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Rapidly Evolving Pre- and Post-surgical Systemic Treatment of Melanoma 快速发展的黑色素瘤术前和术后系统治疗。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-02-26 DOI: 10.1007/s40257-024-00852-5
Ryan C. Augustin, Jason J. Luke

With the development of effective BRAF-targeted and immune-checkpoint immunotherapies for metastatic melanoma, clinical trials are moving these treatments into earlier adjuvant and perioperative settings. BRAF-targeted therapy is a standard of care in resected stage III–IV melanoma, while anti-programmed death-1 (PD1) immunotherapy is now a standard of care option in resected stage IIB through IV disease. With both modalities, recurrence-free survival and distant-metastasis-free survival are improved by a relative 35–50%, yet no improvement in overall survival has been demonstrated. Neoadjuvant anti-PD1 therapy improves event-free survival by approximately an absolute 23%, although improvements in overall survival have yet to be demonstrated. Understanding which patients are most likely to recur and which are most likely to benefit from treatment is now the highest priority question in the field. Biomarker analyses, such as gene expression profiling of the primary lesion and circulating DNA, are preliminarily exciting as potential biomarkers, though each has drawbacks. As in the setting of metastatic disease, markers that inform positive outcomes include interferon-γ gene expression, PD-L1, and high tumor mutational burden, while negative predictors of outcome include circulating factors such as lactate dehydrogenase, interleukin-8, and C-reactive protein. Integrating and validating these markers into clinically relevant models is thus a high priority. Melanoma therapeutics continues to advance with combination adjuvant approaches now investigating anti-PD1 with lymphocyte activation gene 3 (LAG3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and individualized neoantigen therapies. How this progress will be integrated into the management of a unique patient to reduce recurrence, limit toxicity, and avoid over-treatment will dominate clinical research and patient care over the next decade.

随着针对转移性黑色素瘤的有效 BRAF 靶向疗法和免疫检查点免疫疗法的开发,临床试验正在将这些疗法推向早期辅助治疗和围手术期治疗。BRAF靶向疗法是切除的III-IV期黑色素瘤的标准治疗方法,而抗程序性死亡-1(PD1)免疫疗法目前是切除的IIB期至IV期疾病的标准治疗方法。采用这两种疗法后,无复发生存期和无远处转移生存期相对提高了35%-50%,但总生存期却没有得到改善。新辅助抗PD1疗法可将无事件生存期绝对值提高约23%,但总生存期的改善尚未得到证实。了解哪些患者最有可能复发,哪些患者最有可能从治疗中获益是目前该领域最优先考虑的问题。生物标志物分析,如原发病灶和循环 DNA 的基因表达谱分析,作为潜在的生物标志物初步令人兴奋,但每种方法都有缺点。与转移性疾病的情况一样,能预测阳性结果的标志物包括干扰素-γ 基因表达、PD-L1 和高肿瘤突变负荷,而预测阴性结果的标志物包括乳酸脱氢酶、白细胞介素-8 和 C 反应蛋白等循环因子。因此,将这些标记物整合并验证到临床相关模型中是当务之急。黑色素瘤疗法也在不断进步,目前正在研究抗PD1与淋巴细胞活化基因3(LAG3)、带Ig和ITIM结构域的T细胞免疫受体(TIGIT)以及个体化新抗原疗法的联合辅助疗法。在未来十年中,如何将这些进展整合到对特殊患者的管理中,以减少复发、限制毒性并避免过度治疗,将成为临床研究和患者护理的主要方向。
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引用次数: 0
The Impact of Dermatologic Adverse Events on the Quality of Life of Oncology Patients: A Review of the Literature 皮肤科不良事件对肿瘤患者生活质量的影响:文献综述
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-02-16 DOI: 10.1007/s40257-024-00847-2
Annika Belzer, Jolanta J. Pach, Kailyn Valido, Jonathan S. Leventhal

