M. Filippi, A. Bar-or, F. Piehl, P. Preziosa, A. Solari et al., Multiple sclerosis. Nat Rev Dis Primer, vol.4, p.43, 2018.
URL : https://hal.archives-ouvertes.fr/hal-00826733

S. Klineova and F. D. Lublin, Clinical Course of Multiple Sclerosis, Cold Spring Harb Perspect Med. sept, vol.8, issue.9, p.28928, 2018.

B. Stankoff, S. Mrejen, A. Tourbah, B. Fontaine, O. Lyon-caen et al., Age at onset determines the occurrence of the progressive phase of multiple sclerosis, Neurology. 6 mars, vol.68, issue.10, pp.779-81, 2007.

. Revue-arsep, , 2018.

S. Foulon, G. Maura, M. Dalichampt, A. F. Debouverie, M. Moreau et al., Prevalence and mortality of patients with multiple sclerosis in France in 2012: a study based on French health insurance data, J Neurol. juin, vol.264, issue.6, pp.1185-92, 2017.

, Définition et chiffres -Fondation Sclérose en plaques

B. Zeydan and O. H. Kantarci, Progressive Forms of Multiple Sclerosis: Distinct Entity or Age-Dependent Phenomena, Neurol Clin. févr, vol.36, issue.1, pp.163-71, 2018.

M. Sospedra and R. Martin, Immunology of Multiple Sclerosis, Semin Neurol. avr, vol.36, issue.2, pp.115-142, 2016.

C. A. Dendrou, L. Fugger, and M. A. Friese, Immunopathology of multiple sclerosis, Nat Rev Immunol. 15 sept, vol.15, issue.9, pp.545-58, 2015.

F. Barkhof, M. Filippi, D. H. Miller, P. Scheltens, A. Campi et al., Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis, Brain J Neurol, vol.120, pp.2059-69, 1997.

P. Labauge, Critères diagnostiques de la sclérose en plaques, Prat Neurol -FMC. mars, vol.8, issue.2, pp.118-139, 2017.

F. D. Lublin and S. C. Reingold, Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis, Neurology. avr, vol.46, issue.4, pp.907-918, 1996.

F. D. Lublin, S. C. Reingold, J. A. Cohen, G. R. Cutter, P. S. Sørensen et al., Defining the clinical course of multiple sclerosis, Neurology. 15 juill, vol.83, issue.3, pp.278-86, 2014.

D. T. Okuda, E. M. Mowry, A. Beheshtian, E. Waubant, S. E. Baranzini et al., Incidental MRI anomalies suggestive of multiple sclerosis: The radiologically isolated syndrome, Neurology. 3 mars, vol.72, issue.9, pp.800-805, 2009.

, CT-16878_OCREVUS_PICins_SEP-R_avis2_CT16878_def.pdf

D. Sur,

A. Manouchehrinia, F. Zhu, D. Piani-meier, M. Lange, D. G. Silva et al., Predicting risk of secondary progression in multiple sclerosis: A nomogram, Mult Scler Houndmills Basingstoke Engl. 1 juin, 2018.

,

C. Confavreux and S. Vukusic, The clinical course of multiple sclerosis, Handb Clin Neurol, vol.122, pp.343-69, 2014.

A. Scalfari, A. Neuhaus, A. Degenhardt, G. P. Rice, P. A. Muraro et al., The natural history of multiple sclerosis, a geographically based study 10: relapses and long-term disability, Brain. juill, vol.133, issue.7, pp.1914-1943, 2010.

M. Koch, M. Uyttenboogaart, A. Van-harten, D. Keyser, and J. , Factors associated with the risk of secondary progression in multiple sclerosis, Mult Scler Houndmills Basingstoke Engl. juill, vol.14, issue.6, pp.799-803, 2008.

L. Kappos, J. Kuhle, J. Multanen, M. Kremenchutzky, V. Di-cantogno et al., Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15, J Neurol Neurosurg Psychiatry, vol.86, issue.11, pp.1202-1209, 2015.

