the United States, affecting up to 50 million people.¹ Approximately 12% of adult women are affected.² The main contributing factors include increased sebum production, follicular hyperkeratinization, microbial follicular colonization with Propionibacterium acnes, and an inflammatory reaction.³

Treatment is available in both topical and oral forms. Topical antibiotics are used predominantly for treating mild-to-moderate inflammatory acne. They are not recommended as monotherapy due to the risk for bacterial resistance; this can be prevented by adding benzoyl peroxide, which exfoliates and acts as an antibacterial agent. Clindamycin 1% solution or gel is the preferred topical antibiotic for treatment of acne.⁴

Topical retinoids can be used as monotherapy or in combination with antibiotics. They also can be used for maintenance after treatment goals are reached and systemic antibiotics are discontinued. Retinoids generally are applied in the evening because the sun weakens their effect. Patients on retinoids also are more sensitive to the sun and should be counseled to use sunscreen daily. Counseling on pregnancy risks and appropriate use of contraception also should be offered to patients using retinoids. It is advisable to consider the use of combination oral contraceptives, particularly in women who have adult-onset acne or experience flare-ups around the time of their menstrual cycle.³

Azelaic acid has anticomedonal, antibacterial, and anti-inflammatory properties and may be effective in treating mild-to-moderate inflammatory acne and hyperpigmentation. Salicylic acid also has comedolytic properties, although there have been limited studies examining its effectiveness. Both azelaic and salicylic acid are considered safe for use in pregnancy.

Oral antibiotics are recommended in the treatment of moderate-to-severe acne. Both doxycycline and minocycline are more effective than tetracycline for treating acne, with no clear superiority between the two.⁴ Macrolides also can be effective in treating acne, although their use should be limited to those who cannot tolerate tetracyclines. Systemic antibiotic use should be limited to 3 to 4 months due to decreasing efficacy over time and to minimize the development of bacterial resistance. If treatment goals are attained, the antibiotics can be replaced with retinoids.

Oral isotretinoin is reserved for treatment of severe nodular acne or moderate acne that is treatment resistant. Patients should be counseled on contraceptive methods, as isotretinoin is highly teratogenic and therefore prescribed through the iPLEDGE program.^3,4

Given this patient’s persistent symptoms despite use of topical antibiotics and topical tretinoin, she decided to try oral antibiotics (doxycycline 100 mg twice daily) for 3 months and to start long-term oral contraceptives. If her symptoms continue, she will enroll in the iPLEDGE program and start treatment with oral isotretinoin.

‌

Photo courtesy of Ayo Sorunke, MD. Text courtesy of Ayo Sorunke, MD, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.

These tender nodules are classic for cystic acne and are common in women older than 20 years. Instead of outgrowing acne in their teenage years, some people (such as this patient) develop frequent tender cystic acne lesions that often heal with hyperpigmented scars.

Acne is the most prevalent chronic skin condition in the United States, affecting up to 50 million people.¹ Approximately 12% of adult women are affected.² The main contributing factors include increased sebum production, follicular hyperkeratinization, microbial follicular colonization with Propionibacterium acnes, and an inflammatory reaction.³

Treatment is available in both topical and oral forms. Topical antibiotics are used predominantly for treating mild-to-moderate inflammatory acne. They are not recommended as monotherapy due to the risk for bacterial resistance; this can be prevented by adding benzoyl peroxide, which exfoliates and acts as an antibacterial agent. Clindamycin 1% solution or gel is the preferred topical antibiotic for treatment of acne.⁴

Topical retinoids can be used as monotherapy or in combination with antibiotics. They also can be used for maintenance after treatment goals are reached and systemic antibiotics are discontinued. Retinoids generally are applied in the evening because the sun weakens their effect. Patients on retinoids also are more sensitive to the sun and should be counseled to use sunscreen daily. Counseling on pregnancy risks and appropriate use of contraception also should be offered to patients using retinoids. It is advisable to consider the use of combination oral contraceptives, particularly in women who have adult-onset acne or experience flare-ups around the time of their menstrual cycle.³

Azelaic acid has anticomedonal, antibacterial, and anti-inflammatory properties and may be effective in treating mild-to-moderate inflammatory acne and hyperpigmentation. Salicylic acid also has comedolytic properties, although there have been limited studies examining its effectiveness. Both azelaic and salicylic acid are considered safe for use in pregnancy.

Oral antibiotics are recommended in the treatment of moderate-to-severe acne. Both doxycycline and minocycline are more effective than tetracycline for treating acne, with no clear superiority between the two.⁴ Macrolides also can be effective in treating acne, although their use should be limited to those who cannot tolerate tetracyclines. Systemic antibiotic use should be limited to 3 to 4 months due to decreasing efficacy over time and to minimize the development of bacterial resistance. If treatment goals are attained, the antibiotics can be replaced with retinoids.

Oral isotretinoin is reserved for treatment of severe nodular acne or moderate acne that is treatment resistant. Patients should be counseled on contraceptive methods, as isotretinoin is highly teratogenic and therefore prescribed through the iPLEDGE program.^3,4

Given this patient’s persistent symptoms despite use of topical antibiotics and topical tretinoin, she decided to try oral antibiotics (doxycycline 100 mg twice daily) for 3 months and to start long-term oral contraceptives. If her symptoms continue, she will enroll in the iPLEDGE program and start treatment with oral isotretinoin.

‌

Photo courtesy of Ayo Sorunke, MD. Text courtesy of Ayo Sorunke, MD, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.

These tender nodules are classic for cystic acne and are common in women older than 20 years. Instead of outgrowing acne in their teenage years, some people (such as this patient) develop frequent tender cystic acne lesions that often heal with hyperpigmented scars.

Acne is the most prevalent chronic skin condition in the United States, affecting up to 50 million people.¹ Approximately 12% of adult women are affected.² The main contributing factors include increased sebum production, follicular hyperkeratinization, microbial follicular colonization with Propionibacterium acnes, and an inflammatory reaction.³

Treatment is available in both topical and oral forms. Topical antibiotics are used predominantly for treating mild-to-moderate inflammatory acne. They are not recommended as monotherapy due to the risk for bacterial resistance; this can be prevented by adding benzoyl peroxide, which exfoliates and acts as an antibacterial agent. Clindamycin 1% solution or gel is the preferred topical antibiotic for treatment of acne.⁴

Topical retinoids can be used as monotherapy or in combination with antibiotics. They also can be used for maintenance after treatment goals are reached and systemic antibiotics are discontinued. Retinoids generally are applied in the evening because the sun weakens their effect. Patients on retinoids also are more sensitive to the sun and should be counseled to use sunscreen daily. Counseling on pregnancy risks and appropriate use of contraception also should be offered to patients using retinoids. It is advisable to consider the use of combination oral contraceptives, particularly in women who have adult-onset acne or experience flare-ups around the time of their menstrual cycle.³

Azelaic acid has anticomedonal, antibacterial, and anti-inflammatory properties and may be effective in treating mild-to-moderate inflammatory acne and hyperpigmentation. Salicylic acid also has comedolytic properties, although there have been limited studies examining its effectiveness. Both azelaic and salicylic acid are considered safe for use in pregnancy.

Oral antibiotics are recommended in the treatment of moderate-to-severe acne. Both doxycycline and minocycline are more effective than tetracycline for treating acne, with no clear superiority between the two.⁴ Macrolides also can be effective in treating acne, although their use should be limited to those who cannot tolerate tetracyclines. Systemic antibiotic use should be limited to 3 to 4 months due to decreasing efficacy over time and to minimize the development of bacterial resistance. If treatment goals are attained, the antibiotics can be replaced with retinoids.

Oral isotretinoin is reserved for treatment of severe nodular acne or moderate acne that is treatment resistant. Patients should be counseled on contraceptive methods, as isotretinoin is highly teratogenic and therefore prescribed through the iPLEDGE program.^3,4

Given this patient’s persistent symptoms despite use of topical antibiotics and topical tretinoin, she decided to try oral antibiotics (doxycycline 100 mg twice daily) for 3 months and to start long-term oral contraceptives. If her symptoms continue, she will enroll in the iPLEDGE program and start treatment with oral isotretinoin.

‌

Photo courtesy of Ayo Sorunke, MD. Text courtesy of Ayo Sorunke, MD, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.

A teledermatology clinic pioneered by clinicians at George Washington University, Washington, to provide care for underserved populations will serve as a model for four other teledermatology clinics, according to a press release from the university.

Four institutions will receive grants to implement the George Washington University model, which involved partnering with a local organization to provide an entry point for individuals in areas with limited access to medical care, with support from Pfizer Global Medical Grants.

“Targeting those who lack access to quality-based care for inflammatory dermatologic conditions, including atopic dermatitis (AD) and others, the grants will reach communities in Miami-Dade County, Fla., Los Angeles County, Calif., rural communities in Oregon, and downtown Philadelphia,” according to the announcement. GW’s Teledermatology Free Clinic was conceived in the wake of the COVID-19 pandemic, which further highlighted disparities in access to dermatologic care, Adam Friedman, M.D., professor and chair of dermatology at George Washington University, said in the press release.

