Do immune checkpoint inhibitors affect the course of multiple sclerosis? A systematic review and meta-analysis

Abstract

Background and purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: MRI lesion; disease activity; immune checkpoint inhibitors; multiple sclerosis; relapse.

FIGURE 1

Forest plots of the relapse rate (a) and the new magnetic resonance imaging lesion rate (b). The relapse rate is represented as the event rate per patient‐year. The 95% confidence interval (CI) is provided in parentheses for each study and for the pooled effect size. In the graphs, the squares represent the event rate of individual studies, with sizes proportional to the sample sizes and horizontal bars representing the 95% CI. The pooled effect size is represented by the red diamond, with the width representing the 95% CI. The dashed vertical line indicates the pooled effect size on the x‐axis. RE, random effect.