Pub Date : 2024-10-01Epub Date: 2024-09-21DOI: 10.1007/s13555-024-01275-0
Alison M Layton, Girish Gupta, Daron Seukeran, Thivi Maruthappu, Stephanie Gaillard, Heather Whitehouse, Faisal R Ali, Angelika Razzaque, Firas Al-Niaimi, Sarah Copperwheat
Introduction: Acne remains one of the most common inflammatory dermatoses seen worldwide. There are significant challenges when managing acne relating to a variety of factors, including (1) lack of consensus on the use of the numerous available grading systems and outcome measures, (2) appreciation of the numerous areas that relate to severity, (3) the chronic nature of acne which requires a longitudinal approach to management (including both facial and truncal disease), and (4) the need to target acne early to avoid physical and psychosocial scarring. Consideration of these aspects when managing acne should result in improved outcomes. Acne guidelines review the available evidence based on robust clinical trials and are usually supplemented with some expert opinion when evidence is not available.
Methods: In this paper, the UK Acne Working Group reflects on the latest National Institute for Health and Care Excellence (NICE) acne guidelines with a goal of providing additional practical insights.
Conclusion: The group have identified areas where new evidence has now become available since the formulation of the NICE acne guidelines. This publication considers newly approved acne medications in the UK, guidance on assessing acne severity, approaches to managing truncal acne, acne sequelae, and adult female acne with hormonal therapies.
{"title":"What's New After NICE Acne Guidelines.","authors":"Alison M Layton, Girish Gupta, Daron Seukeran, Thivi Maruthappu, Stephanie Gaillard, Heather Whitehouse, Faisal R Ali, Angelika Razzaque, Firas Al-Niaimi, Sarah Copperwheat","doi":"10.1007/s13555-024-01275-0","DOIUrl":"10.1007/s13555-024-01275-0","url":null,"abstract":"<p><strong>Introduction: </strong>Acne remains one of the most common inflammatory dermatoses seen worldwide. There are significant challenges when managing acne relating to a variety of factors, including (1) lack of consensus on the use of the numerous available grading systems and outcome measures, (2) appreciation of the numerous areas that relate to severity, (3) the chronic nature of acne which requires a longitudinal approach to management (including both facial and truncal disease), and (4) the need to target acne early to avoid physical and psychosocial scarring. Consideration of these aspects when managing acne should result in improved outcomes. Acne guidelines review the available evidence based on robust clinical trials and are usually supplemented with some expert opinion when evidence is not available.</p><p><strong>Methods: </strong>In this paper, the UK Acne Working Group reflects on the latest National Institute for Health and Care Excellence (NICE) acne guidelines with a goal of providing additional practical insights.</p><p><strong>Conclusion: </strong>The group have identified areas where new evidence has now become available since the formulation of the NICE acne guidelines. This publication considers newly approved acne medications in the UK, guidance on assessing acne severity, approaches to managing truncal acne, acne sequelae, and adult female acne with hormonal therapies.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vorasidenib, an oral dual inhibitor targeting mutant enzymes isocitrate dehydrogenase 1 and 2, is utilized in the management of diffuse low-grade gliomas. Despite limited documentation of its adverse events, we present the case of a 44-year-old male who exhibited trichomegaly and hypertrichosis of body hair, eyebrows, and eyelashes following one month of vorasidenib treatment. Notably, the patient experienced diffuse hair regrowth on the scalp, including in areas affected by severe androgenetic alopecia. This report holds significance as it highlights a previously unreported side effect, thereby enhancing our understanding of emerging therapies for brain tumors and their associated adverse reactions.
{"title":"Vorasidenib-Induced Trichomegaly and Hypertrichosis: a New Side Effect in a Patient with Diffuse Astrocytoma.","authors":"Michela Starace, Stephano Cedirian, Luca Rapparini, Francesca Bruni, Bianca Maria Piraccini","doi":"10.1007/s13555-024-01263-4","DOIUrl":"10.1007/s13555-024-01263-4","url":null,"abstract":"<p><p>Vorasidenib, an oral dual inhibitor targeting mutant enzymes isocitrate dehydrogenase 1 and 2, is utilized in the management of diffuse low-grade gliomas. Despite limited documentation of its adverse events, we present the case of a 44-year-old male who exhibited trichomegaly and hypertrichosis of body hair, eyebrows, and eyelashes following one month of vorasidenib treatment. Notably, the patient experienced diffuse hair regrowth on the scalp, including in areas affected by severe androgenetic alopecia. This report holds significance as it highlights a previously unreported side effect, thereby enhancing our understanding of emerging therapies for brain tumors and their associated adverse reactions.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1007/s13555-024-01273-2
Hanane Chajra, Thibaut Saguet, Corinne Granger, Lionel Breton, Pedro Contreiras Pinto, Mickael Machicoane, Jean Marc Le Doussal
<h3 data-test="abstract-sub-heading">Introduction</h3><p>Skin aging, which results from intrinsic and extrinsic factors, is characterized by a rough, uneven and wrinkled appearance of the skin at the macroscopic level. At the microscopic level, aging shows lowered keratinocyte turnover, flattened dermal-epidermal junction and reduced collagen fiber density; however, use of skin biopsies to evaluate characteristic properties of these microscopic changes is too limiting for panelists and rarely used. The development of non-invasive techniques is an opportunity to be considered for such evaluations. Our objective was to demonstrate the rejuvenating effects of XEP™-716 Miniprotein™ on skin, a miniprotein having TGF-β beta-like properties, in vitro on normal human fibroblasts and at the clinical level.</p><h3 data-test="abstract-sub-heading">Methods</h3><p>In vitro, the skin rejuvenation properties of XEP™-716 Miniprotein™ were studied by quantification of well-known dermal components such as collagen type I, hyaluronic acid and elastin. At the clinical level, we used a non-invasive technique, the confocal laser scanning microscopy (CLSM) system, which enabled non-invasive morphological characterization of skin structures (stratum corneum thickness, viable epidermis, full epidermis, dermal-epidermal junction, papillae, dermal collagen density) and high-frequency ultrasonography to quantify the dermal density and thickness, which are useful parameters for quantifying rejuvenating effects on skin. Lastly, a cutometer was used to assess the skin's biomechanical properties, mainly firmness and elasticity. This monocentric double-blind, split-face, randomized, placebo-controlled clinical trial compared the active ingredient XEP™-716 Miniprotein™ in a vehicle on one hemiface versus vehicle alone on the other (placebo) and enrolled panelists aged 40 to 60 years old. All measurements were carried out on the malar area before and after 28 and 56 days of twice daily application of a cosmetic cream formulation containing either 2.5% or 5% XEP™-716 Miniprotein™. The skin rejuvenating properties were demonstrated by studying dermo-epidermal junction (DEJ) flattening reduction using the measure of two parameters by CLSM: the DEJ length and number of edged papillae. Dermis rejuvenation was assessed by measuring the collagen fiber perimeters (CLSM), dermal density and dermal thickness (ultrasonography).</p><h3 data-test="abstract-sub-heading">Results</h3><p>The in vitro results confirmed the ability of XEP™-716 Miniprotein™ to stimulate the key extracellular macromolecules, namely collagen type I, hyaluronic acid and elastin, at a level comparable to that induced by TGF beta growth factor. The clinical data showed that after 28 and 56 days of topical XEP™-716 Miniprotein™ application, there was a statistically significant increase of DEJ length, number of edged papillae and collagen fiber perimeters. At the same time point, the B-scan images of facial skin showed a s
{"title":"A New TGF-β Mimetic, XEP™-716 Miniprotein™, Exhibiting Regenerative Properties Objectivized by Instrumental Evaluation","authors":"Hanane Chajra, Thibaut Saguet, Corinne Granger, Lionel Breton, Pedro Contreiras Pinto, Mickael Machicoane, Jean Marc Le Doussal","doi":"10.1007/s13555-024-01273-2","DOIUrl":"https://doi.org/10.1007/s13555-024-01273-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Skin aging, which results from intrinsic and extrinsic factors, is characterized by a rough, uneven and wrinkled appearance of the skin at the macroscopic level. At the microscopic level, aging shows lowered keratinocyte turnover, flattened dermal-epidermal junction and reduced collagen fiber density; however, use of skin biopsies to evaluate characteristic properties of these microscopic changes is too limiting for panelists and rarely used. The development of non-invasive techniques is an opportunity to be considered for such evaluations. Our objective was to demonstrate the rejuvenating effects of XEP™-716 Miniprotein™ on skin, a miniprotein having TGF-β beta-like properties, in vitro on normal human fibroblasts and at the clinical level.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In vitro, the skin rejuvenation properties of XEP™-716 Miniprotein™ were studied by quantification of well-known dermal components such as collagen type I, hyaluronic acid and elastin. At the clinical level, we used a non-invasive technique, the confocal laser scanning microscopy (CLSM) system, which enabled non-invasive morphological characterization of skin structures (stratum corneum thickness, viable epidermis, full epidermis, dermal-epidermal junction, papillae, dermal collagen density) and high-frequency ultrasonography to quantify the dermal density and thickness, which are useful parameters for quantifying rejuvenating effects on skin. Lastly, a cutometer was used to assess the skin's biomechanical properties, mainly firmness and elasticity. This monocentric double-blind, split-face, randomized, placebo-controlled clinical trial compared the active ingredient XEP™-716 Miniprotein™ in a vehicle on one hemiface versus vehicle alone on the other (placebo) and enrolled panelists aged 40 to 60 years old. All measurements were carried out on the malar area before and after 28 and 56 days of twice daily application of a cosmetic cream formulation containing either 2.5% or 5% XEP™-716 Miniprotein™. The skin rejuvenating properties were demonstrated by studying dermo-epidermal junction (DEJ) flattening reduction using the measure of two parameters by CLSM: the DEJ length and number of edged papillae. Dermis rejuvenation was assessed by measuring the collagen fiber perimeters (CLSM), dermal density and dermal thickness (ultrasonography).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The in vitro results confirmed the ability of XEP™-716 Miniprotein™ to stimulate the key extracellular macromolecules, namely collagen type I, hyaluronic acid and elastin, at a level comparable to that induced by TGF beta growth factor. The clinical data showed that after 28 and 56 days of topical XEP™-716 Miniprotein™ application, there was a statistically significant increase of DEJ length, number of edged papillae and collagen fiber perimeters. At the same time point, the B-scan images of facial skin showed a s","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1007/s13555-024-01261-6
Matthias Augustin, Alice B. Gottlieb, Mark Lebwohl, Andreas Pinter, Richard B. Warren, Luis Puig, Rhys Warham, Jérémy Lambert, Susanne Wiegratz, Balint Szilagyi, Andrew Blauvelt
Introduction
With newer biologics, the achievement of complete skin clearance has become an attainable treatment goal for patients with plaque psoriasis. We evaluate how improvements in Psoriasis Area and Severity Index (PASI) responses, particularly at incremental improvements approaching complete skin clearance (PASI 100), translate into improvements in health-related quality of life (HRQoL) and patient-perceived symptoms.
