AUBAGIO is indicated for the treatment of adult patients and paediatric patients aged 10 years and older with relapsing remitting multiple sclerosis (RRMS).1

SmPC

SmPC for AUBAGIO®14mg film-coated tablets:

Legal category: POM

Evidence

AUBAGIO has demonstrated continued efficacy in patients with RRMS over 9 years2–4

AUBAGIO achieved its primary endpoint, reduction in annualised relapse rate, and secondary endpoint, sustained accumulation in disability, in two placebo-controlled trials.2,3

At 9 years in TEMSO, patients taking AUBAGIO were only experiencing ~1 relapse every 6 years (annualised relapse rate with up to 7 years of extension treatment was 0.171 for the AUBAGIO/AUBAGIO group vs. 0.177 for the placebo/AUBAGIO group).4

In a post-hoc analysis of TEMSO, AUBAGIO significantly decreases the rate of cognitive decline vs. placebo (p=0.0435, absolute risk reduction= -0.09 improvement in the PASAT-3 Z-score at week 96 vs. placebo).5

Read about the long-term treatment effect of AUBAGIO on cognitive outcomes in our clinical trial summary.

AUBAGIO has demonstrated relatively stable Extended Disability Status Scale (Disability progression was defined as an increase from baseline of at least 1.0 points in the EDSS score (or at least 0.5 points for patients with a baseline EDSS score >5.5) that persisted for at least 12 weeks) scores of ≤2.5 over 9 years vs. baseline in the TEMSO extension trial.4

AUBAGIO significantly slowed brain volume loss vs. placebo at both year 1 and 2 of the TEMSO study (post-hoc analysis).6

Read more about the impact of brain volume loss on cognition.

Early treatment inititation

Treat newly-diagnosed RRMS patients early to reduce the risk of disability progression vs. delayed initiation7

In a post-hoc analysis, those originally randomised to AUBAGIO had a significantly reduced risk of confirmed disability progression vs. delayed initiation after 48 weeks of placebo (p=0.0495, relative risk reduction= ~26.7% vs. ~30.2% respectively).7

*Patients completing the core TOWER study were eligible to enter an open-label extension, in which those originally randomised to AUBAGIO continued treatment (early treatment) and those previously receiving placebo switched to AUBAGIO (delayed treatment). TOWER ended 48 weeks after the last patient was randomised.

Study Design

TEMSO Overview3

  • 2-year, randomised, double-blind, multicentre, placebo-controlled phase III trial of 1,088 patients with relapsing multiple sclerosis. 721 patients received the licensed dose of AUBAGIO or placebo
  • Primary endpoint = annualised relapse rate
  • Secondary endpoint = sustained accumulation of disability, defined as an increase of ≥1 point on the EDSS from baseline (or ≥0.5 points for patients with a baseline EDSS score >5.5) that persisted for ≥12 weeks
  • The extension phase consists of patients who either continued with the licensed dose of AUBAGIO (n=253) or were switched from placebo to AUBAGIO treatment (n=108)4

TOWER Overview2

  • Randomised, double-blind, multicentre, parallel study of 1,169 patients with relapsing multiple sclerosis. 758 patients received the licensed dose of AUBAGIO or placebo
  • Variable treatment follow-up duration of ≥48 weeks
    • Median duration of exposure: 588 days AUBAGIO, 581 days placebo
  • Primary endpoint = annualised relapse rate
  • Secondary endpoint = sustained accumulation of disability, defined as an increase of ≥1 point on the EDSS from baseline (or ≥0.5 points for patients with a baseline EDSS score >5.5) that persisted for ≥12 weeks
  • The extension phase consists of patients who either continued with the licensed dose of AUBAGIO (n=232) or were switched from placebo to AUBAGIO treatment (n=253)7

Safety

Liver monitoring

Understanding the new Liver Monitoring Requirements for AUBAGIO

For patients without additional risk factors* the liver monitoring requirements for AUBAGIO have been updated and now mean that liver enzymes should be assessed every 4 weeks, instead of every 2 weeks.

    * Consider additional monitoring when AUBAGIO is given in patients with pre-existing liver disorders, given with other potentially hepatotoxic drugs or as indicated by clinical signs and symptoms such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine.

    Liver enzymes should be assessed every two weeks during the first 6 months of treatment, and at least every 8 weeks thereafter for at least 2 years from initiation of treatment.

AUBAGIO has 12 years of generally consistent safety data from clinical trials1,9

  • No new or unexpected adverse events (AEs) observed during clinical trials with >2,200 patients, over 12 years9
  • The most common AEs across clinical trials consistently included headache, diarrhoea, nausea, hair thinning and increased alanine transaminase (ALT). These AEs were mild-to-moderate, transient and rarely led to discontinuation1

Common AEs leading to treatment discontinuation9

Pooled safety data from 4 placebo-controlled AUBAGIO trials and extension studies:

In the AUBAGIO group:

  • Diarrhoea and nausea were generally mild-to-moderate in severity9
  • Most cases of hair thinning were mild-to-moderate, occurred during the first 6 months of treatment and resolved while treatment was continued9
  • No confirmed cases of progressive multifocal leukoencephalopathy (PML)9
  • No increase in serious infections was observed with teriflunomide 14mg (2.7%) as compared to placebo (2.2%). Serious opportunistic infections occurred in 0.2% of each group.9

Mechanism of Action

Understanding the AUBAGIO mechanism of action

Although the mechanism by which AUBAGIO exerts its therapeutic effect in MS is not completely understood, it is thought to selectively and reversibly reduce the number of activated lymphocytes in the central nervous system. This results in lower numbers of both B-cells and T-cells, two types of white blood cell involved in the nervous system damage associated with MS.1

    1. AUBAGIO (teriflunomide) Summary of Product Characteristics (last date of revision: January 2022)
    2. Confavreux C, O'Connor P, Comi G, et al. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Neurology 2014;13:247–256.
    3. O'Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365:1293–1303.
    4. O’Connor P, Comi G, Freedman MS, et al. Long-term safety and efficacy of teriflunomide. Nine-year follow-up of the randomized TEMSO study. Neurology. 2016;86(10):920–930.
    5. Sprenger T, Sormani MP, Wolinsky JS, et al. Evaluation of the Long-term Treatment Effect of Teriflunomide on Cognitive Outcomes and Association with Brain Volume Change: Data from TEMSO and its Extension Study. Poster presented at ECTRIMS/ACTRIMS 2017. P685.
    6. Radue E-W, Sprenger T, Gaetano L, et al. Teriflunomide Slows Brain Volume Loss in Relapsing MS: A SIENA Analysis of the TEMSO MRI Dataset. Poster presented at AAN 2016. P3-089.
    7. O’Connor PW, Wolinsky JS, Thangavelu K, et al. Reduced Risk of Disability Progression in Patients With MS Treated With Early vs Delayed Teriflunomide 14 mg. Poster presented at ECTRIMS 2015. P555.
    8. Kappos L, Freedman MS, Comi G, et al. Teriflunomide efficacy on annualized relapse rate and Extended Disability Status Scores:2.5-year follow-up in the TOWER extension study in patients with relapsing multiple sclerosis. Poster presented at ECTRIMS 2015. P1099.
    9. Comi G, Freedman MS, Kappos L, et al. Pooled safety and tolerability data from four placebo-controlled teriflunomide studies and extensions. Mult Scler Relat Discard. 2016;5:97–104.

MAT-XU-2200676 (v1.0)
Date of preparation: May 2022