Tomas Kalincik1, Vilija Jokubaitis2, Guillermo Izquierdo3, Pierre Duquette4, Marc Girard4, Pierre Grammond5, Alessandra Lugaresi6, Celia Oreja-Guevara7, Roberto Bergamaschi8, Raymond Hupperts9, Francois Grand'Maison10, Eugenio Pucci11, Vincent Van Pesch12, Cavit Boz13, Gerardo Iuliano14, Ricardo Fernandez-Bolanos15, Shlomo Flechter16, Daniele Spitaleri17, Edgardo Cristiano18, Freek Verheul19, Jeannette Lechner-Scott20, Maria Pia Amato21, Jose Antonio Cabrera-Gomez22, Maria Laura Saladino23, Mark Slee24, Fraser Moore25, Orla Gray26, Mark Paine27, Michael Barnett28, Eva Havrdova29, Dana Horakova29, Timothy Spelman2, Maria Trojano30, Helmut Butzkueven31. 1. Department of Medicine, University of Melbourne, Melbourne, Australia and Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia tomas.kalincik@unimelb.edu.au. 2. Department of Medicine, University of Melbourne, Melbourne, Australia and Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. 3. Hospital Universitario Virgen Macarena, Sevilla, Spain. 4. Hôpital Notre Dame, Montreal, Canada. 5. Hotel-Dieu de Levis, Quebec, Canada. 6. MS Center, Neuroscience, Imaging and Clinical Sciences, University 'G. d'Annunzio', Chieti, Italy. 7. University Hospital San Carlos, IdISSC, Madrid, Spain. 8. National Neurological Institute C. Mondino, Pavia, Italy. 9. Orbis Medical Center, Sittard, the Netherlands. 10. Neuro Rive-Sud, Hôpital Charles LeMoyne, Quebec, Canada. 11. Ospedale di Macerata, Macerata, Italy. 12. Cliniques Universitaires Saint-Luc, Brussels, Belgium. 13. Karadeniz Technical University, Trabzon, Turkey. 14. Ospedali Riuniti di Salerno, Salerno, Italy. 15. Hospital Universitario Virgen de Valme, Seville, Spain. 16. Assaf Harofeh Medical Center, Beer-Yaakov, Israel. 17. AORN San Giuseppe Moscati, Avellino, Italy. 18. Hospital Italiano, Buenos Aires, Argentina. 19. Groen Hart Ziekenhuis, Gouda, the Netherlands. 20. John Hunter Hospital, Newcastle, Australia. 21. Department NEUROFARBA, Section of Neurosciences, University of Florence, Florence, Italy. 22. Centro Internacional de Restauracion Neurologica, Havana, Cuba. 23. INEBA, Buenos Aires, Argentina. 24. Flinders University and Medical Centre, Adelaide, Australia. 25. Jewish General Hospital, Montreal, Canada. 26. Craigavon Area Hospital, Portadown, UK. 27. St Vincent's Hospital, Melbourne, Australia. 28. Brain and Mind Research Institute, Sydney, Australia. 29. Department of Neurology and Center of Clinical Neuroscience, 1st Faculty of Medicine, General University Hospital and Charles University in Prague, Czech Republic. 30. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy/These authors contributed equally to the manuscript. 31. Department of Medicine, University of Melbourne, Melbourne, Australia, Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia, and Department of Neurology, Box Hill Hospital, Monash University, Box Hill, Australia.
Abstract
BACKGROUND: The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed. OBJECTIVE: We aimed to compare, in a real-world setting, relapse and disability outcomes among patients with multiple sclerosis (MS) treated with injectable immunomodulators. METHODS: Pairwise analysis of the international MSBase registry data was conducted using propensity-score matching. The four injectable immunomodulators were compared in six head-to-head analyses of relapse and disability outcomes using paired mixed models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity and power analyses were conducted. RESULTS: Of the 3326 included patients, 345-1199 patients per therapy were matched (median pairwise-censored follow-up was 3.7 years). Propensity matching eliminated >95% of the identified indication bias. Slightly lower relapse incidence was found among patients treated with glatiramer acetate or subcutaneous interferon β-1a relative to intramuscular interferon β-1a and interferon β-1b (p≤0.001). No differences in 12-month confirmed progression of disability were observed. CONCLUSION: Small but statistically significant differences in relapse outcomes exist among the injectable immunomodulators. MSBase is sufficiently powered to identify these differences and reflects practice in tertiary MS centres. While the present study controlled indication, selection and attrition bias, centre-dependent variance in data quality was likely.
