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Natalizumab Induces Changes of Cerebrospinal Fluid Measures in Multiple Sclerosis
Ranjani Ganapathy Subramanian1, Dana Horakova1, Manuela Vaneckova2
1Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, 128 21 Prague, Czech Republic.
Background:
There is a lack of knowledge about the evolution of cerebrospinal fluid (CSF) markers in multiple sclerosis (MS) patients undergoing natalizumab treatment.
Aim:
We aimed to evaluate the effect of natalizumab on basic inflammatory CSF and MRI measures.
Methods:
Together, 411 patients were screened for eligibility and 93 subjects with ≥2 CSF examinations ≤6 months before and ≥12 months after natalizumab initiation were recruited. The effect of natalizumab on CSF as well as clinical and paraclinical measures was analyzed using adjusted mixed models.
Results:
Natalizumab induced a decrease in CSF leukocytes (p < 1 × 10-15), CSF protein (p = 0.00007), the albumin quotient (p = 0.007), the IgG quotient (p = 6 × 10-15), the IgM quotient (p = 0.0002), the IgG index (p = 0.0004), the IgM index (p = 0.003) and the number of CSF-restricted oligoclonal bands (OCBs) (p = 0.0005). CSF-restricted OCBs positivity dropped from 94.6% to 86% but 26 patients (28%) had an increased number of OCBs at the follow-up. The baseline to follow-up EDSS and T2-LV were stable; a decrease in the relapse rate was consistent with a decrease in the CSF inflammatory markers and previous knowledge about the effectiveness of natalizumab. The average annualized brain volume loss during the follow-up was -0.50% (IQR = -0.96, -0.16) and was predicted by the baseline IgM index (B = -0.37; p = 0.003).
Conclusions:
Natalizumab is associated with a reduction of basic CSF inflammatory measures supporting its strong anti-inflammatory properties. The IgM index at the baseline predicted future brain volume loss during the course of natalizumab treatment.
