I. .. Sujet,

.. .. Sclérose-en-plaques-;-généralités-et-Épidémiologie,

S. .. Diagnostic-de,

. , Evolution de la maladie et évaluation du handicap

L. S. Traitement-de, Remise en cause de l'utilité des traitements de fond à long terme au vu de l'évolution naturelle de la maladie

. , Etudes publiées sur l'arrêt

.. .. Objectif-de-notre-Étude,

, Présentation de la cohorte ReLSEP et méthodologies utilisées pour cette étude, p.30

. .. Bibliographie,

. , II COULD DISEASE-MODIFYING THERAPIES BE STOPPED OVER AGE 50 IN THE ABSENCE OF RELAPSE FOR PATIENTS WITH MULTIPLE SCLEROSIS ?

. , 38 2.1 Definition of the population and inclusion criteria

. .. Results, 40 3.1 Characteristics of the population and follow-up

. , Subgroup analysis (only the patients with a RR form at baseline)

. .. Discussion,

. .. Tables,

F. .. ,

. .. Bibliography,

. , 62 3. Résultats principaux de notre étude et discussion

J. Correale, M. I. Gaitán, M. C. Ysrraelit, and M. P. Fiol, « Progressive multiple sclerosis: from pathogenic mechanisms to treatment, Brain, vol.140, issue.3, pp.527-546, 2017.

D. M. Wingerchuk and B. G. Weinshenker, « Disease modifying therapies for relapsing multiple sclerosis, BMJ, vol.354, p.3518, 2016.

S. Foulon, G. Maura, and M. Dalichampt, « Prevalence and mortality of patients with multiple sclerosis in France in 2012: a study based on French health insurance data, J. Neurol, vol.264, issue.6, pp.1185-1192, 2017.

D. Pivot, M. Debouverie, and M. Grzebyk, « Geographical Heterogeneity of Multiple Sclerosis Prevalence in France, PLoS ONE, vol.11, p.12, 2016.

C. H. Polman, S. C. Reingold, and B. Banwell, « Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria, Ann. Neurol, vol.69, issue.2, pp.292-302, 2011.

C. Confavreux and S. Vukusic, « Natural history of multiple sclerosis: a unifying concept, Brain, vol.129, issue.3, pp.606-616, 2006.

M. Debouverie, S. Pittion-vouyovitch, S. Louis, F. Guillemin, and L. Group, « Natural history of multiple sclerosis in a population-based cohort », Eur. J. Neurol, vol.15, issue.9, pp.916-921, 2008.

M. Butler, M. L. Forte, N. Schwehr, A. Carpenter, and R. L. Kane, Decisional Dilemmas in Discontinuing Prolonged Disease-Modifying Treatment for Multiple Sclerosis, p.150, 2015.

F. D. Lublin, S. C. Reingold, and J. A. Cohen, « Defining the clinical course of multiple sclerosis, Neurology, vol.83, issue.3, pp.278-286, 2014.

H. Tedeholm, J. Lycke, and B. Skoog, « Time to secondary progression in patients with multiple sclerosis who were treated with first generation immunomodulating drugs, Mult. Scler, vol.19, issue.6, pp.765-774, 2013.

C. Confavreux, S. Vukusic, and P. Adeleine, « Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process, Brain J. Neurol, vol.126, pp.770-782, 2003.

W. I. Mcdonald, A. Compston, and G. Edan, « Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis, Ann. Neurol, vol.50, issue.1, pp.121-127, 2001.

C. H. Polman, S. C. Reingold, and G. Edan, Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria" », vol.58, pp.840-846, 2005.

A. J. Thompson, B. L. Banwell, and F. Barkhof, Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria, vol.17, pp.162-173, 2018.

J. F. Kurtzke, Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS), Neurology, vol.33, issue.11, pp.1444-1452, 1983.

C. Confavreux, S. Vukusic, T. Moreau, and P. Adeleine, « Relapses and progression of disability in multiple sclerosis, N. Engl. J. Med, vol.343, pp.1430-1438, 2000.

