Dermatologikum Hamburg, Hamburg, Germany Dalhousie University, Halifax, NS, Canada.
Br J Dermatol. 2011 Apr;164(4):862-72. doi: 10.1111/j.1365-2133.2011.10257.x.
Patients with psoriasis are believed to be at an increased risk of cardiovascular (CV) morbidity, and the effect of biological agents on CV safety is not fully understood.
To evaluate the effect of ustekinumab on CV events using detailed analyses of pooled data from the phase II/III clinical studies of its use in moderate to severe psoriasis.
The incidence of major adverse CV events [MACE: myocardial infarction (MI), stroke or CV death] is reported. Meta-analyses using risk difference and odds ratio estimates are presented based on data collected during the placebo-controlled period of ustekinumab trials. The cumulative numbers of events and rates of MIs and strokes over time were compared with those expected in the psoriasis and/or general populations.
During the placebo-controlled period (12/20 weeks), five MACE were reported in 1582 ustekinumab-treated patients [0·3%; 95% confidence interval (CI) 0·1-0·7%] compared with no events in 732 placebo-treated patients (0·0%; 95% CI 0·0-0·5%). MACE rates were stable over time during both the controlled and uncontrolled study periods, with 19 of 3117 ustekinumab-treated patients (0·6%) experiencing 21 events for a combined event rate per 100 patient-years of follow-up of 0·44 (95% CI 0·27-0·67) through up to 3 years. Standardized incidence ratios for comparison of ustekinumab clinical data with external data sources ranged from 0·34 to 0·52, suggesting no increased risk of MI or stroke in ustekinumab-treated patients compared with the general U.S. and psoriasis populations.
The totality of available clinical data suggests neither a detrimental nor a beneficial effect of ustekinumab on serious CV events. Additional data are needed to define the net effect of ustekinumab on CV events.
据信，银屑病患者发生心血管（CV）发病率的风险增加，而生物制剂对 CV 安全性的影响尚不完全清楚。
通过对其在中度至重度银屑病中的使用的 II/III 期临床研究的汇总数据进行详细分析，评估乌司奴单抗对 CV 事件的影响。
报告了主要不良 CV 事件（MACE：心肌梗死（MI）、中风或 CV 死亡）的发生率。根据乌司奴单抗试验的安慰剂对照期收集的数据，使用风险差异和优势比估计值进行了荟萃分析。随着时间的推移，比较了事件的累积数量以及 MI 和中风的发生率与银屑病和/或一般人群中的预期发生率。
在安慰剂对照期（12/20 周），1582 名乌司奴单抗治疗患者中有 5 例发生 MACE[0.3%；95%置信区间（CI）0.1-0.7%]，而 732 名安慰剂治疗患者中无事件（0.0%；95% CI 0.0-0.5%）。在对照和未对照研究期间，MACE 发生率随时间保持稳定，3117 名乌司奴单抗治疗患者中有 19 名（0.6%）经历了 21 次事件，在 3 年的随访中每 100 名患者年的合并事件发生率为 0.44（95%CI 0.27-0.67）。将乌司奴单抗临床数据与外部数据源进行比较的标准化发病率比范围为 0.34 至 0.52，表明与一般美国人群和银屑病人群相比，乌司奴单抗治疗患者发生 MI 或中风的风险没有增加。
现有临床数据的总体情况表明，乌司奴单抗对严重 CV 事件既没有不利影响，也没有有益影响。需要更多的数据来确定乌司奴单抗对 CV 事件的净影响。
