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Home - 12.10.2012 - Risk management for disease modifying treatments


Risk management for disease modifying treatments

Friday, October 12, 2012, 15:30 - 17:00

Natalizumab discontinuation in clinical practice: a systematic observational study from the national TYSEDMUS cohort of 577 multiple sclerosis patients treated with natalizumab in France

C. Papeix, S. Vukusic, N. Passante, I. Ionescu, B. Frangoulis, B. Stankoff, S. Oporto, S. Mrejen, E. Van ganse, F. Rocher, A. Castot, M. Clanet, C. Lubetzki, C. Confavreux on behalf of the TYSEDMUS Group

Background: Natalizumab (NZ), an anti-integrin monoclonal antibody, has shown efficacy in reducing the relapse rate and delaying disability accumulation in multiple sclerosis (MS) patients. In clinical practice, NZ may be discontinued because of concern about progressive multifocal leucoencephalopathy (PML), adverse events, inefficacy or desire to become pregnant. In phase 2 trials, disease activity after NZ interruption returned to levels similar to those seen prior to treatment. However, recent reports suggested that unusually severe relapses with high number of new T2 and gadolinium-enhancing lesions might occur following NZ interruption.
Objective: To assess disease activity within the 12 months period after NZ discontinuation in the TYSEDMUS study
Methods: In France, patients exposed at least once to NZ are included in the TYSEDMUS study, an observational and multicentric cohort, part of the French NZ Risk management Programme. We analyzed the relapse rate, relapse severity and confirmed disability (EDSS score) during a one year period (M0-M12) of all patients who stopped NZ and compared them to pre-treatment and on-treatment data. Time to first relapse after NZ withdrawal was calculated using Kaplan-Meier analysis.
Preliminary results: In May 2012, 3730 MS patients treated with NZ were included in the TYSEDMUS study and 2921 files have been fully analyzed so far. Among them, 577 patients (19.75%) discontinued treatment for various reasons. Kaplan Meier analysis showed that 50% of the patients experienced a relapse within one year. Most of these relapses occurred 3 to 5 months after NZ withdrawal. The relapse rate post NZ discontinuation was correlated to the relapse rate during the 12-month period before NZ initiation (OR =1.23) with no rebound effect. The influence of other disease-modifying treatments other than NZ and possibly initiated during this one year survey period is currently evaluated. In addition, data collection is currently completed to assess first relapse severity and recovery . The database will be closed in September 2012 and updated results will be presented at the meeting. .
Conclusions: This large and systematic survey of MS patients after NZ withdrawal did not show a rebound effect concerning the relapse rate. relapse severity post-NZ is currently evaluated. This study is the first attempt, to our knowledge, to provide large scale, multicenter, systematic and unbiased data after NZ cessation in real life settings.

Caroline Papeix reports receiving consulting fees from Biogen Idec, Novartis, Bayer- schering, Sanofi Aventis and Teva Pharma, Roche ; lecture fees from Bayer-Schering, Biogen Idec, Sanofi Aventis and Teva ; and participating in clinical trials for Biogen Idec, Novartis, Merck Serono, Bayer- schering, Sanofi Aventis and Teva Pharma , Genzyme and Roche Sandra. Vukusic reports receiving consulting fees from Biogen Idec, Novartis, Merck Serono, Sanofi Aventis and Teva Pharma ; lecture fees from Bayer-Schering, Biogen Idec, Merck Serono, Sanofi Aventis and Teva ; and research support from Bayer-Schering, Biogen Idec, Merck Serono, Sanofi Aventis and Teva. Nadine Passante has nothing to disclose Iuliana Ionescu has nothing to disclose Bernard Frangoulis has nothing to disclose Bruno Stankoff reports receiving consulting fees from Biogen Idec, Novartis, Merck Serono, Sanofi Aventis and Teva Pharma Bayer- schering ; lecture fees from Bayer-Schering, Biogen Idec, Merck Serono, Sanofi Aventis and Teva ; and research support from Bayer-Schering, Biogen Idec, Merck Serono, Sanofi Aventis and Teva. Sabrina Oporto has nothing to disclose Serge Mrejen has nothing to disclose Eric Van Ganse, has nothing to disclose Fanny Rocher has nothing to disclose Anne Castot has nothing to disclose Michel Clanet reports receiving consulting fees or research support from Biogen Idec, Genzyme Corporation, Novartis, Merck Serono, Sanofi Aventis, Teva Pharma, Roche Catherine Lubetzki reports consulting fees from Roche, Novartis, Sanofi Aventis and Teva Pharma, lecture fees from Merck-Serono, Biogen-Idec, Sanofi Aventis and Teva, participating in clinical trials for Biogen Idec, Novartis, Merck Serono, Bayer- schering, Sanofi Aventis and Teva Pharma , Genzyme and Roche. Christian Confavreux reports receiving consulting fees from Biogen Idec, Genzyme Corporation, Novartis, Merck Serono, Sanofi Aventis, Teva Pharma and UCB Pharma ; lecture fees from Bayer-Schering, Biogen Idec, LFB, Merck Serono, Sanofi Aventis and Teva Pharma ; and research support from Bayer-Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi Aventis and Teva Pharma.