Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials
Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials
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DOI：
10.1016/j.jaad.2017.08.024
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发表时间：
2018-01-01
影响因子：
13.8
通讯作者：
Israel, Robert J.
中科院分区：
文献类型：
--
作者：
Lebwohl, Mark G.;Papp, Kim A.;Israel, Robert J.
背景资料：银屑病患者的精神共病风险增加，包括自杀意念和行为（SIB）。目的：在接受brodalumab（一种全人抗白细胞介素17受体A单克隆抗体）治疗的银屑病患者中，区分潜在风险和治疗诱导的精神不良事件的可能性。2期临床试验的开放标签、长期扩展;和3个3期、随机、双盲、对照临床试验（AMAGINE-1、AMAGINE-2和AMAGINE-3）及其对中重度银屑病患者的开放标签、长期扩展。在整个52周对照阶段，brodalumab组和乌司奴单抗组之间的随访时间校正SIB事件发生率相当（0.20 vs 0.60/100患者-年）。在brodalumab组中，报告了4例自杀完成，其中1例后来被裁定为不确定;所有患者都有潜在的精神疾病或应激源。对照研究期间没有权力检测罕见事件的差异，如suicid.Conclusions：与对照组和事件的时间比较并不表明SIB和brodalumab治疗之间的因果关系。
Background: Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB).Objective: To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti-interleukin 17 receptor A monoclonal antibody.Methods: Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis.Results: The analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time-adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors.Limitations: There was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide.Conclusions: Comparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment.