Effect of lateral therapy switches to oral moderate-efficacy drugs in multiple sclerosis: a nationwide cohort study.


Journal

Journal of neurology, neurosurgery, and psychiatry
ISSN: 1468-330X
Titre abrégé: J Neurol Neurosurg Psychiatry
Pays: England
ID NLM: 2985191R

Informations de publication

Date de publication:
May 2021
Historique:
received: 12 08 2020
revised: 05 12 2020
accepted: 14 12 2020
pubmed: 14 1 2021
medline: 4 1 2022
entrez: 13 1 2021
Statut: ppublish

Résumé

Switching between first-line disease-modifying therapies in patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) due to reasons other than disease activity is frequent, but evidence on the effect of this practice is limited. We investigated the effect of switching patients with stable RRMS on occurrences of disability accumulation, relapses and future treatment discontinuation. Using the Danish Multiple Sclerosis Registry, we identified patients with RRMS without disease activity who either (1) stayed on injectable platform therapy (interferon-β or glatiramer acetate) or (2) switched to dimethyl fumarate (DMF) or teriflunomide (TFL) and compared treatment outcomes using propensity-score-based methods and marginal structural models (MSM). We included 3206 patients in the study. We found no change in risk of 6-month confirmed Expanded Disability Status Scale score worsening in patients switching to DMF (HR: 1.15, 95% CI 0.88 to 1.50) or TFL (HR: 1.16, 95% CI 0.92 to 1.46). The risk of suffering any relapse tended to decrease when switching to DMF (HR: 0.73, 95% CI 0.51 to 1.04) and tended to increase when switching to TFL (HR: 1.25, 95% CI 0.96 to 1.63). Absolute risk differences were small. MSM analyses showed similar results but did not find an increased relapse risk in TFL switchers. Switching from injectable platform therapies to oral first-line therapies in patients with clinically stable RRMS does not increase the risk of disability accumulation. While the postswitch risk of relapses trended towards marginally higher on TFL, this trend was eliminated by adjustment for time-variant confounders.

Sections du résumé

BACKGROUND BACKGROUND
Switching between first-line disease-modifying therapies in patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) due to reasons other than disease activity is frequent, but evidence on the effect of this practice is limited. We investigated the effect of switching patients with stable RRMS on occurrences of disability accumulation, relapses and future treatment discontinuation.
METHODS METHODS
Using the Danish Multiple Sclerosis Registry, we identified patients with RRMS without disease activity who either (1) stayed on injectable platform therapy (interferon-β or glatiramer acetate) or (2) switched to dimethyl fumarate (DMF) or teriflunomide (TFL) and compared treatment outcomes using propensity-score-based methods and marginal structural models (MSM).
RESULTS RESULTS
We included 3206 patients in the study. We found no change in risk of 6-month confirmed Expanded Disability Status Scale score worsening in patients switching to DMF (HR: 1.15, 95% CI 0.88 to 1.50) or TFL (HR: 1.16, 95% CI 0.92 to 1.46). The risk of suffering any relapse tended to decrease when switching to DMF (HR: 0.73, 95% CI 0.51 to 1.04) and tended to increase when switching to TFL (HR: 1.25, 95% CI 0.96 to 1.63). Absolute risk differences were small. MSM analyses showed similar results but did not find an increased relapse risk in TFL switchers.
CONCLUSION CONCLUSIONS
Switching from injectable platform therapies to oral first-line therapies in patients with clinically stable RRMS does not increase the risk of disability accumulation. While the postswitch risk of relapses trended towards marginally higher on TFL, this trend was eliminated by adjustment for time-variant confounders.

Identifiants

pubmed: 33436501
pii: jnnp-2020-324869
doi: 10.1136/jnnp-2020-324869
doi:

Substances chimiques

Immunosuppressive Agents 0
Glatiramer Acetate 5M691HL4BO
Interferon-beta 77238-31-4

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

556-562

Commentaires et corrections

Type : CommentIn

Informations de copyright

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: MDB reports non-financial support from Roche, outside the submitted work. TK reports grants from NHMRC, grants from UK MS Society, during the conduct of the study; grants from University of Melbourne, grants, personal fees and non-financial support from Biogen, personal fees from Roche, personal fees and non-financial support from Genzyme-Sanofi, personal fees and non-financial support from Merck, personal fees from Novartis, personal fees from WebMD Global, personal fees from Teva, personal fees from BioCSL, outside the submitted work. FS reports grants from Biogen, Merck, Novartis, Roche, Sanofi Genzyme, personal fees from Biogen, Merck, Novartis, Roche, Sanofi Genzyme and Teva, outside the submitted work; PSS reports personal fees from Biogen, personal fees from Merck, personal fees from Novartis, personal fees from TEVA, personal fees from GlaxoSmithKline, personal fees from Celgene, outside the submitted work. MM reports grants and personal fees from Biogen, Novartis, Roche, Merck, Sanofi, outside the submitted work.

Auteurs

Mathias Due Buron (MD)

Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark mathias.buron@regionh.dk.
Danish Multiple Sclerosis Registry, Rigshospitalet, Copenhagen, Denmark.

Tomas Kalincik (T)

CORe, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Finn Sellebjerg (F)

Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Per Soelberg Sørensen (PS)

Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Melinda Magyari (M)

Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Danish Multiple Sclerosis Registry, Rigshospitalet, Copenhagen, Denmark.

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Classifications MeSH