D. Ontaneda, R. J. Fox, and J. Chataway, Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives, Lancet Neurol. févr, vol.14, issue.2, pp.208-231, 2015.

C. Confavreux and S. Vukusic, Natural history of multiple sclerosis: a unifying concept, Brain J Neurol. mars, vol.129, pp.606-622, 2006.

J. Lorscheider, K. Buzzard, V. Jokubaitis, T. Spelman, E. Havrdova et al., Defining secondary progressive multiple sclerosis, Brain J Neurol, vol.139, pp.2395-405, 2016.

M. Koch, E. Kingwell, P. Rieckmann, H. Tremlett, U. Ms-clinic et al., The natural history of secondary progressive multiple sclerosis, J Neurol Neurosurg Psychiatry. 1 sept, vol.81, issue.9, pp.1039-1082, 2010.

F. Coret, F. C. Pérez-miralles, F. Gascón, C. Alcalá, A. Navarré et al., Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies, Mult Scler J -Exp Transl Clin [Internet]. 26 juin, vol.4, issue.2, 2018.

D. Sur,

M. Koch, J. Mostert, D. Heersema, D. Keyser, and J. , Progression in multiple sclerosis: further evidence of an age dependent process, J Neurol Sci. 15 avr, vol.255, issue.1-2, pp.35-41, 2007.

A. Scalfari, A. Neuhaus, M. Daumer, G. C. Ebers, and P. A. Muraro, Age and disability accumulation in multiple sclerosis, Neurology. 27 sept, vol.77, issue.13, pp.1246-52, 2011.

C. Confavreux and S. Vukusic, Age at disability milestones in multiple sclerosis, Brain. 1 mars, vol.129, issue.3, pp.595-605, 2006.

A. Manouchehrinia, O. Beiki, and J. Hillert, Clinical course of multiple sclerosis: A nationwide cohort study. Mult Scler Houndmills Basingstoke Engl, vol.23, pp.1488-95, 2017.

H. Tremlett, Y. Zhao-null, and V. Devonshire, Natural history of secondaryprogressive multiple sclerosis, Mult Scler Houndmills Basingstoke Engl. avr, vol.14, issue.3, pp.314-338, 2008.

K. A. Ribbons, P. Mcelduff, C. Boz, M. Trojano, G. Izquierdo et al., Male Sex Is Independently Associated with Faster Disability Accumulation in Relapse-Onset MS but Not in Primary Progressive MS, PLoS ONE [Internet]. 5 juin, vol.10, issue.6, 2015.

D. Sur,

A. Scalfari, C. Romualdi, R. S. Nicholas, M. Mattoscio, R. Magliozzi et al., The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis, Neurology. 12 juin, vol.90, issue.24, pp.2107-2125, 2018.

C. Vasconcelos, J. Aurenção, L. Thuler, S. Camargo, M. P. Alvarenga et al., Prognostic factors associated with long-term disability and secondary progression in patients with Multiple Sclerosis, Mult Scler Relat Disord. juill, vol.8, pp.27-34, 2016.

M. P. Amato and G. Ponziani, A prospective study on the prognosis of multiple sclerosis, Neurol Sci. 23 déc, vol.21, issue.0, pp.831-839, 2000.

S. Vukusic and C. Confavreux, Prognostic factors for progression of disability in the secondary progressive phase of multiple sclerosis, J Neurol Sci. 15 févr, vol.206, issue.2, pp.135-142, 2003.

J. F. Kurtzke, Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS), Neurology. nov, vol.33, issue.11, pp.1444-52, 1983.

H. Tedeholm, J. Lycke, B. Skoog, V. Lisovskaja, J. Hillert et al., Time to secondary progression in patients with multiple sclerosis who were treated with first generation immunomodulating drugs, Mult Scler Houndmills Basingstoke Engl. mai, vol.19, issue.6, pp.765-74, 2013.

E. Leray, T. Moreau, A. Fromont, and G. Edan, Epidemiology of multiple sclerosis, Rev Neurol (Paris). janv, vol.172, issue.1, pp.3-13, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01255824

A. E. Handel, A. J. Williamson, G. Disanto, R. Dobson, G. Giovannoni et al., Smoking and Multiple Sclerosis: An Updated Meta-Analysis, PLoS ONE [Internet]. 13 janv, vol.6, issue.1, 2011.

