甲氨蝶呤联合或不联合早期引入为期6个月的依那西普疗程的桥接糖皮质激素在早期类风湿关节炎中的疗效：为期2年的实用随机CareRA2020试验结果
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.
作者信息
Bertrand Delphine, Joly Johan, Neerinckx Barbara, Durez Patrick, Lenaerts Jan, Joos Rik, Thevissen Kristof, Zwaenepoel Tom, Vanhoof Johan, Di Romana Silvana, Taelman Veerle, Van Essche Els, Corluy Luk, Ribbens Clio, Vanden Berghe Marc, Devinck Mieke, Ajeganova Sofia, Durnez Anne, Boutsen Yves, Margaux Joëlle, Peene Isabelle, Van Offel Jan, Doumen Michaël, Pazmino Sofia, De Meyst Elias, Kulyk Myroslava, Creten Nelly, Westhovens René, Verschueren Patrick
机构信息
Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Flanders, Belgium
Department of Rheumatology, UZ Leuven, Leuven, Vlaams-Brabant, Belgium.
出版信息
RMD Open. 2024 Aug 7;10(3):e004535. doi: 10.1136/rmdopen-2024-004535.
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.
目的
研究早期类风湿关节炎患者在对初始甲氨蝶呤（MTX）和桥接糖皮质激素（GCs）反应不足时，早期短期引入依那西普作为第二次诱导缓解尝试是否有益。
方法
CareRA2020（NCT03649061）是一项为期2年的开放标签、多中心、实用性随机对照试验。未接受过治疗的患者开始使用MTX和GC桥接治疗（COBRA-Slim：CS）。在第8周（W）至第32周的时间窗口内，早期反应不足者（在第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或在第32周时≥2.6）被随机分配至标准CS策略（先加用来氟米特）或生物诱导CS策略（加用依那西普24周）。额外的治疗调整遵循达标治疗原则。比较随机分组组间104周的纵向疾病活动度（DAS28-CRP）（主要结局）、随机分组后28周时DAS28-CRP<2.6的达成情况以及第104周时生物制剂或靶向合成改善病情抗风湿药物（b/tsDMARD）的使用情况。
结果
接受CS治疗后，142例患者为早期反应者；55例早期反应不足者接受标准CS治疗，55例接受生物诱导CS治疗。对于主要结局，无法证明生物诱导CS优于标准CS（ß=-0.204，（95%CI -0.486至0.078），p=0.157）。在随机分组后28周时，更多接受生物诱导CS治疗的患者实现了DAS28-CRP<2.6（59%（95%CI 44%至72%），而标准CS组为44%（95%CI 31%至59%）），并且在第104周时，与标准CS组（29/55，53%）相比，他们接受b/tsDMARD治疗的频率更低（19/55，35%）。
结论
一半的患者对初始COBRA-Slim诱导治疗反应良好。在早期反应不足者中，与先加用来氟米特相比，加用依那西普6个月在104周内并未改善疾病控制。然而，依那西普的短期引入在随机分组后早期改善了疾病控制，并且在第104周时接受b/tsDMARD治疗的患者更少。
试验注册号
NCT03649061。
比利时CTR试验批准号：S59474，欧盟临床试验编号：2017-004054-41。
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