To assess risk of disease activity in PwMS receiving ICI (PwMS+ICI) compared with PwMS who did not receive ICI treatment. 

MS disease activity in patients with multiple sclerosis (PwMS) receiving immune checkpoint inhibitor therapy (ICI) has been reported. However, this risk is not fully understood. 

In this retrospective cohort study, adult PwMS who received ICI between 2017-2023 were identified. PwMS+ICI were matched (1:3) with controls (PwMS not treated with ICI) based on age, sex, disease duration, DMT and MS type. Time to clinical relapse and MRI relapse were compared using Kaplan-Meier curves and Cox regression models.

Among 9158 PwMS, 108 patients were identified (27 PwMS+ICI and 81 matched PwMS controls). In both groups, mean age was 59 +/- 11 years and 67% were female. MS phenotypes included; relapsing remitting or clinically isolated syndrome (74%), missing phenotype (15%) and primary or secondary progressive (11%). Among both groups, proportion of DMTs were high (30%) and low efficacy (11%). ICIs included; pembrolizumab (15, [55%]), nivolumab (10, [37%]) and durvalumab (2, [7%]). Of PwMS+ICI, 18 had MRI follow-up after ICI with a median follow up of 1 year (IQR=0.22-1.8). Five patients experienced new disease activity; 1 (4%) had clinical relapse with new MRI lesions (no DMT, fingolimod paused) and 4 (15%) developed new MRI lesions without clinical symptoms (no DMT, fingolimod paused [1], ocrelizumab [1], dimethyl fumarate [1], natalizumab [1]). Compared to PwMS controls, there was no significant difference for either time to MRI activity (hazard ratio (HR): 2.55, 95% CI [0.72, 9.06], p=0.15) and time to clinical relapse (HR: 3.00, 95% CI [0.31, 28.84], p=0.34). 

No statistical significance in either clinical or radiological relapse between PwMS+ICI and PwMS controls was seen, suggesting that ICI does not infer a greater risk of disease activity. However, further studies with a larger sample size needed.