The experts are very enthusiastic about starting disease-modifying treatment as early as possible. This abstract is from the ECTRIMS conference (Paris), October 26, 2017:
The effect of disease-modifying treatments on conversion to secondary progressive multiple sclerosis
J.W.L. Brown1,2,3, A. Coles1, D. Horakova4, E. Havrdova4, M. Trojano5, G. Izquierdo6, A. Prat7,8, M. Girard7,8, R. Hupperts9, V. Van Pesch10, D. Ferraro11, R. Alroughani12, R. Bergamaschi13, E. Pucci14, G. Iuliano15, J. Lechner-Scott16,17, T. Spelman18,19, V. Jokubaitis18,19, C. Ramo-Tello20, D. Spitaleri21, F. Granella22, C. Solaro23, R. Ampapa24, N. Deri25, P. McCombe26,27, T. Petersen28, B. Van Wijmeersch29, J. Prevost30, J.L. Sanchez-Menoyo31, A. Soysal32, M. Barnett33, F. Moore34, C. Rice35,36, N. Scolding35,36, A. Wilkins35, C. McGuigan37,38, M. Hutchinson37,38, T. Ziemssen39, O. Pearson40, K. Harding41, P. Duquette7,8, A. Lugaresi42,43,44, P. Grammond45, F. Grand'Maison46, M. Terzi47, V. Shaygannejad48, P. Sola49, H. Butzkueven18,19,50, T. Kalincik3,18,19, N. Robsertson41,51
1Department of Clinical Neurosciences, University of Cambridge, Cambridge, 2NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, United Kingdom, 3University of Melbourne, CORe Unit, Department of Medicine, Melbourne, VIC, Australia, 4Department of Clinical Neurosciences, Charles University and General University in Prague, Prague, Czech Republic, 5Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy, 6Hospital Universitario Virgen Macarena, Sevilla, Spain, 7Hopital Notre Dame, 8CHUM and Universite de Montreal, Montreal, QC, Canada, 9Zuyderland Medical Center, Sittard-Geleen, The Netherlands, 10Cliniques Universitaires Saint-Luc, Brussels, Belgium, 11Azienda Ospedaliera Universitaria, Modena, Italy, 12Amiri Hospital, Kuwait City, Kuwait, 13C. Mondino National Neurological Institute, Pavia, 14Azienda Sanitaria Unica Regionale Marche, Macerata, 15Ospedali Riuniti di Salerno, Salerno, Italy, 16School of Medicine and Public Health, University Newcastle, 17Department of Neurology, John Hunter Hospital, Newcastle, NSW, 18Department of Medicine, 19Department of Neurology, University of Melbourne, Royal Melbourne Hospital, Melbourne, VIC, Australia, 20Hospital Germans Trias i Pujol, Badalona, Spain, 21Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avvelino, 22University of Parma, Parma, 23Ospedale P. A. Micone, Genova, Italy, 24Nemocnice Jihlava, Jihlava, Czech Republic, 25Hospital Fernandez, Capital Federal, Argentina, 26University of Queensland, 27Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia, 28Kommunehospitalet, Arhus, Denmark, 29Rehabilitation and MS-Centre Overpelt and Hasselt University, Hasselt, Belgium, 30CSSS Saint-Jérôme, Saint-Jerome, QC, Canada, 31Hospital de Galdakao-Usansolo, San Sebastian, Spain, 32Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey, 33Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia, 34Jewish General Hospital, Montreal, QC, Canada, 35Department of Neurology, Southmead Hospital, 36Department of Clinical Neurosciences, University of Bristol, Bristol, United Kingdom, 37School of Medicine and Medical Sciences, University College Dublin, 38St Vincent's University Hospital, Dublin, Ireland, 39Center of Clinical Neuroscience, Department of Neurology, MS Center Dresden, University of Dresden, Dresden, Germany, 40Abertawe Bro, Morgannwg University Local Health Board, Swansea, 41Institute for Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom, 42Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio, Chieti, 43Department of Biomedical and Neuromotor Sciences, University of Bologna, University of Bologna, 44IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, 45CISSS Chaudière-Appalache, Levis, 46Neuro Rive-Sud, Montreal, QC, Canada, 4719 Mayis University, Medical Faculty, Samsun, Turkey, 48Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran, 49Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy, 50Department of Neurology, Box Hill Hospital, Monash University, Melbourne, VIC, Australia, 51University Hospital of Wales, Cardiff, United Kingdom
Background:
Licensed immunotherapies do not slow secondary progressive multiple sclerosis (SPMS) once it has begun. The extent to which SPMS reflects early inflammation - and whether conversion to SPMS might be modified by immunomodulatory disease-modifying therapies (DMTs) during the relapsing-remitting (RR) phase - remains unclear.