GW implemented its clinic for residents in underserved areas of Washington, D.C., in partnership with the Rodham Institute and the Temple of Praise Church. “We set up a free clinic at the church through which patients were integrated into the GW medical records system, provided instruction on telemedicine best practices, exposed to comprehensive education about AD and underwent a free telemedicine visit with a member of the department of dermatology,” Dr. Friedman explained.

Most participants – 70% – did not have a dermatologist, 94% were extremely satisfied with the experience, and 90% reported that the clinic had a significant impact on the management of their AD, according to the results of a recently published postengagement survey.

The following are the recipients of the “Quality Improvement Initiative: Bridging the Inflammatory Dermatosis Care Divide with Teledermatology Grant Program”:

• Scott Elman, MD, assistant professor of clinical dermatology and medical director of outpatient dermatology at the University of Miami and his team will create a clinic in partnership with Lotus House, a resource center and residential facility serving homeless women and infants, with focus on interventions in both English and Spanish.
• Nada Elbuluk, MD, associate professor of clinical dermatology and director of the Skin of Color and Pigmentary Disorders Program, at the University of Southern California, will lead a team to expand the role of two programs she created, Derm RISES, which targets inner city students, and Dermmunity, a community-based program that provides dermatology education to underserved communities in the Los Angeles area.
• Alex Ortega-Loayza, MD, associate professor of dermatology at Oregon Health & Science University and his team will partner with the Oregon Rural Practice-based Research Network to implement their teledermatology program at five clinics that serve different portions of rural and underserved communities across Oregon.
• Jules Lipoff, MD, clinical associate professor of dermatology, Temple University, Philadelphia, will lead a pilot program to establish a telemedicine dermatology clinic with Philadelphia FIGHT, a federally qualified health center in downtown Philadelphia where many patients lack high-speed Internet, and patients will be allowed direct access to telemedicine dermatology appointments within the primary care facility. The clinic’s patient population includes patients living with HIV, people who identify as LGBTQ+ and those who identify as trans or with a gender not matching their sex assigned at birth.

All four projects will complete postassessment surveys and quality assessment initiatives.

The GW clinic is ongoing, with plans for expansion and the establishment of additional programs with community partners in the Washington area, Dr. Friedman said in an interview.

“While these partnerships are in their infancy, I have high hopes that we will be able to impact even more individuals afflicted with dermatologic diseases and gain more insights into best practices for community engagement,” he added. “Many individuals who have come through our free clinic have followed up, by telehealth and/or in person at GW, depending on the clinical need to maintain continuity of care. In numerous cases, my impression is that this first point of contact is the key to ongoing treatment success, because it enables the access that may have been missing and engenders trust and confidence.”

A teledermatology clinic pioneered by clinicians at George Washington University, Washington, to provide care for underserved populations will serve as a model for four other teledermatology clinics, according to a press release from the university.

Four institutions will receive grants to implement the George Washington University model, which involved partnering with a local organization to provide an entry point for individuals in areas with limited access to medical care, with support from Pfizer Global Medical Grants.

“Targeting those who lack access to quality-based care for inflammatory dermatologic conditions, including atopic dermatitis (AD) and others, the grants will reach communities in Miami-Dade County, Fla., Los Angeles County, Calif., rural communities in Oregon, and downtown Philadelphia,” according to the announcement. GW’s Teledermatology Free Clinic was conceived in the wake of the COVID-19 pandemic, which further highlighted disparities in access to dermatologic care, Adam Friedman, M.D., professor and chair of dermatology at George Washington University, said in the press release.

GW implemented its clinic for residents in underserved areas of Washington, D.C., in partnership with the Rodham Institute and the Temple of Praise Church. “We set up a free clinic at the church through which patients were integrated into the GW medical records system, provided instruction on telemedicine best practices, exposed to comprehensive education about AD and underwent a free telemedicine visit with a member of the department of dermatology,” Dr. Friedman explained.

Most participants – 70% – did not have a dermatologist, 94% were extremely satisfied with the experience, and 90% reported that the clinic had a significant impact on the management of their AD, according to the results of a recently published postengagement survey.

The following are the recipients of the “Quality Improvement Initiative: Bridging the Inflammatory Dermatosis Care Divide with Teledermatology Grant Program”:

• Scott Elman, MD, assistant professor of clinical dermatology and medical director of outpatient dermatology at the University of Miami and his team will create a clinic in partnership with Lotus House, a resource center and residential facility serving homeless women and infants, with focus on interventions in both English and Spanish.
• Nada Elbuluk, MD, associate professor of clinical dermatology and director of the Skin of Color and Pigmentary Disorders Program, at the University of Southern California, will lead a team to expand the role of two programs she created, Derm RISES, which targets inner city students, and Dermmunity, a community-based program that provides dermatology education to underserved communities in the Los Angeles area.
• Alex Ortega-Loayza, MD, associate professor of dermatology at Oregon Health & Science University and his team will partner with the Oregon Rural Practice-based Research Network to implement their teledermatology program at five clinics that serve different portions of rural and underserved communities across Oregon.
• Jules Lipoff, MD, clinical associate professor of dermatology, Temple University, Philadelphia, will lead a pilot program to establish a telemedicine dermatology clinic with Philadelphia FIGHT, a federally qualified health center in downtown Philadelphia where many patients lack high-speed Internet, and patients will be allowed direct access to telemedicine dermatology appointments within the primary care facility. The clinic’s patient population includes patients living with HIV, people who identify as LGBTQ+ and those who identify as trans or with a gender not matching their sex assigned at birth.

All four projects will complete postassessment surveys and quality assessment initiatives.

The GW clinic is ongoing, with plans for expansion and the establishment of additional programs with community partners in the Washington area, Dr. Friedman said in an interview.

“While these partnerships are in their infancy, I have high hopes that we will be able to impact even more individuals afflicted with dermatologic diseases and gain more insights into best practices for community engagement,” he added. “Many individuals who have come through our free clinic have followed up, by telehealth and/or in person at GW, depending on the clinical need to maintain continuity of care. In numerous cases, my impression is that this first point of contact is the key to ongoing treatment success, because it enables the access that may have been missing and engenders trust and confidence.”

A teledermatology clinic pioneered by clinicians at George Washington University, Washington, to provide care for underserved populations will serve as a model for four other teledermatology clinics, according to a press release from the university.

Four institutions will receive grants to implement the George Washington University model, which involved partnering with a local organization to provide an entry point for individuals in areas with limited access to medical care, with support from Pfizer Global Medical Grants.

“Targeting those who lack access to quality-based care for inflammatory dermatologic conditions, including atopic dermatitis (AD) and others, the grants will reach communities in Miami-Dade County, Fla., Los Angeles County, Calif., rural communities in Oregon, and downtown Philadelphia,” according to the announcement. GW’s Teledermatology Free Clinic was conceived in the wake of the COVID-19 pandemic, which further highlighted disparities in access to dermatologic care, Adam Friedman, M.D., professor and chair of dermatology at George Washington University, said in the press release.

GW implemented its clinic for residents in underserved areas of Washington, D.C., in partnership with the Rodham Institute and the Temple of Praise Church. “We set up a free clinic at the church through which patients were integrated into the GW medical records system, provided instruction on telemedicine best practices, exposed to comprehensive education about AD and underwent a free telemedicine visit with a member of the department of dermatology,” Dr. Friedman explained.

Most participants – 70% – did not have a dermatologist, 94% were extremely satisfied with the experience, and 90% reported that the clinic had a significant impact on the management of their AD, according to the results of a recently published postengagement survey.

The following are the recipients of the “Quality Improvement Initiative: Bridging the Inflammatory Dermatosis Care Divide with Teledermatology Grant Program”:

• Scott Elman, MD, assistant professor of clinical dermatology and medical director of outpatient dermatology at the University of Miami and his team will create a clinic in partnership with Lotus House, a resource center and residential facility serving homeless women and infants, with focus on interventions in both English and Spanish.
• Nada Elbuluk, MD, associate professor of clinical dermatology and director of the Skin of Color and Pigmentary Disorders Program, at the University of Southern California, will lead a team to expand the role of two programs she created, Derm RISES, which targets inner city students, and Dermmunity, a community-based program that provides dermatology education to underserved communities in the Los Angeles area.
• Alex Ortega-Loayza, MD, associate professor of dermatology at Oregon Health & Science University and his team will partner with the Oregon Rural Practice-based Research Network to implement their teledermatology program at five clinics that serve different portions of rural and underserved communities across Oregon.
• Jules Lipoff, MD, clinical associate professor of dermatology, Temple University, Philadelphia, will lead a pilot program to establish a telemedicine dermatology clinic with Philadelphia FIGHT, a federally qualified health center in downtown Philadelphia where many patients lack high-speed Internet, and patients will be allowed direct access to telemedicine dermatology appointments within the primary care facility. The clinic’s patient population includes patients living with HIV, people who identify as LGBTQ+ and those who identify as trans or with a gender not matching their sex assigned at birth.

