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 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 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 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.
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Contributors MDB: conception and design of the work, data collection, data analysis and interpretation, drafting the article, critical revision of the article. TK: conception and design of the work, data analysis and interpretation, critical revision of the article. FS and PSS: data collection, critical revision of the article, data analysis and interpretation. MM: conception and design of the work, data collection, data analysis and interpretation, critical revision of the article.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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.
Patient consent for publication Not required.
Ethics approval This study was approved by the Danish Data Protection Agency (journal no. RH-2017-347, I-Suite no: 06058). Non-interventional register-based studies do not require ethical approval in Denmark.
Data availability statement Data are available upon reasonable request. Anonymised data will be shared on request from any qualified investigator under approval from the Danish Data Protection Agency and the board of the DMSR.
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