Contributions
Abstract: 154
Type: Oral
Abstract Category: Clinical aspects of MS - Natural course
Background: Over the last decades several natural history studies on primary progressive MS (PPMS) patients were reported from international registries. In this population a consistent heterogeneity was observed in the rate of disability accumulation, as time to reach the milestone of EDSS 6 ranged between 7 and 14 years1-3 from onset.
Objectives: To identify subgroups of PPMS patients with similar longitudinal trajectories of EDSS over time.
Methods: All PPMS patients collected within MSBase international registry, who had their first EDSS assessment within 5 years from onset were included in the analysis. Longitudinal EDSS scores were modelled by a latent class mixed model (LCMM), using a nonlinear function of time from onset. LCMM is an advanced statistical approach that models heterogeneity between patients by classifying them into unobserved groups (latent classes) showing similar characteristics.
Results: A total of 853 PPMS (51.7% females) from 24 countries with a mean age at onset of 42.4 yrs (SD: 10.8 yrs), a median baseline EDSS of 4 (IQR: 2.5-5.5) and 2.4 yrs of disease duration (SD: 1.5 yrs) were included. LCMM detected 3 different subgroups of patients with, respectively, a mild (n=143 ;16.8%), a moderate (n=378; 44.3%) and a severe (n=332; 38.9%) disability trajectory. Median time to EDSS 4 was 14, 5 and 3.7 years, for the 3 groups respectively; the probability to reach EDSS 6 at 10 years was 0%, 46.5% and 83.1% respectively. Increasing the severity of the disability time course was related to a decreased frequency of patients with at least one relapse during follow-up from 47.6% to 36.5% (p=0.033). Using this modelling approach it is possible to predict the future disease course of a subject with PPMS using early EDSS assessments: by using only 1 year of EDSS monitoring 73% of patients are correctly classified in their disability trajectory group (mild, moderate or severe); after 3 years this proportion is 87% and after 5 years it is 92%.
Conclusions: Using long term observations and a LCMM modelling approach it is possible to build a dynamic model, to predict the future disability trajectory of a new patient with PPMS. In the design of future clinical trials in PPMS, with time to reach disability milestones as the primary endpoint, the existence of heterogeneous classes of patients should be considered.
References:
1.Koch M. Neurology 2009; 73
2. Leray E. Brain. 2010; 133.
3. Koch M. J Neurol Neurosurg Psychiatry 2015; 86.
Disclosure:
Alessio Signori has received research grant from MSBase Foundation and fee from Novartis for teaching activities
Guillermo Izquierdo received consulting fees from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, and Teva.
Alessandra Lugaresi has served as a Bayer, Biogen, Merck Serono, Novartis and Genzyme Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla and research grants for her Institution from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla.
Raymond Hupperts received honoraria as consultant on scientific advisory boards from Merck-Serono, Biogen, Genzyme-Sanofi and Teva, research funding from Merck-Serono and Biogen, and speaker honoraria from Sanofi-Genzyme and Novartis.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Patrizia Sola has received research support for her Institution from Merck Serono, TEVA, Biogen Idec, Novartis, Genzyme Sanofi Aventis and has received a speaker honorarium from TEVA, Genzyme, Bayer Schering Pharma and Biogen Idec.
Dana Horakova was supported by the Czech Ministry of Education (Research Program MSM 0021620849) and by the Czech Science Foundation (GA CR 16-03322S). She also received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, and Teva, as well as support for research activities from Biogen Idec.
Eva Havrdova received speaker honoraria and consultant fees from Biogen, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen, Merck Serono and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
Alexandre Prat: nothing to disclose.
Marc Girard received compensation for Scientific Advisory Board and speaker honoraria from Biogen, Genzyme, EMD Serono, Teva Canada Innovation and Novartis.
Pierre Duquette served on editorial boards and has been supported to attend meetings by EMDSerono, 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.
Cavit Boz received conference travel support from Biogen, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Pierre Gramond serves on Scientific Advisory board for Biogen Idec, Merk-Serono, Genzyme, Novartis; he has received support for lectures from Teva neuroscience, Merk-Serono, Genzyme and Biogen idec; he has received support for travel/accomodation from Teva Neuroscience, Merk-Serono and Novartis; he has received Research Support from Biogen Idec, Sanofi-Avantis, MSBase, EMD-Serono.