All four projects will complete postassessment surveys and quality assessment initiatives.

The GW clinic is ongoing, with plans for expansion and the establishment of additional programs with community partners in the Washington area, Dr. Friedman said in an interview.

“While these partnerships are in their infancy, I have high hopes that we will be able to impact even more individuals afflicted with dermatologic diseases and gain more insights into best practices for community engagement,” he added. “Many individuals who have come through our free clinic have followed up, by telehealth and/or in person at GW, depending on the clinical need to maintain continuity of care. In numerous cases, my impression is that this first point of contact is the key to ongoing treatment success, because it enables the access that may have been missing and engenders trust and confidence.”

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

Researchers have identified two genes that may contribute to Raynaud’s phenomenon, a condition where blood vessels in the extremities constrict and limit blood flow.

Raynaud’s is a relatively common condition, affecting 2%-5% of the general population. Though Raynaud’s can be an annoyance for some, it can also cause severe pain and can require medication.

Barb Elkin/iStock/Getty Images Plus

These newly identified genes will hopefully lead to new therapeutic options, said Maik Pietzner, PhD, chair in health data modeling at Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and group leader in the Computational Medicine Group at the Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Germany.

Berlin Institute of Health at Charité - Universitätsmedizin Berlin

Dr. Pietzner led the research along with Claudia Langenberg, MD, PhD, director of PHURI.

The study was published in Nature Communications.


 

Largest genomic study of Raynaud’s to date

The researchers looked through electronic medical records from the UK Biobank, a large-scale database that contains genetic and health information on half a million participants. They identified more than 5,100 individuals with Raynaud’s, of which 68% had primary Raynaud’s. These participants were compared with more than 439,000 controls who did not have Raynaud’s.

In a secondary analysis, the team also used health records from the Queen Mary University of London Genes & Health Study, which contains health information on individuals of South Asian ancestry.

The researchers identified two genes that are likely involved with Raynaud’s. The first, ADRA2A, encodes for the alpha-2A adrenergic receptor that can cause vasoconstriction of small blood vessels in response to stress hormones. Researchers have long suspected that this type of receptor could be involved with Raynaud’s, but there was debate over which receptor subtype was responsible.

“Our finding of alpha-2A receptors is quite interesting because the focus has always been on alpha-2C receptors,” said Dr. Pietzner. “It’s only a letter, but it’s a massive difference in terms of biology and physiology,” he said, and could be why therapies targeting 2C receptors have been ineffective.

The second strongest association was for the transcription factor IRX1. Less is known about this gene, but the data we do have suggest that it is involved with regulating the dilation of blood vessels, Dr. Pietzner noted.

“There might be balance between the ADRA2A finding being responsible for constriction and the IRX1 finding indirectly linked to the dilation of those vessels following constrictions. Having both may explain why these prolonged episodes of vasoconstriction lead to a loss of oxygen to the tissues,” so they turn white and then blue, he said.

Because the Biobank cohort was European-centric, Dr. Pietzner and colleagues also identified 400 cases of Raynaud’s in British individuals of Bangladeshi and Pakistani ancestry and were able to replicate the association between IRX1 and Raynaud’s. Data on ADRA2A were unavailable.

The genes identified are associated with primary Raynaud’s. Secondary Raynaud’s is a rarer type of the condition that occurs along with autoimmune disorders, such as scleroderma, and is generally more severe.

It’s long been suspected that Raynaud’s had some genetic component, because half of patients with Raynaud’s have another family member with the same condition, said Laura Hummers, MD, who codirects the John Hopkins Scleroderma Center in Baltimore. She was not involved with the study.

Johns Hopkins University

This is “the largest study of this kind that’s been done,” she said, and the first to show a potential mechanism behind this genetic association.

The main gene finding, ADRA2A, “points to a receptor on the cells that regulate the tone of these blood vessels,” she continued. “It suggests maybe there’s too many of these receptors or they’re overly sensitive; something about them is different that makes patients more susceptible to these cold triggers. Knowing that is potentially really important, because it could give you a direct way to intervene, if true.”
 

New therapeutic avenues

The first-line treatment for primary Raynaud’s is behavioral interventions, such as maintaining body and extremity warmth and avoiding certain vasoconstricting drugs, said Kimberly Lakin, MD, a rheumatologist at the Hospital for Special Surgery in New York, who not involved in the research. These drugs could include over-the-counter decongestants and certain medications for attention-deficit/hyperactivity disorder.

Hospital for Special Surgery

If these behavioral interventions are not enough, clinicians most commonly prescribe calcium channel blockers. These medications are vasodilators but can be a concern for people with normal or already low blood pressure, Dr. Lakin said. They can also cause symptoms such as headache, leg swelling, constipation, and other gastrointestinal symptoms.

Other medications, such as fluoxetine, may also be considered as a later-line therapy, “but the effectiveness is fairly limited in Raynaud’s,” she said. “Certainly, other medication options that would be helpful and driven by the mechanisms of Raynaud’s would add to our ability to help patients.”

As it turns out, one of the genes identified in the study, ADRA2A, “is actually one of the most commonly targeted genes by drugs,” said Dr. Pietzner. Because the findings suggest that ADRA2A is overexpressed in Raynaud, a selective inhibitor like the antidepressant mirtazapine could be a promising candidate to repurpose for treating Raynaud’s, he said.
 

Limitations to electronic medical record analyses

Both Dr. Hummers and Dr. Lakin noted that research using diagnostic codes from medical records to identify cases has some limitations. The study may have included patients misdiagnosed with Raynaud’s when perhaps they had another condition. Patients with milder Raynaud’s who have not sought medical attention for the condition would not be represented in the study, Dr. Lakin said.

The UK Biobank includes individuals of mostly European descent, so an analysis confirming these findings in a more diverse population would be helpful, she said.

However, both Dr. Lakin and Dr. Hummers agreed that the study contributes to the understanding of the mechanisms behind Raynaud’s. Although the two identified genes were tied to primary Raynaud’s, the study’s findings could potentially apply to secondary Raynaud’s as well, Dr. Hummers said.

“Anything we learn about primary Raynaud’s may have implication for Raynaud’s more broadly,” she noted.

Dr. Hummers and Dr. Lakin disclosed no relevant financial relationships. Dr. Pietzner has received partnership funding for the MRC Clinical Pharmacology Training Scheme (cofunded by MRC and Roche, UCB, Eli Lilly, and Novartis) and a PhD studentship jointly funded by the UK Engineering and Physical Sciences Research Council and AstraZeneca. Dr. Pietzner also has unrestricted educational grant support for the UK Pharmacogenetics and Stratified Medicine Network from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

Researchers have identified two genes that may contribute to Raynaud’s phenomenon, a condition where blood vessels in the extremities constrict and limit blood flow.

Raynaud’s is a relatively common condition, affecting 2%-5% of the general population. Though Raynaud’s can be an annoyance for some, it can also cause severe pain and can require medication.

Barb Elkin/iStock/Getty Images Plus

These newly identified genes will hopefully lead to new therapeutic options, said Maik Pietzner, PhD, chair in health data modeling at Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and group leader in the Computational Medicine Group at the Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Germany.

Berlin Institute of Health at Charité - Universitätsmedizin Berlin

Dr. Pietzner led the research along with Claudia Langenberg, MD, PhD, director of PHURI.

The study was published in Nature Communications.


 

Largest genomic study of Raynaud’s to date

The researchers looked through electronic medical records from the UK Biobank, a large-scale database that contains genetic and health information on half a million participants. They identified more than 5,100 individuals with Raynaud’s, of which 68% had primary Raynaud’s. These participants were compared with more than 439,000 controls who did not have Raynaud’s.

In a secondary analysis, the team also used health records from the Queen Mary University of London Genes & Health Study, which contains health information on individuals of South Asian ancestry.

The researchers identified two genes that are likely involved with Raynaud’s. The first, ADRA2A, encodes for the alpha-2A adrenergic receptor that can cause vasoconstriction of small blood vessels in response to stress hormones. Researchers have long suspected that this type of receptor could be involved with Raynaud’s, but there was debate over which receptor subtype was responsible.

“Our finding of alpha-2A receptors is quite interesting because the focus has always been on alpha-2C receptors,” said Dr. Pietzner. “It’s only a letter, but it’s a massive difference in terms of biology and physiology,” he said, and could be why therapies targeting 2C receptors have been ineffective.

The second strongest association was for the transcription factor IRX1. Less is known about this gene, but the data we do have suggest that it is involved with regulating the dilation of blood vessels, Dr. Pietzner noted.

“There might be balance between the ADRA2A finding being responsible for constriction and the IRX1 finding indirectly linked to the dilation of those vessels following constrictions. Having both may explain why these prolonged episodes of vasoconstriction lead to a loss of oxygen to the tissues,” so they turn white and then blue, he said.