C. Confavreux and S. Vukusic, « Age at disability milestones in multiple sclerosis, Brain J. Neurol, vol.129, pp.595-605, 2006.

H. Tremlett, Y. Zhao, and V. Devonshire, « Defining the natural history of MS: the need for complete data and rigorous definitions, Mult. Scler, vol.14, issue.8, pp.1142-1143, 2008.

A. Gajofatto and M. D. Benedetti, « Treatment strategies for multiple sclerosis: When to start, when to change, when to stop? », World J. Clin. Cases WJCC, vol.3, issue.7, pp.545-555, 2015.

D. L. Rotstein, B. C. Healy, M. T. Malik, T. Chitnis, and H. L. Weiner, « Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort, JAMA Neurol, vol.72, issue.2, pp.152-158, 2015.

D. K. Li, G. J. Zhao, and D. W. Paty, University of British Columbia MS/MRI Analysis Research Group. The SPECTRIMS Study Group, « Randomized controlled trial of interferonbeta-1a in secondary progressive MS: MRI results, Neurology, vol.56, issue.11, pp.1505-1513, 2001.

H. Tremlett, Y. Zhao, J. Joseph, V. Devonshire, and . Neurologists, « Relapses in multiple sclerosis are age-and time-dependent, J. Neurol. Neurosurg. Psychiatry, vol.79, pp.1368-1374, 2008.

M. M. Paz-soldán, M. Novotna, and N. Abou-zeid, « Relapses and disability accumulation in progressive multiple sclerosis, Neurology, vol.84, issue.1, pp.81-88, 2015.

J. M. Frischer, S. Bramow, and A. Dal-bianco, The relation between inflammation and neurodegeneration in multiple sclerosis brains, vol.132, pp.1175-1189, 2009.

A. Shirani, Y. Zhao, and M. E. Karim, « Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis, JAMA, vol.308, issue.3, pp.247-256, 2012.

, Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-Beta-1a in MS (SPECTRIMS) Study Group, « Randomized controlled trial of interferon-beta-1a in secondary progressive MS: Clinical results, Neurology, vol.56, issue.11, pp.1496-1504, 2001.

O. Andersen, I. Elovaara, and M. Farkkila, « Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis, J. Neurol. Neurosurg. Psychiatry, vol.75, issue.5, pp.706-710, 2004.

H. Panitch, A. Miller, D. Paty, and B. , Weinshenker, and North American Study Group on Interferon beta-1b in Secondary Progressive MS, « Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study, Neurology, vol.63, issue.10, pp.1788-1795, 2004.

J. A. Cohen, G. R. Cutter, and J. S. Fischer, « Benefit of interferon beta-1a on MSFC progression in secondary progressive MS, Neurology, vol.59, issue.5, pp.679-687, 2002.

R. Bergamaschi, S. Quaglini, and E. Tavazzi, « Immunomodulatory therapies delay disease progression in multiple sclerosis, Mult. Scler, vol.22, issue.13, pp.1732-1740, 2016.

, « Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS, Lancet Lond. Engl, vol.352, pp.1491-1497, 1998.

E. Grebenciucova and A. Pruitt, Infections in Patients Receiving Multiple Sclerosis Disease-Modifying Therapies, vol.17, p.88, 2017.

E. Grebenciucova, J. R. Berger, and . Immunosenescence, the Role of Aging in the Predisposition to Neuro-Infectious Complications Arising from the Treatment of Multiple Sclerosis, Curr. Neurol. Neurosci. Rep, vol.17, issue.8, p.61, 2017.

K. E. O'rourke and M. Hutchinson, « Stopping beta-interferon therapy in multiple sclerosis: an analysis of stopping patterns, Mult. Scler, vol.11, issue.1, pp.46-50, 2005.