Murat Terzi received travel grants from Merck Serono, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Bhim Singhal received consultancy honoraria and compensation for travel from Biogen and Merck-Serono.
Raed Alroughani Received speaker´s honoraria from Biogen, Bayer, Merck-Sorono, Novartis, GSK, and Genzyme. Served on scientific advisory board of Bayer, Genzyme, Biogen, Merck-Sorono and Novartis.
Thor Petersen received funding or speaker honoraria from Biogen, Merck Serono, Novartis, Bayer Schering, Sanofi-Aventis, Roche, and Genzyme.
Cristina Ramo received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Genzyme and Almirall.
Celia Oreja-Guevara has served on scientific Advisory Boards for Biogen, Roche and Genzyme and has received speaker honoraria from Biogen-Idec, Genzyme, Merck-Serono, Teva, Roche, and Novartis.
Daniele Spitaleri received honoraria as consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen Idec, Sanofi Aventis, Teva and Merck Serono.
Vahid Shaygannejad: nothing to disclose.
Helmut Butzkueven serves on Scientific Advisory Boards for the MSBase Foundation, Novartis, Biogen, Genzyme, Merck, Roche and Multiple Sclerosis Research Australia. He has received speaker and travel support from Novartis, Biogen, Genzyme, Merck and Medscape. Dr Butzkueven has a consultancy arrangement for the MS Brain Health Initiative with Oxford Pharmagenesis. He has received Research Support from Biogen, Merck, and Novartis.
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme, Novartis, Merck and Biogen, has received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi, Genzyme, Teva, BioCSL and Merck and has received research support from Biogen.
Vilija Jokubaitis has received conference travel support from Merck and Novartis; and speakers honoraria from Novartis and Biogen.
Mark Slee has nothing to disclose.
Ricardo Fernandez Bolaños received speaking honoraria from Biogen, Novartis, Merck Serono and Teva.
Jose Luis Sanchez-Menoyo received travel compensation from Novartis, Merch Serono and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen.
Eugenio Pucci reports personal fees and non-financial support from Biogen Idec, Merck Serono, Teva, Genzyme and Novartis.
Franco Granella has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and has received funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall.
Jeannette Lechner-Scott has accepted travel compensation from Novartis, Biogen and Merck Serono. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Bayer Health Care, Biogen Idec, CSL, Genzyme Sanofi, Merck, Novartis and TEVA.
Gerardo Iuliano had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi Aventis, and Teva.
Stella Hughes did not declare any competing interests.
Roberto Bergamaschi has served on scientific advisory boards for Biogen Idec and Almirall; has received honoraria for speaking from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva; has received funding for congress and travel/accommodation expenses for scientific meetings from Sanofi-Aventis, Genzyme, Biogen Idec , Bayer Schering, Teva, Merck Serono, Almirall, and Novartis; has received research grants from Merck Serono, Biogen Idec, Teva Neurosciences, Bayer Schering, Novartis, Sanofi-Aventis, Genzym
Maria Edite Rio : nothing to disclose
Maria Pia Amato has served on scientific Advisory Boards for Biogen, Novartis, Almirall, Roche and Genzyme; has received speaker honoraria from Biogen-Idec, Sanofi Aventis, Merck-Serono, Teva, Genzyme, Almirall and Novartis; has received research grants from Biogen-Idec, Merck-Serono, Novartis and Teva.
Seyed Aidin Sajedi: nothing to disclose
Nastaran Majdinasab: nothing to disclose
Vincent van Pesch has 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.
Maria Pia Sormani has received personal compensation for consulting services and for speaking activities from Genzyme, Merck Serono, Teva, Synthon, Roche, Novartis and Biogen .
Maria Trojano has served on scientific Advisory Boards for Biogen, Novartis, Almirall, Roche and Genzyme; has received speaker honoraria from Biogen-Idec, Sanofi Aventis, Merck-Serono, Teva, Genzyme, Almirall and Novartis; has received research grants for her Institution from Biogen Idec, Merck-Serono and Novartis.
Abstract: 154
Type: Oral
Abstract Category: Clinical aspects of MS - Natural course
Background: Over the last decades several natural history studies on primary progressive MS (PPMS) patients were reported from international registries. In this population a consistent heterogeneity was observed in the rate of disability accumulation, as time to reach the milestone of EDSS 6 ranged between 7 and 14 years1-3 from onset.
