JAK inhibitors

JAK 抑制剂
  • 文章类型: Journal Article
    背景:几种全身疗法已被批准用于治疗重度AD。特别是,Janus激酶抑制剂(JAKI),包括abrocitinib,baricitinib,和upadacitinib,在多项临床试验中进行评估后,最近获得了用于治疗重度AD患者的批准.然而,人们对这些药物的长期安全性和实际临床实践中这些药物的管理提出了一些担忧.在本文中,我们描述了Delphi共识的结果,该共识旨在描述有关JAKI和聚焦的知识,特别是,关于在日常实践中为皮肤科医生提供有关使用这些药物的临床建议。
    方法:12位意大利皮肤科医生回顾了有关JAKI疗效和安全性的最新文献,并提出了24项陈述。
    结果:就三个主要主题达成了共识:(1)在中重度AD患者中使用JAKi治疗;(2)不同表型的JAK抑制剂的有效性和安全性;(3)在临床实践中使用JAKi治疗患者的不同方法。小组就所有发言提出了几项建议。
    结论:鉴于JAKI在临床实践中的广泛应用,为每个患者的表型建立特定的随访是至关重要的,以实现可能的最佳临床结局并将潜在的不良事件降至最低.
    BACKGROUND: Several systemic therapies have been approved for the treatment of severe AD. In particular, Janus kinase inhibitors (JAKi), including abrocitinib, baricitinib, and upadacitinib, recently received approval for the treatment of patients with severe AD after being evaluated in several clinical trials. However, a few concerns have been raised regarding their long-term safety and the management of these drugs in real-world clinical practice. In this article we described the results of a Delphi consensus aimed at describing the knowledge on JAKi and focusing, in particular, on providing clinical recommendations for dermatologists in daily practice regarding the use of these drugs.
    METHODS: Twelve Italian dermatologists reviewed the most recent literature regarding the efficacy and safety profiles of JAKi and proposed 24 statements.
    RESULTS: Agreement was reached for statements focusing on three main topics: (1) place in therapy of JAKi in patients with moderate-to-severe AD; (2) effectiveness and safety of JAK inhibitors in different phenotypes; (3) different approaches to the management of patients treated with JAKi in clinical practice. The panel proposed several recommendations regarding all the statements.
    CONCLUSIONS: Given the wide use of JAKi in clinical practice, it is crucial to establish a specific follow-up for each patient\'s phenotype in order to achieve the best possible clinical outcome and minimize potential adverse events.
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  • 文章类型: Journal Article
    目的:更新证据基础,以告知2024年JCR临床实践指南(CPGs)用于治疗老年人类风湿性关节炎(RA)。
    方法:评估了关于药物治疗的有效性和安全性的四个临床问题(CQs)。用CQ1寻址甲氨蝶呤(MTX),CQ2生物疾病缓解抗风湿药(bDMARDs),CCD3Janus激酶(JAK)抑制剂,和CQ4糖皮质激素(GC)。使用建议分级评估来评估证据的质量,发展,和评价体系。
    结果:观察性研究证实了MTX在老年RA患者治疗中的关键作用。荟萃分析显示,肿瘤坏死因子抑制剂和JAK抑制剂在老年RA患者中明确有效。没有数据表明bDMARDs对老年患者不安全。没有老年患者使用JAK抑制剂的安全性数据。一项随机对照试验表明,低剂量GC的长期治疗会增加GC相关不良事件的风险。对于所有CQ,总体证据的确定性非常低。
    结论:本系统综述为开发2024个JCRCPGs治疗老年RA患者提供了必要的证据。需要继续更新JAK抑制剂和GC的证据。
    OBJECTIVE: To update an evidence base informing the 2024 JCR clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) in older adults.
    METHODS: Four clinical questions (CQs) regarding efficacy and safety of drug treatment were evaluated, with CQ1 addressing methotrexate (MTX), CQ2 biological disease-modifying antirheumatic drugs (bDMARDs), CQ3 Janus kinase (JAK) inhibitors, and CQ4 glucocorticoids (GCs). Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system.
