Teriflunomide reduces relapse-related neurological sequelae, hospitalizations and steroid use

Abstract

Multiple sclerosis (MS) relapses impose a substantial clinical and economic burden. Teriflunomide is a new oral disease-modifying therapy approved for the treatment of relapsing MS. We evaluated the effects of teriflunomide treatment on relapse-related neurological sequelae and healthcare resource use in a post hoc analysis of the Phase III TEMSO study. Confirmed relapses associated with neurological sequelae [defined by an increase in Expanded Disability Status Scale/Functional System (sequelae-EDSS/FS) ≥ 30 days post relapse or by the investigator (sequelae-investigator)] were analyzed in the modified intention-to-treat population (n = 1086). Relapses requiring hospitalization or intravenous (IV) corticosteroids, all hospitalizations, emergency medical facility visits (EMFV), and hospitalized nights for relapse were also assessed. Annualized rates were derived using a Poisson model with treatment, baseline EDSS strata, and region as covariates. Risks of sequelae and hospitalization per relapse were calculated as percentages and groups were compared with a χ(2) test. Compared with placebo, teriflunomide reduced annualized rates of relapses with sequelae-EDSS/FS [7 mg by 32 % (p = 0.0019); 14 mg by 36 % (p = 0.0011)] and sequelae-investigator [25 % (p = 0.071); 53 % (p < 0.0001)], relapses leading to hospitalization [36 % (p = 0.015); 59 % (p < 0.0001)], and relapses requiring IV corticosteroids [29 % (p = 0.001); 34 % (p = 0.0003)]. Teriflunomide-treated patients spent fewer nights in hospital for relapse (p < 0.01). Teriflunomide 14 mg also decreased annualized rates of all hospitalizations (p = 0.01) and EMFV (p = 0.004). The impact of teriflunomide on relapse-related neurological sequelae and relapses requiring healthcare resources may translate into reduced healthcare costs.

Fig. 1

Adjusted annualized rates (i) and risk per relapse (ii) for each outcome analyzed: a relapses with sequelae-EDSS/FS; b relapses with sequelae-investigator; c relapses leading to hospitalization; d relapses requiring IV corticosteroids. Relative change: a positive sign shows a relative increase and a negative sign shows a relative decrease. Adjusted annualized rates were derived using a Poisson model with the total number of the outcome of interest as the response variable and treatment, Expanded Disability Status Scale (EDSS) strata at baseline and region as covariates, and log-transformed standardized study treatment duration as an offset variable. Relapses with sequelae: incomplete neurological recovery, defined by an increase of EDSS or Functional System (FS) 30 days post relapse, assessed every 30 days from 30 to 180 days after relapse or incomplete neurological recovery as assessed by the investigator at the end of relapse. Missing data regarding intravenous (IV) corticosteroid use were reported in 12.6 % of relapses

Fig. 2

Adjusted annualized rate of relapse with sequelae-EDSS/FS assessed over time. Relapses with sequelae: incomplete neurological recovery, defined by an increase of EDSS Expanded Disability Status Scale or FS Functional System between last assessment before relapse and at least 30 days post relapse, and assessed every 30 days from 30 to 180 days after relapse

Fig. 3

Adjusted annualized rates of a all hospitalizations and b emergency medical facility visits