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 1 of ECTRIMS 2024.
Does the MS prodrome exist?
Early initiation of ofatumumab
sNfL predictive of enlarging T2 lesions
Relapse during pregnancy may speed progression
PIRA? Which PIRA?
Clinical tip of the day
CONGRESS HIGHLIGHTS – WEDNESDAY EDITION
Does the MS prodrome exist?
An analysis of two national databases in France has questioned whether an MS prodrome is a real phenomenon (Lebrun-Frenay et al. ECTRIMS 2024;P034). The databases included MRI utilization unlike previous analyses. A total of 482 individuals with radiologically isolated syndrome (RIS) were identified in the period 2009-2019. A total of 46% of RIS individuals did not have higher use of healthcare resources prior to the first abnormal MRI scan. In the group that did show increased utilization in the three years prior to RIS, most services were related to GP visits for headache (odds ratio 3.34) and anti-migraine drugs (OR 2.61). A comparison of RIS that did vs. did not evolve into MS showed no difference in the frequency of nonspecific symptoms, comorbidities, sick leaves or sociodemographic characteristics in the years prior to RIS diagnosis.
Similarly, an analysis of the Barcelona cohort found no increase in healthcare resource utilization in the years prior to MS diagnosis (Cardenas-Robledo et al. ECTRIMS 2024;O001). The authors suggested that what is assumed to be an MS prodrome actually represents diagnostic delay.
Early initiation of ofatumumab
Patients who initiate treatment with ofatumumab have less disability accrual at six years compared to those who start on teriflunomide, according to an analysis of the ALITHIOS long-term extension of the ASCLEPIOS I/II studies (Bar-Or et al. ECTRIMS 2024;P058). A total of 1367 patients entered the extension. The cumulative rate of six-month confirmed disability worsening (CDW) at six years was 21.09% in the continuous ofatumumab group versus 24.77% in the teriflunomide/ofatumumab switch group. The rates of six-month confirmed progression independent of relapse activity (PIRA) (15.45% vs. 16.56%) and relapse-associated worsening (RAW) (5.24% vs. 5.81%) were also lower for the continuous ofatumumab group. The effect size for early vs. delayed ofatumumab was greater in the subgroup of recently-diagnosed/treatment-naive patients (n=615). For the ofatumumab group, the rate of six-month CDW was 16.61% (vs. 23.74% for teriflunomide/ofatumumab); for six-month PIRA was 11.12% (vs. 16.75%); and for six-month RAW was 4.26% (vs. 4.82%).
sNfL predictive of enlarging T2 lesions
A retrospective analysis examined sNfL levels in 171 early MS patients with and without enlarging T2 lesions on MRI (Brummer et al. ECTRIMS 2024;P769). Patients with enlarging lesions had a higher median EDSS score at baseline (1.5 vs. 1.0) and at one year (1.9 vs. 1.3) compared to patients without enlarging lesions. Enlarging lesions and EDSS progression were associated with higher sNfL z-scores. sNfL level was an independent risk factor in patients with worsening progression and no other signs of disease activity.
A separate study looked at how sNfL z-scores might be incorporated into clinical practice (Fernandez et al. ECTRIMS 2024;O022). The study analysed 342 initiations of a disease-modifying therapy (injectables, orals and MAbs) and whether sNfL was predictive of evidence of disease activity (EDA). At one year, if treatment failed to decrease sNfL z-scores by ≥0.5 from baseline, there was an increased risk of EDA at two years (odds ratio 2.39); if the z-score increased from baseline, the risk of EDA was somewhat higher (OR 2.84). EDA risk was higher in treatment-naïve patients (OR 11.47). An increase in sNfL z-score in patients with a high Rio score was associated with a high risk of EDA (OR 42.659).
Relapse during pregnancy may speed progression
A Swiss study analysed the impact of relapses during pregnancy for 96 pregnancies in women with MS at the University Hospital Zurich in the period 2010-2023 (Walter et al. ECTRIMS 2024;P086). Overall, there were 33 cases (34%) of relapse during pregnancy or in the one year postpartum. Relapse was most common in the first trimester and commonly involved isolated sensory deficits. There was a higher risk of relapse in women with spinal lesions at the time of diagnosis and conception. Disability progression in the one year postpartum was more likely in women who relapsed during pregnancy or the first postpartum year compared to those who did not relapse (25.8% vs. 5.5%). Relapse frequency was lower in women receiving a disease-modifying therapy (66.7% vs. 87.3%).
PIRA? Which PIRA?
While progression independent of relapse activity (PIRA) has emerged as an important concept in MS, a significant limitation is the lack of a unified definition. Indeed, in its database analysis, the MSBase group were able to come up with 288 different definitions of PIRA (Muller et al. ECTRIMS 2024 ;P565). Definitions were various permutations of baseline disability, EDSS change, time from relapse and duration of the confirmation period. As expected, the frequency of PIRA events varied considerably depending on the definition, from 2.1 to 4.0 PIRA events/decade. The proportion of PIRA events without subsequent improvement ranged from 83% to 91%.
Clinical tip of the day
Vaping is a poor substitute for smoking cessation for people with MS (Odogwu et al. ECTRIMS 2024;P538). An analysis of the MS Register in the U.K. (N=12,293) found that disability scores were only slightly higher in current smokers compared to ex-smokers who now vape. Disability scores were lowest in non-smokers and ex-smokers who did not vape.