Real-World Relapsing-Remitting Multiple Sclerosis (RRMS) Patients in the Tysabri® Observational Program (TOP) Who Discontinued Natalizumab: Why They Stopped, Which Therapies They Switched To, and How Their Disease Activity Changed (P2.399)

Objective: To examine the reasons patients discontinue natalizumab, subsequent therapies used, and post-discontinuation changes in disease activity. Background: TOP is an ongoing, 10-year, multinational observational study following natalizumab-treated RRMS patients in clinical practice settings. Design/Methods: The yearly likelihood of discontinuation was estimated using Kaplan-Meier analysis. Reasons patients (N=2896) discontinued were assessed by year. Subsequent therapy was described for patients with ≥1 year of post-discontinuation follow-up (n=1457). Patients who discontinued after ≥2 years receiving natalizumab with ≥1 year of post-discontinuation follow-up were assessed for disease activity. Results: The probability of discontinuation was higher during year 2–3 of natalizumab treatment (15.7%) than during years 0–1 (10.1%), 1–2 (11.2%), or 3–4 (9.5%). Overall, progressive multifocal leukoencephalopathy (PML) risk concern was the most common reason for discontinuation (45% of patients) followed by insufficient efficacy (14.0%), non-PML related safety (9.7%) and tolerability (6.9%). Most patients discontinuing natalizumab switched to fingolimod (58.6%), dimethyl fumarate (10.6%), interferon beta (10.2%), or glatiramer acetate (9.5%). The disease activity analysis population had median (range) time on natalizumab of 2.9 (2.0–7.2) years and post-discontinuation follow-up time of 2.6 (1.0–7.0) years. On-treatment annualized relapse rates (ARRs) were 86.6% lower than pre-natalizumab ARRs; after discontinuation, ARRs increased by 34.2% but remained lower than pre-natalizumab rates (n=1024). More patients had improved EDSS scores (38.3%) and fewer patients had worsened EDSS scores (27.0%) on natalizumab (n=992) than on the first post-discontinuation therapy (17.4% and 38.3%, respectively; n=904). Effectiveness by post-discontinuation therapy was also assessed. Conclusions: Overall, the majority of discontinuations were because of PML concerns, most of which occurred during year 2–3. Among patients with sufficient data to assess treatment effectiveness, increases in relapse activity and EDSS scores were observed after natalizumab discontinuation. Study Supported by: Biogen Disclosure: Dr. Trojano has received personal compensation for activities with Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals, Teva neuroscience as a consultant and speaker. Dr. Trojano has received research support from Biogen Idec, Merck Serono, and Novartis. Dr. Butzhueven has received personal compensation for activities with Oxford Pharmagenesis, Medscape, TTY Pharma; Biogen, Novartis, Teva; Merck, and Genzyme as a consultant, speaker or member of a scientific advisory board. Dr. Kappos has reveived personal compensation for activities with University Hospital Basel as an advisory board member. Dr. Kappos has received research support from Swiss Multiple Sclerosis Society, Swiss National Research Foundation, European Union, Gianni Rubatto Foundation, Novartis Research Foundation, and Roche Research Foundation. Dr. Spelman has received personal compensation for activities with Biogen Idec and Novartis as a speaker. Dr. Wiendl has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi Aventis, Bayer Vital GmbH, Bayer Schering AG, Biogen Idec, and CS. Dr. Wiendl has received research support from Bayer HealthCare, Biogen Idec, the German Ministry for Education and Research, Deutsche Forschungsgesellschaft, and the Else Kroner Fresenius Foundation Dr. Chen 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.