JAK1 inhibitors for the treatment of atopic dermatitis: a focus on pharmacokinetic considerations

医学 特应性皮炎 托法替尼 社会心理的 鲁索利替尼 安全概况 药代动力学 临床试验 杜皮鲁玛 生活质量(医疗保健) 药理学 皮肤病科 不利影响 内科学 精神科 类风湿性关节炎 骨髓 护理部 骨髓纤维化
作者
Hannah Kopelman,Christina Kontzias,Christopher Alihosseni,Steven R. Feldman
出处
期刊:Expert Opinion on Drug Metabolism & Toxicology [Taylor & Francis]
卷期号:19 (8): 537-542
标识
DOI:10.1080/17425255.2023.2256227
摘要

ABSTRACTIntroduction Atopic dermatitis (AD) is associated with reduced quality of life, depression, and anxiety, making efficacious and safe treatments a priority. We will focus on the safety, efficacy, and pharmacokinetics of JAK1 inhibitors used in the treatment of AD.Areas Covered In this review, the pharmacodynamics, pharmacokinetics, safety, and efficacy of JAK1 inhibitors for the treatment of atopic dermatitis are discussed. The data was obtained by searching ClinicalTrials.gov, PubMed, and Google Scholar. Articles between January 2012 and March 2023 were considered for inclusion.Expert Opinion Given the rare, but serious black box warnings with JAK inhibitors, patients and providers may be weary of initiating treatment. In these instances, clinicians may weigh the risks and benefits of treatment with this class. Risk is relative, and while there are risks to treating AD with JAK inhibitors, there are also risks to untreated or undertreated AD, including infection and impairments in mental, physical, and psychosocial function. While JAK1 inhibitors appear to be safe, they were only recently approved for AD in January 2022, and more long-term safety data is needed. We expect to see additional FDA approval of these drugs, new formulations, and more safety and efficacy data in the future.KEYWORDS: AtopicdermatitisJAKpharmacodynamicspharmacokineticssafetyefficacy Article highlights JAK inhibitors are small molecules that bind to JAK receptors and block the downstream signaling from cytokines implicated in atopic dermatitis (AD), specifically IL-4 and IL-13.There are two classes of JAK inhibitors. The first generation – baricitinib, delgocitinib, tofacitinib, and ruxolitinib – inhibit multiple JAK isoforms. The second generation – abrocitinib and uadacitinib – are more selective, targeting primarily only one JAK isoform and inhibiting a smaller range of cytokines.JAK inhibitors were efficacious for AD in phase II and III clinical trials. In particular, upadacitinib was more efficacious than dupilumab in a head-to-head trial.As a class, the JAK inhibitors have similar safety profiles with the most frequent adverse events including nasopharyngitis and upper respiratory infections.Given the rare, but serious black box warnings for an increased risk of serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis with JAK inhibitors, conversations surrounding using JAK inhibitors should involve risk stratification and shared decision-making between patients and their doctors.Declaration of interestS Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, Ono, Micreos, Eurofins, Informa, UpToDate and the National Psoriasis Foundation. He is founder and part owner of Causa Research and holds stock in Sensal Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresOne reviewer has served on the advisory board of or as a consultant for; Regeneron, Sanofi Genzyme, AbbVie, Pfizer, Janssen-Cilag, LEO Pharma, Novartis, Eli-Lilly, Teva, L’Oreal, Pierre Fabre, Cantabria Labs, Organon, Viatris, Evelo Biosciences and Amgen. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.Additional informationFundingThis paper was not funded.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
ivyjianjie完成签到 ,获得积分10
2秒前
DaDA完成签到 ,获得积分10
7秒前
晚晚完成签到,获得积分10
7秒前
大陆完成签到,获得积分0
10秒前
猪猪女孩完成签到,获得积分10
11秒前
欢喜板凳完成签到 ,获得积分10
11秒前
lu完成签到,获得积分10
14秒前
郭元强完成签到,获得积分10
16秒前
小许完成签到 ,获得积分10
16秒前
17秒前
xiaofeiyan完成签到 ,获得积分10
19秒前
llhh2024完成签到,获得积分10
23秒前
心系天下完成签到 ,获得积分10
26秒前
David完成签到 ,获得积分10
27秒前
monoanan完成签到 ,获得积分10
28秒前
无极2023完成签到 ,获得积分0
28秒前
瘦瘦的铅笔完成签到 ,获得积分10
32秒前
pengyh8完成签到 ,获得积分10
36秒前
37秒前
xxxx完成签到 ,获得积分10
39秒前
mojito完成签到 ,获得积分10
40秒前
ZYN完成签到,获得积分10
43秒前
666星爷完成签到,获得积分10
47秒前
故意的冰淇淋完成签到 ,获得积分10
51秒前
牛奶面包完成签到 ,获得积分10
54秒前
羊羊羊完成签到 ,获得积分10
1分钟前
怕黑道消完成签到 ,获得积分10
1分钟前
mengmenglv完成签到 ,获得积分0
1分钟前
SOL完成签到 ,获得积分10
1分钟前
包容的剑完成签到 ,获得积分10
1分钟前
YJ完成签到,获得积分10
1分钟前
ii完成签到 ,获得积分10
1分钟前
MS903完成签到,获得积分10
1分钟前
1分钟前
刻苦的宛白应助张祖伦采纳,获得30
1分钟前
Lyw完成签到 ,获得积分10
1分钟前
Ying发布了新的文献求助20
1分钟前
1分钟前
alexlpb完成签到,获得积分0
1分钟前
浮尘完成签到 ,获得积分0
1分钟前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3968559
求助须知:如何正确求助?哪些是违规求助? 3513391
关于积分的说明 11167370
捐赠科研通 3248808
什么是DOI,文献DOI怎么找? 1794465
邀请新用户注册赠送积分活动 875116
科研通“疑难数据库(出版商)”最低求助积分说明 804664