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Comparative Study
. 2018 Dec;265(12):2980-2992.
doi: 10.1007/s00415-018-9083-5. Epub 2018 Oct 16.

Comparative effectiveness of delayed-release dimethyl fumarate versus interferon, glatiramer acetate, teriflunomide, or fingolimod: results from the German NeuroTransData registry

Stefan Braune  1 , Sarah Grimm  2 , Philip van Hövell  2 , Ulrich Freudensprung  3 , Fabio Pellegrini  3 , Robert Hyde  3 , Arnfin Bergmann  4 ; NTD Study Group
Affiliations
Comparative Study

Comparative effectiveness of delayed-release dimethyl fumarate versus interferon, glatiramer acetate, teriflunomide, or fingolimod: results from the German NeuroTransData registry

Stefan Braune et al. J Neurol. 2018 Dec.

Abstract

Background: Comparative effectiveness (CE) research allows real-world treatment comparisons using outcome measurements important to physicians/patients. This German NeuroTransData registry-based analysis compared delayed-release dimethyl fumarate (DMF) effectiveness with interferons (IFN), glatiramer acetate (GA), teriflunomide (TERI), or fingolimod (FTY) in patients with relapsing-remitting multiple sclerosis (RRMS) using propensity score matching (PSM).

Methods: Data from registry patients aged ≥ 18 years with RRMS, ≥ 1 relapse, and Expanded Disability Status Scale (EDSS) assessment(s) after index therapy initiation underwent 1:1 PSM to match DMF with comparator populations baseline characteristics. Primary outcome measurement was time to first relapse (TTFR). Secondary outcome measurements included annualised relapse rate (ARR), proportion of patients relapse free at 12 and 24 months, time to index therapy discontinuation (TTD), and reasons for discontinuation. Exploratory analyses included time to 3- and 6-month EDSS confirmed disability progression (CDP). Non-pairwise censoring was the primary analysis method; pairwise censoring was the main sensitivity analysis method.

Findings: Post-matched cohorts were well-balanced. By non-pairwise censoring, TTFR and ARR were significantly lower in DMF populations versus matched IFN, GA, and TERI, but there was no evidence of difference between DMF and FTY. TTD was similar between DMF and IFN, GA, and TERI, but significantly shorter versus FTY. Time to CDP generally showed no evidence of difference between DMF and comparator populations. Pairwise censored analysis results confirmed the non-pairwise censoring results.

Interpretation: These results support previous CE studies in demonstrating relative improvement in real-world effectiveness with DMF versus first-line agents IFN, GA, and TERI, and similar effectiveness versus FTY.

Keywords: Comparative effectiveness research; Dimethyl fumarate; Multiple sclerosis; Observational data; Propensity score matching; Registry.

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Conflict of interest statement

Conflicts of interest

SB received honoraria from Kassenärztliche Vereinigung Bayerns and health maintenance organisations for patient care, and from Biogen, MedDay, NeuroTransData, Novartis, and Roche for consulting, project management, clinical studies, and lectures; he also received honoraria and expense compensation as a board member of NeuroTransData. SG and PvH are employees of PwC, which was contracted to perform the statistical analysis for NeuroTransData. UF, RH, and FP are employees of and hold stock/stock options in Biogen. AB received honoraria from NeuroTransData for project management, clinical studies, and travel expenses from Novartis and Servier; he also received honoraria and expense compensation as a board member of NeuroTransData.

Ethical approval

The manuscript does not contain clinical studies or individually identifiable patient data.

Figures

Fig. 1
Fig. 1
Hazard ratios of time to first relapse for DMF versus comparator populations. DMF delayed-release dimethyl fumarate, FTY fingolimod, GA glatiramer acetate, IFN interferons, TERI teriflunomide
Fig. 2
Fig. 2
Time to first relapse KM survival curves. a DMF versus IFN all-comer population; b DMF versus GA all-comer population; c DMF versus TERI all-comer population; d DMF versus FTY all-comer population, and e DMF versus FTY label population. DMF delayed-release dimethyl fumarate, FTY fingolimod, GA glatiramer acetate, IFN interferons, KM Kaplan–Meier, TERI teriflunomide
Fig. 3
Fig. 3
Forest plot of annualised relapse rate for DMF versus comparator populations. DMF delayed-release dimethyl fumarate, FTY fingolimod, GA glatiramer acetate, IFN interferons, TERI teriflunomide
Fig. 4
Fig. 4
Time to index therapy discontinuation KM survival curves. a DMF versus IFN all-comer population; b DMF versus GA all-comer population; c DMF versus TERI all-comer population; d DMF versus FTY all-comer population; e DMF versus FTY label population. DMF delayed-release dimethyl fumarate, FTY fingolimod, GA glatiramer acetate, IFN interferons, KM Kaplan–Meier, TERI teriflunomide
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