Changes in Whole Brain Volume and Cortical Gray Matter over 2 Years of Natalizumab Treatment: Results from the Strive Study

Background: The STRIVE study has demonstrated improvements in disability and cognitive function with natalizumab treatment over 2 years in patients with early relapsing-remitting multiple sclerosis (RRMS; <3 years post diagnosis). In STRIVE, 56.1% of STRIVE patients achieved no evidence of disease activity (NEDA) in the first year of treatment and 73.6% of patients achieved NEDA in the second year of treatment. However, brain volume changes have not been previously described in this study population.

Objectives: To evaluate temporal patterns of changes in whole brain volume and cortical gray matter over 2 years of natalizumab treatment in patients with early RRMS.

Methods: STRIVE is an ongoing, multicenter, observational, open-label study in anti-JC virus antibody negative patients with early RRMS initiating natalizumab. Magnetic resonance imaging (MRI) was conducted at baseline, year 1, and year 2. MRI scans were read by NeuroRX. Percent brain volume change (PBVC) was assessed using the Structural Image Evaluation, using Normalisation, of Atrophy (SIENA) method. Brain parenchyma and cortical gray matter volumes were calculated using SIENAX, and cortical gray matter atrophy is assessed as a percent of total brain parenchyma volume. 

Results: At baseline, the intent-to-treat population (N=222) had a mean (standard deviation [SD]) age of 34.0 (8.97) years, mean (SD) time since RRMS diagnosis of 1.6 (0.8) years, and a mean (SD) EDSS score of 2.0 (1.1). During the first year of treatment, patients exhibited a median (95% confidence interval [CI]) PBVC of −0.61 (−0.80, −0.57) (n=177). Over 2 years, median (95% CI) PBVC was −1.00 (−1.31, −0.96) (n=137). Median (95% CI) cortical gray matter fraction change from baseline was −0.17 (−0.25, 0.04) (n=167) in the first year and −0.34 (−0.47, −0.17) (n=139) over 2 years.

Conclusions: Over 2 years of natalizumab treatment in STRIVE, a median of 1% whole brain volume loss was observed, and temporal patterns of whole brain volume change were consistent with previous studies of natalizumab. Additional analyses will be performed to further characterize these brain volume changes, and to determine baseline predictors of subsequent atrophy and NEDA status in patients on natalizumab.

Support: Biogen