Zavarella Matteo, Cecchetti Giordano, Rugarli Giulia, Ghirelli Alma, Bottale Ilaria, Orlandi Francesca, Spinelli Edoardo G, Santangelo Roberto, Caso Francesca, Calloni Sonia Francesca, Vezzulli Paolo Quintiliano, Falini Andrea, Magnani Giuseppe, Agosta Federica, Filippi Massimo
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
J Neurol. 2025 Jan 24;272(2):168. doi: 10.1007/s00415-025-12910-x.
The large-scale approval of anti-amyloid monoclonal antibodies for treating Alzheimer's disease (AD) has raised concerns about their safety due to treatment-emergent amyloid-related imaging abnormalities (ARIA).
We present two cases of patients diagnosed with mild cognitive impairment due to AD who were enrolled in the GRADUATE I clinical trial. They received subcutaneous gantenerumab every two weeks during the study period.
Both patients experienced recurrent ARIA-Effusion/Edema type (ARIA-E). One developed symptomatic and severe ARIA, leading to hospitalization and study withdrawal. We report a long follow-up post-randomization (65 and 54 months), during which the adverse events did not appear to have a negative impact on disease progression. Additionally, one patient had a negative amyloid-PET over a year after treatment cessation.
These cases suggest that recurrent ARIA-E do not inevitably lead to accelerated progression, instead, may relate to possible long-term benefits. The mechanisms underlying these findings warrant further real-life evidence.
用于治疗阿尔茨海默病（AD）的抗淀粉样蛋白单克隆抗体的大规模获批引发了人们对其安全性的担忧，因为治疗过程中会出现与淀粉样蛋白相关的影像学异常（ARIA）。
我们介绍了两例因AD诊断为轻度认知障碍的患者，他们参加了GRADUATE I临床试验。在研究期间，他们每两周接受一次皮下注射甘特奈单抗。
两名患者均出现复发性ARIA-积液/水肿型（ARIA-E）。其中一名患者出现有症状的严重ARIA，导致住院并退出研究。我们报告了随机分组后的长期随访（65和54个月），在此期间，不良事件似乎未对疾病进展产生负面影响。此外，一名患者在停药一年多后淀粉样蛋白PET检查结果为阴性。
这些病例表明，复发性ARIA-E并不一定会导致疾病加速进展，相反，可能与潜在的长期益处有关。这些发现背后的机制需要更多实际证据。
