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 number NCT02433184

中文翻译：

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早期依那西普联合 MTX 与 MTX 联合延迟依那西普治疗 RA 的实用随机对照试验：VEDERA 试验


目的 我们试图证实，在极早期类风湿性关节炎 (ERA) 中，一线依那西普 + 甲氨蝶呤 (ETN+MTX) 比靶向治疗 MTX (MTX-TT) 的优越性 (30%) 比之前在 ERA 中报道的要大得多(14%)；并探讨初始 MTX 之后的 ETN 是否能获得与一线 ETN+MTX 相当的反应。方法 针对初治 ERA（症状≤12 个月）、疾病活动评分 28 关节 (DAS28)-红细胞沉降率 (ESR) ≥3.2、类风湿因子 (RF)+/- 抗瓜氨酸肽的实用、开放标签、随机对照试验如果 RF 和 ACPA 阴性，则抗体 (ACPA) 阳性或超声功率多普勒 (PD)。受试者按 1:1 随机分配至 ETN+MTX；或 MTX-TT，如果第 24 周 DAS28-ESR ≥2.6，则升级为 ETN，并在方案时间点肌内注射皮质类固醇。主要终点为第 48 周 DAS28ESR 缓解，以及临床和影像学次要终点。结果 我们将 120 名患者随机分为每组 60 名（71% 女性，73% RF/84% 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)）。第 24 周时，ETN+MTX 和 MTX-TT 的缓解率分别为 38% 和 33%；第 48 周时为 52% vs 38%（OR 1.6，95% CI 0.8 至 3.5，p=0.211）。与 MTX-TT 相比，ETN+MTX 观察到更持久的 DAS28-ESR 缓解（分别为 42% 和 27%；p=0.035）。到第 48 周时，每组中超过 90% 的 PD 均得到完全抑制。计划的探索性分析显示，与 MTX 后给药相比，一线 ETN 给药 24 周后实现缓解的 OR 为 2.84，95% CI 0.8 至 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 的缓解率相比，我们没有证明在非常 ERA 中具有更大的效果。 尽管超声证实了局部炎症抑制，但这两种策略都未能使大多数患者得到缓解。还表明 MTX-TT 失败后 ETN 反应较差。试用注册号NCT02433184