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Molecular insights suggest novel therapies for hidradenitis suppurativa
at the virtual annual congress of the European Academy of Dermatology and Venereology.
He presented highlights of a multicenter translational study, which utilized whole transcriptome analysis of lesional and nonlesional skin from patients with HS and normal controls along with quantitative real-time PCR and immunohistochemistry. The purpose was to further define the molecular taxonomy of this inflammatory disease. And while this objective was achieved, the results also underscored a truism regarding the painful and scarring disease: “HS is characterized by an ever-growing complexity, which translates into multiple potential mechanistic drivers,” observed Dr. da Costa, head of immunology precision medicine at AstraZeneca in Gothenburg, Sweden.
Indeed, the study identified a panel of immune-related drivers in HS that influence innate immunity and cell differentiation in follicular and epidermal keratinocytes. The research by Dr. da Costa and coinvestigators identified a broad array of promising novel therapeutic targets in HS.
“Our findings provide evidence of an inflammatory process coupled with impaired barrier function, altered epidermal cell differentiation, and possibly abnormal microbiome activity which can be seen at the follicular and epidermal keratinocytes and also to a minor degree at the level of the skin glands,” Dr. da Costa said.
There is a huge unmet need for new therapies for HS, since at present adalimumab (Humira) is the only approved medication for this debilitating inflammatory disease. Some good news that emerged from this translational study is that some of the novel molecular mediators implicated in HS are targeted by multiple Food and Drug Administration–approved therapies that have other indications. From a drug development standpoint, repurposing a commercially available drug for a novel indication is a much more efficient and less costly endeavor than is necessary to establish the safety and efficacy of an unproven new agent.
The translational work demonstrated that the proteins calgranulin-A and -B and serpin-B4 were strongly expressed in the hair root sheaths of patients with HS. Connexin-32 and koebnerisin were present in stratum granulosum, matrix metallopeptidase-9 was strongly expressed in resident monocytes, small prolin-rich protein 3 in apocrine sweat glands and ducts as well as in sebaceous glands and ducts, and transcobalamin-1 was prominent in stratum spinosum.
Of the 19 key molecular mediators of HS identified in the study, FDA-approved agents are already available that target 12 of them. For example, apremilast (Otezla) targets interferon-gamma and tumor necrosis factor–alpha. Gentamicin targets growth arrest-specific 6 (GAS6) and interleukin-17 (IL-17). Secukinumab (Cosentyx) and ixekizumab (Taltz) target IL-17A, and brodalumab (Siliq) more broadly targets IL-17A as well as all the other IL-17 receptors. Thalidomide targets hepatocyte growth factor (HGF) and TNF-alpha. Spironolactone targets androgen receptor (AR) and TNF-alpha. Colchicine targets tubulin. Anakinra (Kineret) homes in on the IL-1 receptor. And prednisone targets NFxB.
Other key molecular mediators of HS, which are targeted by commercially available drugs, include epidermal growth factor (EGF), macrophage colony-stimulating factor (MCSF), epiregulin (EREG), fibroblast growth factor 1 (FGF1), FGF2, insulin-like growth factor 2 (IGF2), and IL-6, according to Dr. da Costa.
In addition, clinical trials are underway in HS involving totally investigational agents, including several Janus kinase inhibitors and tyrosine kinase 2 inhibitors.
The work described by Dr. da Costa had multiple funding sources, including the European Hidradenitis Suppurativa Foundation, the University of Copenhagen, the Icahn School of Medicine at Mount Sinai, AstraZeneca, and the German Federal Ministry of Education and Research. Dr. da Costa is an employee of AstraZeneca, Gothenburg, Sweden.
at the virtual annual congress of the European Academy of Dermatology and Venereology.
He presented highlights of a multicenter translational study, which utilized whole transcriptome analysis of lesional and nonlesional skin from patients with HS and normal controls along with quantitative real-time PCR and immunohistochemistry. The purpose was to further define the molecular taxonomy of this inflammatory disease. And while this objective was achieved, the results also underscored a truism regarding the painful and scarring disease: “HS is characterized by an ever-growing complexity, which translates into multiple potential mechanistic drivers,” observed Dr. da Costa, head of immunology precision medicine at AstraZeneca in Gothenburg, Sweden.
Indeed, the study identified a panel of immune-related drivers in HS that influence innate immunity and cell differentiation in follicular and epidermal keratinocytes. The research by Dr. da Costa and coinvestigators identified a broad array of promising novel therapeutic targets in HS.
“Our findings provide evidence of an inflammatory process coupled with impaired barrier function, altered epidermal cell differentiation, and possibly abnormal microbiome activity which can be seen at the follicular and epidermal keratinocytes and also to a minor degree at the level of the skin glands,” Dr. da Costa said.
There is a huge unmet need for new therapies for HS, since at present adalimumab (Humira) is the only approved medication for this debilitating inflammatory disease. Some good news that emerged from this translational study is that some of the novel molecular mediators implicated in HS are targeted by multiple Food and Drug Administration–approved therapies that have other indications. From a drug development standpoint, repurposing a commercially available drug for a novel indication is a much more efficient and less costly endeavor than is necessary to establish the safety and efficacy of an unproven new agent.
The translational work demonstrated that the proteins calgranulin-A and -B and serpin-B4 were strongly expressed in the hair root sheaths of patients with HS. Connexin-32 and koebnerisin were present in stratum granulosum, matrix metallopeptidase-9 was strongly expressed in resident monocytes, small prolin-rich protein 3 in apocrine sweat glands and ducts as well as in sebaceous glands and ducts, and transcobalamin-1 was prominent in stratum spinosum.
Of the 19 key molecular mediators of HS identified in the study, FDA-approved agents are already available that target 12 of them. For example, apremilast (Otezla) targets interferon-gamma and tumor necrosis factor–alpha. Gentamicin targets growth arrest-specific 6 (GAS6) and interleukin-17 (IL-17). Secukinumab (Cosentyx) and ixekizumab (Taltz) target IL-17A, and brodalumab (Siliq) more broadly targets IL-17A as well as all the other IL-17 receptors. Thalidomide targets hepatocyte growth factor (HGF) and TNF-alpha. Spironolactone targets androgen receptor (AR) and TNF-alpha. Colchicine targets tubulin. Anakinra (Kineret) homes in on the IL-1 receptor. And prednisone targets NFxB.
Other key molecular mediators of HS, which are targeted by commercially available drugs, include epidermal growth factor (EGF), macrophage colony-stimulating factor (MCSF), epiregulin (EREG), fibroblast growth factor 1 (FGF1), FGF2, insulin-like growth factor 2 (IGF2), and IL-6, according to Dr. da Costa.
In addition, clinical trials are underway in HS involving totally investigational agents, including several Janus kinase inhibitors and tyrosine kinase 2 inhibitors.
The work described by Dr. da Costa had multiple funding sources, including the European Hidradenitis Suppurativa Foundation, the University of Copenhagen, the Icahn School of Medicine at Mount Sinai, AstraZeneca, and the German Federal Ministry of Education and Research. Dr. da Costa is an employee of AstraZeneca, Gothenburg, Sweden.
at the virtual annual congress of the European Academy of Dermatology and Venereology.
He presented highlights of a multicenter translational study, which utilized whole transcriptome analysis of lesional and nonlesional skin from patients with HS and normal controls along with quantitative real-time PCR and immunohistochemistry. The purpose was to further define the molecular taxonomy of this inflammatory disease. And while this objective was achieved, the results also underscored a truism regarding the painful and scarring disease: “HS is characterized by an ever-growing complexity, which translates into multiple potential mechanistic drivers,” observed Dr. da Costa, head of immunology precision medicine at AstraZeneca in Gothenburg, Sweden.
Indeed, the study identified a panel of immune-related drivers in HS that influence innate immunity and cell differentiation in follicular and epidermal keratinocytes. The research by Dr. da Costa and coinvestigators identified a broad array of promising novel therapeutic targets in HS.
“Our findings provide evidence of an inflammatory process coupled with impaired barrier function, altered epidermal cell differentiation, and possibly abnormal microbiome activity which can be seen at the follicular and epidermal keratinocytes and also to a minor degree at the level of the skin glands,” Dr. da Costa said.
There is a huge unmet need for new therapies for HS, since at present adalimumab (Humira) is the only approved medication for this debilitating inflammatory disease. Some good news that emerged from this translational study is that some of the novel molecular mediators implicated in HS are targeted by multiple Food and Drug Administration–approved therapies that have other indications. From a drug development standpoint, repurposing a commercially available drug for a novel indication is a much more efficient and less costly endeavor than is necessary to establish the safety and efficacy of an unproven new agent.
The translational work demonstrated that the proteins calgranulin-A and -B and serpin-B4 were strongly expressed in the hair root sheaths of patients with HS. Connexin-32 and koebnerisin were present in stratum granulosum, matrix metallopeptidase-9 was strongly expressed in resident monocytes, small prolin-rich protein 3 in apocrine sweat glands and ducts as well as in sebaceous glands and ducts, and transcobalamin-1 was prominent in stratum spinosum.
Of the 19 key molecular mediators of HS identified in the study, FDA-approved agents are already available that target 12 of them. For example, apremilast (Otezla) targets interferon-gamma and tumor necrosis factor–alpha. Gentamicin targets growth arrest-specific 6 (GAS6) and interleukin-17 (IL-17). Secukinumab (Cosentyx) and ixekizumab (Taltz) target IL-17A, and brodalumab (Siliq) more broadly targets IL-17A as well as all the other IL-17 receptors. Thalidomide targets hepatocyte growth factor (HGF) and TNF-alpha. Spironolactone targets androgen receptor (AR) and TNF-alpha. Colchicine targets tubulin. Anakinra (Kineret) homes in on the IL-1 receptor. And prednisone targets NFxB.
Other key molecular mediators of HS, which are targeted by commercially available drugs, include epidermal growth factor (EGF), macrophage colony-stimulating factor (MCSF), epiregulin (EREG), fibroblast growth factor 1 (FGF1), FGF2, insulin-like growth factor 2 (IGF2), and IL-6, according to Dr. da Costa.
In addition, clinical trials are underway in HS involving totally investigational agents, including several Janus kinase inhibitors and tyrosine kinase 2 inhibitors.
The work described by Dr. da Costa had multiple funding sources, including the European Hidradenitis Suppurativa Foundation, the University of Copenhagen, the Icahn School of Medicine at Mount Sinai, AstraZeneca, and the German Federal Ministry of Education and Research. Dr. da Costa is an employee of AstraZeneca, Gothenburg, Sweden.
FROM THE EADV CONGRESS
Anybody for a nanobody? Novel psoriasis therapy impresses in phase 2b
in a phase 2b randomized trial, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
A nanobody is a tiny antibody fragment with a much smaller molecular weight than the monoclonal antibodies utilized today in treating psoriasis or atopic dermatitis. The sonelokinab nanobody, derived from animals in the camel family, is a recombinant sequence-optimized nanobody specific for human IL-17F, IL-17A, the heterodimer IL-17A/F, and serum albumin. The binding to serum albumin give sonelokinab a lengthy half-life of 10-12 hours, which may be therapeutically relevant, explained Dr. Papp, president and founder of Probity Medical Research in Waterloo, Ont.
He presented the 24-week results of a multicenter, double-blind, double-dummy randomized trial including 313 North American and European adults with an average 18-year history of psoriasis and a baseline Psoriasis Area and Severity Index (PASI) score of about 21. They were randomized to one of six treatment arms for the first 12 weeks: subcutaneous injection of sonelokinab at 30, 60, or 120 mg at weeks 0, 2, 4, and 8; enhanced–loading-dose sonelokinab at 120 mg every 2 weeks through week 10; the IL-17A inhibitor secukinumab (Cosentyx) at its standard dosing as an active comparator; or placebo. Data analysis was by rigorous nonresponder imputation, meaning anyone who didn’t complete the study was scored as a nonresponder.
“This yields a conservative data analysis somewhat biased against sonelokinab,” the dermatologist pointed out.
The primary outcome in the trial was the week-12 rate of an Investigator’s Global Assessment score of 0 or 1, indicative of clear or almost clear skin. This was achieved in 88.2% of patients in the highest-dose arm of sonelokinab. That group also had a week-12 PASI 90 response rate of 76.5% and a PASI 100 response rate of 33.3%. By comparison, patients on standard-dose secukinumab had a less robust week-12 IGA 0/1 rate of 77.4%, a PASI 90 of 64.2%, and a PASI 100 of 28.3%. Of note, however, this secukinumab performance was better than seen in the 30-mg sonelokinab group, and comparable to outcomes with 60 mg of sonelokinab.
Dose escalation was performed from weeks 12-24. Patients with a week-12 IGA score greater than 1 after being on sonelokinab at 30 or 60 mg were upgraded to 120 mg at week 12 and again every 4 weeks thereafter. Placebo-treated controls were switched to 120 mg at weeks 12, 14, 16, and every 4 weeks thereafter. The group on the enhanced–loading-dose sonelokinab moved to 120 mg every 4 weeks, while those who had gotten four doses of sonelokinab at 120 mg during the first 12 weeks were switched to 120 mg every 8 weeks. The secukinumab group remained on the approved dosing through week 24.
At week 24, superior outcomes were seen in the enhanced–loading-dose sonelokinab group, with an IGA 0/1 response rate of 94.2%, a PASI 90 of 90.4%, and a PASI 100 of 56.9%. The corresponding week-24 rates in patients on 120 mg of sonelokinab every 8 weeks from week 12 on were 80.4%, 79.2%, and 40.4%, outcomes similar to those seen with secukinumab.
The rapidity of response to sonelokinab at 120 mg was striking, with approximately one-third of treated patients achieving a PASI 90 response by week 4.
“This could reflect the smaller molecular profile. There is possibly rapid increased absorption or bioavailability, quicker time to achieving serum half-life, better penetration into target tissue, and perhaps more effective engagement at the target. All of those things are possibilities. These are things that are yet to be explored, but it’s very enticing to see that uncharacteristically rapid initial response. It’s all very gratifying – and tantalizing,” Dr. Papp said in response to an audience question.
The safety profile of sonelokinab was reassuring. The most common adverse events were nasopharyngitis in 13.5% of patients and pruritus in 6.7%, with most cases being mild or moderate. As with other IL-17 blockers, there was an increase in oral candidiasis. This side effect appeared to occur in dose-dependent fashion: The incidence was zero in the 30-mg group, 1.9% with 60 mg, 3.8% with sonelokinab at 120 mg without an enhanced loading dose, and 5.9% with the enhanced loading dose.
The study was conducted by Avillion in partnership with Merck. Dr. Papp reported receiving research funding from and serving as a consultant to those and numerous other pharmaceutical companies.
in a phase 2b randomized trial, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
A nanobody is a tiny antibody fragment with a much smaller molecular weight than the monoclonal antibodies utilized today in treating psoriasis or atopic dermatitis. The sonelokinab nanobody, derived from animals in the camel family, is a recombinant sequence-optimized nanobody specific for human IL-17F, IL-17A, the heterodimer IL-17A/F, and serum albumin. The binding to serum albumin give sonelokinab a lengthy half-life of 10-12 hours, which may be therapeutically relevant, explained Dr. Papp, president and founder of Probity Medical Research in Waterloo, Ont.
He presented the 24-week results of a multicenter, double-blind, double-dummy randomized trial including 313 North American and European adults with an average 18-year history of psoriasis and a baseline Psoriasis Area and Severity Index (PASI) score of about 21. They were randomized to one of six treatment arms for the first 12 weeks: subcutaneous injection of sonelokinab at 30, 60, or 120 mg at weeks 0, 2, 4, and 8; enhanced–loading-dose sonelokinab at 120 mg every 2 weeks through week 10; the IL-17A inhibitor secukinumab (Cosentyx) at its standard dosing as an active comparator; or placebo. Data analysis was by rigorous nonresponder imputation, meaning anyone who didn’t complete the study was scored as a nonresponder.
“This yields a conservative data analysis somewhat biased against sonelokinab,” the dermatologist pointed out.
The primary outcome in the trial was the week-12 rate of an Investigator’s Global Assessment score of 0 or 1, indicative of clear or almost clear skin. This was achieved in 88.2% of patients in the highest-dose arm of sonelokinab. That group also had a week-12 PASI 90 response rate of 76.5% and a PASI 100 response rate of 33.3%. By comparison, patients on standard-dose secukinumab had a less robust week-12 IGA 0/1 rate of 77.4%, a PASI 90 of 64.2%, and a PASI 100 of 28.3%. Of note, however, this secukinumab performance was better than seen in the 30-mg sonelokinab group, and comparable to outcomes with 60 mg of sonelokinab.
Dose escalation was performed from weeks 12-24. Patients with a week-12 IGA score greater than 1 after being on sonelokinab at 30 or 60 mg were upgraded to 120 mg at week 12 and again every 4 weeks thereafter. Placebo-treated controls were switched to 120 mg at weeks 12, 14, 16, and every 4 weeks thereafter. The group on the enhanced–loading-dose sonelokinab moved to 120 mg every 4 weeks, while those who had gotten four doses of sonelokinab at 120 mg during the first 12 weeks were switched to 120 mg every 8 weeks. The secukinumab group remained on the approved dosing through week 24.
At week 24, superior outcomes were seen in the enhanced–loading-dose sonelokinab group, with an IGA 0/1 response rate of 94.2%, a PASI 90 of 90.4%, and a PASI 100 of 56.9%. The corresponding week-24 rates in patients on 120 mg of sonelokinab every 8 weeks from week 12 on were 80.4%, 79.2%, and 40.4%, outcomes similar to those seen with secukinumab.
The rapidity of response to sonelokinab at 120 mg was striking, with approximately one-third of treated patients achieving a PASI 90 response by week 4.
“This could reflect the smaller molecular profile. There is possibly rapid increased absorption or bioavailability, quicker time to achieving serum half-life, better penetration into target tissue, and perhaps more effective engagement at the target. All of those things are possibilities. These are things that are yet to be explored, but it’s very enticing to see that uncharacteristically rapid initial response. It’s all very gratifying – and tantalizing,” Dr. Papp said in response to an audience question.
The safety profile of sonelokinab was reassuring. The most common adverse events were nasopharyngitis in 13.5% of patients and pruritus in 6.7%, with most cases being mild or moderate. As with other IL-17 blockers, there was an increase in oral candidiasis. This side effect appeared to occur in dose-dependent fashion: The incidence was zero in the 30-mg group, 1.9% with 60 mg, 3.8% with sonelokinab at 120 mg without an enhanced loading dose, and 5.9% with the enhanced loading dose.
The study was conducted by Avillion in partnership with Merck. Dr. Papp reported receiving research funding from and serving as a consultant to those and numerous other pharmaceutical companies.
in a phase 2b randomized trial, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
A nanobody is a tiny antibody fragment with a much smaller molecular weight than the monoclonal antibodies utilized today in treating psoriasis or atopic dermatitis. The sonelokinab nanobody, derived from animals in the camel family, is a recombinant sequence-optimized nanobody specific for human IL-17F, IL-17A, the heterodimer IL-17A/F, and serum albumin. The binding to serum albumin give sonelokinab a lengthy half-life of 10-12 hours, which may be therapeutically relevant, explained Dr. Papp, president and founder of Probity Medical Research in Waterloo, Ont.
He presented the 24-week results of a multicenter, double-blind, double-dummy randomized trial including 313 North American and European adults with an average 18-year history of psoriasis and a baseline Psoriasis Area and Severity Index (PASI) score of about 21. They were randomized to one of six treatment arms for the first 12 weeks: subcutaneous injection of sonelokinab at 30, 60, or 120 mg at weeks 0, 2, 4, and 8; enhanced–loading-dose sonelokinab at 120 mg every 2 weeks through week 10; the IL-17A inhibitor secukinumab (Cosentyx) at its standard dosing as an active comparator; or placebo. Data analysis was by rigorous nonresponder imputation, meaning anyone who didn’t complete the study was scored as a nonresponder.
“This yields a conservative data analysis somewhat biased against sonelokinab,” the dermatologist pointed out.
The primary outcome in the trial was the week-12 rate of an Investigator’s Global Assessment score of 0 or 1, indicative of clear or almost clear skin. This was achieved in 88.2% of patients in the highest-dose arm of sonelokinab. That group also had a week-12 PASI 90 response rate of 76.5% and a PASI 100 response rate of 33.3%. By comparison, patients on standard-dose secukinumab had a less robust week-12 IGA 0/1 rate of 77.4%, a PASI 90 of 64.2%, and a PASI 100 of 28.3%. Of note, however, this secukinumab performance was better than seen in the 30-mg sonelokinab group, and comparable to outcomes with 60 mg of sonelokinab.
Dose escalation was performed from weeks 12-24. Patients with a week-12 IGA score greater than 1 after being on sonelokinab at 30 or 60 mg were upgraded to 120 mg at week 12 and again every 4 weeks thereafter. Placebo-treated controls were switched to 120 mg at weeks 12, 14, 16, and every 4 weeks thereafter. The group on the enhanced–loading-dose sonelokinab moved to 120 mg every 4 weeks, while those who had gotten four doses of sonelokinab at 120 mg during the first 12 weeks were switched to 120 mg every 8 weeks. The secukinumab group remained on the approved dosing through week 24.
At week 24, superior outcomes were seen in the enhanced–loading-dose sonelokinab group, with an IGA 0/1 response rate of 94.2%, a PASI 90 of 90.4%, and a PASI 100 of 56.9%. The corresponding week-24 rates in patients on 120 mg of sonelokinab every 8 weeks from week 12 on were 80.4%, 79.2%, and 40.4%, outcomes similar to those seen with secukinumab.
The rapidity of response to sonelokinab at 120 mg was striking, with approximately one-third of treated patients achieving a PASI 90 response by week 4.
“This could reflect the smaller molecular profile. There is possibly rapid increased absorption or bioavailability, quicker time to achieving serum half-life, better penetration into target tissue, and perhaps more effective engagement at the target. All of those things are possibilities. These are things that are yet to be explored, but it’s very enticing to see that uncharacteristically rapid initial response. It’s all very gratifying – and tantalizing,” Dr. Papp said in response to an audience question.
The safety profile of sonelokinab was reassuring. The most common adverse events were nasopharyngitis in 13.5% of patients and pruritus in 6.7%, with most cases being mild or moderate. As with other IL-17 blockers, there was an increase in oral candidiasis. This side effect appeared to occur in dose-dependent fashion: The incidence was zero in the 30-mg group, 1.9% with 60 mg, 3.8% with sonelokinab at 120 mg without an enhanced loading dose, and 5.9% with the enhanced loading dose.
