The following summarizes some of the highlights from Day 1 of the Americas Committee for Treatment and Research in MS (ACTRIMS) Forum 2025.

Ocrelizumab 11-year data
Neurological assessment using eye tracking
DMT discontinuation – the Toronto experience
Anti-CD20 treatment in patients aged ≥70 years
PIRA vs. relapse biology
Cytokines elevated in RIS and MS
Intranasal MS treatment in development

CONGRESS HIGHLIGHTS – FRIDAY EDITION

Ocrelizumab 11-year data
Sustained treatment with ocrelizumab is associated with low rates of confirmed disability worsening (CDW) and brain atrophy in previously untreated RMS patients at 11-year follow-up, according to the results from the OPERA I/II extension (Cerqueira et al. ACTRIMS 2025;P071). The study included 757 patients who were treatment-naïve at study entry; mean time from symptom onset to treatment initiation was three years. After a median time on treatment of 10.6 years, continuous ocrelizumab was associated with a low rate of 48-week CDW (17.6%), a low annualized relapse rate (mean 0.054) and a low whole-brain volume loss (mean -3.35% from baseline). The brain atrophy rate was comparable to that seen with normal aging.

Neurological assessment using eye tracking
A novel eye-tracking tool has been in development over the past few years as a non-invasive biomarker of physical and cognitive changes in MS (de Villers-Sidani et al. Front Neurol 2023;14:1243594). The Eye-Tracking Neurological Assessment technology (ETNA) uses an iPad camera to evaluate eye movements (for more information listen to the NeuroSound podcast at (https://neuro-sens.com/eye-tracking-as-a-biomarker-of-ms-severity-neurosound-podcast/). A new validation study has reported that about 85% of the EDSS estimates were within 0.5 EDSS points from the clinical assessment (Giacomini et al. ACTRIMS 2025;P057). The mean error for SDMT scores was 6.38, which was below the clinically significant change (8 points). The test-retest reliability was >95% for EDSS and SDMT. A Canadian trial of ofatumumab (ELIOS) plans to evaluate the usefulness of eye tracking in patients with active RRMS (Devonshire et al. ACTRIMS 2025;P059).

DMT discontinuation – the Toronto experience
An analysis of the MS clinic registry at St. Michael’s Hospital, Toronto, identified 253 patients who discontinued DMT treatment after age 55 years (mean age 61.3 years) (Tsai et al. ACTRIMS 2025;P395). The mean follow-up was 7.9 years after stopping treatment. Most patients (62%) were taking a platform injectable at the time of discontinuation. The most common reasons for stopping were onset of SPMS (23%), patient choice (16%) and tolerability concerns (14%). After discontinuation, 14% experienced a relapse and 31% had MRI disease activity. The rates of relapses and new/expanding lesions were lower in the DISCOMS study (4.7% and 12.2%, respectively) (Corboy et al. Lancet Neurol 2023;22:568-577). The authors concluded that DMT discontinuation may be a reasonable strategy for many older MS patients.

Anti-CD20 treatment in patients aged ≥70 years
A retrospective single-centre study looked at the safety of ocrelizumab in patients aged ≥70 years (Lee et al. ACTRIMS 2025;P157). Observation time was 2186 person-months while patients were in their seventies or eighties. Mean disease duration was 23.7 years. The mean duration of ocrelizumab exposure was 3.4 years; the median EDSS score was 6.0 at treatment start and was unchanged at the most recent observation. Overall, 58% of patients had a low serum IgG level at some point during therapy. The infection rate was 81.4 infections/1000 person-months. The most common infections were UTIs, COVID-19, and upper respiratory tract infections. Females had a higher odds of infection (odds ratio 13.49).

PIRA vs. relapse biology
A University of Calgary study investigated the frequency of progression independent of relapse activity (PIRA) in real-world and trial cohorts (Yong et al. ACTRIMS 2025;P396). The goal was to identify progression independent of relapse biology (PIRB), defined as disability accumulation in the absence of relapses, MRI inflammatory activity, fluctuations in EDSS, or onset of SPMS. Data were obtained from the Clinical Impact of MS (CIMS) observational study of ocrelizumab and fingolimod (N=541), and the phase III minocycline study in CIS (MinoCIS, n=142). In the CIMS study, the proportion with disability accumulation was 14.86% in the ocrelizumab group at three years, and 30.20% in the fingolimod group at five years. The rate of disability accumulation was 14.1% in MinoCIS. However, only a small proportion (<4%) of patients in the three treatment groups exhibited PIRB. The authors concluded that disability worsening is predominantly driven by inflammatory disease activity (relapses, MRI lesions) in RRMS, with few patients experiencing PIRB.

Cytokines elevated in RIS and MS
A study at the Barlo MS Centre, Toronto, analysed plasma obtained from individuals with radiologically isolated syndrome (RIS), RRMS and PPMS to identify potential biomarkers of CNS inflammation (Arsenault et al. ACTRIMS 2025;P047). All samples had significantly elevated concentrations vs. controls of hepatocyte growth factor (HGF), which acts on hematopoietic progenitor cells and T cells; interleukin-6 (IL-6), a pro-inflammatory cytokine; and chemokine ligand 23 (CCL23), a ligand for the chemokine receptor CCR1 found on peripheral blood lymphocytes and monocytes. HGF concentrations were significantly higher in RRMS vs. RIS. The authors concluded that the pathobiology of MS is already present in some individuals with RIS.

Intranasal MS treatment in development
Foralumab (OKT3) is monoclonal antibody targeting CD3 T cells that is currently being investigated in non-active SPMS and long COVID. In vitro studies showed induction of CD8+ T cells, reduced CD4+ T cell proliferation and reduced expression of interferon-gamma, IL-17 and TNF-alpha (Chitnis et al. Front Immunol 2022:13:956907). Preliminary data (n=6) were presented at ECTRIMS 2023 (Chitnis et al. ECTRIMS 2023;P281). The present study (n=10) examined the effect of foralumab on grey-matter lesions and leptomeningeal enhancement (LME) in na-SPMS patients (mean age 57 years) using 7T MRI (Zurawski et al. ACTRIMS 2025;V096). At nine months, GM lesion volume was stable compared to baseline; lesion number increased in four patients. LME foci number was stable in 40%, increased in 30%, and decreased in 30%. There was no reduction in whole-brain or deep GM volume with treatment.