Keesler AFB, 301 Fisher Avenue, Biloxi, MS, 39534, USA.
Rheumatol Int. 2018 Jan;38(1):59-66. doi: 10.1007/s00296-017-3842-y. Epub 2017 Oct 24.
Acute myocardial infarction (MI) occurs when blood supply falls below critical levels and normal cellular maintenance mechanisms fail. Interleukin-6 (IL-6) is a proinflammatory cytokine released in MI and associated with poor clinical outcomes. Tocilizumab (TCZ) is a humanized monoclonal antibody against the IL-6 receptor. In a randomized, double-blinded, placebo controlled trial we assigned subjects admitted with MI a single TCZ dose of 162 mg subcutaneously vs. placebo in addition to standard of care medications and interventions. Primary outcome was a change in major adverse cardiac events (MACE) 30 days after enrollment. Secondary outcomes assessed changes in CRP 30 days after enrollment, changes in QT/QTc, and monitoring for trends in adverse events. Futility analysis was performed as subject enrollment slowed and no trends were noted in either the primary or secondary outcomes. Twenty-eight subjects were enrolled; 12 to TCZ and 16 to placebo. No statistically significant differences were noted between study arms regarding demographics, comorbidities, or medical/interventional therapies received. No statistically significant differences in MACE were observed. CRP increased after administration of TCZ but this was not statistically significant. No adverse events or safety signals were observed. Though futility analysis suggested that the primary outcome was not likely achievable as our recruitment slowed, we did not observe any adverse events or safety trends. Building on this information, future studies should be conducted to assess a true benefit from TCZ as adjunct therapy for MI. The work reported herein was performed under United States Air Force Surgeon General approved Clinical Investigation FKE20140029 and has been registered at ClinicalTrials.gov under identifier NCT02419937.
急性心肌梗死（MI）发生在血液供应低于临界水平且正常细胞维持机制失效时。白细胞介素-6（IL-6）是一种在 MI 中释放的促炎细胞因子，与不良临床结局相关。托珠单抗（TCZ）是一种针对 IL-6 受体的人源化单克隆抗体。在一项随机、双盲、安慰剂对照试验中，我们将 MI 入院患者随机分配接受单次 TCZ 162mg 皮下注射，或安慰剂加标准护理药物和干预措施。主要终点是 30 天后主要不良心脏事件（MACE）的变化。次要终点评估了 30 天后 CRP 的变化、QT/QTc 的变化以及对不良事件趋势的监测。由于受试者入组速度放缓，且主要或次要结局均未出现趋势，因此进行了无效性分析。共纳入 28 例患者，12 例接受 TCZ，16 例接受安慰剂。研究组在人口统计学、合并症或接受的医疗/介入治疗方面无统计学显著差异。两组间 MACE 无统计学显著差异。TCZ 给药后 CRP 升高，但无统计学显著差异。未观察到不良事件或安全信号。尽管无效性分析表明，随着我们的招募速度放缓，主要结局不太可能实现，但我们没有观察到任何不良事件或安全趋势。在此基础上，应开展未来的研究以评估 TCZ 作为 MI 辅助治疗的真正获益。本报告所述工作是在美国空军军医局长批准的临床研究 FKE20140029 下进行的，并已在 ClinicalTrials.gov 上注册，标识符为 NCT02419937。
