Methods: A total of 147 patients who completed the core study entered an open-label extension. Teriflunomide patients continued their assigned dose, and placebo patients were re-allocated to teriflunomide, 7 mg/day or 14 mg/day. An interim analysis was performed at a cut-off on January 8 2010.
Results: The mean and median duration of study treatment, including both the core and extension phase, from baseline to the interim cut-off, was 5.6 years (standard deviation: 2.7 years) and 7.1 years (range: 0.05–8.5 years), respectively. Of 147 patients, 62 (42.2%) discontinued (19% due to treatment-emergent adverse events (TEAEs)). The most common TEAEs were mild infections, fatigue, sensory disturbances and diarrhoea. No serious opportunistic infections occurred, with no discontinuations due to infection. Asymptomatic alanine aminotransferase increases (≤3× upper limit of normal (ULN)) were common (7 mg, 64.2%; 14 mg, 62.1%); increases greater thanv ;3×ULN were similar across groups (7 mg, 12.3%; 14 mg, 12.1%). Mild decreases in neutrophil counts occurred; none led to discontinuation. The incidence of malignancies was comparable to that of the general population, and cases were not reminiscent of those observed in immunocompromised patients.
Annualised relapse rates remained low, minimal disability progression was observed, with a dose-dependent benefit with teriflunomide 14 mg for several MRI parameters.
Conclusion: Teriflunomide had a favourable safety profile for up to 8.5 years.
Although Teriflunomide may appear to be relatively safe, the issue of level of efficacy may determine how well this orally-active compound is recieved. So whilst teriflunomide is effective it is not that effective. In the initial phase II trial , from which the followi-up is derived there was no significant inhibition of the relapse rate but did affect some other outcomes. However this drug has been studied in a phase III trial involving over 1000 people and oral Teriflunomide (Trade name Aubagio-Who comes up with these names?) inhibits the relapse rate only by about 30% and is no better than beta interferon when compared in a head to head fashion in recent studies involving over 300 hundered MSers. Whilst it has the advantage of being an oral drug verses interferons, it will be interesting to see how it will do compared to Gilenya and BG-12 that are much more active. However, this will depend on safety profiles and we have yet to see if the recent deaths of people taking Gilenya are going to impact on the use of the drug.