Disability accrual in primary and secondary progressive multiple sclerosis

Sam Harding-Forrester¹, Izanne Roos^{1

2}, Ai-Lan Nguyen^{1

2}, Charles B Malpas^{1

2}, Ibrahima Diouf^{1

2}, Nahid Moradi^{1

2}, Sifat Sharmin^{1

2}, Guillermo Izquierdo³, Sara Eichau³, Francesco Patti⁴, Dana Horakova⁵, Eva Kubala Havrdova⁵, Alexandre Prat^{6

7}, Marc Girard^{6

8}, Pierre Duquette^{6

8}, Francois Grand'Maison⁹, Marco Onofrj¹⁰, Alessandra Lugaresi^{11

12}, Pierre Grammond¹³, Serkan Ozakbas¹⁴, Maria Pia Amato^{15

16}, Oliver Gerlach¹⁷, Patrizia Sola¹⁸, Diana Ferraro^{19

20}, Katherine Buzzard²¹, Olga Skibina²¹, Jeannette Lechner-Scott^{22

23}, Raed Alroughani²⁴, Cavit Boz²⁵, Vincent Van Pesch²⁶, Elisabetta Cartechini²⁷, Murat Terzi²⁸, Davide Maimone²⁹, Cristina Ramo-Tello³⁰, Bassem Yamout^{31

32}, Samia Joseph Khoury^{31

33}, Daniele La Spitaleri³⁴, Maria Jose Sa^{35

36}, Yolanda Blanco³⁷, Franco Granella³⁸, Mark Slee³⁹, Ernest Butler⁴⁰, Youssef Sidhom⁴¹, Riadh Gouider⁴², Roberto Bergamaschi⁴³, Rana Karabudak⁴⁴, Radek Ampapa⁴⁵, José Luis Sánchez-Menoyo⁴⁶, Julie Prevost⁴⁷, Tamara Castillo-Trivino⁴⁸, Pamela A McCombe⁴⁹, Richard Macdonell⁵⁰, Guy Laureys⁵¹, Liesbeth Van Hijfte⁵¹, Jiwon Oh⁵², Ayse Altintas^{53

54}, Koen de Gans⁵⁵, Recai Turkoglu⁵⁶, Anneke van der Walt⁵⁷, Helmut Butzkueven^{58

59}, Steve Vucic⁶⁰, Michael Barnett⁶¹, Edgardo Cristiano⁶², Suzanne Hodgkinson⁶³, Gerardo Iuliano⁶⁴, Ludwig Kappos^{65

66}, Jens Kuhle^{65

66}, Vahid Shaygannejad⁶⁷, Aysun Soysal⁶⁸, Bianca Weinstock-Guttman⁶⁹, Bart Van Wijmeersch^{70