Because the Biobank cohort was European-centric, Dr. Pietzner and colleagues also identified 400 cases of Raynaud’s in British individuals of Bangladeshi and Pakistani ancestry and were able to replicate the association between IRX1 and Raynaud’s. Data on ADRA2A were unavailable.

The genes identified are associated with primary Raynaud’s. Secondary Raynaud’s is a rarer type of the condition that occurs along with autoimmune disorders, such as scleroderma, and is generally more severe.

It’s long been suspected that Raynaud’s had some genetic component, because half of patients with Raynaud’s have another family member with the same condition, said Laura Hummers, MD, who codirects the John Hopkins Scleroderma Center in Baltimore. She was not involved with the study.

Johns Hopkins University

This is “the largest study of this kind that’s been done,” she said, and the first to show a potential mechanism behind this genetic association.

The main gene finding, ADRA2A, “points to a receptor on the cells that regulate the tone of these blood vessels,” she continued. “It suggests maybe there’s too many of these receptors or they’re overly sensitive; something about them is different that makes patients more susceptible to these cold triggers. Knowing that is potentially really important, because it could give you a direct way to intervene, if true.”
 

New therapeutic avenues

The first-line treatment for primary Raynaud’s is behavioral interventions, such as maintaining body and extremity warmth and avoiding certain vasoconstricting drugs, said Kimberly Lakin, MD, a rheumatologist at the Hospital for Special Surgery in New York, who not involved in the research. These drugs could include over-the-counter decongestants and certain medications for attention-deficit/hyperactivity disorder.

Hospital for Special Surgery

If these behavioral interventions are not enough, clinicians most commonly prescribe calcium channel blockers. These medications are vasodilators but can be a concern for people with normal or already low blood pressure, Dr. Lakin said. They can also cause symptoms such as headache, leg swelling, constipation, and other gastrointestinal symptoms.

Other medications, such as fluoxetine, may also be considered as a later-line therapy, “but the effectiveness is fairly limited in Raynaud’s,” she said. “Certainly, other medication options that would be helpful and driven by the mechanisms of Raynaud’s would add to our ability to help patients.”

As it turns out, one of the genes identified in the study, ADRA2A, “is actually one of the most commonly targeted genes by drugs,” said Dr. Pietzner. Because the findings suggest that ADRA2A is overexpressed in Raynaud, a selective inhibitor like the antidepressant mirtazapine could be a promising candidate to repurpose for treating Raynaud’s, he said.
 

Limitations to electronic medical record analyses

Both Dr. Hummers and Dr. Lakin noted that research using diagnostic codes from medical records to identify cases has some limitations. The study may have included patients misdiagnosed with Raynaud’s when perhaps they had another condition. Patients with milder Raynaud’s who have not sought medical attention for the condition would not be represented in the study, Dr. Lakin said.

The UK Biobank includes individuals of mostly European descent, so an analysis confirming these findings in a more diverse population would be helpful, she said.

However, both Dr. Lakin and Dr. Hummers agreed that the study contributes to the understanding of the mechanisms behind Raynaud’s. Although the two identified genes were tied to primary Raynaud’s, the study’s findings could potentially apply to secondary Raynaud’s as well, Dr. Hummers said.

“Anything we learn about primary Raynaud’s may have implication for Raynaud’s more broadly,” she noted.

Dr. Hummers and Dr. Lakin disclosed no relevant financial relationships. Dr. Pietzner has received partnership funding for the MRC Clinical Pharmacology Training Scheme (cofunded by MRC and Roche, UCB, Eli Lilly, and Novartis) and a PhD studentship jointly funded by the UK Engineering and Physical Sciences Research Council and AstraZeneca. Dr. Pietzner also has unrestricted educational grant support for the UK Pharmacogenetics and Stratified Medicine Network from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

Researchers have identified two genes that may contribute to Raynaud’s phenomenon, a condition where blood vessels in the extremities constrict and limit blood flow.

Raynaud’s is a relatively common condition, affecting 2%-5% of the general population. Though Raynaud’s can be an annoyance for some, it can also cause severe pain and can require medication.

Barb Elkin/iStock/Getty Images Plus

These newly identified genes will hopefully lead to new therapeutic options, said Maik Pietzner, PhD, chair in health data modeling at Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and group leader in the Computational Medicine Group at the Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Germany.

Berlin Institute of Health at Charité - Universitätsmedizin Berlin

Dr. Pietzner led the research along with Claudia Langenberg, MD, PhD, director of PHURI.

The study was published in Nature Communications.


 

Largest genomic study of Raynaud’s to date

The researchers looked through electronic medical records from the UK Biobank, a large-scale database that contains genetic and health information on half a million participants. They identified more than 5,100 individuals with Raynaud’s, of which 68% had primary Raynaud’s. These participants were compared with more than 439,000 controls who did not have Raynaud’s.

In a secondary analysis, the team also used health records from the Queen Mary University of London Genes & Health Study, which contains health information on individuals of South Asian ancestry.

The researchers identified two genes that are likely involved with Raynaud’s. The first, ADRA2A, encodes for the alpha-2A adrenergic receptor that can cause vasoconstriction of small blood vessels in response to stress hormones. Researchers have long suspected that this type of receptor could be involved with Raynaud’s, but there was debate over which receptor subtype was responsible.

“Our finding of alpha-2A receptors is quite interesting because the focus has always been on alpha-2C receptors,” said Dr. Pietzner. “It’s only a letter, but it’s a massive difference in terms of biology and physiology,” he said, and could be why therapies targeting 2C receptors have been ineffective.

The second strongest association was for the transcription factor IRX1. Less is known about this gene, but the data we do have suggest that it is involved with regulating the dilation of blood vessels, Dr. Pietzner noted.

“There might be balance between the ADRA2A finding being responsible for constriction and the IRX1 finding indirectly linked to the dilation of those vessels following constrictions. Having both may explain why these prolonged episodes of vasoconstriction lead to a loss of oxygen to the tissues,” so they turn white and then blue, he said.

Because the Biobank cohort was European-centric, Dr. Pietzner and colleagues also identified 400 cases of Raynaud’s in British individuals of Bangladeshi and Pakistani ancestry and were able to replicate the association between IRX1 and Raynaud’s. Data on ADRA2A were unavailable.

The genes identified are associated with primary Raynaud’s. Secondary Raynaud’s is a rarer type of the condition that occurs along with autoimmune disorders, such as scleroderma, and is generally more severe.

It’s long been suspected that Raynaud’s had some genetic component, because half of patients with Raynaud’s have another family member with the same condition, said Laura Hummers, MD, who codirects the John Hopkins Scleroderma Center in Baltimore. She was not involved with the study.

Johns Hopkins University

This is “the largest study of this kind that’s been done,” she said, and the first to show a potential mechanism behind this genetic association.

The main gene finding, ADRA2A, “points to a receptor on the cells that regulate the tone of these blood vessels,” she continued. “It suggests maybe there’s too many of these receptors or they’re overly sensitive; something about them is different that makes patients more susceptible to these cold triggers. Knowing that is potentially really important, because it could give you a direct way to intervene, if true.”
 

New therapeutic avenues

The first-line treatment for primary Raynaud’s is behavioral interventions, such as maintaining body and extremity warmth and avoiding certain vasoconstricting drugs, said Kimberly Lakin, MD, a rheumatologist at the Hospital for Special Surgery in New York, who not involved in the research. These drugs could include over-the-counter decongestants and certain medications for attention-deficit/hyperactivity disorder.

Hospital for Special Surgery

If these behavioral interventions are not enough, clinicians most commonly prescribe calcium channel blockers. These medications are vasodilators but can be a concern for people with normal or already low blood pressure, Dr. Lakin said. They can also cause symptoms such as headache, leg swelling, constipation, and other gastrointestinal symptoms.

Other medications, such as fluoxetine, may also be considered as a later-line therapy, “but the effectiveness is fairly limited in Raynaud’s,” she said. “Certainly, other medication options that would be helpful and driven by the mechanisms of Raynaud’s would add to our ability to help patients.”

As it turns out, one of the genes identified in the study, ADRA2A, “is actually one of the most commonly targeted genes by drugs,” said Dr. Pietzner. Because the findings suggest that ADRA2A is overexpressed in Raynaud, a selective inhibitor like the antidepressant mirtazapine could be a promising candidate to repurpose for treating Raynaud’s, he said.
 

Limitations to electronic medical record analyses

Both Dr. Hummers and Dr. Lakin noted that research using diagnostic codes from medical records to identify cases has some limitations. The study may have included patients misdiagnosed with Raynaud’s when perhaps they had another condition. Patients with milder Raynaud’s who have not sought medical attention for the condition would not be represented in the study, Dr. Lakin said.

The UK Biobank includes individuals of mostly European descent, so an analysis confirming these findings in a more diverse population would be helpful, she said.

