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Systemic psoriasis treatments less often prescribed in elderly with psoriasis, despite comparable response rates
MILAN – an analysis of German and Swiss registry data shows.
There was an “imbalance” in the types of medications prescribed for older and younger patients in the registry, with biologics used more frequently in younger patients, according to investigator Matthias Augustin, MD, director of the Institute For Health Services Research in Dermatology and Nursing in Hamburg, Germany.
However, the efficacy of systemic treatments, including nonbiologic therapies, was comparable between older and younger patients, other than a few differences in response rates early in treatment that disappeared with longer follow-up, Dr. Augustin said at the World Congress of Dermatology. Coupled with evidence from the medical literature, results of this registry data analysis suggest there are “very few reasons” to avoid use of systemic drugs in elderly patients.
“I think we should create awareness and discuss possible reasons that deter dermatologists from prescribing systemic antipsoriatics in elderly patients,” he said.
Concerns about safety and drug interactions in the elderly may be one barrier to prescribing systemic therapy in this patient population: More data on this issue are needed, since the elderly are taking more medications than younger patients and have more contraindications, Dr. Augustin said. “I think this is a job for all registries for the future.”
Older individuals have typically been excluded from psoriasis clinical trials, making it difficult to extrapolate existing safety and efficacy data to those patients, he pointed out.
Accordingly, Dr. Augustin and coinvestigators evaluated prospectively collected data for patients with moderate to severe psoriasis who were included in either the German Psoriasis registry (PsoBest) or the Swiss Dermatology Network for Targeted Therapies (SDNTT). They split the cohort into a control group of those younger than 65 years (about 4,600 individuals) and those 65 years or older (about 740 individuals).
A few systemic drugs were used more frequently in the elderly, including apremilast and methotrexate, while most other drugs, including biologics, were used more frequently in younger patients, Dr. Augustin and colleagues found in their analysis. There were a few differences between the elderly and controls related to weight, smoking, and other factors, but not so pronounced that they would explain differences in the use of the systemic therapy.
Response rates to systemic therapies were generally comparable between the elderly and controls, as measured by Psoriasis Area Severity Index (PASI) 75 responses, PASI scores of 3 or less, and Dermatology Life Quality Index scores of one or less, he added.
One exception was methotrexate, which was more effective in the elderly after 3 and 6 months of treatment, but that difference was no longer apparent after 12 months of treatment, he said. Likewise, cyclosporine showed a higher response rate in younger patients at 3 months, but not at 6 or 12 months.
Based on the findings, “overall, we observed comparable responses between the controls and the elderly,” Dr. Augustin concluded.
The PsoBest registry is sponsored by CVderm, DDG, and BVDD, and “has been established and is operated in close cooperation with the involved pharmaceutical companies whose statutory pharmacovigilance requirements are taken into account,” according to a statement on the PsoBest website. The Swiss registry is supported by Janssen, AbbVie, Pfizer, Celgene, Lilly, and Novartis. The investigators did not report any disclosures.
MILAN – an analysis of German and Swiss registry data shows.
There was an “imbalance” in the types of medications prescribed for older and younger patients in the registry, with biologics used more frequently in younger patients, according to investigator Matthias Augustin, MD, director of the Institute For Health Services Research in Dermatology and Nursing in Hamburg, Germany.
However, the efficacy of systemic treatments, including nonbiologic therapies, was comparable between older and younger patients, other than a few differences in response rates early in treatment that disappeared with longer follow-up, Dr. Augustin said at the World Congress of Dermatology. Coupled with evidence from the medical literature, results of this registry data analysis suggest there are “very few reasons” to avoid use of systemic drugs in elderly patients.
“I think we should create awareness and discuss possible reasons that deter dermatologists from prescribing systemic antipsoriatics in elderly patients,” he said.
Concerns about safety and drug interactions in the elderly may be one barrier to prescribing systemic therapy in this patient population: More data on this issue are needed, since the elderly are taking more medications than younger patients and have more contraindications, Dr. Augustin said. “I think this is a job for all registries for the future.”
Older individuals have typically been excluded from psoriasis clinical trials, making it difficult to extrapolate existing safety and efficacy data to those patients, he pointed out.
Accordingly, Dr. Augustin and coinvestigators evaluated prospectively collected data for patients with moderate to severe psoriasis who were included in either the German Psoriasis registry (PsoBest) or the Swiss Dermatology Network for Targeted Therapies (SDNTT). They split the cohort into a control group of those younger than 65 years (about 4,600 individuals) and those 65 years or older (about 740 individuals).
A few systemic drugs were used more frequently in the elderly, including apremilast and methotrexate, while most other drugs, including biologics, were used more frequently in younger patients, Dr. Augustin and colleagues found in their analysis. There were a few differences between the elderly and controls related to weight, smoking, and other factors, but not so pronounced that they would explain differences in the use of the systemic therapy.
Response rates to systemic therapies were generally comparable between the elderly and controls, as measured by Psoriasis Area Severity Index (PASI) 75 responses, PASI scores of 3 or less, and Dermatology Life Quality Index scores of one or less, he added.
One exception was methotrexate, which was more effective in the elderly after 3 and 6 months of treatment, but that difference was no longer apparent after 12 months of treatment, he said. Likewise, cyclosporine showed a higher response rate in younger patients at 3 months, but not at 6 or 12 months.
Based on the findings, “overall, we observed comparable responses between the controls and the elderly,” Dr. Augustin concluded.
The PsoBest registry is sponsored by CVderm, DDG, and BVDD, and “has been established and is operated in close cooperation with the involved pharmaceutical companies whose statutory pharmacovigilance requirements are taken into account,” according to a statement on the PsoBest website. The Swiss registry is supported by Janssen, AbbVie, Pfizer, Celgene, Lilly, and Novartis. The investigators did not report any disclosures.
MILAN – an analysis of German and Swiss registry data shows.
There was an “imbalance” in the types of medications prescribed for older and younger patients in the registry, with biologics used more frequently in younger patients, according to investigator Matthias Augustin, MD, director of the Institute For Health Services Research in Dermatology and Nursing in Hamburg, Germany.
However, the efficacy of systemic treatments, including nonbiologic therapies, was comparable between older and younger patients, other than a few differences in response rates early in treatment that disappeared with longer follow-up, Dr. Augustin said at the World Congress of Dermatology. Coupled with evidence from the medical literature, results of this registry data analysis suggest there are “very few reasons” to avoid use of systemic drugs in elderly patients.
“I think we should create awareness and discuss possible reasons that deter dermatologists from prescribing systemic antipsoriatics in elderly patients,” he said.
Concerns about safety and drug interactions in the elderly may be one barrier to prescribing systemic therapy in this patient population: More data on this issue are needed, since the elderly are taking more medications than younger patients and have more contraindications, Dr. Augustin said. “I think this is a job for all registries for the future.”
Older individuals have typically been excluded from psoriasis clinical trials, making it difficult to extrapolate existing safety and efficacy data to those patients, he pointed out.
Accordingly, Dr. Augustin and coinvestigators evaluated prospectively collected data for patients with moderate to severe psoriasis who were included in either the German Psoriasis registry (PsoBest) or the Swiss Dermatology Network for Targeted Therapies (SDNTT). They split the cohort into a control group of those younger than 65 years (about 4,600 individuals) and those 65 years or older (about 740 individuals).
A few systemic drugs were used more frequently in the elderly, including apremilast and methotrexate, while most other drugs, including biologics, were used more frequently in younger patients, Dr. Augustin and colleagues found in their analysis. There were a few differences between the elderly and controls related to weight, smoking, and other factors, but not so pronounced that they would explain differences in the use of the systemic therapy.
Response rates to systemic therapies were generally comparable between the elderly and controls, as measured by Psoriasis Area Severity Index (PASI) 75 responses, PASI scores of 3 or less, and Dermatology Life Quality Index scores of one or less, he added.
One exception was methotrexate, which was more effective in the elderly after 3 and 6 months of treatment, but that difference was no longer apparent after 12 months of treatment, he said. Likewise, cyclosporine showed a higher response rate in younger patients at 3 months, but not at 6 or 12 months.
Based on the findings, “overall, we observed comparable responses between the controls and the elderly,” Dr. Augustin concluded.
The PsoBest registry is sponsored by CVderm, DDG, and BVDD, and “has been established and is operated in close cooperation with the involved pharmaceutical companies whose statutory pharmacovigilance requirements are taken into account,” according to a statement on the PsoBest website. The Swiss registry is supported by Janssen, AbbVie, Pfizer, Celgene, Lilly, and Novartis. The investigators did not report any disclosures.
REPORTING FROM WCD2019
Atopic dermatitis patients achieved freedom from itch on JAK inhibitor upadacitinib
MILAN – according to a report presented at the World Congress of Dermatology.
Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).
These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.
“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”
Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.
In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.
Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).
In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.
The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).
Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.
That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”
Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.
The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.
Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.
Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.
MILAN – according to a report presented at the World Congress of Dermatology.
Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).
These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.
“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”
Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.
In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.
Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).
In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.
The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).
Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.
That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”
Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.
The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.
Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.
Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.
MILAN – according to a report presented at the World Congress of Dermatology.
Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).
These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.
“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”
Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.
In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.
Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).
In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.
The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).
Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.
That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”
Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.
The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.
Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.
Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.
REPORTING FROM WCD2019
Topical ruxolitinib looks good for facial vitiligo, in phase 2 study
MILAN – Targeting the Janus kinase (JAK) 1 and 2 pathways in vitiligo resulted in significant reduction of facial depigmentation after 24 weeks of treatment, in a phase 2b trial of topical ruxolitinib cream.
compared with vehicle alone, said David Rosmarin, MD, speaking in a late-breaking abstracts session at the World Congress of Dermatology.
The highest response rate was seen with a higher dose: Among patients receiving ruxolitinib cream 1.5% once daily, 50% met the 50% clearing mark at 24 weeks, as did 45.5% of those with twice-daily 1.5% dosing of the 1.5% formulation. At 24 weeks, 3.1% of those receiving vehicle had 50% facial vitiligo resolution (P less than .0001, compared with vehicle for both doses).
Vitiligo affects about 3,000,000 people in the United States, and it is a plausible treatment target for the JAK inhibitor ruxolitinib, explained Dr. Rosmarin, a dermatologist at Tufts University, Boston. “Interferon-gamma, signaling through JAK1 and JAK2, is central to the pathogenesis of vitiligo,” he said. “Ruxolitinib is a potent inhibitor of JAK1 and JAK2, so it made sense to investigate it as a treatment for vitiligo.”
The 24-month randomized, double-blind, vehicle-controlled phase 2 study of ruxolitinib cream for vitiligo compared the vehicle to four different concentrations of ruxolitinib during the first phase of the study. For the first 24 weeks, patients were randomized to receive vehicle twice daily, or various doses of ruxolitinib ranging from 0.15% once daily to 1.5% twice daily.
At this point, the study’s primary endpoint was assessed, with investigators comparing the proportion of patients treated with ruxolitinib who had at least 50% improvement in facial repigmentation from baseline on the Facial Vitiligo Area Scoring Index (F-VASI50) compared with those who received vehicle. A secondary endpoint, also assessed at week 24, was the proportion of patients who were clear, or almost clear, of facial vitiligo; safety and tolerability were also assessed.
In addition to the F-VASI50 measure, Dr. Rosmarin and his coinvestigators also tracked 75% facial clearing (F-VASI75). Here, the 1.5% twice daily regimen topped the others, with 30% of those receiving that dose achieving F-VASI75, compared with almost 10%-17% of those on other doses.
Using another measure, More than one-third of patients using ruxolitinib (35.3%) had clear (no signs of vitiligo) or almost clear (only specks of depigmentation) facial skin at week 24, according to a clinician assessment tool. No patients on placebo had clear or almost clear facial skin at that point. “It is my hope that with continued use beyond week 24, more patients will meet this very stringent endpoint,” Dr. Rosmarin said.
