Real-world experience on first line oral therapies DMF and teriflunomide

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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.

Background:

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.

Methods:

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.

Results:

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.

Conclusions:

DMF and TRF significantly impacted RRMS disease activity in our study. Serious safety concerns were recorded in less than 2% of the studied population.

Figure: Frequency of adverse events on tecfidera (DMF) and aubagio (teriflunomide)

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.

About the author

Neuro Doc Gnanapavan

8 comments

  • Isn't DMF the industrial fungicide which caused terrible skin reactions when it was used in sachets in sofas imported from China?

    • Yes it is, which is why you can get it so cheaply. I have a 25kg bag of dimethyl fumarate I bought from a Chinese company at home which cost me 625 USD, including freight.I have managed my p and psa with the 98% crystals since December 2012 with excellent results. I currently use about 2 USD of the chemical per year. Comparatively, one 120mg Fumaderm tablet would cost as much and I would need 41 tablets every three weeks. I am currently testing the idea that the drop in neutrophils and lymphocytes can be reversed substantially with iron supplementation.

    • If you do not buy chemiclas designed for human use, you may get all sorts of unwelcome contamination with potential undesirable consequences.

      Not sure of the logic as to why neutrophils and lymphocytes populate due to iron.

    • Just very concerned, Anon, that anyone would put any industrial grade chemical into their body. In my humble opinion, you should stop doing this, because you may well be doing more harm than good. This information gives an idea of the complexity of processes involved in purifying DMF to pharmaceutical grade and the potential nastiness (geno toxicity) of possible impurities:

      https://patents.google.com/patent/WO2017013672A1/en

  • I appreciate your concern and thank you for the link. I have only noted benefit from the drug. Even with industrial grade, the harmful impurities are in minute quantities. At least you have provided me with a way to make my dimethyl fumarate safer, so thanks again. As to why iron supplementation has had an effect on neutrophils and lymphocytes I can only speculate, but that is what I observed.

  • I have had regular blood tests through a pathology lab and authorised by my GP. There has only been a positive outcome for my health. I do have the equipment needed to purify my dimethyl fumarate and may try this. Dimethyl maleate is a strong irritant, but I would be taking a maximum of less than 20mg, probably less than 10mg, per dose. Given an oral ld50 value of 1410mg/kg for rats and dermal ld50 value of 610mg/kg for rabbits, I don't see reason for alarm. But thank you for your concern.

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