However, both Dr. Lakin and Dr. Hummers agreed that the study contributes to the understanding of the mechanisms behind Raynaud’s. Although the two identified genes were tied to primary Raynaud’s, the study’s findings could potentially apply to secondary Raynaud’s as well, Dr. Hummers said.

“Anything we learn about primary Raynaud’s may have implication for Raynaud’s more broadly,” she noted.

Dr. Hummers and Dr. Lakin disclosed no relevant financial relationships. Dr. Pietzner has received partnership funding for the MRC Clinical Pharmacology Training Scheme (cofunded by MRC and Roche, UCB, Eli Lilly, and Novartis) and a PhD studentship jointly funded by the UK Engineering and Physical Sciences Research Council and AstraZeneca. Dr. Pietzner also has unrestricted educational grant support for the UK Pharmacogenetics and Stratified Medicine Network from Bristol-Myers Squibb.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx) for the treatment of moderate to severe plaque psoriasis in adults, the manufacturer announced in a press release.

The indication is for adults who are candidates for systemic therapy or phototherapy.

With this approval, bimekizumab becomes the only interleukin (IL)-17A and IL-17F inhibitor approved for the treatment of these patients. Psoriasis affects more than 7.5 million U.S. adults, according to the National Psoriasis Foundation.

“We have been eagerly awaiting bimekizumab,” Mark Lebwohl, MD, bimekizumab investigator and dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, New York City, said in the press release.

Dr. Lebwohl states that bimekizumab “achieved superior levels of skin clearance at week 16 compared to placebo and three existing biologics for psoriasis, with responses being rapid and lasting up to a year. Long-term data have also shown that the majority of patients maintained high levels of clinical response through three years.”

The most common adverse reactions (occurring in at least 1% of patients) are upper respiratory infections, oral candidiasis, headache, tinea infections, gastroenteritis, herpes simplex infections, acne, folliculitis, other Candida infections, fatigue, and injection site reactions, according to the company, UCB.
 

Available in about 1 month in U.S.

Bimekizumab can be administered by a health care provider or it can be self-injected by a patient after training. It is available as a single-dose prefilled autoinjector and a single-dose prefilled syringe and will be available in the United States in about 1 month.

The recommended dosage of bimekizumab for patients with psoriasis is 320 mg (two subcutaneous injections of 160 mg each) at baseline, then on weeks 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing at least 120 kg (about 265 lb), a dosage of 320 mg every 4 weeks after week 16 may be considered, the company states.

Three phase 3 trials

Approval was based on three phase 3 multicenter, randomized, placebo and/or active comparator-controlled trials: bimekizumab versus placebo and ustekinumab (BE VIVID); versus placebo (BE READY); and versus adalimumab (BE SURE).

“All studies met their co-primary endpoints and all ranked secondary endpoints,” the company reports. Secondary endpoints included the Psoriasis Area and Severity Index (PASI) 75 at week 4 and PASI 100 (complete skin clearance) at week 16.

Highlights from the trials include the following results, according to UCB:

• Clear or almost clear skin: More than 8 out of 10 patients achieved a 90% or greater reduction from baseline in the PASI 90 and an Investigator’s Global Assessment score of 0/1 at week 16.
• Complete skin clearance: About 60% of patients achieved PASI 100 at week 16.
• Time to response: More than 70% of patients achieved PASI 75 at week 4 following one 320-mg dose.

Safety information

The safety information includes the statement that bimekizumab may increase the risk for suicidal ideation and behavior, though a causal association has not been established. Prescribers should advise patients, caregivers, and families “to monitor for emergence or worsening of depression, suicidal ideation, or other mood changes,” according to the prescribing information.

Bimekizumab is being studied for other conditions, including hidradenitis suppurativa. In the European Union, it was approved for the treatment of psoriasis in 2021 and for the treatment of psoriatic arthritis and ankylosing spondylitis in June 2023.

Dr. Lebwohl is an investigator for UCB. He has not accepted any consulting payments from UCB.

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

The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx) for the treatment of moderate to severe plaque psoriasis in adults, the manufacturer announced in a press release.

The indication is for adults who are candidates for systemic therapy or phototherapy.

With this approval, bimekizumab becomes the only interleukin (IL)-17A and IL-17F inhibitor approved for the treatment of these patients. Psoriasis affects more than 7.5 million U.S. adults, according to the National Psoriasis Foundation.

“We have been eagerly awaiting bimekizumab,” Mark Lebwohl, MD, bimekizumab investigator and dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, New York City, said in the press release.

Dr. Lebwohl states that bimekizumab “achieved superior levels of skin clearance at week 16 compared to placebo and three existing biologics for psoriasis, with responses being rapid and lasting up to a year. Long-term data have also shown that the majority of patients maintained high levels of clinical response through three years.”

The most common adverse reactions (occurring in at least 1% of patients) are upper respiratory infections, oral candidiasis, headache, tinea infections, gastroenteritis, herpes simplex infections, acne, folliculitis, other Candida infections, fatigue, and injection site reactions, according to the company, UCB.
 

Available in about 1 month in U.S.

Bimekizumab can be administered by a health care provider or it can be self-injected by a patient after training. It is available as a single-dose prefilled autoinjector and a single-dose prefilled syringe and will be available in the United States in about 1 month.

The recommended dosage of bimekizumab for patients with psoriasis is 320 mg (two subcutaneous injections of 160 mg each) at baseline, then on weeks 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing at least 120 kg (about 265 lb), a dosage of 320 mg every 4 weeks after week 16 may be considered, the company states.

Three phase 3 trials

Approval was based on three phase 3 multicenter, randomized, placebo and/or active comparator-controlled trials: bimekizumab versus placebo and ustekinumab (BE VIVID); versus placebo (BE READY); and versus adalimumab (BE SURE).

“All studies met their co-primary endpoints and all ranked secondary endpoints,” the company reports. Secondary endpoints included the Psoriasis Area and Severity Index (PASI) 75 at week 4 and PASI 100 (complete skin clearance) at week 16.

Highlights from the trials include the following results, according to UCB:

• Clear or almost clear skin: More than 8 out of 10 patients achieved a 90% or greater reduction from baseline in the PASI 90 and an Investigator’s Global Assessment score of 0/1 at week 16.
• Complete skin clearance: About 60% of patients achieved PASI 100 at week 16.
• Time to response: More than 70% of patients achieved PASI 75 at week 4 following one 320-mg dose.

Safety information

The safety information includes the statement that bimekizumab may increase the risk for suicidal ideation and behavior, though a causal association has not been established. Prescribers should advise patients, caregivers, and families “to monitor for emergence or worsening of depression, suicidal ideation, or other mood changes,” according to the prescribing information.

Bimekizumab is being studied for other conditions, including hidradenitis suppurativa. In the European Union, it was approved for the treatment of psoriasis in 2021 and for the treatment of psoriatic arthritis and ankylosing spondylitis in June 2023.

Dr. Lebwohl is an investigator for UCB. He has not accepted any consulting payments from UCB.

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

The Food and Drug Administration has approved bimekizumab-bkzx (Bimzelx) for the treatment of moderate to severe plaque psoriasis in adults, the manufacturer announced in a press release.

The indication is for adults who are candidates for systemic therapy or phototherapy.

With this approval, bimekizumab becomes the only interleukin (IL)-17A and IL-17F inhibitor approved for the treatment of these patients. Psoriasis affects more than 7.5 million U.S. adults, according to the National Psoriasis Foundation.

“We have been eagerly awaiting bimekizumab,” Mark Lebwohl, MD, bimekizumab investigator and dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai, New York City, said in the press release.

Dr. Lebwohl states that bimekizumab “achieved superior levels of skin clearance at week 16 compared to placebo and three existing biologics for psoriasis, with responses being rapid and lasting up to a year. Long-term data have also shown that the majority of patients maintained high levels of clinical response through three years.”

The most common adverse reactions (occurring in at least 1% of patients) are upper respiratory infections, oral candidiasis, headache, tinea infections, gastroenteritis, herpes simplex infections, acne, folliculitis, other Candida infections, fatigue, and injection site reactions, according to the company, UCB.
 

Available in about 1 month in U.S.

Bimekizumab can be administered by a health care provider or it can be self-injected by a patient after training. It is available as a single-dose prefilled autoinjector and a single-dose prefilled syringe and will be available in the United States in about 1 month.

The recommended dosage of bimekizumab for patients with psoriasis is 320 mg (two subcutaneous injections of 160 mg each) at baseline, then on weeks 4, 8, 12, and 16, then every 8 weeks thereafter. For patients weighing at least 120 kg (about 265 lb), a dosage of 320 mg every 4 weeks after week 16 may be considered, the company states.

Three phase 3 trials

Approval was based on three phase 3 multicenter, randomized, placebo and/or active comparator-controlled trials: bimekizumab versus placebo and ustekinumab (BE VIVID); versus placebo (BE READY); and versus adalimumab (BE SURE).