D. M. Hartung, D. N. Bourdette, S. M. Ahmed, and R. H. Whitham, « The cost of multiple sclerosis drugs in the US and the pharmaceutical industry, Neurology, vol.84, pp.2185-2192, 2015.

C. A. Carroll, K. A. Fairman, and M. J. Lage, « Updated cost-of-care estimates for commercially insured patients with multiple sclerosis: retrospective observational analysis of medical and pharmacy claims data, BMC Health Serv. Res, vol.14, p.286, 2014.

R. Lonergan, K. Kinsella, M. Duggan, S. Jordan, M. Hutchinson et al., « Discontinuing disease-modifying therapy in progressive multiple sclerosis: can we stop what we have started?, Mult. Scler, vol.15, pp.1528-1531, 2009.

I. Kister, T. Spelman, and R. Alroughani, « Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study, J Neurol Neurosurg Psychiatry, vol.87, issue.10, pp.1133-1137, 2016.

G. Birnbaum, Stopping Disease-Modifying Therapy in Nonrelapsing Multiple Sclerosis, vol.19, pp.11-14, 2017.

J. Bonenfant, E. Bajeux, V. Deburghgraeve, E. L. Page, G. Edan et al., « Can we stop immunomodulatory treatments in secondary progressive multiple sclerosis? », Eur. J. Neurol, vol.24, issue.2, pp.237-244, 2017.

G. Bsteh, J. Feige, and R. Ehling, « Discontinuation of disease-modifying therapies in multiple sclerosis-Clinical outcome and prognostic factors, Mult. Scler. J, vol.23, issue.9, pp.1241-1248, 2017.

G. S. Olival, V. B. Cavenaghi, V. Serafim, R. B. Thomaz, and C. P. Tilbery, « Medication withdrawal may be an option for a select group of patients in relapsingremitting multiple sclerosis, Arq. Neuropsiquiatr, vol.71, issue.8, pp.516-520, 2013.

M. Siger, A. Durko, A. Nicpan, M. Konarska, M. Grudziecka et al., « Discontinuation of interferon beta therapy in multiple sclerosis patients with high pretreatment disease activity leads to prompt return to previous disease activity, J. Neurol. Sci, vol.303, issue.2, pp.50-52, 2011.

L. Prosperini, C. R. Mancinelli, and C. Pozzilli, « From high-to low-frequency administered interferon-beta for multiple sclerosis: a multicenter study, Eur. Neurol, vol.71, pp.233-241, 2014.

X. Wu, P. Dastidar, H. Kuusisto, M. Ukkonen, H. Huhtala et al., « Increased disability and MRI lesions after discontinuation of IFN-beta-1a in secondary progressive MS, Acta Neurol. Scand, vol.112, issue.4, pp.242-247, 2005.

P. Barbero, E. Verdun, and M. Bergui, « High-dose, frequently administered interferon beta therapy for relapsing-remitting multiple sclerosis must be maintained over the long term: the interferon beta dose-reduction study, J. Neurol. Sci, vol.222, issue.2, pp.13-19, 2004.

J. Fagius, A. Feresiadou, E. Larsson, and J. Burman, « Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients. First line drugs vs natalizumab, Mult. Scler. Relat. Disord, vol.12, pp.82-87, 2017.

T. Stürmer, M. Joshi, R. J. Glynn, J. Avorn, K. J. Rothman et al., « A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods, J. Clin. Epidemiol, 2006.

P. R. Rosenbaum and D. B. Rubin, « The Central Role of the Propensity Score in Observational Studies for Causal Effects, Biometrika, vol.70, issue.1, pp.41-55, 1983.

T. Filleron and F. Kwiatowski, « Le score de propension, une alternative crédible à la randomisation ?, Bull. Cancer (Paris), vol.103, issue.1, pp.113-122, 2016.

S. Foulon, G. Maura, and M. Dalichampt, « Prevalence and mortality of patients with multiple sclerosis in France in 2012: a study based on French health insurance data, J. Neurol, vol.264, issue.6, pp.1185-1192, 2017.

