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Ongoing Neuronal Loss Is Greater in Secondary Progressive MS Than Primary Progressive MS

Serum levels of neurofilament light chain may be a prognostic biomarker of brain atrophy.


 

BERLIN—Levels of neurofilament light chain (NfL) indicate that patients with secondary progressive multiple sclerosis (MS) have more ongoing neuronal loss than patients with primary progressive MS of comparable age, both in the presence and in absence of gadolinium enhancing lesions, according to research presented at ECTRIMS 2018. In secondary progressive MS and primary progressive MS, NfL may serve as a prognostic marker of brain atrophy, said the investigators.

NfL is considered a blood biomarker for monitoring neuronal damage, disease activity, and treatment response in MS. Most studies of blood NfL have focused on patients with relapsing-remitting MS, and little is known about blood NfL levels in patients with progressive MS.

Jens Kuhle, MD, PhD

Jens Kuhle, MD, PhD, Head of the MS Center at University Hospital Basel in Switzerland, and colleagues, compared baseline blood NfL levels and assessed the prognostic potential of NfL for brain atrophy in patients with primary progressive MS and secondary progressive MS in placebo-controlled phase III trials of fingolimod (ie, INFORMS) and siponimod (ie, EXPAND).

The researchers retrospectively analyzed blood NfL levels in 1,452 patients with secondary progressive MS (mean age, 48.2; Expanded Disability Status Scale [EDSS], 5.4) and 378 patients with primary progressive MS (mean age, 48.7; EDSS, 4.6). They quantified NfL levels at baseline using single molecule array technology and grouped them into the categories of low (< 30 pg/mL), medium (30–60 pg/mL), and high (> 60 pg/mL). High and low baseline NfL categories were compared using Chi-square and Wilcoxon rank sum tests. Dr. Kuhle and colleagues examined the association of baseline NfL levels with MRI parameters by Spearman rank correlation (gadolinium enhancing lesion count, T2 lesion volume) and the Jonckheere Terpstra test (brain volume change).

NfL levels at baseline were higher in patients with secondary progressive MS than in patients with primary progressive MS (32.1 pg/mL vs 22.0 pg/mL). A similar trend was observed when patients of the same age were compared. Patients with secondary progressive MS had higher NfL levels than those with primary progressive MS.

Similarly, patients with no gadolinium enhancing lesions at baseline had NfL levels of 29.2 pg/mL and 21.0 pg/mL in secondary progressive MS and primary progressive MS, respectively, while patients with gadolinium enhancing lesions had NfL levels of 45.0 pg/mL in secondary progressive MS and 34.0 pg/mL in primary progressive MS. The gadolinium enhancing lesion count and T2 lesion volume at baseline correlated best with baseline NfL. In secondary progressive MS and primary progressive MS, high NfL at baseline was associated with higher percentage of brain volume loss at Month 12 (high NfL vs low NfL: −0.8% vs −0.2% in secondary progressive MS and −0.8% vs −0.4% in primary progressive MS) and at Month 24 (−1.5% vs −0.5% in secondary progressive MS and −1.9% vs −0.8% in primary progressive MS).

The study was funded by Novartis Pharma.

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