Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Ann Rheum Dis. 2020 Apr;79(4):464-471. doi: 10.1136/annrheumdis-2019-216539. Epub 2020 Jan 29.
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.
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.
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.
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. NCT02433184.
我们旨在早期类风湿关节炎（ERA）中证实，一线依那西普+甲氨蝶呤（ETN+MTX）的疗效（30%）明显优于之前报道的靶向治疗甲氨蝶呤（MTX-TT）（14%）；并探讨最初使用甲氨蝶呤后，依那西普是否能确保与一线 ETN+MTX 相当的反应。
这是一项针对治疗初发 ERA（≤12 个月症状）的实用、开放性、随机对照试验，疾病活动度评分 28 关节（DAS28）-红细胞沉降率（ESR）≥3.2、类风湿因子（RF）+/抗瓜氨酸肽抗体（ACPA）阳性或如果 RF 和 ACPA 阴性则为超声功率多普勒（PD）。受试者按 1:1 随机分为 ETN+MTX 组或 MTX-TT 组，在第 24 周 DAS28-ESR≥2.6 时和在方案规定的时间点给予肌内皮质类固醇时，可升级为 ETN。主要终点为第 48 周 DAS28-ESR 缓解，次要终点包括临床和影像学。
我们随机分配了 120 名患者，每组 60 名（71%为女性，73%为 RF/84%为 ACPA 阳性，中位（IQR）症状持续时间 20.3（13.1，30.8）周；平均（SD）DAS28 为 5.1（1.1））。分别在第 24 周和第 48 周，ETN+MTX 和 MTX-TT 的缓解率分别为 38%和 33%（OR 1.6，95%CI 0.8 至 3.5，p=0.211）。与 MTX-TT 相比，ETN+MTX 观察到更大、更持久的 DAS28-ESR 缓解（分别为 42%和 27%，p=0.035）。在每一组中，超过 90%的患者在第 48 周时 PD 完全得到抑制。计划的探索性分析显示，与 MTX 后给予 ETN 相比，第 24 周后首次给予 ETN 的缓解率（OR 2.84，95%CI 0.8 至 9.6）更高。
与一线肿瘤坏死因子抑制剂+MTX 与 MTX-TT 相比，我们通常报告的缓解率相比，在早期 ERA 中并没有显示出更大的效果。两种策略都没有使大多数患者达到缓解，尽管超声证实了局部炎症的抑制。在 MTX-TT 失败后，依那西普的反应较差也提示。NCT02433184。
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