Discontinuation of disease-modifying therapies in multiple sclerosis – Clinical outcome and prognostic factors

Bsteh, Gabriel; Feige, Julia; Ehling, Rainer; Auer, Michael; Hegen, Harald; Pauli, Franziska Di; Deisenhammer, Florian; Reindl, Markus; Berger, Thomas

doi:10.1177/1352458516675751

Cited by 69 publications

(59 citation statements)

References 30 publications

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“…It has also been shown that demographic and clinical data can be predicted well without MRI data. The predictors of EDSS increase after discontinuation of therapy were high EDSS scores, age over 45 years, and long disease duration (32).…”

Section: Clinical Biomarkersmentioning

confidence: 97%

Prognostic-disability Biomarkers in Multiple Sclerosis: Review of the Literature from the Last Five Years

Kıylıoğlu¹

2018

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With the advent of new agents in the treatment of multiple sclerosis, new treatment modalities have emerged (escalation-induction therapy) and the increased efficacy of the drugs has led to increased drug-related risks. The risk/benefit balance has become more carefully assessed. The increased need for reliable markers to predict prognosis-disability has also led to an increase in research conducted in this area. In this short review, studies published between 2012-2017, especially those related to prognosis and disability, were compiled.

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Section: Clinical Biomarkersmentioning

confidence: 97%

Prognostic-disability Biomarkers in Multiple Sclerosis: Review of the Literature from the Last Five Years

Kıylıoğlu¹

2018

tnd

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“…Twenty-two articles were included in the review, including 12 studies on discontinuation of DMTs [6][7][8][9][10][11][12][13][14][15][16][17] in MS and ten articles with practice recommendations from published guidelines and national organizations. [18][19][20][21][22][23][24][25][26][27] Of the 12 discontinuation studies, seven were prospective cohort studies, three retrospective cohort studies, one a combined prospective/retrospective cohort study, and one a randomized clinical trial.…”

Section: Overview Of Selected Articles For Narrative Reviewmentioning

confidence: 99%

“…The only statistically independent predictors of disability progression were longer duration of disease (HR, 1.21), EDSS score at discontinuation (HR, 1.47), and age at discontinuation (HR, 1.33). 7 In SPMS, a retrospective cohort study was conducted in France with 100 consecutive clinic patients who had stopped treatment. 8 The ARRs 1 and 3 years after treatment discontinuation were similar, with 16 people experiencing relapses after treatment stop.…”

Section: Eligibility Criteriamentioning

confidence: 99%

“…Of the four studies reporting on first-line DMTs, two examined patients with RRMS, 6,7 one examined patients with SPMS, 8 and one examined patients with an unspecified MS phenotype. 9 A prospective cohort study was conducted in Poland with 43 patients with RRMS who discontinued IFNβ.…”

Section: Discontinuation Of First-line Dmtsmentioning

confidence: 99%

“…6 Another prospective cohort study conducted in Austria included 221 patients with RRMS and at least 2 years of follow-up. 7 On multivariate analysis, the combination of age older than 45 years and the A retrospective cohort study recruited 132 patients with RRMS from two Italian MS centers. 12 Ninety-five participants were switched to another treatment after a median natalizumab washout period of 5 months, including 57 participants who switched to fingolimod.…”

Section: Discontinuation Of First-line Dmtsmentioning

confidence: 99%

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The Dilemma of When to Stop Disease-Modifying Therapy in Multiple Sclerosis

Knox¹,

Saini²,

Levin³

2020

International Journal of MS Care

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Background: Disease-modifying therapy (DMT) has changed the landscape of multiple sclerosis (MS) care. However, there is lack of consensus on the duration of treatment and the selection of individuals most likely to benefit from continued treatment. Current evidence, practice guidelines, health policy, and ethical considerations presented together may further inform challenging clinical decision making and future directions. The objectives of this study were to conduct a narrative review of original research and practice guideline recommendations on discontinuation of DMTs in MS; to collect information regarding Canadian regional reimbursement policies for DMT coverage in MS; and to present ethical considerations applicable to such decision making. Methods: A literature review was conducted of the MEDLINE/PubMed, OneFile (GALE), Scopus (Elsevier), and ProQuest Biological Science Collection databases. Data regarding Canadian regional reimbursement policies for DMT coverage in MS were collected from the ministry/government websites. Ethical considerations were reviewed in the context of the identified evidence, guidelines, and policies. Results: The literature lacks evidence from prospective randomized controlled trials that directly addresses the issue of discontinuation of DMTs in MS. Current practice guidelines advocate the vital role of patient choice in decision making. There are regional variations in Expanded Disability Status Scale criteria scores for continuing MS DMT coverage among Canadian provinces/territories. Conclusions: In the absence of strong evidence on discontinuation of DMTs, shared decision making and consideration of the ethical complexities could help in the decision-making process.

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High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS

Jouvenot,

Courbon,

Lefort

et al. 2024

JAMA Neurol

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ImportanceA recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity.ObjectiveTo determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET.Design, Setting, and ParticipantsThis observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques [OFSEP] database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022.ExposuresNatalizumab, fingolimod, rituximab, and ocrelizumab.Main Outcomes and MeasuresTime to first relapse.ResultsOf 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean [SD] age, 57.7 [5.5] years; mean [SD] delay since the last inflammatory activity, 5.6 [3.8] years; mean [SD] follow-up duration after propensity score matching, 2.5 [2.1] years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P &lt; .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy.Conclusion and RelevanceAs in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice.

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Discontinuation of disease-modifying therapies in multiple sclerosis – Clinical outcome and prognostic factors

Cited by 69 publications

References 30 publications

Prognostic-disability Biomarkers in Multiple Sclerosis: Review of the Literature from the Last Five Years

Prognostic-disability Biomarkers in Multiple Sclerosis: Review of the Literature from the Last Five Years

The Dilemma of When to Stop Disease-Modifying Therapy in Multiple Sclerosis

High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS

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