The effect of disease-modifying treatments on conversion to secondary progressive multiple sclerosis
ECTRIMS Online Library. Brown J. 10/26/17; 202481; 128
J William L Brown
J William L Brown
Contributions
Abstract

Abstract: 128

Type: Oral

Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring

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.
Disclosure: William Brown reports travel expenses for attending conferences or teaching courses from Novartis, Biogen, and Sanofi Genzyme.
Alasdair Coles reports personal fees and honoraria, consulting fees, and travel expenses for attending meetings from Genzyme; AC has a patent on the dose regime of alemtuzumab as a treatment of multiple sclerosis pending.
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck, Teva and Novartis, as well as support for research activities from Biogen and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
Eva Havrdova received speaker honoraria and consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva, and support for research activities from Czech Ministry of Education, project Progres Q27/LF1.
Maria Trojano received speaker honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck, Teva, Novartis and Almirall; has received research grants for her Institution from Biogen-Idec, Merck, and Novartis.
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck and Teva.
Alexandre Prat did not declare any competing interests.
Marc Girard received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research.
Raymond Hupperts received honoraria as consultant on scientific advisory boards from Merck, Biogen, Genzyme-Sanofi and Teva, research funding from Merck and Biogen, and speaker honoraria from Sanofi-Genzyme and Novartis.
Vincent Van Pesch received travel grants from Biogen, Bayer Schering, Genzyme, Merck, Teva and Novartis Pharma. His institution receives honoraria for consultancy and lectures from Biogen, Bayer Schering, Genzyme, Merck, Roche, Teva and Novartis Pharma as well as research grants from Novartis Pharma and Bayer Schering.
Diana Ferraro received travel grants and/or speaker honoraria from Merck, TEVA, Novartis, Biogen and Sanofi-Genzyme.
Raed Alroughani received honororia from Biologix, Biogen, Bayer, Genpharm, Genzyme, Merck, GSK and Novartis, and served on advisory board for Biologix, Biogen, Bayer, Genpharm, Genzyme, Novartis, Genzyme, Merck and Novartis.
Roberto Bergamaschi received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, Teva; research grants from Bayer Schering, Biogen, Merck, Novartis, Sanofi-Aventis, Teva; congress and travel/accommodation expense compensations by Almirall, Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, Teva.
Eugenio Pucci served on scientific advisory boards for Merck, Genzyme and Biogen; he has received honoraria and travel grants from Sanofi Aventis, UCB, Lundbeck, Novartis, Bayer Schering, Biogen, Merck, Genzyme and Teva; he has received travel grants and equipment from 'Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche'.
Gerardo Iuliano had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis, and Teva.
Jeannette Lechner-Scott accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Bayer Health Care, Biogen, Genzyme Sanofi, Merck, Novartis and Teva, has been involved in clinical trials with Biogen, Novartis and Teva.
Tim Spelman received honoraria for consultancy, funding for travel and compensation for serving on scientific advisory boards from Biogen and speaker honoraria from Novartis.
Vilija Jokubaitis received conference travel support from Teva, Novartis and Merck, and speaker honoraria from Biogen.
Cristina Ramo-Tello received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Genzyme and Almirall.
Daniele Spitaleri received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck.
Franco Granella served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and received funding for travel and speaker honoraria from Biogen Idec, Merck, and Almirall.
Claudio Solaro did not declare any competing interests.
Radek Ampapa received conference travel support from Novartis, Teva, Biogen, Bayer and Merck and has participated in a clinical trials by Biogen, Novartis, Teva and Actelion.
Norma Deri received funding from Bayer, Merck, Biogen, Genzyme and Novartis.
Pamela McCombe did not declare any competing interests.
Thor Petersen received funding or speaker honoraria from Biogen, Merck, Novartis, Bayer Schering, Sanofi-Aventis, Roche, and Genzyme.
Bart Van Wijmeersch did not declare any competing interests.
Julie Prevost accepted travel compensation from Novartis, Biogen, Genzyme, Teva, and speaking honoraria from Biogen, Novartis, Genzyme and Teva.
Jose Luis Sanchez-Menoyo accepted travel compensation from Novartis and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen.
Aysun Soysal did not declare any competing interests.
Michael Barnett served on scientific advisory boards for Biogen, Novartis and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis.
Fraser Moore participated in clinical trials sponsored by EMD and Novartis.
Claire Rice reports no competing interests.
Neil Scolding reports grants from Biogen, Sanofi Genzyme, Merck Serono, Teva, and Novartis.
Alastair Wilkins declares no competing interests.
Christopher McGuigan has received grants and personal fees from Biogen, Novartis, Genzyme, Merck and Roche.
Michael Hutchinson served on a medical advisory board for the CONFIRM study (BG00012) for Biogen; has received speaker´s honoraria from Novartis, Biogen, and Bayer Schering; and receives research support from Dystonia Ireland, the Health Research Board of Ireland, and the European Dystonia Foundation.
Tjalf Ziemssen reports grants from Novartis; grants and personal fees from Bayer, Biogen, Teva, Genzyme, and Novartis; and personal fees from Merck, Almirall, GlaxoSmithKline, and Roche.
Owen Pearson declares no competing interests.
Katharine Harding has received one research grant from Novartis.
Pierre Duquette served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme, and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM).
Pierre Grammond is a Merck, Novartis, Teva-neuroscience, Biogen and Genzyme advisory board member, consultant for Merck, received payments for lectures by Merck, Teva-Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva-Neuroscience and Novartis.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Murat Terzi received travel grants from Merck, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Vahid Shaygannejad did not declare any competing interests.
Patrizia Sola served on scientific advisory boards for Biogen Idec and TEVA, she has received funding for travel and speaker honoraria from Biogen Idec, Merck, Teva, Sanofi Genzyme, Novartis and Bayer and research grants for her Institution from Bayer, Biogen, Merck, Novartis, Sanofi, Teva.
Helmut Butzkueven served on scientific advisory boards for Biogen, Novartis and Sanofi-Aventis and has received conference travel support from Novartis, Biogen and Sanofi Aventis. He serves on steering committees for trials conducted by Biogen and Novartis, and has received research support from Merck, Novartis and Biogen.
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme-Sanofi, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme-Sanofi, Teva, BioCSL and Merck and received research support from Biogen.
Neil Robertson reports personal and institutional research grant from Genzyme and Novartis.

