Comparative effectiveness of teriflunomide and dimethyl fumarate

Abstract

ObjectiveTo compare on-treatment efficacy and discontinuation outcomes in teriflunomide (TFL) and dimethyl fumarate (DMF) in the treatment of relapsing-remitting multiple sclerosis (RRMS) in a real-world setting.MethodsWe identified all patients starting TFL or DMF from the Danish Multiple Sclerosis Registry and compared on-treatment efficacy outcomes between DMF using TFL, adjusted for clinical baseline variables and propensity score-based methods.ResultsWe included 2,236 patients in the study: 1,469 patients on TFL and 767 on DMF. Annualized relapse rates (ARRs) in TFL and DMF were 0.16 (95% confidence interval [CI] 0.13–0.20) and 0.09 (95% CI 0.07–0.12), respectively. Relapse rate ratio for DMF/TFL was 0.58 (95% CI 0.46–0.73, p < 0.001). DMF had a higher relapse-free survival proportion at 48 months of follow-up (p < 0.05). We observed no difference in Expanded Disability Status Scale score worsening. Discontinuations due to disease breakthrough were 10.2% (95% CI 7.6%–12.8%) and 22.1% (95% CI 19.2%–25.0%) for DMF and TFL, respectively. A subgroup analysis of ARRs in 708 patients with available baseline MRI T2 lesion amount reported similar results after adjustment.ConclusionWe found lower ARR, higher relapse-free survival, and lower incidence of discontinuation due to disease breakthrough on treatment with DMF compared with TFL.Classification of evidenceThis study provides Class II evidence that for patients with RRMS, DMF is more effective in preventing relapses and has lower discontinuation due to disease breakthrough compared with TFL.

Comparative effectiveness of dimethyl fumarate in Multiple Sclerosis

“…their age was 40 years on average, they were mostly female and had an annual rate of relapses of 0.13 during the pre-index period. These ndings are consistent with those of other studies 4,[6][7][8]22,23 . Conversely, some baseline characteristics differed between DMF and FTY patients, although their age at treatment initiation was very similar.…”

“…Many observational studies have been used to assess the real-world comparative effectiveness of DMF and a number of alternative treatments, using claims based-analyses or registries with mixed results. The variability of these results may be explained by the various durations of follow-up limited to 1 year in some studies [3][4][5] , or by the use of simple propensity score (PS)-based methods in other studies 3,[5][6][7][8][9][10] , which although they can balance observed baseline covariates between groups, do nothing to balance unmeasured characteristics and confounders. In this context, comparative studies from real world practice in large population-based healthcare databases using robust statistical methods to handle confounders are needed to provide valuable evidence that will help clinicians in the choice of treatment.…”

The Danish Multiple Sclerosis Registry

“… Reduced disease activity in MS patients treated with dimethyl fumarate compared with patients treated with teriflunomide (Buron et al, 2019). Natalizumab and fingolimod had equal clinical effect in RRMS (Koch‐Henriksen et al, 2017).…”

Immunological Aspects of Approved MS Therapeutics

“…Comparison of the pooled phase-III trial data from 14 mg of teriflunomide and dimethyl-fumarate (DMF) (TEMSO/TOWER vs. DEFINE/CONFIRM) revealed similar numbers needed to treat (NNT) to prevent one relapse or worsening disability (121, 138). However, in a recent registry-based study, the ARR was ~49% lower in patients treated with DMF, and teriflunomide treatment was associated with an increased risk of first relapse and increased incidence of discontinuation due to disease breakthrough (139). In another recent registry-based study with large patient populations, the ARR was similar between teriflunomide and DMF, and discontinuation rate was also similar; nevertheless, ARR were lower in patients treated with fingolimod compared to both DMF and teriflunomide, while disability accumulation was the same (140).…”