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Discontinuation of disease-modifying therapy for patients with relapsing-remitting multiple sclerosis: Effect on clinical and MRI outcomes

  • Hajime Yano
    Affiliations
    Ann Romney Center for Neurologic Diseases and Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA, USA
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  • Cindy Gonzalez
    Affiliations
    Ann Romney Center for Neurologic Diseases and Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA, USA
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  • Brian C. Healy
    Affiliations
    Ann Romney Center for Neurologic Diseases and Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA, USA
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  • Bonnie I. Glanz
    Affiliations
    Ann Romney Center for Neurologic Diseases and Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA, USA
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  • Howard L. Weiner
    Affiliations
    Ann Romney Center for Neurologic Diseases and Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA, USA
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  • Tanuja Chitnis
    Correspondence
    Corresponding author at: Partners Multiple Sclerosis Center, 60 Fenwood Road, Office 9002K, Boston, MA 02115-6128, USA.
    Affiliations
    Ann Romney Center for Neurologic Diseases and Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA, USA
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      Highlights

      • Clinical and radiological stability for ≥2 years can be a milestone to stop DMT.
      • We utilized MRI activity as an inclusion criteria and also as an outcome measure.
      • The impact of stopping DMT may differ based on the age at the discontinuation.
      • Younger patients may have a higher risk of new disease activities after stopping DMT.

      Abstract

      Background

      Disease-modifying therapy (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS) have been shown to reduce relapses and new MRI lesions. However, few studies have assessed the impact of discontinuing DMT after a period of disease inactivity.

      Objective

      To investigate the impact of DMT discontinuation on clinical and radiological outcomes in RRMS patients.

      Methods

      69 RRMS patients who discontinued DMT after a period of disease inactivity were identified from the Comprehensive Longitudinal Investigation of MS study at the Brigham and Women's Hospital, based on the following inclusion criteria: age 18 or older; treated with DMT ≥2 years; no clinical and radiological relapse ≥2 years until the discontinuation; not restarting DMT for ≥6 months after discontinuation. Patients matched by age, gender, treatment, treatment duration, disease duration and Expanded Disability Status Scale score who remained on DMT were identified. Univariate and multivariable Cox proportional hazard models with robust standard errors to account for the paired data were used to test the differences based on DMT discontinuation with the outcome measures: time to clinical relapse, MRI event, disability progression, and disease activity (either clinical relapse or MRI event).

      Results

      Based on the 69 pairs of patients, discontinuation was not associated with time to clinical relapse (HR = 0.87, 95% CI = 0.44–1.72, p = 0.69), MRI event (HR = 0.95, 95% CI = 0.57 to 1.59, p = 0.84), disability progression (HR = 1.24, 95% CI = 0.61 to 2.53, p = 0.55) and disease activity (HR = 0.89, 95% CI = 0.56 to 1.42, p = 0.62). When we performed subgroup analysis to compare the impact of DMT discontinuation between older (age > 45) and younger (age ≤ 45) patients, we found a significant difference in the association between young and old for time to MRI event (p = 0.012) and time to new disease activity (p = 0.0005).

      Conclusions

      This study found that patients who discontinued treatment after a period of disease inactivity had a similar time to next event compared to subjects who remained on first-generation DMTs. In our cohort, we found that discontinuation after age 45 was associated with a stable disease course, while patients younger than age 45 who discontinued treatment were more likely to experience a new clinical relapse or MRI event.

      Keywords

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