Klinik für Neurologie, Philipps-Universität und Universitätsklinikum Marburg, Baldingerstr. 1, Marburg 35043, Germany.
Klinik für Neurologie, Philipps-Universität und Universitätsklinikum Marburg, Baldingerstr. 1, Marburg 35043, Germany.
EBioMedicine. 2018 Feb;28:143-150. doi: 10.1016/j.ebiom.2018.01.007. Epub 2018 Jan 10.
It is a continuous matter of discussion whether immune activation by vaccination in general and Influenza vaccination in particular increases the risk for clinical deterioration of autoimmune diseases. This prospective study investigated the serological and clinical course of autoimmune Myasthenia gravis (MG) after a seasonal influenza vaccination.
This randomized, placebo-controlled, double-blind study enrolled MG patients with antibodies against acetylcholine-receptors (AChR-ab). They were allocated to receive seasonal influenza vaccine or placebo. The primary endpoint was the relative change of AChR-ab-titer over 12weeks. A relative increase of 20% was set as non-inferiority margin. Secondary endpoints were clinical changes in the modified Quantitative Myasthenia Gravis Score (QMG), increase of anti-influenza-ELISA-antibodies, and changes of treatment. The study is registered with Clinicaltrialsregister.eu, EudraCT number 2006-004374-27.
62 patients were included. Mean±standard deviation (median) in the vaccine and placebo group were AChR-ab-titer changes of -6.0%±23.3% (-4.0%) and -2.8%±22.0% (-0.5%) and QMG score changes of -0.08±0.27 (0.17) and 0.11±0.31 (0.00), respectively. The difference between groups (Hodges-Lehmann estimate with 95% CI) was - for the AChR-ab-titer change 4·0% [-13.3%, 4.5%] (p=0.28 for testing a difference, p<0.0001 for testing non-inferiority) and for the QMG change 0·00 [-0.17, 0.00] (p=0.79 for testing a difference). The occurrence of 74 adverse events (AE) was comparable between groups. The most common AE was flu-like symptoms. One serious AE (hospitalisation following gastrointestinal haemorrhage) in the verum group was not related to the vaccine.
Influenza vaccination in MG is safe. Uprating the potential risk of a severe course of MG exacerbation during influenza infection compared to the 95% CI differences for the endpoints, vaccination is principally indicated in this patient population.
疫苗接种引起的免疫激活是否会增加自身免疫性疾病临床恶化的风险，这一直是一个持续讨论的话题。本前瞻性研究调查了季节性流感疫苗接种后自身免疫性重症肌无力（MG）的血清学和临床过程。
这项随机、安慰剂对照、双盲研究纳入了抗乙酰胆碱受体（AChR-ab）抗体阳性的 MG 患者。他们被分配接受季节性流感疫苗或安慰剂。主要终点是 12 周时 AChR-ab 滴度的相对变化。设定相对增加 20%作为非劣效性边界。次要终点是改良定量重症肌无力评分（QMG）的临床变化、抗流感 ELISA 抗体的增加以及治疗的变化。该研究在 Clinicaltrialsregister.eu 上注册，EudraCT 编号为 2006-004374-27。
62 例患者入组。疫苗组和安慰剂组的平均±标准偏差（中位数）AChR-ab 滴度变化分别为-6.0%±23.3%（-4.0%）和-2.8%±22.0%（-0.5%），QMG 评分变化分别为-0.08±0.27（0.17）和 0.11±0.31（0.00）。两组间的差异（95%CI 的 Hodges-Lehmann 估计值）分别为 AChR-ab 滴度变化 4·0%[-13.3%，4.5%]（p=0.28 用于检验差异，p<0.0001 用于检验非劣效性）和 QMG 变化 0·00[-0.17，0.00]（p=0.79 用于检验差异）。两组间不良事件（AE）的发生情况相似。最常见的 AE 是流感样症状。vero 组发生的 1 例严重 AE（胃肠道出血后住院）与疫苗无关。
MG 患者接种流感疫苗是安全的。与终点的 95%CI 差异相比，MG 感染期间严重发作的潜在风险增加，疫苗接种在该患者人群中主要是适应证。
