The 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis – 24-26 September 2025

The following summarizes some of the highlights from Day 3 of ECTRIMS 2025.

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Ocrelizumab safety during pregnancy and breastfeeding
HE-DMT use in pediatric MS in Canada
Increasing importance of PIRA with aging
Use of sNfL in clinical practice
Frexalimab long-term data
Clinical tip of the day

CONGRESS HIGHLIGHTS – SATURDAY EDITION

Ocrelizumab safety during pregnancy and breastfeeding
Two studies have examined the safety of ocrelizumab exposure during pregnancy and breastfeeding. The MINORE study evaluated 35 women who received an ocrelizumab infusion <6 months after their last menstrual period (median 3.2 months); preliminary data were presented at ECTRIMS 2024 (Hellwig et al. P087, Bove et al. O039) and updated at ACTRIMS Forum (Hellwig et al. P106). Ocrelizumab was undetectable in 94.3% of cord blood samples at birth and 97.0% of serum samples at week 6 (see ACTRIMS Forum 2025 Highlights – Update on Ocrelizumab, NeuroSens, March 24, 2025). In the SOPRANINO study (N=13), ocrelizumab was administered 2-24 weeks postpartum. Transfer in breast milk was near to the lower limit of quantification and B cell levels were within the normal range in all infants (Hellwig et al. ACTRIMS Forum 2025;P101).

Results at 1-year follow-up are now available (Bove et al. ECTRIMS 2025;O102). The objective was to examine the potential effects of ocrelizumab exposure on infants’ B cell kinetics, humoral responses to vaccination, and growth and development. Growth and development were evaluated with the WHO child growth standards and the Ages and Stages Questionnaire (ASQ-3) at months 2, 4, 6, 9 and 12. All infants were vaccinated against MMR at least once in the first year of life. Infants’ B cell levels were within the normal range at week 6 and month 13 in the two studies. Seroprotective humoral responses in MINORE and SOPRANINO, respectively, were 96% and 100% for measles, 85% and 78% for mumps, 96% and 100% for rubella, 100% and 100% for tetanus, 95% and 100% for hepatitis B, 83% and 80% for Hemophilus influenzae, 85% and 100% for multiple strains of pneumococcus, and 100% and 100% for diphtheria. Growth percentiles in MINORE and SOPRANINO were within the normal range for head circumference (90-100% in both studies), weight (92-97% and 83-100%) and height/length (67-97% and 80-100%).

Also noteworthy was the Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS), which examined the relapse risk during pregnancy and postpartum (Krysko et al. ECTRIMS 2025;P587). The study included 131 women (139 pregnancies); median age was 32.4 years; 16% experienced a relapse in the year before pregnancy. The proportion of patients who relapsed during pregnancy was 5.8%, increasing to 14.4% in the one-year postpartum period. A significantly higher risk of postpartum relapse was seen in patients who had been treated with fingolimod vs. first-line injectables (rate ratio 6.43); relapses were numerically higher in patients previously treated with natalizumab. Postpartum relapses were less common in patients receiving ocrelizumab or alemtuzumab prior to conception.

The lead author of the CANPREG-MS study was Dr. Kristen Krysko, BARLO MS Centre, who is this year’s recipient of the Rachel Horne Prize for Women’s Research in MS. The prize was awarded in recognition of her research on pregnancy and breastfeeding in MS. Congratulations to Dr. Krysko for her important contributions to MS research from everyone at NeuroSens! (Click here to view Dr. Krysko on our Clinical Cases in MS series.)

HE-DMT use in pediatric MS in Canada
An analysis of 155 pediatric MS cases at the Hospital for Sick Children, Toronto, reported that two-thirds were treated with a moderate-efficacy DMT, 21.3% with a higher-efficacy DMT, and 11.0% were untreated (Strasser et al. ECTRIMS 2025;P1636). The most common initial therapies were peginterferon-beta and dimethyl fumarate. However, use of higher-efficacy DMTs has been more common since 2018: 57.8% received a moderate-efficacy DMT, 32.2% received a higher-efficacy DMT and 10.0% were untreated. A majority of patients (56.2%) initiated on a moderate-efficacy DMT required a treatment switch compared to 24.2% started on a higher-efficacy DMT.

Increasing importance of PIRA with aging
An Italian single-centre study examined the long-term course of disability of MS patients (N=1499) followed from 1980 to 2022 to determine the impact of age of onset on the rate of progression independent of relapse activity (PIRA) (Montobbio et al. ECTRIMS 2025;P561). PIRA accounted for 0.3 EDSS points/decade for those aged 18-29 years at onset, 0.7 EDSS points/decade for those aged 30-49 years at onset, and 1.18 points/decade for those aged ≥50 years at onset. Relapse-associated worsening (RAW) was unaffected by age of onset. RAW accounted for 0.34 EDSS points/decade for the 18-29-year group, 0.32 points/decade in the 30-49-year group, and 0.28 points/decade for the ≥50 year-group.

Use of sNfL in clinical practice
An MS clinic in Germany analysed 1026 serum neurofilament light chain (sNfL) samples collected from 638 MS patients in 2024 to determine the impact of demographic and disease factors on the test results (Vardakas et al. ECTRIMS 2025;P239). The median sNfL concentration was 13 pg/mL. sNfL Z-scores were higher in patients with active disease across all phenotypes, and in patients with relapses or new MRI lesions. The probability of an sNfL Z-score >1.5 was higher in males (odds ratio 0.628 females vs. males), in patients with higher EDSS scores (odds ratio 1.22), and during a period of disease activity (relapse or MRI lesion, OR 1.89). Z-scores were somewhat predictive (AUC 0.69) of patients who were switched from a first-line injectable or oral therapy to another DMT.

Frexalimab long-term data
Frexalimab is a monoclonal antibody targeting the CD40-CD40L costimulatory pathway that regulates the adaptive and innate immune response. A phase II study reported that frexalimab 1200 mg IV q4wks significantly reduced new Gd+ lesions by 89% versus placebo at 12 weeks; a dose of 300 mg subcutaneously q2wks reduced new Gd+ lesions by 79% (Vermersch et al. N Engl J Med 2024;390:589-600). For the open-label extension, the placebo group was switched to one of the two frexalimab groups at week 12. The subcutaneous dose was increased to 1800 mg q4wk. A total of 79% of participants remained on study at week 120 (Vermersch et al. ECTRIMS 2025;O111). The number of Gd+ lesions remained low in the continuous IV (mean 0.2) and subcutaneous groups (mean 0.1). The annualized relapse rate was 0.09 in the IV group; 88% were relapse-free. The most common adverse events were nasopharyngitis, headache and COVID-19. Plasma NfL was reduced a median of 37-44% from baseline at week 120 (Bar-Or et al. ECTRIMS 2025;O030). Serum levels of TREM2 (Triggering Receptor Expressed on Myeloid Cells 2), an innate immune receptor on microglia and other myeloid cells, were reduced 24-35% from baseline.

Clinical tip of the day
Dr. ChatGPT is keen to consult but is not quite ready (yet), according to a new Italian study (Signori et al. ECTRIMS 2025;P1737). ChatGPT-4o was provided data on 799 patients who initiated therapy in the period 2015-2023 and was asked to recommend a DMT. Patient data included age, sex, disease duration, EDSS score, relapse rate in the previous year and most recent MRI. The overall disagreement between ChatGPT and clinicians on treatment choice was 83.7%. The preferred therapy by ChatGPT-4o was teriflunomide, whereas clinicians preferred an injectable platform therapy or ocrelizumab. The authors concluded that further refinement of AI is needed.

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