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C 反应蛋白基线水平和早期变化对托珠单抗治疗类风湿关节炎患者后续临床结局的影响。

Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab.

机构信息

Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria.

Internal Medicine D, Chaim Sheba Medical Center, Tel Hashomer, Israel.

出版信息

Ann Rheum Dis. 2020 Jul;79(7):874-882. doi: 10.1136/annrheumdis-2019-215987. Epub 2020 May 5.

Abstract

BACKGROUND

Rheumatoid arthritis (RA) is characterised by clinical joint swelling and elevation of acute phase reactant levels, typically measured by the C-reactive protein (CRP). Clinical and inflammatory responses are usually concordant, except for inhibition of IL-6, which often disproportionally reduces the CRP due to direct inhibition of its hepatic production. We investigated whether pre-treatment CRP is a useful marker that can guide a preferential treatment choice towards IL-6 inhibition.

METHODS

Data of 1126 treatment courses with tocilizumab (TCZ; early RA), 250 courses of rituximab (RTX; established RA) and 249 courses of methotrexate (MTX; established RA) were analysed. We compared clinical disease activity index (CDAI) values and change along 24 weeks' follow-up to CRP values at baseline or its early change. We validated the results using data from a separate TCZ trial in early RA.

RESULTS

CRP levels in the TCZ group on average dropped by 74% within 4 weeks. Patients who attained CDAI remission at 24 weeks on TCZ had the highest baseline CRP levels while patients in high disease activity had the lowest; this association was reverse in the RTX and MTX groups. TCZ patients who achieved remission at 24 weeks showed the largest reductions of CRP levels by week 4 compared with those reaching higher disease activity states. Early CRP non-response was indicative of a risk of not achieving clinical treatment goals (p=0.038).

CONCLUSION

Baseline CRP appears to have a positive association with reaching the therapeutic target on TCZ treatment, but is a negative predictor for RTX and MTX. Patients on TCZ without an early CRP response have a lower chance of achieving remission. CRP and its early course may inform, to some extent, the estimation of potential therapeutic success in patients with RA.

摘要

背景

类风湿关节炎(RA)的特征是临床关节肿胀和急性期反应物水平升高,通常通过 C 反应蛋白(CRP)来测量。临床和炎症反应通常是一致的,但白细胞介素 6(IL-6)的抑制除外,由于其对肝脏产生的直接抑制作用,通常不成比例地降低 CRP。我们研究了治疗前 CRP 是否是一个有用的标志物,可以指导选择对 IL-6 抑制的优先治疗。

方法

分析了托珠单抗(TCZ;早期 RA)的 1126 个疗程、利妥昔单抗(RTX;已确立的 RA)的 250 个疗程和甲氨蝶呤(MTX;已确立的 RA)的 249 个疗程的数据。我们比较了基线或早期变化时的 CRP 值与 24 周随访期间临床疾病活动指数(CDAI)值和变化的关系。我们使用单独的 TCZ 早期 RA 试验的数据验证了结果。

结果

TCZ 组的 CRP 水平在 4 周内平均下降了 74%。在 24 周达到 CDAI 缓解的 TCZ 患者的基线 CRP 水平最高,而处于高疾病活动的患者的基线 CRP 水平最低;这种关联在 RTX 和 MTX 组中相反。在第 4 周达到缓解的 TCZ 患者的 CRP 水平下降幅度比达到更高疾病活动状态的患者大。在第 4 周时早期 CRP 无反应预示着不能达到临床治疗目标的风险(p=0.038)。

结论

基线 CRP 似乎与 TCZ 治疗达到治疗目标呈正相关,但对 RTX 和 MTX 是负预测因子。没有早期 CRP 反应的 TCZ 患者达到缓解的机会较低。CRP 及其早期过程在一定程度上可以预测 RA 患者的潜在治疗成功。

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