Rommer Paulus S, Berger Klaus, Ellenberger David, Fneish Firas, Simbrich Alexandra, Stahmann Alexander, Zettl Uwe K
Neuroimmunological Section, Department of Neurology, University of Rostock, Rostock, Germany.
Department of Neurology, Medical University of Vienna, Vienna, Austria.
Front Neurol. 2020 Sep 8;11:996. doi: 10.3389/fneur.2020.00996. eCollection 2020.
Daclizumab was approved by the FDA and the EMA in 2016 for the treatment of relapsing forms of multiple sclerosis (MS). Cases of severe inflammatory brain disease with fatal outcome led to the withdrawal of approval in Europe and the US on March 2, 2018. Approximately 8,000 patients worldwide received daclizumab, but little is known about the further therapy management of these patients after the withdrawal of daclizumab. The aim of this study is to further analyze therapy management in MS patients after safety warnings and market withdrawal. Data from two registries in Germany, the German MS Registry (GMSR) and REGIMS, were used for this analysis. In total, 267 patients were included in this study. For almost 25% of patients (in the GMSR) daclizumab was the initial treatment. Most common pre-treatments were fingolimod, dimethyl fumarate, and natalizumab; various injectables summed up to 25.9%. The most common follow-up therapies were ocrelizumab and fingolimod. In most patients, follow-up therapies were administered shortly after discontinuation of daclizumab. The wash-out time for subsequent therapies varied between 1.2 and 4.0 months. Warnings and decisions by authorities led to a rapid decline and termination of therapies in both cohorts, indicating that such warnings have an immediate impact on the treatment landscape. Therapies that were started within a short time after the discontinuation of daclizumab were subsequently replaced by other therapies and may be considered as bridging therapies.
达克珠单抗于2016年获美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准，用于治疗复发型多发性硬化症（MS）。2018年3月2日，因出现导致致命后果的严重炎症性脑病病例，欧洲和美国撤销了该药物的批准。全球约8000名患者接受过达克珠单抗治疗，但在达克珠单抗撤市后，这些患者的后续治疗管理情况鲜为人知。本研究的目的是在发出安全警告和撤市后，进一步分析MS患者的治疗管理情况。本分析使用了德国两个登记处的数据，即德国MS登记处（GMSR）和REGIMS。本研究共纳入267例患者。在近25%的患者中（在GMSR中），达克珠单抗是初始治疗药物。最常见的预处理药物是芬戈莫德、富马酸二甲酯和那他珠单抗；各种注射剂总计占25.9%。最常见的后续治疗药物是奥瑞珠单抗和芬戈莫德。在大多数患者中，达克珠单抗停用后不久即开始后续治疗。后续治疗的洗脱期在1.2至4.0个月之间。当局发出的警告和做出的决定导致两个队列中的治疗迅速减少并终止，这表明此类警告对治疗格局有直接影响。在达克珠单抗停用后短时间内开始的治疗随后被其他治疗所取代，可被视为过渡治疗。
