Natalizumab in Anti-JCV Antibody Negative Patients with Early RRMS: Prespecified Analysis of Optical Coherence Tomography (OCT) and Visual Acuity Data

Background: Earlier use of highly effective MS therapies have been shown to significantly improve clinical outcomes. Efficacy measures have typically included relapse rates and MRI changes. OCT is a non-invasive imaging technique that allows for quantitative measurement of retinal nerve fiber layer (RNFL) thickness. RNFL thinning has been seen in MS patients even in the absence of optic neuritis and may be a surrogate measure of overall disease activity and possibly neurodegeneration. Low contrast letter acuity has also been utilized as an efficacy measure in relapsing MS populations.

Objectives: In this analysis, natalizumab’s effects on RNFL thickness and high (100%) and low contrast (2.5%, 1.25%) visual acuity (VA) were assessed in a STRIVE study population subset.

Methods: STRIVE is a phase 4, multicenter, observational, open-label, single-arm study of natalizumab in anti-JC virus antibody negative patients early in their disease course. RNFL thickness (via OCT) and VA were assessed in a patient subset at baseline and month 24. Baseline characteristics were analyzed via summary statistics for continuous variables and frequency distribution for categorical variables. Clinical/radiologic changes from baseline were summarized using frequency distribution. Generalized estimating equation models, adjusting for age and baseline RNFL thickness, were used to assess changes from baseline in RNFL thickness.

Results: Baseline characteristics for the 41 patients with available 24-month OCT data confirm active early MS disease population with a mean time since time to first MS symptoms of 2.85 years. At baseline, the mean Expanded Disability Status Scale score was 1.89, annualized relapse rate was 1.8, and 39% of patients had not received prior disease-modifying therapies. Mean (SD) baseline RNFL was 97.20 (13.22) μm. At month 24, the overall change ranged from –1.14 to –1.29 μm (overall percentage changes from baseline ranged from –1.14% to –1.29%). This population also had slight visual changes, as assessed by high and low contrast acuity measurements. A small percentage of patients (10.5%) experienced a loss defined by ≥5 letters at high contrast. At low contrast (2.5% and 1.25%), worsening defined by ≥7 letters was experienced by 9.8% and 22.0% of patients, respectively.

Conclusions: In MS patients treated early in their disease course, natalizumab treatment was associated with relative preservation of RNFL and low contrast VA in a 2-year follow-up.

Support: Biogen