Methods
Data from the BE RADIANT phase 3b trial (NCT03536884) and its open-label extension (OLE), pooled across all study visits and treatments over 16 weeks (randomised patients) and 2 years (patients entering the OLE), were analysed using mixed-effects logistic regression models. Proportions of patients achieving a Dermatology Life Quality Index (DLQI) of 0/1, DLQI item scores of 0, and Psoriasis Symptoms and Impacts Measure (P-SIM) item scores of 0 for itching, scaling, and skin pain at specific PASI improvement levels were estimated.
Results
Seven hundred and forty-three patients were randomised to treatment; 654 entered the OLE. Using 16-week pooled data, there were incremental improvements in the proportions of patients estimated by our model to achieve DLQI 0/1 with PASI 100 compared with 95% (PASI = 95%) and 90% (PASI = 90%) improvements in PASI (93.0%, 89.3%, and 83.8% achieving DLQI 0/1, respectively). Estimated proportions achieving DLQI item scores of 0 had the greatest increases at higher PASI improvement levels for Items 1 (itchy, sore, painful, or stinging skin), 2 (embarrassment), and 4 (choice of clothing). Estimated proportions of patients achieving P-SIM = 0 were also higher for PASI 100 (itching: 61.7%; scaling: 82.2%; skin pain: 96.9%) than for PASI = 95% (50.8%; 72.3%; 95.7%) and PASI = 90% (39.8%; 59.5%; 94.0%). Similar benefits of incremental PASI improvements were estimated using 2-year data.
Conclusions
Complete skin clearance translated into the greatest benefits to HRQoL and patient-perceived symptoms, over and above skin clearance between 90% and 100%, highlighting the importance of targeting PASI 100 as a treatment outcome for patients with psoriasis.
Trial Registration Number
NCT03536884.
导言随着生物制剂的更新换代,实现皮肤完全清除已成为斑块状银屑病患者可以达到的治疗目标。我们评估了银屑病面积和严重程度指数(PASI)反应的改善,尤其是在接近皮肤完全清除(PASI 100)时的递增改善,如何转化为健康相关生活质量(HRQoL)和患者感知症状的改善。方法 使用混合效应逻辑回归模型分析了 BE RADIANT 3b 期试验(NCT03536884)及其开放标签扩展试验(OLE)的数据,这些数据汇集了 16 周(随机患者)和 2 年(进入 OLE 的患者)的所有研究访问和治疗。估算了在特定 PASI 改善水平下,皮肤科生活质量指数 (DLQI) 达到 0/1、DLQI 项目得分达到 0,以及瘙痒、脱屑和皮肤疼痛方面的银屑病症状和影响测量 (P-SIM) 项目得分达到 0 的患者比例。使用 16 周的汇总数据,与 PASI 改善程度达到 95% (PASI = 95%) 和 90% (PASI = 90%) 的患者相比,我们的模型估计 PASI 100 达到 DLQI 0/1 的患者比例有所提高(分别为 93.0%、89.3% 和 83.8% 达到 DLQI 0/1)。达到 DLQI 项目 0 分的估计比例在项目 1(皮肤瘙痒、疼痛或刺痛)、项目 2(尴尬)和项目 4(衣服的选择)的 PASI 改善水平较高时增幅最大。PASI = 100(瘙痒:61.7%;脱屑:82.2%;皮肤疼痛:96.9%)患者达到 P-SIM = 0 的估计比例也高于 PASI = 95% (50.8%;72.3%;95.7%)和 PASI = 90% (39.8%;59.5%;94.0%)。结论皮肤完全清除可为患者的 HRQoL 和患者感知的症状带来最大益处,超过 90% 至 100% 之间的皮肤清除率,突出了将 PASI 100 作为银屑病患者治疗结果目标的重要性。
{"title":"Complete Skin Clearance is Associated with the Greatest Benefits to Health-Related Quality of Life and Perceived Symptoms for Patients with Psoriasis","authors":"Matthias Augustin, Alice B. Gottlieb, Mark Lebwohl, Andreas Pinter, Richard B. Warren, Luis Puig, Rhys Warham, Jérémy Lambert, Susanne Wiegratz, Balint Szilagyi, Andrew Blauvelt","doi":"10.1007/s13555-024-01261-6","DOIUrl":"https://doi.org/10.1007/s13555-024-01261-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>With newer biologics, the achievement of complete skin clearance has become an attainable treatment goal for patients with plaque psoriasis. We evaluate how improvements in Psoriasis Area and Severity Index (PASI) responses, particularly at incremental improvements approaching complete skin clearance (PASI 100), translate into improvements in health-related quality of life (HRQoL) and patient-perceived symptoms.