The following summarizes some of the highlights from the Americas Committee for Treatment and Research in MS (ACTRIMS) Forum, held February 5-7, 2026 in San Diego, California.
Tolebrutinib in PPMS: PERSEUS results
Ofatumumab in patients with low disease activity
ORATORIO-HAND study of ocrelizumab in PPMS
GLP-1R agonist use in MS
Integrating fluid and digital biomarkers
Delayed physician visits for MOGAD patients in rural Ontario
Obexelimab phase II results in RMS
CONGRESS HIGHLIGHTS – TUESDAY EDITION
Tolebrutinib in PPMS: PERSEUS results
PERSEUS is a phase III trial of the BTK inhibitor tolebrutinib 60 mg/day vs. placebo in 767 PPMS patients (Reich et al. ACTRIMS Forum 2026;LB1.4). Mean age was 45 years, mean time from MS diagnosis was about 4 years, and mean baseline EDSS score was 4.9. Most patients (57-61%) were treatment-naïve and few (10-14%) had Gd+ lesions at baseline. Tolebrutinib failed to reduce the rate of 6-month confirmed disability progression (CDP) compared to placebo. The cumulative incidence of 6-month CDP was 36.9% with tolebrutinib and 37.7% with placebo. Tolebrutinib was also associated with nominally significant reductions in new/enlarging T2 lesions and brain-volume loss. Three percent of tolebrutinib-treated patients experienced liver enzyme elevations >5 times the upper limit of normal; one patient met Hy’s Law criteria for liver injury. The discontinuation rate was 24.6% in the tolebrutinib arm and 22.7% in the placebo arm. (see also Tolebrutinib in nrSPMS: North American results, NeuroSens, February 9, 2026).
Ofatumumab in patients with low disease activity
A post-hoc analysis of the ASCLEPIOS I/II trials of ofatumumab vs. teriflunomide examined efficacy in the subgroup of 261 newly-diagnosed treatment-naïve patients with low disease activity (Wiendl et al. ACTRIMS Forum 2026;P134). Low disease activity was defined as 1 relapse in the two years prior to enrollment. Mean age was about 36 years; mean time since diagnosis was about 20 weeks. In the continuous ofatumumab arm, the proportion achieving no evidence of disease activity (NEDA) was 43.9% in year 1 (vs. 28.9% with teriflunomide; odds ratio 2.38), and 89.9% in year 2 (vs. 34.4% with teriflunomide; OR 18.27). There were greater reductions in annualized relapse rate (relative risk 0.63), Gd+ lesions (RR 0.08), new/enlarging T2 lesions (RR 0.17), and 6-month CDP (0.64) in patients starting treatment with ofatumumab rather than teriflunomide. The rate of serious adverse events was lower with ofatumumab vs. teriflunomide (5.8% vs. 7.1%). The authors concluded that the results support the first-line use of ofatumumab even in patients with low disease activity.
A separate real-world study examined safety outcomes in early MS patients with low disease activity starting treatment with ofatumumab, interferon-beta or glatiramer acetate (Nelles et al. ACTRIMS Forum 2026;P426). Mean age was 35 years; mean baseline EDSS score was 1.0-1.3. According to the interim analysis (n=497), ofatumumab was associated with fewer adverse events (4.0% vs. 6.5%), a lower rate of injection-site reactions (6.7% vs. 38.7%), and a lower rate of adverse effects leading to treatment discontinuation (1.5% vs. 12.9%) compared to older injectables. In addition, fewer patients receiving ofatumumab experienced ≥2 infections compared to those in the IFN/GA cohort (9.9% vs. 18.3%). The treatment retention rate at 24 months was 96% for ofatumumab, 75% for interferon-beta and 65% for glatiramer acetate.
ORATORIO-HAND study of ocrelizumab in PPMS
The ORATORIO-HAND study evaluated ocrelizumab versus placebo in 1013 PPMS patients aged ≤65 years (Giovannoni et al. ACTRIMS Forum 2026;P124). Median age was 48 years and median EDSS score was 6.0. Ocrelizumab was associated with a lower risk of 24-week CDP on the 9HPT (13.3% vs. 21.9%). The treatment benefit was greater in the subgroup with Gd+ and/or T2 lesions at baseline/screening (10.9% vs. 27.6%) compared to an inactive MRI (14.6% vs. 18.6%). There was also a lower risk of requiring a wheelchair (EDSS ≥7.0). The proportion requiring a wheelchair at 144 weeks was 4.5% in the ocrelizumab group vs. 10.6% in the placebo group (HR 0.59). Risk reductions were greater in the active vs. nonactive MRI subgroups (86% vs. 35% reduction) but were statistically significant for both groups.
