Multiple sclerosisMonday, June 22, 2009, 17:30 - 19:00Natalizumab improves physical disability in patients with relapsing multiple sclerosisG. Giovannoni, F. Munschauer, P.W. O’Connor, J.T. Phillips, C.H. Polman, A. Pace, R. Kim, M.A. Panzara (London, UK; Buffalo, US; Toronto, CA; Dallas, US; Amsterdam, NL; Cambridge, US)
Objective: Sustained progression in disability, measured by an increase in Expanded Disability Status Scale (EDSS) score, is a standard measure of neurologic disability in clinical studies of patients with relapsing multiple sclerosis (MS). In the AFFIRM study, natalizumab (TYSABRI[R]) reduced the risk of sustained disability progression by 42%-54% over 2 years (P < 0.001). In addition, recent analyses from this study have shown that 83.6% of natalizumab-treated patients were free of disability progression over 2 years. In light of these results, it was of interest to explore the effects of natalizumab on the cumulative probability of sustained improvement in disability as measured by the EDSS.
Methods: This was a post hoc analysis of data from AFFIRM patients who had an EDSS score of 2.0 or higher 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 that was sustained for 12 weeks. Treatment effects and baseline factors associated with sustained improvement in disability at 2 years were estimated from a Cox proportional hazards model.
Results: The cumulative probability of a 1.0-point EDSS improvement sustained for 12 weeks over 2 years was increased by 69% with natalizumab relative to placebo (hazard ratio [HR] = 1.69; 95% confidence interval [CI], 1.16-2.45; P = 0.006). Sensitivity analyses showed that the effect of natalizumab remained significant when the definition of sustained improvement was extended to 24 and 48 weeks. Baseline disease variables that were associated significantly with improvement included higher EDSS score, shorter disease duration, and greater brain parenchymal fraction; the treatment effect remained significant after adjusting for these variables (HR = 1.69, 95% CI = 1.16-2.47; P = 0.006). Natalizumab significantly increased the cumulative probability of 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. The effects of natalizumab versus placebo also were significant for 1.5-point (P = 0.001) and 2.0-point (P = 0.040) EDSS improvements sustained for 24 weeks.
Conclusions: Natalizumab significantly increased the cumulative probability of sustained improvement in physical disability.
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