The study was conducted by Avillion in partnership with Merck. Dr. Papp reported receiving research funding from and serving as a consultant to those and numerous other pharmaceutical companies.
FROM the eadv congress
Adalimumab enhances primary wound closure after HS surgery
, a pilot study suggests.
“Our experience suggests that under the effects of treatment with adalimumab, wound healing disorders with primary wound closure occur less often. And primary wound closure offers advantages over secondary wound healing: shorter length of inpatient stay, lower morbidity, fewer functional problems, and better quality of life,” Gefion Girbig, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
She noted that primary wound closure following surgery for HS is controversial. For example, current German guidelines recommend complete surgical excision of HS lesions, followed by secondary wound healing; the guidelines advise against primary wound closure. But those guidelines were issued back in 2012, years before adalimumab (Humira) achieved regulatory approval as the first and to date only medication indicated for treatment of HS.
Experts agree that while adalimumab has been a difference maker for many patients with HS, surgery is still often necessary. And many surgeons prefer secondary wound healing in HS. That’s because healing by first intention has historically often resulted in complications involving wound healing disorders and infection. These complications necessitate loosening of the primary closure to permit further wound healing by second intention, with a resultant prolonged healing time, explained Dr. Girbig, of the Institute for Health Sciences Research in Dermatology and Nursing at University Medical Center Hamburg-Eppendorf (Germany).
She and her coinvestigators hypothesized that the disordered wound healing is a consequence of the underlying inflammatory disease that lies at the core of HS, and that quelling the inflammation with adalimumab for at least 6 months before performing surgery with primary closure while the anti-TNF therapy continues would reduce the incidence of wound healing disorders.
This was borne out in the group’s small observational pilot study. It included 10 patients with HS who underwent surgery only after at least 6 months on adalimumab. Six had surgery for axillary HS and four for inguinal disease. Only 2 of the 10 developed a wound healing disorder. Both had surgical reconstruction in the inguinal area. Neither case involved infection. Surgical management entailed opening part of the suture to allow simultaneous secondary wound closure.
This 20% incidence of disordered wound healing when primary closure was carried out while systemic inflammation was controlled via adalimumab is markedly lower than rates reported using primary closure without adalimumab. Dr. Girbig and her coinvestigators are now conducting a larger controlled study to confirm their findings.
She reported having no financial conflicts regarding her study.
, a pilot study suggests.
“Our experience suggests that under the effects of treatment with adalimumab, wound healing disorders with primary wound closure occur less often. And primary wound closure offers advantages over secondary wound healing: shorter length of inpatient stay, lower morbidity, fewer functional problems, and better quality of life,” Gefion Girbig, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
She noted that primary wound closure following surgery for HS is controversial. For example, current German guidelines recommend complete surgical excision of HS lesions, followed by secondary wound healing; the guidelines advise against primary wound closure. But those guidelines were issued back in 2012, years before adalimumab (Humira) achieved regulatory approval as the first and to date only medication indicated for treatment of HS.
Experts agree that while adalimumab has been a difference maker for many patients with HS, surgery is still often necessary. And many surgeons prefer secondary wound healing in HS. That’s because healing by first intention has historically often resulted in complications involving wound healing disorders and infection. These complications necessitate loosening of the primary closure to permit further wound healing by second intention, with a resultant prolonged healing time, explained Dr. Girbig, of the Institute for Health Sciences Research in Dermatology and Nursing at University Medical Center Hamburg-Eppendorf (Germany).
She and her coinvestigators hypothesized that the disordered wound healing is a consequence of the underlying inflammatory disease that lies at the core of HS, and that quelling the inflammation with adalimumab for at least 6 months before performing surgery with primary closure while the anti-TNF therapy continues would reduce the incidence of wound healing disorders.
This was borne out in the group’s small observational pilot study. It included 10 patients with HS who underwent surgery only after at least 6 months on adalimumab. Six had surgery for axillary HS and four for inguinal disease. Only 2 of the 10 developed a wound healing disorder. Both had surgical reconstruction in the inguinal area. Neither case involved infection. Surgical management entailed opening part of the suture to allow simultaneous secondary wound closure.
This 20% incidence of disordered wound healing when primary closure was carried out while systemic inflammation was controlled via adalimumab is markedly lower than rates reported using primary closure without adalimumab. Dr. Girbig and her coinvestigators are now conducting a larger controlled study to confirm their findings.
She reported having no financial conflicts regarding her study.
, a pilot study suggests.
“Our experience suggests that under the effects of treatment with adalimumab, wound healing disorders with primary wound closure occur less often. And primary wound closure offers advantages over secondary wound healing: shorter length of inpatient stay, lower morbidity, fewer functional problems, and better quality of life,” Gefion Girbig, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
She noted that primary wound closure following surgery for HS is controversial. For example, current German guidelines recommend complete surgical excision of HS lesions, followed by secondary wound healing; the guidelines advise against primary wound closure. But those guidelines were issued back in 2012, years before adalimumab (Humira) achieved regulatory approval as the first and to date only medication indicated for treatment of HS.
Experts agree that while adalimumab has been a difference maker for many patients with HS, surgery is still often necessary. And many surgeons prefer secondary wound healing in HS. That’s because healing by first intention has historically often resulted in complications involving wound healing disorders and infection. These complications necessitate loosening of the primary closure to permit further wound healing by second intention, with a resultant prolonged healing time, explained Dr. Girbig, of the Institute for Health Sciences Research in Dermatology and Nursing at University Medical Center Hamburg-Eppendorf (Germany).
She and her coinvestigators hypothesized that the disordered wound healing is a consequence of the underlying inflammatory disease that lies at the core of HS, and that quelling the inflammation with adalimumab for at least 6 months before performing surgery with primary closure while the anti-TNF therapy continues would reduce the incidence of wound healing disorders.
This was borne out in the group’s small observational pilot study. It included 10 patients with HS who underwent surgery only after at least 6 months on adalimumab. Six had surgery for axillary HS and four for inguinal disease. Only 2 of the 10 developed a wound healing disorder. Both had surgical reconstruction in the inguinal area. Neither case involved infection. Surgical management entailed opening part of the suture to allow simultaneous secondary wound closure.
This 20% incidence of disordered wound healing when primary closure was carried out while systemic inflammation was controlled via adalimumab is markedly lower than rates reported using primary closure without adalimumab. Dr. Girbig and her coinvestigators are now conducting a larger controlled study to confirm their findings.
She reported having no financial conflicts regarding her study.
FROM THE EADV CONGRESS
Topical brepocitinib for atopic dermatitis meets endpoints in phase 2b study
, and with a safety profile essentially indistinguishable from vehicle cream in a phase 2b randomized trial, Megan N. Landis, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.
The study included 240 adolescents and adults with mild to moderate AD at 70 sites in the United States and nine other countries. Patients’ mean baseline Eczema Area and Severity Index (EASI) score was 7.3, with 9.2% of their body surface area being involved. Participants were equally split between mild and moderate disease. They were randomized to 6 weeks of double-blind treatment in one of eight study arms: once-daily topical brepocitinib at a concentration of 0.1%, 0.3%, 1%, or 3%; twice-daily brepocitinib at 1% or 3%; or once- or twice-daily vehicle cream.
The primary endpoint was change in EASI score from baseline to week 6. Brepocitinib 1% and 3% once daily and 1% twice daily outperformed vehicle, with EASI score reductions of 70.1%, 67.9%, and 75%, respectively, compared with a 44.4% decrease among those in the once-daily vehicle control group and a 47.6% reduction among those in the twice-daily vehicle control group, according to Dr. Landis, a dermatologist at the University of Louisville (Ky).
The key secondary efficacy endpoint was the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 or 1 – clear or almost clear skin – plus at least a 2-point reduction at week 6. This occurred in a dose-dependent fashion in 27.8%-44.4% of patients on once-daily brepocitinib, all significantly better results than the 10.8% rate in once-daily controls. Patients on the TYK2/JAK1 inhibitor at 0.3% twice daily had a 33.3% IGA response rate, versus 13.9% with twice-daily vehicle, also a significant difference.
A 90% reduction in EASI score at week 6, or EASI 90 response, occurred in a dose-dependent fashion in 27.8%-41.7% of patients on 0.3%, 1%, and 3% of patients on once-daily brepocitinib, all significantly better than the 10.8% rate with once-daily vehicle, and in 27% of patients on brepocitinib 1% twice daily, versus 8.3% with twice-daily vehicle.
Improvement in itch was another secondary endpoint. A clinically meaningful week-6 improvement of at least 4 points on the Peak Pruritus Numerical Rating Scale was documented in 45.2% of patients on 1% brepocitinib once daily, 50% on 3% once daily, and 40.7% on 1% brepocitinib twice daily, all significantly better than the roughly 17% itch response rate in controls.
Treatment-emergent adverse events were about one-third more frequent in controls than in brepocitinib-treated patients. These events were overwhelmingly mild and were similar in nature in the two groups. There was no dose-dependent increase in treatment-emergent adverse events in the brepocitinib patients. Moreover, no serious treatment-emergent adverse events occurred during the study, nor were there any cases of herpes zoster or malignancies, and no changes in laboratory parameters or ECG findings.
Pfizer sponsored the phase 2b AD trial of the topical TYK2/JAK1 inhibitor, which is also in phase 2 studies for psoriatic arthritis, psoriasis, lupus, and alopecia areata.
Dr. Landis reported serving as a paid investigator for Pfizer and numerous other pharmaceutical companies.
, and with a safety profile essentially indistinguishable from vehicle cream in a phase 2b randomized trial, Megan N. Landis, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.
The study included 240 adolescents and adults with mild to moderate AD at 70 sites in the United States and nine other countries. Patients’ mean baseline Eczema Area and Severity Index (EASI) score was 7.3, with 9.2% of their body surface area being involved. Participants were equally split between mild and moderate disease. They were randomized to 6 weeks of double-blind treatment in one of eight study arms: once-daily topical brepocitinib at a concentration of 0.1%, 0.3%, 1%, or 3%; twice-daily brepocitinib at 1% or 3%; or once- or twice-daily vehicle cream.
The primary endpoint was change in EASI score from baseline to week 6. Brepocitinib 1% and 3% once daily and 1% twice daily outperformed vehicle, with EASI score reductions of 70.1%, 67.9%, and 75%, respectively, compared with a 44.4% decrease among those in the once-daily vehicle control group and a 47.6% reduction among those in the twice-daily vehicle control group, according to Dr. Landis, a dermatologist at the University of Louisville (Ky).
The key secondary efficacy endpoint was the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 or 1 – clear or almost clear skin – plus at least a 2-point reduction at week 6. This occurred in a dose-dependent fashion in 27.8%-44.4% of patients on once-daily brepocitinib, all significantly better results than the 10.8% rate in once-daily controls. Patients on the TYK2/JAK1 inhibitor at 0.3% twice daily had a 33.3% IGA response rate, versus 13.9% with twice-daily vehicle, also a significant difference.
A 90% reduction in EASI score at week 6, or EASI 90 response, occurred in a dose-dependent fashion in 27.8%-41.7% of patients on 0.3%, 1%, and 3% of patients on once-daily brepocitinib, all significantly better than the 10.8% rate with once-daily vehicle, and in 27% of patients on brepocitinib 1% twice daily, versus 8.3% with twice-daily vehicle.
