Effectiveness of methotrexate and bridging glucocorticoids with or without early introduction of a 6-month course of etanercept in early RA: results of the 2-year, pragmatic, randomised CareRA2020 trial.

IF 5.1 2区 医学 Q1 RHEUMATOLOGY
Delphine Bertrand, Johan Joly, Barbara Neerinckx, Patrick Durez, Jan Lenaerts, Rik Joos, Kristof Thevissen, Tom Zwaenepoel, Johan Vanhoof, Silvana Di Romana, Veerle Taelman, Els Van Essche, Luk Corluy, Clio Ribbens, Marc Vanden Berghe, Mieke Devinck, Sofia Ajeganova, Anne Durnez, Yves Boutsen, Joëlle Margaux, Isabelle Peene, Jan Van Offel, Michaël Doumen, Sofia Pazmino, Elias De Meyst, Myroslava Kulyk, Nelly Creten, René Westhovens, Patrick Verschueren
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引用次数: 0

Abstract

Objectives: To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt.

Methods: CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score - C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups.

Results: Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=-0.204, (95% CI -0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%).

Conclusion: Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104.

Trial registration number: NCT03649061.

Ctr pilot approval belgium: S59474, EudraCT number: 2017-004054-41.

甲氨蝶呤和桥接糖皮质激素与或不提前引入 6 个月疗程的依那西普对早期 RA 的疗效:为期 2 年的实用随机 CareRA2020 试验结果。
研究目的研究对初始甲氨蝶呤(MTX)和桥接性糖皮质激素(GCs)反应不充分的早期类风湿关节炎患者是否能从早期但暂时性引入依那西普(etanercept)作为第二次缓解诱导尝试中获益:CareRA2020(NCT03649061)是一项为期2年的开放标签、多中心、实用随机对照试验。治疗无效的患者开始使用 MTX 和 GC 桥接疗法(COBRA-Slim:CS)。在第8周至第32周的时间窗口内,早期反应不足者(第8周至第32周期间28关节疾病活动评分-C反应蛋白(DAS28-CRP)>3.2或第32周时≥2.6)被随机分配到标准-CS策略(首先加入来氟米特)或生物诱导-CS策略(加入依那西普,持续24周)。其他治疗调整遵循靶向治疗原则。104周的纵向疾病活动度(DAS28-CRP)(主要结果)、DAS28-CRP的达标结果:CS 治疗后,142 名患者为早期应答者;55 名早期应答不足者接受了标准-CS,55 名接受了生物诱导-CS。在主要结果方面,生物诱导综合疗法优于标准综合疗法(ß=-0.204, (95% CI -0.486 to 0.078), p=0.157)。更多接受生物诱导-CS治疗的患者达到了DAS28-CRP结论:半数患者对最初的 COBRA-Slim 诱导疗法反应良好。在早期反应不充分的患者中,与首先加入来氟米特相比,在104周内加入依那西普治疗6个月并不能改善疾病控制。然而,临时使用依那西普能改善随机化后早期的疾病控制,并减少W104时使用b/tsDMARDs的患者人数:NCT03649061.Ctr 试点批准比利时:S59474, EudraCT number: 2017-004054-41.
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来源期刊
RMD Open
RMD Open RHEUMATOLOGY-
CiteScore
7.30
自引率
6.50%
发文量
205
审稿时长
14 weeks
期刊介绍: RMD Open publishes high quality peer-reviewed original research covering the full spectrum of musculoskeletal disorders, rheumatism and connective tissue diseases, including osteoporosis, spine and rehabilitation. Clinical and epidemiological research, basic and translational medicine, interesting clinical cases, and smaller studies that add to the literature are all considered.
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