Levels of interleukin-1 beta can predict response to tocilizumab therapy in rheumatoid arthritis: the PETITE (predictors of effectiveness of tocilizumab therapy) study
Levels of interleukin-1 beta can predict response to tocilizumab therapy in rheumatoid arthritis: the PETITE (predictors of effectiveness of tocilizumab therapy) study
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DOI：
10.1007/s00296-015-3379-x
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发表时间：
2016-03-01
影响因子：
4
通讯作者：
Nakamura, Hiroaki
中科院分区：
文献类型：
--
作者：
Okano, Tadashi;Inui, Kentaro;Nakamura, Hiroaki
预测类风湿关节炎（RA）患者对托珠单抗的反应是困难的，因为炎症标志物如C反应蛋白迅速恢复正常，而不管临床疗效如何。我们的目的是确定可以预测托珠单抗反应的因素。65例患者完成了52周的托珠单抗治疗。在基线和治疗4周后测定血清纤维蛋白原、D-二聚体和白细胞介素（IL）-1 β水平。在基线和治疗52周后，使用疾病活动性评分28-红细胞沉降率和临床疾病活动性指数评估托珠单抗的临床应答（UMIN临床试验注册号UMIN 00002246）。平均年龄为60.5岁（范围22-85岁）。平均病程为11.2年（范围0-45年）。所有患者均有中度至重度疾病活动性，对缓解疾病的抗风湿药物和/或其他生物制剂耐药。应答者的基线IL-1 β水平显著低于无应答者（p = 0.045），但多元逻辑回归分析发现无显著差异（调整后的比值比2.74; 95%置信区间0.84-8.95; p = 0.096）。治疗4周时D-二聚体和IL-1 β水平较低，预示治疗52周后疾病活动性下降幅度较大（分别为p = 0.005和p < 0.001）。托珠单抗治疗4周后的D-二聚体和IL-1 β水平可以预测托珠单抗在52周时的作用。这些标志物可能比目前的炎症标志物更有用，用于早期预测RA患者对托珠单抗的反应。
Predicting the responses of patients with rheumatoid arthritis (RA) to tocilizumab is difficult, because inflammatory markers such as C-reactive protein rapidly normalize regardless of clinical efficacy. We aimed to identify factors that could predict response to tocilizumab. Sixty-five patients completed 52 weeks of tocilizumab therapy. Serum fibrinogen, D-dimer and interleukin (IL)-1 beta levels were measured at baseline and after 4 weeks of therapy. Clinical responses to tocilizumab were assessed using disease activity score 28-erythrocyte sedimentation rate and the clinical disease activity index at baseline and after 52 weeks of therapy (UMIN Clinical Trials Registry No. UMIN000002246). Mean age was 60.5 years (range 22-85 years). Mean disease duration was 11.2 years (range 0-45 years). All patients had moderate-to-severe disease activity and were resistant to disease-modifying anti rheumatic drugs and/or other biologics. Baseline IL-1 beta levels were significantly lower in responders than in non responders (p = 0.045), but multiple logistic regression analysis found no significant difference (adjusted odds ratio 2.74; 95 % confidence interval 0.84-8.95; p = 0.096). Low D-dimer and IL-1 beta levels at 4 weeks predicted greater decrease in disease activity after 52 weeks of treatment (p = 0.005 and p < 0.001, respectively). Effects of tocilizumab at 52 weeks could be predicted from D-dimer and IL-1 beta levels after 4 weeks of tocilizumab treatment. These markers might be more useful than current inflammatory markers for early-stage prediction of response to tocilizumab in RA.