Contributions
Abstract: 170
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - Environmental factors
Background: A dynamic model for predicting long-term prognosis incorporating age, sex, topography of CIS, oligoclonal bands (OB) and number of T2 lesions was presented.
Objectives: The aim is to include modifiable environmental factors such as vitamin D (VitD) and cotinine (Cot) serum levels (as a surrogate for smoking status) to our modelling strategy for predicting long-term prognosis.
Methods: From 1995 to 2016, 1088 CIS patients were prospectively recruited for clinical assessment and brain MRI follow-up. Baseline hazard for EDSS 3.0 was calculated after fitting several parametric models (Weibull, generalized Gamma) for a linear combination of baseline domains: age, sex, topography, OB and baseline T2 lesions. A recursive partitioning regression tree (RPART) method was used to stratify in risk groups according to their predicted median time to EDSS 3.0. This prognostic model was further updated adding VitD deficiency (N= 472; cut-off 8ng/ml), smoking (N= 435; Cot cut-off 14ng/ml) and their interactions with risk groups. Harrell C statistic was used to evaluate performance of these models.
Results: The model is based on1062 patients with more than one year of follow up. After fitting several models, a final Weibull (proportional hazard) model, was selected. RPART allowed stratifying patients in three groups: low risk (N=442; HR1.0 reference), medium risk (N=561: HR 3.0; 95%CI 2.0-4.6) and high Risk (N=51: HR 9.6; 95%CI 5.6-16.4) with a Harrell C of 0.65. For patients with VitD determination, an interaction was observed for VitD deficiency and risk group. Thus, Vit D deficiency increased the risk for EDSS progression and patients with low risk moved to the medium risk group and patients with medium risk moved to high risk. In patients already with high risk, the impact VitD deficiency was minor. Overall Harrell C increased from 0.65 to 0.69. For patients with Cot determination an interaction was observed for smoking and risk group. High Cot levels increased the risk for EDSS progression and patients with low risk moved to the medium risk group and patients with medium risk moved to high risk. For high-risk group, adding smoking status raised their HRs from 13.8 (95%CI 5.4-35.2) to 64.2 (123.2-311.9). Harrell C improved from 0.68 to 0.73.
Conclusion: Smoking and low vitamin D levels are key modifiable prognostic factors that show a dramatic interaction with risk of EDSS progression. Design of preventive strategies is warranted.
Disclosure: M Tintore has received compensation for consulting services and speaking honoraria from Almirall, Bayer Schering Pharma, , Biogen-Idec, Genzyme, Merck-Serono, Novartis, Roche, Sanofi-Aventis, and Teva Pharmaceuticals. MT is co-editor of Multiple Sclerosis Journal-ETC
G Arrambide has received compensation for consulting services from Biogen-Idec, research support and travel expenses for scientific meetings from Novartis, and speaking honoraria from Sanofi-Aventis.
S Otero-Romero has received compensation for consulting services from Biogen-Idec and Genzyme, and research support from Novartis.
J Río has received speaking honoraria and personal compensation for participating on Advisory Boards from Almirall, Bayer-Schering Healthcare, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Teva, and Sanofi-Aventis.
M Comabella has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, and Novartis.
C Nos has received funding for travel from Biogen Idec and F. Hoffmann-La Roche, Ltd., and speaker honoraria from Novartis.
A Vidal-Jordana has received speaking honoraria and consulting fees from Novartis, Roche, and Sanofi-Aventis.
C Auger has received speaking honoraria from Novartis, Biogen and Stendhal.
J Sastre-Garriga has has received compensation for participating on Advisory Boards, speaking honoraria and travel expenses for scientific meetings, consulting services or research support from Celgene, Novartis, Biogen, Teva, Merck, Almirall, and Genzyme.
A Rovira serves on scientific advisory boards for Biogen Idec, Novartis, Genzyme, and OLEA Medical, and on the editorial board of the American Journal of Neuroradiology, Neuroradiology and European Radiology, has received speaker honoraria from Bayer, Genzyme, Sanofi-Aventis, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, OLEA Medical, Stendhal, Novartis and Biogen Idec, and has research agreements with Siemens AG.
X Montalban has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past with Actelion, Amirall, Bayer, Biogen, Celgene, Genzyme, Hoffmann-La Roche, Novartis, Oryzon Genomics, Sanofi-Genzyme and Teva Pharmaceutical.
S Pérez-Hoyos has attend a Statistical workshop organized by Biogen.
C Tur, MJ Arévalo, E Anglada, R Menendez, L Midaglia, I Galán, R Meza, C Espejo, J Castilló, P Mulero, B Rodríguez-Acevedo, R Mitjana, D Pareto, M Rodriguez and A Zabalza report no disclosures.
This work has been financed with grants of the Spanish Ministry of Economy and Competitiveness by the Fondo de Investigación Sanitaria (FIS), the Instituto de Salud Carlos III (PI15/00170) granted to M.T. and PI14/01439 granted to X.M. It has also received support by a grant from Genzyme foundation (GENZYME - 2015-01) granted to MT and from the “Red Española de Esclerosis Múltiple (REEM)”, which is sponsored by FIS, the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness in Spain, and the “Ajuts per donar Suport als Grups de Recerca de Catalunya, which is sponsored by the “Agència de Gestió d'Ajuts Universitaris i de Recerca” (AGAUR) of the Generalitat de Catalunya in Spain. Novartis has contributed to the salaries of two investigators.