D. L. Rotstein, B. C. Healy, M. T. Malik, T. Chitnis, and H. L. Weiner, « Evaluation of No Evidence of Disease Activity in a 7-Year Longitudinal Multiple Sclerosis Cohort, JAMA Neurol, vol.72, issue.2, pp.152-158, 2015.

H. Tremlett, Y. Zhao, J. Joseph, V. Devonshire, and . Neurologists, « Relapses in multiple sclerosis are age-and time-dependent, J. Neurol. Neurosurg. Psychiatry, vol.79, pp.1368-1374, 2008.

J. M. Frischer, S. Bramow, and A. Dal-bianco, The relation between inflammation and neurodegeneration in multiple sclerosis brains, vol.132, pp.1175-1189, 2009.

M. M. Paz-soldán, M. Novotna, and N. Abou-zeid, « Relapses and disability accumulation in progressive multiple sclerosis, Neurology, vol.84, issue.1, pp.81-88, 2015.

E. Grebenciucova and A. Pruitt, Infections in Patients Receiving Multiple Sclerosis Disease-Modifying Therapies, vol.17, p.88, 2017.

A. T. Reder, J. F. Oger, L. Kappos, P. O'connor, and M. Rametta, Short-term and longterm safety and tolerability of interferon ?-1b in multiple sclerosis, Mult. Scler. Relat. Disord, vol.3, pp.294-302, 2014.

, Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-Beta-1a in MS (SPECTRIMS) Study Group, « Randomized controlled trial of interferon-beta-1a in secondary progressive MS: Clinical results, Neurology, vol.56, issue.11, pp.1496-1504, 2001.

O. Andersen, I. Elovaara, and M. Farkkila, « Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis, J. Neurol. Neurosurg. Psychiatry, vol.75, issue.5, pp.706-710, 2004.

H. Panitch, A. Miller, D. Paty, and B. , Weinshenker, and North American Study Group on Interferon beta-1b in Secondary Progressive MS, «Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study, Neurology, vol.63, pp.1788-1795, 2004.

J. A. Cohen, G. R. Cutter, and J. S. Fischer, « Benefit of interferon beta-1a on MSFC progression in secondary progressive MS, Neurology, vol.59, issue.5, pp.679-687, 2002.

J. Bonenfant, E. Bajeux, V. Deburghgraeve, E. L. Page, G. Edan et al., « Can we stop immunomodulatory treatments in secondary progressive multiple sclerosis? », Eur. J. Neurol, vol.24, issue.2, pp.237-244, 2017.

G. S. Olival, V. B. Cavenaghi, V. Serafim, R. B. Thomaz, and C. P. Tilbery, « Medication withdrawal may be an option for a select group of patients in relapsing-remitting multiple sclerosis, Arq. Neuropsiquiatr, vol.71, pp.516-520, 2013.

M. Siger, A. Durko, A. Nicpan, M. Konarska, M. Grudziecka et al., « Discontinuation of interferon beta therapy in multiple sclerosis patients with high pretreatment disease activity leads to prompt return to previous disease activity, J. Neurol. Sci, vol.303, pp.50-52, 2011.

L. Prosperini, C. R. Mancinelli, and C. Pozzilli, « From high-to low-frequency administered interferon-beta for multiple sclerosis: a multicenter study, Eur. Neurol, vol.71, pp.233-241, 2014.

X. Wu, P. Dastidar, H. Kuusisto, M. Ukkonen, H. Huhtala et al., « Increased disability and MRI lesions after discontinuation of IFN-beta-1a in secondary progressive MS, Acta Neurol. Scand, vol.112, pp.242-247, 2005.

R. J. Fox, B. A. Cree, and J. De-sèze, MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study, vol.82, pp.1491-1498, 2014.

P. Barbero, E. Verdun, and M. Bergui, « High-dose, frequently administered interferon beta therapy for relapsing-remitting multiple sclerosis must be maintained over the long term: the interferon beta dose-reduction study, J. Neurol. Sci, vol.222, pp.13-19, 2004.

