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Evaluation of the Tolerability of Hedgehog Pathway Inhibitors in the Treatment of Advanced Basal Cell Carcinoma: A Narrative Review of Treatment Strategies 评估刺猬通路抑制剂治疗晚期基底细胞癌的耐受性:治疗策略综述。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-06-19 DOI: 10.1007/s40257-024-00870-3
Aaron S. Farberg, Dustin Portela, Divya Sharma, Meenal Kheterpal

Hedgehog pathway inhibitors (HHIs) have broadened the treatment options available for patients with advanced basal cell carcinoma (BCC) for whom traditional therapeutic approaches are not feasible or effective. Sonidegib and vismodegib are oral HHIs that were approved for treatment of patients with advanced BCC after demonstrating promising efficacy in the pivotal Phase II BOLT (NCT01327053) and ERIVANCE (NCT00833417) trials, respectively. However, the incidence and types of treatment-emergent adverse events (AEs) observed with these agents may limit continuous use of HHIs and ultimately impact clinical outcomes. In this review, we summarize the safety and tolerability profiles of sonidegib and vismodegib and discuss potential management strategies for HHI class-effect AEs, including muscle spasms, creatine phosphokinase increase, alopecia, and dysgeusia. These AEs primarily occur early in treatment and can lead to treatment discontinuation. Differences in the pharmacokinetic profiles of sonidegib and vismodegib may contribute to the variability noted in times to onset and resolution of these and other AEs. Evidence suggests that protocol modifications, such as treatment interruptions and dose reductions, are effective ways to manage AEs while maintaining disease control. Nonpharmacologic and pharmacologic interventions may also be considered as part of an AE management strategy. Overall, healthcare providers and patients with advanced BCC should be aware of the HHI class-effect AEs and plan effective management strategies to avoid treatment discontinuation and optimize therapeutic response.

对于传统治疗方法不可行或无效的晚期基底细胞癌(BCC)患者,刺猬通路抑制剂(HHIs)拓宽了他们的治疗选择。Sonidegib和vismodegib是口服HHIs,分别在关键的II期BOLT(NCT01327053)和ERIVANCE(NCT00833417)试验中显示出良好的疗效,因此被批准用于晚期BCC患者的治疗。然而,使用这些药物时观察到的治疗突发不良事件(AEs)的发生率和类型可能会限制 HHIs 的持续使用,并最终影响临床结果。在这篇综述中,我们总结了索尼吉布和维斯莫吉布的安全性和耐受性,并讨论了针对 HHI 类效应 AEs(包括肌肉痉挛、肌酸磷酸激酶升高、脱发和消化不良)的潜在管理策略。这些 AEs 主要发生在治疗早期,可导致治疗中断。sonidegib和vismodegib的药代动力学特征存在差异,这可能是导致上述AEs和其他AEs的发生和缓解时间存在差异的原因。有证据表明,修改治疗方案(如中断治疗和减少剂量)是在维持疾病控制的同时控制AEs的有效方法。作为 AE 管理策略的一部分,还可考虑采取非药物和药物干预措施。总之,医护人员和晚期 BCC 患者应了解 HHI 类效应 AE,并制定有效的管理策略,以避免治疗中断并优化治疗反应。
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引用次数: 0
Integrated Safety Update of Abrocitinib in 3802 Patients with Moderate-to-Severe Atopic Dermatitis: Data from More than 5200 Patient-Years with Up to 4 Years of Exposure 阿昔替尼治疗 3802 例中度至重度特应性皮炎患者的综合安全性更新:来自 5200 多名患者长达 4 年暴露期的数据。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-06-18 DOI: 10.1007/s40257-024-00869-w
Eric L. Simpson, Jonathan I. Silverberg, Audrey Nosbaum, Kevin Winthrop, Emma Guttman-Yassky, Karin M. Hoffmeister, Alexander Egeberg, Hernan Valdez, Haiyun Fan, Saleem A. Farooqui, Gary Chan, Justine Alderfer, William Romero, Kanti Chittuluru
<div><h3>Background</h3><p>Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile.</p><h3>Objective</h3><p>We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program.</p><h3>Methods</h3><p>Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed.</p><h3>Results</h3><p>Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 10<sup>3</sup>/mm<sup>3</sup> before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs neve
背景:阿昔替尼是一种口服、每日一次的 Janus 激酶 1 选择性抑制剂,对中重度特应性皮炎疗效显著,且长期安全性可控:阿罗西替尼是一种口服、每日一次的 Janus 激酶 1 选择性抑制剂,对中重度特应性皮炎疗效显著,且具有可控的长期安全性:我们的目的是根据JADE临床开发项目中对中重度特应性皮炎患者最长近4年的现有数据,提供阿罗西替尼最新的长期安全性综合结果:分析包括3802例患者(暴露:5213.9患者年),这些患者来自II期单药研究(NCT02780167)和III期研究JADE MONO-1(NCT03349060)、JADE MONO-2(NCT03575871)、JADE TEEN(NCT03796676)、JADE COMPARE(NCT03720470)、JADE DARE(NCT04345367;仅 200 毫克)、JADE REGIMEN(NCT03627767)和 JADE EXTEND(NCT03422822;数据截止日期 2021 年 9 月 25 日)。接受一种或多种剂量阿罗西替尼200毫克或100毫克治疗的患者的数据被汇集到一致剂量队列(患者在合格的母研究和/或长期研究中被分配接受相同剂量的阿罗西替尼治疗)或可变剂量队列(患者接受开放标签阿罗西替尼200毫克治疗;应答者被随机分配到阿罗西替尼200毫克、100毫克或安慰剂,然后可接受阿罗西替尼200毫克加局部皮质类固醇治疗)。对特别关注的不良事件发生率进行了评估。对带状疱疹和严重感染的风险因素进行了Cox回归分析:总体而言,这项对阿罗西替尼暴露时间最长达 4 年的长期数据进行的安全性分析表明,与之前报告的风险概况相比没有发生任何变化。使用一致剂量的阿罗西替尼 200 毫克和 100 毫克时,最常见的严重感染(根据《监管活动医学字典》首选术语)是带状疱疹(0.5% 和 0.2%)、肺炎(两种剂量均为 0.2%)和单纯疱疹(两种剂量均为 0.1%)。带状疱疹的风险因素包括带状疱疹病史、阿昔替尼 200 毫克剂量、年龄≥ 65 岁、发病前绝对淋巴细胞计数为 3/mm3,以及居住在亚洲。对于严重感染,体重大于 100 千克是一个风险因素。老年患者(年龄≥65岁)与年轻患者(年龄在18岁至60岁之间)相比,使用阿罗西替尼200毫克和100毫克一致剂量的发病率/100患者年(95%置信区间)更高:本次安全性更新显示,阿罗西替尼的安全性表现一致,没有出现新的安全性信号,并继续证明阿罗西替尼在中重度特应性皮炎患者中具有可控的长期安全性。特定不良事件的风险在某些患者人群中较高,尤其是年龄≥65岁的患者。[临床试验注册:NCT02780167;研究开始日期:2016 年 4 月;主要完成日期:2017 年 3 月;研究完成日期:2017 年 4 月。NCT03349060;研究开始日期:2017 年 12 月 7 日;研究完成日期:2019 年 3 月 26 日。NCT03575871;研究开始日期:2018 年 6 月 29 日;研究完成日期:2019 年 8 月 13 日。NCT03720470;研究开始日期:2018 年 10 月 29 日;主要完成日期:2019 年 12 月 27 日;研究完成日期:2020 年 3 月 6 日。NCT03796676;研究开始日期:2019 年 2 月 18 日;研究完成日期:2020 年 4 月 8 日。NCT03627767;研究开始日期:2018 年 6 月 11 日;主要完成日期:2020 年 9 月 2 日;研究完成日期:2020 年 10 月 7 日。NCT04345367;研究开始日期:2020 年 6 月 11 日;主要完成日期:2020 年 12 月 16 日;研究完成日期:2021 年 7 月 13 日。NCT03422822;研究开始日期:2018 年 3 月 8 日;研究完成日期:进行中(预计完成日期:2026 年 1 月 31 日)。
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引用次数: 0
Adherence to Hidradenitis Suppurativa Treatment 坚持化脓性扁桃体炎治疗。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-06-11 DOI: 10.1007/s40257-024-00871-2
Caitlyn B. Dagenet, Swetha Atluri, Elaine Ma, Lauren Tong, Khiem A. Tran, Joshua Hekmatajah, Rahul Masson, Jennifer L. Hsiao, Vivian Y. Shi

