Abrocitinib

abrocitinib
  • 文章类型: Case Reports
    结节性痒疹(PN)是一种由于剧烈瘙痒而难以治疗的慢性神经免疫皮肤病。致痒细胞因子,特别是IL-4,IL-13,IL-22,IL-31和制瘤素M(OSM),在PN的发病机制中起着至关重要的作用,可能涉及JAK1-STAT途径。一种口服JAK1抑制剂,abrocitinib,目前正在接受治疗PN的2期试验。我们评估了每日剂量为100mg的abrocitinib治疗两名影响双下肢的PN患者的疗效:一名50岁的男性,有16年的疾病史,一名38岁的女性,有三年以上的疾病史。两人对多种常规治疗均无反应.治疗一周后,两名患者反应迅速,并表现出明显的改善。经过八周的治疗,瘙痒和病变几乎完全消退,无不良反应报告.此外,在继续治疗的最初4个月内,没有报告副作用.阿布西替尼是一种有效的PN靶向治疗,为难治性患者提供了一个有希望的新选择。
    Prurigo nodularis (PN) is a debilitating chronic neuroimmunologic skin condition due to the intense pruritus and difficult to treat. The pruritogenic cytokines, particularly IL-4, IL-13, IL-22, IL-31, and oncostatin M (OSM), play a crucial role in the pathogenesis of PN, potentially involving the JAK1-STAT pathway. An oral JAK1 inhibitor, abrocitinib, is presently undergoing Phase 2 trials for the treatment of PN. We evaluated the efficacy of abrocitinib at a daily dosage of 100 mg in treating two patients with PN affecting both lower limbs: a 50-year-old male with a 16-year disease history and a 38-year-old female with over three years of disease history, both of whom had failed to respond to multiple conventional treatments. Both patients responded rapidly after one week of treatment and exhibited a marked improvement. Following eight weeks of therapy, near-complete resolution of both pruritus and lesions was achieved, and no adverse effects were reported. Additionally, there were no reported side effects during the initial four months of continued treatment. Abrocitinib is an effective targeted therapy for PN, offering a promising new option for refractory patients.
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  • 文章类型: Journal Article
    目的:分析Janus激酶抑制剂(JAKi)治疗小儿AD的疗效和安全性。
    结果:患有中度和重度特应性皮炎(AD)的青少年需要系统治疗,正如最近的几个实践指南所述。(JAKI)已显示出它们在治疗成人AD中的功效,然而,缺乏有关其在小儿AD中使用的有效性和安全性的信息。我们发现JAKI的abrocitinib(ABRO),巴利替尼(BARI),和upadacitinib(UPA),对于患有中度至重度AD的青少年,都是一种有效的治疗选择,起效非常快。BARI对2至10岁的中度至重度AD儿童无效。幸运的是,JAKI在青少年AD患者中的主要安全问题尚未在试验中得到记录,到目前为止,与成人AD的报道相比,这些事件很少发生。在JAKI上有一些青少年带状疱疹(HZ)感染的报道,但这不是主要的安全问题。痤疮是青少年UPA相对常见的AE;然而,它对标准治疗有反应。本综述将有助于临床医生根据中重度AD患者的需求和临床特征选择JAKi。在接下来的几年里,随着新生物制品和JAKI的出现,这些疗法将在AD患者发展的每个阶段实施.
    OBJECTIVE: To analyze the efficacy and safety of Janus kinase inhibitors (JAKi) in the treatment of pediatric AD.
    RESULTS: Adolescents with moderate and severe atopic dermatitis (AD) need systemic therapies, as stated several recent practice guidelines. (JAKi) have shown their efficacy in the treatment of adult AD, however, there is a lack of information concerning efficacy and safety of their use in pediatric AD. We found that the JAKi\'s abrocitinib (ABRO), baricitinib (BARI), and upadacitinib (UPA), are all an effective treatment option with a very fast onset of action for adolescents with moderate-to-severe AD. BARI was not effective in children between 2 and 10 years with moderate-to-severe AD. Fortunately, major safety issues with JAKi in adolescents with AD have not been documented in the trials, so far, contrasting with the reports in adults with AD, where these events have very rarely occurred. There are some reports of herpes zoster (HZ) infection in adolescents on JAKi, but it is not a major safety concern. Acne is a relatively common AE with UPA in adolescents; however, it is responsive to standard treatment. This review will help the clinician to choose among the JAKi according to the needs and clinical features of patients with moderate and severe AD. In the following years, with the advent of new biologicals and JAKi, these therapies will fall into place in each phase of the evolution of patients with AD.
