Data Sheet 1_Safety profile and efficacy of secukinumab in the treatment of autoimmune myasthenia gravis: a single-center retrospective study.pdf

BackgroundMyasthenia gravis (MG) is a chronic autoimmune disease caused by autoantibodies attacking the neuromuscular junction. Traditional treatments are often accompanied by side effects and lack specificity. Recent studies have found that Th17 cells and the inflammatory factor IL-17, which they secrete, play a key role in the pathogenesis of MG and have become potential therapeutic targets. Secukinumab, an IL-17 inhibitor, has shown efficacy in other autoimmune diseases, but its role in MG remains unexplored.
ObjectiveThis study aimed to evaluate the clinical efficacy and immunomodulatory effects of secukinumab in acetylcholine receptor antibody-positive generalized MG (AChR+ gMG).
MethodsIn this single-center retrospective study, 29 AChR+ gMG patients received subcutaneous secukinumab (150 mg weekly for 4 weeks, then monthly for 24 weeks). Clinical outcomes (QMG, MG-QOL15, MG-ADL scores), AChR antibody titers, Th17 cell frequency, and IL-17 levels were assessed at baseline and during treatment. Correlations between biomarkers and clinical improvements were analyzed.
ResultsBy week 24, secukinumab treatment led to significant reductions in disease severity scores (QMG: 60.7%; MG-QOL15: 58.3%; MG-ADL: 64.1%) and AChR antibody levels (69.23%). Th17 cell frequency and IL-17 levels decreased by 68 and 84.47%, respectively. Strong baseline correlations were observed between IL-17, Th17, and clinical scores (r = 0.642–0.970, p < 0.001), with progressive uncoupling of these relationships during treatment. No severe adverse events were reported.
ConclusionSecukinumab demonstrated rapid and sustained clinical benefits in AChR+ gMG, linked to suppression of the Th17/IL-17 pathway. These findings highlight IL-17 inhibition as a promising targeted strategy for MG. Limitations include small sample size and retrospective design, warranting validation in larger randomized trials.

背景：重症肌无力（Myasthenia Gravis, MG）是一种由自身抗体攻击神经肌肉接头所引发的慢性自身免疫性疾病。传统治疗手段常伴随不良反应且缺乏特异性。近期研究证实，Th17细胞及其分泌的炎症因子白细胞介素-17（IL-17）在重症肌无力的发病机制中发挥关键作用，已成为潜在的治疗靶点。司库奇尤单抗（Secukinumab）作为IL-17抑制剂，已在其他自身免疫性疾病中展现出临床疗效，但其在重症肌无力中的作用尚未得到探索。
研究目标：本研究旨在评估司库奇尤单抗针对乙酰胆碱受体抗体阳性全身性重症肌无力（acetylcholine receptor antibody-positive generalized MG, AChR+ gMG）的临床疗效与免疫调节作用。
研究方法：本项单中心回顾性研究共纳入29例AChR+ gMG患者，予以皮下注射司库奇尤单抗（初始剂量为每周150mg，持续4周，后续改为每月150mg，维持治疗24周）。在基线状态与治疗期间，分别对临床结局指标（重症肌无力定量评分（Quantitative Myasthenia Gravis Score, QMG）、重症肌无力生活质量量表15项版（Myasthenia Gravis Quality of Life 15-item scale, MG-QOL15）、重症肌无力日常生活活动量表（Myasthenia Gravis Activities of Daily Living Scale, MG-ADL））、乙酰胆碱受体抗体滴度、Th17细胞频率及IL-17水平进行检测与评估，并分析生物标志物与临床改善之间的相关性。
研究结果：至第24周时，司库奇尤单抗治疗可显著降低疾病严重程度相关评分：QMG评分下降60.7%、MG-QOL15评分下降58.3%、MG-ADL评分下降64.1%，同时乙酰胆碱受体抗体水平下降69.23%。Th17细胞频率与IL-17水平分别下降68%与84.47%。基线状态下，IL-17、Th17与临床评分之间存在显著强相关性（相关系数r=0.642~0.970，p<0.001），且在治疗过程中这些关联逐渐减弱。本研究未报告严重不良事件。
研究结论：司库奇尤单抗在AChR+ gMG患者中展现出快速且持久的临床获益，该效应与Th17/IL-17通路的抑制密切相关。本研究结果提示IL-17抑制有望成为重症肌无力的极具前景的靶向治疗策略。本研究存在样本量较小、回顾性研究设计等局限性，需在更大规模的随机对照试验中进一步验证。