Long-Term Effectiveness, Safety and Tolerability of Fingolimod in Patients with Multiple Sclerosis in Real-World Treatment Settings in France: The VIRGILE Study - EHESP - École des hautes études en santé publique Access content directly
Journal Articles Neurology and Therapy Year : 2022

Long-Term Effectiveness, Safety and Tolerability of Fingolimod in Patients with Multiple Sclerosis in Real-World Treatment Settings in France: The VIRGILE Study

Caroline Papeix , Giovanni Castelnovo , Emmanuelle Leray (1, 2, 3, 4) , Marc Coustans , Pierre Levy , Jean-Marc Visy , Gisela Kobelt , Fabienne Lamy , Bashar Allaf , François Heintzmann , Isabelle Chouette , Eric Raponi , Barbara Durand , Emmanuelle Grevat , Driss Kamar , Marc Debouverie , Christine Lebrun-Frenay , Abdelhakim Abdelmoumni , Mouhmmad Jamal Al Aloucy , Abdullatif Al Khedr , Amer Al Najjar Carpentier , Bernard Alonzo , Tony Altarcha , Amevi Ananivi , Géraldine Androdias , Gilles Angibaud , Marie-Sylvie Artaud-Uriot , Dominique Audry-Chaboud , Marie Barre , Philippe Barres , Rabah Benrabah , Eric Berger , François-Xavier Bergouignan , Patricia Bernady , Christophe Billy , Christian Blanchard , Mickaël Bonnan , Jean-Paul Borsotti , Catherine Bossu-van Nieuwenhuyse , Jean-Claude Bouffeteau , Sophie Bouillaguet , Yassine Boukriche , Jean-Marc Boulesteix , Bertrand Bourre , David Brassat , Alain Bredin , Bruno Brochet , Helene Brugeilles Baguelin , Ousmane Camara , Jean-Philippe Camdessanche , William Camu , Christophe Carel , Bertrand Carlander , Olivier Casez , Marie-Pierre Chanel-Soulier , Stéphane Chapuis , Mirella Cimpoesu , Jonathan Ciron , Pierre Clavelou , Christine Clerc , Renato Colamarino , Christophe Couratier , Sylvie Courtois , Alain Creange , Antoine Danielli , Thomas de Broucker , Jérôme de Seze , Gilles Defer , Jérôme Delorme , Béatrice Denis , Fayçal Derouiche , Philippe Devos , Anne-Marie Deyrolle , Michel Dib , Joseph Dib , Eric Diot , Emmanuelle Doury , Sophie Dufourd-Delalande , Corinne Dupel-Pottier , Patrick Dussaux , Gilles Edan , Thibault Edouard , Jean-Pierre Escaillas , Didier Ferriby , Nicolas Fouillet , Guillaume Fromager , Tsouria Gaida-Rostane , Philippe Gaida , Guillaume Gal , Guillaume Garrigues , Annick Gayou-Joyeux , Arnaud Gentil , Philippe Gerard , Julien Gere , Laurence Gignoux , Philippe Girard , Pierric Giraud , Michel Gouttard , Pierre Gras , Anne Marie Guennoc , Michel Gugenheim , Laurent Guilloton , Karim Hadjout , Patrick Hautecoeur , Yawo Hegbe , Olivier Heinzlef , Patrice Henry , Yann Herve , Jihad Hijazi , Pascale Homeyer , Bernard Huttin , Olivier Ille , Alain Jager , Laurentiu Jomir , Nabil Kardous , Agnès Kerouanton , Comlan Paul Kpade , Christophe Kubler , Pierre Labauge , François Lallement , Nicolas Landragin , David Axel Laplaud , Henda Laribi , Gilles Lavernhe , Pierre-Éric Le Biez , Françoise Le Bras , Patrick Le Coz , Josette Leche , Sara Julia Leder , Alain Legout , Michele Levasseur , Alberta Lorenzi-Pernot , Pierre Louchart , Fabien Louillet , Laurent Magy , Sophie Maillard , Elisabeth Maillart , Marcel Maillet-Vioud , Catherine Mallecourt-Emberger , Éric Manchon , Alexandre Mania , Laurent Martinez-Almoyna , Mikel Martinez , Serge Massengo , Dominique Maugin , Souraya Medjbeur , Gayané Meliksetyan , Michael Menassa , Dalia Meshaka-Dimitri-Boulos , Gérard Mick , Thibault Moreau , Antoine Moulignier , Isabelle Mourand , Jean-Philippe Muller , Philippe Neuschwander , Argentino Nibbio , Chantal Nifle , Jean-Bertin Nkendjuo , Ghislain Nokam Talom , Sophie Ory , Ivania Patry , Bernard Pedespan , Jean Pelletier , Delia-Gianina Pencu , Bruno Perrouty , Stéphane Peysson , Irène Popa-Coman , André Pouliquen , Christophe Prat , Adriana Prundean , Fataï Radji , Haja Tiana