Objective:
We examined whether DMTs delay or reduce conversion from RRMS to SPMS using an objective definition of SPMS (Lorscheider 2016, Brain).
Methods:
Patients from MSBase with RRMS treated with a single DMT (injectables (interferons/glatiramer acetate, n=240), fingolimod (n=109), natalizumab (n=93) or alemtuzumab (n=44) with at least 4 years' on-treatment follow-up were each propensity matched to 1) untreated patients with RRMS from a historical cohort (n=622, mean follow-up 9.2 years); then 2) different DMT groups. Patients were matched on gender plus baseline age, annualised-relapse rate, EDSS score and disease duration.
Weighted conditional proportional hazards models adjusted for EDSS frequency with pair-wise censoring compared the proportions of each group free from conversion to SPMS. Lower efficacy drug groups may have been biased towards milder disease through excluding patients with multiple DMTs (such as treatment escalators). We therefore limited the injectables group to patients followed-up before higher-efficacy drugs (for treatment escalation) became available in 2006.
Results:
Injectables (HR 0.31, p< 0.001, median censored on-treatment follow-up 7.9 years), fingolimod (HR 0.23, p< 0.001, follow-up 4.6 years), natalizumab (HR 0.50, p=0.001, follow-up 4.9 years) and alemtuzumab (HR 0.60, p=0.01, follow-up 7.2 years) reduced the hazard of conversion to SPMS compared to different groups of matched untreated patients in a series of pairwise analyses.
When matching between the treated cohorts there was no significant difference in conversion to SPMS between alemtuzumab and natalizumab patients (p=0.2). Alemtuzumab and natalizumab were therefore combined as 'high-efficacy therapies' (n=118) and matched and compared to the injectables group (n=236). High-efficacy therapies conferred greater protection against conversion to SPMS than injectables (HR 0.65, p=0.038, follow-up 5.7 years).
Conclusion:
SPMS is - at least partially - a consequence of early inflammation. The risk of conversion from RRMS to SPMS is modifiable over 5 years with existing DMTs, more so with high-efficacy therapies, alemtuzumab and natalizumab.
