Prognostic blood and MRI biomarkers

In a Norwegian study, serum vitamin D levels were found to predict the long-term disease course of MS. Higher 25-hydroxy-vitamin D (25-OH-D) levels were associated with lower long-term disability in MS [1]. Neurofilament light chain (NfL) was found to correlate with cognitive impairment [2], while patients at higher risk of secondary progressive MS had more severe early brain atrophy [3].

Over a period of 2 years, serum levels of 25-OH-D were measured 9 times in 88 relapsing-remitting MS patients included in a randomised trial of omega 3 fatty acids (the OFAMS study). In 92% of participants, the expanded disability status scale (EDSS) could be assessed 10 years later [1]. The overall mean 25-OH-D levels in the baseline period was 74.0. The median EDSS score increased from 2.0 at baseline to 2.5 at follow-up. Higher 25-OH-D was associated with significantly lower disability progression 10 years later. Change in EDSS score per 20-unit increase in 25-OH-D was -0.5 (P=0.01).

CSF as well as blood NfL holds promise as a biomarker of disease course and treatment response in relapsing-remitting MS. The predictive value of NfL levels for cognitive impairment in patients with secondary progressive MS has now also been explored [2]. In consented participants of the EXPAND trial of siponimod, high baseline NfL levels were associated with an elevated risk for cognitive worsening, regardless of focal lesion activity. Patients with Gd+ T1 lesions at baseline had a more pronounced risk of cognitive worsening. A previous finding in the EXPAND study was that high NfL levels at baseline correlated with low baseline Symbol Digit Modalities Test (SDMT) scores. In 1,397 patients, high baseline NfL levels were associated with a 41.4% higher risk of reaching a 6-month confirmed worsening on SDMT (6mCWSDMT) by 4-points from baseline, compared to patients with low NfL levels. This higher risk was especially pronounced in patients with Gd+ T1 lesions at baseline (n=296/1,397; see Table).

Table: Risk of reaching 6-month confirmed worsening on Symbol Digit Modalities Test [2]

A study assessing long-term predictors of global cortical thinning found that patients with more severe early cortical pathology and demonstrating a faster rate of cortical thinning are at higher risk of converting to secondary progressive MS [3]. A total of 219 relapsing-remitting MS patients were followed for 7.9 mean years; 59 (27%) patients converted to secondary progressive MS. In a multivariate model, more severe global cortical thinning loss over time was independently predicted by:

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  • larger accumulation of cortical lesions (OR=3.47; P=0.01);
  • faster cortical thinning during the first 2 years (OR=1.43; P=0.001);
  • ≥3 early relapses (OR=8.41; P<0.001).

The authors concluded that early focal cortical damage and early relapses affect the severity of grey matter loss in the long term, and can be used to identify groups potentially benefiting from early aggressive treatment.

1. 
   
   1. Wesnes K, et al. EAN 2019, EPO3216.
   2. Kuhle J, et al. EAN 2019, EPO2201.
   3. Scalfari A, et al. EAN 2019, EPR2085.

 



Posted on 27 August, 201927 March, 2024