I. Kister, T. Spelman, and R. Alroughani, « Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study, J Neurol Neurosurg Psychiatry, vol.87, pp.1133-1137, 2016.

H. E. Adssi, M. Debouverie, F. Guillemin, and L. Group, « Estimating the prevalence and incidence of multiple sclerosis in the Lorraine region, France, by the capturerecapture method, Mult. Scler, vol.18, pp.1244-1250, 2012.

M. Debouverie, S. Pittion-vouyovitch, S. Louis, F. Guillemin, and L. Group, « Natural history of multiple sclerosis in a population-based cohort », Eur. J. Neurol, vol.15, pp.916-921, 2008.

C. Confavreux, D. A. Compston, O. R. Hommes, W. I. Mcdonald, and A. J. Thompson, « EDMUS, a European database for multiple sclerosis, J. Neurol. Neurosurg. Psychiatry, vol.55, pp.671-676, 1992.

C. M. Poser, D. W. Paty, and L. Scheinberg, « New diagnostic criteria for multiple sclerosis: Guidelines for research protocols, Ann. Neurol, vol.13, pp.227-231, 1983.

W. I. Mcdonald, A. Compston, and G. Edan, « Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis, Ann. Neurol, vol.50, issue.1, pp.121-127, 2001.

C. H. Polman, S. C. Reingold, and G. Edan, Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria" », vol.58, pp.840-846, 2005.

C. H. Polman, S. C. Reingold, and B. Banwell, « Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria, Ann. Neurol, vol.69, issue.2, pp.292-302, 2011.

J. F. Kurtzke, Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS), Neurology, vol.33, issue.11, pp.1444-1452, 1983.

C. Confavreux, S. Vukusic, T. Moreau, and P. Adeleine, « Relapses and progression of disability in multiple sclerosis, N. Engl. J. Med, vol.343, pp.1430-1438, 2000.

C. Confavreux and S. Vukusic, « Age at disability milestones in multiple sclerosis, Brain J. Neurol, vol.129, pp.595-605, 2006.

L. H. Hua, T. H. Fan, D. Conway, N. Thompson, and T. G. Kinzy, « Discontinuation of disease-modifying therapy in patients with multiple sclerosis over age 60, Mult. Scler, p.1352458518765656, 2018.

G. Birnbaum, « Stopping Disease-Modifying Therapy in Nonrelapsing Multiple Sclerosis », Int. J. MS Care, vol.19, issue.1, pp.11-14, 2017.

J. Fagius, A. Feresiadou, E. Larsson, and J. Burman, « Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients. First line drugs vs natalizumab, Mult. Scler. Relat. Disord, vol.12, pp.82-87, 2017.

, « Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS), p.24, 2015.

, Sclérose en Plaques (SEP) serait de réduire l'inflammation et donc l'activité de la maladie, d'éviter les poussées cliniques et les nouvelles lésions à l'imagerie par résonance magnétique (IRM), et de limiter la progression du handicap. Or, l'évolution de la SEP avec l'âge se caractérise par une diminution de l'inflammation, de l'activité de la maladie, Sclérose en Plaques : rappel du contexte L'objectif des traitements de fond dans les formes récurrentes rémittentes (RR) de

, Les traitements de fond ayant une activité anti-inflammatoire pourraient ainsi devenir inutiles à partir d'un certain âge. De plus, dans les phases tardives de la maladie, l'efficacité des thérapies sur la prévention de la progression du handicap et la prévention du passage en forme secondairement progressive (SP)

H. Tremlett, Y. Zhao, and V. Devonshire, « Defining the natural history of MS: the need for complete data and rigorous definitions, Mult. Scler, vol.14, issue.8, pp.1142-1143, 2008.

