The 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis – 18-20 September 2024

The following summarizes some of the highlights from Day 3 of ECTRIMS 2024.

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Discontinuing treatment in older patients
Effect of frexalimab on PRLs
sNfL often normal after relapse
No loss of prior immunity with anti-CD20 therapy
Eye tracking may predict cognitive worsening
Prior epilepsy worsens MS
Clinical tip of the day

CONGRESS HIGHLIGHTS – FRIDAY EDITION

Discontinuing treatment in older patients
An Italian study examined outcomes in 71 older MS patients who discontinued their disease-modifying therapy (Frau et al. ECTRIMS 2024;P821). Mean age at DMT discontinuation was 65.6 years, and mean duration of disease was 23.8 years. Two-thirds of patients had been treated with a first-line DMT; median EDSS score at discontinuation was 6.0. Disease activity on MRI was evident in 8.5% in the year prior to stopping treatment and in 18.3% after discontinuation; differences were not significant. Six patients restarted therapy. The authors concluded that discontinuation may be considered in older patients with stable disease. It is unclear if there would be a benefit of treatment in older patients with ongoing disease activity and less EDSS progression.

Effect of frexalimab on PRLs
Frexalimab is a monoclonal antibody that targets CD40 ligand and inhibits the CD40/CD40L pathway, which is involved in innate and adaptive immune activation. A phase II placebo-controlled study (N=129) reported a reduction in new Gd+ lesions with frexalimab at week 12 (Vermersch et al. N Engl J Med 2024;390:589-600). The frexalimab doses used were 1200 mg IV q4weeks (with an 1800 mg loading dose) and 300 mg SC q2weeks (with a 600 mg loading dose). Plasma NfL levels decreased 24-41% from baseline to week 48 in the frexalimab groups. Data were presented at this year’s European Academy of Neurology meeting (see Report from AAN 2024, NeuroSens, April 16, 2024). At the start of the open-label extension, 19 of 46 patients (41%) had paramagnetic rim lesions (PRLs) (Arnold et al. ECTRIMS 2024;P830). New PRLs occurred in weeks 8-20 in the 300 mg SC group, however, no PRLs occurred from baseline to week 48 in the 1200 mg IV group. The number of new Gd+ lesions remained low to week 48.

In addition, extension data at week 72 (n=125; n=111 at week 72) were presented (Giovannoni et al. ECTRIMS 2024;O066). After week 12, the placebo group was switched to the frexalimab IV or SC groups. During the extension, the SC dose was increased to 1800 mg q4weeks. For patients on continuous frexalimab, the number of new Gd+ lesions was 0.1 for the IV group and 0.4 for the SC group. The most common adverse effects were nasopharyngitis (13%), COVID-19 (12%) and headache (11%).

sNfL often normal after relapse
An Italian group analysed 113 sNfL samples of RMS patients at the time of relapse and/or MRI activity (Giorgi et al. ECTRIMS 2024;P755). sNfL levels were normal in 78% of samples taken from patients following a relapse without accompanying MRI activity; sNfL level was normal in 44% with relapses + MRI activity. There was a greater likelihood of normal sNfL level if relapses affected sensory (67%) or visual (78%) systems compared to pyramidal involvement (44%). Most patients with elevated sNfL demonstrated EDSS progression after six months compared to those with normal sNfL level (69% vs. 41%). The authors noted that sNfL could be used to better characterize relapses and the extent of neurological damage associated with disease activity.

No loss of prior immunity with anti-CD20 therapy
A study in Spain reported that patients receiving an anti-CD20 monoclonal antibody do not lose their pre-existing humoral immunity to varicella zoster virus (VZV) or measles (Carvajal et al. ECTRIMS 2024;O030). The prospective study compared 326 MS patients (mean age 47 years) treated with rituximab or ocrelizumab vs. those receiving natalizumab. The seroprotection rate was based on a cutoff titre of >165 mIU/mL for VZV and 16.5 AU/mL for measles. Median time from DMT exposure to follow-up serology was 3.7 years. There was no significant difference in seroprotection rate between anti-CD20 agents and natalizumab for VZV (98% vs. 98%) or measles (96% vs. 93%). In addition, there was no significant difference in the two groups with respect to IgG titres for VZV (1587 vs 1429 IU/L) or measles (300 vs 300 UA/mL). Overall, 6% on ocrelizumab, 4% on rituximab and 9% on natalizumab lost seroprotection. Risk factors for loss of seroprotection were younger age and lower antibody titres at baseline.

Eye tracking may predict cognitive worsening
Novel eye-tracking technology is currently in development as a non-invasive biomarker of physical and cognitive dysfunction. A Montreal group previously reported correlations between eye-movement measures and Symbol Digit Modalities Test (SDMT) and EDSS scores in a preliminary analysis of an iPad-enabled eye-tracking tool (de Villers-Sidani et al. Front Neurol 2023;14:1243594). A follow-on analysis of 88 patients now reports that 14 eye-movement parameters from three visual tasks were able to predict SDMT worsening at six months (sensitivity 91%, specificity 57%) (Giacomini et al. ECTRIMS 2024;P787). The authors concluded that eye tracking may soon be employed as a biomarker of cognitive dysfunction and may aid in treatment optimization. (Click here to listen to a previous NeuroSound podcast with lead author Dr. Paul Giacomini.)

Prior epilepsy worsens MS
A retrospective single-centre study examined outcomes in patients with MS for >10 years with comorbid epilepsy (Menascu et al. ECTRIMS 2024;P1313). Overall, 53 of 4600 patients (1.1%) had comorbid epilepsy. The proportion of patients with RRMS and PMS did not differ in patients with and without epilepsy, suggesting that epilepsy does not affect the clinical course of MS. However, in the subgroup of 40 patients with epilepsy who later developed MS, the median EDSS score was significantly higher (3.0 vs. 2.0) compared to those without prior epilepsy. The average duration of epilepsy prior to an MS diagnosis was 7.5 years.

Clinical tip of the day
A recent meta-analysis found that vitamin D supplementation did not improve clinical outcomes in people with MS (see No benefit with adjuvant vitamin D in MS: meta-analysis, NeuroSens, February 12, 2024). Now a single-centre study in Australia reports that higher serum 25(OH)D levels may be harmful (Arnett et al. ECTRIMS 2024;P1183). The study of 453 MS patients found a U-shaped relationship between vitamin D levels and outcome measures. Both low and high vitamin D levels were associated with worse outcomes.

Watch for the phase III results of the tolebrutinib trials presented at ECTRIMS in an upcoming issue of NeuroSens.

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