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阿仑单抗诱导的甲状腺疾病:一项丹麦队列研究。

Alemtuzumab-induced thyroid disease: A Danish cohort study.

机构信息

Copenhagen University Hospital Amager and Hvidovre, Department of Endocrinology Amager, Copenhagen S, Denmark; Copenhagen University Hospital, Rigshospitalet, Department of Endocrinology and Metabolism, Copenhagen, Denmark.

Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Mult Scler Relat Disord. 2024 Nov;91:105880. doi: 10.1016/j.msard.2024.105880. Epub 2024 Sep 6.

Abstract

OBJECTIVES

Alemtuzumab, a monoclonal antibody against the cluster of differentiation 52 (CD52) molecule, is used in the treatment of multiple sclerosis (MS). A side effect of the treatment is development of secondary autoimmune thyroid disease. The aim of this study was to evaluate the rate, type and course of thyroid disease in Danish patients with multiple sclerosis (MS) treated with alemtuzumab.

METHODS

We conducted a retrospective cohort study of patients treated with a first series of alemtuzumab for MS in the Capital and Zealand regions of Denmark (population: 2.6 million) between 2014 and 2018 (n = 60 RESULTS: The duration of follow-up was median 81 months (range 54-105). Thyroid disease occurred in 47 % of the patients with the following distribution: Graves' disease (GD), thyrotropin (TSH) receptor antibody (TRAb) positive hyper- or hypothyroidism 35 %; multinodular goitre 5 %; silent thyroiditis, gestational transient thyrotoxicosis or unclassified hyperthyroidism 7 %. Of patients with GD, 14 % had an additional silent or postpartum thyroiditis before onset or after remission of GD. Unusual courses of GD occurred in 67 %, most commonly fluctuation from hypo- to hyperthyroidism or vice versa, mainly treated with antithyroid drug alone or thyroxine substitution regime but switched to concomitant block and replace treatment in 25 % and/or subsequent total thyroidectomy in less than 25 %.

CONCLUSION

Data from the largest Danish MS center supports previous observations of unusual, long-lasting and unpredictable courses of alemtuzumab-induced GD. Thus, follow-up of these patients may require long lasting and more frequent biochemical measurements compared to other patients with GD. Also, concomitant block and replace treatment or definitive treatment, such as thyroidectomy, should be considered in a subgroup of patients.

摘要

目的

抗 CD52 单克隆抗体阿仑单抗被用于多发性硬化症(MS)的治疗。其治疗的一个副作用是继发性自身免疫性甲状腺疾病的发生。本研究旨在评估丹麦接受阿仑单抗治疗的 MS 患者的甲状腺疾病的发生率、类型和病程。

方法

我们对在 2014 年至 2018 年期间,在丹麦首都大区和西兰大区接受首次阿仑单抗系列治疗的 MS 患者进行了一项回顾性队列研究(人口:260 万)(n=60)。

结果

中位随访时间为 81 个月(范围 54-105)。47%的患者发生了甲状腺疾病,其分布如下:Graves 病(GD)、促甲状腺激素(TSH)受体抗体(TRAb)阳性的甲状腺功能亢进或减退症 35%;多结节性甲状腺肿 5%;静默性甲状腺炎、妊娠期一过性甲状腺毒症或未分类的甲状腺功能亢进症 7%。GD 患者中,14%在 GD 发病前或缓解后发生了另外的静默性或产后甲状腺炎。GD 的罕见病程发生在 67%的患者中,最常见的是从甲状腺功能减退症转变为甲状腺功能亢进症或反之,主要采用抗甲状腺药物单独或甲状腺素替代治疗,但有 25%的患者转为同时进行阻断和替代治疗,以及/或随后有 25%以下的患者接受了全甲状腺切除术。

结论

来自丹麦最大的 MS 中心的数据支持了之前关于阿仑单抗诱导的 GD 不常见、持久和不可预测病程的观察结果。因此,与其他 GD 患者相比,这些患者的随访可能需要更持久和更频繁的生化测量。此外,对于一部分患者,应考虑同时进行阻断和替代治疗或确定性治疗,如甲状腺切除术。

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