Objectives: To identify subgroups of PPMS patients with similar longitudinal trajectories of EDSS over time.
Methods: All PPMS patients collected within MSBase international registry, who had their first EDSS assessment within 5 years from onset were included in the analysis. Longitudinal EDSS scores were modelled by a latent class mixed model (LCMM), using a nonlinear function of time from onset. LCMM is an advanced statistical approach that models heterogeneity between patients by classifying them into unobserved groups (latent classes) showing similar characteristics.
Results: A total of 853 PPMS (51.7% females) from 24 countries with a mean age at onset of 42.4 yrs (SD: 10.8 yrs), a median baseline EDSS of 4 (IQR: 2.5-5.5) and 2.4 yrs of disease duration (SD: 1.5 yrs) were included. LCMM detected 3 different subgroups of patients with, respectively, a mild (n=143 ;16.8%), a moderate (n=378; 44.3%) and a severe (n=332; 38.9%) disability trajectory. Median time to EDSS 4 was 14, 5 and 3.7 years, for the 3 groups respectively; the probability to reach EDSS 6 at 10 years was 0%, 46.5% and 83.1% respectively. Increasing the severity of the disability time course was related to a decreased frequency of patients with at least one relapse during follow-up from 47.6% to 36.5% (p=0.033). Using this modelling approach it is possible to predict the future disease course of a subject with PPMS using early EDSS assessments: by using only 1 year of EDSS monitoring 73% of patients are correctly classified in their disability trajectory group (mild, moderate or severe); after 3 years this proportion is 87% and after 5 years it is 92%.
Conclusions: Using long term observations and a LCMM modelling approach it is possible to build a dynamic model, to predict the future disability trajectory of a new patient with PPMS. In the design of future clinical trials in PPMS, with time to reach disability milestones as the primary endpoint, the existence of heterogeneous classes of patients should be considered.
References:
1.Koch M. Neurology 2009; 73
2. Leray E. Brain. 2010; 133.
3. Koch M. J Neurol Neurosurg Psychiatry 2015; 86.
Disclosure:
Alessio Signori has received research grant from MSBase Foundation and fee from Novartis for teaching activities
Guillermo Izquierdo received consulting fees from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, and Teva.
Alessandra Lugaresi has served as a Bayer, Biogen, Merck Serono, Novartis and Genzyme Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla and research grants for her Institution from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla.
Raymond Hupperts received honoraria as consultant on scientific advisory boards from Merck-Serono, Biogen, Genzyme-Sanofi and Teva, research funding from Merck-Serono and Biogen, and speaker honoraria from Sanofi-Genzyme and Novartis.
Francois Grand´Maison received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals.
Patrizia Sola has received research support for her Institution from Merck Serono, TEVA, Biogen Idec, Novartis, Genzyme Sanofi Aventis and has received a speaker honorarium from TEVA, Genzyme, Bayer Schering Pharma and Biogen Idec.
Dana Horakova was supported by the Czech Ministry of Education (Research Program MSM 0021620849) and by the Czech Science Foundation (GA CR 16-03322S). She also received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, and Teva, as well as support for research activities from Biogen Idec.
Eva Havrdova received speaker honoraria and consultant fees from Biogen, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen, Merck Serono and research grants from Charles University in Prague (PRVOUK-P26/LF1/4 and Czech Ministry of Health (NT13237-4/2012).
Alexandre Prat: nothing to disclose.
Marc Girard received compensation for Scientific Advisory Board and speaker honoraria from Biogen, Genzyme, EMD Serono, Teva Canada Innovation and Novartis.
Pierre Duquette served on editorial boards and has been supported to attend meetings by EMDSerono, 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.
Cavit Boz received conference travel support from Biogen, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Pierre Gramond serves on Scientific Advisory board for Biogen Idec, Merk-Serono, Genzyme, Novartis; he has received support for lectures from Teva neuroscience, Merk-Serono, Genzyme and Biogen idec; he has received support for travel/accomodation from Teva Neuroscience, Merk-Serono and Novartis; he has received Research Support from Biogen Idec, Sanofi-Avantis, MSBase, EMD-Serono.
Murat Terzi received travel grants from Merck Serono, Novartis, Bayer-Schering, Merck-Serono and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis.
