Comparison of CSF biomarkers in multiple sclerosis patients treated with natalizumab and rituximab.

BACKGROUND

Patients with relapsing remitting multiple sclerosis (RRMS) treated with the high-efficacy drugs natalizumab (NTZ) or rituximab (RTX) generally show no evidence of disease activity. Currently, there is no head-to-head comparison between NTZ and RTX of neurodegenerative and neuroinflammatory biomarkers in cerebrospinal fluid (CSF).

OBJECTIVES

To compare CSF biomarkers in a stable RRMS cohort treated with NTZ or RTX. A secondary objective was to explore potential associations between CSF biomarkers, fatigue, and cognition.

METHODS

This Swedish multicentre cross-sectional study assessed kappa-free light chain (k-FLC) index, oligoclonal bands (OCBs), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in CSF of 30 RRMS patients on NTZ or RTX for at least 24 months. A longitudinal comparison of biomarkers was performed for IgG Indices. Fatigue and cognition outcomes were explored in relation to CSF biomarkers.

RESULTS

GFAP level was significantly higher in the NTZ group compared to RTX (mean difference (CI): 2 716 (155; 5278) ng/L, p=0.047). NfL concentration did not differ between the groups. OCBs and k-FLC index were present and elevated in 97 % and 87 % of participants, respectively. IgG-index was significantly reduced only for NTZ. No significant associations were found between fatigue, cognition and the biomarkers.

CONCLUSION

Our results support that intrathecal inflammatory activity is still ongoing in patients with NTZ and RTX. Cross-sectional GFAP might indicate a lower risk for long-term disability in the RTX group. Our data should be interpreted with caution because of small sample size, making it difficult to control for multiple confounders.