The safety profile was good, with no serious treatment-related adverse events, and no application site reactions that reached clinical significance, although numerically more patients reported acne with ruxolitinib than with vehicle alone.
In the trial, patients aged 18-75 years with vitiligo were eligible if they had facial depigmentation that constituted at least half of their body surface area (BSA), as well as depigmentation of at least 3% of BSA on nonfacial areas. Patients were excluded if they had another dermatologic disease, infection, prior JAK inhibitor therapy, or recent use of biologic or experimental drugs, laser or light-based treatments, or immunomodulators. Of the 157 patients who were randomized, 18 patients (11.5%) had discontinued treatment by week 24, with 3 patients stopping for adverse events, 3 for protocol deviation or noncompliance, and 10 withdrawals. Two patients were lost to follow-up; all patients were included in analysis of the primary and secondary endpoints.
In the second year of the study, investigators rerandomized patients who had been receiving vehicle to an active arm of the study, and patients who had less than 25% improvement on a facial vitiligo scoring scale were rerandomized to one of the different doses. Twenty-eight weeks after rerandomization, all participants were given the opportunity to participate in a year-long open-label extension, receiving 1.5% ruxolitinib cream twice daily. Phototherapy was allowed in the extension arm, but not in the first year of the study.
Data beyond 24 weeks have not yet been reported, and the 2-year study plan acknowledged that “repigmentation takes a while,” Dr. Rosmarin said. He added that patients were allowed to use the study drug on body vitiligo as well, and many saw improvement there, although these results weren’t tracked in the study. “This isn’t a drug that’s meant just for the face,” he said.
Dr. Rosmarin and his coauthors reported financial arrangements with several pharmaceutical companies, including Incyte, which funded the study. An oral formulation of ruxolitinib (Jakafi), marketed by Incyte, was approved by the Food and Drug Administration in 2011, for myelofibrosis, and was recently approved for steroid-refractory acute graft-versus-host disease in adults and children aged 12 years and older.
MILAN – Targeting the Janus kinase (JAK) 1 and 2 pathways in vitiligo resulted in significant reduction of facial depigmentation after 24 weeks of treatment, in a phase 2b trial of topical ruxolitinib cream.
compared with vehicle alone, said David Rosmarin, MD, speaking in a late-breaking abstracts session at the World Congress of Dermatology.
The highest response rate was seen with a higher dose: Among patients receiving ruxolitinib cream 1.5% once daily, 50% met the 50% clearing mark at 24 weeks, as did 45.5% of those with twice-daily 1.5% dosing of the 1.5% formulation. At 24 weeks, 3.1% of those receiving vehicle had 50% facial vitiligo resolution (P less than .0001, compared with vehicle for both doses).
Vitiligo affects about 3,000,000 people in the United States, and it is a plausible treatment target for the JAK inhibitor ruxolitinib, explained Dr. Rosmarin, a dermatologist at Tufts University, Boston. “Interferon-gamma, signaling through JAK1 and JAK2, is central to the pathogenesis of vitiligo,” he said. “Ruxolitinib is a potent inhibitor of JAK1 and JAK2, so it made sense to investigate it as a treatment for vitiligo.”
The 24-month randomized, double-blind, vehicle-controlled phase 2 study of ruxolitinib cream for vitiligo compared the vehicle to four different concentrations of ruxolitinib during the first phase of the study. For the first 24 weeks, patients were randomized to receive vehicle twice daily, or various doses of ruxolitinib ranging from 0.15% once daily to 1.5% twice daily.
At this point, the study’s primary endpoint was assessed, with investigators comparing the proportion of patients treated with ruxolitinib who had at least 50% improvement in facial repigmentation from baseline on the Facial Vitiligo Area Scoring Index (F-VASI50) compared with those who received vehicle. A secondary endpoint, also assessed at week 24, was the proportion of patients who were clear, or almost clear, of facial vitiligo; safety and tolerability were also assessed.
In addition to the F-VASI50 measure, Dr. Rosmarin and his coinvestigators also tracked 75% facial clearing (F-VASI75). Here, the 1.5% twice daily regimen topped the others, with 30% of those receiving that dose achieving F-VASI75, compared with almost 10%-17% of those on other doses.
Using another measure, More than one-third of patients using ruxolitinib (35.3%) had clear (no signs of vitiligo) or almost clear (only specks of depigmentation) facial skin at week 24, according to a clinician assessment tool. No patients on placebo had clear or almost clear facial skin at that point. “It is my hope that with continued use beyond week 24, more patients will meet this very stringent endpoint,” Dr. Rosmarin said.
The safety profile was good, with no serious treatment-related adverse events, and no application site reactions that reached clinical significance, although numerically more patients reported acne with ruxolitinib than with vehicle alone.
In the trial, patients aged 18-75 years with vitiligo were eligible if they had facial depigmentation that constituted at least half of their body surface area (BSA), as well as depigmentation of at least 3% of BSA on nonfacial areas. Patients were excluded if they had another dermatologic disease, infection, prior JAK inhibitor therapy, or recent use of biologic or experimental drugs, laser or light-based treatments, or immunomodulators. Of the 157 patients who were randomized, 18 patients (11.5%) had discontinued treatment by week 24, with 3 patients stopping for adverse events, 3 for protocol deviation or noncompliance, and 10 withdrawals. Two patients were lost to follow-up; all patients were included in analysis of the primary and secondary endpoints.
In the second year of the study, investigators rerandomized patients who had been receiving vehicle to an active arm of the study, and patients who had less than 25% improvement on a facial vitiligo scoring scale were rerandomized to one of the different doses. Twenty-eight weeks after rerandomization, all participants were given the opportunity to participate in a year-long open-label extension, receiving 1.5% ruxolitinib cream twice daily. Phototherapy was allowed in the extension arm, but not in the first year of the study.
Data beyond 24 weeks have not yet been reported, and the 2-year study plan acknowledged that “repigmentation takes a while,” Dr. Rosmarin said. He added that patients were allowed to use the study drug on body vitiligo as well, and many saw improvement there, although these results weren’t tracked in the study. “This isn’t a drug that’s meant just for the face,” he said.
Dr. Rosmarin and his coauthors reported financial arrangements with several pharmaceutical companies, including Incyte, which funded the study. An oral formulation of ruxolitinib (Jakafi), marketed by Incyte, was approved by the Food and Drug Administration in 2011, for myelofibrosis, and was recently approved for steroid-refractory acute graft-versus-host disease in adults and children aged 12 years and older.
MILAN – Targeting the Janus kinase (JAK) 1 and 2 pathways in vitiligo resulted in significant reduction of facial depigmentation after 24 weeks of treatment, in a phase 2b trial of topical ruxolitinib cream.
compared with vehicle alone, said David Rosmarin, MD, speaking in a late-breaking abstracts session at the World Congress of Dermatology.
The highest response rate was seen with a higher dose: Among patients receiving ruxolitinib cream 1.5% once daily, 50% met the 50% clearing mark at 24 weeks, as did 45.5% of those with twice-daily 1.5% dosing of the 1.5% formulation. At 24 weeks, 3.1% of those receiving vehicle had 50% facial vitiligo resolution (P less than .0001, compared with vehicle for both doses).
Vitiligo affects about 3,000,000 people in the United States, and it is a plausible treatment target for the JAK inhibitor ruxolitinib, explained Dr. Rosmarin, a dermatologist at Tufts University, Boston. “Interferon-gamma, signaling through JAK1 and JAK2, is central to the pathogenesis of vitiligo,” he said. “Ruxolitinib is a potent inhibitor of JAK1 and JAK2, so it made sense to investigate it as a treatment for vitiligo.”
The 24-month randomized, double-blind, vehicle-controlled phase 2 study of ruxolitinib cream for vitiligo compared the vehicle to four different concentrations of ruxolitinib during the first phase of the study. For the first 24 weeks, patients were randomized to receive vehicle twice daily, or various doses of ruxolitinib ranging from 0.15% once daily to 1.5% twice daily.
At this point, the study’s primary endpoint was assessed, with investigators comparing the proportion of patients treated with ruxolitinib who had at least 50% improvement in facial repigmentation from baseline on the Facial Vitiligo Area Scoring Index (F-VASI50) compared with those who received vehicle. A secondary endpoint, also assessed at week 24, was the proportion of patients who were clear, or almost clear, of facial vitiligo; safety and tolerability were also assessed.
In addition to the F-VASI50 measure, Dr. Rosmarin and his coinvestigators also tracked 75% facial clearing (F-VASI75). Here, the 1.5% twice daily regimen topped the others, with 30% of those receiving that dose achieving F-VASI75, compared with almost 10%-17% of those on other doses.
Using another measure, More than one-third of patients using ruxolitinib (35.3%) had clear (no signs of vitiligo) or almost clear (only specks of depigmentation) facial skin at week 24, according to a clinician assessment tool. No patients on placebo had clear or almost clear facial skin at that point. “It is my hope that with continued use beyond week 24, more patients will meet this very stringent endpoint,” Dr. Rosmarin said.
The safety profile was good, with no serious treatment-related adverse events, and no application site reactions that reached clinical significance, although numerically more patients reported acne with ruxolitinib than with vehicle alone.
In the trial, patients aged 18-75 years with vitiligo were eligible if they had facial depigmentation that constituted at least half of their body surface area (BSA), as well as depigmentation of at least 3% of BSA on nonfacial areas. Patients were excluded if they had another dermatologic disease, infection, prior JAK inhibitor therapy, or recent use of biologic or experimental drugs, laser or light-based treatments, or immunomodulators. Of the 157 patients who were randomized, 18 patients (11.5%) had discontinued treatment by week 24, with 3 patients stopping for adverse events, 3 for protocol deviation or noncompliance, and 10 withdrawals. Two patients were lost to follow-up; all patients were included in analysis of the primary and secondary endpoints.
In the second year of the study, investigators rerandomized patients who had been receiving vehicle to an active arm of the study, and patients who had less than 25% improvement on a facial vitiligo scoring scale were rerandomized to one of the different doses. Twenty-eight weeks after rerandomization, all participants were given the opportunity to participate in a year-long open-label extension, receiving 1.5% ruxolitinib cream twice daily. Phototherapy was allowed in the extension arm, but not in the first year of the study.
Data beyond 24 weeks have not yet been reported, and the 2-year study plan acknowledged that “repigmentation takes a while,” Dr. Rosmarin said. He added that patients were allowed to use the study drug on body vitiligo as well, and many saw improvement there, although these results weren’t tracked in the study. “This isn’t a drug that’s meant just for the face,” he said.
Dr. Rosmarin and his coauthors reported financial arrangements with several pharmaceutical companies, including Incyte, which funded the study. An oral formulation of ruxolitinib (Jakafi), marketed by Incyte, was approved by the Food and Drug Administration in 2011, for myelofibrosis, and was recently approved for steroid-refractory acute graft-versus-host disease in adults and children aged 12 years and older.
REPORTING FROM WCD2019
Bullous disorders linked to frequent interruption of immune checkpoint inhibitor treatment
MILAN – Among the dermatologic adverse effects of immune checkpoint inhibitor therapy, bullous disorders are relatively infrequent but associated with a high likelihood of treatment interruption, according to results of a single-center study described at the World Congress of Dermatology.
, and nearly all required systemic steroids and were associated with interruptions and discontinuations of the anti-cancer treatment, reported Jonathan Leventhal, MD, director of the oncodermatology clinic at Yale University, New Haven, Conn.
“This series highlights a very important, clinically relevant, cutaneous immune-related adverse event,” Dr. Leventhal said in an oral presentation at the congress. “These disorders manifested in most patients as bullous pemphigoid, occurred several months after starting therapy, and at a frequency rate of 1%” among all patients treated with these agents, “at least in our institution.”
The retrospective review presented by Dr. Leventhal was based on medical records of patients evaluated at Yale New Haven Hospital between 2016 and 2018. This included a total of 853 patients who received anti-PD-1/PD-L1 therapy, of whom 98 (11.5%) were evaluated at the oncodermatology clinic or inpatient consultative service.
