University of Oulu

Tiina Mustonen, Ilkka Rauma, Päivi Hartikainen, Johanna Krüger, Marja Niiranen, Tuomas Selander, Sakari Simula, Anne M. Remes, Hanna Kuusisto, Risk factors for reactivation of clinical disease activity in multiple sclerosis after natalizumab cessation, Multiple Sclerosis and Related Disorders, Volume 38, 2020, 101498, ISSN 2211-0348, https://doi.org/10.1016/j.msard.2019.101498

Risk factors for reactivation of clinical disease activity in multiple sclerosis after natalizumab cessation

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Author: Mustonen, Tiina1; Rauma, Ilkka2; Hartikainen, Päivi1,3;
Organizations: 1Kuopio University Hospital, Neuro Center, Puijonlaaksontie 2, P.O. Box 100, 70029 KYS, Finland
2Tampere University Hospital, Department of Neurology, Teiskontie 35, 33520 Tampere, Finland
3University of Eastern Finland, Department of Neurology, Yliopistonranta 1, 70210 Kuopio, Finland
4University of Oulu, Research Unit of Clinical Neuroscience, P.O. Box 8000, 90014 University of Oulu, Finland
5Northern Ostrobothnia Hospital District, MRC Oulu, P.O. Box 8000, 90014 University of Oulu, Finland
6Kuopio University Hospital, Science Service Center, Puijonlaaksontie 2, P.O. Box 100, 70029 KYS, Finland
7Mikkeli Central Hospital, Department of Neurology, Porrassalmenkatu 35-37, 50100 Mikkeli, Finland
8University of Eastern Finland, Department of Health and Social Management, Yliopistonranta 1, 70210 Kuopio, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2020051127252
Language: English
Published: Elsevier, 2020
Publish Date: 2020-11-05
Description:

Abstract

Background: Natalizumab (NTZ) is widely used for highly active relapsing-remitting multiple sclerosis (MS). Inflammatory disease activity often returns after NTZ treatment discontinuation. We aimed to identify predictive factors for such reactivation in a real-life setting.

Methods: We conducted a retrospective survey in four Finnish hospitals. A computer-based search was used to identify all patients who had received NTZ for multiple sclerosis. Patients were included if they had received at least six NTZ infusions, had discontinued treatment for at least three months, and follow-up data was available for at least 12 months after discontinuation. Altogether 89 patients were analyzed with Cox regression model to identify risk factors for reactivation, defined as having a corticosteroid-treated relapse.

Results: At 6 and 12 months after discontinuation of NTZ, a relapse was documented in 27.0% and 35.6% of patients, whereas corticosteroid-treated relapses were documented in 20.2% and 30.3% of patients, respectively. A higher number of relapses during the year prior to the introduction of NTZ was associated with a significantly higher risk for reactivation at 6 months (Hazard Ratio [HR] 1.65, p < 0.001) and at 12 months (HR 1.53, p < 0.001). Expanded Disability Status Scale (EDSS) of 5.5 or higher before NTZ initiation was associated with a higher reactivation risk at 6 months (HR 3.70, p = 0.020). Subsequent disease-modifying drugs (DMDs) failed to prevent reactivation of MS in this cohort. However, when subsequent DMDs were used, a washout time longer than 3 months was associated with a higher reactivation risk at 6 months regardless of whether patients were switched to first-line (HR 7.69, p = 0.019) or second-line therapies (HR 3.94, p = 0.035). Gender, age, time since diagnosis, and the number of NTZ infusions were not associated with an increased risk for reactivation.

Conclusion: High disease activity and a high level of disability prior to NTZ treatment seem to predict disease reactivation after treatment cessation. When switching to subsequent DMDs, the washout time should not exceed 3 months. However, subsequent DMDs failed to prevent the reactivation of MS in this cohort.

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Series: Multiple sclerosis and related disorders
ISSN: 2211-0348
ISSN-E: 2211-0356
ISSN-L: 2211-0348
Volume: 38
Article number: 101498
DOI: 10.1016/j.msard.2019.101498
OADOI: https://oadoi.org/10.1016/j.msard.2019.101498
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Subjects:
Funding: This work was in part supported by VTR grant 5772804 of Kuopio University Hospital and the personal grants of IR from Orion Research Foundation sr and The Finnish Medical Foundation.
Copyright information: © 2019 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
  https://creativecommons.org/licenses/by-nc-nd/4.0/