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Pragmatic randomised controlled trial of very early etanercept and MTX versus MTX with delayed etanercept in RA: the VEDERA trial.

极早期依那西普和 MTX 与 MTX 联合延迟依那西普治疗 RA 的实用性随机对照试验: VEDERA 试验。

  • 影响因子:9.18
  • DOI:10.1136/annrheumdis-2019-216539
  • 作者列表:"Emery P","Horton S","Dumitru RB","Naraghi K","van der Heijde D","Wakefield RJ","Hensor EMA","Buch MH
  • 发表时间:2020-01-29
Abstract

OBJECTIVES:We sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX. METHODS:Pragmatic, open-label, randomised controlled trial of treatment-naïve ERA (≤12 months symptom), Disease Activity Score 28 joint (DAS28)-erythrocyte sedimentation rate (ESR) ≥3.2, rheumatoid factor (RF)+/-anticitrullinated peptide antibody (ACPA) positive or ultrasound power Doppler (PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR ≥2.6 and intramuscular corticosteroid at protocolised time points. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints. RESULTS:We randomised 120 patients, 60 to each arm (71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3 (13.1, 30.8) weeks; mean (SD) DAS28 5.1 (1.1)). Remission rates with ETN+MTX and MTX-TT, respectively, were 38% vs 33% at week 24; 52% vs 38% at week 48 (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211). Greater, sustained DAS28-ESR remission observed with ETN+MTX versus MTX-TT (42% and 27%, respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR 2.84, 95% CI 0.8 to 9.6) of achieving remission after 24 weeks of ETN administered first line compared with administered post-MTX. CONCLUSIONS:Compared with remission rates typically reported with first-line tumour necrosis factor inhabitor+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested.Trial registration numberNCT02433184.

摘要

目的: 我们试图在非常早期的类风湿关节炎 (ERA) 中证实一线依那西普 + 甲氨蝶呤 (ETN + MTX) 的更大优势 (30%) 与 ERA (14%) 中以前报道的相比,治疗靶向 MTX (MTX-TT) 过度; 并探讨初始 MTX 后的 ETN 是否可获得与一线 ETN + MTX 相当的应答。 方法: 治疗初始时代 (症状 ≤ 12 个月),疾病活动评分 28 关节 (DAS28)-红细胞沉降率 (ESR) 的务实、开放标签、随机对照试验 ≥ 3.2,类风湿因子 (RF) +/-抗瓜氨酸肽抗体 (ACPA) 阳性或超声能量多普勒 (PD) 如果 RF 和 ACPA 阴性。受试者 1:1 随机分配至 ETN + MTX; 或 MTX-TT,如果第 24 周 DAS28-ESR ≥ 2.6,则升级至 ETN,并在计划时间点肌肉注射皮质类固醇。第 48 周 DAS28ESR 缓解的主要终点与临床和影像学次要终点。 结果: 我们随机选择了 120 例患者,每组 60 例 (71% 例女性,73% 例 RF/84% 例 ACPA 阳性,中位 (IQR) 症状持续时间 20.3 (13.1,30.8) 周; 平均 (SD) DAS28 5.1 (1.1))。24 周时 ETN + MTX 和 MTX-TT 的缓解率分别为 38% vs 33%; 48 周时 52% vs 38% (ORs 1.6,95% ci 0.8 ~ 3.5, p = 0.211)。ETN + MTX 相比 MTX-TT 观察到更大、持续的 DAS28-ESR 缓解 (分别为 42% 和 27%; p = 0.035)。PD 在 48 周时每臂超过 90% 得到完全抑制。计划的探索性分析显示,与 MTX 后给药相比,ETN 一线给药 24 周后达到缓解的 OR 为 2.84,95% ci 0.8 ~ 9.6)。 结论: 与通常报道的一线肿瘤坏死因子抑制剂 + MTX 与 MTX-TT 相比的缓解率相比,我们并没有证明在非常时代有更大的影响。尽管超声证实局部炎症抑制,但两种策略均未使大多数患者获得缓解。MTX-TT 失败后 ETN 反应较差。试验注册 numbernct02433184。

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DOI:10.1080/08916934.2019.1710831
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METHODS:ZNF804a and CDK1 genes code for proteins involved in inflammatory pathways. This study aimed to investigate the correlation of ZNF804a and CDK1 expression profiles in RA with the activity and the severity of the disease and to assess their association with inflammatory reactions in the Egyptian RA patients. ZNF804a and CDK1 expression profiles were assessed using quantitative PCR (qRT-PCR). Clinical and laboratory parameters were evaluated. ZNF804a expression was down-regulated by 0.177-fold while CDK1 expression was up-regulated to 3.29-fold in RA patients compared with healthy controls ( < .001). ZNF804a down-regulation was negatively correlated with CRP, RF, disease activity score of 28 joints (DAS) using CRP (DAS-CRP) and TNF-α. CDK1 overexpression was correlated with IFN-1 and ACPA in RA patients. ZNF804a and CDK1 genes are implicated in RA pathogenesis due to their influences on TNF-α and IFN-1 which contribute to inflammation in RA patients.

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影响因子:9.18
发表时间:2020-01-29
DOI:10.1136/annrheumdis-2019-216539
作者列表:["Emery P","Horton S","Dumitru RB","Naraghi K","van der Heijde D","Wakefield RJ","Hensor EMA","Buch MH"]

METHODS:OBJECTIVES:We sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX. METHODS:Pragmatic, open-label, randomised controlled trial of treatment-naïve ERA (≤12 months symptom), Disease Activity Score 28 joint (DAS28)-erythrocyte sedimentation rate (ESR) ≥3.2, rheumatoid factor (RF)+/-anticitrullinated peptide antibody (ACPA) positive or ultrasound power Doppler (PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR ≥2.6 and intramuscular corticosteroid at protocolised time points. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints. RESULTS:We randomised 120 patients, 60 to each arm (71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3 (13.1, 30.8) weeks; mean (SD) DAS28 5.1 (1.1)). Remission rates with ETN+MTX and MTX-TT, respectively, were 38% vs 33% at week 24; 52% vs 38% at week 48 (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211). Greater, sustained DAS28-ESR remission observed with ETN+MTX versus MTX-TT (42% and 27%, respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR 2.84, 95% CI 0.8 to 9.6) of achieving remission after 24 weeks of ETN administered first line compared with administered post-MTX. CONCLUSIONS:Compared with remission rates typically reported with first-line tumour necrosis factor inhabitor+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested.Trial registration numberNCT02433184.

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