The 10th Joint meeting of the Americas and European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS)
The following summarizes some of the highlights from Day 1 of MSToronto 2026.
MS risk with infectious mononucleosis
sNfL elevation postpartum
PRLs contribute to treatment failure
Update on frexalimab
Daratumumab effective in AQ4-IgG+ NMOSD
One-quarter of MS patients are untreated
Clinical tip of the day
MS risk with infectious mononucleosis
A retrospective database analysis from three Nordic countries identified all MS patients with hospital-diagnosed infectious mononucleosis (IM) for varying periods from 1978-2020 and matched them with non-MS individuals (Kunzweiler et al. MSToronto 2026;1030). Overall, the relative risk of MS for IM patients vs. matched comparators was 2.6 (pooled). MS risk was highest in Denmark and Finland for those diagnosed with IM during adolescence (hazard ratio 2.9-3.8). In Sweden, the MS risk was highest if IM was diagnosed during childhood (HR 7.8). Risk was lowest if IM was diagnosed during adulthood (HR 1.8).
sNfL elevation postpartum
Serum Nfl levels reportedly rise postpartum in women with MS, although this change does not appear to be associated with increased disease activity (Proschmann et al. Front Immunol 2021;12:715195). A similar sNfL elevation occurs in healthy women, according to a newly-published study (Bertolotto et al. MSToronto 2026;459; published as Brain Behav Immun 2026:137:106831). Blood samples were obtained on the day before delivery, days 1, 2-5 and 6-10 days postpartum. sNfL levels doubled on day 1 postpartum, peaked on days 6-10 and normalized after 40 days. sNfL levels were lower in multiparous women. The authors proposed that sNfL changes may reflect pregnancy-induced neuroplasticity rather than neuroaxonal damage.
PRLs contribute to treatment failure
The presence of paramagnetic rim lesions (PRLs) is an independent risk factor for treatment failure, according to a retrospective study of 163 RMS patients (Marrodan et al. MSToronto 2026;503). Median age at onset was 35 years; median follow-up was 4.8 years; median PRL count was 1.0. About 70% of the cohort were started on a lower-efficacy DMT. The overall rate of treatment failure was 28.8%. Each additional PRL was associated with a 5.5% increased risk of treatment failure. Older age at onset and treatment with a higher-efficacy DMT were associated with a lower risk of treatment failure.
Update on frexalimab
Frexalimab is an anti-CD40-CD40L mAb that targets the pathway involved in innate and adaptive immune activation. The phase II dosing was 1200 mg IV q4wk (1800 mg loading dose) or 300 mg SC q2wk (600 mg loading dose). For the open-label extension, the dosing was changed to 1200 mg IV q4wk and 1800 mg SC q4wk. Results at 144 weeks were presented at EAN (Vermersch et al. EAN 2026;EPO-0785). At 3.5 years (week 168), treatment continued to be well-tolerated (Vermersch et al. MSToronto 2026;1490). The most common adverse effects were nasopharyngitis, headache, COVID-19 and back pain. However, 14% experienced serious adverse events, such as pyelonephritis, lower respiratory tract infection, ovarian fibroma and papillary thyroid cancer. The phase III FREVIVA trial in non-relapsing SPMS is ongoing (Krieger et al. MSToronto 2026;2033). A total of 943 patients have been enrolled. Mean age is 49.5 years; median EDSS is 6.0; mean time since SPMS diagnosis is 5.2 years; and 94% are free of Gd+ lesions at baseline. See also Update on frexalimab, NeuroSens, Highlights of EAN 2026 – Part 1.
Daratumumab effective in AQ4-IgG+ NMOSD
Daratumumab is a mAb targeting CD38 on plasmablasts and plasma cells that is currently approved for the treatment of multiple myeloma. The DAWN trial (N=135) evaluated IV daratumumab vs. placebo in AQP4-IgG+ NMOSD at eight centres in China (Zhang et al. MSToronto 2026;2804). Daratumumab dosing was 8 mg/kg every two weeks for the first two doses followed by 4 mg/kg every four weeks. Overall, 19% in the daratumumab arm and 60% in the placebo arm experienced relapses (hazard ratio 0.26). ARR was 0.13 vs. 0.51. Daratumumab was also associated with a mean improvement in EDSS score compared to an EDSS worsening with placebo (-0.7 vs. +0.6).
One-quarter of MS patients are untreated
An analysis of the German NeuroTransData registry (N=7456) for the period 2018-2024 looked at MS untreated patients who had never started therapy or had opted to discontinue their medication (Braune et al. MSToronto 2026;674). The proportion of untreated RMS patients declined from 36.3% in 2018 to 24.4% in 2024. Similar declines were also seen for untreated SPMS (73.7% to 61.8%) and untreated PPMS (85.6% to 64.7%). The annualized relapse rate was 0.18 for patients who stopped treatment and 0.16 for never-treated patients; mean EDSS score was 2.6 and 1.5 for the two groups, respectively. The authors noted that the decision not to treat appears to be driven primarily by patients not being convinced of the benefits of treatment, and physicians’ uncertainty about the treatment rationale in specific scenarios.
Clinical tip of the day
Annual MRI scans in stable patients on ocrelizumab may not be necessary (Schoof et al. MSToronto 2026;169). The Amsterdam group examined routine MRIs for 342 asymptomatic MS patients taking ocrelizumab (mean age 40.3 years). Overall, radiological disease activity was seen in 1.8% of scans over a median treatment duration of 49 months. Routine MRIs never led to a change in treatment. The authors suggested that in stable patients, the interval between MRIs could be doubled after the initial scans (rebaseline, year 1, year 2, year 4, year 8, etc.).