    RESULTS: Observational studies confirmed a pivotal role of MTX in the treatment of older RA patients. The meta-analysis showed that tumor necrosis factor inhibitors and JAK inhibitors were unequivocally effective in older RA patients. No data indicated that bDMARDs were unsafe for older patients. No safety data for JAK inhibitor use in older patients were available. One randomized controlled trial demonstrated that long-term treatment with low-dose GCs increased risks of GC-associated adverse events. The certainty of overall evidence was very low for all CQs.
    CONCLUSIONS: This systematic review provides the necessary evidence for developing 2024 JCR CPGs for managing older patients with RA. Continued updates on the evidence of JAK inhibitors and GC are desired.
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  • 文章类型: English Abstract
    With the advancement of knowledge in relation to the physiopathogenesis of atopic dermatitis (AD), several new therapeutic forms have been developed. There are also new guidelines for self-care. On the other hand, there is still an underdiagnosis of AD in Mexico. Thus, the need was seen to develop a national guide, with a broad base among the different medical groups that care for patients with AD. The Atopic Dermatitis Guidelines for Mexico (GUIDAMEX) was developed with the ADAPTE methodology, with the endorsement and participation of ten national medical societies, from physicians in Primary Healthcare to allergists and dermatologists. Throughout the manuscript, key clinical questions are answered that lead to recommendations and suggestions for the diagnosis of AD (including differential diagnosis with immunodeficiency syndromes), the recognition of comorbidities and complications, non-pharmacological treatment including therapeutic education, treatment of flares and maintenance therapy. The latter encompasses general measures to avoid triggering factors, first-line treatment focussed on repair of the skin barrier, second-line treatment (topical proactive therapy), and third-line phototherapy or systemic treatment, including dupilumab and JAK inhibitors.
    Con el avance de los conocimientos en relación con la fisiopatogenia de la dermatitis atópica (DA) se han desarrollado varias formas terapéuticas nuevas. Asimismo, existen nuevos lineamientos para el autocuidado. Por otro lado, aún existe un subdiagnóstico de la DA en México. Así, se vio la necesidad de desarrollar una guía nacional, con base amplia entre las diferentes agrupaciones médicos que atienden pacientes con DA. Se desarrolló la Guía de DA para México (GUIDAMEX) con la metodología ADAPTE, con el aval y la participación de diez sociedades médicas nacionales, desde médicos del primer contacto hasta alergólogos y dermatólogos. A lo largo del escrito se contestan preguntas clínicas clave que llevan a recomendaciones y sugerencias para el diagnóstico de la DA (incluyendo diagnóstico diferencial con síndromes de inmunodeficiencia), el reconocer de las comorbilidades y complicaciones, las medidas generales (tratamiento no farmacológico) incluyendo la educación terapéutica, el tratamiento de los brotes y el tratamiento de mantenimiento. Este último abarca las medidas generales de evitar agravantes, el tratamiento de primera línea reparador de la barrera cutánea, de segunda línea (manejo proactivo tópico), hasta la fototerapia y el tratamiento sistémico de la tercera línea, incluyendo dupilumab y los inhibidores de la cinasa de Jano.
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  • 文章类型: Journal Article
    目的:为老年人类风湿性关节炎(RA)的临床治疗指南提供依据。
    方法:PubMed,科克伦图书馆,并在日本CentraRevuoMedicina数据库中搜索了1990年至2019年之间发表的文章。使用建议分级评估来评估证据的质量,开发和评估系统,有一些修改。
    结果:在702篇确定的文章中,有5项随机对照试验和10项观察性研究的事后分析.前者的荟萃分析得出,使用肿瘤坏死因子抑制剂治疗的vanderHeijde改良的Sharp总评分的平均差为-2.79(95%置信区间[CI]-3.74至-1.84)。美国风湿病学会50%反应率的风险比(RR),严重不良事件为2.83(95CI1.90-4.21)和1.32(95CI0.53-3.31),分别,用于Janus激酶抑制剂。观察性研究的荟萃分析得出,对于接受生物疾病缓解抗风湿药物的老年患者和年轻患者,疾病活动评分-28缓解和严重感染的RR为0.76(95CI0.64-0.91)和1.92(95CI1.31-2.81)。分别。
    结论:本系统综述为发展CPG治疗老年人RA提供了必要的证据。
    OBJECTIVE: To provide an evidence base for clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) in older adults.
