TNF-alpha inhibitors

TNF - α 抑制剂
  • 文章类型: Journal Article
    在商业索赔数据库分析中,<0.5%的炎症性肠病或类风湿关节炎患者在开始TNF-α治疗后一年内发展为FI。组织胞浆菌病是最常见的FI类型。总体FI发病率因地区而异,潜在条件,使用某些免疫抑制药物。
    In a commercial claims database analysis, <0.5% of patients with inflammatory bowel disease or rheumatoid arthritis developed an IFI within one year of initiating TNF-alpha therapy. Histoplasmosis was the most common IFI type. Overall IFI incidence varied based on region, underlying conditions, and use of certain immunosuppressive medications.
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  • 文章类型: Case Reports
    本报告描述了一名接受阿达木单抗治疗的克罗恩病患者面部色素沉着过度的病例,肿瘤坏死因子(TNF)-α抑制剂。色素沉着过度的发作与阿达木单抗给药同时发生,它的终止导致了显著的改善。组织病理学发现提示皮肤-表皮交界处的炎症后过程。然而,确切机制尚不清楚.
    This report describes a case of facial hyperpigmentation in a patient with Crohn\'s disease receiving adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. The onset of hyperpigmentation coincided with adalimumab administration, and its discontinuation resulted in significant improvement. Histopathological findings suggest a postinflammatory process at the dermo-epidermal junction. However, the precise mechanism remains unclear.
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  • 文章类型: Journal Article
    组织胞浆菌病是美国中西部和东南部特有的一种基于土壤的双态真菌,是通过吸入分生孢子引起感染的原因。感染通常无症状,因为肉芽肿的形成包含了真菌的生长。然而,由于缺乏干扰素γ的最佳活性,可以在免疫受损的宿主中传播,肿瘤坏死因子α(TNF-α)和白细胞介素-17。组织胞浆菌病和肉芽肿性多血管炎(GPA)的症状之间存在显着重叠。我们报告一例48岁女性高烧,全身无力和心动过速恶化。她以前有双侧空洞性肺病变的病史,并在外部设施进行了评估。由于她的整个感染调查均为阴性,并且发现抗中性粒细胞胞浆抗体(ANCA)呈阳性,做出了GPA的诊断,她在就诊至我们机构前7周接受了利妥昔单抗输注.在我们的设施中进行的重复感染调查对(1-3)-β-D-葡聚糖测试和尿组织血浆抗原呈阳性。迅速停药利妥昔单抗和开始全身抗真菌治疗导致临床改善。根据这些经验,我们强调了组织血浆与ANCA阳性的相关性,以及密切监测这些患者在开始使用TNF-α抑制剂后可能的临床恶化的重要性,尽管有负面的传染性工作。也不建议在开始使用TNF抑制剂之前对组织胞浆菌病进行常规筛查或抢先治疗。
    结论:组织胞浆菌病与ANCA阳性相关。尽管组织胞浆菌病研究呈阴性,且符合GPA标准,在开始免疫抑制治疗后,应密切监测患者是否可能出现临床恶化,尤其是TNF-α抑制剂.目前的指南不建议在开始使用TNF-α抑制剂之前对组织胞浆菌病进行常规筛查或抢先治疗。
    Histoplasmosis is a soil-based dimorphic fungus endemic to the Midwest and Southeastern United States and is responsible for infection through inhalation of conidia. Infection is usually asymptomatic, as the fungal growth is contained by formation of granulomas. However, dissemination can occur in immunocompromised hosts due to the lack of optimal activity of interferon gamma, tumour necrosis factor alpha (TNF-alpha) and interleukin-17. There is a significant overlap between the symptomatology of histoplasmosis and granulomatosis with polyangiitis (GPA). We report a case of a 48-year-old female who presented with high-grade fever, worsening generalised weakness and tachycardia. She had a previous history of bilateral cavitary lung lesions for which she was evaluated at an outside facility. As her entire infectious investigation was negative and found to be positive for antineutrophil cytoplasmic antibody (ANCA), a diagnosis of GPA was made, and she was initiated on rituximab infusions 7 weeks prior to her presentation to our facility. Repeat infectious investigations at our facility were positive for (1-3)-β-D-glucan test and urine histoplasma antigen. Prompt discontinuation of rituximab and initiation of systemic antifungal therapy led to clinical improvement. Based on this experience, we highlight the association of histoplasma with ANCA positivity along with the importance of closely monitoring these patients for possible clinical worsening after the initiation of TNF-alpha inhibitors, despite the negative infectious work-up. Also routine screening or pre-emptive therapy for histoplasmosis before the initiation of TNF-inhibitors is not recommended.
