[P06.131] Sustained Improvement in Physical Disability with Natalizumab in Patients with Relapsing Multiple Sclerosis

Fredrick Munschauer, Buffalo, NY, Gavin Giovannoni, London, United Kingdom, Fred Lublin, New York, NY, Paul O'Connor, Toronto, ON, Canada, J. T. Phillips, Dallas, TX, Chris Polman, Amsterdam, The Netherlands, Amy Pace, Richard Kim, Michael Panzara, Wellesley, MA

OBJECTIVE: To evaluate the effect of natalizumab (TYSABRI) on sustained improvement in physical disability in patients with relapsing multiple sclerosis (MS). BACKGROUND: The risk of developing sustained disability progression, as measured by the Expanded Disability Status Scale (EDSS), is the most commonly used measure of neurologic disability in MS clinical studies. In the pivotal AFFIRM study, the risk of sustained disability progression was reduced by 42%54% over 2 years with natalizumab (P<0.001). However, sustained improvements on the EDSS have rarely been explored. DESIGN/METHODS: Post hoc analysis of data from patients enrolled in AFFIRM with an EDSS score 2.0 at baseline (natalizumab, n=417; placebo, n=203). Improvement in disability was defined as a 1.0-, 1.5-, or 2.0-point decrease in EDSS score sustained for 12 weeks. Treatment effects and baseline factors associated with sustained improvement at 2 years were estimated from a Cox proportional hazards model. RESULTS: Natalizumab significantly increased the cumulative probability of a 1.0-point EDSS improvement over 2 years by 69% relative to placebo (HR=1.69; 95% CI, 1.162.45; P=0.006). Sensitivity analyses showed that the effect of natalizumab was robust for up to 48-week sustained improvement. Higher EDSS score, shorter disease duration, and larger brain parenchymal fraction at baseline were significantly associated with this improvement; the treatment effect remained significant after adjusting for these variables (HR=1.69, CI=1.16-2.47; P=0.006). Natalizumab significantly increased the cumulative probability of both a 1.5-point EDSS improvement (HR=1.91; 95% CI, 1.06-3.45; P=0.030) and a 2.0-point EDSS improvement (HR=2.80; 95% CI, 1.17-6.66; P=0.020) over 2 years relative to placebo. Treatment effects were also significant for 24-week sustained 1.5-point and 2.0-point EDSS improvements (P=0.001 and P=0.040, respectively). CONCLUSIONS/RELEVANCE: Natalizumab significantly increased the cumulative probability of achieving a sustained improvement in disability in patients with relapsing MS. Supported by: Biogen Idec, Inc. and Elan Pharmaceuticals, Inc.
Category - MS and Related Diseases - Clinical Science

Wednesday, April 29, 2009 4:00 PM

Poster Session VI: Multiple Sclerosis: Therapeutics I (4:00 PM-7:00 PM)