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 2 of MSToronto 2026.
DOT-MS discontinuation study
OPERETTA 2 results for ocrelizumab in POMS
PIRA in early- and late-onset MS
Impact of anti-CD20 on PIRA
Low rate of postpartum relapses with anti-CD20 therapy
Does EBV seronegativity preclude MS diagnosis?
Update on FENhance trials of fenebrutinib
Clinical tip of the day
DOT-MS discontinuation study
The DOT-MS trial was terminated early when younger patients (range 47-59 years) on lower-efficacy therapies showed they were at risk of recurrence of inflammatory activity despite disease stability for >5 years (Coerver et al. JAMA Neurol 2024;82:123-131). For the extension study, 9 of 32 patients in the discontinuation group restarted therapy; disease activity recurred in 21.4% (16.0% off treatment and 29.4% in restart group) compared to 23.5% of the continuation group (Holwerda et al. MSToronto 2026;1195). Over the combined trial + extension periods, the risk of disease activity was non-significantly higher in the discontinuation vs. continuation groups (hazard ratio 2.3).
OPERETTA 2 results for ocrelizumab in POMS
The OPERETTA 2 trial (N=185) reportedly showed that ocrelizumab was noninferior to fingolimod in pediatric-onset MS (Banwell et al. ECTRIMS 2025), although the data have not yet been published. In a post-hoc analysis at 96 weeks, ARR was significantly lower with ocrelizumab compared to fingolimod (0.021 vs. 0.143) (Deiva et al. MSToronto 2026;931). A separate analysis found that most pediatric patients treated with ocrelizumab or fingolimod maintained seropositivity for mumps, pneumococcus, rubella and varicella zoster. (Banwell et al. MSToronto 2026;930). No cases of mumps, rubella, pneumococcus or VZV infections were reported in previously vaccinated patients.
PIRA in early- and late-onset MS
A Canadian study compared the PIRA rate in patients with early- vs. late-onset MS (Ciftci et al. MSToronto 2026;2444). Mean age was 36 and 62 years, respectively. Early-onset MS was defined as symptom onset before age 20, and late-onset as onset after age 50. The PIRA rate at last assessment was 33% for the late-onset and 27% for the early-onset MS groups. The time from symptom onset to treatment initiation was longer in early-onset patients (48 vs. 15 months). Mean sNfL levels were higher in late-onset patients (14.3 vs. 9.9).
Impact of anti-CD20 on PIRA
A real-world multicentre study (N=325) examined the impact of ofatumumab on progression independent of relapse activity (PIRA) and PIRA + MRI activity (PIRMA) over a two-year period (Stepien et al. MSToronto 2026;2555). After ofatumumab initiation, ARR decreased to 0.03 in previously untreated patients and to 0.09 in previously treated patients. The PIRA rate decreased from 11.2% in year 1 to 8.1% in year 2. The rate of PIRMA similarly declined from 10.0% to 8.1%.
Low rate of postpartum relapses with anti-CD20 therapy
A U.K. study evaluated disease activity during and after pregnancy in 52 patients who interrupted anti-CD20 therapy (Bongol et al. MSToronto 2026;2197). Mean maternal age was 33-34 years. ARR in the year prior to pregnancy was 0.12 with ocrelizumab and 0.11 with ofatumumab. Ocrelizumab-treated patients had a longer disease duration (11.1 vs. 8.0 years) and longer treatment duration prior to pregnancy (28.8 vs. 14.8 months). Patients on ocrelizumab interrupted treatment for a mean of 13.2 months compared to 9.2 months for ofatumumab. The time to restarting treatment was similar (mean 5.2 vs. 4.3 weeks). All patients were relapse-free during pregnancy and postpartum. The rate of MRI activity was low in both groups (12% vs. 11%). Both treatments were associated with low third trimester CD19 counts. Pregnancy outcomes were similar. Most adverse events were predominantly maternal or infant infections.
Does EBV seronegativity preclude MS diagnosis?
Epstein-Barr virus (EBV) seropositivity is generally considered a necessary but not sufficient factor for the development of MS. But does EBV seronegativity rule out MS? A real-world study of 231 individuals with suspected MS found that no diagnosed MS patient was double-seronegative for EBV nuclear antigen (EBNA)-1 IgG and viral capsid antigen (VCA)-IgG whereas 14% (4/29) without MS were double-seronegative (Fottinger et al. MSToronto 2026;1801). The authors suggest that double-seronegativity may be a useful adjunct to the diagnostic work-up in ambiguous cases.
Update on FENhance trials of fenebrutinib
The Bruton’s tyrosine kinase inhibitor (BTKi) fenebrutinib was reportedly superior to teriflunomide in reducing relapses in the FENhance 1 and 2 trials (ARR 0.061 and 0.054 vs. 0.125 and 0.13), although the full results have not yet been published (Oh et al. AAN 2026;LB2.5) (see NeuroSens, AAN Daily Highlights, Wednesday, April 22, 2026). The rate of no evidence of disease activity (NEDA) was also higher with fenebrutinib, according to a new analysis (Cerqueira et al. MSToronto 2026;1047). The estimated pooled NEDA rate was 67% with fenebrutinib compared to 26% with teriflunomide at two years. There was a lower risk of disease activity (hazard ratio 0.30) with fenebrutinib, although no significant difference in 24-week confirmed disability progression (HR 0.76).
Clinical tip of the day
Anti-CD20 therapy does not appear to impair the CD4⁺ T cell response to a trivalent seasonal influenza vaccine, according to a small German study (Stogbauer et al. MSToronto 2026;891). The humoral response was limited with little change in anti-influenza A/B IgG levels. The robust vaccine response was not affected by patient age, time since last anti-CD20 dose or treatment duration.