A Five-Year Clinical Follow-Up Study Of Patients With Multiple Sclerosis Who Started Natalizumab (P7.215)

OBJECTIVE: To investigate the 5-year clinical outcomes of patients with relapsing-remitting multiple sclerosis (RRMS) who started natalizumab soon after the authorization by the Italian Pharmaceutical Agency. BACKGROUND: Natalizumab is a very effective treatment to prevent relapses and accumulation of disability due to RRMS, as shown in both pivotal trials and real-life studies. However, there are only few data on its long-term impact. DESIGN/METHODS: Data on patients who had at least 5-year follow-up after starting natalizumab were collected. They were divided into two groups according to treatment status at end of follow-up, i.e. continuing or discontinuing treatment. Annualised relapse rate (ARR), change from baseline in Expanded Disability Status Scale (EDSS) score, and proportion of patients free from clinical disease activity were defined as outcome measures. RESULTS: A total of 145 patients (100 F, 45 M) with mean (SD) age of 35.2 (8.9), median EDSS score of 3.0 (range 1.5-6.5), and mean number of relapses in pre-natalizumab year of 2.1 (0.9) were considered. Two patients were lost to follow-up. Continuing and discontinuing treatment groups accounted for 80 and 63 patients, respectively; there were no baseline between-group differences. Reasons for discontinuation were safety concerns for PML risk (n=34), anti-natalizumab antibodies (n=15), adverse events (n=6), pregnancy (n=4), shift to secondary progression (n=4). At the end of follow-up, we found significant differences between patients continuing and discontinuing treatment in terms of mean ARR (0.08 vs. 0.37, p<0.001), mean EDSS change (-0.17 vs. 0.68, p<0.001) and proportion of patients free from clinical disease activity (67% versus 19%, p<0.001). Other than discontinuing treatment (OR=16.31, p<0.001), female gender (OR=3.42, p=0.012) and greater number of pre-natalizumab relapses (OR=1.74, p=0.025), were independent predictors of disease activity during follow-up. CONCLUSIONS: Our findings support the notion of high and sustained clinical effectiveness of ongoing natalizumab treatment. Its discontinuation should be carefully evaluated, especially in highly active female patients. Study Supported by: None Disclosure: Dr. Prosperini has received personal compensation for activities with Biogen Idec, Teva Neuroscience, Novartis, and Bayer Schering. Dr. Barletta has nothing to disclose. Dr. De Giglio has nothing to disclose. Dr. Fanelli has nothing to disclose. Dr. Borriello has received personal compensation for activities with Biogen Idec, Bayer Schering Pharma, Merck & Co. Inc., Teva Neuroscience, and Novartis. Dr. Pozzilli has received personal compensation for activities with Merck Serono, Genzyme Corp., Biogen Idec, Bayer Pharmaceuticals Corp., Novartis, and Teva Neuroscience.