From the Department of Neurology (J. Oh, S.S., P.A.C., S.D.N.), Johns Hopkins University, Baltimore; and Neuroimmunology Branch (I.C., J. Ohayon, B.B.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
Neurology. 2014 Mar 18;82(11):984-8. doi: 10.1212/WNL.0000000000000222. Epub 2014 Feb 14.
To report 3 patients with multiple sclerosis (MS) who presented with daclizumab-related adverse events (AEs) in multiple organ systems.
A retrospective chart review was performed of patients with MS who had clinical and histopathologic findings suggestive of daclizumab-induced AEs between 2004 and 2010 at the Johns Hopkins MS Clinic. This study met criteria for exemption from review from the institutional review board.
Of 20 total patients with MS who had been treated with daclizumab, 3 patients with clinical and histopathologic findings suggestive of daclizumab-induced AEs were identified. All patients were treated with Zenapax (1 mg/kg monthly IV infusions) outside of a clinical trial setting. Clinical manifestations after a mean treatment duration of 20 months consisted of diffuse rash and alopecia, diffuse lymphadenopathy, and breast nodules. Tissue histopathology demonstrated lymphocytic infiltrates with CD56-expressing cells in 2 patients (lymph node, breast nodule). On daclizumab discontinuation, the rash/alopecia and diffuse lymphadenopathy resolved, while the breast nodules stabilized.
Daclizumab-induced AEs can occur in various organ systems after a relatively prolonged duration of exposure and require clinician awareness. Future studies are needed to better understand the relationship between natural killer cells and daclizumab-related AEs.
报告 3 例多发性硬化症（MS）患者，他们出现了与达珠单抗相关的多器官系统不良事件（AE）。
对 2004 年至 2010 年期间在约翰霍普金斯 MS 诊所就诊的多发性硬化症患者进行了回顾性图表审查，这些患者具有临床和组织病理学发现，提示与达珠单抗诱导的 AE 有关。该研究符合机构审查委员会免除审查的标准。
在接受达珠单抗治疗的 20 例多发性硬化症患者中，有 3 例患者具有临床和组织病理学发现，提示与达珠单抗诱导的 AE 有关。所有患者均在临床试验之外接受 Zenapax（1mg/kg 每月静脉输注）治疗。在平均治疗 20 个月后，出现弥漫性皮疹和脱发、弥漫性淋巴结病和乳房结节等临床表现。2 例患者（淋巴结、乳房结节）的组织病理学表现为淋巴细胞浸润和表达 CD56 的细胞。停用达珠单抗后，皮疹/脱发和弥漫性淋巴结病得到缓解，而乳房结节稳定。
达珠单抗诱导的 AE 在暴露时间相对较长后可能发生在多个器官系统中，需要临床医生注意。需要进一步研究以更好地了解自然杀伤细胞与达珠单抗相关 AE 之间的关系。
