Maëlle Chappuis1, Chloé Rousseau2, Emma Bajeux3, Sandrine Wiertlewski4, David Laplaud4, Emmanuelle Le Page5,6, Laure Michel5,6, Gilles Edan5,6, Anne Kerbrat5,6. 1. Department of Neurology, University Hospital, Rennes, France. maelle.chappuis@chu-rennes.fr. 2. Research Management Department, University Hospital, Rennes, France. 3. Department of Epidemiology and Public Health, University Hospital, Rennes, France. 4. Department of Neurology, University Hospital, Nantes, France. 5. Department of Neurology, University Hospital, Rennes, France. 6. CIC-P 1414 Inserm, University Hospital, Rennes, France.
Abstract
BACKGROUND AND PURPOSE: There has been scant research on the consequences of discontinuing second-line disease-modifying treatment (DMT) in middle-aged patients with multiple sclerosis (MS). The objective was therefore to examine the occurrence of focal inflammatory activity after the discontinuation of second versus first-line DMT in patients over 45 years. METHODS: Patients who had been treated for at least 6 months with second (natalizumab, fingolimod, anti CD20) or first-line DMT and who stopped their DMT were retrospectively included. Kaplan-Meier survival curves were used to study the occurrence of relapse and MRI activity according to the type of DMT stopped. Proportional hazard Cox models were calculated to identify factors associated with focal inflammatory activity. The annualized relapse rate was calculated under treatment and for every 3 months after DMT discontinuation. RESULTS: We included 232 patients (median age: 52.8 years), 49 of whom stopped second-line DMT. The probability of having a relapse within the year following discontinuation was 6% for first-line DMT, 9% for fingolimod and 43% for natalizumab. In multivariate analysis, the probability of relapse after DMT discontinuation was significantly increased with natalizumab compared to first-line DMT (HR = 3.24; 95% CI [1.52; 6.90]). A peak of relapse was observed at 0-3 months after stopping natalizumab or fingolimod. CONCLUSION: Our study suggests that the risk of inflammatory activity is greater after discontinuation of natalizumab compared to other DMT even in middle-aged patients. As for younger patients, natalizumab discontinuation should only be considered if there is an adequate substitution of a different therapy. .
BACKGROUND AND PURPOSE: There has been scant research on the consequences of discontinuing second-line disease-modifying treatment (DMT) in middle-aged patients with multiple sclerosis (MS). The objective was therefore to examine the occurrence of focal inflammatory activity after the discontinuation of second versus first-line DMT in patients over 45 years. METHODS: Patients who had been treated for at least 6 months with second (natalizumab, fingolimod, anti CD20) or first-line DMT and who stopped their DMT were retrospectively included. Kaplan-Meier survival curves were used to study the occurrence of relapse and MRI activity according to the type of DMT stopped. Proportional hazard Cox models were calculated to identify factors associated with focal inflammatory activity. The annualized relapse rate was calculated under treatment and for every 3 months after DMT discontinuation. RESULTS: We included 232 patients (median age: 52.8 years), 49 of whom stopped second-line DMT. The probability of having a relapse within the year following discontinuation was 6% for first-line DMT, 9% for fingolimod and 43% for natalizumab. In multivariate analysis, the probability of relapse after DMT discontinuation was significantly increased with natalizumab compared to first-line DMT (HR = 3.24; 95% CI [1.52; 6.90]). A peak of relapse was observed at 0-3 months after stopping natalizumab or fingolimod. CONCLUSION: Our study suggests that the risk of inflammatory activity is greater after discontinuation of natalizumab compared to other DMT even in middle-aged patients. As for younger patients, natalizumab discontinuation should only be considered if there is an adequate substitution of a different therapy. .
Authors: Per Soelberg Sørensen; Antonio Bertolotto; Gilles Edan; Gavin Giovannoni; Ralf Gold; Eva Havrdova; Ludwig Kappos; Bernd C Kieseier; Xavier Montalban; Tomas Olsson Journal: Mult Scler Date: 2012-02 Impact factor: 6.312
Authors: Peter Alping; Johan Askling; Joachim Burman; Katharina Fink; Anna Fogdell-Hahn; Martin Gunnarsson; Jan Hillert; Annette Langer-Gould; Jan Lycke; Petra Nilsson; Jonatan Salzer; Anders Svenningsson; Magnus Vrethem; Tomas Olsson; Fredrik Piehl; Thomas Frisell Journal: Ann Neurol Date: 2020-03-09 Impact factor: 10.422
Authors: Gustavo Luna; Peter Alping; Joachim Burman; Katharina Fink; Anna Fogdell-Hahn; Martin Gunnarsson; Jan Hillert; Annette Langer-Gould; Jan Lycke; Petra Nilsson; Jonatan Salzer; Anders Svenningsson; Magnus Vrethem; Tomas Olsson; Fredrik Piehl; Thomas Frisell Journal: JAMA Neurol Date: 2020-02-01 Impact factor: 18.302
Authors: Ann Marie Weideman; Marco Aurelio Tapia-Maltos; Kory Johnson; Mark Greenwood; Bibiana Bielekova Journal: Front Neurol Date: 2017-11-10 Impact factor: 4.003