Assessment of Baseline Characteristics, Treatment Efficacy, and Serious Adverse Events among Natalizumab-Treated MS Patients without Prior Treatment (P06.172)

Abstract

Objective: Evaluate geographic region, enrollment time, baseline characteristics, postbaseline efficacy, and safety in natalizumab-treated multiple sclerosis (MS) patients with and without prior treatment. Background The ongoing natalizumab (TYSABRI®) Observational Program (TOP) assesses long-term outcomes in natalizumab-treated patients with relapsing-remitting MS in Europe, Australia, and Canada. Design/Methods: Baseline characteristics of treatment-naive and previously treated patients were compared. The association between prior treatment status and postbaseline annualized relapse rates (ARRs) was examined using a negative binomial regression model. Time to improvement on the Expanded Disability Status Scale (EDSS) was analyzed using a Cox proportional hazards model. Serious adverse events (SAEs) were compared using a Pearson chi-square or Fisher exact test. Results: As of June 1, 2011, 337 of 3484 natalizumab-treated patients (10%) had been treatment naive before natalizumab treatment. Proportions of treatment-naive patients varied significantly by country (Slovakia, 0%; Great Britain, 36%) and time since enrollment (0–12 months, 12%; 13–24 months, 7%; >24 months, 9%). Baseline differences between treatment-naive and previously treated patients included mean age (35.8 vs 37.6 years), median disease duration (1.9 vs 7.8 years), and median EDSS score (3.0 vs 3.5) (all P ≤0.013). Treatment-naive patients had a lower postbaseline ARR (0.18 vs 0.26; P =0.002) and were more likely to show improvement in EDSS at 3 years (HR [95% confidence interval]=1.59 [1.14–2.22]; P =0.007). Treatment-naive and previously treated groups did not significantly differ in incidence of SAEs (4.2% vs 5.2%; P =0.340), infection-related SAEs (0.9% vs 1.2%; P =0.640), or progressive multifocal leukoencephalopathy (0.0% vs 0.2%; P =1.00). Conclusions: Treatment-naive patients were younger than previously treated patients, had shorter disease duration and lower baseline EDSS, were more likely to show EDSS improvement, and differed significantly in geographic distribution and enrollment time. While relapses decreased in both groups, postbaseline ARR was significantly lower in treatment-naive patient, whereas SAE incidence was similar. Supported by: Biogen Idec Inc. and Elan Pharmaceuticals, Inc. Disclosure: 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. 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. 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. 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.