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  • 文章类型: Case Reports
    传统的酒渣鼻治疗方法并不普遍,不良反应可能会限制其效用。JAK1抑制剂upadacitinib和abrocitinib治疗难治性酒渣鼻的临床应用很少被探索。
    我们介绍了2例接受JAK1抑制剂upadacitinib的患者和4例接受JAK1抑制剂abrocitinib治疗难治性酒渣鼻的患者。
    JAK1抑制剂upadacitinib和abrocitinib可能是难治性酒渣鼻患者的有希望的药物选择。然而,upadacitinib和abrocitinib的长期安全性和有效性需要前瞻性对照研究来更全面地评估.
    UNASSIGNED: Conventional rosacea treatments are not uniformly pervasive, and the adverse reactions can potentially constrain their utility. The clinical use of JAK1 inhibitors upadacitinib and abrocitinib in the treatment of refractory rosacea has rarely been explored.
    UNASSIGNED: We presented two cases of patients who received the JAK1 inhibitor upadacitinib and four cases of patients who received the JAK1 inhibitor abrocitinib for the treatment of refractory rosacea.
    UNASSIGNED: The JAK1 inhibitors upadacitinib and abrocitinib may be promising medical options for patients with refractory rosacea. However, the long-term safety and efficacy of upadacitinib and abrocitinib require prospective controlled studies to assess them more comprehensively.
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  • 文章类型: Journal Article
    阿布西替尼,一个口头,每天一次,Janus激酶(JAK)1-选择性抑制剂,已被批准用于治疗患有中度至重度特应性皮炎(AD)的成人和青少年。阿布西替尼在3期试验中显示出快速和持续的疗效,长期研究中可管理的安全性。与dupilumab相比,使用200mg每日剂量的abrocitinib更有可能实现快速瘙痒缓解和皮肤清除。所有口服JAK抑制剂都与特别关注的不良事件和实验室变化有关。初步风险评估和后续监测非常重要。适当选择患者和充分监测是安全使用JAK抑制剂的关键。这里,我们回顾了abrocitinib的实际使用情况,并讨论了适合abrocitinib治疗的患者的特点.总的来说,abrocitinib可用于所有需要全身治疗的中度至重度AD患者,如果没有禁忌症,例如,在患有活动性严重全身感染和严重肝功能损害的患者中,以及孕妇或哺乳期妇女。对于年龄≥65岁的患者,当前长期或过去长期吸烟者,那些有静脉血栓栓塞危险因素的人,主要不良心血管事件,或者恶性肿瘤,建议进行细致的效益风险评估,建议从100毫克的剂量开始,当abrocitinib是选定的治疗方案时。
    Abrocitinib, an oral, once-daily, Janus kinase (JAK) 1-selective inhibitor, is approved for the treatment of adults and adolescents with moderate-to-severe atopic dermatitis (AD). Abrocitinib has shown rapid and sustained efficacy in phase 3 trials and a consistent, manageable safety profile in long-term studies. Rapid itch relief and skin clearance are more likely to be achieved with a 200-mg daily dose of abrocitinib than with dupilumab. All oral JAK inhibitors are associated with adverse events of special interest and laboratory changes, and initial risk assessment and follow-up monitoring are important. Appropriate selection of patients and adequate monitoring are key for the safe use of JAK inhibitors. Here, we review the practical use of abrocitinib and discuss characteristics of patients who are candidates for abrocitinib therapy. In general, abrocitinib may be used in all appropriate patients with moderate-to-severe AD in need of systemic therapy, provided there are no contraindications, e.g., in patients with active serious systemic infections and those with severe hepatic impairment, as well as pregnant or breastfeeding women. For patients aged ≥ 65 years, current long-time or past long-time smokers, and those with risk factors for venous thromboembolism, major adverse cardiovascular events, or malignancies, a meticulous benefit-risk assessment is recommended, and it is advised to start with the 100-mg dose, when abrocitinib is the selected treatment option.
