Natalizumab stabilizes physical, cognitive, MRI, and OCT markers of disease activity: A prospective, non-randomized pilot study.

Garrick D Talmage,Oscar J M Coppes,Adil Javed,Jacqueline Bernard

doi:10.1371/journal.pone.0173299

Abstract

Natalizumab is an effective therapy for multiple sclerosis (MS). Its effectiveness has been demonstrated in several clinical and imaging studies. The objective of this study was to further demonstrate the efficacy of natalizumab using a comprehensive battery of clinical and imaging markers in the same cohort of patients followed longitudinally, hence capturing the multi-faceted nature of the MS disease process. A prospective, open-label, pilot study of 20 MS patients treated with natalizumab was conducted. High resolution MRI, Symbol-Digit Modalities Test (SDMT), and Optical Coherence Tomography (OCT) scans were obtained at baseline, 48, and 96 weeks. 15 patients completed the study. Natalizumab treatment decreased Expanded Disability Status Scale score (EDSS) and no change in SDMT, Brain Parenchymal Fraction (BPF), or any of the OCT markers of retinal degeneration was observed. Thalamic and whole brain volume as assessed by Percentage Brain Volume Change (PBVC) showed continuous deterioration. Higher baseline T2 lesion load correlated with increased rate of PBVC at 96-weeks (r = 0.566, R2 = 0.320, p = 0.035) and thalamic volume loss (r = -0.586, R2 = 0.344, p = 0.027). Most patients, 93%, achieved no evidence of disease activity (NEDA) at 2 years, likely due to early disease duration and lower initial baseline lesion load. This study further demonstrates stabilization of clinical and imaging markers of disease activity during natalizumab treatment.

Highlights

Relapsing-remitting multiple sclerosis (RRMS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) resulting in progressive neuronal and axonal loss in the gray and white matter, leading to both physical and cognitive disability [1]
Reported p-values are for Type III tests of Metric* Oral Symbol-Digit Modalities Test (SDMT) z-score Expanded Disability Status Scale score (EDSS), median (IQR) Brain Parenchymal Fraction Gray Matter Fraction White Matter Fraction Normalized Thalamic Volume Normalized Hippocampal Volume Retinal Nerve Fiber Layer thickness Macular Volume
This prospective, open-label, observational study showed that natalizumab treatment over a 96-week period was associated with disease stability as measured by EDSS and SDMT and as per MRI surrogate markers of disease activity

Summary

Introduction

Relapsing-remitting multiple sclerosis (RRMS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) resulting in progressive neuronal and axonal loss in the gray and white matter, leading to both physical and cognitive disability [1]. Cognitive dysfunction occurs early in the disease course of MS and is an important factor in the quality of life of patients [2,3,4]. Physical and cognitive decline in RRMS has been correlated to changes in several imaging modalities [5,6,7]. These studies have hypothesized that irreversible neurodegeneration may occur early in the disease course and may be central to the development of long-term physical and cognitive disability.

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