Comparable efficacy and safety of dimethyl fumarate and teriflunomide treatment in Relapsing-Remitting Multiple Sclerosis: an Italian real-word multicenter experience
E D’Amico, A Zanghì, G Callari, G Borriello, A Gallo, G Graziano, P Valentino, M Buccafusca, S Cottone, G Salemi, P Ragonese, R B Bossio, R Docimo, L M E Grimaldi, C Pozzilli, G Tedeschi, M Zappia, F Patti
Ther Adv Neurol Disord. 2018; 11: 1756286418796404. Published online 2018 Sep 10.
The aim of the study was to evaluate the achievement of ‘no evidence of disease activity’ (NEDA) over a 12-month period in a large multicenter population with relapsing remitting multiple sclerosis (RRMS) treated with delayed-release dimethyl fumarate (DMF) and teriflunomide (TRF) using a propensity-score adjustment.
A time-to-event method was used to determine the percentages of patients with RRMS (pwRRMS) in both groups achieving NEDA 3 (no relapses, no 12-week confirmed disability progression, and no new T2/gadolinium-enhancing brain lesions). We described the safety profile of the investigated drugs.
Of the 587 pwRRMS treated with DMF and the 316 pwRRMS treated with TRF, 468 pwRRMS were successfully paired by propensity score: 234 on DMF and 234 on TRF. The percentages of pwRRMS who achieved NEDA 3 were 80.3% in the DMF group and 77.2% in the TRF group. Serious adverse events occurred in four (1.9%) pwRRMS on DMF and in three (1.3%) pwRRMS on TRF.
DMF and TRF significantly impacted RRMS disease activity in our study. Serious safety concerns were recorded in less than 2% of the studied population.
Last week I looked at a paper comparing the highly active monoclonals, and this week it’s the turn of first line oral therapies: dimethyl fumarate (tecfidera) and teriflunomide (aubagio) in RRMS. This study proves something that I’ve suspected for some time now, which is that aubagio is not half-bad.
At the time of its advent it was probably the least likely to be prescribed of the two; firstly it’s unpopular two weekly liver function blood monitoring over a 6 month period, and then there is its unattractive elimination procedure. But, over the years I’ve come to the realization that tecfidera itself is not straightforward as directed on the packet. The management of lymphopenia on tecfidera, particularly the grade 3 lymphopenias is not an easy task (<500-200m^3 or 0.5-0.2×10^9), and in my practice has directly resulted in a number of lateral swaps to using aubagio instead (some of you reading this are probably nodding your head). I may even go as so far as to say that aubagio is the tortoise in this saga; and we all know how that one ended.
D’Amico and colleagues findings of a head-to-head performance of the two drugs is therefore not surprising. After one year of treatment, NEDA (no evidence of disease activity, based on clinical and MRI parameters) was 80.3% on tecfidera and 77.2% for aubagio. Furthermore, there was no difference in the time to 1st relapse after starting treatment. Among those who discontinued treatment it was 4.3% on tecfidera and 3% on teriflunomide (6 on tecfidera due to lack of efficacy vs. 2 on aubagio – not statistically significant). Those on tecfidera were more likely to have not been on an MS drug before as opposed to aubagio, suggesting that the latter has good efficacy. Adverse events (detailed above) were 26.5% on tecfidera was 12% on teriflunomide (p<0.001), but serious adverse events were similar in both treatments (severe lymphopenia and diarrhoea with tecfidera, and severe vomiting and two cancers with teriflunomide).
Whether the long-term outlook of both drugs is the same is unanswered by this work. Real-life practice is messy, but for the time being looking at short-term objectives is a start.