Nine patients – five men, four women – developed bullous disorders, representing about 1% of patients treated with PD-1/PD-L1 blocking therapy, according to Dr. Leventhal. The mean age of the patients was 67.4 years. Seven of the nine patients had received PD-1 inhibitors, while two received PD-L1 inhibitors, for tumors of the lung in four cases, melanoma in two, genitourinary tumors in two, and acute myeloid leukemia in one.
“The time from rash onset to first administration of the drug was over 6 months, which is quite long compared to a lot of the other (checkpoint inhibitor–associated) toxicities that we see more commonly, which often occur in several weeks to just a few months,” Dr. Leventhal said.
Of the 853 patients in this retrospective study, 463 (54.3%) were treated with nivolumab (Opdivo) and 242 (28.4%) were treated with pembrolizumab (Keytruda), both PD-1 blockers. Of the remainder, 112 (13.1%) received the PD-L1 blockers atezolizumab (Tecentriq), 29 (3.4%) received durvalumab (Imfinzi), and 7 (0.8%) received avelumab (Bavencio), Dr. Leventhal reported.
All these patients presented with both pruritus and vesiculobullous eruptions seen mainly on the trunk and extremities, while two patients had oral ulcerations. Other presentations included urticarial-predominant bullous pemphigoid, dyshidrosiform pemphigoid, and lichenoid papules and vesicles. The diagnosis was bullous pemphigoid in seven of nine cases, Dr. Leventhal said.
The best management approach for immune-related bullous disorders would be use of high-potency topical steroids to avoid systemic steroids and avoid interruptions in checkpoint inhibitor therapy, he pointed out. However, eight of the nine patients in this retrospective series required systemic steroids due to progression of the bullae, he added.
Several notable cases were described, including one patient refractory to prednisone and omalizumab who eventually achieved control with methotrexate, a second patient who was well controlled with omalizumab monotherapy and able to resume treatment with an anti PD-1 inhibitor, and another patient who responded to prednisone and dapsone maintenance therapy.
The immunotherapy treatment for cancer was interrupted in four of nine patients due to the bullous disorders, and was permanently discontinued in another four, Dr. Leventhal said.
It’s not clear why patients receiving cancer immunotherapy treatment develop bullous pemphigoid. However, the 180-kd bullous pemphigoid antigen (BP180) is expressed in melanoma and non-small cell lung cancer, which may lead to production of antibodies against tumor cell antigens that also impact the skin, according to Dr. Leventhal.
Further studies are needed to evaluate whether immune-related bullous disorders have any prognostic significance in cancer patients, he added.
Dr. Leventhal reported that he had no relevant disclosures.
MILAN – Among the dermatologic adverse effects of immune checkpoint inhibitor therapy, bullous disorders are relatively infrequent but associated with a high likelihood of treatment interruption, according to results of a single-center study described at the World Congress of Dermatology.
, and nearly all required systemic steroids and were associated with interruptions and discontinuations of the anti-cancer treatment, reported Jonathan Leventhal, MD, director of the oncodermatology clinic at Yale University, New Haven, Conn.
“This series highlights a very important, clinically relevant, cutaneous immune-related adverse event,” Dr. Leventhal said in an oral presentation at the congress. “These disorders manifested in most patients as bullous pemphigoid, occurred several months after starting therapy, and at a frequency rate of 1%” among all patients treated with these agents, “at least in our institution.”
The retrospective review presented by Dr. Leventhal was based on medical records of patients evaluated at Yale New Haven Hospital between 2016 and 2018. This included a total of 853 patients who received anti-PD-1/PD-L1 therapy, of whom 98 (11.5%) were evaluated at the oncodermatology clinic or inpatient consultative service.
Nine patients – five men, four women – developed bullous disorders, representing about 1% of patients treated with PD-1/PD-L1 blocking therapy, according to Dr. Leventhal. The mean age of the patients was 67.4 years. Seven of the nine patients had received PD-1 inhibitors, while two received PD-L1 inhibitors, for tumors of the lung in four cases, melanoma in two, genitourinary tumors in two, and acute myeloid leukemia in one.
“The time from rash onset to first administration of the drug was over 6 months, which is quite long compared to a lot of the other (checkpoint inhibitor–associated) toxicities that we see more commonly, which often occur in several weeks to just a few months,” Dr. Leventhal said.
Of the 853 patients in this retrospective study, 463 (54.3%) were treated with nivolumab (Opdivo) and 242 (28.4%) were treated with pembrolizumab (Keytruda), both PD-1 blockers. Of the remainder, 112 (13.1%) received the PD-L1 blockers atezolizumab (Tecentriq), 29 (3.4%) received durvalumab (Imfinzi), and 7 (0.8%) received avelumab (Bavencio), Dr. Leventhal reported.
All these patients presented with both pruritus and vesiculobullous eruptions seen mainly on the trunk and extremities, while two patients had oral ulcerations. Other presentations included urticarial-predominant bullous pemphigoid, dyshidrosiform pemphigoid, and lichenoid papules and vesicles. The diagnosis was bullous pemphigoid in seven of nine cases, Dr. Leventhal said.
The best management approach for immune-related bullous disorders would be use of high-potency topical steroids to avoid systemic steroids and avoid interruptions in checkpoint inhibitor therapy, he pointed out. However, eight of the nine patients in this retrospective series required systemic steroids due to progression of the bullae, he added.
Several notable cases were described, including one patient refractory to prednisone and omalizumab who eventually achieved control with methotrexate, a second patient who was well controlled with omalizumab monotherapy and able to resume treatment with an anti PD-1 inhibitor, and another patient who responded to prednisone and dapsone maintenance therapy.
The immunotherapy treatment for cancer was interrupted in four of nine patients due to the bullous disorders, and was permanently discontinued in another four, Dr. Leventhal said.
It’s not clear why patients receiving cancer immunotherapy treatment develop bullous pemphigoid. However, the 180-kd bullous pemphigoid antigen (BP180) is expressed in melanoma and non-small cell lung cancer, which may lead to production of antibodies against tumor cell antigens that also impact the skin, according to Dr. Leventhal.
Further studies are needed to evaluate whether immune-related bullous disorders have any prognostic significance in cancer patients, he added.
Dr. Leventhal reported that he had no relevant disclosures.
MILAN – Among the dermatologic adverse effects of immune checkpoint inhibitor therapy, bullous disorders are relatively infrequent but associated with a high likelihood of treatment interruption, according to results of a single-center study described at the World Congress of Dermatology.
, and nearly all required systemic steroids and were associated with interruptions and discontinuations of the anti-cancer treatment, reported Jonathan Leventhal, MD, director of the oncodermatology clinic at Yale University, New Haven, Conn.
“This series highlights a very important, clinically relevant, cutaneous immune-related adverse event,” Dr. Leventhal said in an oral presentation at the congress. “These disorders manifested in most patients as bullous pemphigoid, occurred several months after starting therapy, and at a frequency rate of 1%” among all patients treated with these agents, “at least in our institution.”
The retrospective review presented by Dr. Leventhal was based on medical records of patients evaluated at Yale New Haven Hospital between 2016 and 2018. This included a total of 853 patients who received anti-PD-1/PD-L1 therapy, of whom 98 (11.5%) were evaluated at the oncodermatology clinic or inpatient consultative service.
Nine patients – five men, four women – developed bullous disorders, representing about 1% of patients treated with PD-1/PD-L1 blocking therapy, according to Dr. Leventhal. The mean age of the patients was 67.4 years. Seven of the nine patients had received PD-1 inhibitors, while two received PD-L1 inhibitors, for tumors of the lung in four cases, melanoma in two, genitourinary tumors in two, and acute myeloid leukemia in one.
“The time from rash onset to first administration of the drug was over 6 months, which is quite long compared to a lot of the other (checkpoint inhibitor–associated) toxicities that we see more commonly, which often occur in several weeks to just a few months,” Dr. Leventhal said.
Of the 853 patients in this retrospective study, 463 (54.3%) were treated with nivolumab (Opdivo) and 242 (28.4%) were treated with pembrolizumab (Keytruda), both PD-1 blockers. Of the remainder, 112 (13.1%) received the PD-L1 blockers atezolizumab (Tecentriq), 29 (3.4%) received durvalumab (Imfinzi), and 7 (0.8%) received avelumab (Bavencio), Dr. Leventhal reported.
All these patients presented with both pruritus and vesiculobullous eruptions seen mainly on the trunk and extremities, while two patients had oral ulcerations. Other presentations included urticarial-predominant bullous pemphigoid, dyshidrosiform pemphigoid, and lichenoid papules and vesicles. The diagnosis was bullous pemphigoid in seven of nine cases, Dr. Leventhal said.
The best management approach for immune-related bullous disorders would be use of high-potency topical steroids to avoid systemic steroids and avoid interruptions in checkpoint inhibitor therapy, he pointed out. However, eight of the nine patients in this retrospective series required systemic steroids due to progression of the bullae, he added.
Several notable cases were described, including one patient refractory to prednisone and omalizumab who eventually achieved control with methotrexate, a second patient who was well controlled with omalizumab monotherapy and able to resume treatment with an anti PD-1 inhibitor, and another patient who responded to prednisone and dapsone maintenance therapy.
The immunotherapy treatment for cancer was interrupted in four of nine patients due to the bullous disorders, and was permanently discontinued in another four, Dr. Leventhal said.
It’s not clear why patients receiving cancer immunotherapy treatment develop bullous pemphigoid. However, the 180-kd bullous pemphigoid antigen (BP180) is expressed in melanoma and non-small cell lung cancer, which may lead to production of antibodies against tumor cell antigens that also impact the skin, according to Dr. Leventhal.
Further studies are needed to evaluate whether immune-related bullous disorders have any prognostic significance in cancer patients, he added.
Dr. Leventhal reported that he had no relevant disclosures.
REPORTING FROM WCD2019
Antimalarial may be effective, safe for erosive oral lichen planus
MILAN – an investigator reported at the World Congress of Dermatology.
In a small retrospective study, 85% of patients treated with the oral antimalarial agent had marked improvement or full remission, according to Ziyad Khamaysi, MD, a dermatologist at Rambam Health Care Campus, Haifa, Israel. Adverse effects leading to discontinuation occurred in a minority of patients and included elevated kidney function tests, hyperpigmentation, and an abnormal eye exam, he said.
“It may be a useful and convenient alternative treatment either as a monotherapy or where a rapid symptomatic relief during periods of exacerbations is needed,” he said in an oral presentation at the meeting.
A variety of medications have been used for palliation of oral lichen planus, including corticosteroids, cyclosporine, calcineurin inhibitors, retinoids, and biologics, but few have been evaluated in larger series of patients, he pointed out.
In the retrospective, nonrandomized study, 15 women and 6 men with erosive, recalcitrant oral lichen planus were treated with hydroxychloroquine (Plaquenil) at a dose of 200 mg/day, which was increased to 400 mg/day at one month. The mean age of the patients was 55 years.
In one patient, treatment was stopped after a month because of side effects, Dr. Khamaysi said. Among the remaining patients, 5 (25%) had a complete remission, while 12 (60%) had moderate to marked improvement, and 3 (15%) had no improvement, he said. In the patients who did respond, improvement was noted within 2-4 months of treatment initiation, he added. “Hydroxychloroquine kept the disease under control, with either full remission or marked improvement as long as the patients took it.”
Treatment appeared to be more effective in male patients and those under age 65 years, the investigator commented.
These data corroborate the findings of a smaller study evaluating hydroxychloroquine for oral lichen planus, published in 1993, according to Dr. Khamaysi. In that report, 9 of 10 patients had an “excellent” response to treatment, according to the investigator (J Am Acad Dermatol. 1993 Apr;28[4]:609-12).
Of the 10 patients in that study, 6 had erosions at the start of treatment, and 3 of these patients had complete healing with 3-6 months of therapy, and the other 3 had reepithelialization and at least a 50% reduction in lesion size, according to the report.
