Natalizumab in Anti-JCV Seronegative Patients with Early MS: STRIVE Study

Background: In the ongoing TYSABRI^®Observational Program (TOP), natalizumab appears most effective in treatment-naïve MS patients and in MS patients with lower Expanded Disability Status Scale (EDSS) scores. However, use of natalizumab in early MS stages has not been systematically studied.

Objectives: To determine characteristics associated with freedom from overall disease activity (no 24-week confirmed EDSS progression, no relapses, no gadolinium-enhancing lesions, and no new or enlarging T2-hyperintense lesions) at years 1 and 2 and freedom from clinical disease activity (no 24-week confirmed EDSS progression and no relapses) at years 3 and 4 in natalizumab-treated patients with relapsing-remitting MS (RRMS).

Methods: STRIVE is a prospective, multicenter, single-arm observational study (duration up to 4 years) of patients initiating treatment with natalizumab. Patients 18–50 years of age with a RRMS diagnosis of ≤3 years’ duration and an EDSS score ≤4.0 and who test negative for anti-JCV antibodies ≤6 months prescreening or at baseline are eligible. Less than 36 months’ total prior treatment with interferon beta, glatiramer acetate, or fingolimod is permitted.

Results: Enrollment began December 2011, with plans to enroll approximately 300 patients at 60 US centers. Primary endpoints are proportion of patients free of overall disease activity at years 1 and 2 and proportion of patients free of clinical disease activity at years 3 and 4. Additional endpoints include 24-week confirmed EDSS progression, relapse rate, magnetic resonance imaging measures, and patient-reported outcomes of cognitive function (Symbol Digit Modalities Test), capacity to work (Work Productivity and Activity Impairment Questionnaire), and quality of life (Multiple Sclerosis Impact Scale). Associations between early and long-term responses (relevant response factors identified by predictor analysis method), adjusting for potential confounding factors, will be examined. In a subset of approximately 100 patients, retinal function and vision will be evaluated through optical coherence tomography and low-contrast visual acuity testing. Baseline data will be presented.

Conclusions: STRIVE will systematically examine natalizumab use in early MS and will provide data on patient characteristics associated with freedom from disease activity over 2–4 years. This may assist in benefit/risk–based treatment decisions for anti-JCV antibody negative patients with early RRMS.