Sustained Disability Improvement as Assessed by a Multicomponent Endpoint in Secondary Progressive Multiple Sclerosis (SPMS) Patients: A Post Hoc Analysis from ASCEND (P5.359)

Objective: To examine sustained disability improvement in ASCEND. Background: Previous analyses in relapsing-remitting multiple sclerosis patients demonstrated improvements in baseline disability and functional impairment with natalizumab treatment, but such outcomes have never been explored in SPMS patients. Design/Methods: ASCEND, a multicenter, double-blind, phase 3 trial, enrolled natalizumab-naive patients diagnosed with SPMS ≥2 years prior and had disability progression unrelated to clinical relapses in the past year; patients were randomized to 300 mg natalizumab (n=439) or placebo (n=448) intravenous treatment for 2 years. Disability improvement was defined as a multicomponent endpoint of improvement on ≥1 of 3 components (Expanded Disability Status Scale [EDSS; ≥0.5-point decrease from baseline score of 6.0–6.5 or ≥1.0-point decrease from baseline score of 3.0–5.5], Timed 25-Foot Walk [T25FW; ≥15% decrease from baseline], or 9-Hole Peg Test [9HPT; ≥15% decrease from baseline on either hand]) confirmed at all consecutive visits over a ≥6 month period and improved or stable at last visit. Alternative definitions of improvement were explored with similar results. Data were analyzed via logistic regression model adjusted for baseline EDSS, T25FW, and 9HPT. Results: Most participants had advanced disability at baseline (63% had EDSS scores of 6.0–6.5), and 71% had no relapses within the 2 years before enrollment. Significantly more participants receiving natalizumab (32%) than placebo (22%) met the multicomponent criteria (OR=1.67 [95% CI: 1.23–2.26]; P =0.001). Analysis of individual components showed improvement consistently favored natalizumab patients on all components. Among those meeting T25FW or 9HPT improvement criteria, average magnitudes of improvement from baseline were 12.4%–15.4% at week 12 and 27.1%–28.2% at week 96. Conclusions: In this post hoc analysis, natalizumab was associated with disability improvements over 2 years in an SPMS population with severe baseline disability, suggesting additional benefits beyond the treatment effect of slowing disability progression on the 9HPT component of ASCEND’s primary endpoint. Study Supported by: Biogen Disclosure: Dr. Giovannoni has received personal compensation for activities with AbbVie, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, Merck Serono, Novartis, Protein Discovery Laboratories, Roche, Synthon, Teva Neuroscience, UCB, and Vertex for honoraria. Dr. Giovannoni has received personal compensation from Elsevier in a co-chief editor capacity of MS and Related Disorders. Dr. Giovannoni has received research support from Biogen, Ironwood, Merck Serono, Merz, and Novartis. Dr. Steiner has nothing to disclose. Dr. Sellebjerg has received personal compensation for activities with Biogen, EMD Serono, Genzyme, Lundbeck, Merck Serono, Novartis, and Teva. Dr. Sellebjerg has received research support from Biogen, EMD Serono, Genzyme, Lundbeck, Merck Serono, Novartis, and Teva. Dr. Cohan has received personal compensation for activities with Biogen, Mallinckrodt, Novartis and Sanofi-Genzyme, Acorda, Genentech. Dr. Cohan has received research support from Biogen, Genentech, Mallinckrodt, Novartis, Opexa, Roche and Sanofi-Genzyme. Dr. Jeffery has received personal compensation for activities with Acorda, Bayer, Biogen, Genentech, GlaxoSmithKline, Novartis, Questcor, Serono, and Teva as a speaker and consultant. Dr. Jeffery has received research support from Biogen and Genentech. Dr. Rog has received research support from Biogen Idec, Genzyme, GW Pharma, Merck Serono, Mitsubishi, Novartis, and Teva Neuroscience. Dr. Chen has received personal compensation for activities with Biogen as an employee. Dr. Dong has received personal compensation for activities with Biogen as an employee. Dr. Ho has received personal compensation for activities with Biogen as an employee. Dr. Ho holds stock and/or stock options in Biogen. Dr. Campbell has received personal compensation for activities with Biogen as an employee. Dr. Cadavid has received personal compensation for activities with Biogen as a holder of stock and/or stock options and as an employee. Dr. Amarante has received personal compensation from Biogen as an employee. Dr. Amarante holds stock and/or stock options in Biogen.