Sunday, 22 November 2015

NEDA-4 and fingo

Kappos L, De Stefano N, Freedman MS, Cree BA, Radue EW, Sprenger T, Sormani MP, Smith T, Häring DA, Piani Meier D, Tomic D. Inclusion of brain volume loss in a revised measure of 'no evidence of disease activity' (NEDA-4) in relapsing-remitting multiple sclerosis. Mult Scler. 2015 pii: 1352458515616701. [Epub ahead of print]

BACKGROUND:'No evidence of disease activity' (NEDA), defined as absence of magnetic resonance imaging activity (T2 and/or gadolinium-enhanced T1 lesions), relapses and disability progression ('NEDA-3'), is used as a comprehensive measure of treatment response in relapsingmultiple sclerosis (RMS), but is weighted towards inflammatory activity. Accelerated brain volume loss (BVL) occurs in RMS and is an objective measure of disease worsening and progression.
OBJECTIVE: To assess the contribution of individual components of NEDA-3 and the impact of adding BVL to NEDA-3 ('NEDA-4') METHODS: We analysed data pooled from two placebo-controlled phase 3 fingolimod trials in RMS and assessed NEDA-4 using different annual BVL mean rate thresholds (0.2%-1.2%).
RESULTS: At 2 years, 31.0% (217/700) of patients receiving fingolimod 0.5 mg achieved NEDA-3 versus 9.9% (71/715) on placebo (odds ratio (OR) 4.07; p < 0.0001). Adding BVL (threshold of 0.4%), the respective proportions of patients achieving NEDA-4 were 19.7% (139/706) and 5.3% (38/721; OR 4.41; p < 0.0001). NEDA-4 status favoured fingolimod across all BVL thresholds tested (OR 4.01-4.41; p < 0.0001).
CONCLUSION: NEDA-4 has the potential to capture the impact of therapies on both inflammation and neurodegeneration, and deserves further evaluation across different compounds and in long-term studies.

We have been saying for some time that we should be aiming for NEDA and brain volume loss is an extra player in this aim and whilst you do not want to be loosing brain volume this data shows that volume loss and disease activity was occuring in 80% of people treated with fingolimod. This says we can do better. Brain volume has its problems because it is liable to shrink if the drug is good as it gets rid of swelling and inflammation and therefore you have to be on treatment for a year before you baseline.

4 comments:

  1. Gilenya is not really highly effective.

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  2. So, this analysis looked at brain volume loss from start of treatment to 96/104 weeks? Or did they adjust the baseline to one year?

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  3. How did they measure BVL?

    Tony

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