Dermatologic adverse events resulting from oncologic therapy are common and negatively impact patients’ quality of life. Dermatologic adverse events include toxicity of the skin, oral mucosa, nails, and hair and are seen with cytotoxic chemotherapy, targeted therapy, immunotherapy, and radiation therapy, with distinct patterns of dermatologic adverse events by drug class. Here, we review the literature on the impact of dermatologic adverse events on quality of life. Studies on quality of life in patients with cancer have relied on scales such as the Dermatologic Life Quality Index and Skindex to demonstrate the association between dermatologic adverse events and declining quality of life. This relationship is likely due to a variety of factors, including physical discomfort, changes to body image, decreased self-esteem, and an effect on social interactions. Addressing such quality-of-life concerns for patients with cancer is critical, not only for patients’ well-being but also because decreased satisfaction with treatment can lead to discontinuation of treatment or dose reduction. Prophylactic treatment and early management of dermatologic adverse events by experienced dermatologists can alleviate the negative effects on quality of life and allow continuation of life-prolonging treatment.

肿瘤治疗引起的皮肤不良反应很常见,会对患者的生活质量产生负面影响。皮肤科不良事件包括皮肤、口腔粘膜、指甲和头发的毒性,常见于细胞毒性化疗、靶向治疗、免疫治疗和放射治疗,不同药物类别的皮肤科不良事件有不同的模式。在此,我们回顾了有关皮肤病不良事件对生活质量影响的文献。有关癌症患者生活质量的研究依赖于皮肤病生活质量指数(Dermatologic Life Quality Index)和Skindex等量表来证明皮肤病不良事件与生活质量下降之间的关系。这种关系可能是由多种因素造成的,包括身体不适、身体形象改变、自尊心下降以及对社会交往的影响。解决癌症患者的这些生活质量问题至关重要,这不仅关系到患者的福祉,还因为对治疗的满意度下降可能导致治疗中断或剂量减少。由经验丰富的皮肤科医生进行预防性治疗并及早处理皮肤科不良反应,可减轻对生活质量的负面影响,使延长生命的治疗得以继续。
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引用次数: 0
Field Cancerization Therapies for the Management of Actinic Keratosis: An Updated Review 治疗角化性皮炎的野战癌化疗法:最新综述。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-02-13 DOI: 10.1007/s40257-023-00839-8
Ishita Aggarwal, Carolina Puyana, Neha Chandan, Nathan Jetter, Maria Tsoukas

Field cancerization theory highlights that the skin surrounding actinic keratoses (AK) is also at increased risk for possible malignant transformation; thus, field-directed treatments may both reduce the risk of AK recurrence and potentially reduce the risk of development of cutaneous squamous cell carcinoma (cSCC). Photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL), as well as topical treatments such as 5-fluorouracil (5-FU), diclofenac gel, piroxicam, imiquimod, and ingenol mebutate, have all shown higher efficacy than vehicle treatments. PDT is widely recognized for its high efficacy; however, concerns for associated pain have driven new studies to begin using alternative illumination and pretreatment techniques, including lasers. Among topical treatments, a combination of 5-FU and salicylic acid (5-FU–SA) has shown to be the most effective but also causes the most adverse reactions. Tirbanibulin, a new topical agent approved for use in 2020, boasts a favorable safety profile in comparison with imiquimod, 5-FU, and diclofenac. Meanwhile, ingenol mebutate is no longer recommended for the treatment of AKs due to concerns for increased risk of cSCC development. Moving forward, an increasing number of studies push for standardization of outcome measures to better predict risk of future cSCC and use of more effective measures of cost to better guide patients. Here, we present an updated and comprehensive narrative review both confirming the efficacy of previously mentioned therapies as well as highlighting new approaches to PDT and discussing the use of lasers and novel topical treatments for treatment of AK.

