Abstract

BACKGROUND: Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Data on clinical and imaging measures predictive of disease activity and progression during treatment is limited.

OBJECTIVE: To determine clinical and imaging predictors of long-term inflammatory disease activity and disability progression in RRMS patients on natalizumab.

METHODS: Patients (n = 135) were selected from our prospective observational natalizumab cohort and monitored using brain MRI and extensive clinical testing. Progression and improvement on the Expanded Disability Status Scale (EDSS), no evidence of disease activity (NEDA) and no evidence of progression or active disease (NEPAD) status were determined using measurements after the initial phase of inflammation and the early anti-inflammatory impact of natalizumab.

RESULTS: EDSS progression was seen in 43.7% of patients and EDSS improvement in 17.8%. Median follow-up was 4.9 years (IQR 3.6-6.0). Patients with a longer disease duration at natalizumab initiation have a higher hazard for earlier EDSS progression (HR 1.05, CI 1.00-1.09, p = 0.037) and a higher pre-baseline relapse rate predicted a longer NEPAD status (HR 1.70, CI 1.06-2.72, p = 0.028).

CONCLUSION: The results suggest that starting natalizumab early, during active inflammatory disease results in a more favourable outcome. When taking into account early inflammation and the impact of natalizumab on disease activity during the initial treatment phase, a higher than expected proportion of patients showed disability progression.

Original languageEnglish
Pages (from-to)82-87
Number of pages6
JournalMultiple Sclerosis and Related Disorders
Volume33
DOIs
Publication statusPublished - 1 Aug 2019

Cite this

@article{170025e9cbcb41a2af40d1606d575fae,
title = "Long-term disease activity and disability progression in relapsing-remitting multiple sclerosis patients on natalizumab",
abstract = "BACKGROUND: Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Data on clinical and imaging measures predictive of disease activity and progression during treatment is limited.OBJECTIVE: To determine clinical and imaging predictors of long-term inflammatory disease activity and disability progression in RRMS patients on natalizumab.METHODS: Patients (n = 135) were selected from our prospective observational natalizumab cohort and monitored using brain MRI and extensive clinical testing. Progression and improvement on the Expanded Disability Status Scale (EDSS), no evidence of disease activity (NEDA) and no evidence of progression or active disease (NEPAD) status were determined using measurements after the initial phase of inflammation and the early anti-inflammatory impact of natalizumab.RESULTS: EDSS progression was seen in 43.7{\%} of patients and EDSS improvement in 17.8{\%}. Median follow-up was 4.9 years (IQR 3.6-6.0). Patients with a longer disease duration at natalizumab initiation have a higher hazard for earlier EDSS progression (HR 1.05, CI 1.00-1.09, p = 0.037) and a higher pre-baseline relapse rate predicted a longer NEPAD status (HR 1.70, CI 1.06-2.72, p = 0.028).CONCLUSION: The results suggest that starting natalizumab early, during active inflammatory disease results in a more favourable outcome. When taking into account early inflammation and the impact of natalizumab on disease activity during the initial treatment phase, a higher than expected proportion of patients showed disability progression.",
keywords = "Disability progression, Disease activity, Disease modifying treatment, Multiple sclerosis, Natalizumab",
author = "I Dekker and Leurs, {C E} and Hagens, {M H J} and {van Kempen}, {Z L E} and I Kleerekooper and Lissenberg-Witte, {B I} and F Barkhof and Uitdehaag, {B M J} and Balk, {L J} and Wattjes, {M P} and J Killestein",
note = "Copyright {\circledC} 2019 Elsevier B.V. All rights reserved.",
year = "2019",
month = "8",
day = "1",
doi = "10.1016/j.msard.2019.05.017",
language = "English",
volume = "33",
pages = "82--87",
journal = "Multiple Sclerosis and Related Disorders",
issn = "2211-0348",
publisher = "Elsevier",

}

TY - JOUR

T1 - Long-term disease activity and disability progression in relapsing-remitting multiple sclerosis patients on natalizumab

AU - Dekker, I

AU - Leurs, C E

AU - Hagens, M H J

AU - van Kempen, Z L E

AU - Kleerekooper, I

AU - Lissenberg-Witte, B I

AU - Barkhof, F

AU - Uitdehaag, B M J

AU - Balk, L J

AU - Wattjes, M P

AU - Killestein, J

N1 - Copyright © 2019 Elsevier B.V. All rights reserved.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - BACKGROUND: Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Data on clinical and imaging measures predictive of disease activity and progression during treatment is limited.OBJECTIVE: To determine clinical and imaging predictors of long-term inflammatory disease activity and disability progression in RRMS patients on natalizumab.METHODS: Patients (n = 135) were selected from our prospective observational natalizumab cohort and monitored using brain MRI and extensive clinical testing. Progression and improvement on the Expanded Disability Status Scale (EDSS), no evidence of disease activity (NEDA) and no evidence of progression or active disease (NEPAD) status were determined using measurements after the initial phase of inflammation and the early anti-inflammatory impact of natalizumab.RESULTS: EDSS progression was seen in 43.7% of patients and EDSS improvement in 17.8%. Median follow-up was 4.9 years (IQR 3.6-6.0). Patients with a longer disease duration at natalizumab initiation have a higher hazard for earlier EDSS progression (HR 1.05, CI 1.00-1.09, p = 0.037) and a higher pre-baseline relapse rate predicted a longer NEPAD status (HR 1.70, CI 1.06-2.72, p = 0.028).CONCLUSION: The results suggest that starting natalizumab early, during active inflammatory disease results in a more favourable outcome. When taking into account early inflammation and the impact of natalizumab on disease activity during the initial treatment phase, a higher than expected proportion of patients showed disability progression.

AB - BACKGROUND: Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Data on clinical and imaging measures predictive of disease activity and progression during treatment is limited.OBJECTIVE: To determine clinical and imaging predictors of long-term inflammatory disease activity and disability progression in RRMS patients on natalizumab.METHODS: Patients (n = 135) were selected from our prospective observational natalizumab cohort and monitored using brain MRI and extensive clinical testing. Progression and improvement on the Expanded Disability Status Scale (EDSS), no evidence of disease activity (NEDA) and no evidence of progression or active disease (NEPAD) status were determined using measurements after the initial phase of inflammation and the early anti-inflammatory impact of natalizumab.RESULTS: EDSS progression was seen in 43.7% of patients and EDSS improvement in 17.8%. Median follow-up was 4.9 years (IQR 3.6-6.0). Patients with a longer disease duration at natalizumab initiation have a higher hazard for earlier EDSS progression (HR 1.05, CI 1.00-1.09, p = 0.037) and a higher pre-baseline relapse rate predicted a longer NEPAD status (HR 1.70, CI 1.06-2.72, p = 0.028).CONCLUSION: The results suggest that starting natalizumab early, during active inflammatory disease results in a more favourable outcome. When taking into account early inflammation and the impact of natalizumab on disease activity during the initial treatment phase, a higher than expected proportion of patients showed disability progression.

KW - Disability progression

KW - Disease activity

KW - Disease modifying treatment

KW - Multiple sclerosis

KW - Natalizumab

UR - http://www.scopus.com/inward/record.url?scp=85066434679&partnerID=8YFLogxK

U2 - 10.1016/j.msard.2019.05.017

DO - 10.1016/j.msard.2019.05.017

M3 - Article

VL - 33

SP - 82

EP - 87

JO - Multiple Sclerosis and Related Disorders

JF - Multiple Sclerosis and Related Disorders

SN - 2211-0348

ER -