Dr. Khamaysi had no disclosures relevant to his presentation.
MILAN – an investigator reported at the World Congress of Dermatology.
In a small retrospective study, 85% of patients treated with the oral antimalarial agent had marked improvement or full remission, according to Ziyad Khamaysi, MD, a dermatologist at Rambam Health Care Campus, Haifa, Israel. Adverse effects leading to discontinuation occurred in a minority of patients and included elevated kidney function tests, hyperpigmentation, and an abnormal eye exam, he said.
“It may be a useful and convenient alternative treatment either as a monotherapy or where a rapid symptomatic relief during periods of exacerbations is needed,” he said in an oral presentation at the meeting.
A variety of medications have been used for palliation of oral lichen planus, including corticosteroids, cyclosporine, calcineurin inhibitors, retinoids, and biologics, but few have been evaluated in larger series of patients, he pointed out.
In the retrospective, nonrandomized study, 15 women and 6 men with erosive, recalcitrant oral lichen planus were treated with hydroxychloroquine (Plaquenil) at a dose of 200 mg/day, which was increased to 400 mg/day at one month. The mean age of the patients was 55 years.
In one patient, treatment was stopped after a month because of side effects, Dr. Khamaysi said. Among the remaining patients, 5 (25%) had a complete remission, while 12 (60%) had moderate to marked improvement, and 3 (15%) had no improvement, he said. In the patients who did respond, improvement was noted within 2-4 months of treatment initiation, he added. “Hydroxychloroquine kept the disease under control, with either full remission or marked improvement as long as the patients took it.”
Treatment appeared to be more effective in male patients and those under age 65 years, the investigator commented.
These data corroborate the findings of a smaller study evaluating hydroxychloroquine for oral lichen planus, published in 1993, according to Dr. Khamaysi. In that report, 9 of 10 patients had an “excellent” response to treatment, according to the investigator (J Am Acad Dermatol. 1993 Apr;28[4]:609-12).
Of the 10 patients in that study, 6 had erosions at the start of treatment, and 3 of these patients had complete healing with 3-6 months of therapy, and the other 3 had reepithelialization and at least a 50% reduction in lesion size, according to the report.
Dr. Khamaysi had no disclosures relevant to his presentation.
MILAN – an investigator reported at the World Congress of Dermatology.
In a small retrospective study, 85% of patients treated with the oral antimalarial agent had marked improvement or full remission, according to Ziyad Khamaysi, MD, a dermatologist at Rambam Health Care Campus, Haifa, Israel. Adverse effects leading to discontinuation occurred in a minority of patients and included elevated kidney function tests, hyperpigmentation, and an abnormal eye exam, he said.
“It may be a useful and convenient alternative treatment either as a monotherapy or where a rapid symptomatic relief during periods of exacerbations is needed,” he said in an oral presentation at the meeting.
A variety of medications have been used for palliation of oral lichen planus, including corticosteroids, cyclosporine, calcineurin inhibitors, retinoids, and biologics, but few have been evaluated in larger series of patients, he pointed out.
In the retrospective, nonrandomized study, 15 women and 6 men with erosive, recalcitrant oral lichen planus were treated with hydroxychloroquine (Plaquenil) at a dose of 200 mg/day, which was increased to 400 mg/day at one month. The mean age of the patients was 55 years.
In one patient, treatment was stopped after a month because of side effects, Dr. Khamaysi said. Among the remaining patients, 5 (25%) had a complete remission, while 12 (60%) had moderate to marked improvement, and 3 (15%) had no improvement, he said. In the patients who did respond, improvement was noted within 2-4 months of treatment initiation, he added. “Hydroxychloroquine kept the disease under control, with either full remission or marked improvement as long as the patients took it.”
Treatment appeared to be more effective in male patients and those under age 65 years, the investigator commented.
These data corroborate the findings of a smaller study evaluating hydroxychloroquine for oral lichen planus, published in 1993, according to Dr. Khamaysi. In that report, 9 of 10 patients had an “excellent” response to treatment, according to the investigator (J Am Acad Dermatol. 1993 Apr;28[4]:609-12).
Of the 10 patients in that study, 6 had erosions at the start of treatment, and 3 of these patients had complete healing with 3-6 months of therapy, and the other 3 had reepithelialization and at least a 50% reduction in lesion size, according to the report.
Dr. Khamaysi had no disclosures relevant to his presentation.
REPORTING FROM WCD2019
Ovarian reserve markers fall on isotretinoin, but rebound after stopping treatment
MILAN – according to data presented at the World Congress of Dermatology.
Although markers for ovarian reserve, including anti-Müllerian hormone (AMH) serum levels, ovarian volume, and antral follicle count, were significantly lower during a period of isotretinoin use than at baseline, these values were were not significantly different from pretreatment levels by 1 month after stopping isotretinoin.
For patients taking isotretinoin at a dose of 0.5 mg/kg/day, AMH levels fell from a baseline level of 5.29 ng/mL to 4.16 ng/mL during treatment, but rebounded to 4.77 ng/mL 1 month after stopping treatment (P less than .001 for difference between baseline and on-drug values), Tuğba Özkök Akbulut, MD, said during a late-breaking abstracts session.
For women taking isotretinoin 1 mg/kg/day, AMH levels went from 5.14 ng/mL at baseline to 4.24 ng/mL on treatment, to 4.65 ng/mL 1 month after treatment (P less than .001 for difference between baseline and on-drug values), reported Dr. Akbulut a dermatologist at the Haseki Training Research Hospital, Istanbul.
Women on the higher dose of isotretinoin had a similar pattern of decline while on treatment and rebound after ceasing isotretinoin for ovarian volume and antral follicle count (P less than .001 for all values). These differences were not statistically significant for women taking 0.5 mg/kg/day of isotretinoin, except for right ovarian volume (P = 0.013).
Although values were numerically lower for many markers of ovarian reserve after ceasing treatment, compared with baseline figures, these differences were not statistically significantly different. Markers of ovarian reserve did not change significantly for a control group of women without acne.
Dr. Akbulut and her colleagues conducted this prospective case-control study of 42 women of reproductive age who sought dermatologist care for severe acne unresponsive to conservative therapy; 26 women who did not have acne constituted the control group. Smokers, patients with thyroid disease, and those with known polycystic ovary syndrome were excluded from participation.
The women with acne received oral isotretinoin dosed either at 0.5 or 1.0 mg/kg/day, with treatment lasting 5-9 months. For each patient, treatment was stopped when the cumulative dose reached 120 mg/kg.
After an initial visit at which blood was collected from all participants to measure serum AMH levels, those receiving isotretinoin were seen every 4 weeks to check serum lipid and liver enzyme levels.
At the 3-month mark during the study period and 1 month after the end of completing isotretinoin treatment, or at the end of the study period for the control group, blood samples also were drawn for AMH levels.
To measure hormone levels, also blood was drawn between days 2 and 5 of the follicular phase of the menstrual cycle. Participants received ultrasounds to measure antral follicle count and ovarian volume between days 2 and 5 of the menstrual cycle at the initial visit, at the 3-month visit, and at the final visit. Results were interpreted by a trained gynecologist.
Patients, who were mostly in their early 20s, had a mean body mass index of about 22 kg/m2. Hormone levels, ovarian volume, and antral follicle count did not differ among study arms at baseline.
“There are contradictory reports in the literature regarding the effect of retinoic acid on ovarian reserve,” noted Dr. Akbulut. Some preclinical studies found that retinoic acid increased fertility and ovarian reserve in rodents; however, some human studies had shown lower serum AMH concentrations in patients using isotretinoin.
This new demonstration of the reversibility of isotretinoin’s negative effect on ovarian reserve helps clarify a confused picture in the medical literature, said Dr. Akbulut. “The results of our study demonstrated that systemic isotretinoin had a reversible effect on ovarian reserve.”
Dr. Akbulut reported no outside sources of funding and that she had no relevant financial disclosures.
MILAN – according to data presented at the World Congress of Dermatology.
Although markers for ovarian reserve, including anti-Müllerian hormone (AMH) serum levels, ovarian volume, and antral follicle count, were significantly lower during a period of isotretinoin use than at baseline, these values were were not significantly different from pretreatment levels by 1 month after stopping isotretinoin.
For patients taking isotretinoin at a dose of 0.5 mg/kg/day, AMH levels fell from a baseline level of 5.29 ng/mL to 4.16 ng/mL during treatment, but rebounded to 4.77 ng/mL 1 month after stopping treatment (P less than .001 for difference between baseline and on-drug values), Tuğba Özkök Akbulut, MD, said during a late-breaking abstracts session.
For women taking isotretinoin 1 mg/kg/day, AMH levels went from 5.14 ng/mL at baseline to 4.24 ng/mL on treatment, to 4.65 ng/mL 1 month after treatment (P less than .001 for difference between baseline and on-drug values), reported Dr. Akbulut a dermatologist at the Haseki Training Research Hospital, Istanbul.
Women on the higher dose of isotretinoin had a similar pattern of decline while on treatment and rebound after ceasing isotretinoin for ovarian volume and antral follicle count (P less than .001 for all values). These differences were not statistically significant for women taking 0.5 mg/kg/day of isotretinoin, except for right ovarian volume (P = 0.013).
Although values were numerically lower for many markers of ovarian reserve after ceasing treatment, compared with baseline figures, these differences were not statistically significantly different. Markers of ovarian reserve did not change significantly for a control group of women without acne.
Dr. Akbulut and her colleagues conducted this prospective case-control study of 42 women of reproductive age who sought dermatologist care for severe acne unresponsive to conservative therapy; 26 women who did not have acne constituted the control group. Smokers, patients with thyroid disease, and those with known polycystic ovary syndrome were excluded from participation.
The women with acne received oral isotretinoin dosed either at 0.5 or 1.0 mg/kg/day, with treatment lasting 5-9 months. For each patient, treatment was stopped when the cumulative dose reached 120 mg/kg.
After an initial visit at which blood was collected from all participants to measure serum AMH levels, those receiving isotretinoin were seen every 4 weeks to check serum lipid and liver enzyme levels.
At the 3-month mark during the study period and 1 month after the end of completing isotretinoin treatment, or at the end of the study period for the control group, blood samples also were drawn for AMH levels.
To measure hormone levels, also blood was drawn between days 2 and 5 of the follicular phase of the menstrual cycle. Participants received ultrasounds to measure antral follicle count and ovarian volume between days 2 and 5 of the menstrual cycle at the initial visit, at the 3-month visit, and at the final visit. Results were interpreted by a trained gynecologist.
Patients, who were mostly in their early 20s, had a mean body mass index of about 22 kg/m2. Hormone levels, ovarian volume, and antral follicle count did not differ among study arms at baseline.
“There are contradictory reports in the literature regarding the effect of retinoic acid on ovarian reserve,” noted Dr. Akbulut. Some preclinical studies found that retinoic acid increased fertility and ovarian reserve in rodents; however, some human studies had shown lower serum AMH concentrations in patients using isotretinoin.
This new demonstration of the reversibility of isotretinoin’s negative effect on ovarian reserve helps clarify a confused picture in the medical literature, said Dr. Akbulut. “The results of our study demonstrated that systemic isotretinoin had a reversible effect on ovarian reserve.”
Dr. Akbulut reported no outside sources of funding and that she had no relevant financial disclosures.
MILAN – according to data presented at the World Congress of Dermatology.
Although markers for ovarian reserve, including anti-Müllerian hormone (AMH) serum levels, ovarian volume, and antral follicle count, were significantly lower during a period of isotretinoin use than at baseline, these values were were not significantly different from pretreatment levels by 1 month after stopping isotretinoin.
For patients taking isotretinoin at a dose of 0.5 mg/kg/day, AMH levels fell from a baseline level of 5.29 ng/mL to 4.16 ng/mL during treatment, but rebounded to 4.77 ng/mL 1 month after stopping treatment (P less than .001 for difference between baseline and on-drug values), Tuğba Özkök Akbulut, MD, said during a late-breaking abstracts session.
