Long-Term Safety and Efficacy and Association between Baseline Treatment History and Postbaseline Relapses in Multiple Sclerosis Patients Treated with Natalizumab in the TYSABRI(R) Observational Program (TOP) (P04.134)

Abstract

Objective: Evaluate long-term safety, efficacy, and associations between baseline treatment history and postbaseline annualized relapse rate (ARR) in multiple sclerosis (MS) patients treated with natalizumab. Background The ongoing natalizumab (TYSABRI®) Observational Program (TOP) study is an open-label, multinational, observational study assessing long-term outcomes in relapsing-remitting MS patients in the postmarketing setting in Europe, Australia, and Canada. Design/Methods: As of June 2011, 3484 patients from 15 countries were enrolled. Incidence of serious adverse events (SAEs) was analyzed. ARR and Expanded Disability Status Scale (EDSS) scores were assessed. Associations between baseline therapy and postbaseline ARR were analyzed using negative binomial regression for 5 baseline groups: therapy naive (n=337), interferon (IFN) only (n=1626), glatiramer acetate (GA) only (n=288), switched between GA and IFN in either order (n=595), or immunosuppressant (IS) use (n=487). Results: - 53]) natalizumab infusions. Overall, 5.1% of patients experienced ≥1 SAE; infections (1.1%) and hypersensitivity reactions (0.7%) were most frequent. Seven cases of progressive multifocal leukoencephalopathy (PML) occurred after 35, 29, 28, 26, 24, 24, and 12 natalizumab infusions. Three of them were previously exposed to mitoxantrone. Overall, the mean EDSS score was 3.5 at baseline and 3.4 after 3 years. ARR was significantly decreased regardless of baseline treatment history; mean ARR decreased (n=3458) from baseline (1.98) to postbaseline (0.28; P Conclusions: The overall incidence and type of SAEs reported in TOP are consistent with natalizumab9s known safety profile. EDSS scores were stable and ARR was significantly reduced after 3 years of natalizumab therapy. ARRs were lowest in therapy-naive patients and highest in patients with prior IS. Supported by: Biogen Idec Inc. and Elan Pharmaceuticals, Inc. Disclosure: Dr. Kappos has received research support from Acorda Therapeutics, Actelion, Allozyne, BaroFold, Inc., Bayer Pharmaceuticals Corporation, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim Pharmaceuticals, Inc, Elan Corporation, Genmab, GlaxoSmithKline, Inc., Glenmark Pharma, Merck Serono, MediciNova, Novartis, Sanofi-Aventis Pharmaceuticals, Santhera Pharmaceuticals, Shire, Roche Diagnostics, Teva Neuroscience, UCB Pharma, Pfizer Inc, Swiss MS Society, Swiss National Research Foundation, European Union, Gianni Rubatto Foundation, Novartis and Roche Research Foundations. Dr. Belachew has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec and Merck Serono as a consultant. Dr. Belachew has received research support from Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals, and Teva Neuroscience. Dr. Butzkueven has received personal compensation for activities with Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals, Inc., National Health and Medical Research Council, and National MS Society. Dr. Butzkueven has received personal compensation in an editorial capacity for Multiple Sclerosis International Federation and Multiple Sclerosis. Dr Butzkueven has received research support from Biogen Idec, Merck Serono, and Novartis. Dr. Pellegrini has received personal compensation for activities with Biogen Idec as a consultant. Dr. Trojano has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec and Sanofi-Aventis Pharmaceuticals, Inc. as a consultant and/or speaker. Dr. Trojano has received research support from Merck & Co., Inc. Dr. Wiendl has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Merck Serono, Novo Nordisk, Sanofi-Aventis Pharmaceuticals, Inc., Schering AG and Teva Neuroscience. Dr. Wiendl has received research support from Bayer Pharmaceuticals Corporation, Biogen Idec, Medac, Merck-Serono, Novo Nordisk, Sanofi-Aventis Pharmaceuticals, Inc., Schering AG and Teva Neuroscience. Dr. Zhang has received personal compensation for activities with Biogen Idec as an employee. Dr. Hotermans has received personal compensation for activities with Biogen Idec as an employee.Dr. Hotermans holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Hotermans was involved as an investigator.