现场癌化理论强调,光化性角化病(AK)周围皮肤发生恶性转化的风险也会增加;因此,现场定向治疗既可以降低 AK 复发的风险,也有可能降低皮肤鳞状细胞癌(cSCC)的发病风险。使用氨基乙酰乙酸(ALA)或甲氨基乙酰乙酸甲酯(MAL)的光动力疗法(PDT),以及 5-氟尿嘧啶(5-FU)、双氯芬酸凝胶、吡罗昔康、咪喹莫特和甲丁酸依地孕酮等外用疗法,都显示出比药物疗法更高的疗效。光导疗法因其疗效显著而得到广泛认可;然而,对相关疼痛的担忧促使新的研究开始使用其他照明和预处理技术,包括激光。在局部治疗中,5-FU 和水杨酸(5-FU-SA)的组合被证明是最有效的,但也会引起最多的不良反应。将于2020年获批使用的新型外用药物Tirbanibulin与咪喹莫特、5-FU和双氯芬酸相比,具有良好的安全性。同时,由于担心 cSCC 发展风险增加,已不再推荐使用甲丁酸伊戈灵治疗 AK。展望未来,越来越多的研究推动结果测量的标准化,以更好地预测未来 cSCC 的风险,并使用更有效的成本测量方法为患者提供更好的指导。在此,我们将发表一篇最新的全面综述,既肯定了之前提到的疗法的疗效,又重点介绍了PDT的新方法,并讨论了激光和新型局部疗法在治疗AK中的应用。
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引用次数: 0
Correction to: OX40 in the Pathogenesis of Atopic Dermatitis—A New Therapeutic Target 更正:特应性皮炎发病机制中的 OX40--新的治疗靶点。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-02-10 DOI: 10.1007/s40257-024-00850-7
Michael Croft, Ehsanollah Esfandiari, Camilla Chong, Hailing Hsu, Kenji Kabashima, Greg Kricorian, Richard B. Warren, Andreas Wollenberg, Emma Guttman-Yassky
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引用次数: 0
Autoimmune, Autoinflammatory Disease and Cutaneous Malignancy Associations with Hidradenitis Suppurativa: A Cross-Sectional Study 自身免疫性疾病、自身炎症性疾病和皮肤恶性肿瘤与扁平苔藓的关联:一项横断面研究
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-02-09 DOI: 10.1007/s40257-024-00844-5
Hilliard T. Brydges, Ogechukwu C. Onuh, Rebecca Friedman, Joy Barrett, Rebecca A. Betensky, Catherine P. Lu, Avrom S. Caplan, Afsaneh Alavi, Ernest S. Chiu

Background

Hidradenitis suppurativa (HS) is a debilitating cutaneous disease characterized by severe painful inflammatory nodules/abscesses. At present, data regarding the epidemiology and pathophysiology of this disease are limited.

Objective

To define the prevalence and comorbidity associations of HS.

Methods

This was a cross-sectional study of EPICTM Cosmos© examining over 180 million US patients. Prevalences were calculated by demographic and odds ratios (OR) and identified comorbidity correlations.

Results

All examined metabolism-related, psychological, and autoimmune/autoinflammatory (AI) diseases correlated with HS. The strongest associations were with pyoderma gangrenosum [OR 26.56; confidence interval (CI): 24.98–28.23], Down syndrome (OR 11.31; CI 10.93–11.70), and polycystic ovarian syndrome (OR 11.24; CI 11.09–11.38). Novel AI associations were found between HS and lupus (OR 6.60; CI 6.26–6.94) and multiple sclerosis (MS; OR 2.38; CI 2.29–2.48). Cutaneous malignancies were largely not associated in the unsegmented cohort; however, among Black patients, novel associations with melanoma (OR 2.39; CI 1.86–3.08) and basal cell carcinoma (OR 2.69; CI 2.15–3.36) were identified.

Limitations

International Classification of Diseases (ICD)-based disease identification relies on coding fidelity and diagnostic accuracy.

Conclusion

This is the first study to identify correlations between HS with melanoma and basal cell carcinoma (BCC) among Black patients as well as MS and lupus in all patients with HS.