For women taking isotretinoin 1 mg/kg/day, AMH levels went from 5.14 ng/mL at baseline to 4.24 ng/mL on treatment, to 4.65 ng/mL 1 month after treatment (P less than .001 for difference between baseline and on-drug values), reported Dr. Akbulut a dermatologist at the Haseki Training Research Hospital, Istanbul.
Women on the higher dose of isotretinoin had a similar pattern of decline while on treatment and rebound after ceasing isotretinoin for ovarian volume and antral follicle count (P less than .001 for all values). These differences were not statistically significant for women taking 0.5 mg/kg/day of isotretinoin, except for right ovarian volume (P = 0.013).
Although values were numerically lower for many markers of ovarian reserve after ceasing treatment, compared with baseline figures, these differences were not statistically significantly different. Markers of ovarian reserve did not change significantly for a control group of women without acne.
Dr. Akbulut and her colleagues conducted this prospective case-control study of 42 women of reproductive age who sought dermatologist care for severe acne unresponsive to conservative therapy; 26 women who did not have acne constituted the control group. Smokers, patients with thyroid disease, and those with known polycystic ovary syndrome were excluded from participation.
The women with acne received oral isotretinoin dosed either at 0.5 or 1.0 mg/kg/day, with treatment lasting 5-9 months. For each patient, treatment was stopped when the cumulative dose reached 120 mg/kg.
After an initial visit at which blood was collected from all participants to measure serum AMH levels, those receiving isotretinoin were seen every 4 weeks to check serum lipid and liver enzyme levels.
At the 3-month mark during the study period and 1 month after the end of completing isotretinoin treatment, or at the end of the study period for the control group, blood samples also were drawn for AMH levels.
To measure hormone levels, also blood was drawn between days 2 and 5 of the follicular phase of the menstrual cycle. Participants received ultrasounds to measure antral follicle count and ovarian volume between days 2 and 5 of the menstrual cycle at the initial visit, at the 3-month visit, and at the final visit. Results were interpreted by a trained gynecologist.
Patients, who were mostly in their early 20s, had a mean body mass index of about 22 kg/m2. Hormone levels, ovarian volume, and antral follicle count did not differ among study arms at baseline.
“There are contradictory reports in the literature regarding the effect of retinoic acid on ovarian reserve,” noted Dr. Akbulut. Some preclinical studies found that retinoic acid increased fertility and ovarian reserve in rodents; however, some human studies had shown lower serum AMH concentrations in patients using isotretinoin.
This new demonstration of the reversibility of isotretinoin’s negative effect on ovarian reserve helps clarify a confused picture in the medical literature, said Dr. Akbulut. “The results of our study demonstrated that systemic isotretinoin had a reversible effect on ovarian reserve.”
Dr. Akbulut reported no outside sources of funding and that she had no relevant financial disclosures.
REPORTING FROM WCD2019
Response endures in cemiplimab-treated patients with cutaneous SCC
MILAN – In an updated analysis of a pivotal phase 2 study, Michael R. Migden, MD, said at the World Congress of Dermatology.
Median duration of response was not reached at the time of the analysis, with probability of no progression or death above 80% at the 20-month mark, according to Dr. Migden, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston.
The safety profile of cemiplimab in this study was comparable with what has been reported for other anti–programmed death agents, he said in an oral presentation at the meeting.
While the median time to response was less than 2 months, about one-fifth of patients with locally advanced disease had “unconventional” late responses, occurring up to 10 months after starting treatment, Dr. Migden said. “If you’re just putting someone on some agent like this for a few months, and say, ‘well, I don’t see anything improving,’ it could be one of these patients in this 20% that deserve a little bit longer therapy.”
Cemiplimab (Libtayo) is the only Food and Drug Administration–approved treatment for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not suitable for curative surgery or radiation, Dr. Migden said in his presentation. That approval was based in part on previously reported results from the phase 2 study, known as EMPOWER-CSCC-1, which demonstrated that cemiplimab had substantial antitumor activity and durable responses.
In this update on EMPOWER-CSCC-1, Dr. Migden described results for 78 patients with locally advanced CSCC and 59 with metastatic CSCC who received weight-based intravenous cemiplimab for up to 96 weeks, with optional retreatment for those who had disease progression during the follow-up period. This was an older population, with a mean age of 72 years, and more than 80% were male. About one-third had prior systemic therapy, and the majority had prior cancer-related radiotherapy and surgery.
The objective response rate was 43.6% in the locally advanced group and 49.2% in the metastatic group; this numerical difference of less than 3 percentage points was not statistically significant, according to Dr. Migden.
More importantly, he said, the disease control rate (responses, stable disease, and noncomplete response/nonprogressive disease) was 79.5% in the locally advanced group and 71.2% in the metastatic group.
Time to response was “quite rapid” at a median of 1.9 months in both groups, though 7 of the 34 responders in the locally advanced group had unconventional late responses, taking 6-10 months to get to the point of response, Dr. Migden said.
The probability of being event free (such as no progression or death) has remained relatively flat, he added. In the metastatic cohort, event-free probability was 96.4% at 6 months, 88.9% at 12 months, and 82.5% at 20 months, with a 16.5-month median duration of follow-up, while in the locally advanced cohort, the event-free probability was 96.2% at 6 months, 87.8% at both 12 months and 20 months, with a median follow-up of 9.3 months.
Serious treatment-emergent adverse events were reported for 28.5% in these patients, though Dr. Migden noted that treatment emergent does not necessarily mean related to the study drug. Immune-related adverse events of grade 3 or greater were seen in 11.7% of patients, and adverse events leading to discontinuation were reported for 8.8%.
Dr. Migden reported disclosures related to Regeneron, Novartis, Genentech, Eli Lilly, and Sun Pharmaceutical.
MILAN – In an updated analysis of a pivotal phase 2 study, Michael R. Migden, MD, said at the World Congress of Dermatology.
Median duration of response was not reached at the time of the analysis, with probability of no progression or death above 80% at the 20-month mark, according to Dr. Migden, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston.
The safety profile of cemiplimab in this study was comparable with what has been reported for other anti–programmed death agents, he said in an oral presentation at the meeting.
While the median time to response was less than 2 months, about one-fifth of patients with locally advanced disease had “unconventional” late responses, occurring up to 10 months after starting treatment, Dr. Migden said. “If you’re just putting someone on some agent like this for a few months, and say, ‘well, I don’t see anything improving,’ it could be one of these patients in this 20% that deserve a little bit longer therapy.”
Cemiplimab (Libtayo) is the only Food and Drug Administration–approved treatment for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not suitable for curative surgery or radiation, Dr. Migden said in his presentation. That approval was based in part on previously reported results from the phase 2 study, known as EMPOWER-CSCC-1, which demonstrated that cemiplimab had substantial antitumor activity and durable responses.
In this update on EMPOWER-CSCC-1, Dr. Migden described results for 78 patients with locally advanced CSCC and 59 with metastatic CSCC who received weight-based intravenous cemiplimab for up to 96 weeks, with optional retreatment for those who had disease progression during the follow-up period. This was an older population, with a mean age of 72 years, and more than 80% were male. About one-third had prior systemic therapy, and the majority had prior cancer-related radiotherapy and surgery.
The objective response rate was 43.6% in the locally advanced group and 49.2% in the metastatic group; this numerical difference of less than 3 percentage points was not statistically significant, according to Dr. Migden.
More importantly, he said, the disease control rate (responses, stable disease, and noncomplete response/nonprogressive disease) was 79.5% in the locally advanced group and 71.2% in the metastatic group.
Time to response was “quite rapid” at a median of 1.9 months in both groups, though 7 of the 34 responders in the locally advanced group had unconventional late responses, taking 6-10 months to get to the point of response, Dr. Migden said.
The probability of being event free (such as no progression or death) has remained relatively flat, he added. In the metastatic cohort, event-free probability was 96.4% at 6 months, 88.9% at 12 months, and 82.5% at 20 months, with a 16.5-month median duration of follow-up, while in the locally advanced cohort, the event-free probability was 96.2% at 6 months, 87.8% at both 12 months and 20 months, with a median follow-up of 9.3 months.
Serious treatment-emergent adverse events were reported for 28.5% in these patients, though Dr. Migden noted that treatment emergent does not necessarily mean related to the study drug. Immune-related adverse events of grade 3 or greater were seen in 11.7% of patients, and adverse events leading to discontinuation were reported for 8.8%.
Dr. Migden reported disclosures related to Regeneron, Novartis, Genentech, Eli Lilly, and Sun Pharmaceutical.
MILAN – In an updated analysis of a pivotal phase 2 study, Michael R. Migden, MD, said at the World Congress of Dermatology.
Median duration of response was not reached at the time of the analysis, with probability of no progression or death above 80% at the 20-month mark, according to Dr. Migden, of the department of dermatology at the University of Texas MD Anderson Cancer Center, Houston.
The safety profile of cemiplimab in this study was comparable with what has been reported for other anti–programmed death agents, he said in an oral presentation at the meeting.
While the median time to response was less than 2 months, about one-fifth of patients with locally advanced disease had “unconventional” late responses, occurring up to 10 months after starting treatment, Dr. Migden said. “If you’re just putting someone on some agent like this for a few months, and say, ‘well, I don’t see anything improving,’ it could be one of these patients in this 20% that deserve a little bit longer therapy.”
Cemiplimab (Libtayo) is the only Food and Drug Administration–approved treatment for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not suitable for curative surgery or radiation, Dr. Migden said in his presentation. That approval was based in part on previously reported results from the phase 2 study, known as EMPOWER-CSCC-1, which demonstrated that cemiplimab had substantial antitumor activity and durable responses.
In this update on EMPOWER-CSCC-1, Dr. Migden described results for 78 patients with locally advanced CSCC and 59 with metastatic CSCC who received weight-based intravenous cemiplimab for up to 96 weeks, with optional retreatment for those who had disease progression during the follow-up period. This was an older population, with a mean age of 72 years, and more than 80% were male. About one-third had prior systemic therapy, and the majority had prior cancer-related radiotherapy and surgery.
The objective response rate was 43.6% in the locally advanced group and 49.2% in the metastatic group; this numerical difference of less than 3 percentage points was not statistically significant, according to Dr. Migden.
More importantly, he said, the disease control rate (responses, stable disease, and noncomplete response/nonprogressive disease) was 79.5% in the locally advanced group and 71.2% in the metastatic group.
Time to response was “quite rapid” at a median of 1.9 months in both groups, though 7 of the 34 responders in the locally advanced group had unconventional late responses, taking 6-10 months to get to the point of response, Dr. Migden said.
The probability of being event free (such as no progression or death) has remained relatively flat, he added. In the metastatic cohort, event-free probability was 96.4% at 6 months, 88.9% at 12 months, and 82.5% at 20 months, with a 16.5-month median duration of follow-up, while in the locally advanced cohort, the event-free probability was 96.2% at 6 months, 87.8% at both 12 months and 20 months, with a median follow-up of 9.3 months.
Serious treatment-emergent adverse events were reported for 28.5% in these patients, though Dr. Migden noted that treatment emergent does not necessarily mean related to the study drug. Immune-related adverse events of grade 3 or greater were seen in 11.7% of patients, and adverse events leading to discontinuation were reported for 8.8%.
Dr. Migden reported disclosures related to Regeneron, Novartis, Genentech, Eli Lilly, and Sun Pharmaceutical.
REPORTING FROM WCD2019
Visual examinations yield signs to guide vitiligo treatment
MILAN – Subtle signs beyond depigmentation alone can guide management of vitiligo, Michelle Rodrigues, MBBS, said at the World Congress of Dermatology.
Signs of high disease activity can be visually observed and, when found, can compel urgent treatment, Dr. Rodrigues said. “If we identify and understand these [signs, they] can change our management plan, and the patient’s outcomes ... picking these up quickly, getting the best response you can, can help our patients tremendously.”
To assess clinical signs of severity in vitiligo, “use the tools that you have in your practice – your dermatoscope, your Wood’s lamp.”
Showing an image of the leg of a patient with vitiligo, Dr. Rodrigues said, “I know this patient’s vitiligo is very, very active. Why?” Clues come when there are areas of hypopigmentation at the rim of lesions, with depigmentation at the center. The presence of pigmentation, hypopigmentation, and depigmentation within the same lesion indicates high disease activity. This finding is the trichrome sign, also called the “blurry borders” sign in some regions, said Dr. Rodrigues, a dermatologist in Melbourne and the founder of Chroma Dermatology, which specializes in treating pigment problems and diagnosing and managing skin conditions in patients with skin of color.
Next, Dr. Rodrigues said, look at hair growth within the vitiliginous area. “If you’re unable to see that clinically, it’s really important to get that dermatoscope onto the patient, and look within a patch, to see whether or not you can actually see white hairs or normal colored hairs,” she said. This finding will help to determine both treatment plan and prognosis, since leukotrichia is a marker of disease severity in vitiligo.
Be alert to Koebnerization, said Dr. Rodrigues; the presentation may be subtle. As an example, she shared an image of a patient with depigmented patches on the dorsum of each foot. It wasn’t until the patient removed her foot gear – rubber slide-type sandals with a single broad strap over the dorsum – that Dr. Rodrigues recognized that “there was clear Koebnerization from the constant friction as a result of the wearing of the shoes.
“This can also be seen when patients scratch themselves, as can be seen with the itch that vitiligo can sometimes cause,” she said.
She noted that about 10% of patients with vitiligo have pruritus as a prominent symptom. Here, she said, is where a Wood’s lamp can be helpful as well. “Sometimes we can’t appreciate the very, very subtle Koebnerization, especially in patients with lighter skin. Getting out that Wood’s lamp and looking at other areas of involvement is really important,” she said. Areas of high disease activity and signs of progression that might otherwise be missed will be more obvious under the ultraviolet light.
It’s important to look beyond the obvious patches of vitiligo to examine the surrounding skin. Searching for “confetti depigmentation” – tiny white dots of depigmentation scattered over the otherwise normally pigmented skin – also marks high disease activity. An area with these dots – each often only a few millimeters in diameter – is likely destined for rapid depigmentation unless aggressive treatment is started. “We know that without treating these areas there will be very, very rapid and aggressive depigmentation. And remember that in areas that have a paucity of hair follicles, it might be irreversible ... so recognizing these signs is absolutely critical.”
The final clue to highly active disease that’s likely to move quickly without intervention can be found at the border of a vitiligo lesion. Look for a fine rim of erythema and some scale, Dr. Rodrigues said. This sign is common, and often seen early in the disease course. When this erythematous region is biopsied, ”You’ll see an intense inflammatory response, with an interface dermatitis. Again, this tells us that the patient may have a poorer prognosis if we don’t commence treatment early on.”
As a final clinical tip, Dr. Rodrigues reminded attendees that when one sign of disease activity is seen, others are often present. A thorough clinical examination is needed to document aggressive disease. “Please make sure that if you find one, you’re looking for other signs of disease severity as well.”
Dr. Rodrigues reported that she had no disclosures relevant to her presentation.
MILAN – Subtle signs beyond depigmentation alone can guide management of vitiligo, Michelle Rodrigues, MBBS, said at the World Congress of Dermatology.
Signs of high disease activity can be visually observed and, when found, can compel urgent treatment, Dr. Rodrigues said. “If we identify and understand these [signs, they] can change our management plan, and the patient’s outcomes ... picking these up quickly, getting the best response you can, can help our patients tremendously.”
To assess clinical signs of severity in vitiligo, “use the tools that you have in your practice – your dermatoscope, your Wood’s lamp.”
Showing an image of the leg of a patient with vitiligo, Dr. Rodrigues said, “I know this patient’s vitiligo is very, very active. Why?” Clues come when there are areas of hypopigmentation at the rim of lesions, with depigmentation at the center. The presence of pigmentation, hypopigmentation, and depigmentation within the same lesion indicates high disease activity. This finding is the trichrome sign, also called the “blurry borders” sign in some regions, said Dr. Rodrigues, a dermatologist in Melbourne and the founder of Chroma Dermatology, which specializes in treating pigment problems and diagnosing and managing skin conditions in patients with skin of color.
Next, Dr. Rodrigues said, look at hair growth within the vitiliginous area. “If you’re unable to see that clinically, it’s really important to get that dermatoscope onto the patient, and look within a patch, to see whether or not you can actually see white hairs or normal colored hairs,” she said. This finding will help to determine both treatment plan and prognosis, since leukotrichia is a marker of disease severity in vitiligo.
Be alert to Koebnerization, said Dr. Rodrigues; the presentation may be subtle. As an example, she shared an image of a patient with depigmented patches on the dorsum of each foot. It wasn’t until the patient removed her foot gear – rubber slide-type sandals with a single broad strap over the dorsum – that Dr. Rodrigues recognized that “there was clear Koebnerization from the constant friction as a result of the wearing of the shoes.
“This can also be seen when patients scratch themselves, as can be seen with the itch that vitiligo can sometimes cause,” she said.
She noted that about 10% of patients with vitiligo have pruritus as a prominent symptom. Here, she said, is where a Wood’s lamp can be helpful as well. “Sometimes we can’t appreciate the very, very subtle Koebnerization, especially in patients with lighter skin. Getting out that Wood’s lamp and looking at other areas of involvement is really important,” she said. Areas of high disease activity and signs of progression that might otherwise be missed will be more obvious under the ultraviolet light.
It’s important to look beyond the obvious patches of vitiligo to examine the surrounding skin. Searching for “confetti depigmentation” – tiny white dots of depigmentation scattered over the otherwise normally pigmented skin – also marks high disease activity. An area with these dots – each often only a few millimeters in diameter – is likely destined for rapid depigmentation unless aggressive treatment is started. “We know that without treating these areas there will be very, very rapid and aggressive depigmentation. And remember that in areas that have a paucity of hair follicles, it might be irreversible ... so recognizing these signs is absolutely critical.”
The final clue to highly active disease that’s likely to move quickly without intervention can be found at the border of a vitiligo lesion. Look for a fine rim of erythema and some scale, Dr. Rodrigues said. This sign is common, and often seen early in the disease course. When this erythematous region is biopsied, ”You’ll see an intense inflammatory response, with an interface dermatitis. Again, this tells us that the patient may have a poorer prognosis if we don’t commence treatment early on.”
As a final clinical tip, Dr. Rodrigues reminded attendees that when one sign of disease activity is seen, others are often present. A thorough clinical examination is needed to document aggressive disease. “Please make sure that if you find one, you’re looking for other signs of disease severity as well.”
Dr. Rodrigues reported that she had no disclosures relevant to her presentation.
MILAN – Subtle signs beyond depigmentation alone can guide management of vitiligo, Michelle Rodrigues, MBBS, said at the World Congress of Dermatology.
Signs of high disease activity can be visually observed and, when found, can compel urgent treatment, Dr. Rodrigues said. “If we identify and understand these [signs, they] can change our management plan, and the patient’s outcomes ... picking these up quickly, getting the best response you can, can help our patients tremendously.”
To assess clinical signs of severity in vitiligo, “use the tools that you have in your practice – your dermatoscope, your Wood’s lamp.”
Showing an image of the leg of a patient with vitiligo, Dr. Rodrigues said, “I know this patient’s vitiligo is very, very active. Why?” Clues come when there are areas of hypopigmentation at the rim of lesions, with depigmentation at the center. The presence of pigmentation, hypopigmentation, and depigmentation within the same lesion indicates high disease activity. This finding is the trichrome sign, also called the “blurry borders” sign in some regions, said Dr. Rodrigues, a dermatologist in Melbourne and the founder of Chroma Dermatology, which specializes in treating pigment problems and diagnosing and managing skin conditions in patients with skin of color.
Next, Dr. Rodrigues said, look at hair growth within the vitiliginous area. “If you’re unable to see that clinically, it’s really important to get that dermatoscope onto the patient, and look within a patch, to see whether or not you can actually see white hairs or normal colored hairs,” she said. This finding will help to determine both treatment plan and prognosis, since leukotrichia is a marker of disease severity in vitiligo.
Be alert to Koebnerization, said Dr. Rodrigues; the presentation may be subtle. As an example, she shared an image of a patient with depigmented patches on the dorsum of each foot. It wasn’t until the patient removed her foot gear – rubber slide-type sandals with a single broad strap over the dorsum – that Dr. Rodrigues recognized that “there was clear Koebnerization from the constant friction as a result of the wearing of the shoes.
“This can also be seen when patients scratch themselves, as can be seen with the itch that vitiligo can sometimes cause,” she said.
She noted that about 10% of patients with vitiligo have pruritus as a prominent symptom. Here, she said, is where a Wood’s lamp can be helpful as well. “Sometimes we can’t appreciate the very, very subtle Koebnerization, especially in patients with lighter skin. Getting out that Wood’s lamp and looking at other areas of involvement is really important,” she said. Areas of high disease activity and signs of progression that might otherwise be missed will be more obvious under the ultraviolet light.
It’s important to look beyond the obvious patches of vitiligo to examine the surrounding skin. Searching for “confetti depigmentation” – tiny white dots of depigmentation scattered over the otherwise normally pigmented skin – also marks high disease activity. An area with these dots – each often only a few millimeters in diameter – is likely destined for rapid depigmentation unless aggressive treatment is started. “We know that without treating these areas there will be very, very rapid and aggressive depigmentation. And remember that in areas that have a paucity of hair follicles, it might be irreversible ... so recognizing these signs is absolutely critical.”
The final clue to highly active disease that’s likely to move quickly without intervention can be found at the border of a vitiligo lesion. Look for a fine rim of erythema and some scale, Dr. Rodrigues said. This sign is common, and often seen early in the disease course. When this erythematous region is biopsied, ”You’ll see an intense inflammatory response, with an interface dermatitis. Again, this tells us that the patient may have a poorer prognosis if we don’t commence treatment early on.”
As a final clinical tip, Dr. Rodrigues reminded attendees that when one sign of disease activity is seen, others are often present. A thorough clinical examination is needed to document aggressive disease. “Please make sure that if you find one, you’re looking for other signs of disease severity as well.”
Dr. Rodrigues reported that she had no disclosures relevant to her presentation.
EXPERT ANALYSIS FROM WCD2019
Skin plus GI adverse events with checkpoint inhibitors linked to risk of additional adverse events
MILAN – Patients on checkpoint inhibitors who experience both dermatologic and gastrointestinal side effects may be at increased risk of further immune-related adverse events, even though they may have better odds of a favorable outcome on the cancer treatment, results of a study presented at the World Congress of Dermatology suggest.
The co-occurrence of dermatologic and gastrointestinal immune-related adverse events (irAEs), which was usually seen early in the course of treatment, was independently associated with favorable progression-free and overall survival in this study, said Gabriel E. Molina, a medical student at Harvard Medical School, Boston.
Compared with patients with colitis alone, those patients who had both immune checkpoint inhibitor-induced rash and colitis were at significantly increased risk of additional irAEs affecting other organ systems, according to Mr. Molina. As a result, patients with both dermatologic and gastrointestinal irAEs may warrant earlier or closer monitoring, and need prompt referral to specialty care at first sign of emerging toxicity.
“We are really excited by the possibility that this co-occurrence of rash and colitis may be a unique and early clinical marker of both high-risk irAE patients and favorable treatment response,” Mr. Molina said.
The single-center, retrospective cohort study reported by Mr. Molina included 67 patients treated with immune checkpoint inhibitors who subsequently developed colitis. Of that group, 28 (or about 42%) also had a rash induced by that treatment.