Improvement in itch was another secondary endpoint. A clinically meaningful week-6 improvement of at least 4 points on the Peak Pruritus Numerical Rating Scale was documented in 45.2% of patients on 1% brepocitinib once daily, 50% on 3% once daily, and 40.7% on 1% brepocitinib twice daily, all significantly better than the roughly 17% itch response rate in controls.
Treatment-emergent adverse events were about one-third more frequent in controls than in brepocitinib-treated patients. These events were overwhelmingly mild and were similar in nature in the two groups. There was no dose-dependent increase in treatment-emergent adverse events in the brepocitinib patients. Moreover, no serious treatment-emergent adverse events occurred during the study, nor were there any cases of herpes zoster or malignancies, and no changes in laboratory parameters or ECG findings.
Pfizer sponsored the phase 2b AD trial of the topical TYK2/JAK1 inhibitor, which is also in phase 2 studies for psoriatic arthritis, psoriasis, lupus, and alopecia areata.
Dr. Landis reported serving as a paid investigator for Pfizer and numerous other pharmaceutical companies.
, and with a safety profile essentially indistinguishable from vehicle cream in a phase 2b randomized trial, Megan N. Landis, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.
The study included 240 adolescents and adults with mild to moderate AD at 70 sites in the United States and nine other countries. Patients’ mean baseline Eczema Area and Severity Index (EASI) score was 7.3, with 9.2% of their body surface area being involved. Participants were equally split between mild and moderate disease. They were randomized to 6 weeks of double-blind treatment in one of eight study arms: once-daily topical brepocitinib at a concentration of 0.1%, 0.3%, 1%, or 3%; twice-daily brepocitinib at 1% or 3%; or once- or twice-daily vehicle cream.
The primary endpoint was change in EASI score from baseline to week 6. Brepocitinib 1% and 3% once daily and 1% twice daily outperformed vehicle, with EASI score reductions of 70.1%, 67.9%, and 75%, respectively, compared with a 44.4% decrease among those in the once-daily vehicle control group and a 47.6% reduction among those in the twice-daily vehicle control group, according to Dr. Landis, a dermatologist at the University of Louisville (Ky).
The key secondary efficacy endpoint was the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 or 1 – clear or almost clear skin – plus at least a 2-point reduction at week 6. This occurred in a dose-dependent fashion in 27.8%-44.4% of patients on once-daily brepocitinib, all significantly better results than the 10.8% rate in once-daily controls. Patients on the TYK2/JAK1 inhibitor at 0.3% twice daily had a 33.3% IGA response rate, versus 13.9% with twice-daily vehicle, also a significant difference.
A 90% reduction in EASI score at week 6, or EASI 90 response, occurred in a dose-dependent fashion in 27.8%-41.7% of patients on 0.3%, 1%, and 3% of patients on once-daily brepocitinib, all significantly better than the 10.8% rate with once-daily vehicle, and in 27% of patients on brepocitinib 1% twice daily, versus 8.3% with twice-daily vehicle.
Improvement in itch was another secondary endpoint. A clinically meaningful week-6 improvement of at least 4 points on the Peak Pruritus Numerical Rating Scale was documented in 45.2% of patients on 1% brepocitinib once daily, 50% on 3% once daily, and 40.7% on 1% brepocitinib twice daily, all significantly better than the roughly 17% itch response rate in controls.
Treatment-emergent adverse events were about one-third more frequent in controls than in brepocitinib-treated patients. These events were overwhelmingly mild and were similar in nature in the two groups. There was no dose-dependent increase in treatment-emergent adverse events in the brepocitinib patients. Moreover, no serious treatment-emergent adverse events occurred during the study, nor were there any cases of herpes zoster or malignancies, and no changes in laboratory parameters or ECG findings.
Pfizer sponsored the phase 2b AD trial of the topical TYK2/JAK1 inhibitor, which is also in phase 2 studies for psoriatic arthritis, psoriasis, lupus, and alopecia areata.
Dr. Landis reported serving as a paid investigator for Pfizer and numerous other pharmaceutical companies.
FROM THE EADV CONGRESS
Expert highlights advances in DRESS
Mounting evidence suggests , Sarah Walsh, MD, said at the virtual annual congress of the European Academy of Dermatology and Venereology.
The standard dictum has been that diagnosis of this severe T-cell-mediated drug reaction requires more than a 2-week delay in symptom onset following initial drug intake. But this can steer physicians in the wrong direction and lead to stopping an innocent drug while the true culprit medication remains on board. This adversely affects patient prognosis, since a longer duration of drug exposure after symptom onset is associated with increased hospital length of stay and greater mortality risk, explained Dr. Walsh, clinical lead for dermatology at King’s College Hospital, London.
In addition to . These include clues provided by rash morphology and histopathology, HLA testing, and a novel scoring system to assess DRESS severity and the risk of potentially fatal cytomegalovirus reactivation.
Short-delay DRESS onset
In a retrospective study of 41 patients with a first episode of DRESS in three French dermatology departments, 14 (34%) had onset within 15 days or less of initial exposure to the causative drug. In 6 of 14 patients in the rapid-onset group the offending drug was an antibiotic, while in another 5 the culprit was iodinated contrast media. In the delayed-onset DRESS group, the chief sensitizers were allopurinol in 8 patients, lamotrigine in 6, carbamazepine in 4, and sulfasalazine in 2; of note, none of these 4 delayed-onset DRESS drugs were implicated in any cases of rapid-onset DRESS. There were no differences in the clinical manifestations of DRESS between the rapid- and delayed-onset groups.
Similarly, dermatologists at Government Medical College in Kerala, India, reported in a retrospective study of 100 consecutive patients with DRESS, the drug reaction emerged within 2 weeks after starting the culprit medication in 36% of cases. Indeed, 11 patients became symptomatic within 3-7 days after beginning the medication; in 10 of the 11 cases, the offending agent was an antibiotic, and in 1 patient it was terbinafine. In the 25 cases of DRESS that arose on day 8-14 of drug therapy, the culprit was phenytoin in 14, antibiotics in 6, and 1 each for clopidogrel, hydroxychloroquine, sodium valproate, lamotrigine, and vitamin D3.
Both groups of investigators concluded that a short time lag between starting a drug and development of symptoms of a drug reaction shouldn’t rule out DRESS as a possibility provided other criteria consistent with the diagnosis are present. Hallmarks of DRESS include an acute extensive rash, fever greater than 38 degrees C, enlarged lymph nodes at two or more sites, internal organ involvement, a low platelet count, elevated eosinophils, and abnormal lymphocyte levels.
Rash morphology and histology as prognostic indicators
Dr. Walsh was the lead investigator in a study that identified four distinct patterns of skin involvement in patients with DRESS. The most common type of rash in this single-center retrospective study of 27 consecutive patients was an urticated papular exanthem, present in 13 of the 27 patients. An erythema multiforme-like reaction was present in 8, exfoliative erythroderma in 3, and a morbilliform erythema in 3 others. The worst prognosis was in the subgroup with an erythema multiforme-like rash.
All 27 patients had hepatic involvement, which was severe in 9 cases. Six of the 9 with severe liver impairment had an erythema multiforme-like rash, compared with just 2 of the 18 with mild or moderate liver involvement; thus, an erythema multiforme-like skin eruption was associated with a fivefold increased likelihood of severe hepatic involvement.
“It is a clinical sign that we take seriously at presentation if atypical target lesions are present,” the dermatologist said.
Separately, Taiwanese investigators compared clinical and histopathologic features in a study of 32 patients with DRESS and 17 with maculopapular exanthem. Interface vacuolization, which was present in 29 of the 32 patients with DRESS, was far more prominent than in the comparator group. Moreover, severe dyskeratosis was significantly associated with more severe liver impairment in the DRESS group.
HLA testing
Testing for HLA haplotypes associated with severe drug reactions has a useful role as a screening tool prior to prescribing selected high-risk drugs, Dr. Walsh said. For example, it’s known that 6.8% of individuals of European ancestry carry HLA-A*32:01, an allele that was strongly associated with an increased rate of vancomycin-associated DRESS in a case-control study at Vanderbilt University, Nashville, Tenn. Indeed, 19 of 23 individuals with vancomycin-associated DRESS were HLA-A*32:01 positive, compared with none of 46 vancomycin-tolerant controls. Nineteen percent of HLA-A*32:01-positive patients developed DRESS during treatment with vancomycin, and the drug reaction occurred within 4 weeks.
The investigators noted that testing for HLA-A*32:01 is also useful in DRESS occurring in patients on vancomycin and multiple other drugs because the test’s high negative predictive value may safely allow continued therapy with this potent antibiotic for Gram-positive infections.
A DRESS prognostic scoring system
Japanese researchers have developed a scoring system for DRESS for use in monitoring severity of the drug reaction, predicting prognosis, and estimating the risk of developing cytomegalovirus disease and its potentially fatal complications. The scoring system incorporates patient factors, including age, duration of drug exposure after symptom onset; rash characteristics, such as percentage of body surface area involved and presence or absence of erythroderma; appetite loss; and laboratory values.
“It yields a prognostic score that can be used to determine treatment choices, such as immediate intervention with anti-CMV agents. It’s a very useful tool,” Dr. Walsh said.
She reported having no financial conflicts regarding her presentation.
Mounting evidence suggests , Sarah Walsh, MD, said at the virtual annual congress of the European Academy of Dermatology and Venereology.
The standard dictum has been that diagnosis of this severe T-cell-mediated drug reaction requires more than a 2-week delay in symptom onset following initial drug intake. But this can steer physicians in the wrong direction and lead to stopping an innocent drug while the true culprit medication remains on board. This adversely affects patient prognosis, since a longer duration of drug exposure after symptom onset is associated with increased hospital length of stay and greater mortality risk, explained Dr. Walsh, clinical lead for dermatology at King’s College Hospital, London.
In addition to . These include clues provided by rash morphology and histopathology, HLA testing, and a novel scoring system to assess DRESS severity and the risk of potentially fatal cytomegalovirus reactivation.
Short-delay DRESS onset
In a retrospective study of 41 patients with a first episode of DRESS in three French dermatology departments, 14 (34%) had onset within 15 days or less of initial exposure to the causative drug. In 6 of 14 patients in the rapid-onset group the offending drug was an antibiotic, while in another 5 the culprit was iodinated contrast media. In the delayed-onset DRESS group, the chief sensitizers were allopurinol in 8 patients, lamotrigine in 6, carbamazepine in 4, and sulfasalazine in 2; of note, none of these 4 delayed-onset DRESS drugs were implicated in any cases of rapid-onset DRESS. There were no differences in the clinical manifestations of DRESS between the rapid- and delayed-onset groups.
Similarly, dermatologists at Government Medical College in Kerala, India, reported in a retrospective study of 100 consecutive patients with DRESS, the drug reaction emerged within 2 weeks after starting the culprit medication in 36% of cases. Indeed, 11 patients became symptomatic within 3-7 days after beginning the medication; in 10 of the 11 cases, the offending agent was an antibiotic, and in 1 patient it was terbinafine. In the 25 cases of DRESS that arose on day 8-14 of drug therapy, the culprit was phenytoin in 14, antibiotics in 6, and 1 each for clopidogrel, hydroxychloroquine, sodium valproate, lamotrigine, and vitamin D3.
Both groups of investigators concluded that a short time lag between starting a drug and development of symptoms of a drug reaction shouldn’t rule out DRESS as a possibility provided other criteria consistent with the diagnosis are present. Hallmarks of DRESS include an acute extensive rash, fever greater than 38 degrees C, enlarged lymph nodes at two or more sites, internal organ involvement, a low platelet count, elevated eosinophils, and abnormal lymphocyte levels.