D. Sur,

S. Hempel, G. D. Graham, N. Fu, E. Estrada, A. Y. Chen et al., A systematic review of modifiable risk factors in the progression of multiple sclerosis, Mult Scler Houndmills Basingstoke Engl. avr, vol.23, issue.4, pp.525-558, 2017.

E. M. Mowry, Natural history of multiple sclerosis: early prognostic factors, Neurol Clin. mai, vol.29, issue.2, pp.279-92, 2011.

M. A. Hernán, S. S. Jick, G. Logroscino, M. J. Olek, A. Ascherio et al., Cigarette smoking and the progression of multiple sclerosis, Brain J Neurol. juin, vol.128, pp.1461-1466, 2005.

O. Ciccarelli, Multiple sclerosis in 2018: new therapies and biomarkers, Lancet Neurol. janv, vol.18, issue.1, pp.10-12, 2019.

A. He, T. Spelman, V. Jokubaitis, E. Havrdova, D. Horakova et al., Comparison of switch to fingolimod or interferon beta/glatiramer acetate in active multiple sclerosis, JAMA Neurol. avr, vol.72, issue.4, pp.405-418, 2015.

T. Spelman, T. Kalincik, V. Jokubaitis, A. Zhang, F. Pellegrini et al., Comparative efficacy of first-line natalizumab vs IFN-? or glatiramer acetate in relapsing MS, Neurol Clin Pract. avr, vol.6, issue.2, pp.102-117, 2016.

T. Kalincik, J. Brown, N. Robertson, M. Willis, N. Scolding et al., Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study, Lancet Neurol, vol.16, issue.4, pp.271-81, 2017.

A. J. Coles, D. Compston, K. W. Selmaj, S. L. Lake, and S. Moran, Alemtuzumab vs. interferon beta-1a in early multiple sclerosis, CAMMS223 Trial Investigators, vol.359, pp.1786-801, 2008.

R. Bergamaschi, S. Quaglini, E. Tavazzi, M. P. Amato, D. Paolicelli et al., Immunomodulatory therapies delay disease progression in multiple sclerosis, Mult Scler Houndmills Basingstoke Engl, vol.22, issue.13, pp.1732-1772, 2016.

J. Brown, A. Coles, D. Horakova, E. Havrdova, G. Izquierdo et al., Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis, JAMA. 15 janv, vol.321, issue.2, pp.175-87, 2019.

A. Signori, F. Gallo, F. Bovis, D. Tullio, N. Maietta et al., Long-term impact of interferon or Glatiramer acetate in multiple sclerosis: A systematic review and meta-analysis, Mult Scler Relat Disord. mars, vol.6, pp.57-63, 2016.

T. Zhang, A. Shirani, Y. Zhao, M. E. Karim, P. Gustafson et al., Betainterferon exposure and onset of secondary progressive multiple sclerosis, Eur J Neurol. juin, vol.22, issue.6, pp.990-1000, 2015.

G. C. Ebers, A. Traboulsee, D. Li, D. Langdon, A. T. Reder et al., Analysis of clinical outcomes according to original treatment groups 16 years after the pivotal IFNB-1b trial, J Neurol Neurosurg Psychiatry. 1 août, vol.81, issue.8, pp.907-919, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00557446

, EDMUS : Le projet

D. Sur,

S. Vukusic, R. Casey, F. Rollot, B. Brochet, J. Pelletier et al., Observatoire Français de la Sclérose en Plaques (OFSEP): A unique multimodal nationwide MS registry in France, Mult Scler Houndmills Basingstoke Engl. 13 déc, 2018.

E. Leray, J. Yaouanq, L. Page, E. Coustans, M. Laplaud et al., Evidence for a two-stage disability progression in multiple sclerosis, Brain. juill, vol.133, issue.7, pp.1900-1913, 2010.

