D. Bates, Treatment effects of immunomodulatory therapies at different stages of multiple sclerosis in short-term trials, Neurology, vol.76, issue.1, pp.14-25, 2011.

H. Bronnum-hansen, N. Koch-henriksen, and E. Stenager, Trends in survival and cause of death in Danish patients with multiple sclerosis, Brain, vol.127, pp.844-50, 2004.

C. Confavreux, S. Vukusic, T. Moreau, and P. Adeleine, Relapses and progression of disability in multiple sclerosis, N Engl J Med, vol.343, issue.20, pp.1430-1438, 2000.

H. De-jong, E. Kingwell, A. Shirani, C. Tervaert, J. W. Hupperts et al., Evaluating the safety of beta-interferons in MS: A series of nested case-control studies, Neurology, 2017.

R. A. Deyo, D. C. Cherkin, and M. A. Ciol, Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases, J Clin Epidemiol, vol.45, issue.6, pp.613-622, 1992.

S. Dhib-jalbut and S. Marks, Interferon-beta mechanisms of action in multiple sclerosis, Neurology, vol.74, issue.1, pp.17-24, 2010.

V. Essebag, R. W. Platt, M. Abrahamowicz, and L. Pilote, Comparison of nested case-control and survival analysis methodologies for analysis of time-dependent exposure, BMC Med Res Methodol, vol.5, issue.1, p.5, 2005.

, Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis, European Study Group on Interferon B-1b in Secondary Progressive MS, vol.352, pp.1491-1498, 1998.

C. Evans, F. Zhu, E. Kingwell, A. Shirani, M. L. Van-der-kop et al., Association between beta-interferon exposure and hospital events in multiple sclerosis, Pharmacoepidemiol Drug Saf, vol.23, issue.11, pp.1213-1235, 2014.

M. S. Freedman, Long-term follow-up of clinical trials of multiple sclerosis therapies, Neurology, vol.76, issue.1, pp.26-34, 2011.

S. Goodbourn, L. Didcock, and R. E. Randall, Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures, J Gen Virol, vol.81, pp.2341-64, 2000.

D. S. Goodin, M. Corwin, D. Kaufman, H. Golub, S. Reshef et al., Causes of death among commercially insured multiple sclerosis patients in the United States, PLoS One, 2014.

D. S. Goodin, G. C. Ebers, G. Cutter, S. D. Cook, O. Donnell et al., Cause of death in MS: long-term follow-up of a randomised cohort, 21 years after the start of the pivotal IFNbeta-1b study, BMJ Open, vol.2, issue.6, 2012.

D. S. Goodin and A. T. Reder, Evidence-based medicine: promise and pitfalls, Mult Scler, vol.18, issue.7, 2012.

D. S. Goodin, A. T. Reder, G. C. Ebers, G. Cutter, M. Kremenchutzky et al., Survival in MS: A randomized cohort study 21 years after the start of the pivotal IFNbeta-1b trial, Neurology, vol.78, pp.1315-1337, 2012.

G. S. Gronseth and E. Ashman, The AAN response to evidence-based medicine: promise and pitfalls

, Mult Scler, vol.18, issue.7, pp.949-50, 2012.

N. Grytten-torkildsen, S. Lie, J. Aarseth, H. Nyland, and K. Myhr, Survival and cause of death in multiple sclerosis: results from a 50-year follow-up in Western Norway, Mult Scler, vol.14, issue.9, 2008.

, Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebocontrolled trial. The IFNB Multiple Sclerosis Study Group, Neurology, vol.43, issue.4, pp.655-61, 1993.

L. D. Jacobs, D. L. Cookfair, R. A. Rudick, R. M. Herndon, J. R. Richert et al.,

, Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG), Ann Neurol, vol.39, issue.3, pp.285-94, 1996.

K. P. Johnson, B. R. Brooks, J. A. Cohen, C. C. Ford, J. Goldstein et al., Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group, Neurology, vol.45, issue.7, pp.1268-76, 1995.

D. Karussis, L. D. Biermann, S. Bohlega, A. Boiko, M. Chofflon et al., A recommended treatment algorithm in relapsing multiple sclerosis: report of an international consensus meeting

, Eur J Neurol, vol.13, issue.1, pp.61-71, 2006.

E. Kingwell, M. Van-der-kop, Y. Zhao, A. Shirani, F. Zhu et al., Relative mortality and survival in multiple sclerosis: findings from British Columbia, Canada, J Neurol Neurosurg Psychiatry, vol.83, issue.1, pp.61-67, 2012.

N. Koch-henriksen, H. Bronnum-hansen, and E. Stenager, Underlying cause of death in Danish patients with multiple sclerosis: results from the Danish Multiple Sclerosis Registry, J Neurol Neurosurg Psychiatry, vol.65, issue.1, pp.56-65, 1998.

E. Leray, S. P. Morrissey, J. Yaouanq, M. Coustans, L. Page et al., Long-term survival of patients with multiple sclerosis in West France, Mult Scler, vol.13, issue.7, pp.865-74, 2007.

E. Leray, S. Vukusic, M. Debouverie, M. Clanet, B. Brochet et al., Excess Mortality in Patients with Multiple Sclerosis Starts at 20 Years from Clinical Onset: Data from a Large-Scale French Observational Study, PLoS One, vol.10, issue.7, p.132033, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01201656

H. Lunde, J. Assmus, K. M. Myhr, L. Bo, and N. Grytten, Survival and cause of death in multiple sclerosis: a 60-year longitudinal population study, J Neurol Neurosurg Psychiatry, vol.88, issue.8, 2017.