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Data from the BE RADIANT phase 3b trial (NCT03536884) and its open-label extension (OLE), pooled across all study visits and treatments over 16 weeks (randomised patients) and 2 years (patients entering the OLE), were analysed using mixed-effects logistic regression models. Proportions of patients achieving a Dermatology Life Quality Index (DLQI) of 0/1, DLQI item scores of 0, and Psoriasis Symptoms and Impacts Measure (P-SIM) item scores of 0 for itching, scaling, and skin pain at specific PASI improvement levels were estimated.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Seven hundred and forty-three patients were randomised to treatment; 654 entered the OLE. Using 16-week pooled data, there were incremental improvements in the proportions of patients estimated by our model to achieve DLQI 0/1 with PASI 100 compared with 95% (PASI = 95%) and 90% (PASI = 90%) improvements in PASI (93.0%, 89.3%, and 83.8% achieving DLQI 0/1, respectively). Estimated proportions achieving DLQI item scores of 0 had the greatest increases at higher PASI improvement levels for Items 1 (itchy, sore, painful, or stinging skin), 2 (embarrassment), and 4 (choice of clothing). Estimated proportions of patients achieving P-SIM = 0 were also higher for PASI 100 (itching: 61.7%; scaling: 82.2%; skin pain: 96.9%) than for PASI = 95% (50.8%; 72.3%; 95.7%) and PASI = 90% (39.8%; 59.5%; 94.0%). Similar benefits of incremental PASI improvements were estimated using 2-year data.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Complete skin clearance translated into the greatest benefits to HRQoL and patient-perceived symptoms, over and above skin clearance between 90% and 100%, highlighting the importance of targeting PASI 100 as a treatment outcome for patients with psoriasis.</p><h3 data-test=\"abstract-sub-heading\">Trial Registration Number</h3><p>NCT03536884.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1007/s13555-024-01258-1
Philip J. Mease, Andrew Blauvelt, Adam P. Sima, Silky W. Beaty, Robert Low, Braulio Gomez, Marie Gurrola, Mark G. Lebwohl
Introduction
Patients with psoriasis (PSO) and psoriatic arthritis (PsA) may frequently switch biologic therapies over the course of treatment because of symptom variability and individual responses. Real-world studies analyzing patient characteristics and clinical factors associated with biologic switching are limited.
Methods
This longitudinal cohort study used real-world data from the CorEvitas Psoriasis Registry to evaluate the relationship between associated disease factors and biologic switching among patients with PSO and PsA in the United States (US) and Canada following initiation of a biologic. Patients were evaluated between April 2015–August 2022. Combinations of disease severity (as measured by Psoriasis Area Severity Index [PASI]) and Dermatology Life Quality Index (DLQI) as a measure of health-related quality of life (HRQoL) were assessed, and the association with time to switching was calculated using Cox proportional hazards regression modeling.
Results
Among 2580 patient-initiations (instances of patients initiating a biologic), 504 (19.5%) switched biologics within 30 months of initiation. Switching was more frequent when either PASI > 10 or DLQI > 5 compared with PASI ≤ 10 or DLQI ≤ 5 at follow-up. Patients with higher skin involvement (PASI > 10) and impact on HRQoL (DLQI > 5) were 14 times more likely to switch (hazard ratio = 14.2, 95% confidence interval: 10.7, 18.9) than those with lower skin involvement (PASI ≤ 10) and HRQoL (DLQI ≤ 5).
Conclusions
Patients with PSO and PsA treated in a real-world dermatology setting with substantial disease factors following biologic initiation were more likely to switch therapies. Those with PASI > 10 and DLQI > 5 switched more frequently than those with PASI ≤ 10 and DLQI ≤ 5.