Rash morphology and histology as prognostic indicators
Dr. Walsh was the lead investigator in a study that identified four distinct patterns of skin involvement in patients with DRESS. The most common type of rash in this single-center retrospective study of 27 consecutive patients was an urticated papular exanthem, present in 13 of the 27 patients. An erythema multiforme-like reaction was present in 8, exfoliative erythroderma in 3, and a morbilliform erythema in 3 others. The worst prognosis was in the subgroup with an erythema multiforme-like rash.
All 27 patients had hepatic involvement, which was severe in 9 cases. Six of the 9 with severe liver impairment had an erythema multiforme-like rash, compared with just 2 of the 18 with mild or moderate liver involvement; thus, an erythema multiforme-like skin eruption was associated with a fivefold increased likelihood of severe hepatic involvement.
“It is a clinical sign that we take seriously at presentation if atypical target lesions are present,” the dermatologist said.
Separately, Taiwanese investigators compared clinical and histopathologic features in a study of 32 patients with DRESS and 17 with maculopapular exanthem. Interface vacuolization, which was present in 29 of the 32 patients with DRESS, was far more prominent than in the comparator group. Moreover, severe dyskeratosis was significantly associated with more severe liver impairment in the DRESS group.
HLA testing
Testing for HLA haplotypes associated with severe drug reactions has a useful role as a screening tool prior to prescribing selected high-risk drugs, Dr. Walsh said. For example, it’s known that 6.8% of individuals of European ancestry carry HLA-A*32:01, an allele that was strongly associated with an increased rate of vancomycin-associated DRESS in a case-control study at Vanderbilt University, Nashville, Tenn. Indeed, 19 of 23 individuals with vancomycin-associated DRESS were HLA-A*32:01 positive, compared with none of 46 vancomycin-tolerant controls. Nineteen percent of HLA-A*32:01-positive patients developed DRESS during treatment with vancomycin, and the drug reaction occurred within 4 weeks.
The investigators noted that testing for HLA-A*32:01 is also useful in DRESS occurring in patients on vancomycin and multiple other drugs because the test’s high negative predictive value may safely allow continued therapy with this potent antibiotic for Gram-positive infections.
A DRESS prognostic scoring system
Japanese researchers have developed a scoring system for DRESS for use in monitoring severity of the drug reaction, predicting prognosis, and estimating the risk of developing cytomegalovirus disease and its potentially fatal complications. The scoring system incorporates patient factors, including age, duration of drug exposure after symptom onset; rash characteristics, such as percentage of body surface area involved and presence or absence of erythroderma; appetite loss; and laboratory values.
“It yields a prognostic score that can be used to determine treatment choices, such as immediate intervention with anti-CMV agents. It’s a very useful tool,” Dr. Walsh said.
She reported having no financial conflicts regarding her presentation.
Mounting evidence suggests , Sarah Walsh, MD, said at the virtual annual congress of the European Academy of Dermatology and Venereology.
The standard dictum has been that diagnosis of this severe T-cell-mediated drug reaction requires more than a 2-week delay in symptom onset following initial drug intake. But this can steer physicians in the wrong direction and lead to stopping an innocent drug while the true culprit medication remains on board. This adversely affects patient prognosis, since a longer duration of drug exposure after symptom onset is associated with increased hospital length of stay and greater mortality risk, explained Dr. Walsh, clinical lead for dermatology at King’s College Hospital, London.
In addition to . These include clues provided by rash morphology and histopathology, HLA testing, and a novel scoring system to assess DRESS severity and the risk of potentially fatal cytomegalovirus reactivation.
Short-delay DRESS onset
In a retrospective study of 41 patients with a first episode of DRESS in three French dermatology departments, 14 (34%) had onset within 15 days or less of initial exposure to the causative drug. In 6 of 14 patients in the rapid-onset group the offending drug was an antibiotic, while in another 5 the culprit was iodinated contrast media. In the delayed-onset DRESS group, the chief sensitizers were allopurinol in 8 patients, lamotrigine in 6, carbamazepine in 4, and sulfasalazine in 2; of note, none of these 4 delayed-onset DRESS drugs were implicated in any cases of rapid-onset DRESS. There were no differences in the clinical manifestations of DRESS between the rapid- and delayed-onset groups.
Similarly, dermatologists at Government Medical College in Kerala, India, reported in a retrospective study of 100 consecutive patients with DRESS, the drug reaction emerged within 2 weeks after starting the culprit medication in 36% of cases. Indeed, 11 patients became symptomatic within 3-7 days after beginning the medication; in 10 of the 11 cases, the offending agent was an antibiotic, and in 1 patient it was terbinafine. In the 25 cases of DRESS that arose on day 8-14 of drug therapy, the culprit was phenytoin in 14, antibiotics in 6, and 1 each for clopidogrel, hydroxychloroquine, sodium valproate, lamotrigine, and vitamin D3.
Both groups of investigators concluded that a short time lag between starting a drug and development of symptoms of a drug reaction shouldn’t rule out DRESS as a possibility provided other criteria consistent with the diagnosis are present. Hallmarks of DRESS include an acute extensive rash, fever greater than 38 degrees C, enlarged lymph nodes at two or more sites, internal organ involvement, a low platelet count, elevated eosinophils, and abnormal lymphocyte levels.
Rash morphology and histology as prognostic indicators
Dr. Walsh was the lead investigator in a study that identified four distinct patterns of skin involvement in patients with DRESS. The most common type of rash in this single-center retrospective study of 27 consecutive patients was an urticated papular exanthem, present in 13 of the 27 patients. An erythema multiforme-like reaction was present in 8, exfoliative erythroderma in 3, and a morbilliform erythema in 3 others. The worst prognosis was in the subgroup with an erythema multiforme-like rash.
All 27 patients had hepatic involvement, which was severe in 9 cases. Six of the 9 with severe liver impairment had an erythema multiforme-like rash, compared with just 2 of the 18 with mild or moderate liver involvement; thus, an erythema multiforme-like skin eruption was associated with a fivefold increased likelihood of severe hepatic involvement.
“It is a clinical sign that we take seriously at presentation if atypical target lesions are present,” the dermatologist said.
Separately, Taiwanese investigators compared clinical and histopathologic features in a study of 32 patients with DRESS and 17 with maculopapular exanthem. Interface vacuolization, which was present in 29 of the 32 patients with DRESS, was far more prominent than in the comparator group. Moreover, severe dyskeratosis was significantly associated with more severe liver impairment in the DRESS group.
HLA testing
Testing for HLA haplotypes associated with severe drug reactions has a useful role as a screening tool prior to prescribing selected high-risk drugs, Dr. Walsh said. For example, it’s known that 6.8% of individuals of European ancestry carry HLA-A*32:01, an allele that was strongly associated with an increased rate of vancomycin-associated DRESS in a case-control study at Vanderbilt University, Nashville, Tenn. Indeed, 19 of 23 individuals with vancomycin-associated DRESS were HLA-A*32:01 positive, compared with none of 46 vancomycin-tolerant controls. Nineteen percent of HLA-A*32:01-positive patients developed DRESS during treatment with vancomycin, and the drug reaction occurred within 4 weeks.
The investigators noted that testing for HLA-A*32:01 is also useful in DRESS occurring in patients on vancomycin and multiple other drugs because the test’s high negative predictive value may safely allow continued therapy with this potent antibiotic for Gram-positive infections.
A DRESS prognostic scoring system
Japanese researchers have developed a scoring system for DRESS for use in monitoring severity of the drug reaction, predicting prognosis, and estimating the risk of developing cytomegalovirus disease and its potentially fatal complications. The scoring system incorporates patient factors, including age, duration of drug exposure after symptom onset; rash characteristics, such as percentage of body surface area involved and presence or absence of erythroderma; appetite loss; and laboratory values.
“It yields a prognostic score that can be used to determine treatment choices, such as immediate intervention with anti-CMV agents. It’s a very useful tool,” Dr. Walsh said.
She reported having no financial conflicts regarding her presentation.
FROM THE EADV CONGRESS
Oral JAK1 inhibitor shows promise for hidradenitis suppurativa
A (HS) in a pair of small, randomized, phase 2 studies that established proof-of-concept for the novel agent, Afsaneh Alavi, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.
These favorable clinical findings were buttressed by a proteomic analysis demonstrating dose-dependent reductions in circulating inflammatory mediators, added Dr. Alavi, a dermatologist at the Mayo Clinic in Rochester, Minn.
The investigational oral small molecule, known for now as INCB54707, is 52 times more selective for JAK1 than JAK2.
Both multicenter studies entailed 8 weeks of active treatment with INCB54707 followed by a 4-week safety observation. In one study, 10 patients received 15 mg of the investigational agent once daily in open-label fashion. The other trial randomized 35 patients to the JAK1 inhibitor at 30 mg, 60 mg, or 90 mg per day or placebo. About 70% of participants in the studies had Hurley stage II HS; the rest were stage III.
Safety and tolerability were the primary outcomes in the two studies. One patient in the open-label study dropped out because of a flare of fibromyalgia. In the larger randomized trial, four patients – all in the group assigned to 90 mg/day of the JAK1 inhibitor – developed thrombocytopenia, resulting in temporary discontinuation of treatment for up to 2 weeks. In all four instances, the laboratory abnormality was reversed after temporary interruption of treatment, with no sequelae upon restarting the drug. There were no serious treatment-emergent adverse events in either study.
In the low-dose, open-label study, four of nine completers (44%) experienced a Hidradenitis Suppurativa Clinical Response (HiSCR) at week 8, defined as at least a 50% reduction in inflammatory lesion count with no increase in abscesses or draining fistulae compared to baseline. In the randomized trial, the week-8 HiSCR rate was 57% in placebo-treated controls, 56% in those on 30 mg/day or 60 mg/day of the JAK1 inhibitor, and significantly better at 88% in the group on 90 mg/day.
The rapidity of response to the JAK1 inhibitor was noteworthy. After just 1 week of treatment, an abscess and inflammatory nodule count of zero to two lesions was present in 22% of patients on INCB54707 at 60 mg/day and 29% of those on 90 mg/day, compared with none of the patients on 30 mg/day or placebo. At week 2, an abscess and nodule count of 0-2 was documented in 33% of participants on the JAK1 inhibitor at 30 mg/day, 58% at 60 mg/day, and 50% with 90 mg/day. At week 8, the rates were 57% with placebo, 44% with active treatment at 30 or 60 mg/day, and 63% in patients on 90 mg/day.
A dose-dependent significant improvement in Hidradenitis Suppurativa Quality of Life scores was documented in response to the JAK1 inhibitor.
There is an unmet need for effective therapies for HS, a chronic, extremely painful inflammatory condition with a large negative impact on quality of life. At present, the only Food and Drug Administration–approved medication for HS is the tumor necrosis factor inhibitor, adalimumab (Humira), noted Dr. Alavi. Ongoing studies are evaluating other JAK inhibitors, as well as TNF inhibitors and interleukin-17 and -23 blockers.
She reported receiving research funding from and serving as a consultant to Incyte, the studies’ sponsor, and more than a dozen other pharmaceutical companies.
A (HS) in a pair of small, randomized, phase 2 studies that established proof-of-concept for the novel agent, Afsaneh Alavi, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.
