Thursday, 10 July 2014

Dimethyl fumarate in early MS

Dimethyl fumarate works best when used first-line. #MSBlog #MSResearch

"The study below shows that dimethyl fumarate, or DMF, is more effective when used in MSers with early disease (<12 months since diagnosed) and who have not been treated with another DMT. The relapse reduction relative to placebo was 56-60%. The corollary of this that the subset left behind do worse; i.e.  those who have a longer disease duration and who have failed a prior disease modifying therapy in the past. These results clearly position DMF as the most effective of the so called first-line DMTs and explains why the drug is doing so well were it has been launched."

"We still don't have it available in England; we need to wait for NICE and NHS England to green-light it for use. I note that it is already available in Scotland."



Epub: Gold et al. Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing-remitting multiple sclerosis (RRMS).Mult Scler. 2014 Jul 2. pii: 1352458514537013. 

BACKGROUND: Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in the Phase 3 DEFINE and CONFIRM trials.

OBJECTIVE: To evaluate delayed-release DMF in newly diagnosed relapsing-remitting MSers, in a post-hoc analysis of integrated data from DEFINE and CONFIRM.

METHODS: MSers included in the analysis were diagnosed with RRMS within 1 year prior to study entry and naive to MS disease-modifying therapy.

RESULTS: The newly diagnosed population comprised 678 MSers treated with placebo (n = 223) or delayed-release DMF 240 mg BID (n = 221) or TID (n = 234). At 2 years, delayed-release DMF BID and TID reduced the annualized relapse rate by 56% and 60% (both p < 0.0001), risk of relapse by 54% and 57% (both p < 0.0001), and risk of 12-week confirmed disability progression by 71% (p < 0.0001) and 47% (p = 0.0085) versus placebo. In a subset of MSers (MRI cohort), delayed-release DMF BID and TID reduced the mean number of new or enlarging T2-hyperintense lesions by 80% and 81%, gadolinium-enhancing lesion activity by 92% and 92%, and mean number of new non-enhancing T1-hypointense lesions by 68% and 70% (all p < 0.0001 versus placebo). Flushing and gastrointestinal events were associated with delayed-release DMF.

CONCLUSION: Delayed-release DMF improved clinical and neuroradiological outcomes relative to placebo in newly diagnosed RRMSers.

CoI: multiple, I am a co-author on the paper and was a member of the DEFINE steering committee

13 comments:

  1. Prof G - what about the data for MSers who have had the disease for a couple of years? I will be starting Tecfidera within weeks and would like to know the relapse rate and progression rate.
    Thank you.

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    1. Re: "Prof G - what about the data for MSers who have had the disease for a couple of years?"

      The drug works in all subgroups; it simply works best when use early and naive MSers. The important thing is to be monitored on treatment with the aim of treating-2-target of NEDA.

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  2. Prof G how does DMF compare to fingolimod? Are they equivalent?

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    1. Re: "Prof G how does DMF compare to fingolimod? Are they equivalent?"

      No they are not. DMF has a 1st-line license and fingolimod has a 2nd-line license. They are different in almost every aspect; I will need to do post on comparing the attributes of the two drugs.

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  3. should I come off rebif44 and go on tecfidera? is there that much of a difference? is it safer after reading recently rebif is the riskiest of all the MS drugs. didn't understand why. surely tysabri is more risky than rebif?!

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  4. Prof G - do you believe that DMF has greater efficacy than fingolimod?

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    1. Re: "Prof G - do you believe that DMF has greater efficacy than fingolimod?"

      No I don't; on average fingolimod appears to have better efficacy and it has a consistent impact on brain atrophy or end-organ damage. I have been involved in a health economic modelling project that controls for baseline variables; in this model fingolimod has better efficacy. But it is horses for courses; someone who responds to DMF may not response to fingolimod and vice versa. It is all about individualized care. In the UK DMF and fingolimod are not head-2-head. Fingolimod is a second-line therapy so the choice is really between fingolimod and natalizumab, that is if you have rapidly evolving severe MS. If you have simply have highly-active MS fingolimod sits alone, unless you want to cycle through other first-line therapies.

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  5. This is positive news (assuming NICE play nice). I have not yet had DMTs and am 9 years post diagnosis (chose not to b/c of relatively mild disease course, desire to have a family and was unimpressed with treatment options available). However, I have finished having children and am mindful that I need to get onto a DMT before my luck runs out. I think rebif et al. have had their day and aubagio doesn't seem much better in terms of efficacy. Could you comment on lemtrada vs tecfidera as first line treatments? I'm particularly interested in impact on progression. Thank you for all you do in updating this blog.

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  6. I so hope that NICE and the NHS get this right! Think of the efect on people's life's and the money saved in the end by using DMF as a first line drug.

    Prof G, would current first line patients on the injectibles be bable to switch if it is approved?

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  7. Dear Prof G. I found out today BG12 has been approved for England. Should be available for patients to begin tablets in Sept or Oct. Is this correct?

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    1. Re: "Dear Prof G. I found out today BG12 has been approved for England."

      We are still waiting for final NICE approval; it should be any day now. It then takes another 90 days for NHS England to make it available. So yes, it may be available late October.

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  8. Dear Prof G, thanks for your excellent blog. Please can you offer any brief comparison of DMF and Alemtuzumab? I am due to be screened for campath trial soon, which looks good, but how would it compare to DMF? (Diagnosed 6 years ago, stuck with fatigue for last 9 months). Thank you.

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  9. Ps .. Sorry, meant CamThy trial, not campath

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