GLP-1R agonist use in MS
Glucagon-like peptide-1 (GLP-1) receptor agonists are effective for body-weight reduction but appear to have little or no impact on the MS clinical course, according to a chart review of 131 patients seen at the MS centre at Brigham & Women’s Hospital, Boston, Massachusetts (Rodin et al. ACTRIMS Forum 2026;P422). At the start of GLP-1 therapy, mean age was 53 years, mean BMI was 36.9 kg/m2, and mean EDSS score was 3.1. A total of 82% were female, 85% were Caucasian and 75% had RMS. After an average of 29 months on treatment, there was a mean 4-point reduction in BMI. EDSS scores did not change overall: EDSS decreased in 17%, increased in 18% and was unchanged in 65%. Moderate/severe adverse effects (1% each) were pancreatitis, severe constipation, brain fog and dysesthesias. Nine percent of patients discontinued GLP-1 therapy due to adverse effects. The authors cautioned that special consideration may be warranted in patients with constipation, dysesthesias and/or brain fog being considered for treatment with a GLP-1 receptor agonist. It is unclear if GLP-1 agents would have an impact on the MS clinical course if administered earlier in younger patients.
Integrating fluid and digital biomarkers
The SPI2 trial found that high-dose biotin (MD1003) was not effective in reducing disability or walking speed in PMS patients (Cree et al. Lancet Neurol 2020;19:988-997). A post-hoc analysis of this trial cohort (n=630) examined whether daily step counts were correlated with changes in serum neurofilament-light chain (sNfL) levels (Abdelhak et al. ACTRIMS Forum 2026;P175). Mean age was 52.7 years; median EDSS score was 6.0; and mean NfL was 15.2 pg/mL. The median daily step count was 3047 steps. Elevated sNfL was associated with a lower daily step count; a 1-unit increase in NfL Z-score corresponded to 3.4% fewer steps. This association was not affected by EDSS category (<5.0 vs. >5.0). The authors noted that NfL and step count were more sensitive than EDSS in identifying subtle changes in disease status.
Delayed physician visits for neuroinflammatory patients in rural Ontario
An Ontario study examined whether social determinants of health affected the diagnosis and management of 242 consecutive patients with neuroinflammatory conditions (Chen et al. ACTRIMS Forum 2026;P337). The conditions included NMOSD, myelin oligodendrocyte glycoprotein antibody disease (MOGAD), double AQP4/MOG-IgG seronegatives, acute necrotizing encephalopathy of childhood, and acute flaccid myelitis. Overall, rural patients experienced a longer delay to hospital admission (11.75 vs. 8.23 days), longer delays in accessing MRI (12.60 vs. 9.13 days) and delayed initiation of acute treatment (14.08 vs. 10.32 days) compared to urban patients. The longest delays were seen for patients with NMOSD and MOGAD. The mean times for hospital admission, MRI and treatment were 26 days, 27 days and 30 days for NMOSD patients, and 11 days, 11 days and 14 days for MOGAD patients. There were no differences in access to care across different ethnic groups.
Obexelimab phase II results in RMS
Obexelimab is a humanized MAb that binds CD19 and engages the inhibitory Fc-gamma-RIIb CD32b) receptor expressed on B cells, myeloid cells and other immune cells (Morelli et al. J Immunol 2026;215:vkaf247). This binding interferes with antibody production and proliferation, antigen presentation to T cells and cytokine secretion without significant lymphocyte depletion. MOONSTONE was a 12-week phase II study of subcutaneous obexelimab 250 mg once weekly vs. placebo in 116 patients with RMS or active SPMS (Okuda et al. ACTRIMS Forum 2026;LB1.3). Mean age was 42 years, median EDSS score was 2.5-3.0, and 21-22% had Gd+ lesions at screening. Treatment was associated with a 95% relative reduction in Gd+ lesions (0.01 vs. 0.23) and an 81% relative reduction in new/enlarging T2 lesions in weeks 8-12. The mean reduction in B cell counts was 37%; mean B cell values remained above the lower limit of normal. The most common adverse effect was injection site erythema (11.5%). There were three serious adverse effects: two infections where treatment was interrupted and one hypersensitivity reaction in which treatment was discontinued. A Phase II study has also been conducted in IgG4-related disease (Perugino et al. Lancet Rheumatol 2023;5:e442-e450). A study in systemic lupus erythematosus failed to achieve its primary endpoint (Merrill et al. Arthritis Rheumatol 2023;75:2185-2194).