Long-term safety experience of ustekinumab in patients with moderate-to-severe psoriasis (Part I of II): Results from analyses of general safety parameters from pooled Phase 2 and 3 clinical trials
Long-term safety experience of ustekinumab in patients with moderate-to-severe psoriasis (Part I of II): Results from analyses of general safety parameters from pooled Phase 2 and 3 clinical trials
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DOI：
10.1016/j.jaad.2011.06.011
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发表时间：
2012-05-01
影响因子：
13.8
通讯作者：
Strober, Bruce
中科院分区：
文献类型：
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作者：
Lebwohl, Mark;Leonardi, Craig;Strober, Bruce
背景：优特克单抗以白细胞介素 (IL)-12 和 IL-23 为靶标治疗中重度银屑病。目的：评估总体汇总研究数据，以评估优特克单抗 3 年治疗的安全性。方法：汇总了 3117 名接受优特克单抗治疗患者的研究的累积安全性数据。结果：在安慰剂对照期间（第 2 期、PHOENIX 1、 PHOENIX 2)，接受安慰剂 (50.4%)、乌特克单抗 45 mg (57.6%) 或乌特克单抗 90 mg (51.6%) 治疗的患者的不良事件 (AE) 发生率相当；在 ACCEPT 试验的对照期间观察到类似的结果（依那西普：70.0%；乌特克单抗 45 mg：66.0%；乌特克单抗 90 mg：69.2%）。整个控制期间的严重 AE (SAE) 发生率较低且各组之间具有可比性（1.2% 至 1.9%）。 3年期间，每100名患者年随访的AE发生率（/100名患者年）（45 mg：305.2/100名患者年；90 mg：305.9/100名患者年）和SAE发生率（45 mg：6.8/100名患者年；90 mg：8.2/100名患者年）在两组之间具有可比性乌司奴单抗剂量。这些试验中没有报告脱髓鞘或结核病例。 3 年来，AE、总体感染或 SAE 发生率均未出现明显的剂量反应。 AE、感染、SAE 和导致研究药物停药的 AE 发生率总体上保持稳定或随着时间的推移而下降。局限性：对照期不超过 12 至 20 周。在 3117 名接受乌特克单抗治疗的患者中，只有 1247 人接受了 2 年或以上的治疗。结论：持续使用乌特克单抗长达 3 年的安全性状况良好，并且与之前的短期报告一致。 (J Am Acad Dermatol 2012；66:731-41。)
Background: Ustekinumab targets interleukin (IL)-12 and IL-23 in the treatment of moderate-to-severe psoriasis.Objective: To evaluate overall pooled study data to assess the safety profile of ustekinumab through 3 years of treatment.Methods: Cumulative safety data were pooled from studies in 3117 ustekinumab-treated patients.Results: During the placebo-controlled periods (Phase 2, PHOENIX 1, PHOENIX 2), rates of adverse events (AEs) were comparable among patients treated with placebo (50.4%), with ustekinumab 45 mg (57.6%), or with ustekinumab 90 mg (51.6%); similar findings were observed during the controlled period of the ACCEPT trial (etanercept: 70.0%; ustekinumab 45 mg: 66.0%; and ustekinumab 90 mg: 69.2%). Rates of serious AEs (SAEs) through the controlled periods were low and comparable among all groups (1.2% to 1.9%). Through 3 years, rates of AEs per 100 patient-years of follow-up (/100 patient-yrs) (45 mg: 305.2/100 patient-yrs; 90 mg: 305.9/100 patient-yrs) and SAEs (45 mg: 6.8/100 patient-yrs; 90 mg: 8.2/100 patient-yrs) were comparable between ustekinumab doses. No cases of demyelination or tuberculosis were reported in these trials. No dose response in rates of AEs, overall infections, or SAEs was apparent through 3 years. Rates of AEs, infections, SAEs, and AEs leading to study agent discontinuation remained generally stable or decreased over time.Limitations: Controlled periods did not extend beyond 12 to 20 weeks. Only 1247 of the 3117 ustekinumab-treated patients were treated for 2 or more years.Conclusions: The safety profile of continued ustekinumab exposure through up to 3 years is favorable and consistent with previous short-term reports. (J Am Acad Dermatol 2012;66:731-41.)