Relative Efficacy of Teriflunomide 14 mg in Relapsing MS: A Mixed-Treatment Comparison

Background: Disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) aim to reduce he occurrence of relapse and to delay disability progression. Teriflunomide is a new oral once daily DMT in the treatment of RMS.

Objectives: To explore the efficacy of teriflunomide 14mg and approved DMTs in the management of RMS.

Methods: Blinded randomized placebo- and active-controlled trials (RCT) were systematically identified (January 1980 to November 2012) in MEDLINE, EMBASE, and CENTRAL. Key conference proceedings were searched from the last 3 years. MS experts were consulted during protocol development. Trials were included in the Bayesian Mixed Treatment Comparison (MTC) analyses if ≥80% of patients had relapsing remitting MS (RRMS) and recruited patients since 2000, to account for new MS diagnostic, earlier treatment, and evidence of decreased relapse rates over time. MTCs were conducted on rate ratio (RR) for annualized relapse rate (ARR) and hazard ratio (HR) for the proportion of patients with 3 month sustained accumulation of disability (SAD).

Results: 30 RCTs (21,724 patients) were eligible for analyses. MTC [95% Credible Interval] showed that compared with placebo ARRs were significantly lower for teriflunomide, interferons (IFN), and glatiramer acetate (GA): teriflunomide 7mg RR=0.76[0.66-0.89], teriflunomide 14mg RR=0.67[0.57-0.77], IFN β1a 30µg-IM RR=0.78[0.67-0.91], IFNβ1b 250µg RR=0.68[0.52-0.87], GA 20mg RR=0.64[0.53-0.76], and IFNβ1a 44µg-SC RR=0.62[0.51-0.76]. SAD was significantly lower than placebo for teriflunomide 14mg HR=0.71[0.53-0.92], but not for teriflunomide 7mg HR=0.83[0.64-1.08], IFNβ1a 30µg-IM HR=0.91[0.61-1.33], IFNβ1b 250µg HR=1.21[0.68-2.16], GA 20mg HR=0.93[0.59-1.45], and IFNβ1a 44µg-SC HR=0.79[0.51-1.24]. There were no significant differences on ARR or SAD for teriflunomide 14mg vs IFNβ1a 30µg-IM (ARR: RR=0.86[0.69-1.05]; SAD: HR=0.77[0.50-1.24]), IFNβ1b 250µg (ARR: RR=0.98[0.73-1.31]; SAD: HR=0.58[0.3-1.12]), GA 20mg (ARR: RR=1.05[0.83-1.31]; SAD: HR=0.76[0.45-1.3]) or IFNβ1a 44µg-SC (ARR: RR=1.06[0.84-1.35]; SAD: HR=0.9[0.54-1.45]). Results for fingolimod 0.5mg and natalizumab 300mg will be provided.

Conclusions: In this MTC, teriflunomide, IFNs and GA achieved significant improvement on ARR compared with placebo, and teriflunomide 14mg achieved a significant improvement on SAD compared with placebo. Based on indirect comparisons, there were no differences in efficacy between teriflunomide 14 mg, IFNβs or GA.