The median time from starting treatment to onset of rash was 32.5 days, according to this report. Median onset of gastrointestinal toxicity was roughly similar between the patients who also had rash, at 73 days, as compared with patients who did not have rash, at 64 days. Most rashes were grade 1-2 in severity, and were treated with topical corticosteroids in 50% of cases or with nothing at all in 43%, according to the report.
The odds of developing an additional irAE such as hepatitis or hypophysitis was 18.5 times higher in the patients who had rash and colitis as compared with those with colitis only, the researchers also found.
In multivariate analysis, the patients with both rash and colitis had longer progression-free survival (hazard ratio, 0.37; 95% confidence interval, 0.17-0.80; P = .012) and overall survival (HR, 0.20; 95% CI, 0.05-0.83; P = .026), as compared with those with just colitis, Mr. Molina reported.
This isn’t the first study to show that the occurrence of an irAE foreshadows a better prognosis. “One promising observation that has consistently emerged in the literature is that cancer patients who develop these toxicities may actually have better oncologic outcomes than those who don’t,” Mr. Molina said.
Harvard now has a multidisciplinary group, including a dermatologist, dedicated to evaluating irAEs, he said. To date, however, a minority of patients are being referred, at which point, the dermatologic toxicity may be quite severe. “There’s this belief – which is generally true – that the rashes are mild and can be treated with topical steroids. So there’s often a delay before they see us.”
While larger studies are needed to validate the findings, just tallying up toxicities isn’t going far enough, according to the investigator.
“Our ultimate goal is to bridge the translational research gap, and to use thoughtful specimen collection to one day identify, ideally at the individualized level, the irAE risk level of the patient as soon as they start their immune checkpoint inhibitor, and then reprognosticate them each time they present with a new toxicity,” Mr. Molina said.
Mr. Molina reported no conflicts of interest.
MILAN – Patients on checkpoint inhibitors who experience both dermatologic and gastrointestinal side effects may be at increased risk of further immune-related adverse events, even though they may have better odds of a favorable outcome on the cancer treatment, results of a study presented at the World Congress of Dermatology suggest.
The co-occurrence of dermatologic and gastrointestinal immune-related adverse events (irAEs), which was usually seen early in the course of treatment, was independently associated with favorable progression-free and overall survival in this study, said Gabriel E. Molina, a medical student at Harvard Medical School, Boston.
Compared with patients with colitis alone, those patients who had both immune checkpoint inhibitor-induced rash and colitis were at significantly increased risk of additional irAEs affecting other organ systems, according to Mr. Molina. As a result, patients with both dermatologic and gastrointestinal irAEs may warrant earlier or closer monitoring, and need prompt referral to specialty care at first sign of emerging toxicity.
“We are really excited by the possibility that this co-occurrence of rash and colitis may be a unique and early clinical marker of both high-risk irAE patients and favorable treatment response,” Mr. Molina said.
The single-center, retrospective cohort study reported by Mr. Molina included 67 patients treated with immune checkpoint inhibitors who subsequently developed colitis. Of that group, 28 (or about 42%) also had a rash induced by that treatment.
The median time from starting treatment to onset of rash was 32.5 days, according to this report. Median onset of gastrointestinal toxicity was roughly similar between the patients who also had rash, at 73 days, as compared with patients who did not have rash, at 64 days. Most rashes were grade 1-2 in severity, and were treated with topical corticosteroids in 50% of cases or with nothing at all in 43%, according to the report.
The odds of developing an additional irAE such as hepatitis or hypophysitis was 18.5 times higher in the patients who had rash and colitis as compared with those with colitis only, the researchers also found.
In multivariate analysis, the patients with both rash and colitis had longer progression-free survival (hazard ratio, 0.37; 95% confidence interval, 0.17-0.80; P = .012) and overall survival (HR, 0.20; 95% CI, 0.05-0.83; P = .026), as compared with those with just colitis, Mr. Molina reported.
This isn’t the first study to show that the occurrence of an irAE foreshadows a better prognosis. “One promising observation that has consistently emerged in the literature is that cancer patients who develop these toxicities may actually have better oncologic outcomes than those who don’t,” Mr. Molina said.
Harvard now has a multidisciplinary group, including a dermatologist, dedicated to evaluating irAEs, he said. To date, however, a minority of patients are being referred, at which point, the dermatologic toxicity may be quite severe. “There’s this belief – which is generally true – that the rashes are mild and can be treated with topical steroids. So there’s often a delay before they see us.”
While larger studies are needed to validate the findings, just tallying up toxicities isn’t going far enough, according to the investigator.
“Our ultimate goal is to bridge the translational research gap, and to use thoughtful specimen collection to one day identify, ideally at the individualized level, the irAE risk level of the patient as soon as they start their immune checkpoint inhibitor, and then reprognosticate them each time they present with a new toxicity,” Mr. Molina said.
Mr. Molina reported no conflicts of interest.
MILAN – Patients on checkpoint inhibitors who experience both dermatologic and gastrointestinal side effects may be at increased risk of further immune-related adverse events, even though they may have better odds of a favorable outcome on the cancer treatment, results of a study presented at the World Congress of Dermatology suggest.
The co-occurrence of dermatologic and gastrointestinal immune-related adverse events (irAEs), which was usually seen early in the course of treatment, was independently associated with favorable progression-free and overall survival in this study, said Gabriel E. Molina, a medical student at Harvard Medical School, Boston.
Compared with patients with colitis alone, those patients who had both immune checkpoint inhibitor-induced rash and colitis were at significantly increased risk of additional irAEs affecting other organ systems, according to Mr. Molina. As a result, patients with both dermatologic and gastrointestinal irAEs may warrant earlier or closer monitoring, and need prompt referral to specialty care at first sign of emerging toxicity.
“We are really excited by the possibility that this co-occurrence of rash and colitis may be a unique and early clinical marker of both high-risk irAE patients and favorable treatment response,” Mr. Molina said.
The single-center, retrospective cohort study reported by Mr. Molina included 67 patients treated with immune checkpoint inhibitors who subsequently developed colitis. Of that group, 28 (or about 42%) also had a rash induced by that treatment.
The median time from starting treatment to onset of rash was 32.5 days, according to this report. Median onset of gastrointestinal toxicity was roughly similar between the patients who also had rash, at 73 days, as compared with patients who did not have rash, at 64 days. Most rashes were grade 1-2 in severity, and were treated with topical corticosteroids in 50% of cases or with nothing at all in 43%, according to the report.
The odds of developing an additional irAE such as hepatitis or hypophysitis was 18.5 times higher in the patients who had rash and colitis as compared with those with colitis only, the researchers also found.
In multivariate analysis, the patients with both rash and colitis had longer progression-free survival (hazard ratio, 0.37; 95% confidence interval, 0.17-0.80; P = .012) and overall survival (HR, 0.20; 95% CI, 0.05-0.83; P = .026), as compared with those with just colitis, Mr. Molina reported.
This isn’t the first study to show that the occurrence of an irAE foreshadows a better prognosis. “One promising observation that has consistently emerged in the literature is that cancer patients who develop these toxicities may actually have better oncologic outcomes than those who don’t,” Mr. Molina said.
Harvard now has a multidisciplinary group, including a dermatologist, dedicated to evaluating irAEs, he said. To date, however, a minority of patients are being referred, at which point, the dermatologic toxicity may be quite severe. “There’s this belief – which is generally true – that the rashes are mild and can be treated with topical steroids. So there’s often a delay before they see us.”
While larger studies are needed to validate the findings, just tallying up toxicities isn’t going far enough, according to the investigator.
“Our ultimate goal is to bridge the translational research gap, and to use thoughtful specimen collection to one day identify, ideally at the individualized level, the irAE risk level of the patient as soon as they start their immune checkpoint inhibitor, and then reprognosticate them each time they present with a new toxicity,” Mr. Molina said.
Mr. Molina reported no conflicts of interest.
REPORTING FROM WCD2019
Teletriage connects uninsured with timely dermatologist care
MILAN – and optimized primary care physicians’ care of nonreferred patients, Cory Simpson, MD, PhD, reported at the World Congress of Dermatology.
With implementation of teledermatology, patient wait times for specialist input dropped from 13.9 days to 1.6 days (P less than .00001).
By allowing dermatologists to evaluate photographs of lesions and perform their own triage of referrals from primary care physicians (PCPs), the teletriage pilot program reduced the number of patients for whom dermatology consults were deemed necessary and also allowed optimal management for the nonreferred patients, said Dr. Simpson, of the University of Pennsylvania, Philadelphia.
“Teledermatology has the potential to increase access to dermatologist-level care, especially for underserved patients,” he commented. “It allows us to educate primary care physicians in resource-limited settings, and it also allows us to avoid suboptimal care of skin disease by nonspecialists – especially the more judicious use of antimicrobial agents and corticosteroids.”
Dr. Simpson explained to the international audience that, for many in the United States, access to a dermatologist requires a lengthy wait that can extend to months.
In Philadelphia, University of Pennsylvania dermatology residents and attending physicians volunteer in an outreach program that serves an uninsured population of primarily Latino immigrants. Operating 1 or 2 evenings a month, the medical and surgical dermatology clinics can accommodate from 8-12 appointments per clinic.
The clinic had been overwhelmed with referrals from PCPs, but Dr. Simpson and his colleagues realized that many of the conditions they were seeing – verruca vulgaris, hand dermatitis, and psoriasis, for example – did not necessarily need a face-to-face dermatologic evaluation.
The AccessDerm app, available at no cost by the American Academy of Dermatology, allows PCPs and dermatologists to communicate and collaborate. “This is a store-and-forward program, meaning the primary physician takes the photos and sends them to an off-site dermatologist who can then review them at his or her convenience,” Dr. Simpson said. “It’s a smartphone-based app, so actually, while I was at this conference, even though I’m thousands of miles from Philadelphia, I got through three consults this morning on my smartphone. It’s a very convenient way to be a volunteer.”
The consultation is between the PCP and the dermatologist, he added. “It’s the dermatologist talking to the PCP, and the patient receives the care recommendations from their primary doctor – so there’s no direct communication with the patient.”
Using the app, PCPs photographed skin lesions and completed simple history and physical exam modules within the app. Then, Dr. Simpson and his dermatology colleagues reviewed the photos and pertinent information.
If diagnostic uncertainty persisted after the teledermatology review, or if Dr. Simpson and his colleagues judged that a procedure such as a biopsy or lesion destruction was required, then the patient was scheduled for an appointment, with an interim plan put in place. Otherwise, patients were managed by teledermatology alone.
Of the 131 patients involved in the pilot study, 48 (37%) were female; the average patient age was 31.7 years (range, 1-92 years).
About 40% of patients were seen for inflammatory conditions, and another 20% for nonpigmented neoplasms. Almost 18% were seen for infectious reasons, with the remainder divided between pigmented neoplasms, hair disorders, and other conditions.
It turned out, said Dr. Simpson, that about two-thirds (65%) of the teletriage consultations ended in a definitive plan not requiring a face-to-face dermatology appointment. About a quarter (23%) were deferred to an in-person dermatology appointment, and the remaining 12% had an interim plan while more information was gathered.
Of the 32 neoplasms addressed by the teletriage strategy, 21 (66%) were deferred to an in-person visit. By contrast, 24 of the 95 non–neoplastic teletriage encounters were deferred to an in-person visit (P less than .001).
Overall, the strategy opened up 18% more appointment slots for new patients, Dr. Simpson said.
As part of the teletriage process, PCPs provided their proposed plan of care before receiving a dermatologist’s advice. When comparing the PCP’s plan to the dermatologist’s final plan, he and his colleagues found that there was a complete change of plan for three-quarters of visits (76%). A partial change happened 14% of the time, and only one in ten patients had no change in treatment plan as a result of the teledermatology consult. “This indicates again that specialist input matters,” he noted.
“This also gives us an opportunity to educate primary care physicians,” Dr. Simpson said, pointing out that in replies, he and his dermatologist colleagues included information about common diagnoses, including first-line treatments and “worrisome features they should be thinking about.”
