Clinic of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.
Clinic of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.
EBioMedicine. 2019 Aug;46:381-386. doi: 10.1016/j.ebiom.2019.07.062. Epub 2019 Jul 29.
Alemtuzumab is approved for the treatment of active relapsing-remitting multiple sclerosis (RRMS). Alemtuzumab-related secondary autoimmune disorders (sAID) are common, with thyroid sAID being the most frequent, and fundamentally affect the risk-benefit ratio. Therefore, biomarkers indicating the development of sAID are urgently needed to instruct clinical decisions.
We evaluated whether the anti-thyroid autoantibodies (ThyAb) anti-thyroglobulin (anti-TG) and anti-thyroid-peroxidase (anti-TPO) detected at baseline by standard testing are able to indicate increased risk for thyroid sAID following alemtuzumab treatment in a multicentre prospective cohort of 106 alemtuzumab-treated RRMS patients. We here present an interim-analysis with a median follow-up of 36 months.
Baseline characteristics demonstrated no significant differences between patients with or without thyroid sAID. 29/106 (27·4%) patients developed thyroid sAID between 5 and 51 months following alemtuzumab treatment initiation. 14/29 patients (48·3%) were positive for ThyAb at baseline and developed thyroid sAID. Hazard ratio for time to thyroid autoimmunity was 12.15 (95% CI 4.73-31.2) indicating a highly increased risk for ThyAb positive patients. Baseline ThyAb were associated with shorter time to sAID, but not with a specific disease entity of thyroid sAID. Hazard ratios for age, sex, previous treatment, disease duration, disability and smoking status demonstrated no significant association with thyroid autoimmunity.
Standard ThyAb-testing for anti-TPO and anti-TG antibodies at baseline was able to indicate increased risk for clinically manifest thyroid sAID and should therefore be used in clinical decisions concerning alemtuzumab treatment initiation. FUND: German Ministry of Education, Science, Research and Technology and the German Research foundation.
阿仑单抗获批用于治疗活跃的复发缓解型多发性硬化症（RRMS）。阿仑单抗相关的继发性自身免疫性疾病（sAID）较为常见，其中甲状腺 sAID 最为常见，且从根本上影响风险效益比。因此，急需能够指示 sAID 发展的生物标志物来指导临床决策。
我们评估了在一项包含 106 名接受阿仑单抗治疗的 RRMS 患者的多中心前瞻性队列研究中，基线时通过标准检测检测到的抗甲状腺自身抗体（ThyAb）抗甲状腺球蛋白（anti-TG）和抗甲状腺过氧化物酶（anti-TPO）是否能够指示阿仑单抗治疗后发生甲状腺 sAID 的风险增加。我们在此呈现了一项中位随访时间为 36 个月的中期分析。
基线特征显示，发生或未发生甲状腺 sAID 的患者之间无显著差异。在阿仑单抗治疗开始后 5 至 51 个月期间，29/106（27.4%）名患者发生了甲状腺 sAID。在 14/29（48.3%）名患者中，基线 ThyAb 阳性且发生了甲状腺 sAID。发生甲状腺自身免疫的时间风险比为 12.15（95%CI 4.73-31.2），表明 ThyAb 阳性患者的风险显著增加。基线 ThyAb 与发生 sAID 的时间较短相关，但与甲状腺 sAID 的特定疾病实体无关。年龄、性别、既往治疗、疾病持续时间、残疾和吸烟状况的风险比与甲状腺自身免疫无显著相关性。
基线时对 anti-TPO 和 anti-TG 抗体进行标准 ThyAb 检测，能够指示发生临床明显甲状腺 sAID 的风险增加，因此应在考虑启动阿仑单抗治疗的临床决策中使用。
德国联邦教育、科学、研究和技术部以及德国研究基金会。