Rakotoharinandrasana , Lilia Razlog , Philippe Remy , Christophe Robin , Gilles Rodier , Jérôme Romero , Brigitte Roualdes , François Rouhart , Irene Ruggieri , Feras Abdul Samad , Irina Sarafiant , Stephane Schaeffer , Nicolas Schmidt , Philippe Schuermans , Nicolas Seiller , Thierry Soisson , Annie Sortais , Bruno Stankoff , Sabrina Stefanizzi-Debuc , Laurent Suchet , Jean Tardy , Gregory Taurin , Florent Thabuy , Marie Theaudin , Caroline Tilikete-Froment , Ayman Tourbah , Patricia Tourniaire , Sylvie Trefouret , Michel Vastene , Pierre Verdure , Patrick Vermersch , Frédérique Viala , Dorothée Videt-Gibou , Elisabeth Vidry , Sandra Vukusic , Marc Wagner , Valery Wattier , Christophe Zaenker , François Ziegler , Jean-Médard Zola
Caroline Papeix
Giovanni Castelnovo
  • Function : Author
Marc Coustans
  • Function : Author
Pierre Levy
  • Function : Author
Jean-Marc Visy
  • Function : Author
Gisela Kobelt
  • Function : Author
Fabienne Lamy
  • Function : Author
Bashar Allaf
  • Function : Author
François Heintzmann
  • Function : Author
Isabelle Chouette
  • Function : Author
Eric Raponi
  • Function : Author
Barbara Durand
  • Function : Author
Emmanuelle Grevat
  • Function : Author
Driss Kamar
  • Function : Author
Marc Debouverie
  • Function : Author
  • PersonId : 762777
  • IdRef : 068986629
Christine Lebrun-Frenay
Abdelhakim Abdelmoumni
  • Function : Author
Mouhmmad Jamal Al Aloucy
  • Function : Author
Abdullatif Al Khedr
  • Function : Author
Amer Al Najjar Carpentier
  • Function : Author
Bernard Alonzo
  • Function : Author
Tony Altarcha
  • Function : Author
Amevi Ananivi
  • Function : Author
Géraldine Androdias
  • Function : Author
Gilles Angibaud
  • Function : Author
Marie-Sylvie Artaud-Uriot
  • Function : Author
Dominique Audry-Chaboud
  • Function : Author
Marie Barre
  • Function : Author
Philippe Barres
  • Function : Author
Rabah Benrabah
  • Function : Author
Eric Berger
  • Function : Author
François-Xavier Bergouignan
  • Function : Author
Patricia Bernady
  • Function : Author
Christophe Billy
  • Function : Author
Christian Blanchard
  • Function : Author
Mickaël Bonnan
  • Function : Author
Jean-Paul Borsotti
  • Function : Author
Jean-Claude Bouffeteau
  • Function : Author
Sophie Bouillaguet
  • Function : Author
Yassine Boukriche
  • Function : Author
Jean-Marc Boulesteix
  • Function : Author
Bertrand Bourre
  • Function : Author
David Brassat
Alain Bredin
  • Function : Author
Bruno Brochet
Helene Brugeilles Baguelin
  • Function : Author
Ousmane Camara
  • Function : Author
Jean-Philippe Camdessanche
William Camu
  • Function : Author
Christophe Carel
  • Function : Author
Bertrand Carlander
  • Function : Author
Olivier Casez
  • Function : Author
Marie-Pierre Chanel-Soulier
  • Function : Author
Stéphane Chapuis
  • Function : Author
Mirella Cimpoesu
  • Function : Author
Jonathan Ciron
Pierre Clavelou
  • Function : Author
Christine Clerc
  • Function : Author
Renato Colamarino
  • Function : Author
Christophe Couratier
  • Function : Author
Sylvie Courtois
  • Function : Author
Alain Creange
  • Function : Author
Antoine Danielli
  • Function : Author
Thomas de Broucker
  • Function : Author
Jérôme de Seze
  • Function : Author
Gilles Defer
  • Function : Author
Jérôme Delorme
  • Function : Author
Béatrice Denis
  • Function : Author
Fayçal Derouiche
  • Function : Author
Philippe Devos
  • Function : Author
Anne-Marie Deyrolle
  • Function : Author
Michel Dib
  • Function : Author
Joseph Dib
  • Function : Author
Eric Diot
  • Function : Author
Emmanuelle Doury
  • Function : Author
Sophie Dufourd-Delalande
  • Function : Author
Corinne Dupel-Pottier
  • Function : Author
Patrick Dussaux
  • Function : Author
Gilles Edan
  • Function : Author
