From the Department of Clinical Neuroscience (P.A., F.P.) and Clinical Epidemiology Division (P.A., T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm; Department of Neuroscience (J.B.), Uppsala University; Department of Clinical Neuroscience (J.L.), Institute of Neuroscience and Physiology, University of Gothenburg; and Academic Specialist Centre (F.P.), Stockholm Health Services, Sweden.
Neurology. 2021 Mar 16;96(11):e1574-e1584. doi: 10.1212/WNL.0000000000011545. Epub 2021 Jan 29.
To assess safety outcomes for the induction therapies alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT) compared to noninduction disease-modifying therapies.
We performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national health care registers. Alemtuzumab, AHSCT, and a matched reference group of noninduction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. Main outcomes were death, thyroid disease, nonthyroid autoimmune disease, and infection.
We identified 132 alemtuzumab-treated and 139 AHSCT-treated (68% high-dose cyclophosphamide and anti-thymocyte globulin [ATG], 32% BCNU, etoposide, cytosine-arabinoside, and melphalan/ATG) patients, together with 2,486 matched patients treated with noninduction therapies. Four patients in the alemtuzumab group died (incidence rate [IR] per 1,000 person-years 8.6, 95% confidence interval [CI] 2.3-22.0) compared to 1 patient in the AHSCT group (IR 1.7, 95% CI 0.0-9.6), and the mortality rate in the reference group was 0.7 (95% CI 0.3-1.3). Thyroid disease was most frequent in the alemtuzumab group (IR 109, 95% CI 75-154) but also occurred more often for AHSCT (IR 34, 95% CI 18-56) compared to the reference (IR 5.3 95% CI 3.9-7.1). The incidence of nonthyroid autoimmune disease was similar in all groups. IR for infection diagnosed ≥6 months from therapy initiation was 53 (95% CI 30-87) for alemtuzumab, 108 (95% CI 75-150) for AHSCT, and 51 (95% CI 46-57) for the reference.
We confirmed a high incidence of thyroid disease in alemtuzumab- and, to a smaller extent, AHSCT-treated patients and found a higher incidence of infection for AHSCT compared to both alemtuzumab and noninduction therapies. The incidence of nonthyroid autoimmune disease was low for both therapies.
This study provides Class III evidence of an increased risk of thyroid disease with alemtuzumab and an increased risk of infection with AHSCT treatment.
评估与非诱导疾病修正疗法相比，阿仑单抗和自体造血干细胞移植（AHSCT）的诱导疗法的安全性结局。
我们进行了一项基于人群的队列研究，将瑞典多发性硬化症登记处与国家卫生保健登记处联系起来。如果在 2008 年至 2017 年期间开始使用阿仑单抗、AHSCT 和非诱导疗法（那他珠单抗、二甲基富马酸、利妥昔单抗、芬戈莫德），则将其纳入研究。主要结局为死亡、甲状腺疾病、非甲状腺自身免疫性疾病和感染。
我们确定了 132 例接受阿仑单抗治疗和 139 例接受 AHSCT 治疗（68%为高剂量环磷酰胺和抗胸腺细胞球蛋白[ATG]，32%为卡氮芥、依托泊苷、胞嘧啶阿拉伯糖苷和马法兰/ATG）的患者，以及 2486 例接受非诱导疗法治疗的匹配患者。阿仑单抗组有 4 例患者死亡（每 1000 人年发病率[IR]为 8.6，95%置信区间[CI]为 2.3-22.0），而 AHSCT 组有 1 例患者死亡（IR 为 1.7，95%CI 为 0.0-9.6），参考组的死亡率为 0.7（95%CI 为 0.3-1.3）。甲状腺疾病在阿仑单抗组最为常见（IR 为 109，95%CI 为 75-154），但在 AHSCT 组（IR 为 34，95%CI 为 18-56）也更为常见，而参考组（IR 为 5.3，95%CI 为 3.9-7.1）则较少见。所有组的非甲状腺自身免疫性疾病发生率相似。从治疗开始≥6 个月后诊断出的感染发生率为阿仑单抗组 53（95%CI 为 30-87）、AHSCT 组 108（95%CI 为 75-150）和参考组 51（95%CI 为 46-57）。
我们证实了阿仑单抗治疗后甲状腺疾病的发生率较高，且在较小程度上 AHSCT 治疗后甲状腺疾病的发生率较高，与阿仑单抗和非诱导疗法相比，AHSCT 治疗后感染的发生率更高。两种疗法的非甲状腺自身免疫性疾病发生率较低。
这项研究提供了 III 级证据，表明阿仑单抗治疗会增加甲状腺疾病的风险，AHSCT 治疗会增加感染的风险。
