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Long-term effect of first-line injectable multiple sclerosis treatments: Input of a time-dependent propensity score.

  • Lefort, Mathilde1, 2
  • Foucher, Yohann3, 4
  • Lenain, Remi3, 5
  • Vukusic, Sandra6, 7, 8, 9
  • Edan, Gilles2, 10
  • Leray, Emmanuelle1, 2, 11
  • 1 Pharmaco-epidemiology and health Services Research Department, Rennes University, EHESP, REPERES - EA 7449, Rennes, France. , (France)
  • 2 Neurology Department, Univ Rennes, CHU Rennes, Inserm, CIC 1414 [(Centre d'Investigation Clinique de Rennes)], Rennes, France. , (France)
  • 3 Biostatistic Department, INSERM UMR 1246 - SPHERE, Nantes University, Tours University, Nantes, France. , (France)
  • 4 Nephrology Department, Nantes University Hospital, Nantes, France. , (France)
  • 5 Nephrology Department, Lille University Hospital, Lille, France. , (France)
  • 6 Neurology Department, Hospices Civils de Lyon, Service de Neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Bron, France. , (France)
  • 7 Neurology Department, Observatoire Français de la Sclérose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292, Lyon, France. , (France)
  • 8 Neurology Department, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France. , (France)
  • 9 Neurology Department, Eugène Devic EDMUS Foundation against Multiple Sclerosis, State-Approved Foundation, Bron, France. , (France)
  • 10 Neurology Department, CHU Pontchaillou, Rennes, France. , (France)
  • 11 METIS Department, EHESP French School of Public Health, Rennes, France. , (France)
Published Article
Pharmacoepidemiology and drug safety
Publication Date
Dec 01, 2020
DOI: 10.1002/pds.5154
PMID: 33078476


The long-term effect of beta-interferon and glatiramer acetate on multiple sclerosis (MS) disability progression has resulted in controversial results, probably due to a lack of appropriate control of biases as raised in observational studies. In particular, the time of the therapeutic decision is difficult to define when the controls are not treated. This retrospective observational study was based on a series of patients from the MS expert center in Rennes, France. We used a time-dependent propensity score defined as the linear predictor of a Cox model estimating the hazard of being treated at each time from MS onset. The matching procedure resulted in two groups: patients matched as treated and as not yet treated. The restricted mean times (RMST) to reach a moderate level of disability or worsening of the disability were compared between the two groups in an intention-to-treat analysis. Of the 2383 patients included in the study, 556 were matched as treated. The matching procedure provided a good balance of both the time-fixed and the time-dependent covariates. A slight difference was observed for the time to reach a moderate level of disability, in favor of the "not yet treated" group (difference in the RMST: -0.62 [-0.91; -0.33]) while no difference was found in terms of worsening of the disability (-0.03 [-0.24; 0.33]). This unexpected result is probably due to unmeasured confounders. However, this time-dependent PS warrants consideration in long-term effectiveness studies. © 2020 John Wiley & Sons Ltd.

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