Hidradenitis suppurativa (HS) is a chronic, debilitating skin condition that requires multimodal treatment. Adherence remains a significant challenge for many patients due to complex nature of treatment, thus presenting a barrier to management success. This review summarizes the current literature on the factors associated with adherence to medications, and lifestyle behaviors in patients with HS and proposes strategies to improve adherence. In February 2023, a systematic literature search was conducted by two independent authors on PubMed and EMBASE for articles from 2000 to 2023 on hidradenitis suppurativa adherence. A total of 21 articles met inclusion/exclusion criteria for this review. Of the studies, 11 addressed systemic medication adherence, 3 addressed topical medication adherence, 2 addressed both systemic and topical medication adherence, and 5 addressed lifestyle/behavioral modification adherence. The generalizability of results was limited by differences in study design, outcome measures, and sample size. English-only articles with full texts were used. The most reported reasons for non-adherence included presence of side effects, cost of medications, low efficacy, and unclear instructions. Proposed strategies to improve adherence in HS patients include management of side effects, use of reminder systems, improved patient education, patient support groups, aid of family and caregivers, personalization of the medication regimen, and regular follow-ups with patients. PROSPERO Registration Number: CRD42023488549.

化脓性扁平湿疹(HS)是一种需要多模式治疗的慢性、衰弱性皮肤病。由于治疗的复杂性,对许多患者来说,坚持治疗仍然是一个巨大的挑战,从而阻碍了治疗的成功。本综述总结了与HS患者坚持用药和生活行为相关的现有文献,并提出了提高患者坚持用药和生活行为的策略。2023 年 2 月,两位独立作者在 PubMed 和 EMBASE 上对 2000 年至 2023 年有关化脓性扁桃体炎依从性的文章进行了系统性文献检索。共有 21 篇文章符合本综述的纳入/排除标准。在这些研究中,11 篇研究了系统用药的依从性,3 篇研究了局部用药的依从性,2 篇研究了系统用药和局部用药的依从性,5 篇研究了生活方式/行为改变的依从性。由于研究设计、结果测量和样本量的差异,研究结果的推广性受到了限制。研究采用了全文为英文的文章。报告最多的不坚持治疗的原因包括副作用、药物费用、疗效低和说明书不明确。提高 HS 患者依从性的建议策略包括:控制副作用、使用提醒系统、加强患者教育、患者支持小组、家庭和护理人员的协助、个性化用药方案以及定期随访患者。PROSPERO 注册编号:CRD42023488549。
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引用次数: 0
Switching to Interleukin-23 Inhibitors After Ineffectiveness of Ustekinumab: Evaluating Real-World Outcomes in Psoriasis Treatment 乌司替库单抗无效后转用白细胞介素-23抑制剂:评估银屑病治疗的实际效果。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-05-27 DOI: 10.1007/s40257-024-00868-x
Sarah E. Thomas, Marieke M. B. Seyger, Josje E. Mangnus, Marisol E. Otero, Antoni H. Gostynski, Marcellus D. Njoo, Paul M. Ossenkoppele, Inge M. Haeck, Judith H. J. Hendricksen-Roelofzen, John E. M. Körver, Sharon R. P. Dodemont, Ron A. Tupker, Maartje A. M. Berends, Lizelotte M. J. T. Weppner-Parren, Romy R. M. C. Keijsers, Annet M. Oostveen, Bas Peters, Roland Mommers, Martijn B. A. van Doorn, Milan Tjioe, Wendelien R. Veldkamp, Astrid L. A. Kuijpers, Marloes M. Kleinpenning, Elke M. G. J. de Jong, Juul M. P. A. van den Reek
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引用次数: 0
Correction to: Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program 更正:来自 ALLEGRO 临床试验项目的口服 JAK3/TEC 家族激酶抑制剂 Ritlecitinib 治疗脱发症的综合安全性分析。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-05-24 DOI: 10.1007/s40257-024-00864-1
Brett King, Jennifer Soung, Christos Tziotzios, Lidia Rudnicka, Pascal Joly, Melinda Gooderham, Rodney Sinclair, Natasha A. Mesinkovska, Carle Paul, Yankun Gong, Susan D. Anway, Helen Tran, Robert Wolk, Samuel H. Zwillich, Alexandre Lejeune
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引用次数: 0
The Use of Biologic Agents for the Treatment of Cutaneous Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Review of Reported Cases 使用生物制剂治疗免疫检查点抑制剂引起的皮肤免疫相关不良事件:报告病例回顾。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-05-20 DOI: 10.1007/s40257-024-00866-z
Jolanta Pach, Kailyn Valido, Annika Belzer, Jonathan S. Leventhal