These favorable clinical findings were buttressed by a proteomic analysis demonstrating dose-dependent reductions in circulating inflammatory mediators, added Dr. Alavi, a dermatologist at the Mayo Clinic in Rochester, Minn.
The investigational oral small molecule, known for now as INCB54707, is 52 times more selective for JAK1 than JAK2.
Both multicenter studies entailed 8 weeks of active treatment with INCB54707 followed by a 4-week safety observation. In one study, 10 patients received 15 mg of the investigational agent once daily in open-label fashion. The other trial randomized 35 patients to the JAK1 inhibitor at 30 mg, 60 mg, or 90 mg per day or placebo. About 70% of participants in the studies had Hurley stage II HS; the rest were stage III.
Safety and tolerability were the primary outcomes in the two studies. One patient in the open-label study dropped out because of a flare of fibromyalgia. In the larger randomized trial, four patients – all in the group assigned to 90 mg/day of the JAK1 inhibitor – developed thrombocytopenia, resulting in temporary discontinuation of treatment for up to 2 weeks. In all four instances, the laboratory abnormality was reversed after temporary interruption of treatment, with no sequelae upon restarting the drug. There were no serious treatment-emergent adverse events in either study.
In the low-dose, open-label study, four of nine completers (44%) experienced a Hidradenitis Suppurativa Clinical Response (HiSCR) at week 8, defined as at least a 50% reduction in inflammatory lesion count with no increase in abscesses or draining fistulae compared to baseline. In the randomized trial, the week-8 HiSCR rate was 57% in placebo-treated controls, 56% in those on 30 mg/day or 60 mg/day of the JAK1 inhibitor, and significantly better at 88% in the group on 90 mg/day.
The rapidity of response to the JAK1 inhibitor was noteworthy. After just 1 week of treatment, an abscess and inflammatory nodule count of zero to two lesions was present in 22% of patients on INCB54707 at 60 mg/day and 29% of those on 90 mg/day, compared with none of the patients on 30 mg/day or placebo. At week 2, an abscess and nodule count of 0-2 was documented in 33% of participants on the JAK1 inhibitor at 30 mg/day, 58% at 60 mg/day, and 50% with 90 mg/day. At week 8, the rates were 57% with placebo, 44% with active treatment at 30 or 60 mg/day, and 63% in patients on 90 mg/day.
A dose-dependent significant improvement in Hidradenitis Suppurativa Quality of Life scores was documented in response to the JAK1 inhibitor.
There is an unmet need for effective therapies for HS, a chronic, extremely painful inflammatory condition with a large negative impact on quality of life. At present, the only Food and Drug Administration–approved medication for HS is the tumor necrosis factor inhibitor, adalimumab (Humira), noted Dr. Alavi. Ongoing studies are evaluating other JAK inhibitors, as well as TNF inhibitors and interleukin-17 and -23 blockers.
She reported receiving research funding from and serving as a consultant to Incyte, the studies’ sponsor, and more than a dozen other pharmaceutical companies.
A (HS) in a pair of small, randomized, phase 2 studies that established proof-of-concept for the novel agent, Afsaneh Alavi, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.
These favorable clinical findings were buttressed by a proteomic analysis demonstrating dose-dependent reductions in circulating inflammatory mediators, added Dr. Alavi, a dermatologist at the Mayo Clinic in Rochester, Minn.
The investigational oral small molecule, known for now as INCB54707, is 52 times more selective for JAK1 than JAK2.
Both multicenter studies entailed 8 weeks of active treatment with INCB54707 followed by a 4-week safety observation. In one study, 10 patients received 15 mg of the investigational agent once daily in open-label fashion. The other trial randomized 35 patients to the JAK1 inhibitor at 30 mg, 60 mg, or 90 mg per day or placebo. About 70% of participants in the studies had Hurley stage II HS; the rest were stage III.
Safety and tolerability were the primary outcomes in the two studies. One patient in the open-label study dropped out because of a flare of fibromyalgia. In the larger randomized trial, four patients – all in the group assigned to 90 mg/day of the JAK1 inhibitor – developed thrombocytopenia, resulting in temporary discontinuation of treatment for up to 2 weeks. In all four instances, the laboratory abnormality was reversed after temporary interruption of treatment, with no sequelae upon restarting the drug. There were no serious treatment-emergent adverse events in either study.
In the low-dose, open-label study, four of nine completers (44%) experienced a Hidradenitis Suppurativa Clinical Response (HiSCR) at week 8, defined as at least a 50% reduction in inflammatory lesion count with no increase in abscesses or draining fistulae compared to baseline. In the randomized trial, the week-8 HiSCR rate was 57% in placebo-treated controls, 56% in those on 30 mg/day or 60 mg/day of the JAK1 inhibitor, and significantly better at 88% in the group on 90 mg/day.
The rapidity of response to the JAK1 inhibitor was noteworthy. After just 1 week of treatment, an abscess and inflammatory nodule count of zero to two lesions was present in 22% of patients on INCB54707 at 60 mg/day and 29% of those on 90 mg/day, compared with none of the patients on 30 mg/day or placebo. At week 2, an abscess and nodule count of 0-2 was documented in 33% of participants on the JAK1 inhibitor at 30 mg/day, 58% at 60 mg/day, and 50% with 90 mg/day. At week 8, the rates were 57% with placebo, 44% with active treatment at 30 or 60 mg/day, and 63% in patients on 90 mg/day.
A dose-dependent significant improvement in Hidradenitis Suppurativa Quality of Life scores was documented in response to the JAK1 inhibitor.
There is an unmet need for effective therapies for HS, a chronic, extremely painful inflammatory condition with a large negative impact on quality of life. At present, the only Food and Drug Administration–approved medication for HS is the tumor necrosis factor inhibitor, adalimumab (Humira), noted Dr. Alavi. Ongoing studies are evaluating other JAK inhibitors, as well as TNF inhibitors and interleukin-17 and -23 blockers.
She reported receiving research funding from and serving as a consultant to Incyte, the studies’ sponsor, and more than a dozen other pharmaceutical companies.
FROM THE EADV CONGRESS
Guselkumab maintains psoriasis efficacy long after discontinuation
Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.
“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.
“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.
The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.
Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.
In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.
He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.
Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.
“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.
“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.
The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.
Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.
In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.
He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.
Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.
“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.
“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.
The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.
Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.
In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.
He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.
FROM THE EADV CONGRESS
Dermatologist survey spotlights psoriasis care deficiencies in reproductive-age women
In a , Jenny Murase, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“In Germany, the UK, and the United States, dermatologists face challenges in discussing pregnancy and child-bearing aspiration with women of reproductive age, in recommending compatible treatments during pregnancy, and engaging patients in the shared decision-making process. These challenges may exist due to suboptimal knowledge, skills, confidence, and attitude in respective areas of care,” said Dr. Murase, a dermatologist at the University of California, San Francisco, and coeditor-in-chief of the International Journal of Women’s Dermatology.
These shortcomings were documented in a survey, which began with Dr. Murase and her coinvestigators conducting detailed, 45-minute-long, semistructured telephone interviews with 24 dermatologists in the three countries. Those interviews provided the basis for subsequent development of a 20-minute online survey on psoriasis and pregnancy completed by 167 American, German, and UK dermatologists. The survey incorporated multiple choice questions and quantitative rating scales.
“Participants expressed challenges engaging in family planning counseling and reproductive health care as part of risk assessments for psoriasis,” Dr. Murase said.
Among the key findings:
- Forty-seven percent of respondents considered their knowledge of the impact of psoriasis on women’s reproductive health to be suboptimal. This knowledge gap was most common among American dermatologists, 59% of whom rated themselves as having suboptimal knowledge, and least common among German practitioners, only 27% of whom reported deficiencies in this area.
Fifty percent of dermatologists rated themselves as having suboptimal skills in discussing contraceptive methods with their psoriasis patients of childbearing potential.
- Forty-eight percent of respondents – and 59% of the American dermatologists – indicated they prefer to leave pregnancy-related discussions to ob.gyns.
- Fifty-five percent of dermatologists had only limited knowledge of the safety data and indications for prescribing biologic therapies before, during, and after pregnancy. Respondents gave themselves an average score of 58 out of 100 in terms of their confidence in prescribing biologics during pregnancy, compared to 74 out of 100 when prescribing before or after pregnancy.
- Forty-eight percent of participants indicated they had suboptimal skills in helping patients counter obstacles to treatment adherence.
Consideration of treatment of psoriasis in pregnancy requires balancing potential medication risks to the fetus versus the possible maternal and fetal harms of under- or nontreatment of their chronic inflammatory skin disease. It’s a matter that calls for shared decision-making between dermatologist and patient. But the survey showed that shared decision-making was often poorly integrated into clinical practice. Ninety-seven percent of the U.S. dermatologists were unaware of the existence of shared decision-making practice guidelines or models, as were 80% of UK respondents and 85% of the Germans. Of the relatively few dermatologists who were aware of such guidance, nearly half dismissed it as inapplicable to their clinical practice. More than one-third of respondents admitted having suboptimal skills in assessing their patients’ desired level of involvement in medical decisions. And one-third of the German dermatologists and roughly one-quarter of those from the United States and United Kingdom reported feeling pressure to make treatment decisions quickly and without patient input.
Dr. Murase added that the survey findings make a strong case for future interventions designed to help dermatologists appreciate the value of shared decision-making and develop the requisite patient-engagement skills. Dr. Murase reported serving as a paid consultant to UCB Pharma, which funded the survey via an educational grant.
In a , Jenny Murase, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“In Germany, the UK, and the United States, dermatologists face challenges in discussing pregnancy and child-bearing aspiration with women of reproductive age, in recommending compatible treatments during pregnancy, and engaging patients in the shared decision-making process. These challenges may exist due to suboptimal knowledge, skills, confidence, and attitude in respective areas of care,” said Dr. Murase, a dermatologist at the University of California, San Francisco, and coeditor-in-chief of the International Journal of Women’s Dermatology.
These shortcomings were documented in a survey, which began with Dr. Murase and her coinvestigators conducting detailed, 45-minute-long, semistructured telephone interviews with 24 dermatologists in the three countries. Those interviews provided the basis for subsequent development of a 20-minute online survey on psoriasis and pregnancy completed by 167 American, German, and UK dermatologists. The survey incorporated multiple choice questions and quantitative rating scales.
“Participants expressed challenges engaging in family planning counseling and reproductive health care as part of risk assessments for psoriasis,” Dr. Murase said.
Among the key findings:
- Forty-seven percent of respondents considered their knowledge of the impact of psoriasis on women’s reproductive health to be suboptimal. This knowledge gap was most common among American dermatologists, 59% of whom rated themselves as having suboptimal knowledge, and least common among German practitioners, only 27% of whom reported deficiencies in this area.
Fifty percent of dermatologists rated themselves as having suboptimal skills in discussing contraceptive methods with their psoriasis patients of childbearing potential.
- Forty-eight percent of respondents – and 59% of the American dermatologists – indicated they prefer to leave pregnancy-related discussions to ob.gyns.
- Fifty-five percent of dermatologists had only limited knowledge of the safety data and indications for prescribing biologic therapies before, during, and after pregnancy. Respondents gave themselves an average score of 58 out of 100 in terms of their confidence in prescribing biologics during pregnancy, compared to 74 out of 100 when prescribing before or after pregnancy.
- Forty-eight percent of participants indicated they had suboptimal skills in helping patients counter obstacles to treatment adherence.