{"title":"Impact of Disease Factors of Patients with Psoriasis and Psoriatic Arthritis on Biologic Therapy Switching: Real-World Evidence from the CorEvitas Psoriasis Registry","authors":"Philip J. Mease, Andrew Blauvelt, Adam P. Sima, Silky W. Beaty, Robert Low, Braulio Gomez, Marie Gurrola, Mark G. Lebwohl","doi":"10.1007/s13555-024-01258-1","DOIUrl":"https://doi.org/10.1007/s13555-024-01258-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Patients with psoriasis (PSO) and psoriatic arthritis (PsA) may frequently switch biologic therapies over the course of treatment because of symptom variability and individual responses. Real-world studies analyzing patient characteristics and clinical factors associated with biologic switching are limited.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This longitudinal cohort study used real-world data from the CorEvitas Psoriasis Registry to evaluate the relationship between associated disease factors and biologic switching among patients with PSO and PsA in the United States (US) and Canada following initiation of a biologic. Patients were evaluated between April 2015–August 2022. Combinations of disease severity (as measured by Psoriasis Area Severity Index [PASI]) and Dermatology Life Quality Index (DLQI) as a measure of health-related quality of life (HRQoL) were assessed, and the association with time to switching was calculated using Cox proportional hazards regression modeling.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among 2580 patient-initiations (instances of patients initiating a biologic), 504 (19.5%) switched biologics within 30 months of initiation. Switching was more frequent when either PASI > 10 or DLQI > 5 compared with PASI ≤ 10 or DLQI ≤ 5 at follow-up. Patients with higher skin involvement (PASI > 10) and impact on HRQoL (DLQI > 5) were 14 times more likely to switch (hazard ratio = 14.2, 95% confidence interval: 10.7, 18.9) than those with lower skin involvement (PASI ≤ 10) and HRQoL (DLQI ≤ 5).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Patients with PSO and PsA treated in a real-world dermatology setting with substantial disease factors following biologic initiation were more likely to switch therapies. Those with PASI > 10 and DLQI > 5 switched more frequently than those with PASI ≤ 10 and DLQI ≤ 5. </p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1007/s13555-024-01257-2
Andrew Blauvelt, Robert R. McLean, Silky W. Beaty, Adam P. Sima, Robert Low, Jeffrey L. Stark, Laura McClung, Jerry Bagel
Introduction
Due to variable psoriasis symptoms, disease progression, and individual responses to therapy, patients may start, stop, or switch biologic therapies. Real-world data on the associated disease burden of patients with psoriasis who do and do not switch biologics are incomplete.
Methods
This study compared disease burden among patients from the CorEvitas Psoriasis Registry (July 2017–December 2021) who switched biologics and those who did not within 4–12 months following initiation. Disease-related patient-reported outcomes (PROs) were recorded, including skin pain, itching, activity impairment, and effects on health-related quality of life (HRQoL). Disease severity was measured by body surface area (BSA) and Psoriasis Area and Severity Index (PASI). Unadjusted and adjusted regression models were used to compare study outcome measures between the two groups.
Results
This study included 2145 patients, with 159 classified as switchers and 1986 as non-switchers. The most common reason for switching therapy was failure to maintain initial response (51.7%; n = 78). Moderate-to-severe disease (BSA ≥ 3) was found among 83.0% (n = 132) of switchers versus 26.1% (n = 516) of non-switchers. PASI > 5 was reported among 49.7% (n = 79) of switchers versus 8.6% (n = 171) of non-switchers. Differences in skin pain, itching, and effects on HRQoL between switchers and non-switchers were larger in magnitude for bio-experienced patients.
Conclusions
Patients who switched biologic therapy experienced a greater disease burden of psoriasis across PROs than non-switchers. Patient-centered factors may be important drivers of biologic switching. Our findings suggest the association between switching and disease burden may be stronger among patients with prior biologic therapy experience.
{"title":"Impact of Disease Burden of Patients with Psoriasis on Biologic Therapy Switching: Real-World Evidence from the CorEvitas Psoriasis Registry","authors":"Andrew Blauvelt, Robert R. McLean, Silky W. Beaty, Adam P. Sima, Robert Low, Jeffrey L. Stark, Laura McClung, Jerry Bagel","doi":"10.1007/s13555-024-01257-2","DOIUrl":"https://doi.org/10.1007/s13555-024-01257-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Due to variable psoriasis symptoms, disease progression, and individual responses to therapy, patients may start, stop, or switch biologic therapies. Real-world data on the associated disease burden of patients with psoriasis who do and do not switch biologics are incomplete.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This study compared disease burden among patients from the CorEvitas Psoriasis Registry (July 2017–December 2021) who switched biologics and those who did not within 4–12 months following initiation. Disease-related patient-reported outcomes (PROs) were recorded, including skin pain, itching, activity impairment, and effects on health-related quality of life (HRQoL). Disease severity was measured by body surface area (BSA) and Psoriasis Area and Severity Index (PASI). Unadjusted and adjusted regression models were used to compare study outcome measures between the two groups.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>This study included 2145 patients, with 159 classified as switchers and 1986 as non-switchers. The most common reason for switching therapy was failure to maintain initial response (51.7%; <i>n</i> = 78). Moderate-to-severe disease (BSA ≥ 3) was found among 83.0% (<i>n</i> = 132) of switchers versus 26.1% (<i>n</i> = 516) of non-switchers. PASI > 5 was reported among 49.7% (<i>n</i> = 79) of switchers versus 8.6% (<i>n</i> = 171) of non-switchers. Differences in skin pain, itching, and effects on HRQoL between switchers and non-switchers were larger in magnitude for bio-experienced patients.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Patients who switched biologic therapy experienced a greater disease burden of psoriasis across PROs than non-switchers. Patient-centered factors may be important drivers of biologic switching. Our findings suggest the association between switching and disease burden may be stronger among patients with prior biologic therapy experience.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1007/s13555-024-01262-5
Ian M. Catlett, Lu Gao, Yanhua Hu, Subhashis Banerjee, James G. Krueger
Background
Psoriasis, a chronic, immune-mediated, inflammatory disease, affects 2‒3% of the population. Tyrosine kinase 2 (TYK2) mediates cytokine signaling involved in adaptive [interleukin (IL)-12, IL-23] and innate (type-I interferons) immune responses; IL-23–driven T-helper (Th)17 pathways play a key role in chronic inflammation in psoriasis. In a phase 2 trial, deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, reduced IL-23/Th17 and type-I interferon pathway expression in the skin of patients with moderate to severe plaque psoriasis, reductions that were accompanied by clinical improvement of psoriatic lesions.