Cutaneous immune-related adverse events encompass a spectrum of dermatological manifestations, including lichenoid reactions, psoriasiform eruptions, eczematous dermatitis, immunobullous disorders, granulomatous reactions, pruritus, vitiligo, and severe cutaneous adverse reactions such as Stevens–Johnson syndrome. The conventional approach to treating high-grade or refractory cutaneous immune-related adverse events has involved high-dose systemic corticosteroids. However, their use is limited owing to the potential disruption of antitumor responses and associated complications. To address this, corticosteroid-sparing targeted immunomodulators have been explored as therapeutic alternatives. Biologic agents, commonly employed for non-cutaneous immune-related adverse events such as colitis, are increasingly recognized for their efficacy in treating various patterns of cutaneous immune-related adverse events, including psoriasiform, immunobullous, and Stevens–Johnson syndrome-like reactions. This review consolidates findings from the English-language literature, highlighting the use of biologic agents in managing diverse cutaneous immune-related adverse event patterns, also encompassing maculopapular, eczematous, and lichenoid eruptions, pruritus, and transient acantholytic dermatosis (Grover disease). Despite the established efficacy of these agents, further research is necessary to explore their long-term effects on antitumor responses.

皮肤免疫相关不良反应包括一系列皮肤病表现,包括苔癣样反应、牛皮癣样糜烂、湿疹性皮炎、免疫嗜血杆菌紊乱、肉芽肿反应、瘙痒、白癜风以及严重的皮肤不良反应,如史蒂文斯-约翰逊综合征。治疗高级别或难治性皮肤免疫相关不良反应的传统方法包括大剂量全身皮质类固醇激素。然而,由于皮质类固醇可能会破坏抗肿瘤反应并引发相关并发症,因此其使用受到限制。为了解决这一问题,人们开始探索使用节省皮质类固醇的靶向免疫调节剂作为替代治疗方法。生物制剂通常用于治疗结肠炎等非皮肤免疫相关不良反应,但在治疗各种皮肤免疫相关不良反应(包括银屑病样、免疫丘疹和史蒂文斯-约翰逊综合征样反应)方面的疗效日益得到认可。本综述汇总了英文文献中的研究结果,重点介绍了生物制剂在治疗各种皮肤免疫相关不良反应中的应用,包括斑丘疹、湿疹、苔藓样疹子、瘙痒和一过性棘层溶解性皮肤病(格罗弗病)。尽管这些药物具有公认的疗效,但仍有必要进一步研究它们对抗肿瘤反应的长期影响。
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引用次数: 0
Management and Long-Term Outcomes of Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) in Children: A Scoping Review 儿童嗜酸性粒细胞增多和全身症状药物反应 (DReSS) 的管理和长期疗效:范围综述》。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-05-16 DOI: 10.1007/s40257-024-00867-y
Nicole Cherepacha, Frances St George-Hyslop, Bindiya Chugani, Yousef Alabdeen, Luis F. Sanchez-Espino, Quenby Mahood, Cathryn Sibbald, Ruud H. J. Verstegen

Drug reaction with eosinophilia and systemic symptoms (DReSS) is known to cause mortality and long-term sequelae in the pediatric population, however there are no established clinical practice guidelines for the management of pediatric DReSS. We conducted a scoping review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the currently available data on treatment, mortality, and long-term sequelae of DReSS in children (aged 0–18 years). Data from 644 individuals revealed that various treatment strategies are being used in the management of pediatric DReSS, and strategies were often used in combination. The diversity in treatment approaches cannot be solely attributed to age or disease severity and reflects the lack of evidence-based management guidelines for DReSS. Children are also at risk of developing autoimmune sequelae following DReSS, most commonly thyroid disease and type 1 diabetes mellitus. We found that the eventual development of autoimmune disease was more often associated with DReSS caused by antibiotics, especially minocycline and sulfamethoxazole, in comparison with individuals who did not develop sequelae. In this study, we identify strengths and weaknesses in the currently available literature and highlight that future prospective studies with structured and long-term follow-up of children with DReSS are needed to better understand potential risk factors for mortality and development of sequelae after DReSS.