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  • 文章类型: Journal Article
    背景:早期预测abrocitinib在特应性皮炎(AD)中的疗效可能有助于确定早期剂量增加的候选者。预测模型基于接受100mg/天的abrocitinib的患者的第4周反应确定第12周功效,并评估abrocitinib剂量增加对血小板计数的影响。
    方法:分析包括JADEMONO-1(NCT03349060),MONO-2(NCT03575871),比较(NCT03720470),和TEEN(NCT03796676)。对于血小板计数和模拟,我们合并了一项2期银屑病试验(NCT02201524)和2b期试验(NCT02780167)和3期试验(MONO-1,MONO-2和REGIMEN(NCT03627767))abrocitinib.训练和验证框架评估了第4周时反应的潜在预测因素:湿疹面积和严重程度指数(EASI)相对于基线的得分和得分变化,调查员全球评估(IGA),和峰值瘙痒数字评分量表(PP-NRS),和EASI中相对于基线的百分比变化。第12周时的因变量为EASI(EASI-75)改善≥75%,IGA评分为0(清除)或1(几乎清除),并且与基线相比改善≥2分。计算每个变量预测第12周EASI-75和IGA反应的概率。
    结果:在训练队列中(n=453),在第4周,有72%的EASI(EASI-50)改善≥50%,有16%的abrocitinib100mg无反应者在第12周达到EASI-75;第4周的48%和6%的EASI-50反应者和无反应者,分别,实现了第12周的IGA响应。第4周IGA=2,PP-NRS从基线改善≥4点,或EASI=8响应者/非响应者。abrocitinib剂量从100mg增加到200mg后的血小板计数与连续给药100mg或200mgabrocitinib时的血小板计数相似。
    结论:使用100mgabrocitinib实现第4周的临床反应可能有助于预测第12周的反应。第4周无应答者可能会从增加200mgabrocitinib的剂量中受益,接受这种剂量增加的患者可能在第12周获得治疗成功,对血小板计数恢复没有显著影响.本文提供的视频摘要。
    背景:NCT03349060、NCT03575871、NCT03720470、NCT03796676、NCT02201524、NCT02780167和NCT03627767。
    Agrocitinib是一种被批准用于中度或重度特应性皮炎患者的治疗方法。阿布西替尼片剂有两种剂量(100和200mg),每天口服一次。一些服用abrocitinib100mg的特应性皮炎患者可能需要将剂量增加到200mg以获得足够的症状缓解。我们研究了特应性皮炎患者在服用abrocitinib100mg治疗4周后是否有皮肤或瘙痒缓解或没有缓解的情况,在治疗12周后是否有可能缓解。我们还定义了治疗4周后的反应水平,可以最好地区分有或没有症状缓解的人,我们确定了谁可能受益于将abrocitinib剂量从100mg增加到200mg.我们发现,特应性皮炎患者在接受abrocitinib100mg治疗4周后症状缓解,12周后症状缓解的可能性更大。4周后未达到症状缓解的患者可从第4周的剂量增加中获益.一些接受200毫克abrocitinib的人在第4周可能会暂时减少称为血小板的某些血细胞数量,但血小板在第12周恢复到接近正常水平。该分析表明,在第4周将abrocitinib剂量从100增加到200mg似乎不会影响第4周后的血小板数量。视频摘要(MP4174529KB)。
    BACKGROUND: Early prediction of abrocitinib efficacy in atopic dermatitis (AD) could help identify candidates for an early dose increase. A predictive model determined week 12 efficacy based on week 4 responses in patients receiving abrocitinib 100 mg/day and assessed the effect of an abrocitinib dose increase on platelet counts.
    METHODS: Analysis included the phase 3 trials JADE MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470), and TEEN (NCT03796676). For platelet counts and simulations, a phase 2 psoriasis trial (NCT02201524) and phase 2b (NCT02780167) and phase 3 (MONO-1, MONO-2, and REGIMEN (NCT03627767)) abrocitinib trials were pooled. A training-and-validation framework assessed potential predictors of response at week 4: score and score change from baseline in the Eczema Area and Severity Index (EASI), Investigator\'s Global Assessment (IGA), and Peak Pruritus Numerical Rating Scale (PP-NRS), and percentage change from baseline in EASI. The dependent variables at week 12 were ≥ 75% improvement in EASI (EASI-75) and IGA score of 0 (clear) or 1 (almost clear) and ≥ 2-point improvement from baseline. The probability of each variable to predict week 12 EASI-75 and IGA responses was calculated.
    RESULTS: In the training cohort (n = 453), 72% of the ≥ 50% improvement in EASI (EASI-50) at week 4 responders and 16% of the nonresponders with abrocitinib 100 mg achieved EASI-75 at week 12; 48% and 6% of the week 4 EASI-50 responders and nonresponders, respectively, achieved week 12 IGA response. Similar results occurred with week 4 IGA = 2, ≥ 4-point improvement from baseline in PP-NRS, or EASI = 8 responders/nonresponders. Platelet counts after an abrocitinib dose increase from 100 to 200 mg were similar to those seen with continuous dosing with abrocitinib 100 mg or 200 mg.
    CONCLUSIONS: Achieving week 4 clinical responses with abrocitinib 100 mg may be useful in predicting week 12 responses. Week 4 nonresponders may benefit from a dose increase to abrocitinib 200 mg, and those that receive this dose increase are likely to achieve treatment success at week 12, with no significant impact on platelet count recovery. Video abstract available for this article.
    BACKGROUND: NCT03349060, NCT03575871, NCT03720470, NCT03796676, NCT02201524, NCT02780167 and NCT03627767.