Objectives
The aim of this study was to identify biomarkers of psoriatic disease in serum from patients enrolled in the phase 2 trial and to assess the effects of deucravacitinib on those biomarkers.
Methods
Serum biomarkers from Olink proteomics and other quantitative assays were evaluated for a pharmacodynamic response to deucravacitinib treatment and correlation with psoriasis disease activity measures.
Results
Serum biomarkers associated with the IL-23/Th17 pathway [IL-17A, IL-17C, IL-19, IL-20, beta-defensin, and peptidase inhibitor 3 (PI3)] were upregulated in patients with psoriasis versus healthy controls. Deucravacitinib treatment reduced IL-17A (adjusted mean change from baseline at Day 85; 12 mg once daily versus placebo; −0.240 versus −0.067), IL-17C (−14.850 versus −1.664), IL-19 (−96.445 versus −8.119), IL-20 (−0.265 versus −0.064), beta-defensin (−65,025.443 versus −7553.961), and PI3 (−14.005 versus −1.360) expression. Reductions in serum biomarker expression occurred in a dose- and time-dependent manner, with significant reductions from baseline seen with deucravacitinib doses ≥ 3 mg twice daily (P ≤ 0.05). Biomarker expression correlated with disease activity measures such as Psoriasis Area and Severity Index (PASI) at baseline. Biomarker expression also correlated with PASI scores at Week 12.
Conclusion
IL-23/Th17 pathway expression in the serum of patients with psoriasis is an indicator of disease activity and response to deucravacitinib treatment.
{"title":"Pharmacodynamic Response to Deucravacitinib, an Oral, Selective, Allosteric TYK2 Inhibitor, in a Global, Phase 2, Randomized, Double-Blind, Placebo-Controlled Psoriasis Trial","authors":"Ian M. Catlett, Lu Gao, Yanhua Hu, Subhashis Banerjee, James G. Krueger","doi":"10.1007/s13555-024-01262-5","DOIUrl":"https://doi.org/10.1007/s13555-024-01262-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Psoriasis, a chronic, immune-mediated, inflammatory disease, affects 2‒3% of the population. Tyrosine kinase 2 (TYK2) mediates cytokine signaling involved in adaptive [interleukin (IL)-12, IL-23] and innate (type-I interferons) immune responses; IL-23–driven T-helper (Th)17 pathways play a key role in chronic inflammation in psoriasis. In a phase 2 trial, deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, reduced IL-23/Th17 and type-I interferon pathway expression in the skin of patients with moderate to severe plaque psoriasis, reductions that were accompanied by clinical improvement of psoriatic lesions.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>The aim of this study was to identify biomarkers of psoriatic disease in serum from patients enrolled in the phase 2 trial and to assess the effects of deucravacitinib on those biomarkers.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Serum biomarkers from Olink proteomics and other quantitative assays were evaluated for a pharmacodynamic response to deucravacitinib treatment and correlation with psoriasis disease activity measures.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Serum biomarkers associated with the IL-23/Th17 pathway [IL-17A, IL-17C, IL-19, IL-20, beta-defensin, and peptidase inhibitor 3 (PI3)] were upregulated in patients with psoriasis versus healthy controls. Deucravacitinib treatment reduced IL-17A (adjusted mean change from baseline at Day 85; 12 mg once daily versus placebo; −0.240 versus −0.067), IL-17C (−14.850 versus −1.664), IL-19 (−96.445 versus −8.119), IL-20 (−0.265 versus −0.064), beta-defensin (−65,025.443 versus −7553.961), and PI3 (−14.005 versus −1.360) expression. Reductions in serum biomarker expression occurred in a dose- and time-dependent manner, with significant reductions from baseline seen with deucravacitinib doses ≥ 3 mg twice daily (<i>P</i> ≤ 0.05). Biomarker expression correlated with disease activity measures such as Psoriasis Area and Severity Index (PASI) at baseline. Biomarker expression also correlated with PASI scores at Week 12.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>IL-23/Th17 pathway expression in the serum of patients with psoriasis is an indicator of disease activity and response to deucravacitinib treatment.</p><h3 data-test=\"abstract-sub-heading\">Trial registration number</h3><p>NCT02931838.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1007/s13555-024-01256-3
Vivian Li, Kelly Frasier, Emily Woolhiser, Kathleen Daly, Sara Christoforides, Courtnee Harpine, Karina Stech, Stefany Acosta, Edwin D. Lephart
