Gelibter Stefano, Saraceno Lorenzo, Susani Emanuela, Pirro Fiammetta, Sessa Maria, Protti Alessandra
Department of Neurosciences, Neurology and Stroke Unit, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Eur J Neurol. 2025 Jan;32(1):e16547. doi: 10.1111/ene.16547. Epub 2024 Nov 18.
Elderly people with multiple sclerosis (pwMS) present higher probability of malignancies. Immune checkpoint inhibitors (ICIs) improve cancer prognosis but pose risk of disease flares in people with pre-existing autoimmune conditions, including MS. Data addressing the impact of ICIs on MS are scarce. This systematic review and meta-analysis evaluates the effects of ICIs on MS disease activity.
A systematic literature search in Google Scholar and PubMed, following PRISMA 2020 guidelines, identified five observational studies. Data on clinical and neuroradiological outcomes were analyzed using random-effects models.
The clinical activity meta-analysis included 90 pwMS undergoing ICI therapy (median follow-up = 0.62-1.85 years, 103.74 patient-years). The pooled relapse rate was 5.45 per 100 patient-years (95% confidence interval [CI] = 1.86-14.92). Median time to relapse was 1 month after the ICI start (range = 0.4-6 months). No relapse occurred after 58 years. The neuroradiological activity meta-analysis was conducted on 36 pwMS (median magnetic resonance imaging [MRI] follow-up = 0.75-1.85 years, 41.94 patient-years). The pooled new MRI lesion rate was 24.9 per 100 patient-years (95% CI = 10.9-47.3), with median time to new MRI lesions of 3 months (range = 1-6 months). In 80% of cases, disease-modifying treatment (DMT) was suspended at ICI initiation.
We found a low relapse rate in pwMS following ICI treatment, with no events in older pwMS. The risk of neuroradiological activity appears higher, but mainly occurs in pwMS who discontinued DMT. All events occurred within the first 6 months of ICI therapy. These conclusions are based on small observational studies, highlighting the urgent need for further research on this topic.
老年多发性硬化症患者（pwMS）患恶性肿瘤的概率更高。免疫检查点抑制剂（ICI）可改善癌症预后，但在包括MS在内的已有自身免疫性疾病患者中会引发疾病复发风险。关于ICI对MS影响的数据很少。本系统评价和荟萃分析评估了ICI对MS疾病活动的影响。
按照PRISMA 2020指南在谷歌学术和PubMed中进行系统文献检索，确定了五项观察性研究。使用随机效应模型分析临床和神经放射学结果的数据。
临床活动荟萃分析纳入了90例接受ICI治疗的pwMS（中位随访时间=0.62 - 1.85年，103.74患者年）。汇总复发率为每100患者年5.45次（95%置信区间[CI]=1.86 - 14.92）。复发的中位时间为ICI开始后1个月（范围=0.4 - 6个月）。58年后未发生复发。对36例pwMS进行了神经放射学活动荟萃分析（中位磁共振成像[MRI]随访时间=0.75 - 1.85年，41.94患者年）。汇总的新MRI病灶率为每100患者年24.9个（95% CI = 10.9 - 47.3），出现新MRI病灶的中位时间为3个月（范围=1 - 6个月）。在80%的病例中，在ICI开始时停用了疾病修饰治疗（DMT）。
我们发现ICI治疗后pwMS的复发率较低，老年pwMS未出现复发事件。神经放射学活动风险似乎更高，但主要发生在停用DMT的pwMS中。所有事件均发生在ICI治疗的前6个月内。这些结论基于小型观察性研究，突出了对该主题进行进一步研究的迫切需求。