    METHODS: PubMed, Cochrane library, and Japan Centra Revuo Medicina databases were searched for articles published between 1990 and 2019. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system, with some modifications.
    RESULTS: Among 702 identified articles, there were 5 post-hoc analyses of randomized controlled trials and 10 observational studies. Meta-analysis of the former yielded a mean difference of the van der Heijde-modified total Sharp score of -2.79 (95% confidence interval [CI] - 3.74 to -1.84) for treatment with tumor necrosis factor inhibitors. The risk ratio (RR) for the American College of Rheumatology 50% response rate, and for serious adverse events was 2.83 (95%CI 1.90-4.21) and 1.32 (95%CI 0.53-3.31), respectively, for Janus kinase inhibitors. Meta-analysis of the observational studies yielded an RR for disease activity score-28 remission and serious infections of 0.76 (95%CI 0.64-0.91) and 1.92 (95%CI 1.31-2.81) for older-versus-younger patients receiving biological disease-modifying antirheumatic drugs, respectively.
    CONCLUSIONS: This systematic review provides the necessary evidence for developing CPG for the management of RA in older adults.
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  • 文章类型: Journal Article
    目的:为老年人类风湿性关节炎(RA)的临床治疗指南提供依据。
    方法:PubMed,科克伦图书馆,并在日本CentraRevuoMedicina数据库中搜索了1990年至2019年之间发表的文章。使用建议分级评估来评估证据的质量,开发和评估系统,有一些修改。
    结果:在702篇确定的文章中,有5项随机对照试验和10项观察性研究的事后分析.前者的荟萃分析得出,使用肿瘤坏死因子抑制剂治疗的vanderHeijde改良的Sharp总评分的平均差为-2.79(95%置信区间[CI]-3.74至-1.84)。美国风湿病学会50%反应率的风险比(RR),严重不良事件为2.83(95CI1.90-4.21)和1.32(95CI0.53-3.31),分别,用于Janus激酶抑制剂。观察性研究的荟萃分析得出,对于接受生物疾病缓解抗风湿药物的老年患者和年轻患者,疾病活动评分-28缓解和严重感染的RR为0.76(95CI0.64-0.91)和1.92(95CI1.31-2.81)。分别。
    结论:本系统综述为发展CPG治疗老年人RA提供了必要的证据。
    OBJECTIVE: To provide an evidence base for clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) in older adults.
    METHODS: PubMed, Cochrane library, and Japan Centra Revuo Medicina databases were searched for articles published between 1990 and 2019. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system, with some modifications.
    RESULTS: Among 702 identified articles, there were 5 post-hoc analyses of randomized controlled trials and 10 observational studies. Meta-analysis of the former yielded a mean difference of the van der Heijde-modified total Sharp score of -2.79 (95% confidence interval [CI] - 3.74 to -1.84) for treatment with tumor necrosis factor inhibitors. The risk ratio (RR) for the American College of Rheumatology 50% response rate, and for serious adverse events was 2.83 (95%CI 1.90-4.21) and 1.32 (95%CI 0.53-3.31), respectively, for Janus kinase inhibitors. Meta-analysis of the observational studies yielded an RR for disease activity score-28 remission and serious infections of 0.76 (95%CI 0.64-0.91) and 1.92 (95%CI 1.31-2.81) for older-versus-younger patients receiving biological disease-modifying antirheumatic drugs, respectively.
    CONCLUSIONS: This systematic review provides the necessary evidence for developing CPG for the management of RA in older adults.
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