Contactin-1 (CNTN1) is a protein that is expressed in paranodal axonal domains and involved in myelin formation in the central nervous system (CNS) by way of axo-glia interaction, which is affected in multiple sclerosis (MS). Studying patients under natalizumab treatment provides a model to investigate correlations of novel biomarkers with non-inflammation induced disease progression in MS.
To investigate longitudinal serum CNTN1 in relation to clinical and radiological disease activity and progression independent of inflammatory disease activity in relapsing-remitting MS (RRMS).
Eighty-nine natalizumab-treated RRMS patients with minimum follow-up of 3 years were selected from an ongoing observational cohort study. Serum CNTN1 was analyzed at baseline before natalizumab initiation, and at 3, 12, 24 months and last follow-up. Clinical and radiological characteristics and CNTN1 levels were compared between patients with either progressive, stable or improved disability according to ‘EDSS plus’ criteria: Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT) and timed 25-foot walk test (T25W) combined. A significant change in at least one assessment was defined as progression (increase) or improvement (decrease), and no significant changes in any assessment as stability.
Forty-three subjects (48%) showed disability progression on EDSS plus between reference and last follow-up visit, 34 (38%) remained stable and 12 (13%) improved (median [interquartile range (IQR)] follow-up 5.2 [4.3-6.7] years). No statistically significant differences were found in the proportion of patients with clinical and radiological evidence of disease activity 1 year prior to baseline or during follow-up. Baseline serum CNTN1 (median [IQR], pg/mL) was significantly lower in the group with progressive disability (920 [798-1283]) compared to patients with either stable (1169 [861-1367] p=0.043) or improved disability (1133 [1046-1378], p=0.031). A 100 pg/ml increase in baseline CNTN1 was consistent with an odds ratio [95% confidence interval] of 0.809 [0.684-0.958] (p=0.014) for disability progression. Longitudinal serum CNTN1 levels remained consistently lower in the group with progressive disability compared to the non-progressive group (stable and improved group together).
Long-term disability progression in MS patients treated with natalizumab was associated with lower serum CNTN1 concentrations compared to patients with either stable or improved disability.