Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study.
Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study.
复制标题
DOI：
10.1186/s13075-015-0913-x
复制
发表时间：
2016-01-20
影响因子：
4.9
通讯作者：
Karsdal MA
中科院分区：
文献类型：
--
作者：
Bay-Jensen AC;Platt A;Siebuhr AS;Christiansen C;Byrjalsen I;Karsdal MA
类风湿性关节炎（RA）的特点是关节逐渐破坏。托珠单抗 (TCZ) 可显着抑制症状，但并非所有患者都能免受关节损伤。我们研究了特定生物标志物的早期测量是否可以预测对托珠单抗的早期关节保护反应。在接受安慰剂或 4 或 8 mg/kg TCZ 治疗的 740 名 RA 患者（LITHE 研究）中测量了血清生物标志物（CRPM、VICM、C1M、C2M、C3M（MMP 降解的 CRP、波形蛋白 I、II 和 III 型胶原）、CTX-I/OC（骨转换）和 CRP）。早期反应者是指在第 16 周时 SJC 或 TJC 改善≥20% 的人。通过 AUROC 和分类回归树分析研究了生物标志物的反应预测能力。用于识别 TCZ 应答者的最佳生物标志物预测是：基线 CTX-I/OC (AUC 0.66, p = 0.0005) 以及 C1M (AUC 0.67, p = 0.0072)、C2M (AUC 0.72, p = 0.0002)、C3M (AUC 0.63, p = 0.018) 和生物标志物的组合（AUC 0.81，p = 0.0025）。骨转换率高 (CTX-I/OC) 和 C2M 低的患者对 TCZ 产生早期反应的可能性是其 6.8 倍 (p = 0.003)。这种增强的药效 (PD) 反应能够识别出具有卓越 TCZ 临床益处的早期反应者。该生物标志物模型可能有助于识别 TCZ 反应性 RA 患者，从而可能使个体患者受益。临床试验.gov：NCT00106535。 2005 年 1 月 本文的在线版本 (doi:10.1186/s13075-015-0913-x) 包含补充材料，可供授权用户使用。
Rheumatoid arthritis (RA) is characterized by gradual joint destruction. Tocilizumab (TCZ) significantly suppresses symptoms, however not all patients are protected from joint damage. We investigated whether early measurement of specific biomarkers could predict early joint protection response to tocilizumab. Serum biomarkers (CRPM, VICM, C1M, C2M, C3M (MMP-degraded CRP, vimentin type I, II and III collagen), CTX-I/OC (bone turnover), and CRP) were measured in 740 RA patients (the LITHE study) treated with Placebo, or 4 or 8 mg/kg TCZ. Early responders were those with ≥20 % improvement in SJC or TJC by week 16. The biomarkers' predictability of response was investigated by AUROC and classification regression tree analysis. The best biomarker predictability for identification of TCZ responders were; baseline CTX-I/OC (AUC 0.66, p = 0.0005) and changes in C1M (AUC 0.67, p = 0.0072), C2M (AUC 0.72, p = 0.0002), C3M (AUC 0.63, p = 0.018) and the combination of biomarkers (AUC 0.81, p = 0.0025). Patients with high bone turnover (CTX-I/OC) and low C2M were 6.8-fold (p = 0.003) more likely to have an early response to TCZ. This enhanced pharmacodynamic (PD) response enabled identification of early responders with a superior TCZ clinical benefit. This biomarker model may assist in the identification of TCZ responsive RA patients and thus potentially benefit individual patients. Clinicaltrials.gov: NCT00106535. JAN 2005 The online version of this article (doi:10.1186/s13075-015-0913-x) contains supplementary material, which is available to authorized users.