Abstract: 128

Type: Oral

Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring

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.
Disclosure: William Brown reports travel expenses for attending conferences or teaching courses from Novartis, Biogen, and Sanofi Genzyme.
Alasdair Coles reports personal fees and honoraria, consulting fees, and travel expenses for attending meetings from Genzyme; AC has a patent on the dose regime of alemtuzumab as a treatment of multiple sclerosis pending.
Dana Horakova received speaker honoraria and consulting fees from Biogen, Merck, Teva and Novartis, as well as support for research activities from Biogen and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
Eva Havrdova received speaker honoraria and consultant fees from Actelion, Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Teva, and support for research activities from Czech Ministry of Education, project Progres Q27/LF1.
Maria Trojano received speaker honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck, Teva, Novartis and Almirall; has received research grants for her Institution from Biogen-Idec, Merck, and Novartis.
Guillermo Izquierdo received speaking honoraria from Biogen, Novartis, Sanofi, Merck and Teva.
Alexandre Prat did not declare any competing interests.
Marc Girard received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research.
Raymond Hupperts received honoraria as consultant on scientific advisory boards from Merck, Biogen, Genzyme-Sanofi and Teva, research funding from Merck and Biogen, and speaker honoraria from Sanofi-Genzyme and Novartis.
Vincent Van Pesch received travel grants from Biogen, Bayer Schering, Genzyme, Merck, Teva and Novartis Pharma. His institution receives honoraria for consultancy and lectures from Biogen, Bayer Schering, Genzyme, Merck, Roche, Teva and Novartis Pharma as well as research grants from Novartis Pharma and Bayer Schering.
Diana Ferraro received travel grants and/or speaker honoraria from Merck, TEVA, Novartis, Biogen and Sanofi-Genzyme.
Raed Alroughani received honororia from Biologix, Biogen, Bayer, Genpharm, Genzyme, Merck, GSK and Novartis, and served on advisory board for Biologix, Biogen, Bayer, Genpharm, Genzyme, Novartis, Genzyme, Merck and Novartis.
Roberto Bergamaschi received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, Teva; research grants from Bayer Schering, Biogen, Merck, Novartis, Sanofi-Aventis, Teva; congress and travel/accommodation expense compensations by Almirall, Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, Teva.
Eugenio Pucci served on scientific advisory boards for Merck, Genzyme and Biogen; he has received honoraria and travel grants from Sanofi Aventis, UCB, Lundbeck, Novartis, Bayer Schering, Biogen, Merck, Genzyme and Teva; he has received travel grants and equipment from 'Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche'.
Gerardo Iuliano had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck, Novartis, Sanofi Aventis, and Teva.
Jeannette Lechner-Scott accepted travel compensation from Novartis, Biogen and Merck. Her institution receives the honoraria for talks and advisory board commitment from Bayer Health Care, Biogen, Genzyme Sanofi, Merck, Novartis and Teva, has been involved in clinical trials with Biogen, Novartis and Teva.
Tim Spelman received honoraria for consultancy, funding for travel and compensation for serving on scientific advisory boards from Biogen and speaker honoraria from Novartis.
Vilija Jokubaitis received conference travel support from Teva, Novartis and Merck, and speaker honoraria from Biogen.
Cristina Ramo-Tello received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Genzyme and Almirall.
Daniele Spitaleri received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck.
Franco Granella served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and received funding for travel and speaker honoraria from Biogen Idec, Merck, and Almirall.