He and his collaborators found that proper treatment would have been provided 30% of the time without a teledermatology consult, but that patients would have been undertreated 27% of the time. Overtreatment would have occurred at a rate of 11%, and care would have been unnecessarily delayed for about one in four patients. Unnecessary ED visits were averted for 6% of patients with the teletriage approach.
Examples of undertreatment included use of a weak topical steroid, missing infections or the need for referral, and using a suboptimal acne regimen. On the other hand, Dr. Simpson said, overtreatment with unnecessary antibiotics, antifungals, and antivirals also was averted; on some occasions, the PCP plan for an oral corticosteroid or an overly potent topical steroid was shifted to a more appropriate plan by teledermatology.
In sum, said Dr. Simpson, “teletriage via AccessDerm allowed us to reduce by tenfold the wait time for specialist input in dermatology cases. We were able to remove almost two-thirds of people from the queue ... waiting for dermatology appointments, which was very helpful to our clinic.”
And most importantly, he added, “this allowed us to allocate the limited number of in-person appointments that we had at this volunteer clinic to those that were more complicated cases.”
Dr. Simpson reported that he had no relevant disclosures. The project was funded by Penn Medicine and the American Academy of Dermatology.
MILAN – and optimized primary care physicians’ care of nonreferred patients, Cory Simpson, MD, PhD, reported at the World Congress of Dermatology.
With implementation of teledermatology, patient wait times for specialist input dropped from 13.9 days to 1.6 days (P less than .00001).
By allowing dermatologists to evaluate photographs of lesions and perform their own triage of referrals from primary care physicians (PCPs), the teletriage pilot program reduced the number of patients for whom dermatology consults were deemed necessary and also allowed optimal management for the nonreferred patients, said Dr. Simpson, of the University of Pennsylvania, Philadelphia.
“Teledermatology has the potential to increase access to dermatologist-level care, especially for underserved patients,” he commented. “It allows us to educate primary care physicians in resource-limited settings, and it also allows us to avoid suboptimal care of skin disease by nonspecialists – especially the more judicious use of antimicrobial agents and corticosteroids.”
Dr. Simpson explained to the international audience that, for many in the United States, access to a dermatologist requires a lengthy wait that can extend to months.
In Philadelphia, University of Pennsylvania dermatology residents and attending physicians volunteer in an outreach program that serves an uninsured population of primarily Latino immigrants. Operating 1 or 2 evenings a month, the medical and surgical dermatology clinics can accommodate from 8-12 appointments per clinic.
The clinic had been overwhelmed with referrals from PCPs, but Dr. Simpson and his colleagues realized that many of the conditions they were seeing – verruca vulgaris, hand dermatitis, and psoriasis, for example – did not necessarily need a face-to-face dermatologic evaluation.
The AccessDerm app, available at no cost by the American Academy of Dermatology, allows PCPs and dermatologists to communicate and collaborate. “This is a store-and-forward program, meaning the primary physician takes the photos and sends them to an off-site dermatologist who can then review them at his or her convenience,” Dr. Simpson said. “It’s a smartphone-based app, so actually, while I was at this conference, even though I’m thousands of miles from Philadelphia, I got through three consults this morning on my smartphone. It’s a very convenient way to be a volunteer.”
The consultation is between the PCP and the dermatologist, he added. “It’s the dermatologist talking to the PCP, and the patient receives the care recommendations from their primary doctor – so there’s no direct communication with the patient.”
Using the app, PCPs photographed skin lesions and completed simple history and physical exam modules within the app. Then, Dr. Simpson and his dermatology colleagues reviewed the photos and pertinent information.
If diagnostic uncertainty persisted after the teledermatology review, or if Dr. Simpson and his colleagues judged that a procedure such as a biopsy or lesion destruction was required, then the patient was scheduled for an appointment, with an interim plan put in place. Otherwise, patients were managed by teledermatology alone.
Of the 131 patients involved in the pilot study, 48 (37%) were female; the average patient age was 31.7 years (range, 1-92 years).
About 40% of patients were seen for inflammatory conditions, and another 20% for nonpigmented neoplasms. Almost 18% were seen for infectious reasons, with the remainder divided between pigmented neoplasms, hair disorders, and other conditions.
It turned out, said Dr. Simpson, that about two-thirds (65%) of the teletriage consultations ended in a definitive plan not requiring a face-to-face dermatology appointment. About a quarter (23%) were deferred to an in-person dermatology appointment, and the remaining 12% had an interim plan while more information was gathered.
Of the 32 neoplasms addressed by the teletriage strategy, 21 (66%) were deferred to an in-person visit. By contrast, 24 of the 95 non–neoplastic teletriage encounters were deferred to an in-person visit (P less than .001).
Overall, the strategy opened up 18% more appointment slots for new patients, Dr. Simpson said.
As part of the teletriage process, PCPs provided their proposed plan of care before receiving a dermatologist’s advice. When comparing the PCP’s plan to the dermatologist’s final plan, he and his colleagues found that there was a complete change of plan for three-quarters of visits (76%). A partial change happened 14% of the time, and only one in ten patients had no change in treatment plan as a result of the teledermatology consult. “This indicates again that specialist input matters,” he noted.
“This also gives us an opportunity to educate primary care physicians,” Dr. Simpson said, pointing out that in replies, he and his dermatologist colleagues included information about common diagnoses, including first-line treatments and “worrisome features they should be thinking about.”
He and his collaborators found that proper treatment would have been provided 30% of the time without a teledermatology consult, but that patients would have been undertreated 27% of the time. Overtreatment would have occurred at a rate of 11%, and care would have been unnecessarily delayed for about one in four patients. Unnecessary ED visits were averted for 6% of patients with the teletriage approach.
Examples of undertreatment included use of a weak topical steroid, missing infections or the need for referral, and using a suboptimal acne regimen. On the other hand, Dr. Simpson said, overtreatment with unnecessary antibiotics, antifungals, and antivirals also was averted; on some occasions, the PCP plan for an oral corticosteroid or an overly potent topical steroid was shifted to a more appropriate plan by teledermatology.
In sum, said Dr. Simpson, “teletriage via AccessDerm allowed us to reduce by tenfold the wait time for specialist input in dermatology cases. We were able to remove almost two-thirds of people from the queue ... waiting for dermatology appointments, which was very helpful to our clinic.”
And most importantly, he added, “this allowed us to allocate the limited number of in-person appointments that we had at this volunteer clinic to those that were more complicated cases.”
Dr. Simpson reported that he had no relevant disclosures. The project was funded by Penn Medicine and the American Academy of Dermatology.
MILAN – and optimized primary care physicians’ care of nonreferred patients, Cory Simpson, MD, PhD, reported at the World Congress of Dermatology.
With implementation of teledermatology, patient wait times for specialist input dropped from 13.9 days to 1.6 days (P less than .00001).
By allowing dermatologists to evaluate photographs of lesions and perform their own triage of referrals from primary care physicians (PCPs), the teletriage pilot program reduced the number of patients for whom dermatology consults were deemed necessary and also allowed optimal management for the nonreferred patients, said Dr. Simpson, of the University of Pennsylvania, Philadelphia.
“Teledermatology has the potential to increase access to dermatologist-level care, especially for underserved patients,” he commented. “It allows us to educate primary care physicians in resource-limited settings, and it also allows us to avoid suboptimal care of skin disease by nonspecialists – especially the more judicious use of antimicrobial agents and corticosteroids.”
Dr. Simpson explained to the international audience that, for many in the United States, access to a dermatologist requires a lengthy wait that can extend to months.
In Philadelphia, University of Pennsylvania dermatology residents and attending physicians volunteer in an outreach program that serves an uninsured population of primarily Latino immigrants. Operating 1 or 2 evenings a month, the medical and surgical dermatology clinics can accommodate from 8-12 appointments per clinic.
The clinic had been overwhelmed with referrals from PCPs, but Dr. Simpson and his colleagues realized that many of the conditions they were seeing – verruca vulgaris, hand dermatitis, and psoriasis, for example – did not necessarily need a face-to-face dermatologic evaluation.
The AccessDerm app, available at no cost by the American Academy of Dermatology, allows PCPs and dermatologists to communicate and collaborate. “This is a store-and-forward program, meaning the primary physician takes the photos and sends them to an off-site dermatologist who can then review them at his or her convenience,” Dr. Simpson said. “It’s a smartphone-based app, so actually, while I was at this conference, even though I’m thousands of miles from Philadelphia, I got through three consults this morning on my smartphone. It’s a very convenient way to be a volunteer.”
The consultation is between the PCP and the dermatologist, he added. “It’s the dermatologist talking to the PCP, and the patient receives the care recommendations from their primary doctor – so there’s no direct communication with the patient.”
Using the app, PCPs photographed skin lesions and completed simple history and physical exam modules within the app. Then, Dr. Simpson and his dermatology colleagues reviewed the photos and pertinent information.
If diagnostic uncertainty persisted after the teledermatology review, or if Dr. Simpson and his colleagues judged that a procedure such as a biopsy or lesion destruction was required, then the patient was scheduled for an appointment, with an interim plan put in place. Otherwise, patients were managed by teledermatology alone.
Of the 131 patients involved in the pilot study, 48 (37%) were female; the average patient age was 31.7 years (range, 1-92 years).
About 40% of patients were seen for inflammatory conditions, and another 20% for nonpigmented neoplasms. Almost 18% were seen for infectious reasons, with the remainder divided between pigmented neoplasms, hair disorders, and other conditions.
It turned out, said Dr. Simpson, that about two-thirds (65%) of the teletriage consultations ended in a definitive plan not requiring a face-to-face dermatology appointment. About a quarter (23%) were deferred to an in-person dermatology appointment, and the remaining 12% had an interim plan while more information was gathered.
Of the 32 neoplasms addressed by the teletriage strategy, 21 (66%) were deferred to an in-person visit. By contrast, 24 of the 95 non–neoplastic teletriage encounters were deferred to an in-person visit (P less than .001).
Overall, the strategy opened up 18% more appointment slots for new patients, Dr. Simpson said.
As part of the teletriage process, PCPs provided their proposed plan of care before receiving a dermatologist’s advice. When comparing the PCP’s plan to the dermatologist’s final plan, he and his colleagues found that there was a complete change of plan for three-quarters of visits (76%). A partial change happened 14% of the time, and only one in ten patients had no change in treatment plan as a result of the teledermatology consult. “This indicates again that specialist input matters,” he noted.
“This also gives us an opportunity to educate primary care physicians,” Dr. Simpson said, pointing out that in replies, he and his dermatologist colleagues included information about common diagnoses, including first-line treatments and “worrisome features they should be thinking about.”
He and his collaborators found that proper treatment would have been provided 30% of the time without a teledermatology consult, but that patients would have been undertreated 27% of the time. Overtreatment would have occurred at a rate of 11%, and care would have been unnecessarily delayed for about one in four patients. Unnecessary ED visits were averted for 6% of patients with the teletriage approach.
Examples of undertreatment included use of a weak topical steroid, missing infections or the need for referral, and using a suboptimal acne regimen. On the other hand, Dr. Simpson said, overtreatment with unnecessary antibiotics, antifungals, and antivirals also was averted; on some occasions, the PCP plan for an oral corticosteroid or an overly potent topical steroid was shifted to a more appropriate plan by teledermatology.
In sum, said Dr. Simpson, “teletriage via AccessDerm allowed us to reduce by tenfold the wait time for specialist input in dermatology cases. We were able to remove almost two-thirds of people from the queue ... waiting for dermatology appointments, which was very helpful to our clinic.”
And most importantly, he added, “this allowed us to allocate the limited number of in-person appointments that we had at this volunteer clinic to those that were more complicated cases.”
Dr. Simpson reported that he had no relevant disclosures. The project was funded by Penn Medicine and the American Academy of Dermatology.
REPORTING FROM WCD2019