“All studies met their co-primary endpoints and all ranked secondary endpoints,” the company reports. Secondary endpoints included the Psoriasis Area and Severity Index (PASI) 75 at week 4 and PASI 100 (complete skin clearance) at week 16.

Highlights from the trials include the following results, according to UCB:

• Clear or almost clear skin: More than 8 out of 10 patients achieved a 90% or greater reduction from baseline in the PASI 90 and an Investigator’s Global Assessment score of 0/1 at week 16.
• Complete skin clearance: About 60% of patients achieved PASI 100 at week 16.
• Time to response: More than 70% of patients achieved PASI 75 at week 4 following one 320-mg dose.

Safety information

The safety information includes the statement that bimekizumab may increase the risk for suicidal ideation and behavior, though a causal association has not been established. Prescribers should advise patients, caregivers, and families “to monitor for emergence or worsening of depression, suicidal ideation, or other mood changes,” according to the prescribing information.

Bimekizumab is being studied for other conditions, including hidradenitis suppurativa. In the European Union, it was approved for the treatment of psoriasis in 2021 and for the treatment of psoriatic arthritis and ankylosing spondylitis in June 2023.

Dr. Lebwohl is an investigator for UCB. He has not accepted any consulting payments from UCB.

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

TOPLINE:

DMT310, a novel topical treatment applied once per week, appears to be safe and effective for moderate to severe acne.

METHODOLOGY:

• Poor patient compliance with topical acne therapies is a common clinical challenge.
• In a 12-week, randomized, controlled, phase 2b trial of 181 patients 12 years of age and older, researchers investigated the safety, tolerability, and efficacy of DMT310, a powdered mixture of Spongilla lacustris for treating moderate to severe acne. (In vitro studies have found that components of S. lacustris, a freshwater sponge, have effects that include antimicrobial activity against Cutibacterium acnes and anti-inflammatory activity in human keratinocytes).
• The study’s primary efficacy endpoint was the absolute change in inflammatory lesion count from baseline to week 12.
• Endpoint success was defined as an Investigator Global Assessment (IGA) score of 0 or 1 and at least a two-grade improvement from baseline at week 12.
•  

TAKEAWAY:

• Of the 181 patients, 91 received DMT310 (applied once a week to the face and washed off after 10-15 minutes), and 90 received placebo.
• Patients in the DMT310 arm showed a significantly greater mean reduction in the number of inflammatory lesions at week 12, compared with those in the placebo arm (–15.64 vs. –10.84, respectively; P < .001).
• Similarly, patients in the DMT310 arm showed a significantly greater mean reduction in the number of noninflammatory lesions at week 12, compared with those in the placebo arm (–18.26 vs. –12.41, respectively; P < .001).
• At week 12, endpoint success based on IGA scores also significantly favored patients in the DMT310 arm, compared with those in the placebo arm (44.40% vs. 17.78%; P < .001).

IN PRACTICE:

This study is too preliminary to have practice application. The researchers concluded that the findings “support further study of DMT310 in larger, confirmatory phase 3 trials.”

SOURCE:

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, led the research. The study was published online June 7 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis did not include an active comparator group and it enrolled a limited number of Asian patients.

DISCLOSURES:

Dr. Eichenfield disclosed that he is a consultant to Dermata, which is developing DMT310, as were three other authors of the study. One author is a company employee. The remaining authors disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

DMT310, a novel topical treatment applied once per week, appears to be safe and effective for moderate to severe acne.

METHODOLOGY:

• Poor patient compliance with topical acne therapies is a common clinical challenge.
• In a 12-week, randomized, controlled, phase 2b trial of 181 patients 12 years of age and older, researchers investigated the safety, tolerability, and efficacy of DMT310, a powdered mixture of Spongilla lacustris for treating moderate to severe acne. (In vitro studies have found that components of S. lacustris, a freshwater sponge, have effects that include antimicrobial activity against Cutibacterium acnes and anti-inflammatory activity in human keratinocytes).
• The study’s primary efficacy endpoint was the absolute change in inflammatory lesion count from baseline to week 12.
• Endpoint success was defined as an Investigator Global Assessment (IGA) score of 0 or 1 and at least a two-grade improvement from baseline at week 12.
•  

TAKEAWAY:

• Of the 181 patients, 91 received DMT310 (applied once a week to the face and washed off after 10-15 minutes), and 90 received placebo.
• Patients in the DMT310 arm showed a significantly greater mean reduction in the number of inflammatory lesions at week 12, compared with those in the placebo arm (–15.64 vs. –10.84, respectively; P < .001).
• Similarly, patients in the DMT310 arm showed a significantly greater mean reduction in the number of noninflammatory lesions at week 12, compared with those in the placebo arm (–18.26 vs. –12.41, respectively; P < .001).
• At week 12, endpoint success based on IGA scores also significantly favored patients in the DMT310 arm, compared with those in the placebo arm (44.40% vs. 17.78%; P < .001).

IN PRACTICE:

This study is too preliminary to have practice application. The researchers concluded that the findings “support further study of DMT310 in larger, confirmatory phase 3 trials.”

SOURCE:

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, led the research. The study was published online June 7 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis did not include an active comparator group and it enrolled a limited number of Asian patients.

DISCLOSURES:

Dr. Eichenfield disclosed that he is a consultant to Dermata, which is developing DMT310, as were three other authors of the study. One author is a company employee. The remaining authors disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

DMT310, a novel topical treatment applied once per week, appears to be safe and effective for moderate to severe acne.

METHODOLOGY:

• Poor patient compliance with topical acne therapies is a common clinical challenge.
• In a 12-week, randomized, controlled, phase 2b trial of 181 patients 12 years of age and older, researchers investigated the safety, tolerability, and efficacy of DMT310, a powdered mixture of Spongilla lacustris for treating moderate to severe acne. (In vitro studies have found that components of S. lacustris, a freshwater sponge, have effects that include antimicrobial activity against Cutibacterium acnes and anti-inflammatory activity in human keratinocytes).
• The study’s primary efficacy endpoint was the absolute change in inflammatory lesion count from baseline to week 12.
• Endpoint success was defined as an Investigator Global Assessment (IGA) score of 0 or 1 and at least a two-grade improvement from baseline at week 12.
•  

TAKEAWAY:

• Of the 181 patients, 91 received DMT310 (applied once a week to the face and washed off after 10-15 minutes), and 90 received placebo.
• Patients in the DMT310 arm showed a significantly greater mean reduction in the number of inflammatory lesions at week 12, compared with those in the placebo arm (–15.64 vs. –10.84, respectively; P < .001).
• Similarly, patients in the DMT310 arm showed a significantly greater mean reduction in the number of noninflammatory lesions at week 12, compared with those in the placebo arm (–18.26 vs. –12.41, respectively; P < .001).
• At week 12, endpoint success based on IGA scores also significantly favored patients in the DMT310 arm, compared with those in the placebo arm (44.40% vs. 17.78%; P < .001).

IN PRACTICE:

This study is too preliminary to have practice application. The researchers concluded that the findings “support further study of DMT310 in larger, confirmatory phase 3 trials.”

SOURCE:

Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, led the research. The study was published online June 7 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The analysis did not include an active comparator group and it enrolled a limited number of Asian patients.

DISCLOSURES:

Dr. Eichenfield disclosed that he is a consultant to Dermata, which is developing DMT310, as were three other authors of the study. One author is a company employee. The remaining authors disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

WASHINGTON – A series of three higher-than-approved induction doses of the interleukin-23 inhibitor risankizumab in patients with psoriasis – and no further subsequent dosing – led to an “unprecedented” level of complete skin clearance at week 52 in a small study investigating whether high-dose IL-23 inhibition can target resident memory T cells and thereby induce long-term remission, Andrew Blauvelt, MD, MBA, reported at the annual research symposium of the National Psoriasis Foundation.

Understanding and trying to target resident memory T (Trm) cells has become a hot topic in psoriasis research, with possible importance for psoriatic arthritis as well. The cells, which normally develop within tissues in a pathogen-specific manner and persist after infections resolve, have been found in healed psoriatic skin and are believed to be responsible for recurrences of psoriasis at the same sites previously affected by the disease. Research suggests, moreover, that Trm cells are dependent on IL-23 for their survival, said Dr. Blauvelt, an investigator with the Oregon Medical Research Center, Portland.

Using an approach he has coined “knockout” therapy, 20 adult patients at the center were randomized 1:1 in double-blinded dosing to receive 300 mg or 600 mg of risankizumab (two and four times the standard initial doses, respectively) at 0, 4, and 16 weeks, and were seen every 4-6 weeks in a double-blinded follow-up period. Skin biopsies of lesional and nonlesional skin were collected at weeks 0 and 52 for RNA sequence analysis to evaluate changes in Trm cell number and effector function.