    CONCLUSIONS: Histoplasmosis is associated with ANCA positivity.Despite the negative investigations for histoplasmosis and criteria for GPA being met, patients should be closely monitored for possible clinical worsening after the initiation of immunosuppressive therapy, especially TNF-alpha inhibitors.Current guidelines are not recommending routine screening or pre-emptive therapy for histoplasmosis before initiation of TNF-alpha inhibitors.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    结节病是一种以非干酪样肉芽肿为特征的疾病,可作为神经结节病累及中枢神经系统。这种具有挑战性的疾病目前是用高剂量类固醇治疗的,有时加用英夫利昔单抗。其他TNA-α抑制剂尚未被严格研究。我们发现了10名神经结节病患者,他们正在服用一种替代的TNA-α抑制剂,阿达木单抗。8例患者对阿达木单抗有积极的临床和影像学反应。
    Sarcoidosis is a disease characterized by non-caseating granulomas that can involve the central nervous system as neurosarcoidosis. This challenging disease is currently managed with high dose steroids, and sometimes the addition of infliximab. Other TNA-alpha inhibitors have not been studied as rigorously. We discovered ten neurosarcoidosis patients who were on an alternative TNA-alpha inhibitor, adalimumab. Eight patients had a positive response clinically and radiographically to adalimumab.
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  • 文章类型: Case Reports
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  • 文章类型: Journal Article
    史蒂文斯-约翰逊综合征(SJS)和毒性表皮坏死松解症(TEN)存在于一系列引起表皮脱离和角质形成细胞坏死的自身免疫疾病中。由于这些情况的罕见发生,治疗算法存在巨大的异质性。为了更好地理解药物免疫抑制疗法对生存的影响,作者查询了一个多机构数据网络。本研究的数据来自TriNetX研究网络,包含来自国际医疗保健组织联盟的ICD-9/ICD-10编码数据的平台。查询了71个机构,以识别诊断为SJS的成年患者,十或SJS-TEN重叠。根据接受的治疗创建队列:全身性类固醇(SS),苯海拉明(DH),环孢菌素(CS),静脉注射免疫球蛋白(IVIG),肿瘤坏死因子α抑制剂(TNFαi),或治疗的组合。然后将队列与接受支持性护理的患者进行倾向匹配。仅接受上述治疗之一的患者90天死亡率没有显着降低。与支持治疗相比,接受CS或IVIG作为多种治疗的患者死亡风险显著增加(CS:RR=1.583,95%CI[1.119,2.240];IVIG:RR=2.132,95%CI[1.485,3.059])。尽管他们经常使用,这项研究的分析提示,这些治疗方法均不比单独的支持治疗具有显著的90天死亡率生存率.这些结果突出了治疗的异质性,并强调了对SJS和TEN结果进行关键前瞻性评估的必要性。
    Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) exist on a spectrum of autoimmune conditions which cause epidermal detachment and keratinocyte necrosis. Due to the rare incidence of these conditions, a dramatic heterogeneity in treatment algorithms exists. To better appreciate pharmacologic immunosuppressive therapies\' impact on survival, the authors queried a multi-institutional data network. Data for this study was extracted from TriNetX Research Network, a platform that contains ICD-9/ICD-10 coding data from a consortium of international healthcare organizations. Seventy-one institutions were queried to identify adult patients diagnosed with SJS, TEN or SJS-TEN Overlap. Cohorts were created based on the therapy received: systemic steroids (SS), diphenhydramine (DH), cyclosporine (CS), intravenous immunoglobulin (IVIG), tumor necrosis factor alpha inhibitors (TNFαi), or a combination of treatments. Cohorts were then propensity matched with patients who received supportive care. Patients who only received one of the above treatments showed no significant reduction in 90-day mortality. Patients who received CS or IVIG as part of their multitherapy showed a significantly increased risk of death when compared to supportive care (CS: RR = 1.583, 95% CI [1.119, 2.240]; IVIG: RR = 2.132, 95% CI [1.485, 3.059]). Despite their frequent utilization, this study\'s analysis suggests that none of these therapies confer significant 90-day mortality survival over supportive care alone. These results highlight the heterogeneity of therapies and emphasize the need for critical prospective appraisal of their outcomes in SJS and TEN.
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  • 文章类型: Observational Study
    目的:评估临床特征,预测因素,和矛盾反应(PR)的实用算法,特别是自相矛盾的牛皮癣(PP)。
    方法:TReasure数据库,是一个基于网络的前瞻性观察队列,包括自2017年以来来自土耳其各地17个中心的类风湿关节炎(RA)和脊柱关节炎(SpA)患者。确定了位于队列中的队列研究和病例对照研究。
    结果:评估了2867例RA和5316例SpA患者。发现第一种生物制剂在发生PR的136名患者中的60%(1.66%)引起PR。PR与生物学发作之间的中位时间间隔为12个月(范围1-132,平均21个月)。最常见的PP类型,占公关的92.6%,脓疱(60.3%)和掌足底(30.9%)。阿达木单抗(30.9%),英夫利昔单抗(19%),和依那西普(17.4%)是引起PP的最常见药物。在大多数PP患者的治疗中(73.2%),转换生物制剂受到青睐,其中肿瘤坏死因子抑制剂(TNFi)占46.03%,非TNFi占26.9%。最常选择的三种药物是依那西普(24.6%),苏金单抗(9.5%),和阿达木单抗(8.7%)。只有5.17%的患者切换到另一个TNFi显示进展。柳氮磺吡啶,RA对照组的羟氯喹和来氟米特使用比值比明显高于PP患者(p=0.033,OR=0.15;p=0.012OR=0.15;p=0.015,OR=0.13)。在含SpA的PP组中,吸烟者人数明显较高(p=0.003,OR:2.0,95%CI:1,05-3,81).