71}, Tomas Kalincik^{72

2}; MSBase investigators

Affiliations

¹ CORe, Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
² Neuroimmunology Centre, Department of Neurology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
³ Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena, Sevilla, Andalucía, Spain.
⁴ Neuroscience, Department of Surgical and Medical Sciences and Advanced Technologies 'G.F. Ingrassia', University of Catania, Catania, Italy.
⁵ Department of Neurology and Centre of Clinical Neuroscience, Charles University First Faculty of Medicine, Praha, Czech Republic.
⁶ Centre Hospitalier, Université de Montréal, Montreal, Québec, Canada.
⁷ Department of Neuroscience, Université de Montréal, Montreal, Québec, Canada.
⁸ Faculté de Médecine, Université de Montréal, Montreal, Québec, Canada.
⁹ Neuro Rive-Sud, Longueuil, Quebec, Canada.
¹⁰ Department of Neurosciences, Imaging and Clinical Sciences, Gabriele d'Annunzio University of Chieti-Pescara, Chieti, Italy.
¹¹ UOSI Riabilitazione Sclerosi Multipla, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
¹² Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
¹³ Centre intégré de santé et de services sociaux de Chaudière-Appalaches du Québec Centre de Recherche, Levis, Québec, Canada.
¹⁴ Department of Neurology, Dokuz Eylul University, İzmir, Turkey.
¹⁵ Department of Neurological Siences, University of Florence, Florence, Italy.
¹⁶ IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
¹⁷ Department of Neurology, Zuyderland Medical Centre, Sittard-Geleen, The Netherlands.
¹⁸ Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy.
¹⁹ Department of Neuroscience, Azienda Ospedaliero-Universitaria di Modena, Modena, Emilia-Romagna, Italy.
²⁰ Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
²¹ Department of Neurology, Box Hill Hospital, Box Hill, Victoria, Australia.
²² School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia.
²³ Department of Neurology, John Hunter Hospital, Newcastle, New South Wales, Australia.
²⁴ Department of Medicine, Al-Amiri Hospital, Kuwait City, Kuwait.
²⁵ Department of Neurology, Karadeniz Technical University, Trabzon, Turkey.
²⁶ Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
²⁷ UOC Neurologia, Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy.
²⁸ Ondokuz Mayis Üniversitesi, Samsun, Turkey.
²⁹ UO Neurologia, Ospedale Garibaldi, Catania, Italy.
³⁰ Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
³¹ Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon.
³² Department of Neurology, American University of Beirut, Beirut, Lebanon.
³³ American University of Beirut, Beirut, Lebanon.
³⁴ UOC Neurologia e Stroke, AORN San Giuseppe Moscati, Avellino, Italy.
³⁵ Department of Neurology, Centro Hospitalar de São João, Porto, Portugal.
³⁶ Health Sciences Faculty, Fernando Pessoa University, Porto, Portugal.
³⁷ Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain.
³⁸ Multiple Sclerosis Centre, Neurosciences, University of Parma, Parma, Italy.
³⁹ Department of Neurology, Flinders Medical Centre, Adelaide, South Australia, Australia.
⁴⁰ Department of Neurology, Monash Medical Centre Clayton, Clayton, Victoria, Australia.
⁴¹ Department of Neurology, Hopital Razi, La Manouba, Tunisia.
⁴² Department of Neurology, Razi Hospital, Rasht, Gilan, Iran.
⁴³ Multiple Sclerosis Centre, Neurological Institute C.Mondino, Pavia, Italy.
⁴⁴ Department of Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
⁴⁵ Department of Neurology, Nemocnice Jihlava, Jihlava, Czech Republic.
⁴⁶ Department of Neurology, Hospital Galdakao-Usansolo, Galdacano, País Vasco, Spain.
⁴⁷ Centre integre de sante et de services sociaux des Laurentides point de service de Saint-Jerome, Saint-Jerome, Quebec, Canada.
⁴⁸ Department of Neurology, Donostia University Hospital, San Sebastian, Spain.
⁴⁹ UQCCR, The University of Queensland, Saint Lucia, Queensland, Australia.
⁵⁰ Department of Neurology, Austin Health, Heidelberg, Victoria, Australia.
⁵¹ Department of Neurology, University Hospital Ghent, Gent, Oost-Vlaanderen, Belgium.
⁵² Division of Neurology, Department of Medicine, St Michael's Hospital, Toronto, Ontario, Canada.
⁵³ Department of Neurology, Koc Universitesi, Istanbul, Turkey.
⁵⁴ Koç University Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey.
⁵⁵ Department of Neurology, Groene Hart Ziekenhuis, Gouda, Zuid-Holland, The Netherlands.
⁵⁶ Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
⁵⁷ Multiple Sclerosis and Neuroimmunology Unit, Monash University Central Clinical School, Melbourne, Victoria, Australia.
⁵⁸ Department of Neuroscience, Monash University Central Clinical School, Melbourne, Victoria, Australia.
⁵⁹ Department of Neurology, The Alfred, Melbourne, Victoria, Australia.
⁶⁰ Department of Neurology, Westmead Hospital, Westmead, New South Wales, Australia.
⁶¹ Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
⁶² Centro de Esclerosis Múltiple de Buenos Aires, Hospital Italiano de Buenos Aires, Buenos Aires, Federal District, Argentina.
⁶³ Department of Neurology, Liverpool Hospital, Liverpool, New South Wales, Australia.
⁶⁴ Ospedali Riuniti di Salerno, Salerno, Italy.
⁶⁵ Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, Basel, Switzerland.
⁶⁶ Research Centre for Clinical Neuroimmunology and Neuroscience, University Hospital Basel, Basel, Switzerland.
⁶⁷ Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran.
⁶⁸ Department of Neurology, Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery, Istanbul, Turkey.
⁶⁹ Department of Neurology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA.
⁷⁰ Universitair MS Centrum, Hasselt University, Hasselt-Pelt, Belgium.
⁷¹ Rehabilitation & MS Centre, Pelt, Belgium.
⁷² CORe, Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia tomas.kalincik@unimelb.edu.au.

PMID: 37068931
DOI: 10.1136/jnnp-2022-330726

Disability accrual in primary and secondary progressive multiple sclerosis

Sam Harding-Forrester et al. J Neurol Neurosurg Psychiatry. 2023 Sep.

. 2023 Sep;94(9):707-717.

doi: 10.1136/jnnp-2022-330726. Epub 2023 Apr 17.

Authors

Affiliations

¹ CORe, Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
² Neuroimmunology Centre, Department of Neurology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
³ Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena, Sevilla, Andalucía, Spain.
⁴ Neuroscience, Department of Surgical and Medical Sciences and Advanced Technologies 'G.F. Ingrassia', University of Catania, Catania, Italy.
⁵ Department of Neurology and Centre of Clinical Neuroscience, Charles University First Faculty of Medicine, Praha, Czech Republic.
⁶ Centre Hospitalier, Université de Montréal, Montreal, Québec, Canada.
⁷ Department of Neuroscience, Université de Montréal, Montreal, Québec, Canada.
⁸ Faculté de Médecine, Université de Montréal, Montreal, Québec, Canada.
⁹ Neuro Rive-Sud, Longueuil, Quebec, Canada.
¹⁰ Department of Neurosciences, Imaging and Clinical Sciences, Gabriele d'Annunzio University of Chieti-Pescara, Chieti, Italy.
¹¹ UOSI Riabilitazione Sclerosi Multipla, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
¹² Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
¹³ Centre intégré de santé et de services sociaux de Chaudière-Appalaches du Québec Centre de Recherche, Levis, Québec, Canada.
¹⁴ Department of Neurology, Dokuz Eylul University, İzmir, Turkey.
¹⁵ Department of Neurological Siences, University of Florence, Florence, Italy.
¹⁶ IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
¹⁷ Department of Neurology, Zuyderland Medical Centre, Sittard-Geleen, The Netherlands.
¹⁸ Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy.
¹⁹ Department of Neuroscience, Azienda Ospedaliero-Universitaria di Modena, Modena, Emilia-Romagna, Italy.
²⁰ Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
²¹ Department of Neurology, Box Hill Hospital, Box Hill, Victoria, Australia.
²² School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia.
²³ Department of Neurology, John Hunter Hospital, Newcastle, New South Wales, Australia.
²⁴ Department of Medicine, Al-Amiri Hospital, Kuwait City, Kuwait.
²⁵ Department of Neurology, Karadeniz Technical University, Trabzon, Turkey.
²⁶ Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
²⁷ UOC Neurologia, Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy.
²⁸ Ondokuz Mayis Üniversitesi, Samsun, Turkey.
²⁹ UO Neurologia, Ospedale Garibaldi, Catania, Italy.
³⁰ Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
³¹ Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon.
³² Department of Neurology, American University of Beirut, Beirut, Lebanon.
³³ American University of Beirut, Beirut, Lebanon.
³⁴ UOC Neurologia e Stroke, AORN San Giuseppe Moscati, Avellino, Italy.
³⁵ Department of Neurology, Centro Hospitalar de São João, Porto, Portugal.
³⁶ Health Sciences Faculty, Fernando Pessoa University, Porto, Portugal.
³⁷ Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain.
³⁸ Multiple Sclerosis Centre, Neurosciences, University of Parma, Parma, Italy.
³⁹ Department of Neurology, Flinders Medical Centre, Adelaide, South Australia, Australia.
⁴⁰ Department of Neurology, Monash Medical Centre Clayton, Clayton, Victoria, Australia.
⁴¹ Department of Neurology, Hopital Razi, La Manouba, Tunisia.
⁴² Department of Neurology, Razi Hospital, Rasht, Gilan, Iran.
⁴³ Multiple Sclerosis Centre, Neurological Institute C.Mondino, Pavia, Italy.
⁴⁴ Department of Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
⁴⁵ Department of Neurology, Nemocnice Jihlava, Jihlava, Czech Republic.
⁴⁶ Department of Neurology, Hospital Galdakao-Usansolo, Galdacano, País Vasco, Spain.
⁴⁷ Centre integre de sante et de services sociaux des Laurentides point de service de Saint-Jerome, Saint-Jerome, Quebec, Canada.
⁴⁸ Department of Neurology, Donostia University Hospital, San Sebastian, Spain.
⁴⁹ UQCCR, The University of Queensland, Saint Lucia, Queensland, Australia.
⁵⁰ Department of Neurology, Austin Health, Heidelberg, Victoria, Australia.
⁵¹ Department of Neurology, University Hospital Ghent, Gent, Oost-Vlaanderen, Belgium.
⁵² Division of Neurology, Department of Medicine, St Michael's Hospital, Toronto, Ontario, Canada.
⁵³ Department of Neurology, Koc Universitesi, Istanbul, Turkey.
⁵⁴ Koç University Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey.
⁵⁵ Department of Neurology, Groene Hart Ziekenhuis, Gouda, Zuid-Holland, The Netherlands.
⁵⁶ Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
⁵⁷ Multiple Sclerosis and Neuroimmunology Unit, Monash University Central Clinical School, Melbourne, Victoria, Australia.
⁵⁸ Department of Neuroscience, Monash University Central Clinical School, Melbourne, Victoria, Australia.
⁵⁹ Department of Neurology, The Alfred, Melbourne, Victoria, Australia.
⁶⁰ Department of Neurology, Westmead Hospital, Westmead, New South Wales, Australia.
⁶¹ Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
⁶² Centro de Esclerosis Múltiple de Buenos Aires, Hospital Italiano de Buenos Aires, Buenos Aires, Federal District, Argentina.
⁶³ Department of Neurology, Liverpool Hospital, Liverpool, New South Wales, Australia.
⁶⁴ Ospedali Riuniti di Salerno, Salerno, Italy.
⁶⁵ Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, Basel, Switzerland.
⁶⁶ Research Centre for Clinical Neuroimmunology and Neuroscience, University Hospital Basel, Basel, Switzerland.
⁶⁷ Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran.
⁶⁸ Department of Neurology, Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery, Istanbul, Turkey.
⁶⁹ Department of Neurology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA.
⁷⁰ Universitair MS Centrum, Hasselt University, Hasselt-Pelt, Belgium.
⁷¹ Rehabilitation & MS Centre, Pelt, Belgium.
⁷² CORe, Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia tomas.kalincik@unimelb.edu.au.

