Don't write off a write-off: a reassessment of Teriflunomide

Mult Scler. 2017 Mar 1:1352458517695468. doi: 10.1177/1352458517695468. [Epub ahead of print]

The efficacy of teriflunomide in patients who received prior disease-modifying treatments: Subgroup analyses of the teriflunomide phase 3 TEMSO and TOWER studies.

Freedman MS, Wolinsky JS, Comi G, Kappos L, Olsson TP, Miller AE, Thangavelu K, Benamor M, Truffinet P, O'Connor PW; TEMSO and TOWER Study Groups.


Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (MS). The objective of this post hoc analysis of the phase 3, pooled TEMSO (NCT00134563) and TOWER (NCT00751881) dataset is to evaluate the effect of teriflunomide treatment on annualised relapse rate and disability worsening across patient subgroups defined according to prior disease-modifying therapy exposure. This analysis provides further supportive evidence for a consistent effect of teriflunomide across a broad range of patients with relapsing MS, including patients who have used and discontinued other disease-modifying therapies.

Figure:   (a) ARR by prior treatment; (b) Disability worsening by prior treatment. Teriflunomide shows a trend towards improvement, including those who have received prior DMT, but the effect is not statistically significant.

Teriflunomide (Aubagio), a first-line oral MS therapy has an Achilles heel, and that is its side-effects; particularly irksome are liver problems (requiring frequent blood tests), diarrhoea, and hair thinning/loss. They occur often enough that they overshadow it's selling point as an alternative to dimethyl fumerate (Tecfidera), which has the PML risk. Teriflunomide blocks rapidly dividing cells and this includes activated T cells by inhibiting pyrimidine (building blocks of genes) synthesis.

Here the TEMSO and TOWER study groups (these were the two of the clinical trials performed prior to licensing of teriflunomide) reanalyse the pooled data by dividing those into ones who received disease-modifying therapies (DMT) before and those who had not, i.e. DMT naïve. Most included in the analysis were DMT naïve with ~30% having used one or more DMT (so this is a 2:1 analysis so to speak). The most frequently used other DMT was interferon beta (IFNβ). Overall, there is a numerical reduction in relapse rate and risk of disability progression with teriflunomide 14mg compared to all the subgroups analysed (see Figure above). The differences, however, are not significant and should be born in mind. The authors point out that this may be due to the small size of the groups analysed but I feel the numbers were sufficient even if it's a post-hoc analysis. Interestingly, they also noted that those who had prior DMTs also had greater MRI activity with more enhancing lesions and relapse rates compared to the treatment-naïve group, which is concerning (those who participated had to be off their DMTs for 3-6 months prior to inclusion) and implies rebound after coming off treatment. The latter is a practical lesson to learn for clinicians swapping treatments.

Overall, despite the less than impressive data, teriflunomide in my books will remain a first-line contender by simply not following the paths trodden by others. It does not pretend to achieve the excellence of the second generation DMTs, nor does it imitate those who are most excellent, and as such, will remain a prudent man's/woman's choice.

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