Claudio Solaro did not declare any competing interests.
Radek Ampapa received conference travel support from Novartis, Teva, Biogen, Bayer and Merck and has participated in a clinical trials by Biogen, Novartis, Teva and Actelion.
Norma Deri received funding from Bayer, Merck, Biogen, Genzyme and Novartis.
Pamela McCombe did not declare any competing interests.
Thor Petersen received funding or speaker honoraria from Biogen, Merck, Novartis, Bayer Schering, Sanofi-Aventis, Roche, and Genzyme.
Bart Van Wijmeersch did not declare any competing interests.
Julie Prevost accepted travel compensation from Novartis, Biogen, Genzyme, Teva, and speaking honoraria from Biogen, Novartis, Genzyme and Teva.
Jose Luis Sanchez-Menoyo accepted travel compensation from Novartis and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen.
Aysun Soysal did not declare any competing interests.
Michael Barnett served on scientific advisory boards for Biogen, Novartis and Genzyme and has received conference travel support from Biogen and Novartis. He serves on steering committees for trials conducted by Novartis. His institution has received research support from Biogen, Merck and Novartis.
Fraser Moore participated in clinical trials sponsored by EMD and Novartis.
Claire Rice reports no competing interests.
Neil Scolding reports grants from Biogen, Sanofi Genzyme, Merck Serono, Teva, and Novartis.
Alastair Wilkins declares no competing interests.
Christopher McGuigan has received grants and personal fees from Biogen, Novartis, Genzyme, Merck and Roche.
Michael Hutchinson served on a medical advisory board for the CONFIRM study (BG00012) for Biogen; has received speaker´s honoraria from Novartis, Biogen, and Bayer Schering; and receives research support from Dystonia Ireland, the Health Research Board of Ireland, and the European Dystonia Foundation.
Tjalf Ziemssen reports grants from Novartis; grants and personal fees from Bayer, Biogen, Teva, Genzyme, and Novartis; and personal fees from Merck, Almirall, GlaxoSmithKline, and Roche.
Owen Pearson declares no competing interests.
Katharine Harding has received one research grant from Novartis.
Pierre Duquette served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme, and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme.
Alessandra Lugaresi is a Bayer, Biogen, Genzyme, Merck Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM). Her institution received research grants from Bayer, Biogen, Merck, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla (FISM).
Pierre Grammond is a Merck, Novartis, Teva-neuroscience, Biogen and Genzyme advisory board member, consultant for Merck, received payments for lectures by Merck, Teva-Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva-Neuroscience and Novartis.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Murat Terzi received travel grants from Merck, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Vahid Shaygannejad did not declare any competing interests.
Patrizia Sola served on scientific advisory boards for Biogen Idec and TEVA, she has received funding for travel and speaker honoraria from Biogen Idec, Merck, Teva, Sanofi Genzyme, Novartis and Bayer and research grants for her Institution from Bayer, Biogen, Merck, Novartis, Sanofi, Teva.
Helmut Butzkueven served on scientific advisory boards for Biogen, Novartis and Sanofi-Aventis and has received conference travel support from Novartis, Biogen and Sanofi Aventis. He serves on steering committees for trials conducted by Biogen and Novartis, and has received research support from Merck, Novartis and Biogen.
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme-Sanofi, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Genzyme-Sanofi, Teva, BioCSL and Merck and received research support from Biogen.
Neil Robertson reports personal and institutional research grant from Genzyme and Novartis.

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies