Predictors of relapse and disability progression in MS patients who discontinue disease-modifying therapy

Ilya Kister, Tim Spelman, Francesco Patti, Pierre Duquette, Maria Trojano, Guillermo Izquierdo, Alessandra Lugaresi, Pierre Grammond, Patrizia Sola, Diana Ferraro, Francois Grand'Maison, Raed Alroughani, Murat Terzi, Cavit Boz, Raymond Hupperts, Jeannette Lechner-Scott, Ludwig Kappos, Eugenio Pucci, Suzanne Hodgkinson, Claudio SolaroHelmut Butzkueven

Research output: Contribution to journalArticle

Abstract

Background: Discontinuation of disease-modifying therapies (DMTs) for MS is common. MSBase, a large global observational registry, affords a unique opportunity to investigate predictors of ‘post-DMT’ relapses and confirmed disability progression (CDP) in a diverse group of patients exposed to different DMTs. Materials/methods: Main inclusion criteria: clinician-confirmed MS diagnosis (2010 McDonald criteria); age ≥ 18 at index DMT start; ≥12 months on index DMT prior to discontinuation; ≥24 months of follow-up post-discontinuation; did not restart DMT for ≥6 months. Predictors of time to first relapse and 3-month CDP were analyzed using Cox proportional hazards regression adjusted for age, gender, baseline EDSS, EDSS stability and relapse-free period for ≥1 year prior to discontinuation, calendar epoch, index DMT and reason for discontinuation. Results: 4842 patients (74.2% female) from 20 MSBase Centers met our inclusion criteria. 3556 (73%) discontinued one of IFNβ preparations, 849 (18%) - glatiramer acetate, 308 (6%) - natalizumab and 129 (3%) – fingolimod; other DMTs were excluded because too few records were available. Overall post-discontinuation annualized relapse rate (95% CI) was 0.224 (0.219, 0.229) and CDP rate was 8.23 (7.72, 8.76) per 100 person-years. Risk of post-DMT relapse was higher in younger patients, female patients, those with moderate disability and a relapse within 1 year of discontinuation. Hazard of CDP increased with increasing disability at baseline and disease progression within 3 years prior to stopping DMT. Of all the DMTs, only natalizumab was associated with increased risk of both post-DMT relapse and CDP. Conclusions: Knowledge of post-DMT relapse and disability progression rates and predictors of post-DMT disease activity allows for a more informed discussion of DMT discontinuation in those patients who are considering this option.

Original languageEnglish
Pages (from-to)72-76
Number of pages5
JournalJournal of the Neurological Sciences
Volume391
DOIs
Publication statusPublished - Aug 15 2018

Keywords

  • Disability
  • Disease modifying therapy
  • Multiple sclerosis
  • Observational cohort study
  • Relapse

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Kister, I., Spelman, T., Patti, F., Duquette, P., Trojano, M., Izquierdo, G., Lugaresi, A., Grammond, P., Sola, P., Ferraro, D., Grand'Maison, F., Alroughani, R., Terzi, M., Boz, C., Hupperts, R., Lechner-Scott, J., Kappos, L., Pucci, E., Hodgkinson, S., ... Butzkueven, H. (2018). Predictors of relapse and disability progression in MS patients who discontinue disease-modifying therapy. Journal of the Neurological Sciences, 391, 72-76. https://doi.org/10.1016/j.jns.2018.06.001