Beyond relapse control: motor and cognitive subclinical progression in RRMS -a real-world longitudinal study of...

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system, with therapeutic goals focused on preventing disability progression and cognitive decline. This prospective, two-year study aimed to analyse the clinical and neuroradiological efficacy, disability progression, cognitive function, and safety profile in people with relapsing-remitting MS (RRMS) treated with ocrelizumab and IFN-beta 1a and 1b.

The study included 140 people with RRMS, evenly distributed into two treatment groups and followed over 24 months. Clinical parameters, test results and validated scales for assessing disease progression, cognitive function, as well as the safety profile were analyzed.

A higher percentage of people with RRMS treated with ocrelizumab achieved no evidence of disease activity (NEDA-3; 74.3% vs. 57.1%; p = 0.033) and no evidence of progression or active disease (NEPAD; 71.4% vs. 51.4%; p = 0.025), with both outcomes showing a significant association with ocrelizumab therapy in binary logistic regression (NEDA-3: OR = 3.566; 95% CI: 1.251-10.169; p = 0.017; NEPAD: OR = 3.675; 95% CI: 1.365-9.893; p = 0.010). Motor function was more stable in ocrelizumab-treated patients, with fewer clinically meaningful deteriorations in walking speed compared with interferon beta (IFN-ß). Although both groups showed a gradual decline in 25FWT and 9HPT, progression was slower and occurred later with ocrelizumab. Cognitive performance remained stable with ocrelizumab, whereas IFN-ß was associated with SDMT decline over time and a significant reduction in MoCA scores (p = 0.002). Progression independent of relapse activity (PIRA) was observed in 13.6%, progression independent of both relapse and MRI activity (PIRMA) in 10.4%, with no significant differences between treatment groups. Significant SDMT decline was noted in 16 patients (11.7%). Among them, 7 (43.8%) had concomitant acute disease activity, while 9 (56.2%) exhibited cognitive PIRMA, mostly independent of EDSS worsening.

The study results indicate the efficacy of ocrelizumab in achieving NEDA-3 and NEPAD, preserving cognitive and motor functions, with a favorable safety profile for both treatments. The results underscore the importance of longitudinal ambulatory and routine cognitive monitoring for detecting subclinical progression.