    Abrocitinib is an approved treatment for people with moderate or severe atopic dermatitis. Abrocitinib tablets are available in two doses (100 and 200 mg) and are taken by mouth once daily. Some people with atopic dermatitis who are taking abrocitinib 100 mg may need to increase the dose to 200 mg to get adequate symptom relief. We studied whether people with atopic dermatitis who did or did not experience clear skin or itch relief after taking abrocitinib 100 mg for 4 weeks are likely or not likely to experience relief after 12 weeks of treatment. We also defined the level of response after 4 weeks of treatment that best differentiates people who did or did not experience symptom relief, and we identified who might benefit from increasing the abrocitinib dose from 100 to 200 mg. We found that people with atopic dermatitis who had symptom relief after 4 weeks of abrocitinib 100 mg treatment were much more likely to have greater relief after 12 weeks, and people who did not achieve symptom relief after 4 weeks may benefit from a dose increase at week 4. Some people who receive abrocitinib 200 mg may have a temporary decrease in the number of certain blood cells called platelets at week 4, but platelets return to near-normal levels by week 12. This analysis showed that increasing the abrocitinib dose from 100 to 200 mg at week 4 did not seem to affect the platelet numbers after week 4. Video abstract (MP4 174529 KB).
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    特应性皮炎(AD)是一种持续性、影响全球约15%至20%的儿童和1%至3%的成年人的炎症性皮肤状况。常见的皮肤表现包括丘疹,丘疹囊泡,和棕色或红色斑块肿胀,结壳,和剥落。因此,药物abrocitinib(ABR)被美国FDA批准作为特应性皮炎的口服治疗药物.本研究概述了创新的发展,热稳定,和通过一步法合成的pH稳定的无有机溶剂氮掺杂碳点(N@CQDs),用于评估ABR,具有33.84%的显着量子产率,以最大程度地减少有机溶剂的使用。他们的成本效益,生态友好的特点,和优异的光催化性能使它们成为传统发光技术如荧光染料和发光衍生技术的有希望的替代品。ABR与N@CQDs的反应导致所产生的绿色和稳定的碳量子点在513nm处的发光响应显着降低。检测范围确定为1.0-150.0ngmL-1,基于线性图,定量下限(LOQ)等于0.52ngmL-1。该绿色方法有效地用于药物片剂中ABR的分析和药代动力学研究,灵敏度高。
    Atopic dermatitis (AD) is a persistent, inflammatory skin condition that impacts approximately 15 to 20% of children and 1 to 3% of adults globally. Common skin manifestations include papules, papulovesicular, and brown or red patches with swelling, crusting, and flaking. Therefore, the drug abrocitinib (ABR) was approved by the US FDA as an oral treatment for atopic dermatitis. The present study outlines the development of innovative, thermostable, and pH-stable organic solvent-free nitrogen-doped carbon dots (N@CQDs) synthesized through a one-step method for evaluating ABR with a notable quantum yield of 33.84% to minimize the use of organic solvents. Their cost-effectiveness, eco-friendly characteristics, and outstanding photocatalytic properties have established them as a promising alternative to conventional luminescent techniques like fluorescent dyes and luminous derivatization technique. The reaction of ABR with N@CQDs led to a significant decrease in the luminescent response of the produced green and stable carbon quantum dots at 513 nm. The detection range was determined to be 1.0-150.0 ng mL-1, with a lower limit of quantitation (LOQ) equal to 0.52 ng mL-1 based on the linear graph. The green method effectively used for analysis of ABR in pharmaceutical tablets and pharmacokinetic study with high sensitivity.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    嗜酸性脓疱性毛囊炎(EPF)是一种罕见的,非传染性,以毛囊皮脂腺内和周围嗜酸性粒细胞为主的浸润为特征的炎症性疾病。有时候,EPF表现为无卵泡区域的爆发,虽然这并不常见,治疗可能很困难。在此案例研究中,我们报告了两名难治性EPF患者,他们出现了经典卵泡区和无卵泡区的爆发。这两名患者在几种传统疗法治疗失败后成功接受了abrocitinib治疗。如吲哚美辛,类固醇,和环孢菌素.一名患者在第4周达到完全缓解,另一名在第1周达到完全缓解,没有报告不良反应。因此,我们认为,abrocitinib可能是治疗难治性EPF的一种可行且安全的治疗选择.
    Eosinophilic pustular folliculitis (EPF) is a rare, non-infectious, inflammatory disease characterized by an eosinophil-dominated infiltrate within and around pilosebaceous units. Sometimes, EPF manifests with eruptions in follicle-free areas, although it is not common, and treatment may be difficult. In this case study we report two patients with refractory EPF who presented with eruptions of both classic follicle areas and follicle-free areas. These two patients were successfully treated with abrocitinib after treatment failure with several traditional therapies, such as indomethacin, steroids, and cyclosporin. One patient achieved complete remission at week 4 and the other at week 1, with no reported adverse effects. Therefore, we believe that abrocitinib may be a viable and safe therapeutic option for refractory EPF.
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