众所周知,伴有嗜酸性粒细胞增多和全身症状的药物反应(DReSS)会导致儿科患者的死亡和长期后遗症,但目前还没有针对儿科DReSS管理的既定临床实践指南。我们根据《系统综述和荟萃分析首选报告项目》(Preferred Reporting Items for Systematic Reviews and Meta-Analyses,PRISMA)指南进行了一次范围界定综述,总结了有关儿童(0-18 岁)DReSS 的治疗、死亡率和长期后遗症的现有数据。来自 644 名患者的数据显示,目前在治疗小儿 DReSS 时采用了多种治疗策略,而且这些策略通常是联合使用的。治疗方法的多样性不能完全归因于年龄或疾病的严重程度,这也反映出 DReSS 缺乏循证管理指南。儿童在接受 DReSS 治疗后还可能出现自身免疫后遗症,其中最常见的是甲状腺疾病和 1 型糖尿病。我们发现,与未出现后遗症的患者相比,抗生素(尤其是米诺环素和磺胺甲噁唑)引起的 DReSS 更容易导致自身免疫性疾病的发生。在这项研究中,我们发现了现有文献的优点和不足,并强调今后需要对患有 DReSS 的儿童进行结构化和长期的前瞻性随访研究,以更好地了解 DReSS 后死亡和后遗症发生的潜在风险因素。
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引用次数: 0
Managing the Patient with Psoriasis and Metabolic Comorbidities 管理银屑病和代谢并发症患者。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-05-15 DOI: 10.1007/s40257-024-00857-0
Francesco Bellinato, Martina Maurelli, Davide Geat, Giampiero Girolomoni, Paolo Gisondi

Epidemiological data demonstrate strong associations between psoriasis and metabolic comorbidities, including obesity, hypertension, diabetes mellitus, dyslipidemia, and non-alcoholic fatty liver disease. The presence of metabolic comorbidities significantly influences the selection and effectiveness of pharmacological treatments. Some drugs should be prescribed with caution in patients with metabolic comorbidities because of an increased risk of adverse events, while others could have a reduced effectiveness. The aim of this narrative review is to highlight the challenges that healthcare professionals may face regarding the management of psoriasis in patients with metabolic comorbidities. In the first part of the article, the epidemiological association between psoriasis and metabolic comorbidities and their pathogenetic mechanisms is summarized. The second part describes the efficacy and safety profile of conventional and biologic drugs in patients with selected metabolic comorbidities including obesity, non-alcoholic fatty liver disease/hepatic steatosis, and diabetes. Finally, the role of pharmacological and non-pharmacological interventions, such as diet, alcohol abstinence, physical activity, and smoking avoidance is discussed. In conclusion, the choice of the best approach to manage patients with psoriasis with metabolic comorbidities should encompass both tailored pharmacological and individualized non-pharmacological interventions.

流行病学数据表明,银屑病与肥胖、高血压、糖尿病、血脂异常和非酒精性脂肪肝等代谢并发症密切相关。代谢并发症的存在会严重影响药物治疗的选择和效果。代谢合并症患者应慎用某些药物,因为会增加不良反应的风险,而另一些药物则可能会降低疗效。这篇叙述性综述旨在强调医护人员在管理有代谢合并症的银屑病患者时可能面临的挑战。文章第一部分概述了银屑病与代谢合并症之间的流行病学关联及其发病机制。第二部分介绍了传统药物和生物药物对肥胖、非酒精性脂肪肝/肝硬变和糖尿病等特定代谢合并症患者的疗效和安全性。最后,讨论了药物和非药物干预措施的作用,如饮食、戒酒、体育锻炼和避免吸烟。总之,在选择最佳方法治疗伴有代谢并发症的银屑病患者时,应同时采取针对性的药物和个体化的非药物干预措施。
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引用次数: 0
Approach to the Atypical Wound 处理非典型伤口的方法。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-05-14 DOI: 10.1007/s40257-024-00865-0
Sarah L. Becker, Shannon Kody, Nicole M. Fett, Alexander Hines, Afsaneh Alavi, Alex G. Ortega-Loayza

The heterogeneity of atypical wounds can present diagnostic and therapeutic challenges; however, as the prevalence of atypical wounds grows worldwide, prompt and accurate management is increasingly an essential skill for dermatologists. Addressing the underlying cause of an atypical wound is critical for successful outcomes. An integrated approach with a focus on pain management and patient engagement is recommended to facilitate enduring wound closure. Advances in treatment, in addition to further research and clinical training, are necessary to address the expanding burden of atypical wounds.

非典型伤口的异质性给诊断和治疗带来了挑战;然而,随着全球非典型伤口发病率的增长,及时、准确的处理日益成为皮肤科医生的一项基本技能。解决非典型伤口的根本原因是取得成功结果的关键。建议采用综合方法,重点关注疼痛管理和患者参与,以促进伤口的持久闭合。除了进一步的研究和临床培训外,治疗方法的进步也是应对非典型伤口日益增加的负担所必需的。
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引用次数: 0
Dupilumab Safety and Efficacy up to 1 Year in Children Aged 6 Months to 5 Years with Atopic Dermatitis: Results from a Phase 3 Open-Label Extension Study 杜匹单抗对 6 个月至 5 岁特应性皮炎患儿长达 1 年的安全性和有效性:3期开放标签扩展研究结果。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-05-14 DOI: 10.1007/s40257-024-00859-y
Amy S. Paller, Elaine C. Siegfried, Eric L. Simpson, Michael J. Cork, Robert Sidbury, Iris H. Chen, Faisal A. Khokhar, Jing Xiao, Ariane Dubost-Brama, Ashish Bansal

Background

Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management.

Objectives

The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE.

Methods

In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg).

Results

Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0–5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator’s Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores.

Conclusions

Consistent with results seen in adults, adolescents, and older children (aged 6–11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population.

Trial Registration

ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).

背景:患有中度至重度特应性皮炎(AD)的儿童患者通常疾病负担较重,且病情持续存在的风险较高。尽管存在持续使用安全性不佳和停药后复发风险的问题,但标准的免疫抑制系统治疗一直被用于儿童特应性皮炎的标示外治疗。生物制剂 dupilumab 是首个获准用于 6 个月大儿童中度至重度 AD 的全身治疗药物。我们需要这一患者群体的长期安全性和疗效数据,以便为持续性 AD 管理提供依据:这项工作的目的是在一项开放标签扩展(OLE)研究[LIBERTY AD PED-OLE(NCT02612454)]中,确定6个月至5岁中重度AD儿童接受长达1年的dupilumab治疗的长期安全性和疗效,这些儿童之前参加了为期16周的双盲3期LIBERTY AD PRESCHOOL试验(NCT03346434 B部分;母研究),随后被纳入PED-OLE:在PED-OLE中,患者按照体重阶梯疗法(体重≥5 kg至<15 kg:200 mg;≥15 kg至<30 kg:300 mg)每4周接受一次dupilumab治疗:对142名患者的数据进行了分析,其中60名患者在数据库锁定时已完成52周的访问。基线时的平均年龄为 4.1 岁 [SD, 1.13; range, 1.0-5.9 years]。大多数患者(78.2%)报告了≥1次治疗突发不良事件(TEAE),其中大多数为轻度或中度,且为一过性。最常报告的 TEAE 为鼻咽炎(19.7%)、咳嗽(15.5%)和发热(14.1%)。有 1 例 TEAE 导致停药(严重荨麻疹,1 天后缓解)。到第52周时,36.2%的患者的研究者总体评估得分达到0/1(皮肤清澈/几乎清澈),96.6%、79.3%和58.6%的患者的湿疹面积和严重程度指数得分分别至少改善了50%、75%或90%:与在成人、青少年和年龄较大的儿童(6-11 岁)身上看到的结果一致,对于 6 个月至 5 岁中度至重度 AD 控制不佳的儿童,使用杜比单抗长达 1 年的治疗显示出了可接受的长期安全性和持续疗效。这些结果支持在这一患者群体中长期持续使用dupilumab:试验注册:ClinicalTrials.gov Identifiers:试验注册:ClinicalTrials.gov Identifiers:NCT02612454 和 NCT03346434(B 部分)。
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引用次数: 0
期刊
American Journal of Clinical Dermatology
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