Bhim Singhal received consultancy honoraria and compensation for travel from Biogen and Merck-Serono.
Raed Alroughani Received speaker´s honoraria from Biogen, Bayer, Merck-Sorono, Novartis, GSK, and Genzyme. Served on scientific advisory board of Bayer, Genzyme, Biogen, Merck-Sorono and Novartis.
Thor Petersen received funding or speaker honoraria from Biogen, Merck Serono, Novartis, Bayer Schering, Sanofi-Aventis, Roche, and Genzyme.
Cristina Ramo received research funding, compensation for travel or speaker honoraria from Biogen, Novartis, Genzyme and Almirall.
Celia Oreja-Guevara has served on scientific Advisory Boards for Biogen, Roche and Genzyme and has received speaker honoraria from Biogen-Idec, Genzyme, Merck-Serono, Teva, Roche, and Novartis.
Daniele Spitaleri received honoraria as consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen Idec, Sanofi Aventis, Teva and Merck Serono.
Vahid Shaygannejad: nothing to disclose.
Helmut Butzkueven serves on Scientific Advisory Boards for the MSBase Foundation, Novartis, Biogen, Genzyme, Merck, Roche and Multiple Sclerosis Research Australia. He has received speaker and travel support from Novartis, Biogen, Genzyme, Merck and Medscape. Dr Butzkueven has a consultancy arrangement for the MS Brain Health Initiative with Oxford Pharmagenesis. He has received Research Support from Biogen, Merck, and Novartis.
Tomas Kalincik served on scientific advisory boards for Roche, Genzyme, Novartis, Merck and Biogen, has received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi, Genzyme, Teva, BioCSL and Merck and has received research support from Biogen.
Vilija Jokubaitis has received conference travel support from Merck and Novartis; and speakers honoraria from Novartis and Biogen.
Mark Slee has nothing to disclose.
Ricardo Fernandez Bolaños received speaking honoraria from Biogen, Novartis, Merck Serono and Teva.
Jose Luis Sanchez-Menoyo received travel compensation from Novartis, Merch Serono and Biogen, speaking honoraria from Biogen, Novartis, Sanofi, Merck Serono, Almirall, Bayer and Teva and has participated in a clinical trial by Biogen.
Eugenio Pucci reports personal fees and non-financial support from Biogen Idec, Merck Serono, Teva, Genzyme and Novartis.
Franco Granella has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and has received funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall.
Jeannette Lechner-Scott has accepted travel compensation from Novartis, Biogen and Merck Serono. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Bayer Health Care, Biogen Idec, CSL, Genzyme Sanofi, Merck, Novartis and TEVA.
Gerardo Iuliano had travel/accommodations/meeting expenses funded by Bayer Schering, Biogen, Merck Serono, Novartis, Sanofi Aventis, and Teva.
Stella Hughes did not declare any competing interests.
Roberto Bergamaschi has served on scientific advisory boards for Biogen Idec and Almirall; has received honoraria for speaking from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva; has received funding for congress and travel/accommodation expenses for scientific meetings from Sanofi-Aventis, Genzyme, Biogen Idec , Bayer Schering, Teva, Merck Serono, Almirall, and Novartis; has received research grants from Merck Serono, Biogen Idec, Teva Neurosciences, Bayer Schering, Novartis, Sanofi-Aventis, Genzym
Maria Edite Rio : nothing to disclose
Maria Pia Amato has served on scientific Advisory Boards for Biogen, Novartis, Almirall, Roche and Genzyme; has received speaker honoraria from Biogen-Idec, Sanofi Aventis, Merck-Serono, Teva, Genzyme, Almirall and Novartis; has received research grants from Biogen-Idec, Merck-Serono, Novartis and Teva.
Seyed Aidin Sajedi: nothing to disclose
Nastaran Majdinasab: nothing to disclose
Vincent van Pesch has 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.
Maria Pia Sormani has received personal compensation for consulting services and for speaking activities from Genzyme, Merck Serono, Teva, Synthon, Roche, Novartis and Biogen .
Maria Trojano has served on scientific Advisory Boards for Biogen, Novartis, Almirall, Roche and Genzyme; has received speaker honoraria from Biogen-Idec, Sanofi Aventis, Merck-Serono, Teva, Genzyme, Almirall and Novartis; has received research grants for her Institution from Biogen Idec, Merck-Serono and Novartis.