PMID: 37068931
DOI: 10.1136/jnnp-2022-330726

Abstract

Background: Some studies comparing primary and secondary progressive multiple sclerosis (PPMS, SPMS) report similar ages at onset of the progressive phase and similar rates of subsequent disability accrual. Others report later onset and/or faster accrual in SPMS. Comparisons have been complicated by regional cohort effects, phenotypic differences in sex ratio and management and variable diagnostic criteria for SPMS.

Methods: We compared disability accrual in PPMS and operationally diagnosed SPMS in the international, clinic-based MSBase cohort. Inclusion required PPMS or SPMS with onset at age ≥18 years since 1995. We estimated Andersen-Gill hazard ratios for disability accrual on the Expanded Disability Status Scale (EDSS), adjusted for sex, age, baseline disability, EDSS score frequency and drug therapies, with centre and patient as random effects. We also estimated ages at onset of the progressive phase (Kaplan-Meier) and at EDSS milestones (Turnbull). Analyses were replicated with physician-diagnosed SPMS.

Results: Included patients comprised 1872 with PPMS (47% men; 50% with activity) and 2575 with SPMS (32% men; 40% with activity). Relative to PPMS, SPMS had older age at onset of the progressive phase (median 46.7 years (95% CI 46.2-47.3) vs 43.9 (43.3-44.4); p<0.001), greater baseline disability, slower disability accrual (HR 0.86 (0.78-0.94); p<0.001) and similar age at wheelchair dependence.

Conclusions: We demonstrate later onset of the progressive phase and slower disability accrual in SPMS versus PPMS. This may balance greater baseline disability in SPMS, yielding convergent disability trajectories across phenotypes. The different rates of disability accrual should be considered before amalgamating PPMS and SPMS in clinical trials.

Keywords: multiple sclerosis.

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Conflict of interest statement

Competing interests: IR served on scientific advisory boards for Novartis and Merck, and received conference travel support and/or speaker honoraria from Roche, Novartis, Biogen, Teva, Sanofi Genzyme, and Merck. A-LN received grants from MS Research Australia; grants, personal fees, and nonfinancial support from Biogen; grants and personal fees from Merck Serono; personal fees from Teva and Novartis; and nonfinancial support from Roche and Sanofi Genzyme. GI received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall, and Teva. SE received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva. FP received speaker honoraria and advisory board fees from Almirall, Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi Genzyme, and Teva, and research funding from Biogen, Merck, FISM (Fondazione Italiana Sclerosi Multipla), Reload Onlus Association, and the University of Catania. DH received speaker honoraria and consulting fees from Biogen, Merck, Teva, Roche, Sanofi Genzyme, and Novartis, and support for research activities from Biogen and the Czech Ministry of Education (project PROGRES Q27/LF1). EVH received honoraria or research support from Biogen, Merck Serono, Novartis, Roche, and Teva; has been a member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novartis, and Sanofi Genzyme; and received research support from the Czech Ministry of Education (project PROGRES Q27/LF1). MG received consulting fees from Teva Canada Innovation, Biogen, Novartis, and Sanofi Genzyme; lecture payments from Teva Canada Innovation, Novartis, and EMD; and research support from the Canadian Institutes of Health Research. PD served on editorial boards for, and has been supported to attend meetings by, EMD, Biogen, Novartis, Genzyme, and Teva Neuroscience; he holds grants from the Canadian Institutes of Health Research and the MS Society of Canada, and received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme. FG’M received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi, and ONO Pharmaceuticals. AL received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi Genzyme, and Teva; her institutions have received research grants from Novartis (in the past 4 years). PG served on advisory boards for Novartis, EMD Serono, Roche, Biogen Idec, Sanofi Genzyme, and Pendopharm; received grant support from Genzyme and Roche; and received research grants for his institution from Biogen Idec, Sanofi Genzyme, and EMD Serono. MPA received honoraria as a consultant on scientific advisory boards for Biogen, Bayer Schering, Merck, Teva, and Sanofi-Aventis, and received research grants by Biogen, Bayer Schering, Merck, Teva, and Novartis. PS served on scientific advisory boards for Biogen Idec and Teva; received funding for travel and speaker honoraria from Biogen Idec, Merck, Teva, Sanofi Genzyme, Novartis, and Bayer; and received research grants for her institution from Bayer, Biogen, Merck, Novartis, Sanofi, and Teva. DF received travel grants and/or speaker honoraria from Merck, Teva, Novartis, Biogen, and Sanofi Genzyme. KB received honoraria and consulting fees from Biogen, Teva, Novartis, Sanofi Genzyme, Roche, Merck, CSL, and Grifols. JL-S received travel compensation from Novartis, Biogen, Roche, and Merck; her institution received honoraria for talks and advisory board commitments, as well as research grants from Biogen, Merck, Roche, Teva, and Novartis. RA received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche, and Sanofi Genzyme. CB received conference travel support from Biogen, Novartis, Bayer Schering, Merck, and Teva, and participated in clinical trials by Sanofi-Aventis, Roche, and Novartis. VVP received travel grants from Merck, Biogen, Sanofi, Celgene, Almirall, and Roche; his institution received research grants and consultancy fees from Roche, Biogen, Sanofi, Celgene, Merck, and Novartis Pharma. MT received travel grants from Novartis, Bayer Schering, Merck, and Teva, and participated in clinical trials by Sanofi-Aventis, Roche, and Novartis. DM received speaker honoraria for advisory board service and travel grants from Almirall, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva. CR-T received research funding, compensation for travel, or speaker honoraria from Biogen, Novartis, Genzyme, and Almirall. DLS received honoraria as a consultant on scientific advisory boards from Bayer Schering, Novartis, and Sanofi-Aventis, and compensation for travel from Novartis, Biogen, Sanofi-Aventis, Teva, and Merck. FG received an institutional research grant from Biogen and Sanofi Genzyme; served on