Consideration of treatment of psoriasis in pregnancy requires balancing potential medication risks to the fetus versus the possible maternal and fetal harms of under- or nontreatment of their chronic inflammatory skin disease. It’s a matter that calls for shared decision-making between dermatologist and patient. But the survey showed that shared decision-making was often poorly integrated into clinical practice. Ninety-seven percent of the U.S. dermatologists were unaware of the existence of shared decision-making practice guidelines or models, as were 80% of UK respondents and 85% of the Germans. Of the relatively few dermatologists who were aware of such guidance, nearly half dismissed it as inapplicable to their clinical practice. More than one-third of respondents admitted having suboptimal skills in assessing their patients’ desired level of involvement in medical decisions. And one-third of the German dermatologists and roughly one-quarter of those from the United States and United Kingdom reported feeling pressure to make treatment decisions quickly and without patient input.
Dr. Murase added that the survey findings make a strong case for future interventions designed to help dermatologists appreciate the value of shared decision-making and develop the requisite patient-engagement skills. Dr. Murase reported serving as a paid consultant to UCB Pharma, which funded the survey via an educational grant.
In a , Jenny Murase, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“In Germany, the UK, and the United States, dermatologists face challenges in discussing pregnancy and child-bearing aspiration with women of reproductive age, in recommending compatible treatments during pregnancy, and engaging patients in the shared decision-making process. These challenges may exist due to suboptimal knowledge, skills, confidence, and attitude in respective areas of care,” said Dr. Murase, a dermatologist at the University of California, San Francisco, and coeditor-in-chief of the International Journal of Women’s Dermatology.
These shortcomings were documented in a survey, which began with Dr. Murase and her coinvestigators conducting detailed, 45-minute-long, semistructured telephone interviews with 24 dermatologists in the three countries. Those interviews provided the basis for subsequent development of a 20-minute online survey on psoriasis and pregnancy completed by 167 American, German, and UK dermatologists. The survey incorporated multiple choice questions and quantitative rating scales.
“Participants expressed challenges engaging in family planning counseling and reproductive health care as part of risk assessments for psoriasis,” Dr. Murase said.
Among the key findings:
- Forty-seven percent of respondents considered their knowledge of the impact of psoriasis on women’s reproductive health to be suboptimal. This knowledge gap was most common among American dermatologists, 59% of whom rated themselves as having suboptimal knowledge, and least common among German practitioners, only 27% of whom reported deficiencies in this area.
Fifty percent of dermatologists rated themselves as having suboptimal skills in discussing contraceptive methods with their psoriasis patients of childbearing potential.
- Forty-eight percent of respondents – and 59% of the American dermatologists – indicated they prefer to leave pregnancy-related discussions to ob.gyns.
- Fifty-five percent of dermatologists had only limited knowledge of the safety data and indications for prescribing biologic therapies before, during, and after pregnancy. Respondents gave themselves an average score of 58 out of 100 in terms of their confidence in prescribing biologics during pregnancy, compared to 74 out of 100 when prescribing before or after pregnancy.
- Forty-eight percent of participants indicated they had suboptimal skills in helping patients counter obstacles to treatment adherence.
Consideration of treatment of psoriasis in pregnancy requires balancing potential medication risks to the fetus versus the possible maternal and fetal harms of under- or nontreatment of their chronic inflammatory skin disease. It’s a matter that calls for shared decision-making between dermatologist and patient. But the survey showed that shared decision-making was often poorly integrated into clinical practice. Ninety-seven percent of the U.S. dermatologists were unaware of the existence of shared decision-making practice guidelines or models, as were 80% of UK respondents and 85% of the Germans. Of the relatively few dermatologists who were aware of such guidance, nearly half dismissed it as inapplicable to their clinical practice. More than one-third of respondents admitted having suboptimal skills in assessing their patients’ desired level of involvement in medical decisions. And one-third of the German dermatologists and roughly one-quarter of those from the United States and United Kingdom reported feeling pressure to make treatment decisions quickly and without patient input.
Dr. Murase added that the survey findings make a strong case for future interventions designed to help dermatologists appreciate the value of shared decision-making and develop the requisite patient-engagement skills. Dr. Murase reported serving as a paid consultant to UCB Pharma, which funded the survey via an educational grant.
FROM THE EADV CONGRESS
Expert panel addresses gaps in acne guidelines
A distinguished .
“The challenge with acne guidelines is they mainly focus on facial acne and they’re informed by randomized controlled trials which are conducted over a relatively short period of time. Given that acne is a chronic disease, this actually produces a lack of clarity on multiple issues, including things like truncal acne, treatment escalation and de-escalation, maintenance therapy, patient perspective, and longitudinal management,” Alison Layton, MBChB, said in presenting the findings of the Personalizing Acne: Consensus of Experts (PACE) panel at the virtual annual congress of the European Academy of Dermatology and Venereology.
The PACE panel highlighted two key unmet needs in acne care as the dearth of guidance on how to implement patient-centered management in clinical practice, and the absence of high-quality evidence on how best to handle long-term maintenance therapy: When to initiate it, the best regimens, and when to escalate, switch, or de-escalate it, added Dr. Layton, a dermatologist at Hull York Medical School, Heslington, England, and associate medical director for research and development at Harrogate and District National Health Service Foundation Trust.
Most of the 13 dermatologists on the PACE panel were coauthors of the current U.S., European, or Canadian acne guidelines, so they are closely familiar with the guidelines’ strengths and shortcomings. For example, the American contingent includes Linda Stein Gold, MD, Detroit; Hilary E. Baldwin, MD, New Brunswick, NJ; Julie C. Harper, MD, Birmingham, Ala.; and Jonathan S. Weiss, MD, of Georgia, all members of the work group that created the current American Academy of Dermatology guidelines.
Strong points of the current guidelines are the high-quality, evidence-based recommendations on initial treatment of facial acne. However, a major weakness of existing guidelines is reflected in the fact that well over 40% of patients relapse after acne therapy, and these relapses can significantly impair quality of life and productivity, said Dr. Layton, one of several PACE panelists who coauthored the current European Dermatology Forum acne guidelines.
The PACE panel utilized a modified Delphi approach to reach consensus on their recommendations. Ten panelists rated current practice guidelines as “somewhat useful” for informing long-term management, two dermatologists deemed existing guidelines “not at all useful” in this regard, and one declined to answer the question.
“None of us felt the guidelines were very useful,” Dr. Layton noted.
It will take time, money, and research commitment to generate compelling data on best practices for long-term maintenance therapy for acne. Other areas in sore need of high-quality studies to improve the evidence-based care of acne include the appropriate length of antibiotic therapy for acne and how to effectively combine topical agents with oral antibiotics to support appropriate use of antimicrobials. In the meantime, the PACE group plans to issue interim practical consensus recommendations to beef up existing guidelines.
With regard to practical recommendations to improve patient-centered care, there was strong consensus among the panelists that acne management in certain patient subgroups requires special attention. These subgroups include patients with darker skin phototypes, heavy exercisers, transgender patients and patients with hormonal conditions, pregnant or breast-feeding women, patients with psychiatric issues, and children under age 10.
PACE panelists agreed that a physician-patient discussion about long-term treatment expectations is “paramount” to effective patient-centered management.
“To ensure a positive consultation experience, physicians should prioritize discussion of efficacy expectations, including timelines and treatment duration,” Dr. Layton continued.
Other key topics to address in promoting patient-centered management of acne include discussion of medication adverse effects and tolerability, application technique for topical treatments, the importance of adherence, and recommendations regarding a daily skin care routine, according to the PACE group.
Dr. Layton reported serving as a consultant to Galderma, which funded the PACE project, as well as half a dozen other pharmaceutical companies.
A distinguished .
“The challenge with acne guidelines is they mainly focus on facial acne and they’re informed by randomized controlled trials which are conducted over a relatively short period of time. Given that acne is a chronic disease, this actually produces a lack of clarity on multiple issues, including things like truncal acne, treatment escalation and de-escalation, maintenance therapy, patient perspective, and longitudinal management,” Alison Layton, MBChB, said in presenting the findings of the Personalizing Acne: Consensus of Experts (PACE) panel at the virtual annual congress of the European Academy of Dermatology and Venereology.
The PACE panel highlighted two key unmet needs in acne care as the dearth of guidance on how to implement patient-centered management in clinical practice, and the absence of high-quality evidence on how best to handle long-term maintenance therapy: When to initiate it, the best regimens, and when to escalate, switch, or de-escalate it, added Dr. Layton, a dermatologist at Hull York Medical School, Heslington, England, and associate medical director for research and development at Harrogate and District National Health Service Foundation Trust.
Most of the 13 dermatologists on the PACE panel were coauthors of the current U.S., European, or Canadian acne guidelines, so they are closely familiar with the guidelines’ strengths and shortcomings. For example, the American contingent includes Linda Stein Gold, MD, Detroit; Hilary E. Baldwin, MD, New Brunswick, NJ; Julie C. Harper, MD, Birmingham, Ala.; and Jonathan S. Weiss, MD, of Georgia, all members of the work group that created the current American Academy of Dermatology guidelines.
Strong points of the current guidelines are the high-quality, evidence-based recommendations on initial treatment of facial acne. However, a major weakness of existing guidelines is reflected in the fact that well over 40% of patients relapse after acne therapy, and these relapses can significantly impair quality of life and productivity, said Dr. Layton, one of several PACE panelists who coauthored the current European Dermatology Forum acne guidelines.
The PACE panel utilized a modified Delphi approach to reach consensus on their recommendations. Ten panelists rated current practice guidelines as “somewhat useful” for informing long-term management, two dermatologists deemed existing guidelines “not at all useful” in this regard, and one declined to answer the question.
“None of us felt the guidelines were very useful,” Dr. Layton noted.
It will take time, money, and research commitment to generate compelling data on best practices for long-term maintenance therapy for acne. Other areas in sore need of high-quality studies to improve the evidence-based care of acne include the appropriate length of antibiotic therapy for acne and how to effectively combine topical agents with oral antibiotics to support appropriate use of antimicrobials. In the meantime, the PACE group plans to issue interim practical consensus recommendations to beef up existing guidelines.
With regard to practical recommendations to improve patient-centered care, there was strong consensus among the panelists that acne management in certain patient subgroups requires special attention. These subgroups include patients with darker skin phototypes, heavy exercisers, transgender patients and patients with hormonal conditions, pregnant or breast-feeding women, patients with psychiatric issues, and children under age 10.
PACE panelists agreed that a physician-patient discussion about long-term treatment expectations is “paramount” to effective patient-centered management.
“To ensure a positive consultation experience, physicians should prioritize discussion of efficacy expectations, including timelines and treatment duration,” Dr. Layton continued.
Other key topics to address in promoting patient-centered management of acne include discussion of medication adverse effects and tolerability, application technique for topical treatments, the importance of adherence, and recommendations regarding a daily skin care routine, according to the PACE group.
Dr. Layton reported serving as a consultant to Galderma, which funded the PACE project, as well as half a dozen other pharmaceutical companies.
A distinguished .
“The challenge with acne guidelines is they mainly focus on facial acne and they’re informed by randomized controlled trials which are conducted over a relatively short period of time. Given that acne is a chronic disease, this actually produces a lack of clarity on multiple issues, including things like truncal acne, treatment escalation and de-escalation, maintenance therapy, patient perspective, and longitudinal management,” Alison Layton, MBChB, said in presenting the findings of the Personalizing Acne: Consensus of Experts (PACE) panel at the virtual annual congress of the European Academy of Dermatology and Venereology.