Thibault Edouard
  • Function : Author
Jean-Pierre Escaillas
  • Function : Author
Didier Ferriby
  • Function : Author
Nicolas Fouillet
  • Function : Author
Guillaume Fromager
  • Function : Author
Tsouria Gaida-Rostane
  • Function : Author
Philippe Gaida
  • Function : Author
Guillaume Gal
  • Function : Author
Guillaume Garrigues
  • Function : Author
Annick Gayou-Joyeux
  • Function : Author
Arnaud Gentil
  • Function : Author
Philippe Gerard
  • Function : Author
Julien Gere
  • Function : Author
Laurence Gignoux
  • Function : Author
Philippe Girard
Pierric Giraud
  • Function : Author
Michel Gouttard
  • Function : Author
Pierre Gras
  • Function : Author
Anne Marie Guennoc
  • Function : Author
Michel Gugenheim
  • Function : Author
Laurent Guilloton
  • Function : Author
Karim Hadjout
  • Function : Author
Patrick Hautecoeur
  • Function : Author
Yawo Hegbe
  • Function : Author
Olivier Heinzlef
  • Function : Author
Patrice Henry
  • Function : Author
Yann Herve
  • Function : Author
Jihad Hijazi
  • Function : Author
Pascale Homeyer
  • Function : Author
Bernard Huttin
  • Function : Author
Olivier Ille
  • Function : Author
Alain Jager
  • Function : Author
Laurentiu Jomir
  • Function : Author
Nabil Kardous
  • Function : Author
Agnès Kerouanton
  • Function : Author
Comlan Paul Kpade
  • Function : Author
Christophe Kubler
  • Function : Author
Pierre Labauge
François Lallement
  • Function : Author
Nicolas Landragin
  • Function : Author
David Axel Laplaud
  • Function : Author
Henda Laribi
  • Function : Author
Gilles Lavernhe
  • Function : Author
Pierre-Éric Le Biez
  • Function : Author
Françoise Le Bras
  • Function : Author
Patrick Le Coz
  • Function : Author
Josette Leche
  • Function : Author
Sara Julia Leder
  • Function : Author
Alain Legout
  • Function : Author
Michele Levasseur
  • Function : Author
Alberta Lorenzi-Pernot
  • Function : Author
Pierre Louchart
  • Function : Author
Fabien Louillet
  • Function : Author
Laurent Magy
  • Function : Author
Sophie Maillard
  • Function : Author
Elisabeth Maillart
  • Function : Author
Marcel Maillet-Vioud
  • Function : Author
Catherine Mallecourt-Emberger
  • Function : Author
Éric Manchon
  • Function : Author
Alexandre Mania
  • Function : Author
Laurent Martinez-Almoyna
  • Function : Author
Mikel Martinez
  • Function : Author
Serge Massengo
  • Function : Author
Dominique Maugin
  • Function : Author
Souraya Medjbeur
  • Function : Author
Gayané Meliksetyan
  • Function : Author
Michael Menassa
  • Function : Author
Dalia Meshaka-Dimitri-Boulos
  • Function : Author
Gérard Mick
  • Function : Author
Thibault Moreau
  • Function : Author
Antoine Moulignier
  • Function : Author
Isabelle Mourand
Jean-Philippe Muller
  • Function : Author
Philippe Neuschwander
  • Function : Author
Argentino Nibbio
  • Function : Author
Chantal Nifle
  • Function : Author
Jean-Bertin Nkendjuo
  • Function : Author
Ghislain Nokam Talom
  • Function : Author
Sophie Ory
  • Function : Author
Ivania Patry
  • Function : Author
Bernard Pedespan
  • Function : Author
Jean Pelletier
Delia-Gianina Pencu
  • Function : Author
Bruno Perrouty
  • Function : Author
Stéphane Peysson
  • Function : Author
Irène Popa-Coman
  • Function : Author
André Pouliquen
  • Function : Author
Christophe Prat
  • Function : Author
Adriana Prundean
  • Function : Author
Fataï Radji
  • Function : Author
Lilia Razlog
  • Function : Author
Philippe Remy
  • Function : Author
Christophe Robin
  • Function : Author
Gilles Rodier
  • Function : Author
Jérôme Romero
  • Function : Author
Brigitte Roualdes
  • Function : Author
François Rouhart
  • Function : Author
Irene Ruggieri
  • Function : Author
Feras Abdul Samad
  • Function : Author
Irina Sarafiant
  • Function : Author
Stephane Schaeffer
  • Function : Author
Nicolas Schmidt
  • Function : Author
Philippe Schuermans
  • Function : Author
Nicolas Seiller
  • Function : Author
Thierry Soisson
  • Function : Author
Annie Sortais
  • Function : Author
Bruno Stankoff
Sabrina Stefanizzi-Debuc
  • Function : Author
Laurent Suchet
  • Function : Author
Jean Tardy
  • Function : Author
Gregory Taurin
  • Function : Author
Florent Thabuy
  • Function : Author
Marie Theaudin
  • Function : Author
Caroline Tilikete-Froment
Ayman Tourbah
  • Function : Author
Patricia Tourniaire
  • Function : Author
Sylvie Trefouret
  • Function : Author
Michel Vastene
  • Function : Author
Pierre Verdure
  • Function : Author
Patrick Vermersch
Frédérique Viala
  • Function : Author
Dorothée Videt-Gibou
  • Function : Author
Elisabeth Vidry
  • Function : Author
Sandra Vukusic
Marc Wagner
  • Function : Author
Valery Wattier
  • Function : Author
Christophe Zaenker
  • Function : Author
François Ziegler
  • Function : Author
Jean-Médard Zola
  • Function : Author

Abstract

Introduction: It is important to confirm the effectiveness and tolerability of disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS) in real-world treatment settings. This prospective observational cohort study (VIRGILE) was performed at the request of the French health authorities. The primary objective was to evaluate the effectiveness of fingolimod 0.5 mg in reducing the annualised relapse rate (ARR) in patients with RRMS. Methods: Participating neurologists enrolled all adult patients with RRMS starting fingolimod treatment between 2014 and 2016, who were followed for 3 years. Follow-up consultations took place at the investigator's discretion. The primary outcome measure was the change in ARR at month 24 after fingolimod initiation. Relapses and adverse events were documented at each consultation; disability assessment (EDSS) and magnetic resonance imagery were performed at the investigator's discretion. Results: Of 1055 eligible patients, 633 patients were assessable at month 36; 405 (64.0%) were treated continuously with fingolimod for 3 years. The ARR decreased from 0.92 ± 0.92 at inclusion to 0.31 ± 0.51 at month 24, a significant reduction of 0.58 [95% CI - 0.51 to - 0.65] relapses/year (p < 0.001). Since starting fingolimod, 461 patients (60.9%) remained relapse-free at month 24 and 366 patients (55.5%) at month 36. In multivariate analysis, no previous disease-modifying treatment, number of relapses in the previous year and lower EDSS score at inclusion were associated with a greater on-treatment reduction in ARR. The mean EDSS score remained stable over the course of the study. Sixty-one out of 289 (21.1%) patients presented new radiological signs of disease activity. Treatment-related serious adverse events were lymphopenia (N = 21), bradycardia (N = 19), elevated transaminases (N = 9) and macular oedema (N = 9). Conclusions: The effectiveness and tolerability of fingolimod in everyday clinical practice are consistent with findings of previous phase III studies. Our study highlights the utility of fingolimod for the long-term management of patients with multiple sclerosis.
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hal-03608016 , version 1 (14-03-2022)

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Caroline Papeix, Giovanni Castelnovo, Emmanuelle Leray, Marc Coustans, Pierre Levy, et al.. Long-Term Effectiveness, Safety and Tolerability of Fingolimod in Patients with Multiple Sclerosis in Real-World Treatment Settings in France: The VIRGILE Study. Neurology and Therapy, 2022, ⟨10.1007/s40120-022-00334-y⟩. ⟨hal-03608016⟩
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