Mikael Cohen1, Elisabeth Maillart2, Ayman Tourbah3, Jérôme De Sèze4, Sandra Vukusic5, David Brassat6, Olivier Anne7, Sandrine Wiertlewski8, William Camu9, Sylvie Courtois10, Aurélie Ruet11, Marc Debouverie12, Emmanuelle Le Page13, Olivier Casez14, Olivier Heinzlef15, Bruno Stankoff16, Bertrand Bourre17, Giovanni Castelnovo18, Audrey Rico19, Eric Berger20, Jean-Philippe Camdessanche21, Gilles Defer22, Pierre Clavelou23, Abdullatif Al Khedr24, Hélène Zephir25, Agnès Fromont26, Caroline Papeix2, Bruno Brochet10, Jean Pelletier18, Christine Lebrun1. 1. Department of Neurology, University Hospital of Nice, Nice, France. 2. Department of Neurology, Salpêtrière Hospital, Paris, France. 3. Department of Neurology, University Hospital of Reims, Reims, France. 4. Department of Neurology, University Hospital of Strasbourg, Strasbourg, France. 5. Department of Neurology, University Hospital of Lyon, Lyon, France. 6. Department of Neurology, University Hospital of Toulouse, Toulouse, France. 7. Department of Neurology, University Hospital of La Rochelle, La Rochelle, France. 8. Department of Neurology, University Hospital of Nantes, Nantes, France. 9. Department of Neurology, University Hospital of Montpellier, Montpellier, France. 10. Department of Neurology, University Hospital of Mulhouse, Mulhouse, France. 11. Department of Neurology, University Hospital of Bordeaux, Bordeaux, France. 12. Department of Neurology, University Hospital of Nancy, Nancy, France. 13. Department of Neurology, University Hospital of Rennes, Rennes, France. 14. Department of Neurology, University Hospital of Grenoble, Grenoble, France. 15. Department of Neurology, University Hospital of Poissy, Poissy, France. 16. Department of Neurology, Tenon Hospital, Paris, France. 17. Department of Neurology, University Hospital of Rouen, Rouen, France. 18. Department of Neurology, University Hospital of Nimes, Nimes, France. 19. Department of Neurology, University Hospital of Marseille, Marseille, France. 20. Department of Neurology, University Hospital of Besançon, Besançon, France. 21. Department of Neurology, University Hospital of Saint Etienne, Saint Etienne, France. 22. Department of Neurology, University Hospital of Caen, Caen, France. 23. Department of Neurology, University Hospital of Clermont Ferrand, Clermont Ferrand, France. 24. Department of Neurology, University Hospital of Amiens, Amiens, France. 25. Department of Neurology, University Hospital of Lille, Lille, France. 26. Department of Neurology, University Hospital of Dijon, Dijon, France.
Abstract
IMPORTANCE: The safety and efficacy of switching from natalizumab to fingolimod have not yet been evaluated in a large cohort of patients with multiple sclerosis (MS) to our knowledge. OBJECTIVE: To collect data from patients with MS switching from natalizumab to fingolimod. DESIGN, SETTING, AND PARTICIPANTS: The Enquête Nationale sur l'Introduction du Fingolimod en Relais au Natalizumab (ENIGM) study, a survey-based, observational multicenter cohort study among MS tertiary referral centers. Participants were patients for whom a switch from natalizumab to fingolimod was planned. Clinical data were collected on natalizumab treatment, duration and management of the washout period (WP), and relapse or adverse events during the WP and after the initiation of fingolimod. MAIN OUTCOMES AND MEASURES: Occurrence of MS relapse during the WP or during a 6-month follow-up period after the initiation of fingolimod. RESULTS: Thirty-six French MS tertiary referral centers participated. In total, 333 patients with MS switched from natalizumab to fingolimod after a mean of 31 natalizumab infusions (female to male ratio, 2.36; mean age, 41 years; and Expanded Disability Status Scale score at the initiation of natalizumab, 3.6). Seventy-one percent were seropositive for the JC polyomavirus. The Expanded Disability Status Scale score remained stable for patients receiving natalizumab. Twenty-seven percent of patients relapsed during the WP. A WP shorter than 3 months was associated with a lower risk of relapse (odds ratio, 0.23; P = .001) and with less disease activity before natalizumab initiation (P = .03). Patients who stopped natalizumab because of poor tolerance or lack of efficacy also had a higher risk of relapse (odds ratio, 3.20; P = .004). Twenty percent of patients relapsed during the first 6 months of fingolimod therapy. Three percent stopped fingolimod for efficacy, tolerance, or compliance issues. In the multivariate analysis, the occurrence of relapse during the WP was the only significant prognostic factor for relapse during fingolimod therapy (odds ratio, 3.80; P = .05). CONCLUSIONS AND RELEVANCE: In this study, switching from natalizumab to fingolimod was associated with a risk of MS reactivation during the WP or shortly after fingolimod initiation. The WP should be shorter than 3 months.
IMPORTANCE: The safety and efficacy of switching from natalizumab to fingolimod have not yet been evaluated in a large cohort of patients with multiple sclerosis (MS) to our knowledge. OBJECTIVE: To collect data from patients with MS switching from natalizumab to fingolimod. DESIGN, SETTING, AND PARTICIPANTS: The Enquête Nationale sur l'Introduction du Fingolimod en Relais au Natalizumab (ENIGM) study, a survey-based, observational multicenter cohort study among MS tertiary referral centers. Participants were patients for whom a switch from natalizumab to fingolimod was planned. Clinical data were collected on natalizumab treatment, duration and management of the washout period (WP), and relapse or adverse events during the WP and after the initiation of fingolimod. MAIN OUTCOMES AND MEASURES: Occurrence of MS relapse during the WP or during a 6-month follow-up period after the initiation of fingolimod. RESULTS: Thirty-six French MS tertiary referral centers participated. In total, 333 patients with MS switched from natalizumab to fingolimod after a mean of 31 natalizumab infusions (female to male ratio, 2.36; mean age, 41 years; and Expanded Disability Status Scale score at the initiation of natalizumab, 3.6). Seventy-one percent were seropositive for the JC polyomavirus. The Expanded Disability Status Scale score remained stable for patients receiving natalizumab. Twenty-seven percent of patients relapsed during the WP. A WP shorter than 3 months was associated with a lower risk of relapse (odds ratio, 0.23; P = .001) and with less disease activity before natalizumab initiation (P = .03). Patients who stopped natalizumab because of poor tolerance or lack of efficacy also had a higher risk of relapse (odds ratio, 3.20; P = .004). Twenty percent of patients relapsed during the first 6 months of fingolimod therapy. Three percent stopped fingolimod for efficacy, tolerance, or compliance issues. In the multivariate analysis, the occurrence of relapse during the WP was the only significant prognostic factor for relapse during fingolimod therapy (odds ratio, 3.80; P = .05). CONCLUSIONS AND RELEVANCE: In this study, switching from natalizumab to fingolimod was associated with a risk of MS reactivation during the WP or shortly after fingolimod initiation. The WP should be shorter than 3 months.
Authors: Maria Trojano; Mar Tintore; Xavier Montalban; Jan Hillert; Tomas Kalincik; Pietro Iaffaldano; Tim Spelman; Maria Pia Sormani; Helmut Butzkueven Journal: Nat Rev Neurol Date: 2017-01-13 Impact factor: 42.937
Authors: Carrie M Hersh; Claire Hara-Cleaver; Richard A Rudick; Jeffrey A Cohen; Robert A Bermel; Daniel Ontaneda Journal: Int J Neurosci Date: 2014-10-29 Impact factor: 2.292
Authors: P Kolber; F Luessi; S G Meuth; L Klotz; T Korn; C Trebst; B Tackenberg; B Kieseier; T Kümpfel; V Fleischer; H Tumani; B Wildemann; M Lang; P Flachenecker; U Meier; W Brück; V Limmroth; A Haghikia; H-P Hartung; M Stangel; R Hohlfeld; B Hemmer; R Gold; H Wiendl; F Zipp Journal: Nervenarzt Date: 2015-10 Impact factor: 1.214