Disease activity after discontinuation of disease-modifying therapies in patients with multiple sclerosis in Argentina: data from the nationwide registry RelevarEM

ABSTRACT Introduction The discontinuation of disease-modifying therapies (DMTs) in multiple sclerosis (MS) is commonly seen in real-world settings due to several factors. Area cover The aim of this study is to describe the frequency of disease activity after discontinuation of DMTs in MS patients included in the Argentinean MS and NMOSD registry. Discusion Patients with relapsing remitting MS (RRMS) and active secondary progressive MS (SPMS) were included based on the following criteria: they discontinued treatment for more than 6 months, they had been treated with a DMT for ≥2 years, and they had at least 6 months of follow-up in the registry after discontinuation. Demographic and clinical data were collected. Disease activity during follow-up was defined as the presence of a clinical relapse or a new magnetic resonance (MRI) lesion (either new lesions on T2-weighted sequence and/or contrast enhancement). Bivariate analysis was applied to identify clinical and demographic factors related to disease activity. Conclusion We included 377 patients (75.5% RRMS, 22.5% SPMS) who had discontinued DMTs. The mean (SD) follow-up after discontinuation was 15.7 (7.9) months. After discontinuation, the presence of relapse was detected in 18.8% and 3.5% in RRMS and SPMS, respectively; and new MRI activity in 22% and 3.5%, respectively. We found that higher risk of relapse and MRI activity was associated with younger age (p < 0.001), shorter disease duration (p < 0.001), and RRMS phenotype (p = 0.006). Males showed higher MRI activity (p 0.011). This study provides real-world data that can guide physicians when considering discontinuation of DMTs.

[1]  L. Massacesi,et al.  Sustained disease remission after discontinuation of disease modifying treatments in relapsing-remitting multiple sclerosis. , 2020, Multiple sclerosis and related disorders.

[2]  F. Leutmezer,et al.  Should I stop or should I go on? Disease modifying therapy after the first clinical episode of multiple sclerosis , 2020, Journal of Neurology.

[3]  H. Weiner,et al.  Discontinuation of disease-modifying therapy for patients with relapsing-remitting multiple sclerosis: Effect on clinical and MRI outcomes. , 2019, Multiple sclerosis and related disorders.

[4]  J. Correale,et al.  The Argentinean multiple sclerosis registry (RelevarEM): Methodological aspects and directions. , 2019, Multiple sclerosis and related disorders.

[5]  Devon S. Conway,et al.  Discontinuation of disease-modifying therapy in patients with multiple sclerosis over age 60 , 2019, Multiple sclerosis.

[6]  X. Montalban,et al.  Multiple sclerosis: clinical aspects , 2018, Current opinion in neurology.

[7]  R. Marrie,et al.  Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis , 2018, Neurology.

[8]  David H. Miller,et al.  Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria , 2017, The Lancet Neurology.

[9]  R. Berkovich Clinical and MRI outcomes after stopping or switching disease-modifying therapy in stable MS patients: a case series report. , 2017, Multiple sclerosis and related disorders.

[10]  M. Reindl,et al.  Discontinuation of disease-modifying therapies in multiple sclerosis – Clinical outcome and prognostic factors , 2017, Multiple sclerosis.

[11]  G. Birnbaum Stopping Disease-Modifying Therapy in Nonrelapsing Multiple Sclerosis: Experience from a Clinical Practice. , 2017, International journal of MS care.

[12]  G. Edan,et al.  Can we stop immunomodulatory treatments in secondary progressive multiple sclerosis? , 2017, European journal of neurology.

[13]  F. Barkhof,et al.  The 11-year long-term follow-up study from the randomized BENEFIT CIS trial , 2016, Neurology.

[14]  J. Lechner-Scott,et al.  Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study , 2016, Journal of Neurology, Neurosurgery & Psychiatry.

[15]  B. Weinshenker,et al.  Stopping immunomodulatory medications in MS: Frequency, reasons and consequences. , 2015, Multiple sclerosis and related disorders.

[16]  Jeffrey A. Cohen,et al.  Defining the clinical course of multiple sclerosis: the 2013 revisions. , 2014, Neurology.

[17]  J. Aarseth,et al.  Stoppers and non‐starters of disease‐modifying treatment in multiple sclerosis , 2013, Acta neurologica Scandinavica.

[18]  Y. Ben-Shlomo,et al.  Long-term outcome of paediatric-onset multiple sclerosis: a population-based study , 2012, Journal of Neurology, Neurosurgery & Psychiatry.

[19]  H. Tremlett,et al.  Long-term persistence with the immunomodulatory drugs for multiple sclerosis: a retrospective database study. , 2012, Clinical therapeutics.

[20]  M. Konarska,et al.  Discontinuation of interferon beta therapy in multiple sclerosis patients with high pre-treatment disease activity leads to prompt return to previous disease activity , 2011, Journal of the Neurological Sciences.

[21]  Yinshan Zhao,et al.  Relapses in multiple sclerosis are age- and time-dependent , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[22]  Ludwig Kappos,et al.  A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. , 2006, The New England journal of medicine.

[23]  M. Trojano,et al.  Age-related gadolinium-enhancement of MRI brain lesions in multiple sclerosis , 2005, Journal of the Neurological Sciences.

[24]  I. Elovaara,et al.  Increased disability and MRI lesions after discontinuation of IFN‐β‐1a in secondary progressive MS , 2005, Acta neurologica Scandinavica.

[25]  X. Montalban,et al.  Interferon beta in relapsing–remitting multiple sclerosis , 2005, Journal of Neurology.

[26]  D. Goodkin,et al.  Side effect profile and adherence to in the treatment of Multiple Sclerosis with interferon beta-la , 1998, Multiple sclerosis.

[27]  Ludwig Kappos,et al.  Placebo-controlled multicentre randomised trial of interferon β-1b in treatment of secondary progressive multiple sclerosis , 1998, The Lancet.

[28]  S. Vermund,et al.  Estimating population prevalence of human immunodeficiency virus infection in urban areas with high rates of intravenous drug use: a model of the Bronx in 1988. , 1989, American journal of epidemiology.

[29]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.