Impact of Natalizumab on Ambulatory Improvement in Secondary Progressive and Disabled Relapsing-Remitting Multiple Sclerosis

Background: There is an unmet need for disease-modifying therapies to improve ambulatory function in disabled subjects with multiple sclerosis. Objectives: Assess the effects of natalizumab on ambulatory function in disabled subjects with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS). Methods: We retrospectively reviewed ambulatory function as measured by timed 25-foot walk (T25FW) in clinical trial subjects with an Expanded Disability Status Scale score >= 3.5, including RRMS subjects from the phase 3 AFFIRM and SENTINEL trials, relapsing SPMS subjects from the phase 2 MS231 study, and nonrelapsing SPMS subjects from the phase 1b DELIVER study. For comparison, SPMS subjects from the intramuscular interferon beta-1a (IM IFN beta-1a) IMPACT study were also analyzed. Improvement in ambulation was measured using T25FW responder status; response was defined as faster walking times over shorter (6-9-month) or longer (24-30-month) treatment periods relative to subjects' best predose walking times. Results: There were two to four times more T25FW responders among disabled MS subjects in the natalizumab arms than in the placebo or IM IFNb-1a arms. Responders walked 25 feet an average of 24%-45% faster than nonresponders. Conclusion: Natalizumab improves ambulatory function in disabled RRMS subjects and may have efficacy in disabled SPMS subjects. Confirmation of the latter finding in a prospective SPMS study is warranted.