M. M. Paz-soldán, M. Novotna, and N. Abou-zeid, « Relapses and disability accumulation in progressive multiple sclerosis, Neurology, vol.84, issue.1, pp.81-88, 2015.

J. M. Frischer, S. Bramow, and A. Dal-bianco, The relation between inflammation and neurodegeneration in multiple sclerosis brains, vol.132, pp.1175-1189, 2009.

H. Tedeholm, J. Lycke, and B. Skoog, « Time to secondary progression in patients with multiple sclerosis who were treated with first generation immunomodulating drugs, Mult. Scler, vol.19, issue.6, pp.765-774, 2013.

A. Shirani, Y. Zhao, and M. E. Karim, « Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis, JAMA, vol.308, issue.3, pp.247-256, 2012.

R. Bergamaschi, S. Quaglini, and E. Tavazzi, « Immunomodulatory therapies delay disease progression in multiple sclerosis, Mult. Scler, vol.22, issue.13, pp.1732-1740, 2016.

O. Andersen, I. Elovaara, and M. Farkkila, « Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis, J. Neurol. Neurosurg. Psychiatry, vol.75, issue.5, pp.706-710, 2004.

H. Panitch, A. Miller, D. Paty, and B. , Weinshenker, and North American Study Group on Interferon beta-1b in Secondary Progressive MS, « Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study, Neurology, vol.63, issue.10, pp.1788-1795, 2004.

J. A. Cohen, G. R. Cutter, and J. S. Fischer, « Benefit of interferon beta-1a on MSFC progression in secondary progressive MS, Neurology, vol.59, issue.5, pp.679-687, 2002.

, « Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS, Lancet Lond. Engl, vol.352, pp.1491-1497, 1998.

, Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-Beta-1a in MS (SPECTRIMS) Study Group, « Randomized controlled trial of interferon-beta-1a in secondary progressive MS: Clinical results, Neurology, vol.56, issue.11, pp.1496-1504, 2001.

D. M. Wingerchuk and B. G. Weinshenker, « Disease modifying therapies for relapsing multiple sclerosis, BMJ, vol.354, p.3518, 2016.

E. Grebenciucova and A. Pruitt, Infections in Patients Receiving Multiple Sclerosis Disease-Modifying Therapies, vol.17, p.88, 2017.

E. Grebenciucova, J. R. Berger, and . Immunosenescence, the Role of Aging in the Predisposition to Neuro-Infectious Complications Arising from the Treatment of Multiple Sclerosis, Curr. Neurol. Neurosci. Rep, vol.17, issue.8, p.61, 2017.

K. E. O'rourke and M. Hutchinson, « Stopping beta-interferon therapy in multiple sclerosis: an analysis of stopping patterns, Mult. Scler, vol.11, issue.1, pp.46-50, 2005.

I. Kister, T. Spelman, and R. Alroughani, « Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study, J Neurol Neurosurg Psychiatry, vol.87, issue.10, pp.1133-1137, 2016.

G. Bsteh, J. Feige, and R. Ehling, « Discontinuation of disease-modifying therapies in multiple sclerosis-Clinical outcome and prognostic factors, Mult. Scler. J, vol.23, issue.9, pp.1241-1248, 2017.

J. Bonenfant, E. Bajeux, V. Deburghgraeve, E. L. Page, G. Edan et al., « Can we stop immunomodulatory treatments in secondary progressive multiple sclerosis? », Eur. J. Neurol, vol.24, issue.2, pp.237-244, 2017.

G. S. Olival, V. B. Cavenaghi, V. Serafim, R. B. Thomaz, and C. P. Tilbery, « Medication withdrawal may be an option for a select group of patients in relapsingremitting multiple sclerosis, Arq. Neuropsiquiatr, vol.71, issue.8, pp.516-520, 2013.

J. Fagius, A. Feresiadou, E. M. Larsson, and J. Burman, « Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients. First line drugs vs natalizumab, Mult. Scler. Relat. Disord, vol.12, pp.82-87, 2017.

, « Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS), pp.24-2015