    结论:与类效应不同,转用另一种TNFi的患者的反应良好.
    The objectives of this study were to assess the clinical characteristics, predictive factors, and practical algorithms of paradoxical reactions (PRs), specifically paradoxical psoriasis (PP).
    The TReasure database is a web-based prospective observational cohort comprised of patients with RA and SpA from 17 centres around Turkey since 2017. A cohort study and a case-control study nestled within the cohort were identified.
    In total, 2867 RA and 5316 SpA patients were evaluated. The first biologic agent was found to have caused PRs in 60% of the 136 patients (1.66%) who developed the PRs. The median time interval between the PRs and biological onset was 12 months (range 1-132 months, mean 21 months). The most common types of PP, constituting 92.6% of PRs, were pustular (60.3%) and palmoplantar (30.9%). Adalimumab (30.9%), infliximab (19%) and etanercept (17.4%) were the most common agents causing the PP. In the treatment of most PP patients (73.2%), switching biologic agents was favoured, with TNF inhibitor (TNFi) chosen in 46.03% and non-TNFi in 26.9% of cases. The three most frequently selected drugs were etanercept (24.6%), secukinumab (9.5%) and adalimumab (8.7%). Only 5.17% of patients who switched to another TNFi showed progression. The odds ratios (s) for SSZ, HCQ, and LEF use were significantly higher in RA controls than in PP patients (P = 0.033, OR = 0.15; P = 0.012, OR = 0.15; and P = 0.015, OR = 0.13, respectively). In the PP group with SpA, the number of smokers was significantly higher (P = 0.003, OR: 2.0, 95% CI: 1.05, 3.81).
    Contrary to expectations based on earlier research suggesting that paradoxical reactions develop with the class effect of biological agents, the response of patients who were shifted to another TNFi was favourable.
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  • 文章类型: Letter
    寻常型牛皮癣是一种系统性的,慢性炎症性疾病影响2-3%的人口。对牛皮癣疾病病理生理学的理解的最新进展促进了具有改善的安全性和有效性的新型治疗选择的开发。本文由患有终身牛皮癣病史的患者共同撰写,该患者经历了多次治疗失败。他详细介绍了他的诊断和治疗经验,以及身体,心理,和他皮肤状况的社会影响。然后,他继续阐述牛皮癣疾病治疗的演变如何影响了他的生活。然后从专门从事炎症性皮肤病的皮肤科医生的角度讨论这种情况。我们强调牛皮癣的临床特征,它的医学和社会心理合并症,以及目前牛皮癣疾病治疗的前景。
    Psoriasis vulgaris is a systemic, chronic inflammatory disease affecting 2-3% of the population. Recent advances in the understanding of the pathophysiology of psoriatic disease have facilitated the development of novel therapeutic options with improved safety and efficacy. This article is coauthored by a patient with a lifelong history of psoriasis who experienced multiple treatment failures. He details his diagnosis and treatment experiences, as well as the physical, mental, and social ramifications of his skin condition. He then goes on to elaborate how evolutions in the treatment of psoriatic disease have impacted his life. This case is then discussed from the perspective of a dermatologist specializing in inflammatory skin disorders. We highlight the clinical features of psoriasis, its medical and psychosocial comorbidities, and the current landscape of psoriatic disease treatments.
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  • 文章类型: Journal Article
    在西方文明中,自身免疫力和癌症发病率都在上升,促使许多人研究这两个实体之间的联系。这篇综述将研究免疫系统的激活和失活与恶性肿瘤发展之间的复杂相互作用。其他重点将放在移植患者和自身免疫性疾病(包括TNF-α)中使用的免疫抑制剂治疗的主要类别上。钙调磷酸酶,mTOR,嘌呤合成拮抗剂和IMPDH抑制剂。
    Autoimmunity and cancer rates have both been on the rise in Western civilization prompting many to investigate the link between the two entities. This review will investigate the complex interactions between the activation and deactivation of the immune system and the development of malignancy. Additional focus will be placed on the main classes of immune inhibitor therapy utilized in transplant patients and in autoimmune disease including TNF-alpha, Calcineurin, mTOR, purine synthesis antagonists and IMPDH inhibitors.
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