背景:化脓性扁平湿疹(HS)是一种使人衰弱的皮肤病,其特征是严重疼痛的炎性结节/脓肿。目前,有关该病流行病学和病理生理学的数据十分有限:方法:这是一项横断面研究,研究对象为美国、加拿大、英国、法国、德国、日本、韩国和中国:这是 EPICTM Cosmos© 的一项横断面研究,对超过 1.8 亿美国患者进行了检查。通过人口统计学和几率比(OR)计算患病率,并确定合并症的相关性:结果:所有受检的代谢相关疾病、心理疾病和自身免疫/自体炎症(AI)疾病均与 HS 相关。与脓皮病[OR 26.56;置信区间(CI):24.98-28.23]、唐氏综合征(OR 11.31;CI 10.93-11.70)和多囊卵巢综合征(OR 11.24;CI 11.09-11.38)的相关性最强。在 HS 与狼疮(OR 6.60;CI 6.26-6.94)和多发性硬化症(MS;OR 2.38;CI 2.29-2.48)之间发现了新的 AI 关联。皮肤恶性肿瘤在未分段队列中基本没有关联;但在黑人患者中,发现了与黑色素瘤(OR 2.39;CI 1.86-3.08)和基底细胞癌(OR 2.69;CI 2.15-3.36)的新关联:局限性:基于国际疾病分类(ICD)的疾病识别依赖于编码的准确性和诊断的准确性:这是首次在黑人患者中发现 HS 与黑色素瘤和基底细胞癌 (BCC) 之间的相关性,以及在所有 HS 患者中发现 MS 与狼疮之间的相关性。
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引用次数: 0
Therapeutic Strategies in BRAF V600 Wild-Type Cutaneous Melanoma BRAF V600 野生型皮肤黑色素瘤的治疗策略
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-02-08 DOI: 10.1007/s40257-023-00841-0
Alexandra Haugh, Adil I. Daud

There have been many recent advances in melanoma therapy. While 50% of melanomas have a BRAF mutation and are a target for BRAF inhibitors, the remaining 50% are BRAF wild-type. Immune checkpoint inhibitors targeting PD-1, cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and lymphocyte activated gene-3 (Lag-3) are all approved for the treatment of patients with advanced BRAF wild-type melanoma; however, treatment of this patient population following initial immune checkpoint blockade is a current therapeutic challenge given the lack of other efficacious options. Here, we briefly review available US FDA-approved therapies for BRAF wild-type melanoma and focus on developing treatment avenues for this heterogeneous group of patients. We review the basics of genomic features of both BRAF mutant and BRAF wild-type melanoma as well as efforts underway to develop new targeted therapies involving the mitogen-activated protein kinase (MAPK) pathway for patients with BRAF wild-type tumors. We then focus on novel immunotherapies, including developing checkpoint inhibitors and agonists, cytokine therapies, oncolytic viruses and tumor-infiltrating lymphocytes, all of which represent potential therapeutic avenues for patients with BRAF wild-type melanoma who progress on currently approved immune checkpoint inhibitors.

