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Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS.
在儿科发病的多发性硬化症中,芬戈莫德与IFN β-1a一致控制疾病活动: 来自范例的进一步见解。
- 影响因子:5.44
- DOI:10.1136/jnnp-2019-321124
- 作者列表:"Deiva K","Huppke P","Banwell B","Chitnis T","Gärtner J","Krupp L","Waubant E","Stites T","Pearce GL","Merschhemke M
- 发表时间:2020-01-01
Abstract
BACKGROUND:In PARADIGMS, a double-blind phase III trial in 215 paediatric patients with multiple sclerosis (MS) (10 to <18 years), fingolimod administered for up to 2 years significantly reduced the annualised relapse rate (ARR) and rate of new/newly enlarged T2 (n/neT2) lesions compared with interferon (IFN) β-1a. OBJECTIVES:To investigate (1) differences between treatment groups across subpopulations (treatment-naïve, younger/prepubertal patients); (2) disability progression. METHODS:ARRs at 10, 11 and 12 years were estimated based on predefined modelling extrapolations. Changes in Expanded Disability Status Scale (EDSS), and in 3 month (3M) and 6 month (6M) confirmed disability progression (CDP) were evaluated post hoc. RESULTS:In the treatment-naïve subpopulation, fingolimod reduced ARR and n/neT2 lesions by 85.8% and 53.4%, respectively versus INF β-1a (both p<0.001), compared with 81.9% and 52.6% in the overall population. Model-based ARR reductions in younger patients (≤12 years) were 91.9%-94.6%. Twice as many IFN β-1a-treated than fingolimod-treated patients had worse EDSS scores at study end (20.6% vs 10.5%, p=0.043). Risk reductions in 3M-CDP and 6M-CDP were 77.2% (p=0.007) and 80.2% (p=0.040), respectively. CONCLUSIONS:Fingolimod in paediatric MS was associated with consistent control of disease activity versus IFN β-1a (including treatment-naïve and younger patients) and resulted in less disability progression for up to 2 years. TRIAL REGISTRATION NUMBER:NCT01892722.
摘要
背景: 在范例中,一项在 2 15 例多发性硬化 (MS) 儿科患者 (10 至 <18 岁) 中进行的双盲III期试验,与干扰素 (IFN) β-1a相比,给予fingolimod长达 2 年显著降低了年复发率 (ARR) 和新扩大T 2 (n/neT 2) 病变的发生率。 目的: 调查 (1) 不同亚群 (初治、年轻/青春期前患者) 治疗组之间的差异; (2) 残疾进展。 方法: 根据预定义的模型外推估计 10 、 11 和 12 年的ARRs。对扩展残疾状态量表 (EDSS) 的变化,以及 3 个月 (3M) 和 6 个月 (6M) 确认残疾进展 (CDP) 的变化进行了事后评估。 结果: 在初治亚群中,与INF β-1a相比,芬戈莫德使ARR和n/neT2 病变分别减少 85.8% 和 53.4% (均p<0.001),而总体人群中分别为 81.9% 和 52.6%。年轻患者 (≤ 12 岁) 基于模型的ARR降低为 91.9%-94.6%。两倍于芬戈莫德治疗的IFN β-1a治疗的患者在研究结束时EDSS评分更差 (20.6% vs 10.5%,p = 0.043)。3M-CDP和 6M-CDP的风险降低分别为 77.2% (p = 0.007) 和 80.2% (p = 0.040)。 结论: Fingolimod在儿科MS患者中与IFN β-1a (包括初治和年轻患者) 的疾病活动性控制一致相关,并导致长达 2 年的残疾进展较少。 试用注册号: nct01892722。
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METHODS::Purpose: To report on ocular Vogt-Koyanagi-Harada (VKH)-like syndrome under vemurafenib treatment for metastatic melanoma.Design: A case report.Method: Description of clinical and imaging manifestations including fundus photography, fluorescein, and indocyanine green angiography.Results: A 46-year-old Thai female was diagnosed with metastatic melanoma of the skin and had been treated with multiple surgical excisions, radiotherapy, and vemurafenib (initial dose 480 mg orally twice daily, subsequently increased to maximum dose of 960 mg twice daily). After 6 months of vemurafenib use, she complained of bilateral redness and photophobia and was diagnosed with bilateral anterior uveitis, which was topically treated. Two weeks later, her visual acuity (VA) sharply deteriorated to 20/80 and counting fingers. Ocular examination at that stage stronly resembled acute VKH disease. She exhibited intraocular inflammation, and her fundus examination revealed bilateral optic disc swelling and serous retinal detachment. Fluorescein angiogram showed disc leakage and multiple pinpoint hyperfluorescence leakage spots and indocyanine green demonstrated multiple hypofluorescent spots. Oral prednisolone 30 mg/day was commenced while vemurafenib medication was ceased. Three weeks later, her vision improved, and serous retinal detachment subsided. However, her cutaneous melanoma recurred.Conclusions: Vemurafenib, a potential adjunct treatment for metastatic melanoma, was complicated by the development of panuveitis, papillitis, and multiple serous detachments. These ocular symptoms were similar to the presentation of acute VKH syndrome.
METHODS::Comprehensive reviews of the clinical characteristics and pathogenesis of Aicardi-Goutières syndrome (AGS), particularly its contextualization within a putative type I interferonopathy framework, already exist. However, recent reports of attempts at treatment suggest that an assessment of the field from a therapeutic perspective is warranted at this time. Here, we briefly summarize the neurological phenotypes associated with mutations in the seven genes so far associated with AGS, rehearse current knowledge of the pathology as it relates to possible treatment approaches, critically appraise the potential utility of therapies, and discuss the challenges in assessing clinical efficacy. WHAT THIS PAPER ADDS: Progress in understanding AGS disease pathogenesis has led to the first attempts at targeted treatment. Further rational therapies are expected to become available in the short- to medium-term.
METHODS::Purpose: To report the efficacy of adalimumab in a case of chronic Vogt-Koyanagi-Harada (VKH) disease refractory to conventional corticosteroids and immunosuppressive therapy and complicated by central serous chorioretinopathy (CSC).Case report: A 66-year-old woman diagnosed with VKH was treated with intravenous corticosteroids followed by oral corticosteroids and cyclosporine. However, systemic corticosteroids could not be tapered because of recurrent ocular inflammation and systemic complications (diabetes mellitus, moon face, bone weakness), while CSC appeared in both eyes. A diagnosis of chronic VKH resistant to medications complicated by corticosteroid-induced CSC was made. Systemic corticosteroids and cyclosporine were tapered and adalimumab initiated. Bilateral ocular inflammation and CSC were gradually reduced and visual acuity improved without any adverse effect. Twelve months after starting adalimumab monotherapy, no signs of active VKH and CSC were present.Conclusions: Adalimumab is one of the effective therapeutic options for refractory VKH disease complicated with corticosteroid-induced adverse effects.
神经系统自身免疫性疾病是以自身免疫细胞、免疫分子等攻击神经系统为主要致病机制的自身免疫性疾病。在免疫反应中,作用于神经系统自身抗原的致病抗体统称为神经系统自身抗体。