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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Article info
Publication history
Published online: July 25, 2019
Accepted:
July 24,
2019
Received in revised form:
July 19,
2019
Received:
March 17,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
