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托珠单抗治疗类风湿关节炎患者的长期疗效,按生物制剂治疗失败次数分层:来自德国 RABBIT 队列的结果。

Long-term effectiveness of tocilizumab in patients with rheumatoid arthritis, stratified by number of previous treatment failures with biologic agents: results from the German RABBIT cohort.

机构信息

Epidemiology Unit, German Rheumatism Research Centre, Charitéplatz 1, 10117, Berlin, Germany.

Otto-von-Guericke University, Magdeburg, Germany.

出版信息

Rheumatol Int. 2018 Apr;38(4):579-587. doi: 10.1007/s00296-017-3870-7. Epub 2017 Nov 16.

Abstract

In Germany, Tocilizumab (TCZ) is used for the treatment of rheumatoid arthritis both in biologic-naïve patients and those with previous failures of biologic disease-modifying antirheumatic drugs (bDMARDs). The long-term effectiveness and retention rates of TCZ in patients with different numbers of prior bDMARD failures has rarely been investigated. We included 885 RA patients in the analyses, enrolled with the start of TCZ between 2009 and 2015 in the German biologics register RABBIT. Patients were stratified according to prior bDMARD failures: no prior bDMARD or 1, 2 or ≥ 3 bDMARD failures. We applied Kaplan-Meier methods and Cox-regression to examine treatment adherence as well as linear mixed effects models to investigate effectiveness over 3 years of follow-up. Compared to biologic-naïve patients, those with prior bDMARD failures at start of TCZ were younger but had significantly longer disease duration and more comorbidities. DAS28 at baseline and loss of physical function were highest in patients with ≥ 3 bDMARD failures. During follow-up, patients with up to two bDMARD failures on average reached low disease activity (LDA, DAS28 < 3.2). Those with ≥ 3 prior bDMARDs had a slightly lower response. However, after 3 years, nearly 50% of them achieved LDA. Treatment continuation on TCZ therapy was similar in patients with ≤ 2 bDMARD failures but significantly lower in those with ≥ 3 bDMARD failures. TCZ seems to be similarly effective in patients with no, one or two prior bDMARD failures. The majority of patients achieved LDA already after 6 months and maintained it over a period of 3 years. TCZ proved effective even in the high-risk group of patients with more than two prior bDMARD failures.

摘要

在德国,托珠单抗(TCZ)被用于治疗生物制剂初治患者和生物制剂失败的患者的类风湿关节炎。TCZ 在不同生物制剂失败次数的患者中的长期疗效和保留率很少被研究。我们在德国生物制剂登记处 RABBIT 中纳入了 885 例 RA 患者,这些患者在 2009 年至 2015 年之间开始使用 TCZ。患者根据之前的生物制剂失败情况分层:无之前的生物制剂或 1、2 或≥3 次生物制剂失败。我们应用 Kaplan-Meier 方法和 Cox 回归来检查治疗依从性,以及线性混合效应模型来研究 3 年随访期间的疗效。与生物制剂初治患者相比,TCZ 起始时存在之前生物制剂失败的患者年龄较小,但疾病持续时间明显较长,合并症更多。基线时 DAS28 和身体功能丧失在≥3 次生物制剂失败的患者中最高。在随访期间,平均有 2 次生物制剂失败的患者平均达到低疾病活动(DAS28<3.2)。有≥3 次之前生物制剂失败的患者反应稍低。然而,3 年后,他们中有近 50%的患者达到低疾病活动。在≤2 次生物制剂失败的患者中,TCZ 治疗的持续治疗率相似,但在≥3 次生物制剂失败的患者中显著降低。TCZ 在无、1 或 2 次之前生物制剂失败的患者中似乎同样有效。大多数患者在 6 个月后达到低疾病活动,并且在 3 年内维持低疾病活动。TCZ 甚至在有超过 2 次之前生物制剂失败的高风险患者中也证明有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1093/5854739/d567f91a30fa/296_2017_3870_Fig1_HTML.jpg

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