Abstract: 170
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - Environmental factors
Background: A dynamic model for predicting long-term prognosis incorporating age, sex, topography of CIS, oligoclonal bands (OB) and number of T2 lesions was presented.
Objectives: The aim is to include modifiable environmental factors such as vitamin D (VitD) and cotinine (Cot) serum levels (as a surrogate for smoking status) to our modelling strategy for predicting long-term prognosis.
Methods: From 1995 to 2016, 1088 CIS patients were prospectively recruited for clinical assessment and brain MRI follow-up. Baseline hazard for EDSS 3.0 was calculated after fitting several parametric models (Weibull, generalized Gamma) for a linear combination of baseline domains: age, sex, topography, OB and baseline T2 lesions. A recursive partitioning regression tree (RPART) method was used to stratify in risk groups according to their predicted median time to EDSS 3.0. This prognostic model was further updated adding VitD deficiency (N= 472; cut-off 8ng/ml), smoking (N= 435; Cot cut-off 14ng/ml) and their interactions with risk groups. Harrell C statistic was used to evaluate performance of these models.
Results: The model is based on1062 patients with more than one year of follow up. After fitting several models, a final Weibull (proportional hazard) model, was selected. RPART allowed stratifying patients in three groups: low risk (N=442; HR1.0 reference), medium risk (N=561: HR 3.0; 95%CI 2.0-4.6) and high Risk (N=51: HR 9.6; 95%CI 5.6-16.4) with a Harrell C of 0.65. For patients with VitD determination, an interaction was observed for VitD deficiency and risk group. Thus, Vit D deficiency increased the risk for EDSS progression and patients with low risk moved to the medium risk group and patients with medium risk moved to high risk. In patients already with high risk, the impact VitD deficiency was minor. Overall Harrell C increased from 0.65 to 0.69. For patients with Cot determination an interaction was observed for smoking and risk group. High Cot levels increased the risk for EDSS progression and patients with low risk moved to the medium risk group and patients with medium risk moved to high risk. For high-risk group, adding smoking status raised their HRs from 13.8 (95%CI 5.4-35.2) to 64.2 (123.2-311.9). Harrell C improved from 0.68 to 0.73.
Conclusion: Smoking and low vitamin D levels are key modifiable prognostic factors that show a dramatic interaction with risk of EDSS progression. Design of preventive strategies is warranted.
Disclosure: M Tintore has received compensation for consulting services and speaking honoraria from Almirall, Bayer Schering Pharma, , Biogen-Idec, Genzyme, Merck-Serono, Novartis, Roche, Sanofi-Aventis, and Teva Pharmaceuticals. MT is co-editor of Multiple Sclerosis Journal-ETC
G Arrambide has received compensation for consulting services from Biogen-Idec, research support and travel expenses for scientific meetings from Novartis, and speaking honoraria from Sanofi-Aventis.
S Otero-Romero has received compensation for consulting services from Biogen-Idec and Genzyme, and research support from Novartis.
J Río has received speaking honoraria and personal compensation for participating on Advisory Boards from Almirall, Bayer-Schering Healthcare, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Teva, and Sanofi-Aventis.
M Comabella has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, and Novartis.
C Nos has received funding for travel from Biogen Idec and F. Hoffmann-La Roche, Ltd., and speaker honoraria from Novartis.
A Vidal-Jordana has received speaking honoraria and consulting fees from Novartis, Roche, and Sanofi-Aventis.
C Auger has received speaking honoraria from Novartis, Biogen and Stendhal.
J Sastre-Garriga has has received compensation for participating on Advisory Boards, speaking honoraria and travel expenses for scientific meetings, consulting services or research support from Celgene, Novartis, Biogen, Teva, Merck, Almirall, and Genzyme.
A Rovira serves on scientific advisory boards for Biogen Idec, Novartis, Genzyme, and OLEA Medical, and on the editorial board of the American Journal of Neuroradiology, Neuroradiology and European Radiology, has received speaker honoraria from Bayer, Genzyme, Sanofi-Aventis, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, OLEA Medical, Stendhal, Novartis and Biogen Idec, and has research agreements with Siemens AG.
X Montalban has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past with Actelion, Amirall, Bayer, Biogen, Celgene, Genzyme, Hoffmann-La Roche, Novartis, Oryzon Genomics, Sanofi-Genzyme and Teva Pharmaceutical.
S Pérez-Hoyos has attend a Statistical workshop organized by Biogen.
C Tur, MJ Arévalo, E Anglada, R Menendez, L Midaglia, I Galán, R Meza, C Espejo, J Castilló, P Mulero, B Rodríguez-Acevedo, R Mitjana, D Pareto, M Rodriguez and A Zabalza report no disclosures.
This work has been financed with grants of the Spanish Ministry of Economy and Competitiveness by the Fondo de Investigación Sanitaria (FIS), the Instituto de Salud Carlos III (PI15/00170) granted to M.T. and PI14/01439 granted to X.M. It has also received support by a grant from Genzyme foundation (GENZYME - 2015-01) granted to MT and from the “Red Española de Esclerosis Múltiple (REEM)”, which is sponsored by FIS, the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness in Spain, and the “Ajuts per donar Suport als Grups de Recerca de Catalunya, which is sponsored by the “Agència de Gestió d'Ajuts Universitaris i de Recerca” (AGAUR) of the Generalitat de Catalunya in Spain. Novartis has contributed to the salaries of two investigators.