________
The abstract mentions MS Base. According to its Website,
The effect of disease-modifying treatments on conversion to secondary progressive multiple sclerosis
J.W.L. Brown1,2,3, A. Coles1, D. Horakova4, E. Havrdova4, M. Trojano5, G. Izquierdo6, A. Prat7,8, M. Girard7,8, R. Hupperts9, V. Van Pesch10, D. Ferraro11, R. Alroughani12, R. Bergamaschi13, E. Pucci14, G. Iuliano15, J. Lechner-Scott16,17, T. Spelman18,19, V. Jokubaitis18,19, C. Ramo-Tello20, D. Spitaleri21, F. Granella22, C. Solaro23, R. Ampapa24, N. Deri25, P. McCombe26,27, T. Petersen28, B. Van Wijmeersch29, J. Prevost30, J.L. Sanchez-Menoyo31, A. Soysal32, M. Barnett33, F. Moore34, C. Rice35,36, N. Scolding35,36, A. Wilkins35, C. McGuigan37,38, M. Hutchinson37,38, T. Ziemssen39, O. Pearson40, K. Harding41, P. Duquette7,8, A. Lugaresi42,43,44, P. Grammond45, F. Grand'Maison46, M. Terzi47, V. Shaygannejad48, P. Sola49, H. Butzkueven18,19,50, T. Kalincik3,18,19, N. Robsertson41,51
1Department of Clinical Neurosciences, University of Cambridge, Cambridge, 2NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, United Kingdom, 3University of Melbourne, CORe Unit, Department of Medicine, Melbourne, VIC, Australia, 4Department of Clinical Neurosciences, Charles University and General University in Prague, Prague, Czech Republic, 5Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy, 6Hospital Universitario Virgen Macarena, Sevilla, Spain, 7Hopital Notre Dame, 8CHUM and Universite de Montreal, Montreal, QC, Canada, 9Zuyderland Medical Center, Sittard-Geleen, The Netherlands, 10Cliniques Universitaires Saint-Luc, Brussels, Belgium, 11Azienda Ospedaliera Universitaria, Modena, Italy, 12Amiri Hospital, Kuwait City, Kuwait, 13C. Mondino National Neurological Institute, Pavia, 14Azienda Sanitaria Unica Regionale Marche, Macerata, 15Ospedali Riuniti di Salerno, Salerno, Italy, 16School of Medicine and Public Health, University Newcastle, 17Department of Neurology, John Hunter Hospital, Newcastle, NSW, 18Department of Medicine, 19Department of Neurology, University of Melbourne, Royal Melbourne Hospital, Melbourne, VIC, Australia, 20Hospital Germans Trias i Pujol, Badalona, Spain, 21Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avvelino, 22University of Parma, Parma, 23Ospedale P. A. Micone, Genova, Italy, 24Nemocnice Jihlava, Jihlava, Czech Republic, 25Hospital Fernandez, Capital Federal, Argentina, 26University of Queensland, 27Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia, 28Kommunehospitalet, Arhus, Denmark, 29Rehabilitation and MS-Centre Overpelt and Hasselt University, Hasselt, Belgium, 30CSSS Saint-Jérôme, Saint-Jerome, QC, Canada, 31Hospital de Galdakao-Usansolo, San Sebastian, Spain, 32Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey, 33Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia, 34Jewish General Hospital, Montreal, QC, Canada, 35Department of Neurology, Southmead Hospital, 36Department of Clinical Neurosciences, University of Bristol, Bristol, United Kingdom, 37School of Medicine and Medical Sciences, University College Dublin, 38St Vincent's University Hospital, Dublin, Ireland, 39Center of Clinical Neuroscience, Department of Neurology, MS Center Dresden, University of Dresden, Dresden, Germany, 40Abertawe Bro, Morgannwg University Local Health Board, Swansea, 41Institute for Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom, 42Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio, Chieti, 43Department of Biomedical and Neuromotor Sciences, University of Bologna, University of Bologna, 44IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, 45CISSS Chaudière-Appalache, Levis, 46Neuro Rive-Sud, Montreal, QC, Canada, 4719 Mayis University, Medical Faculty, Samsun, Turkey, 48Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran, 49Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy, 50Department of Neurology, Box Hill Hospital, Monash University, Melbourne, VIC, Australia, 51University Hospital of Wales, Cardiff, United Kingdom
Background:
Licensed immunotherapies do not slow secondary progressive multiple sclerosis (SPMS) once it has begun. The extent to which SPMS reflects early inflammation - and whether conversion to SPMS might be modified by immunomodulatory disease-modifying therapies (DMTs) during the relapsing-remitting (RR) phase - remains unclear.
Objective:
We examined whether DMTs delay or reduce conversion from RRMS to SPMS using an objective definition of SPMS (Lorscheider 2016, Brain).
