Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
Institute of Neuroradiology, University Medical Center Göttingen, Göttingen, Germany.
Mult Scler. 2019 Oct;25(12):1618-1632. doi: 10.1177/1352458518819098. Epub 2019 Jan 18.
Daclizumab is a monoclonal antibody that binds the high-affinity interleukin-2 receptor and was approved for the treatment of relapsing multiple sclerosis. Due to severe inflammatory brain disorders, the approval was suspended in March 2018.
This retrospective cohort study summarizes clinical, laboratory, radiological, and histological findings of seven patients who developed meningo-/encephalitis after daclizumab therapy.
Patients presented with encephalitis and/or meningitis and suffered from systemic symptoms such as fever (5/7), exanthema (5/7), or gastrointestinal symptoms (4/7). Secondary autoimmune diseases developed. Blood analysis revealed an increase in eosinophils (5/7). Six patients fulfilled the diagnostic criteria for a drug reaction with eosinophilia and systemic symptoms (DRESS). Magnetic resonance imaging (MRI) showed multiple contrast-enhancing lesions, and enhancement of the ependyma (6/7), meninges (5/7), cranial or spinal nerves (2/7), and a vasculitic pattern (3/7). Histology revealed a pronounced inflammatory infiltrate consisting of lymphocytes, plasma cells and eosinophils, and densely infiltrated vessels. Most patients showed an insufficient therapeutic response and a high disability at last follow-up (median Expanded Disability Status Scale (EDSS) 8). Two patients died.
Meningoencephalitis and DRESS may occur with daclizumab therapy. This potential lethal side effect is characterized by a dysregulated immune response. Our findings underline the importance of postmarketing drug surveillance.
达利珠单抗是一种单克隆抗体，可与高亲和力白细胞介素-2 受体结合，已被批准用于治疗复发性多发性硬化症。由于严重的炎症性脑部疾病，该批准于 2018 年 3 月暂停。
本回顾性队列研究总结了 7 名接受达利珠单抗治疗后发生脑膜/脑炎的患者的临床、实验室、影像学和组织学发现。
患者表现为脑炎和/或脑膜炎，并伴有全身症状，如发热（5/7）、皮疹（5/7）或胃肠道症状（4/7）。继发自身免疫性疾病。血液分析显示嗜酸性粒细胞增多（5/7）。6 名患者符合药物反应伴嗜酸性粒细胞增多和全身症状（DRESS）的诊断标准。磁共振成像（MRI）显示多个对比增强病变，室管膜（6/7）、脑膜（5/7）、颅神经或脊神经（2/7）和血管炎样模式（3/7）增强。组织学显示明显的炎症浸润，由淋巴细胞、浆细胞和嗜酸性粒细胞组成，并且密集浸润的血管。大多数患者在最后一次随访时治疗反应不足且残疾程度较高（扩展残疾状态量表（EDSS）中位数为 8）。两名患者死亡。
脑膜脑炎和 DRESS 可能发生在达利珠单抗治疗中。这种潜在的致命副作用的特征是免疫反应失调。我们的发现强调了上市后药物监测的重要性。