最近,黑色素瘤治疗取得了许多进展。50%的黑色素瘤存在BRAF突变,是BRAF抑制剂的靶点,而剩下的50%则是BRAF野生型。针对PD-1、细胞毒性T淋巴细胞相关蛋白4(CTLA4)和淋巴细胞活化基因-3(Lag-3)的免疫检查点抑制剂均已获批用于治疗晚期BRAF野生型黑色素瘤患者;然而,由于缺乏其他有效的选择,在初始免疫检查点阻断后对这一患者群体进行治疗是目前的治疗难题。在此,我们简要回顾了美国 FDA 批准的 BRAF 野生型黑色素瘤现有疗法,并重点探讨了为这一异质性患者群体开发治疗途径的问题。我们回顾了 BRAF 突变型和 BRAF 野生型黑色素瘤基因组特征的基本情况,以及目前为 BRAF 野生型肿瘤患者开发涉及丝裂原活化蛋白激酶 (MAPK) 通路的新型靶向疗法的工作。然后,我们将重点放在新型免疫疗法上,包括开发检查点抑制剂和激动剂、细胞因子疗法、溶瘤病毒和肿瘤浸润淋巴细胞,所有这些都是BRAF野生型黑色素瘤患者在使用目前批准的免疫检查点抑制剂后取得进展的潜在治疗途径。
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引用次数: 0
Autoimmune and Cutaneous Inflammatory Comorbidities in Adult-Onset Morphea in the All of Us Research Program 我们所有人研究计划》中成年发病型莫斐斯病的自身免疫和皮肤炎症并发症。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-02-02 DOI: 10.1007/s40257-024-00843-6
Jill T. Shah, William Mark Richardson, Lavanya Mittal, Emily Hejazi, Daniel R. Mazori, Alisa N. Femia
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引用次数: 0
Treatment of Psoriasis Patients with Latent Tuberculosis Using IL-17 and IL-23 Inhibitors: A Retrospective, Multinational, Multicentre Study 使用 IL-17 和 IL-23 抑制剂治疗患有潜伏肺结核的银屑病患者:一项回顾性、多国、多中心研究。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-01-24 DOI: 10.1007/s40257-024-00845-4
Tiago Torres, Andrea Chiricozzi, Luis Puig, Ana Maria Lé, Angelo Valerio Marzano, Paolo Dapavo, Esteban Dauden, Jόse-Manuel Carrascosa, Elizabeth Lazaridou, Gleison Duarte, André V. E. Carvalho, Ricardo Romiti, Natalia Rompoti, Laetitia Teixeira, Miguel Abreu, Elena Ippoliti, Carlo Alberto Maronese, Mar Llamas-Velasco, Eva Vilarrasa, Elena del Alcázar, Athina-Ioanna Daponte, Marina Papoutsaki, Andrea Carugno, Francesco Bellinato, Paolo Gisondi

Background

Tuberculosis has a major global impact. Immunocompetent hosts usually control this disease, resulting in an asymptomatic latent tuberculosis infection (LTBI). Because TNF inhibitors increase the risk of tuberculosis reactivation, current guidelines recommend tuberculosis screening before starting any biologic drug, and chemoprophylaxis if LTBI is diagnosed. Available evidence from clinical trials and real-world studies suggests that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis reactivation.

Objective

To evaluate psoriasis patients with treated or untreated newly diagnosed LTBI who received IL-17 and IL-23 inhibitors and the tolerability/safety of tuberculosis chemoprophylaxis.

Methods

This is a retrospective, observational, multinational study from a series of 14 dermatology centres based in Portugal, Spain, Italy, Greece and Brazil, which included adult patients with moderate-to-severe chronic plaque psoriasis and newly diagnosed LTBI who were treated with IL-23 or IL-17 inhibitors between January 2015 and March 2022. LTBI was diagnosed in the case of tuberculin skin test and/or interferon gamma release assay positivity, according to local guideline, prior to initiating IL-23 or IL-17 inhibitor. Patients with prior diagnosis of LTBI (treated or untreated) or treated active infection were excluded.

Results

A total of 405 patients were included; complete/incomplete/no chemoprophylaxis was administered in 62.2, 10.1 and 27.7% of patients, respectively. The main reason for not receiving or interrupting chemoprophylaxis was perceived heightened risk of liver toxicity and hepatotoxicity, respectively. The mean duration of biological treatment was 32.87 ± 20.95 months, and only one case of active tuberculosis infection (ATBI) was observed, after 14 months of treatment with ixekizumab. The proportion of ATBI associated with ixekizumab was 1.64% [95% confidence interval (CI): 0–5.43%] and 0% for all other agents and 0.46% (95% CI 0–1.06%) and 0% for IL-17 and IL-23 inhibitors, respectively (not statistically significant).

