Welsh Paul, Tuckwell Katie, McInnes Iain B, Sattar Naveed
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Roche Products Ltd, Welwyn Garden City, UK.
Atherosclerosis. 2016 Nov;254:167-171. doi: 10.1016/j.atherosclerosis.2016.10.016. Epub 2016 Oct 8.
Observational associations between inflammation and cardiovascular disease are interesting, but randomised experimental data are lacking. We investigated the effect of the IL-6 receptor blocker tocilizumab on N terminal pro B type natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hsTnT) in rheumatoid arthritis (RA) patients.
A post-hoc study was performed in a subset of patients with moderate to severe RA participating in a randomised controlled trial. The effect of tocilizumab on cardiac biomarkers was determined using stored serum (baseline and 24 weeks) in recipients of tocilizumab (8 mg/kg every 4 weeks plus DMARDs; n = 225) or placebo (every 4 weeks plus DMARDs; n = 132).
Median NT-proBNP and hsTnT concentrations at baseline were 100 pg/ml and 5.7 pg/ml, respectively. NT-proBNP decreased in both study arms (median at 24 weeks 77 pg/ml in the placebo arm, 79 pg/ml in the tocilizumab arm; p<0.001 for the decrease in both arms), and decreased to a similar extent comparing study arms (tocilizumab effect: -5.5%, p=0.55). hsTnT also decreased in both study arms (median at 24 weeks 3.1 pg/ml in the placebo arm, 4.4 pg/ml in the tocilizumab arm; p<0.001 for the decrease in both arms). The extent of the reduction in hsTnT was greater in the placebo group (tocilizumab effect: +23.3%, p=0.002). Change in NT-proBNP, but not hsTnT, correlated modestly with change in CRP (r = 0.17, p=0.013).
These data argue against a rapid preferential benefit of IL-6 blockade on these specific surrogate markers of cardiovascular risk, but may be consistent with a general cardiovascular benefit of improved RA treatment. CLINICAL TRIALS.
NCT00106574.
炎症与心血管疾病之间的观察性关联很有意思，但缺乏随机实验数据。我们研究了白细胞介素-6受体阻滞剂托珠单抗对类风湿关节炎（RA）患者N末端B型利钠肽原（NT-proBNP）和高敏肌钙蛋白T（hsTnT）的影响。
在参与一项随机对照试验的中度至重度RA患者亚组中进行了一项事后分析研究。使用托珠单抗（每4周8mg/kg加改善病情抗风湿药；n = 225）或安慰剂（每4周加改善病情抗风湿药；n = 132）接受者储存的血清（基线和24周）来确定托珠单抗对心脏生物标志物的影响。
基线时NT-proBNP和hsTnT的中位浓度分别为100 pg/ml和5.7 pg/ml。两个研究组的NT-proBNP均下降（安慰剂组24周时中位值为77 pg/ml，托珠单抗组为79 pg/ml；两组下降均p<0.001），且两组之间下降程度相似（托珠单抗效应：-5.5%，p = 0.55）。两个研究组的hsTnT也均下降（安慰剂组24周时中位值为3.1 pg/ml，托珠单抗组为4.4 pg/ml；两组下降均p<0.001）。安慰剂组hsTnT降低的幅度更大（托珠单抗效应：+23.3%，p = 0.002）。NT-proBNP的变化与CRP的变化有适度相关性（r = 0.17，p = 0.013），但hsTnT与CRP变化无相关性。
这些数据表明白细胞介素-6阻断对这些特定的心血管风险替代标志物并无快速的优先益处，但可能与改善RA治疗带来的总体心血管益处一致。临床试验。
NCT00106574。
