Thursday, 19 February 2015

DMF does not slow down brain atrophy despite inhibiting new lesion formation

Will brain atrophy be the big differentiator amongst the newer DMTs? #MSBlog #MSResearch

"The paper below summarises the effect of DMF on MRI activity in MS. It is clear DMF is very effective at suppressing inflammatory activity in the form of suppressing new MRI lesion formation. Unfortunately, DMF did not have an effect on brain atrophy in year 1 and year 2, although there was a trend. I wonder if this would have been significant if the whole population had been included in the MRI study. As the emphasis in treatment seems to be moving toward preventing end-organ damage this could be construed as a negative for DMF? However, as we start to develop techniques for measuring and using  brain atrophy in individual MSers this may not be a problem. There will be a proportion of MSers treated with DMF who are NEDA-4 (no inflammatory activity and normalised brain volume loss). I would be interested to know how big this populations is. With fingolimod, DMF's main competitor amongst the orals, less than 20% of treated subjects are NEDA-4. Clearly as our treatment targets change in MS simply having an impact on inflammatory activity (MRI lesions and relapses) will not be good enough."

Epub: Miller et al. Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study. Neurology. 2015 Feb. pii: 10.1212/WNL.0000000000001360.

OBJECTIVE: To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study.

METHODS: CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 MSers with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 MSers (MRI cohort).

RESULTS: DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance.
CONCLUSIONS: The robust effects on MRI active lesion counts and total lesion volume in MSers with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS.
CLASSIFICATION OF EVIDENCE: This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment.

CoI: multiple

1 comment:

  1. Clearly as our treatment targets change in MS simply having an impact on inflammatory activity (MRI lesions and relapses) will not be good enough.". If targeting inflammation and the formation of lesions isn't enough, what else should be the target of therapies and when will they become available.

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