Are you a super-responder?

A

Barts-MS rose-tinted-odometer: ★★

For every DMT there are patients who respond and there are those who don’t respond. Trying to predict who will be a responder and non-responder is not possible upfront. This is why we talk in averages, i.e. what happens to populations of patients and extrapolate backwards to the individual. If only we have individualised or personalised prediction tools. 

The study below shows a cohort of glatiramer acetate super-responders who are doing as well a group of patients on fingolimod when it comes to the end-organ, i.e. losing brain volume loss. Could you imagine a world when we didn’t have to gamble with time and we could select the treatment that will do the job we want it to in terms of protecting your brain for when you get older? 

In my talk at the MSVirtual2020 meeting this year I try and communicate these concepts using an actuarial approach. Is it understandable? As it is your brain what have you done? 

<iframe width="560" height="315" src="https://www.youtube.com/embed/owhRLn3XwCs" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe>

Honce et al. Brain Atrophy Rates for Stable Multiple Sclerosis Patients on Long-Term Fingolimod versus Glatiramer Acetate. Frontiers in Neurology 2020 Sep 23;11:1045. 

Background: Clinically stable multiple sclerosis (MS) patients on long-term therapy often have negligible acute inflammation on MRI. Brain atrophy may provide insight into subclinical disease progression in such populations. Objective: This study aims to compare brain atrophy for age- and gender-matched MS patients treated for >2 years with fingolimod (FTY) or glatiramer acetate (GA), examining brain volume, cognition, and patient-reported outcomes (PROs). 

Methods: Stable relapsing-MS patients, age 18-60, on FTY or GA for >2 years were followed up for 2 years. MRI brain and lesion volumes, cognitive measures, and PROs were collected at baseline and annually. 

Results: Forty-four FTY and forty-three GA patients completed baseline and year 2 visits. No differences in age, gender, or education were observed. Median EDSS was 2.0GA and 2.5FTY (p = 0.22). Treatment duration was longer for GA, 6.50GA vs. 3.73FTY years (p < 0.001). Baseline geometric mean T2LV were different, GA = 1,009.29 cm3 vs. FTY = 2,404.67 cm3 (p = 0.0071). Baseline brain volumes were similar, GA = 1,508 cm3 vs. FTY = 1,489 cm3 (p = 0.2381). Annualized atrophy rates, adjusted for baseline and at mean baseline value, were GA = -0.2775% vs. FTY = -0.2967% (p = 0.7979). No differences in cognitive measures or PROs were observed. 

Conclusions: Stable MS patients on long-term treatment with FTY and GA have similar brain volume loss rates. Differences in baseline disease severity may suggest patients with more aggressive disease treated with FTY may achieve similar brain volume loss rates as patients with milder baseline disease on GA.

CoI: multiple

Twitter: @gavinGiovannoni           Medium: @gavin_24211

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

8 comments

  • Can we assume that someone who responds well to a DMT will have good response if they switch to another DMT whose mode of action has similarities (e.g. fingolimod and natalizumab)?

    • Not necessarily; response to one DMT may necessarily predict response to another DMT. There a potentially a large number of personal factors that can impact on the mode of action of DMTs, for example neutralising anti-drug antibodies or variants in the genome that makes someone less responsible to the DMT.

  • In an earlier post you mentioned that a group in the USA has received funding for a clinical trial using HAART. Where can we access this trial on clinical trial.gov or what are the names of the researchers ?

  • A major concern for me with dmt’s is the level of monitoring and derisking that my hospital would employ. How much of it is down to individual artistic flair, is there a minimum requirement and how close is that to what you describe in the video?

  • How do we differentiate between super-responders to first line dmts from people with non-aggressive or mild disease? E.g. I had two relapses in more than 10 years without being on DMTs, I suspect that taking a first line dmt would have changed little in terms of progression (maybe I would have avoided the third relapse, who knows). But I would have been probably identified as super responder.
    How many patients on GA are actually super responders with respect to all patients treated with GA?

    Why someone with ADA should be classified as non responder to a therapy? It seems a dangerous definition to me. If one does not respond to rituximab because of ADA it is possible that will respond to Ofatumumab or ocrelizumab or others anti CD20.

    • How standard in UK is measuring annualized brain volume loss? My MRI reports at large US hospital do not quantify, just note area and that its not equivalent to age. My neuro says measurement method is not standardized. What exactly is a measurement of “geometric mean T2LV” and why is it not universally used?

      • It is not routinely in clinical practice. There are still problems with too much variability in individual patients for the measurement to be used in routine clinical practice.

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