American Academy of Neurology annual meeting – April 17-22, 2021
CONGRESS HIGHLIGHTS – TUESDAY EDITION
A post-hoc analysis of CIS patients in the REFLEX trial of interferon-β-1a demonstrated that high baseline serum NfL levels were prognostic of conversion to clinically-definite MS (Kuhle J. AAN 2021; P.001). High vs. low NfL was defined by a median sNfL concentration cut-off of 26.1 pg/mL. Patients with lower sNfL had a 42% reduced risk of CDMS compared to those with higher baseline values.
Serum NfL was elevated in 17% of MS patients in the MSPATHS network database (N=6,968) (Sotirchos ES. AAN 2021; S25.001). Cut-off values were derived from data from healthy controls. Risk factors for elevated sNfL were diabetes (OR 1.89), progressive MS (odds ratio 1.63), current smoking (OR 1.49) and non-white race (OR 1.43). Risk was lower in obese subjects (OR 0.83 per 5 kg/m2). Overall, the highest levels were seen in younger patients with a shorter disease duration. Higher sNfL was associated with worse physical and cognitive function, lower brain parenchymal fraction and higher T2 lesion volume.
Secondary autoimmunity is a common complication of treatment with alemtuzumab. In an analysis of 54 RRMS patients (median age 28 years) receiving alemtuzumab for a median of 2.8 years, 25.9% developed an autoimmune thyroid condition (Delgado et al. AAN 2021; P.007). Patients with autoimmune complications had a higher percentage of B cells, primarily plasmablasts and naïve cells, and an increase in the proportion of CD4+ T cells producing TNF-α. The ratio of B cells/T cells-TNF was useful to stratify autoimmune risk: a B/T-TNF ratio >0.5 was associated with a 52-fold increased risk of autoimmune adverse events.
Data from the Swedish MS Registry were used to determine the change in EDSS score over time in a population of SPMS patients (N=1635) (Bezlyak et al. AAN 2021; P.043). The index period was 2001 to 2019. The mean annual change in EDSS score was 0.4, 0.6, 0.9, 1.1 and 1.3 in the five years post-index. Notably, about 25% of patients did not have EDSS worsening during the follow-up.
Three imaging studies have reported the effects of siponimod in SPMS patients. In the EXPAND study extension, there was a slower rate of whole-brain volume loss with continuous siponimod vs. placebo/siponimod (-1.62% vs. -1.76%) (Arnold DL. AAN 2021; P.083). Similar advantages were seen with respect to the annualized rate of brain atrophy and grey-matter atrophy, indicating a sustained benefit with earlier treatment.
An exploratory analysis of the EXPAND dataset examined the predictive value of magnetization transfer ratio (MTR) findings on clinical endpoints (Fox RJ. AAN 2021; P.092). Results were compared for the worst quartile vs. best quartile. MTR-cortical grey matter was associated with a higher risk of 6-month confirmed disability progression (hazard ratio 1.93 for worse vs. best quartile). Similar results were seen for cGM volume (HR 1.58). In the core + extension, cGM (HR 1.30) and thalamic volume (HR 1.66) were predictive of a worse composite 6M-CDP + SDMT.
A separate analysis of EXPAND examined MRI predictors of cognitive processing speed (Benedict et al. AAN 2021; P.009). As with physical outcomes, cGM and thalamic volume were significant predictors of 6-month confirmed cognitive worsening. The results suggest that imaging measures may be useful in predicting a decline in cognitive processing speed in SPMS patients.