Highlights
- •4842 patients in MSBase Registry stopped disease modifying therapy (DMT) for >6 months
- •During post-DMT period, the annualized relapse rate was 0.22 and confirmed disability (CDP) progression rate was 8.23 per 100 person-years
- •Younger and moderately disabled patients were at highest risk of post-DMT relapse
- •Patients who entered the progressive phase or were severely impaired at baseline were at highest risk for CDP during post-DMT follow up
- •Former natalizumab users had elevated relapse and CDP rates during follow up compared to other DMTs
Abstract
Background
Discontinuation of disease-modifying therapies (DMTs) for MS is common. MSBase, a
large global observational registry, affords a unique opportunity to investigate predictors
of ‘post-DMT’ relapses and confirmed disability progression (CDP) in a diverse group
of patients exposed to different DMTs.
Materials/methods
Main inclusion criteria: clinician-confirmed MS diagnosis (2010 McDonald criteria);
age ≥ 18 at index DMT start; ≥12 months on index DMT prior to discontinuation; ≥24 months
of follow-up post-discontinuation; did not restart DMT for ≥6 months. Predictors of
time to first relapse and 3-month CDP were analyzed using Cox proportional hazards
regression adjusted for age, gender, baseline EDSS, EDSS stability and relapse-free
period for ≥1 year prior to discontinuation, calendar epoch, index DMT and reason
for discontinuation.
Results
4842 patients (74.2% female) from 20 MSBase Centers met our inclusion criteria. 3556
(73%) discontinued one of IFNβ preparations, 849 (18%) - glatiramer acetate, 308 (6%)
- natalizumab and 129 (3%) – fingolimod; other DMTs were excluded because too few
records were available. Overall post-discontinuation annualized relapse rate (95%
CI) was 0.224 (0.219, 0.229) and CDP rate was 8.23 (7.72, 8.76) per 100 person-years.
Risk of post-DMT relapse was higher in younger patients, female patients, those with
moderate disability and a relapse within 1 year of discontinuation. Hazard of CDP
increased with increasing disability at baseline and disease progression within 3 years
prior to stopping DMT. Of all the DMTs, only natalizumab was associated with increased
risk of both post-DMT relapse and CDP.
Conclusions
Knowledge of post-DMT relapse and disability progression rates and predictors of post-DMT
disease activity allows for a more informed discussion of DMT discontinuation in those
patients who are considering this option.
Keywords
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References
- Persistence to disease-modifying therapies for multiple sclerosis in a Canadian cohort.Patient Prefer. Adherence. 2017 Jun 28; 11 (doi: 10.2147/PPA.S138263.eCollection 2017): 1093-1101
- Stopping beta interferon therapy in multiple sclerosis: an analysis of stopping patterns.Mult. Scler. 2005; 11: 46-50
- Recognizing nonadherence in patients with multiple sclerosis and maintaining treatmentadherence in the long term.Medscape J. Med. 2008; 10: 225
- Discontinuation of disease-modifying therapies in multiple sclerosis - clinical outcome and prognostic factors.Mult. Scler. 2017 Aug; 23 (Epub 2016 Oct 20): 1241-1248https://doi.org/10.1177/1352458516675751
- Sylvia Lawry Centre for MS research. Predictors of relapse rate in MS clinical trials.Neurology. 2005 Dec 13; 65: 1769-1773
- Sex as a determinant of relapse incidence and progressive course of multiple sclerosis.Brain. 2013; 136: 3609-3617
- Relapses in multiple sclerosis are age- and time-dependent.J. Neurol. Neurosurg. Psychiatry. 2008; 79: 1368-1374
- Relapses and progression of disability in multiple sclerosis.N. Engl. J. Med. 2000 Nov 16; 343: 1430-1438
- Evidence for a two-stage disability progression in multiple sclerosis.Brain. 2010 Jul; 133 (Epub 2010 Apr 27): 1900-1913https://doi.org/10.1093/brain/awq076
- Disease activity return after natalizumab cessation in multiple sclerosis.Expert. Rev. Neurother. 2016 May; 16 (Epub 2016 Apr 6): 587-594https://doi.org/10.1586/14737175.2016.1168295
- Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients. First line drugs vs natalizumab.Mult. Scler. Relat. Disord. 2017 Feb; 12 (Epub 2017 Jan 24): 82-87https://doi.org/10.1016/j.msard.2017.01.009
- Natalizumab treatment is associated with peripheral sequestration of proinflammatory T cells.Neurology. 2009 Jun 2; 72: 1922-1930https://doi.org/10.1212/WNL.0b013e3181a8266f
- Risk of relapse after natalizumab withdrawal: results from the French TYSEDMUS cohort.Neurol. Neuroimmunol. Neuroinflamm. 2016 Oct 28; 3e297
- Withdrawal of fingolimod treatment for relapsing-remitting multiple sclerosis: report of six cases.Mult. Scler. 2012 Nov; 18 (Epub 2012 Jul 24): 1636-1639https://doi.org/10.1177/1352458512454773
- Rebound syndrome in patients with multiple sclerosis after cessation of Fingolimod treatment.JAMA Neurol. 2016 Jul 1; 73: 790-794https://doi.org/10.1001/jamaneurol.2016.0826
- Can we stop immunomodulatory treatments in secondary progressive multiple sclerosis?.Eur. J. Neurol. 2017 Feb; 24: 237-244https://doi.org/10.1111/ene.13181
- Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study.J. Neurol. Neurosurg. Psychiatry. 2016 Oct; 87: 1133-1137https://doi.org/10.1136/jnnp-2016-313760
- New natural history of interferon-beta-treated relapsing multiple sclerosis.Ann. Neurol. 2007 Apr; 61: 300-306
- Cause of death in MS: long-term follow-up of a randomised cohort, 21 years after the start of the pivotal IFNβ-1b study.BMJ Open. 2012 Nov 30; 2 (pii: e001972)
- Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS)| PCORI.http://www.pcori.org/research-results/2015/discontinuation-disease-modifying-therapies-dmts-multiple-sclerosis-msDate accessed: November 18, 2015
Article info
Publication history
Published online: June 02, 2018
Accepted:
June 1,
2018
Received in revised form:
May 30,
2018
Received:
April 30,
2018
Identification
Copyright
© 2018 Elsevier B.V. All rights reserved.
