Tuesday, 18 September 2018

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

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 0.5-0.2x10^9), 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.

Monday, 17 September 2018

MSexism take two: The Mystery of the Missing Authors

Recently this blog featured an eye-opening article written by our guest blogger Rachel, about gender inequality in the world of multiple sclerosis, from a patient’s point of view. It’s well worth a read. She also outlines just how few women feature on academic panels. And this investigation has now been taken further, with an analysis of authors on academic papers.


Rachel Horne interviews ProfG to ascertain why the Department of Health and NICE have said no to ocrelizumab for treating people with PPMS. 

Sunday, 16 September 2018

Socks make Myelin

More on experimental myelination

Benign MS. How common is it?

Benign MS is MS is something that I guess you hope for, if you get an MS diagnosis. Likewise if you are a neurologist, benign MS may mean that you don't  commit to treatment.

But how common is this in the UK?

Saturday, 15 September 2018

Fingo Coming of Age

Fingolimod is better than interferon beta in adults so what happens in children.

Yep you got it.

Diagnosis MS.Saving 3 years

The McDonald criteria are diagnostic criteria for multiple sclerosis (MS).They have undergone revisions in 2005, 2010 and 2017

Has this made a difference?

Friday, 14 September 2018

Wakey-wakey people. Read this and it all becomes clear. MS gets simpler

If you are a regular reader of the blog, you may think this work is old hat. This is because you have been watching these ideas evolve over the past year.

Hopefully for others who have not been following us, this could be a day of revelation and the Penny may finally Drop (The penny dropped is a casual idiom outside the United States used to mean a person has belatedly put two and two together or understood something).

If you are a nurse or a neurologist or Junior Doctor, and only read one paper (Click on link below for full paper) a year give this one a read. It may help you conceptualise MS and its treatment better as "MS therapy just got easier".  

Send this post to your friends. Ask them for holes in the arguments.

If you are a person with MS, give it a read and ask questions if you don't understand. It may make your descisions of treatment easier.

However, for all you young-researchers (meaning mentally young even if old in body) out there...the old-ones are probably a lost cause as they are unlikely to want change their ways and will simply ignore this:-(.....Give this a read, spot the holes and the inconsistencies, but maybe look at your research in a different way. Try and disprove the ideas. 

Depletion of CD20 B cells increases active B cells...killing our idea...Maybe not.

To continue on with today’s subject

Are you interested in what happens in mice following CD20 depletion?

Read the paper below and I think it says we have got the "B memory cell idea" all wrong.
However, read the data (and the literatureL) and perhaps we can make some other conclusions. 

Suggesting mouse is not human.....in more ways than one

Interested?

Thursday, 13 September 2018

Will we ever learn? Just need to Read and Assimilate. Is it too much to Ask?

Results of a mycopheylate study in PPMS

Looks like mycophenolate is down the tube as far as progressive MS goes?

I wonder are Neuros doing their upmost to ensure that we don't deliver treatment options