This narrative literature review examined the intricate relationship between body dysmorphic disorder (BDD) and dermatological conditions, with a brief focus on those characterized by conspicuous skin irregularities such as acne vulgaris, psoriasis, and vitiligo. Highlighting the significant prevalence of BDD among individuals afflicted with dermatological issues, our analysis illuminated the profound psychological repercussions stemming from an exaggerated preoccupation with perceived skin imperfections. Through an exploration of the underlying BDD symptoms, we analyzed the complex dynamics between skin health and mental well-being, emphasizing the disorder’s impact on patients’ psychological and social functioning. This narrative review further investigated the consequential effects of BDD on essential aspects of dermatological treatment, including patient adherence to therapeutic regimens, overall quality of life (QOL), and the effectiveness of available treatments. In addition to presenting current therapeutic approaches, we advocate for the integration of psycho-dermatological interventions tailored to mitigate the dual burden of skin conditions and psychological distress. Future research directions proposed include longitudinal studies to assess the long-term effects of BDD on skin disease prognosis and psychosocial well-being, which aim to refine and optimize treatment modalities to contribute to a more holistic understanding of BDD within dermatological practice.
{"title":"Exploring the Intersection of Body Dysmorphic Disorder (BDD) and Dermatological Conditions: A Narrative Review","authors":"Vivian Li, Kelly Frasier, Emily Woolhiser, Kathleen Daly, Sara Christoforides, Courtnee Harpine, Karina Stech, Stefany Acosta, Edwin D. Lephart","doi":"10.1007/s13555-024-01256-3","DOIUrl":"https://doi.org/10.1007/s13555-024-01256-3","url":null,"abstract":"<p>This narrative literature review examined the intricate relationship between body dysmorphic disorder (BDD) and dermatological conditions, with a brief focus on those characterized by conspicuous skin irregularities such as acne vulgaris, psoriasis, and vitiligo. Highlighting the significant prevalence of BDD among individuals afflicted with dermatological issues, our analysis illuminated the profound psychological repercussions stemming from an exaggerated preoccupation with perceived skin imperfections. Through an exploration of the underlying BDD symptoms, we analyzed the complex dynamics between skin health and mental well-being, emphasizing the disorder’s impact on patients’ psychological and social functioning. This narrative review further investigated the consequential effects of BDD on essential aspects of dermatological treatment, including patient adherence to therapeutic regimens, overall quality of life (QOL), and the effectiveness of available treatments. In addition to presenting current therapeutic approaches, we advocate for the integration of psycho-dermatological interventions tailored to mitigate the dual burden of skin conditions and psychological distress. Future research directions proposed include longitudinal studies to assess the long-term effects of BDD on skin disease prognosis and psychosocial well-being, which aim to refine and optimize treatment modalities to contribute to a more holistic understanding of BDD within dermatological practice.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1007/s13555-024-01264-3
Mark G. Lebwohl, April W. Armstrong, Andrew F. Alexis, Edward L. Lain, Abby A. Jacobson
Factors such as obesity, alcohol consumption, and tobacco use are associated with both increased psoriasis severity and inadequate response to systemic and biologic therapies. Obesity is linked to chronic inflammation, which can contribute to psoriasis pathogenesis. Fixed-dose therapies may have reduced efficacy in patients with a higher body mass index, while weight-based dosing can increase the burden of drug-specific side effects. Alcohol and nicotine from tobacco have also been shown to stimulate keratinocyte and immune cell proliferation and production of proinflammatory cytokines. While these risk factors are prevalent among patients with moderate-to-severe psoriasis, their influence on treatment outcomes may be overlooked when evaluating therapeutic options. Brodalumab is a fully human interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe psoriasis. In this review, we describe the lifestyle-related risk factors associated with decreased response to treatment. We further summarize the post hoc analyses of brodalumab in participant subgroups with moderate-to-severe psoriasis and a history of prior biologic failure, obesity, and alcohol or tobacco use from two phase 3 clinical trials (AMAGINE-2 and AMAGINE-3; ClinicalTrials.gov identifiers: NCT01708603 and NCT01708629, respectively). Our review of clinical trial and real-world data suggests that brodalumab is an efficacious and safe treatment option for patients with lifestyle factors that increase the likelihood of treatment failure, allowing them to achieve skin clearance and improve quality of life.