R. Bergamaschi, Prognosis of multiple sclerosis: clinical factors predicting the late evolution for an early treatment decision, Expert Rev Neurother. mars, vol.6, issue.3, pp.357-64, 2006.

J. Howard, S. Trevick, and D. S. Younger, Epidemiology of Multiple Sclerosis, Neurol Clin, vol.34, issue.4, pp.919-958, 2016.

B. D. Trapp and K. Nave, Multiple sclerosis: an immune or neurodegenerative disorder?, Annu Rev Neurosci, vol.31, pp.247-69, 2008.

A. Degenhardt, S. V. Ramagopalan, A. Scalfari, and G. C. Ebers, Clinical prognostic factors in multiple sclerosis: a natural history review, Nat Rev Neurol. déc, vol.5, issue.12, pp.672-82, 2009.

M. Novotna, P. Soldán, M. M. , A. Zeid, N. Kale et al., Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis, Neurology. 25 août, vol.85, issue.8, pp.722-731, 2015.

A. De-soutenance, , 2019.

N. Et and J. De-l'auteur-:-cuche,

T. Français, Facteurs prédictifs de passage de la Sclérose en plaques récurrente-rémittente en forme secondairement progressive en Normandie RESUME

, Peu de données sont disponibles sur le passage à la forme progressive (SEP-SP) chez les patients atteints de sclérose en plaques récurrente-rémittente (SEP-RR). L'objectif de l'étude est d'identifier les facteurs influençant le taux et le délai de passage en forme SP à 11 ans

. L'étude-Était-rétrospective, Les données ont été extraites à partir du registre de l'Observatoire Français de la SEP

, Le « groupe converteur » comportait -moins de femmes (65% vs 74,4% ; p=0,008) -un âge moyen au début de la maladie plus élevée (35,45+/-8,83ans vs 28,66+/-9,49ans ; p<0,001) -un nombre plus élevé de patients ayant fait >2 ou ?3, patients ont été inclus dans le « groupe non converteur » et 120 dans le « groupe converteur, p.5

, La durée de la phase RR était corrélée de façon proportionnelle au délai entre la première et la seconde poussée (délai P1-P2) et au délai d'instauration d'un traitement par rapport au début de la maladie

U. , le sexe masculin, un nombre ? 2 poussées dans les deux premières années de la maladie sont prédictifs d'un passage en forme SP à 11 ans. Bénéficier d'un TPL est plutôt protecteur. La durée de la phase RR est corrélée au délai, pp.1-2

. Mots-cles, Sclérose en plaques -Secondairement progressive -Épidémiologie -Facteurs prédictifs -Normandie

T. De, L. A. These, and . Anglais, Predictive factors for relapsing-remitting multiple sclerosis in secondary progressive form in Normandy RESUME DE LA THESE EN ANGLAIS : In the era of disease modifying treatments, little is known about conversion to the progressive phase (SP-MS) in relapsing-remitting multiple sclerosis (RR-MS) patients. The objective of the study is to identify the factors influencing the rate and the delay of a conversion to SP form within 11 years. The study was retrospective and bi-centered. The data was extracted from Observatoire Français de la SEP registry

, the « non-converter group » and 120 in the « converter group ». The « converter group » had -fewer women, vol.35, p.45

, 49 years ; p<0.001)-a higher number of patients who had > 2 or ?3 relapses in the first two years (25.83% vs 21.30% ; p=0.039 and 17.5% vs 11.13% ; p=0.009 respectively) and a lower number of patients treated with first-line treatment (TPL) +/-associated with second-line treatment (24.17% vs 34.5%, p <0.001 and 11.66%. vs 15.42%, p = 0.029). The duration of the RR phase was correlated proportionally with the delay between the first and the second relapses (delay P1-P2) and with the delay in initiating

, Being older at the beginning of the disease, being male, and having had more than 2 relapses in the first two years of the disease are predictive of a transition to SP form at 11 years. Benefitting from a TPL is rather protective. The duration of the RR phase is correlated with the delay, pp.1-2

. Key-words, Multiple sclerosis -Secondary progressive -Epidemiology -Predictive factors -Normandy