BACKGROUND: The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed. OBJECTIVE: We aimed to compare, in a real-world setting, relapse and disability outcomes among patients with multiple sclerosis (MS) treated with injectable immunomodulators. METHODS: Pairwise analysis of the international MSBase registry data was conducted using propensity-score matching. The four injectable immunomodulators were compared in six head-to-head analyses of relapse and disability outcomes using paired mixed models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity and power analyses were conducted. RESULTS: Of the 3326 included patients, 345-1199 patients per therapy were matched (median pairwise-censored follow-up was 3.7 years). Propensity matching eliminated >95% of the identified indication bias. Slightly lower relapse incidence was found among patients treated with glatiramer acetate or subcutaneous interferon β-1a relative to intramuscular interferon β-1a and interferon β-1b (p≤0.001). No differences in 12-month confirmed progression of disability were observed. CONCLUSION: Small but statistically significant differences in relapse outcomes exist among the injectable immunomodulators. MSBase is sufficiently powered to identify these differences and reflects practice in tertiary MS centres. While the present study controlled indication, selection and attrition bias, centre-dependent variance in data quality was likely.
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: Tim Spelman; Tomas Kalincik; Vilija Jokubaitis; Annie Zhang; Fabio Pellegrini; Heinz Wiendl; Shibeshih Belachew; Robert Hyde; Freek Verheul; Alessandra Lugaresi; Eva Havrdová; Dana Horáková; Pierre Grammond; Pierre Duquette; Alexandre Prat; Gerardo Iuliano; Murat Terzi; Guillermo Izquierdo; Raymond M M Hupperts; Cavit Boz; Eugenio Pucci; Giorgio Giuliani; Patrizia Sola; Daniele L A Spitaleri; Jeannette Lechner-Scott; Roberto Bergamaschi; François Grand'Maison; Franco Granella; Ludwig Kappos; Maria Trojano; Helmut Butzkueven Journal: Neurol Clin Pract Date: 2016-04
Authors: Johannes Lorscheider; Vilija G Jokubaitis; Tim Spelman; Guillermo Izquierdo; Alessandra Lugaresi; Eva Havrdova; Dana Horakova; Maria Trojano; Pierre Duquette; Marc Girard; Alexandre Prat; François Grand'Maison; Pierre Grammond; Eugenio Pucci; Cavit Boz; Patrizia Sola; Diana Ferraro; Daniele Spitaleri; Jeanette Lechner-Scott; Murat Terzi; Vincent Van Pesch; Gerardo Iuliano; Roberto Bergamaschi; Cristina Ramo-Tello; Franco Granella; Celia Oreja-Guevara; Helmut Butzkueven; Tomas Kalincik Journal: Neurology Date: 2017-08-09 Impact factor: 9.910
Authors: Jennifer H Yang; Torge Rempe; Natalie Whitmire; Anastasie Dunn-Pirio; Jennifer S Graves Journal: Front Neurol Date: 2022-06-03 Impact factor: 4.086
Authors: Francesca Bovis; Tomas Kalincik; Fred Lublin; Gary Cutter; Charles Malpas; Dana Horakova; Eva Kubala Havrdova; Maria Trojano; Alexandre Prat; Marc Girard; Pierre Duquette; Marco Onofrj; Alessandra Lugaresi; Guillermo Izquierdo; Sara Eichau; Francesco Patti; Murat Terzi; Pierre Grammond; Roberto Bergamaschi; Patrizia Sola; Diana Ferraro; Serkan Ozakbas; Gerardo Iuliano; Cavit Boz; Raymond Hupperts; Francois Grand'Maison; Celia Oreja-Guevara; Vincent van Pesch; Elisabetta Cartechini; Thor Petersen; Ayse Altintas; Aysun Soysal; Cristina Ramo-Tello; Pamela McCombe; Recai Turkoglu; Helmut Butzkueven; Jerry S Wolinsky; Claudio Solaro; Maria Pia Sormani Journal: Neurology Date: 2020-10-06 Impact factor: 9.910