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.
Fenebrutinib vs. ocrelizumab in PPMS
Effect of higher-efficacy DMTs on PIRMA risk
Switching from ocrelizumab to ofatumumab
Vitamin B a useful adjunct to S1PR modulators?
Tolebrutinib in nrSPMS: North American results
Epidemiology of NMOSD in Ontario
CONGRESS HIGHLIGHTS – MONDAY EDITION
Fenebrutinib vs. ocrelizumab in PPMS
FENtrepid is a phase III non-inferiority trial comparing fenebrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, with ocrelizumab in 985 patients with PPMS for ≥120 weeks (Bar-Or et al. ACTRIMS Forum 2026;LB1.5). The primary endpoint was time to onset of 12-week confirmed disability progression (CDP) using a composite measure (EDSS, T25FW, 9HPT). Mean age was 48.9 years, median EDSS score was 5.0, and mean time from MS symptom onset was 9 years. A low proportion of patients (10.8%) had Gd+ lesions at baseline. Fenebrutinib 200 mg BID PO was non-inferior to ocrelizumab 600 mg IV q24weeks: there were fewer CDP events with fenebrutinib starting at week 12. The proportion with a CDP event at endpoint was 58.8% with fenebrutinib compared to 66.1% with ocrelizumab (12% risk reduction, ns). The treatment effect was consistent across subgroups, including age, sex, baseline EDSS score, baseline Gd+ lesions and prior DMT use. The rate of serious adverse events was similar with fenebrutinib and ocrelizumab (19.1% vs. 18.9%). Serious infections were less common with fenebrutinib (6.1% vs. 9.1%). The rate of liver-enzyme abnormalities was 13.3% with fenebrutinib and 2.0% with ocrelizumab. Two patients in the fenebrutinib arm (0.4%) and one in the ocrelizumab arm (0.2%) met Hy’s Law biochemical criteria; the impact of drug was uncertain since there were alternative etiologies. A total of 14.1% in the fenebrutinib arm discontinued treatment due to liver enzyme elevations as mandated in the study protocol. There were seven deaths during fenebrutinib treatment; all were considered to be unrelated to the study drug. Phase II results from the FENopta trial of RMS were published last year (Bar-Or et al. Lancet Neurol 2025;24:656-666). Two phase III trials in RMS (FENhance 1 and 2) are ongoing.
(See also BTK inhibitors – a look ahead, NeuroSens, January 26, 2026.)
Effect of higher-efficacy DMTs on PIRMA risk
A retrospective observational study examined the rate of progression independent of relapse or MRI activity (PIRMA) in RRMS patients receiving higher-efficacy (MAbs, cladribine) or lower-efficacy (all other therapies) DMTs (Guarnaschelli et al. ACTRIMS Forum 2026;P421). Median age of onset was 31 years; median duration of MS was 7-9 years. According to the interim analysis (n=176), treatment with a moderate- or low-efficacy DMT was associated with a higher risk of PIRMA (hazard ratio 7.05). At the time of the analysis, 43% of patients in the moderate-efficacy group and 74% in the low-efficacy group had switched treatments.
Switching from ocrelizumab to ofatumumab
The OLIKOS phase IIIb study evaluated the efficacy and safety of switching from an infusion anti-CD20 agent to ofatumumab administered by subcutaneous injection in 102 RMS patients (Hua et al. J Neurol 2025;272:725). One patient switched from rituximab; the remainder switched from ocrelizumab. At the time of switching, the mean CD19+ B cell concentration was 25.8 cells/μL; 6.9% had B cell counts within the normal range (mean 7.8 months after last infusion). B cell counts declined to 2.3 cells/μL at 12 months after initiating ofatumumab (Hua et al. ACTRIMS Forum 2026;P055). After changing therapies, B cell counts were reduced to below the lower limit of normal at months 6 and 12 in all patients including those with B cell repletion while on IV anti-CD20 therapy. The authors suggested that monthly dosing may produce a more consistent and sustained effect on B cell concentrations compared to less frequent dosing.
Vitamin B a useful adjunct to S1PR modulators?
S1P receptor modulators (e.g. fingolimod, ozanimod, siponimod) target sphingosine-1-phosphate, a signalling molecule that regulates immune cell trafficking. Treatment blocks lymphocyte egress from lymphoid organs, thereby reducing the passage of immune cells across the blood-brain barrier. Vitamin B6 (pyroxidal 5′-phosphate) is a necessary cofactor for S1P lyase, an enzyme that degrades S1P. A metabolomic study examined the effects of vitamin B6 and B-complex supplementation in 73 early MS patients (Liu et al. ACTRIMS Forum 2026;P022). Mean age was 39 years. Vitamin B supplementation was associated with lower levels of S1P and dihydro-S1P (a saturated analogue of S1P). The authors suggested that vitamin B supplements may modulate S1P metabolism in MS and could be a useful adjunct to S1PR modulator therapy.
Tolebrutinib in nrSPMS: North American results
The HERCULES phase III trial compared the Bruton’s tyrosine kinase (BTK) inhibitor tolebrutinib 60 mg/day with placebo in 1131 patients with non-relapsing SPMS (Fox et al. N Engl J Med 2025;392:1883-1892). The proportion of patients with 6-month confirmed disability progression (CDP) was significantly lower with tolebrutinib than placebo (22.6% vs. 30.7%, hazard ratio 0.69). A new analysis has reported efficacy results in the subgroup of 162 patients (14.3% of total) at Canadian and U.S. centres (Bar-Or et al. ACTRIMS Forum 2026;P127). North American patients were older (mean age 51.8 vs. 48.9 years), had lower EDSS scores (mean 5.2 vs. 5.5), and were less likely to have Gd+ lesions at baseline (4.4% vs. 12.7%). The estimated incidence of 6-month CDP was 54% lower with tolebrutinib in North American patients (62% lower in Americans, 31% lower for the full cohort). The FDA recently rejected tolebrutinib’s application as a treatment for nrSPMS primarily due to safety concerns. The FDA identified six cases of hepatotoxicity meeting Hy’s Law criteria in the drug development program (FDA complete response, 23 December 2026; full text at https://download.open.fda.gov/crl/CRL_NDA219624_20251223.pdf).
Epidemiology of NMOSD in Ontario
An analysis of health claims and laboratory data in Ontario identified 179 cases of neuromyelitis optica spectrum disorder (NMOSD) in the province; mean age at first attack was 47 years. The estimated mean incidence of AQP4+ NMOSD was 0.105 cases/100,000 population per year for the period 2018-2024 (Rotstein et al. ACTRIMS Forum 2026;P343). The point prevalence for 2024 was 1.222/100,000. Prior studies have reported NMOSD incidence rates ranging from 0.053/100,000 in Cuba to 4.4/100,000 in southern Denmark (Etemadifar et al. Mult Scler Int 2015:2015:174720). Prevalence estimates range from 0.52 in Cuba to 4.41/100,000 in southern Denmark (Etemadifar 2015). It should be noted, however, that prior studies have used different diagnostic criteria (e.g. Mayo Clinic criteria in Cuba, Wingerchuk criteria in Denmark).