{"title":"Efficacy of Brodalumab in Patients with Psoriasis and Risk Factors for Treatment Failure: A Review of Post Hoc Analyses","authors":"Mark G. Lebwohl, April W. Armstrong, Andrew F. Alexis, Edward L. Lain, Abby A. Jacobson","doi":"10.1007/s13555-024-01264-3","DOIUrl":"https://doi.org/10.1007/s13555-024-01264-3","url":null,"abstract":"<p>Factors such as obesity, alcohol consumption, and tobacco use are associated with both increased psoriasis severity and inadequate response to systemic and biologic therapies. Obesity is linked to chronic inflammation, which can contribute to psoriasis pathogenesis. Fixed-dose therapies may have reduced efficacy in patients with a higher body mass index, while weight-based dosing can increase the burden of drug-specific side effects. Alcohol and nicotine from tobacco have also been shown to stimulate keratinocyte and immune cell proliferation and production of proinflammatory cytokines. While these risk factors are prevalent among patients with moderate-to-severe psoriasis, their influence on treatment outcomes may be overlooked when evaluating therapeutic options. Brodalumab is a fully human interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe psoriasis. In this review, we describe the lifestyle-related risk factors associated with decreased response to treatment. We further summarize the post hoc analyses of brodalumab in participant subgroups with moderate-to-severe psoriasis and a history of prior biologic failure, obesity, and alcohol or tobacco use from two phase 3 clinical trials (AMAGINE-2 and AMAGINE-3; ClinicalTrials.gov identifiers: NCT01708603 and NCT01708629, respectively). Our review of clinical trial and real-world data suggests that brodalumab is an efficacious and safe treatment option for patients with lifestyle factors that increase the likelihood of treatment failure, allowing them to achieve skin clearance and improve quality of life.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1007/s13555-024-01266-1
Stephanie McKee, Jason Xenakis, Harriet Makin, Chris Marshall, Randall Winnette, Rohit Aggarwal, Sarah Knight
Background
Dermatomyositis (DM) is a rare and severely debilitating autoimmune disease that can affect children and adults; however, there is little understanding of the patient-reported experience and uncertainty around validated clinical outcomes assessments (COAs) that could measure changes in the condition during clinical trials of new treatments.
Objectives
The aim of this study was to understand the patient experience of DM, with a focus on its cutaneous manifestations, to describe the patient experience and determine the suitability of existing COA measures.
Methods
Adult (≥ 18 years) patients (N = 28) with severe active cutaneous manifestations of DM were interviewed. In the 90-min interviews, open-ended questions and probes were used to elicit descriptions of key clinical manifestations and patients’ experiences of DM, including the symptoms and impacts on their daily lives and wellbeing.
Results
Patients reported 13 different skin manifestations of DM. The most common were rash (n = 28, 100%), itch (n = 28, 100%), dry skin (n = 23, 82%), and swelling of the skin (n = 17, 61%). The head and face, followed by hands, were perceived as the most bothersome body areas affected by skin manifestations, because they are exposed and visible to themselves and other people. All patients (n = 28, 100%) reported at least one impact of DM, which varied greatly between patients, but included emotional, psychological, cognitive, and physical impacts, and those affecting daily life, such as work and sleep. Over half of the patients (n = 19, 67%) reported that their daily activities were impacted by DM.
Conclusions
The qualitative interviews with patients revealed that the presentation of DM manifestations is highly variable but affects patients’ emotional wellbeing, physical activities, and daily life significantly.
{"title":"Cutaneous Manifestations in Patients with Dermatomyositis, Are They Only Skin Deep?","authors":"Stephanie McKee, Jason Xenakis, Harriet Makin, Chris Marshall, Randall Winnette, Rohit Aggarwal, Sarah Knight","doi":"10.1007/s13555-024-01266-1","DOIUrl":"https://doi.org/10.1007/s13555-024-01266-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Dermatomyositis (DM) is a rare and severely debilitating autoimmune disease that can affect children and adults; however, there is little understanding of the patient-reported experience and uncertainty around validated clinical outcomes assessments (COAs) that could measure changes in the condition during clinical trials of new treatments.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>The aim of this study was to understand the patient experience of DM, with a focus on its cutaneous manifestations, to describe the patient experience and determine the suitability of existing COA measures.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Adult (≥ 18 years) patients (<i>N</i> = 28) with severe active cutaneous manifestations of DM were interviewed. In the 90-min interviews, open-ended questions and probes were used to elicit descriptions of key clinical manifestations and patients’ experiences of DM, including the symptoms and impacts on their daily lives and wellbeing.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Patients reported 13 different skin manifestations of DM. The most common were rash (<i>n</i> = 28, 100%), itch (<i>n</i> = 28, 100%), dry skin (<i>n</i> = 23, 82%), and swelling of the skin (<i>n</i> = 17, 61%). The head and face, followed by hands, were perceived as the most bothersome body areas affected by skin manifestations, because they are exposed and visible to themselves and other people. All patients (<i>n</i> = 28, 100%) reported at least one impact of DM, which varied greatly between patients, but included emotional, psychological, cognitive, and physical impacts, and those affecting daily life, such as work and sleep. Over half of the patients (<i>n</i> = 19, 67%) reported that their daily activities were impacted by DM.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The qualitative interviews with patients revealed that the presentation of DM manifestations is highly variable but affects patients’ emotional wellbeing, physical activities, and daily life significantly.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}