At week 28, almost all patients – 94% – achieved a Psoriasis Area and Severity Index 90 score, and 83% achieved PASI 100. At week 52, of the 18 still-enrolled patients, 69% had PASI 90 scores and 43% maintained PASI 100 scores. “We’re not curing psoriasis, but that is incredible to have 43% still clear 9 months after the last dose,” Dr. Blauvelt said.

The findings are interim results that pool the two doses of risankizumab (Skyrizi). An evaluation of maintenance of efficacy with the 300-mg versus 600-mg doses and results of the skin biopsies will be presented at the 2024 annual meeting of the American Academy of Dermatology, he said. Patients who have not had recurrences are being followed up to week 100 (unblinded).

Skin biopsy findings together with levels of clearance will “add insight as to whether high-dose IL-23 inhibition is associated with higher levels of complete clearance (i.e., PASI 100) over long periods of time, and whether remissions are associated with more profound knock-down of Trm cells,” Dr. Blauvelt wrote in an editorial on Trm cells in psoriasis published in the Journal of Psoriasis and Psoriatic Arthritis.

Risankizumab was approved by the Food and Drug Administration for moderate to severe plaque psoriasis in 2019, and for active psoriatic arthritis in 2022.
 

Impact of IL-23 inhibition

A 2021 study, Dr. Blauvelt noted in his presentation, showed that the IL-23 inhibitor guselkumab (Tremfya) reduced the number of Trm cells in healed psoriatic skin, while the IL-17A inhibitor secukinumab (Cosentyx) did not affect Trm cells.

Other researchers have concluded that local IL-23 is required for the proliferation and retention of Trm cells in the skin, he said, noting also that, as a class, IL-23 blockers “are associated with the longest disease-free intervals” in patients with psoriasis.

Research showing loss of Trm cells in biopsies of cleared skin is “incredibly important,” as is data showing that IL-23 may be “a critical survival factor” for Trm cells, said Christopher Ritchlin, MD, MPH, a rheumatologist and director of the clinical immunology research unit at the University of Rochester (N.Y.) Medical Center, who attended the NPF meeting and was asked to comment on the growing interest in Trm cells. He did not hear Dr. Blauvelt’s presentation but has followed Trm research in psoriasis.

Measuring Trm cells in synovial tissue of patients with psoriatic disease is, in fact, on the agenda of a new research team coled by Dr. Ritchlin that is part of the Autoimmune and Immune-Mediated Diseases Program of the Accelerating Medicine Partnership – a public-private partnership that aims to collect and analyze troves of biological data in order to illuminate the cellular and molecular interactions leading to autoimmune diseases.

“Resident memory T cells have been thought to be cells that are constrained to being resident in the tissue, and while that’s largely true, there’s more recent data showing that they actually can dedifferentiate and go back to the lymph node and then go back to the joint again,” Dr. Ritchlin noted in an interview. “So it’s a more complicated story,” but nonetheless targeting the cells is a concept worth exploring therapeutically.
 

Moving toward a cure?

The high induction doses of risankizumab in Dr. Blauvelt’s phase 2 “knockout” study were well tolerated through week 40, with safety profiles similar overall to those reported in previous studies of risankizumab and “no new safety signals,” Dr. Blauvelt said at the meeting.

(At baseline, patients had a mean disease duration of 21 years, a mean affected BSA of 21, and a mean PASI of 18.5. Seven had prior treatment with biologic medications, though not in the prior 4 months and not with risankizumab.)

In lieu of a cure, which is still possible in the next 10 years, he said, patients are eager for longer-term remission and the ability to break away from established regular dosing. After publication of a phase 1 study of risankizumab, in which a notable number of patients experienced complete skin clearance up to 1 year following a single high dose, “we started getting numerous calls in our [clinical trials] office from patients who said ‘I want to be on that drug that you give once a year,’ ” Dr. Blauvelt said. (The high dosing was not investigated any further in phase 2 and 3 research, he added.)

While the “knockout” study adopts a “hit hard” approach, it is also possible that a strategy to hit both hard and early after disease onset may induce long-term remission and/or cure of the disease. “I’m talking about using the best things first. There are hints that if we treat early, maybe we can keep [psoriasis] from becoming a chronic disease, keep it from ‘setting up shop’ if you will,” he said, noting that the “hit hard, hit early” concept is not unique to dermatology.

During a discussion period, Dr. Blauvelt said that in a future iteration of the “knockout” study, he would like to evaluate risankizumab in patients with disease duration under 12 months. It may also be valuable to look not only at Trm cells, but more broadly at other elements of the tissue architecture before and after treatment.

Among other strategies for achieving long-term remission and/or cure is the expansion of regulatory T cells, which work to “control inappropriate immune responses” and calm inflammation. Defects in the number and function of regulatory T cells are associated with psoriasis and other autoimmune diseases, and it appears in early research from other investigators that low-dose IL-2 can induce the expansion of regulatory T cells and improve psoriasis. “Keep tuned,” Dr. Blauvelt said.

Dr. Blauvelt disclosed ties with numerous pharmaceutical companies. Dr. Ritchlin had no disclosures.

WASHINGTON – A series of three higher-than-approved induction doses of the interleukin-23 inhibitor risankizumab in patients with psoriasis – and no further subsequent dosing – led to an “unprecedented” level of complete skin clearance at week 52 in a small study investigating whether high-dose IL-23 inhibition can target resident memory T cells and thereby induce long-term remission, Andrew Blauvelt, MD, MBA, reported at the annual research symposium of the National Psoriasis Foundation.

Understanding and trying to target resident memory T (Trm) cells has become a hot topic in psoriasis research, with possible importance for psoriatic arthritis as well. The cells, which normally develop within tissues in a pathogen-specific manner and persist after infections resolve, have been found in healed psoriatic skin and are believed to be responsible for recurrences of psoriasis at the same sites previously affected by the disease. Research suggests, moreover, that Trm cells are dependent on IL-23 for their survival, said Dr. Blauvelt, an investigator with the Oregon Medical Research Center, Portland.

Using an approach he has coined “knockout” therapy, 20 adult patients at the center were randomized 1:1 in double-blinded dosing to receive 300 mg or 600 mg of risankizumab (two and four times the standard initial doses, respectively) at 0, 4, and 16 weeks, and were seen every 4-6 weeks in a double-blinded follow-up period. Skin biopsies of lesional and nonlesional skin were collected at weeks 0 and 52 for RNA sequence analysis to evaluate changes in Trm cell number and effector function.

At week 28, almost all patients – 94% – achieved a Psoriasis Area and Severity Index 90 score, and 83% achieved PASI 100. At week 52, of the 18 still-enrolled patients, 69% had PASI 90 scores and 43% maintained PASI 100 scores. “We’re not curing psoriasis, but that is incredible to have 43% still clear 9 months after the last dose,” Dr. Blauvelt said.

The findings are interim results that pool the two doses of risankizumab (Skyrizi). An evaluation of maintenance of efficacy with the 300-mg versus 600-mg doses and results of the skin biopsies will be presented at the 2024 annual meeting of the American Academy of Dermatology, he said. Patients who have not had recurrences are being followed up to week 100 (unblinded).

Skin biopsy findings together with levels of clearance will “add insight as to whether high-dose IL-23 inhibition is associated with higher levels of complete clearance (i.e., PASI 100) over long periods of time, and whether remissions are associated with more profound knock-down of Trm cells,” Dr. Blauvelt wrote in an editorial on Trm cells in psoriasis published in the Journal of Psoriasis and Psoriatic Arthritis.

Risankizumab was approved by the Food and Drug Administration for moderate to severe plaque psoriasis in 2019, and for active psoriatic arthritis in 2022.
 

Impact of IL-23 inhibition

A 2021 study, Dr. Blauvelt noted in his presentation, showed that the IL-23 inhibitor guselkumab (Tremfya) reduced the number of Trm cells in healed psoriatic skin, while the IL-17A inhibitor secukinumab (Cosentyx) did not affect Trm cells.

Other researchers have concluded that local IL-23 is required for the proliferation and retention of Trm cells in the skin, he said, noting also that, as a class, IL-23 blockers “are associated with the longest disease-free intervals” in patients with psoriasis.

Research showing loss of Trm cells in biopsies of cleared skin is “incredibly important,” as is data showing that IL-23 may be “a critical survival factor” for Trm cells, said Christopher Ritchlin, MD, MPH, a rheumatologist and director of the clinical immunology research unit at the University of Rochester (N.Y.) Medical Center, who attended the NPF meeting and was asked to comment on the growing interest in Trm cells. He did not hear Dr. Blauvelt’s presentation but has followed Trm research in psoriasis.

Measuring Trm cells in synovial tissue of patients with psoriatic disease is, in fact, on the agenda of a new research team coled by Dr. Ritchlin that is part of the Autoimmune and Immune-Mediated Diseases Program of the Accelerating Medicine Partnership – a public-private partnership that aims to collect and analyze troves of biological data in order to illuminate the cellular and molecular interactions leading to autoimmune diseases.

