Natalizumab reduces loss of gray matter and thalamic volume in patients with relapsing-remitting multiple sclerosis: A post hoc analysis from the randomized, placebo-controlled AFFIRM trial.

Background: Loss of brain gray matter fractional volume predicts multiple sclerosis (MS) progression and is associated with worsening physical and cognitive symptoms. Within deep gray matter, thalamic damage is evident in early stages of MS and correlates with physical and cognitive impairment. Natalizumab is a highly effective treatment that reduces disease progression and the number of inflammatory lesions in patients with relapsing-remitting MS (RRMS).
Objective: To evaluate the effect of natalizumab on gray matter and thalamic atrophy.
Methods: A combination of deep learning-based image segmentation and data augmentation was applied to MRI data from the AFFIRM trial.
Results: This post hoc analysis identified a reduction of 64.3% ( p = 0.0044) and 64.3% ( p = 0.0030) in mean percentage gray matter volume loss from baseline at treatment years 1 and 2, respectively, in patients treated with natalizumab versus placebo. The reduction in thalamic fraction volume loss from baseline with natalizumab versus placebo was 57.0% at year 2 ( p < 0.0001) and 41.2% at year 1 ( p = 0.0147). Similar findings resulted from analyses of absolute gray matter and thalamic fraction volume loss.
Conclusion: These analyses represent the first placebo-controlled evidence supporting a role for natalizumab treatment in mitigating gray matter and thalamic fraction atrophy among patients with RRMS.
Clinicaltrials.gov Identifier: NCT00027300URL: https://clinicaltrials.gov/ct2/show/NCT00027300.
Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KN received licensing fees from Biogen; research funding to institution from Biogen, National Institutes of Health, National Multiple Sclerosis Society, Novartis, Patient-Centered Outcomes Research Institute (PCORI), Sanofi Genzyme, US Department of Defense. ZS, CH-C, KB, and RLA are employees of and own stock and/or stock options in Biogen. KB was an employee of and owned stock and/or stock options in Biogen at the time the research was conducted.