Conclusions

The risk of tuberculosis reactivation in patients with psoriasis and LTBI does not seem to increase with IL-17 or IL-23 inhibitors. IL-17 or IL-23 inhibitors should be preferred over TNF antagonists when concerns regarding tuberculosis reactivation exists. In patients with LTBI considered at high risk for developing complications related to chemoprophylaxis, this preventive strategy may be waived before initiating treatment with IL-17 inhibitors and especially IL-23 inhibitors.

背景:结核病对全球具有重大影响。免疫功能正常的宿主通常会控制这种疾病,导致无症状的潜伏结核感染(LTBI)。由于 TNF 抑制剂会增加结核病再活化的风险,现行指南建议在开始使用任何生物药物前进行结核病筛查,并在确诊为 LTBI 时进行化学预防。临床试验和实际研究的现有证据表明,IL-17 和 IL-23 抑制剂不会增加结核病再激活的风险:评估接受 IL-17 和 IL-23 抑制剂治疗或未经治疗的新诊断为 LTBI 的银屑病患者以及结核病化学预防的耐受性/安全性:这是一项回顾性、观察性、跨国研究,由葡萄牙、西班牙、意大利、希腊和巴西的14个皮肤病中心共同完成,研究对象包括2015年1月至2022年3月期间接受IL-23或IL-17抑制剂治疗的中重度慢性斑块状银屑病和新诊断为LTBI的成年患者。根据当地指南,在开始使用IL-23或IL-17抑制剂之前,如果结核菌素皮试和/或γ干扰素释放检测呈阳性,则可诊断为LTBI。既往诊断为LTBI(治疗过或未治疗过)或治疗过活动性感染的患者被排除在外:结果:共纳入405名患者;分别有62.2%、10.1%和27.7%的患者接受了完全/完全/未接受化学预防。未接受或中断化学预防的主要原因分别是认为肝毒性和肝毒性风险增加。生物治疗的平均持续时间为(32.87 ± 20.95)个月,仅观察到一例活动性肺结核感染(ATBI),是在使用ixekizumab治疗14个月后出现的。与ixekizumab相关的ATBI比例为1.64%[95%置信区间(CI):0-5.43%],所有其他药物为0%,IL-17和IL-23抑制剂分别为0.46%(95% CI 0-1.06%)和0%(无统计学意义):结论:IL-17 或 IL-23 抑制剂似乎不会增加银屑病和 LTBI 患者结核病再活化的风险。如果担心结核病再激活,IL-17 或 IL-23 抑制剂应优先于 TNF 拮抗剂。对于被认为极有可能出现与化学预防相关的并发症的LTBI患者,在开始使用IL-17抑制剂,尤其是IL-23抑制剂治疗之前,可以放弃这种预防策略。
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引用次数: 0
Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program 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(来自 ALLEGRO 临床试验项目)。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-01-23 DOI: 10.1007/s40257-024-00846-3
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

Background

The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA).

Objective

The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.

Methods

Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size–adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported.

Results

In the placebo-controlled cohort (n = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2–75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort (n = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events.

Conclusions

Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available).

Trial Registries

ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).