Methods:
Patients from MSBase with RRMS treated with a single DMT (injectables (interferons/glatiramer acetate, n=240), fingolimod (n=109), natalizumab (n=93) or alemtuzumab (n=44) with at least 4 years' on-treatment follow-up were each propensity matched to 1) untreated patients with RRMS from a historical cohort (n=622, mean follow-up 9.2 years); then 2) different DMT groups. Patients were matched on gender plus baseline age, annualised-relapse rate, EDSS score and disease duration.
Weighted conditional proportional hazards models adjusted for EDSS frequency with pair-wise censoring compared the proportions of each group free from conversion to SPMS. Lower efficacy drug groups may have been biased towards milder disease through excluding patients with multiple DMTs (such as treatment escalators). We therefore limited the injectables group to patients followed-up before higher-efficacy drugs (for treatment escalation) became available in 2006.
Results:
Injectables (HR 0.31, p< 0.001, median censored on-treatment follow-up 7.9 years), fingolimod (HR 0.23, p< 0.001, follow-up 4.6 years), natalizumab (HR 0.50, p=0.001, follow-up 4.9 years) and alemtuzumab (HR 0.60, p=0.01, follow-up 7.2 years) reduced the hazard of conversion to SPMS compared to different groups of matched untreated patients in a series of pairwise analyses.
When matching between the treated cohorts there was no significant difference in conversion to SPMS between alemtuzumab and natalizumab patients (p=0.2). Alemtuzumab and natalizumab were therefore combined as 'high-efficacy therapies' (n=118) and matched and compared to the injectables group (n=236). High-efficacy therapies conferred greater protection against conversion to SPMS than injectables (HR 0.65, p=0.038, follow-up 5.7 years).
Conclusion:
SPMS is - at least partially - a consequence of early inflammation. The risk of conversion from RRMS to SPMS is modifiable over 5 years with existing DMTs, more so with high-efficacy therapies, alemtuzumab and natalizumab.
________
The abstract mentions MS Base. According to its Website,
The MSBase Registry is a unique international collaboration dedicated to sharing, tracking and evaluating outcomes data in multiple sclerosis (MS) and other neuro-immunological diseases (NIDs).
The MSBase Foundation has collaborated with participating MS physicians and their healthcare teams to collate the largest organised repository of longitudinal, 'real-world' MS patient data. The Registry commenced in 2004 and has accumulated over 52,000 patient records from 33 participating countries.
The collaboration aims to better our understanding of MS and improve healthcare for those living with MS by answering epidemiological questions that can only be addressed by prospective assessments of many thousands of patient records. The MSBase simplifies the collection of epidemiological information by providing an electronic Data Entry System. The data entry system software is useful in clinical practice for patient tracking and record management, and is freely available to members, who in turn support the collaborative research initiative.
The MSBase Registry is owned and operated by the MSBase Foundation Ltd, a not-for-profit company registered in Australia. The Foundation is governed by a Global Board of Directors that advises and supports the work of the Registry. The MSBase Scientific Leadership Group (SLG) specifically advises the Foundation on the scientific direction of the Registry. The Operations Team are responsible for the maintenance and management of the Registry and are centralised in Melbourne, Australia.
The MSBase Foundation has collaborated with participating MS physicians and their healthcare teams to collate the largest organised repository of longitudinal, 'real-world' MS patient data. The Registry commenced in 2004 and has accumulated over 52,000 patient records from 33 participating countries.
The collaboration aims to better our understanding of MS and improve healthcare for those living with MS by answering epidemiological questions that can only be addressed by prospective assessments of many thousands of patient records. The MSBase simplifies the collection of epidemiological information by providing an electronic Data Entry System. The data entry system software is useful in clinical practice for patient tracking and record management, and is freely available to members, who in turn support the collaborative research initiative.
The MSBase Registry is owned and operated by the MSBase Foundation Ltd, a not-for-profit company registered in Australia. The Foundation is governed by a Global Board of Directors that advises and supports the work of the Registry. The MSBase Scientific Leadership Group (SLG) specifically advises the Foundation on the scientific direction of the Registry. The Operations Team are responsible for the maintenance and management of the Registry and are centralised in Melbourne, Australia.
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