title: Teriflunomide reduces relapses with sequelae and relapses leading to hospitalizations: results from the TOWER study.
abstract: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis. This post hoc analysis of the Phase III TOWER study evaluated the effects of teriflunomide treatment on five severe relapse outcomes: relapses with sequelae defined by an increase in Expanded Disability Status Scale (EDSS)/functional system (FS) score (sequelae-EDSS/FS) 30 days post relapse; relapses with sequelae defined by the investigator (sequelae-investigator); relapses leading to hospitalization; relapses treated with intravenous corticosteroids; and intense relapses using the definition of Panitch et al. from the EVIDENCE study based on specified increases in EDSS for severe relapses. Adjusted annualized rates for the five severe relapse outcomes were derived using a Poisson model with robust error variance, with treatment, baseline EDSS strata and region as covariates. Compared with placebo, teriflunomide significantly reduced annualized rates of relapses with sequelae-EDSS/FS [14 mg, 36.6 % (p = 0.0021); 7 mg, 31.3 % (p = 0.0104)] and sequelae-investigator [14 mg only, 53.5 % (p = 0.0004)], relapses leading to hospitalization [14 mg only, 33.6 % (p = 0.0155)], relapses requiring intravenous corticosteroids [14 mg, 35.7 % (p = 0.0002); 7 mg, 21.5 % (p = 0.0337)], and intense relapses [14 mg only, 52.5 % (p = 0.0015)]. Patients treated with teriflunomide 14 mg spent significantly fewer nights in hospital for relapse (p = 0.009) and had lower annualized rates of all hospitalizations (p = 0.030). Taken together, the positive effects of teriflunomide on severe relapses indicate that teriflunomide may reduce relapse-related healthcare costs.
authors: Icahn School of Medicine at Mount Sinai, 5 East 98th Street, Box 1138, New York, NY, 10028, USA, aaron.miller@mssm.edu.
authors: Aaron E
authors: AE
authors: Miller
authors: Richard
authors: R
authors: Macdonell
authors: Giancarlo
authors: G
authors: Comi
authors: Mark S
authors: MS
authors: Freedman
authors: Ludwig
authors: L
authors: Kappos
authors: Mathias
authors: M
authors: Mäurer
authors: Tomas P
authors: TP
authors: Olsson
authors: Jerry S
authors: JS
authors: Wolinsky
authors: Sylvie
authors: S
authors: Bozzi
authors: Catherine
authors: C
authors: Dive-Pouletty
authors: Paul W
authors: PW
authors: O'Connor
mesh_terms: D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D003437:Crotonates / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D006885:Hydroxybutyrates; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000503:physiopathology; D009570:Nitriles; D012008:Recurrence; D012720:Severity of Illness Index; D014052:Toluidines / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D003437:Crotonates; D005938:Glucocorticoids; D006885:Hydroxybutyrates; D007155:Immunologic Factors; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide