Psychosis as an adverse effect of monoclonal antibody immunotherapy.
Psychosis as an adverse effect of monoclonal antibody immunotherapy.
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DOI：
10.1016/j.bbi.2019.06.002
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发表时间：
2019-10
期刊：
影响因子：
--
通讯作者：
Miller BJ
中科院分区：
文献类型：
--
作者：
Essali N;Goldsmith DR;Carbone L;Miller BJ
免疫疗法是精神分裂症研究的“热门”领域。单克隆抗体（mAb）针对特定的免疫分子，因此提供了无与伦比的机会来直接检验免疫功能障碍在精神分裂症的精神病理学中起因果作用的假设。针对其他疾病的基于细胞因子的免疫疗法与一系列神经精神不良反应有关，包括精神病。本研究的目的是调查单克隆抗体自发报告的精神病症状药物不良反应的发生率，并计算与不直接针对免疫系统的贝伐珠单抗相比，单个单克隆抗体出现精神病的几率。我们检索了公开的 VigiBase，这是一个世界卫生组织全球个案安全报告数据库，从成立到 2019 年 2 月，其中一种单克隆抗体被怀疑为药物不良反应 (ADR)。我们研究了 43 种不同的 mAb，包括 1,298,185 份病例报告和 2025 份精神病 ADR。对于单个 mAb，精神病 ADR 的发生率范围为 0.1% 至 0.4%。七种单克隆抗体与精神病的发病率显着增加相关（OR = 1.42-2.22），其中包括两种针对 CD25 的药物。 8 种单克隆抗体与显着降低精神病发生率相关（OR = 0.28–0.75），其中包括 4 种抗 TNF-α 药物。我们的结果表明，精神病是单克隆抗体治疗的一种相对罕见的不良反应，但风险因特定药物而异。研究结果表明，调节免疫系统有时可能会导致精神病的发展。正在进行的精神分裂症辅助单克隆抗体免疫疗法的临床试验将为免疫系统在精神病中的作用提供有价值的见解。
Immunotherapy is a “hot” area in schizophrenia research. Monoclonal antibodies (mAbs) target specific immune molecules, and therefore offer an unparalleled opportunity to directly test the hypothesis that immune dysfunction plays a causal role in psychopathology in schizophrenia. Cytokine-based immunotherapy for other disorders has been associated with a range of neuropsychiatric adverse effects, including psychosis. The purpose of the present study was to investigate the prevalence of spontaneously-reported adverse drug reactions of psychotic symptoms for mAbs, and to calculate odds of psychosis for individual mAbs, compared to bevacizumab, which does not directly target the immune system. We searched the publicly available VigiBase, a World Health Organization global individual case safety report database from inception through February 2019 for which a mAb was the suspected agent of an adverse drug reaction (ADR). We investigated 43 different mAbs, comprising 1,298,185 case reports and 2025 psychosis ADRs. For individual mAbs, the prevalence of psychosis ADRs ranged from 0.1 to 0.4%. Seven mAbs were associated with a significantly increased odds of psychosis (OR = 1.42–2.22), including two agents that target CD25. Eight mAbs were associated with a significantly decreased odds of psychosis (OR = 0.28–0.75), including 4 anti-TNF-α agents. Our results suggest that psychosis is a relatively rare adverse effect of mAb treatment, but risks vary by specific agents. Findings indicate that modulating the immune system may sometimes lead to the development of psychosis. Ongoing clinical trials of adjunctive mAb immunotherapy in schizophrenia will provide valuable insights into the role of the immune system in psychosis.
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影响因子：
4.5
作者：
Goldsmith DR;Haroon E;Miller AH;Strauss GP;Buckley PF;Miller BJ
通讯作者：
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Hosoda, S;Takimura, H;Kumada, H
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