“Resident memory T cells have been thought to be cells that are constrained to being resident in the tissue, and while that’s largely true, there’s more recent data showing that they actually can dedifferentiate and go back to the lymph node and then go back to the joint again,” Dr. Ritchlin noted in an interview. “So it’s a more complicated story,” but nonetheless targeting the cells is a concept worth exploring therapeutically.
 

Moving toward a cure?

The high induction doses of risankizumab in Dr. Blauvelt’s phase 2 “knockout” study were well tolerated through week 40, with safety profiles similar overall to those reported in previous studies of risankizumab and “no new safety signals,” Dr. Blauvelt said at the meeting.

(At baseline, patients had a mean disease duration of 21 years, a mean affected BSA of 21, and a mean PASI of 18.5. Seven had prior treatment with biologic medications, though not in the prior 4 months and not with risankizumab.)

In lieu of a cure, which is still possible in the next 10 years, he said, patients are eager for longer-term remission and the ability to break away from established regular dosing. After publication of a phase 1 study of risankizumab, in which a notable number of patients experienced complete skin clearance up to 1 year following a single high dose, “we started getting numerous calls in our [clinical trials] office from patients who said ‘I want to be on that drug that you give once a year,’ ” Dr. Blauvelt said. (The high dosing was not investigated any further in phase 2 and 3 research, he added.)

While the “knockout” study adopts a “hit hard” approach, it is also possible that a strategy to hit both hard and early after disease onset may induce long-term remission and/or cure of the disease. “I’m talking about using the best things first. There are hints that if we treat early, maybe we can keep [psoriasis] from becoming a chronic disease, keep it from ‘setting up shop’ if you will,” he said, noting that the “hit hard, hit early” concept is not unique to dermatology.

During a discussion period, Dr. Blauvelt said that in a future iteration of the “knockout” study, he would like to evaluate risankizumab in patients with disease duration under 12 months. It may also be valuable to look not only at Trm cells, but more broadly at other elements of the tissue architecture before and after treatment.

Among other strategies for achieving long-term remission and/or cure is the expansion of regulatory T cells, which work to “control inappropriate immune responses” and calm inflammation. Defects in the number and function of regulatory T cells are associated with psoriasis and other autoimmune diseases, and it appears in early research from other investigators that low-dose IL-2 can induce the expansion of regulatory T cells and improve psoriasis. “Keep tuned,” Dr. Blauvelt said.

Dr. Blauvelt disclosed ties with numerous pharmaceutical companies. Dr. Ritchlin had no disclosures.

WASHINGTON – A series of three higher-than-approved induction doses of the interleukin-23 inhibitor risankizumab in patients with psoriasis – and no further subsequent dosing – led to an “unprecedented” level of complete skin clearance at week 52 in a small study investigating whether high-dose IL-23 inhibition can target resident memory T cells and thereby induce long-term remission, Andrew Blauvelt, MD, MBA, reported at the annual research symposium of the National Psoriasis Foundation.

Understanding and trying to target resident memory T (Trm) cells has become a hot topic in psoriasis research, with possible importance for psoriatic arthritis as well. The cells, which normally develop within tissues in a pathogen-specific manner and persist after infections resolve, have been found in healed psoriatic skin and are believed to be responsible for recurrences of psoriasis at the same sites previously affected by the disease. Research suggests, moreover, that Trm cells are dependent on IL-23 for their survival, said Dr. Blauvelt, an investigator with the Oregon Medical Research Center, Portland.

Using an approach he has coined “knockout” therapy, 20 adult patients at the center were randomized 1:1 in double-blinded dosing to receive 300 mg or 600 mg of risankizumab (two and four times the standard initial doses, respectively) at 0, 4, and 16 weeks, and were seen every 4-6 weeks in a double-blinded follow-up period. Skin biopsies of lesional and nonlesional skin were collected at weeks 0 and 52 for RNA sequence analysis to evaluate changes in Trm cell number and effector function.

At week 28, almost all patients – 94% – achieved a Psoriasis Area and Severity Index 90 score, and 83% achieved PASI 100. At week 52, of the 18 still-enrolled patients, 69% had PASI 90 scores and 43% maintained PASI 100 scores. “We’re not curing psoriasis, but that is incredible to have 43% still clear 9 months after the last dose,” Dr. Blauvelt said.

The findings are interim results that pool the two doses of risankizumab (Skyrizi). An evaluation of maintenance of efficacy with the 300-mg versus 600-mg doses and results of the skin biopsies will be presented at the 2024 annual meeting of the American Academy of Dermatology, he said. Patients who have not had recurrences are being followed up to week 100 (unblinded).

Skin biopsy findings together with levels of clearance will “add insight as to whether high-dose IL-23 inhibition is associated with higher levels of complete clearance (i.e., PASI 100) over long periods of time, and whether remissions are associated with more profound knock-down of Trm cells,” Dr. Blauvelt wrote in an editorial on Trm cells in psoriasis published in the Journal of Psoriasis and Psoriatic Arthritis.

Risankizumab was approved by the Food and Drug Administration for moderate to severe plaque psoriasis in 2019, and for active psoriatic arthritis in 2022.
 

Impact of IL-23 inhibition

A 2021 study, Dr. Blauvelt noted in his presentation, showed that the IL-23 inhibitor guselkumab (Tremfya) reduced the number of Trm cells in healed psoriatic skin, while the IL-17A inhibitor secukinumab (Cosentyx) did not affect Trm cells.

Other researchers have concluded that local IL-23 is required for the proliferation and retention of Trm cells in the skin, he said, noting also that, as a class, IL-23 blockers “are associated with the longest disease-free intervals” in patients with psoriasis.

Research showing loss of Trm cells in biopsies of cleared skin is “incredibly important,” as is data showing that IL-23 may be “a critical survival factor” for Trm cells, said Christopher Ritchlin, MD, MPH, a rheumatologist and director of the clinical immunology research unit at the University of Rochester (N.Y.) Medical Center, who attended the NPF meeting and was asked to comment on the growing interest in Trm cells. He did not hear Dr. Blauvelt’s presentation but has followed Trm research in psoriasis.

Measuring Trm cells in synovial tissue of patients with psoriatic disease is, in fact, on the agenda of a new research team coled by Dr. Ritchlin that is part of the Autoimmune and Immune-Mediated Diseases Program of the Accelerating Medicine Partnership – a public-private partnership that aims to collect and analyze troves of biological data in order to illuminate the cellular and molecular interactions leading to autoimmune diseases.

“Resident memory T cells have been thought to be cells that are constrained to being resident in the tissue, and while that’s largely true, there’s more recent data showing that they actually can dedifferentiate and go back to the lymph node and then go back to the joint again,” Dr. Ritchlin noted in an interview. “So it’s a more complicated story,” but nonetheless targeting the cells is a concept worth exploring therapeutically.
 

Moving toward a cure?

The high induction doses of risankizumab in Dr. Blauvelt’s phase 2 “knockout” study were well tolerated through week 40, with safety profiles similar overall to those reported in previous studies of risankizumab and “no new safety signals,” Dr. Blauvelt said at the meeting.

(At baseline, patients had a mean disease duration of 21 years, a mean affected BSA of 21, and a mean PASI of 18.5. Seven had prior treatment with biologic medications, though not in the prior 4 months and not with risankizumab.)

In lieu of a cure, which is still possible in the next 10 years, he said, patients are eager for longer-term remission and the ability to break away from established regular dosing. After publication of a phase 1 study of risankizumab, in which a notable number of patients experienced complete skin clearance up to 1 year following a single high dose, “we started getting numerous calls in our [clinical trials] office from patients who said ‘I want to be on that drug that you give once a year,’ ” Dr. Blauvelt said. (The high dosing was not investigated any further in phase 2 and 3 research, he added.)

While the “knockout” study adopts a “hit hard” approach, it is also possible that a strategy to hit both hard and early after disease onset may induce long-term remission and/or cure of the disease. “I’m talking about using the best things first. There are hints that if we treat early, maybe we can keep [psoriasis] from becoming a chronic disease, keep it from ‘setting up shop’ if you will,” he said, noting that the “hit hard, hit early” concept is not unique to dermatology.

During a discussion period, Dr. Blauvelt said that in a future iteration of the “knockout” study, he would like to evaluate risankizumab in patients with disease duration under 12 months. It may also be valuable to look not only at Trm cells, but more broadly at other elements of the tissue architecture before and after treatment.

Among other strategies for achieving long-term remission and/or cure is the expansion of regulatory T cells, which work to “control inappropriate immune responses” and calm inflammation. Defects in the number and function of regulatory T cells are associated with psoriasis and other autoimmune diseases, and it appears in early research from other investigators that low-dose IL-2 can induce the expansion of regulatory T cells and improve psoriasis. “Keep tuned,” Dr. Blauvelt said.

Dr. Blauvelt disclosed ties with numerous pharmaceutical companies. Dr. Ritchlin had no disclosures.