Pub Date : 2024-02-26DOI: 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。
{"title":"Rapidly Evolving Pre- and Post-surgical Systemic Treatment of Melanoma","authors":"Ryan C. Augustin, Jason J. Luke","doi":"10.1007/s40257-024-00852-5","DOIUrl":"10.1007/s40257-024-00852-5","url":null,"abstract":"<div><p>With the development of effective <i>BRAF</i>-targeted and immune-checkpoint immunotherapies for metastatic melanoma, clinical trials are moving these treatments into earlier adjuvant and perioperative settings. <i>BRAF</i>-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-<i>γ</i> 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.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 3","pages":"421 - 434"},"PeriodicalIF":8.6,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-16DOI: 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。
{"title":"The Impact of Dermatologic Adverse Events on the Quality of Life of Oncology Patients: A Review of the Literature","authors":"Annika Belzer, Jolanta J. Pach, Kailyn Valido, Jonathan S. Leventhal","doi":"10.1007/s40257-024-00847-2","DOIUrl":"10.1007/s40257-024-00847-2","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 3","pages":"435 - 445"},"PeriodicalIF":8.6,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139745785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-13DOI: 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。
{"title":"Field Cancerization Therapies for the Management of Actinic Keratosis: An Updated Review","authors":"Ishita Aggarwal, Carolina Puyana, Neha Chandan, Nathan Jetter, Maria Tsoukas","doi":"10.1007/s40257-023-00839-8","DOIUrl":"10.1007/s40257-023-00839-8","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 3","pages":"391 - 405"},"PeriodicalIF":8.6,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139728802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-10DOI: 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
{"title":"Correction to: OX40 in the Pathogenesis of Atopic Dermatitis—A New Therapeutic Target","authors":"Michael Croft, Ehsanollah Esfandiari, Camilla Chong, Hailing Hsu, Kenji Kabashima, Greg Kricorian, Richard B. Warren, Andreas Wollenberg, Emma Guttman-Yassky","doi":"10.1007/s40257-024-00850-7","DOIUrl":"10.1007/s40257-024-00850-7","url":null,"abstract":"","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 3","pages":"463 - 463"},"PeriodicalIF":8.6,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11070392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139715738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-09DOI: 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.
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.
Pub Date : 2024-02-08DOI: 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.
{"title":"Therapeutic Strategies in BRAF V600 Wild-Type Cutaneous Melanoma","authors":"Alexandra Haugh, Adil I. Daud","doi":"10.1007/s40257-023-00841-0","DOIUrl":"10.1007/s40257-023-00841-0","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 3","pages":"407 - 419"},"PeriodicalIF":8.6,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139701655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-02DOI: 10.1007/s40257-024-00843-6
Jill T. Shah, William Mark Richardson, Lavanya Mittal, Emily Hejazi, Daniel R. Mazori, Alisa N. Femia
{"title":"Autoimmune and Cutaneous Inflammatory Comorbidities in Adult-Onset Morphea in the All of Us Research Program","authors":"Jill T. Shah, William Mark Richardson, Lavanya Mittal, Emily Hejazi, Daniel R. Mazori, Alisa N. Femia","doi":"10.1007/s40257-024-00843-6","DOIUrl":"10.1007/s40257-024-00843-6","url":null,"abstract":"","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"343 - 345"},"PeriodicalIF":8.6,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 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.
{"title":"Treatment of Psoriasis Patients with Latent Tuberculosis Using IL-17 and IL-23 Inhibitors: A Retrospective, Multinational, Multicentre Study","authors":"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","doi":"10.1007/s40257-024-00845-4","DOIUrl":"10.1007/s40257-024-00845-4","url":null,"abstract":"<div><h3>Background</h3><p>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.</p><h3>Objective</h3><p>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.</p><h3>Methods</h3><p>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.</p><h3>Results</h3><p>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).</p><h3>Conclusions</h3><p>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.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"333 - 342"},"PeriodicalIF":8.6,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10867072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-23DOI: 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).
{"title":"Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program","authors":"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","doi":"10.1007/s40257-024-00846-3","DOIUrl":"10.1007/s40257-024-00846-3","url":null,"abstract":"<div><h3>Background</h3><p>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).</p><h3>Objective</h3><p>The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.</p><h3>Methods</h3><p>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.</p><h3>Results</h3><p>In the placebo-controlled cohort (<i>n</i> = 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 (<i>n</i> = 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.</p><h3>Conclusions</h3><p>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).</p><h3>Trial Registries</h3><p>ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"299 - 314"},"PeriodicalIF":8.6,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10867086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-22DOI: 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.
{"title":"The Skin Microbiome and its Significance for Dermatologists","authors":"Cleo Whiting, Sara Abdel Azim, Adam Friedman","doi":"10.1007/s40257-023-00842-z","DOIUrl":"10.1007/s40257-023-00842-z","url":null,"abstract":"<div><p>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 <i>Demodex</i> 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.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"25 2","pages":"169 - 177"},"PeriodicalIF":8.6,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}