R. A. Marrie, L. Elliott, J. Marriott, M. Cossoy, J. Blanchard et al., Effect of comorbidity on mortality in multiple sclerosis, Neurology, vol.85, issue.3, pp.240-247, 2015.

R. Midgard, G. Albrektsen, T. Riise, G. Kvale, and H. Nyland, Prognostic factors for survival in multiple sclerosis: a longitudinal, population based study in More and Romsdal, Norway, J Neurol Neurosurg Psychiatry, vol.58, issue.4, pp.417-438, 1995.

, Multiple Sclerosis International Federation. Atlas of MS, 2013.

U. K. London,

, PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis, Lancet, vol.352, issue.9139, pp.1498-504, 1998.

A. Rodriguez-antiguedad-zarranz, M. Bilbao, M. , L. Gonzalez, C. Audicana et al.,

, Mortality and Cause of Death in Multiple Sclerosis: Findings from a Prospective PopulationBased Cohort in Bizkaia, Neuroepidemiology, vol.42, issue.4, pp.219-244, 2014.

A. D. Sadovnick, K. Eisen, G. C. Ebers, and D. W. Paty, Cause of death in patients attending multiple sclerosis clinics, Neurology, vol.41, issue.8, pp.1193-1199, 1991.

A. Salter, T. Tyry, G. Wang, R. J. Fox, G. Cutter et al., Examining the joint effect of disability, health behaviors, and comorbidity on mortality in MS, Neurol Clin Pract, vol.6, issue.5, pp.397-408, 2016.

A. Scalfari, V. Knappertz, G. Cutter, D. S. Goodin, R. Ashton et al., Mortality in patients with multiple sclerosis, Neurology, vol.81, issue.2, pp.184-92, 2013.

, Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-Beta-1a in MS Study Group, Neurology, vol.56, issue.11, pp.1496-504, 2001.

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, vol.6, pp.57-63, 2016.

C. Smestad, L. Sandvik, and E. G. Celius, Excess mortality and cause of death in a cohort of Norwegian multiple sclerosis patients, Mult Scler, vol.15, issue.11, pp.1263-70, 2009.

M. P. Sormani and P. Bruzzi, Can we measure long-term treatment effects in multiple sclerosis?, Nat Rev Neurol, vol.11, issue.3, pp.176-82, 2015.

S. Suissa, Immortal time bias in pharmaco-epidemiology, Am J Epidemiol, vol.167, issue.4, pp.492-501, 2008.

M. L. Sumelahti, M. Hakama, I. Elovaara, and E. Pukkala, Causes of death among patients with multiple sclerosis, Mult Scler, vol.16, issue.12, pp.1437-1479, 2010.

O. The and . Group, Evidence of interferon beta-1a dose response in relapsing-remitting MS: the OWIMS Study. The Once Weekly Interferon for MS Study Group, Neurology, 1999.

I. Tramacere, D. Giovane, C. Salanti, G. , D. 'amico et al., Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis

, Cochrane Database Syst Rev, vol.2015, issue.9, p.11381

H. Tremlett, M. Yousefi, V. Devonshire, P. Rieckmann, and Y. Zhao, Impact of multiple sclerosis relapses on progression diminishes with time, Neurology, vol.73, issue.20, pp.1616-1639, 2009.

C. P. Tsai and C. T. Lee, Impact of disease-modifying therapies on the survival of patients with multiple sclerosis in Taiwan, Clin Drug Investig, vol.33, issue.9, pp.647-52, 1997.

A. Westad, A. Venugopal, and E. Snyder, The multiple sclerosis market, Nat Rev Drug Discov, 2017.

, Vital Statistics Deaths. V2. Population Data BC, 2015.

, British Columbia Ministry of Health, PharmaNet. V2. 2015a Available from, 2015.

, Consolidation File (MSP Registration & Premium Billing). V2. Population Data BC, Data Extract MOH. 2015a Available from, 2015.

, British Columbia Ministry of Health [creator, 2015.

, Discharge Abstract Database (Hospital Separations). V2. Popualtion Data BC

M. Data-extract, , 2015.

, British Columbia Ministry of Health [creator, 2015.

, Medical Services Plan (MSP) Payment Information File: Population Data BC

M. Data-extract, , 2015.

E. Leray, S. P. Morrissey, J. Yaouanq, M. Coustans, L. Page et al., Long-term survival of patients with multiple sclerosis in West France, Mult Scler, vol.13, issue.7, pp.865-74, 2007.

W. I. Mcdonald, A. Compston, G. Edan, D. Goodkin, H. P. Hartung et al.,

, Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis, Ann Neurol, vol.50, issue.1, pp.121-128, 2001.

C. M. Poser, D. W. Paty, L. Scheinberg, W. I. Mcdonald, F. A. Davis et al., New diagnostic criteria for multiple sclerosis: guidelines for research protocols, Ann Neurol, vol.13, issue.3, pp.227-258, 1983.

H. Tremlett, Y. Zhao, P. Rieckmann, and M. Hutchinson, New perspectives in the natural history of multiple sclerosis, Neurology, vol.74, issue.24, pp.2004-2019, 2010.