Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria.
Internal Medicine D, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Ann Rheum Dis. 2020 Jul;79(7):874-882. doi: 10.1136/annrheumdis-2019-215987. Epub 2020 May 5.
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.
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.
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).
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.
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。
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。
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)。
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。