研究背景ALLEGRO的2a和2b/3期研究表明,口服JAK3/TEC家族激酶抑制剂利特西替尼对年龄≥12岁的斑秃(AA)患者在剂量≥30毫克时具有疗效:本研究旨在综合分析四项关于AA的研究,评估利特西替尼的安全性:方法:分析了两个队列:安慰剂对照队列和全暴露队列。报告了相关不良事件(AEs)和实验室异常的比例和研究规模调整后的发生率(IRs):在安慰剂对照队列(n = 881;中位暴露期:169 天)中,不同剂量的利特西替尼治疗患者出现 AEs 的比例为 70.2-75.4%,而安慰剂组为 69.5%;出现严重 AEs 的比例为 0-3.2%,而安慰剂组为 1.9%。共有 19 名患者因 AE 永久停药(其中 5 人在接受安慰剂治疗期间停药)。在所有暴露队列(n = 1294)中,瑞替尼的中位暴露期为 624 天[总患者年 (PY) 为 2091.7]。1094名患者(84.5%)出现了不良反应,57名患者(4.4%)出现了严重不良反应;78名患者(6.0%)因不良反应永久停药。最常见的不良反应是头痛(17.7%;11.9/100PY)、严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)检测阳性(15.5%;9.8/100PY)和鼻咽炎(12.4%;8.2/100PY)。有两例死亡病例(乳腺癌和急性呼吸衰竭/心跳骤停)。机会性感染的比例(IRs)小于0.1%(0.05/100PY),带状疱疹的比例为1.5%(0.9/100PY),恶性肿瘤(不包括非黑色素瘤皮肤癌)的比例为0.5%(0.3/100PY),主要不良心血管事件的比例为0.2%(0.1/100PY):在年龄≥12岁的AA患者中,瑞替西尼耐受性良好,24个月内安全性可接受(可提供视频摘要和图解语言摘要):试验登记:ClinicalTrials.gov:NCT02974868(注册日期:2016年11月29日)、NCT04517864(2020年8月18日)、NCT03732807(2018年7月11日)和NCT04006457(2019年5月7日)。
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引用次数: 0
The Skin Microbiome and its Significance for Dermatologists 皮肤微生物组及其对皮肤科医生的意义。
IF 8.6 1区 医学 Q1 DERMATOLOGY Pub Date : 2024-01-22 DOI: 10.1007/s40257-023-00842-z
Cleo Whiting, Sara Abdel Azim, Adam Friedman

The skin is a physical and immunological barrier to the external environment. Its large surface area is colonized by diverse communities of microorganisms, including bacteria, viruses, fungi, and Demodex species mites. These microorganisms and their genetic material together create the skin microbiome. Physiologic and anatomic properties of skin sites create biogeographical habitats (dry, moist, and sebaceous) where distinct microbiota communities reside. Although, in general, the composition of these habitats is maintained from person to person, the skin microbiome of an individual also has unique microbial features. Dysbiosis occurs when the normal abundance, composition, or location of the microbiota is changed, most notably there is a decrease in flora diversity. Certain skin diseases, including atopic dermatitis, rosacea, and psoriasis are associated with cutaneous dysbiosis, and even disruption of the gut microbiota. Studies have shown that current treatments for these dermatologic conditions can alter/stabilize the skin microbiome, and there is emerging research detailing the impact of prebiotics, probiotics, and postbiotics on these conditions. Although clinical guidelines do not currently exist, clinical studies support the safety and possible benefits of using topical prebiotics and postbiotics and oral probiotics for a variety of skin conditions. Until such guidelines exist, utilizing carefully designed clinical studies to inform clinical practice is recommended.

皮肤是外界环境的物理和免疫屏障。皮肤的表面积很大,有多种微生物群落,包括细菌、病毒、真菌和螨虫。这些微生物及其遗传物质共同组成了皮肤微生物群。皮肤部位的生理和解剖特性创造了生物地理栖息地(干燥、潮湿和皮脂腺),不同的微生物群落栖息于此。虽然一般来说,这些栖息地的组成因人而异,但每个人的皮肤微生物群也有其独特的微生物特征。当微生物群的正常丰度、组成或位置发生变化时,就会出现菌群失调,最明显的是菌群多样性减少。某些皮肤病,包括特应性皮炎、红斑痤疮和银屑病,都与皮肤菌群失调,甚至肠道微生物群紊乱有关。研究表明,目前针对这些皮肤病的治疗方法可以改变/稳定皮肤微生物群,而且有新的研究详细说明了益生菌、益生菌和后益生菌对这些疾病的影响。虽然目前还没有临床指南,但临床研究支持使用外用益生菌、益生菌后和口服益生菌治疗各种皮肤病的安全性和可能的益处。在制定此类指南之前,建议利用精心设计的临床研究来指导临床实践。
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American Journal of Clinical Dermatology
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