Saturday, 7 November 2015

Flushing with DMF

Phillips JT, Selmaj K, Gold R, Fox RJ, Havrdova E, Giovannoni G, Abourjaily H, Pace A, Novas M, Hotermans C, Viglietta V, Meltzer L. Clinical Significance of Gastrointestinal and Flushing Events in Patients with Multiple SclerosisTreated with Delayed-Release Dimethyl Fumarate. Int J MS Care. 2015 Sep-Oct;17(5):236-43.

BACKGROUND:In the phase 3 DEFINE and CONFIRM trials, flushing and gastrointestinal (GI) events were associated with delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) treatment in people with relapsing-remitting multiple sclerosis (MS). To investigate these events, a post hoc analysis of integrated data from these trials was conducted, focusing on the initial treatment period (months 0-3) with the recommended DMF dosage (240 mg twice daily).
METHODS:Eligibility criteria included age 18 to 55 years, relapsing-remitting MS diagnosis, and Expanded Disability Status Scale score 0 to 5.0. Patients were randomized and received treatment with placebo (n = 771) or DMF (n = 769) for up to 2 years. Adverse events were recorded at scheduled clinic visits every 4 weeks.
RESULTS:The incidence of GI and flushing events was highest in the first month of treatment. In months 0 to 3, the incidence of GI events was 17% in the placebo group and 27% in the DMF group and the incidence of flushing and related symptoms was 5% in the placebo group and 37% in the DMF group. Most GI and flushing events were of mild or moderate severity and resolved during the study. The events were temporally associated with the use of diverse symptomatic therapies (efficacy not assessed) and infrequently led to DMF discontinuation.
CONCLUSIONS:This integrated analysis indicates that in a clinical trial setting, GI and flushing events associated with DMF treatment are generally transient and mild or moderate in severity and uncommonly lead to treatment discontinuation.

Flushing is one of the side effects of DMF, gut problems is another. This paper by ProfG says it is usually mild and often goes and this is not a reason for discontinuing it use, so what is? ProfG may have more to add. 

CoI ProfG is coauthor on this. Conflicts multiple

8 comments:

  1. This is a post-hoc analysis so any information gathered has to be ignored. The trial has to be re-done and all endpoints identified up-front before the trial is executed according to Team G's reasoning.

    Please follow your own procedural rants that you make for other people's work to include your own work.

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    1. Not my work and I am afraid it is you who are ranting..you are not going to do aother trial to look at a side effect as a primary endpoint

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  2. I was on Tecfidera for two years. I "flushed" two or three times a week for the whole time. Bright red face and neck, ears hurt like sunburn. Diet, aspirin, Benadryl. Nothing worked. I stuck with it because it seemed to be working for me. My neurologist took me off it as I started to have repeated infections, bronchitis, oral thrush.

    So having "done" rebif, Tysabri, Gilenya, Tecfidera, I'm now on Aubagio...with constant abdominal pain for 8 of the 10 weeks, and hair thinning rapidly. I seem to be a side effect magnet. It's a good job some of the side effects are visible, otherwise I'd seem like the biggest wuss out.

    I have a combination of relapsing and progressive forms - and because of this, Prof G's theory that everyone has a progressive bit really resonates with me. As you can probably tell, I totally support taking DMDs. Through my volunteer work I speak to lots of people with MS and I'm often faced with convincing them to try or stay on DMDs. It's not easy when I'm having side effects myself, but being in a wheelchair since 6 months in and having a host of other crappy symptoms, I consider the side effects the paper cuts of MS. Painful, annoying, but nowhere near as bad as my MS.

    Roll on ocrelizumab!

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  3. Why don't "Anonymous" posters register to have a username? Then at least they can "own" their opinions instead of behaving like cowards. This is often a good moderator of behaviour on Facebook-mediated forums.

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    1. It wouldn't make much difference I could register to have a few different usernames. I am no coward.

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  4. I experimented on myself with Tecfidera and flushing. One can hypothesized that flushing is a dose dependent effect of the Tecfidera byproduct (it converts to mono-ethyl within the blood, no?). My flushings, if they occur, are occurring once and from 1 to 4 hours after the intake (tends to be quicker these days). I monitored the hours at which I am taking the Tec. I noticed that the absolute time does not matter. What matters is the time between intakes. So now I try to space my intakes as much as possible (12 hours), it kind of work nicely. If I need to reduce the interval I then use aspirin 30 min before the intake.

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  5. I find the flushing is completely unpredictable. It barely happened at all when I first started but 8 months in, I get a more obvious effect maybe every couple of weeks with a bit of a rash and itching on some other days. I hadn't thought of the 12 hour spacing as an answer but it happens often around 11-midday when I take it at approx 7am. Today was a proper corker which came out of the blue.

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  6. In fact, I agree with you Jim and my test was just an hypothesis. It seems to happen randomly. Extending the time between intakes only partly solves the problem (and I am not sure of it). But there is FOR SURE a rational reason behind flushing. We know that eating or not while the intake does not change a thing (but it might for the gastro-intestinal reactions) the absolute time also do not do something (apart that from 2 to 5 hours later the flushing happens in one episode of approx 10 to 30 mins or not). Even if eating does not influence it. Does the sugar blood level can play a role? (I am buying candies to test this idea). Also aspirin diminished flushing (only tested it a few times). How come?

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