scientific advisory boards for Biogen, Novartis, Merck, Sanofi Genzyme, and Roche; and received funding for travel and speaker honoraria from Biogen, Merck, and Sanofi-Aventis. MS participated in, but did not receive honoraria for, advisory board activity for Biogen, Merck, Bayer Schering, Sanofi-Aventis, and Novartis. RB received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva; research grants from Bayer Schering, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva; and congress, travel, and accommodation expense compensations from Almirall, Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva. RA received conference travel support from Novartis, Teva, Biogen, Bayer, and Merck, and participated in clinical trials by Biogen, Novartis, Teva, and Actelion. JLS-M received travel compensation from Novartis and Biogen; received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer, and Teva; and participated in a clinical trial by Biogen. JP received travel compensation from Novartis, Biogen, Genzyme, and Teva, and speaking honoraria from Biogen, Novartis, Genzyme and Teva. TC-T received speaking or consulting fees and/or travel funding from Bayer, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva. GL received travel and/or consultancy compensation from Sanofi Genzyme, Roche, Teva, Merck, Novartis, Celgene, and Biogen. JO received research funding from the MS Society of Canada, the National MS Society, Brain Canada, Biogen Idec, Roche, and EMD Serono, and personal compensation for consulting or speaking from EMD Serono, Sanofi Genzyme, Biogen Idec, Roche, Celgene, and Novartis. AA received personal fees and speaker honoraria from Teva, Merck, Biogen Gen Pharma, Roche, Novartis, Bayer, and Sanofi Genzyme, and received travel and registration grants from Merck, Biogen Gen Pharma, Roche, Sanofi Genzyme, and Bayer. HB received compensation for consulting, talks, and advisory or steering board activities from Biogen, Merck, Novartis, Genzyme, Alfred Health, and Oxford Health Policy Forum, and research support from Novartis, Biogen, Roche, Merck, the National Health and Medical Research Council of Australia, Pennycook Foundation, and MS Research Australia MB served on scientific advisory boards for Biogen, Novartis, and Genzyme, received conference travel support from Biogen and Novartis, and serves on steering committees for trials conducted by Novartis; his institution received research support from Biogen, Merck, and Novartis. EC Cristiano received honoraria as a consultant on scientific advisory boards for Biogen, Bayer Schering, Merck, Genzyme, and Novartis, and participated in clinical trials or other research projects by Merck, Roche, and Novartis. SH received honoraria and consulting fees from Novartis, Bayer Schering, and Sanofi, and travel grants from Novartis, Biogen Idec, and Bayer Schering. GI received compensation for travel, accommodations, and meeting expenses from Bayer Schering, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva. LK received research support from Acorda, Actelion, Allozyne, BaroFold, Bayer HealthCare, Bayer Schering, Bayhill Therapeutics, Biogen, Elan, European Union, Genmab, Gianni Rubatto Foundation, GlaxoSmithKline, Glenmark, MediciNova, Merck, Novartis, Novartis Research Foundation, Roche, Roche Research Foundation, Sanofi-Aventis, Santhera, the Swiss MS Society, the Swiss National Research Foundation, Teva Neuroscience, UCB, and Wyeth. BW-G participated in speakers' bureaus and/or served as a consultant for Biogen, EMD Serono, Novartis, Genentech, Celgene/Bristol Meyers Squibb, Sanofi Genzyme, Bayer, Janssen, and Horizon; received grant/research support from these same agencies; and serves on editorial boards for BMJ Neurology, Children, CNS Drugs, MS International, and Frontiers Epidemiology. BVW received research and travel grants and honoraria for advisory and speaking fees from Bayer Schering, Biogen, Sanofi Genzyme, Merck, Novartis, Roche, and Teva. TK served on scientific advisory boards for BMS, Roche, Sanofi Genzyme, Novartis, Merck, and Biogen, and the steering committee for the Brain Atrophy Initiative by Sanofi Genzyme; received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi Genzyme, Teva, BioCSL, and Merck; and received support for research or educational events from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck.

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Disability accrual in primary and secondary progressive multiple sclerosis

Affiliations

Disability accrual in primary and secondary progressive multiple sclerosis

Authors

Affiliations

Abstract

Conflict of interest statement

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