The PACE panel highlighted two key unmet needs in acne care as the dearth of guidance on how to implement patient-centered management in clinical practice, and the absence of high-quality evidence on how best to handle long-term maintenance therapy: When to initiate it, the best regimens, and when to escalate, switch, or de-escalate it, added Dr. Layton, a dermatologist at Hull York Medical School, Heslington, England, and associate medical director for research and development at Harrogate and District National Health Service Foundation Trust.
Most of the 13 dermatologists on the PACE panel were coauthors of the current U.S., European, or Canadian acne guidelines, so they are closely familiar with the guidelines’ strengths and shortcomings. For example, the American contingent includes Linda Stein Gold, MD, Detroit; Hilary E. Baldwin, MD, New Brunswick, NJ; Julie C. Harper, MD, Birmingham, Ala.; and Jonathan S. Weiss, MD, of Georgia, all members of the work group that created the current American Academy of Dermatology guidelines.
Strong points of the current guidelines are the high-quality, evidence-based recommendations on initial treatment of facial acne. However, a major weakness of existing guidelines is reflected in the fact that well over 40% of patients relapse after acne therapy, and these relapses can significantly impair quality of life and productivity, said Dr. Layton, one of several PACE panelists who coauthored the current European Dermatology Forum acne guidelines.
The PACE panel utilized a modified Delphi approach to reach consensus on their recommendations. Ten panelists rated current practice guidelines as “somewhat useful” for informing long-term management, two dermatologists deemed existing guidelines “not at all useful” in this regard, and one declined to answer the question.
“None of us felt the guidelines were very useful,” Dr. Layton noted.
It will take time, money, and research commitment to generate compelling data on best practices for long-term maintenance therapy for acne. Other areas in sore need of high-quality studies to improve the evidence-based care of acne include the appropriate length of antibiotic therapy for acne and how to effectively combine topical agents with oral antibiotics to support appropriate use of antimicrobials. In the meantime, the PACE group plans to issue interim practical consensus recommendations to beef up existing guidelines.
With regard to practical recommendations to improve patient-centered care, there was strong consensus among the panelists that acne management in certain patient subgroups requires special attention. These subgroups include patients with darker skin phototypes, heavy exercisers, transgender patients and patients with hormonal conditions, pregnant or breast-feeding women, patients with psychiatric issues, and children under age 10.
PACE panelists agreed that a physician-patient discussion about long-term treatment expectations is “paramount” to effective patient-centered management.
“To ensure a positive consultation experience, physicians should prioritize discussion of efficacy expectations, including timelines and treatment duration,” Dr. Layton continued.
Other key topics to address in promoting patient-centered management of acne include discussion of medication adverse effects and tolerability, application technique for topical treatments, the importance of adherence, and recommendations regarding a daily skin care routine, according to the PACE group.
Dr. Layton reported serving as a consultant to Galderma, which funded the PACE project, as well as half a dozen other pharmaceutical companies.
FROM THE EADV CONGRESS
Patients dislike prurigo nodularis treatment options, survey finds
.
The eye-opening results of the 406-patient, 12-country European patient survey indicate “high levels of disbelief in currently available treatment options and an overall dissatisfaction with treatment,” Manuel P. Pereira, MD, PhD, said in presenting the findings at the annual congress of the European Academy of Dermatology and Venereology.
Only 5.3% of patients pronounced themselves “very satisfied” with their treatment. Another 28% were “rather satisfied.”
“Remarkably, almost 10% of patients were not being treated for prurigo despite having active disease,” said Dr. Pereira, a dermatologist at the Center for Chronic Pruritus at University Hospital Münster (Germany).
When survey participants were asked to identify their most important unmet treatment needs, 79.5% named improvement of itch, 57.2% sought improvement in skin lesions, and 30.5% wanted better sleep.
The most widely used treatments were emollients, prescribed in 84.5% of patients; topical steroids, in 55.7%; antihistamines, 55.2%; and phototherapy, 42.1%. Far fewer patients were on more potent medications: Cyclosporine, systemic corticosteroids, or other immunosuppressants were prescribed for 21.9% of patients; gabapentin and related compounds in 17%; and topical immunomodulators in 8.6%. Twenty-three percent of patients were on antidepressants.
None of the available treatment options, all of which are off label, received high marks from patients. For example, only 1 in 10 patients on antihistamines during the last 6 months rated the drugs as effective. Topical immunomodulators were deemed effective by 1.1% of patients with active prurigo nodularis; gabapentinoids by 3.1%; phototherapy by 9.9%; and antidepressants were rated as effective for the chronic skin disease by only 2.3% of patients. The top-rated therapies were topical steroids, deemed effective by 12.8% of patients; systemic immunosuppressants, favored by 12.2%; and emollients, deemed effective by 10.5% of patients, even though more than 80% of survey participants were using them.
Dr. Pereira said the survey results highlight a pressing need for guidelines aimed at improving clinical care for patients with chronic prurigo nodularis. The first-ever such guidelines on the diagnosis and management of this debilitating disease, developed by Dr. Pereira and other members of the International Forum for the Study of Itch (IFSI), were recently published in the journal Itch. The new guidelines advocate a multimodal treatment approach incorporating a combination of topical and systemic therapies.
At present, there is no approved treatment for prurigo nodularis. Given the unmet need, however, the pace of research has quickened. Innovative potential treatments in the developmental pipeline include Janus kinase inhibitors, topical phosphodiesterase-4 inhibitors, systemic opioid receptor modulators, and neurokinin-1 receptor antagonists.
The patient survey was funded by the EADV and carried out by the EADV’s Pruritus Task Force as part of the European Prurigo Project. Dr. Pereira reported receiving research funding from the EADV and the German Research Foundation. He is a paid speaker for AbbVie, Galderma, Menlo Therapeutics (now VYNE Therapeutics), Novartis, and Trevi.
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The eye-opening results of the 406-patient, 12-country European patient survey indicate “high levels of disbelief in currently available treatment options and an overall dissatisfaction with treatment,” Manuel P. Pereira, MD, PhD, said in presenting the findings at the annual congress of the European Academy of Dermatology and Venereology.
Only 5.3% of patients pronounced themselves “very satisfied” with their treatment. Another 28% were “rather satisfied.”
“Remarkably, almost 10% of patients were not being treated for prurigo despite having active disease,” said Dr. Pereira, a dermatologist at the Center for Chronic Pruritus at University Hospital Münster (Germany).
When survey participants were asked to identify their most important unmet treatment needs, 79.5% named improvement of itch, 57.2% sought improvement in skin lesions, and 30.5% wanted better sleep.
The most widely used treatments were emollients, prescribed in 84.5% of patients; topical steroids, in 55.7%; antihistamines, 55.2%; and phototherapy, 42.1%. Far fewer patients were on more potent medications: Cyclosporine, systemic corticosteroids, or other immunosuppressants were prescribed for 21.9% of patients; gabapentin and related compounds in 17%; and topical immunomodulators in 8.6%. Twenty-three percent of patients were on antidepressants.
None of the available treatment options, all of which are off label, received high marks from patients. For example, only 1 in 10 patients on antihistamines during the last 6 months rated the drugs as effective. Topical immunomodulators were deemed effective by 1.1% of patients with active prurigo nodularis; gabapentinoids by 3.1%; phototherapy by 9.9%; and antidepressants were rated as effective for the chronic skin disease by only 2.3% of patients. The top-rated therapies were topical steroids, deemed effective by 12.8% of patients; systemic immunosuppressants, favored by 12.2%; and emollients, deemed effective by 10.5% of patients, even though more than 80% of survey participants were using them.
Dr. Pereira said the survey results highlight a pressing need for guidelines aimed at improving clinical care for patients with chronic prurigo nodularis. The first-ever such guidelines on the diagnosis and management of this debilitating disease, developed by Dr. Pereira and other members of the International Forum for the Study of Itch (IFSI), were recently published in the journal Itch. The new guidelines advocate a multimodal treatment approach incorporating a combination of topical and systemic therapies.
At present, there is no approved treatment for prurigo nodularis. Given the unmet need, however, the pace of research has quickened. Innovative potential treatments in the developmental pipeline include Janus kinase inhibitors, topical phosphodiesterase-4 inhibitors, systemic opioid receptor modulators, and neurokinin-1 receptor antagonists.
The patient survey was funded by the EADV and carried out by the EADV’s Pruritus Task Force as part of the European Prurigo Project. Dr. Pereira reported receiving research funding from the EADV and the German Research Foundation. He is a paid speaker for AbbVie, Galderma, Menlo Therapeutics (now VYNE Therapeutics), Novartis, and Trevi.
.
The eye-opening results of the 406-patient, 12-country European patient survey indicate “high levels of disbelief in currently available treatment options and an overall dissatisfaction with treatment,” Manuel P. Pereira, MD, PhD, said in presenting the findings at the annual congress of the European Academy of Dermatology and Venereology.
Only 5.3% of patients pronounced themselves “very satisfied” with their treatment. Another 28% were “rather satisfied.”
“Remarkably, almost 10% of patients were not being treated for prurigo despite having active disease,” said Dr. Pereira, a dermatologist at the Center for Chronic Pruritus at University Hospital Münster (Germany).
When survey participants were asked to identify their most important unmet treatment needs, 79.5% named improvement of itch, 57.2% sought improvement in skin lesions, and 30.5% wanted better sleep.
The most widely used treatments were emollients, prescribed in 84.5% of patients; topical steroids, in 55.7%; antihistamines, 55.2%; and phototherapy, 42.1%. Far fewer patients were on more potent medications: Cyclosporine, systemic corticosteroids, or other immunosuppressants were prescribed for 21.9% of patients; gabapentin and related compounds in 17%; and topical immunomodulators in 8.6%. Twenty-three percent of patients were on antidepressants.
None of the available treatment options, all of which are off label, received high marks from patients. For example, only 1 in 10 patients on antihistamines during the last 6 months rated the drugs as effective. Topical immunomodulators were deemed effective by 1.1% of patients with active prurigo nodularis; gabapentinoids by 3.1%; phototherapy by 9.9%; and antidepressants were rated as effective for the chronic skin disease by only 2.3% of patients. The top-rated therapies were topical steroids, deemed effective by 12.8% of patients; systemic immunosuppressants, favored by 12.2%; and emollients, deemed effective by 10.5% of patients, even though more than 80% of survey participants were using them.
Dr. Pereira said the survey results highlight a pressing need for guidelines aimed at improving clinical care for patients with chronic prurigo nodularis. The first-ever such guidelines on the diagnosis and management of this debilitating disease, developed by Dr. Pereira and other members of the International Forum for the Study of Itch (IFSI), were recently published in the journal Itch. The new guidelines advocate a multimodal treatment approach incorporating a combination of topical and systemic therapies.
At present, there is no approved treatment for prurigo nodularis. Given the unmet need, however, the pace of research has quickened. Innovative potential treatments in the developmental pipeline include Janus kinase inhibitors, topical phosphodiesterase-4 inhibitors, systemic opioid receptor modulators, and neurokinin-1 receptor antagonists.
The patient survey was funded by the EADV and carried out by the EADV’s Pruritus Task Force as part of the European Prurigo Project. Dr. Pereira reported receiving research funding from the EADV and the German Research Foundation. He is a paid speaker for AbbVie, Galderma, Menlo Therapeutics (now VYNE Therapeutics), Novartis, and Trevi.
FROM THE EADV CONGRESS