Who would have guessed but DMDs improve survival

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The number of times I’ve been asked whether DMTs have any impact in survival is countless. For those of you who are aware of the effect of MS on survival these study findings will be of great interest to you. It will also hopefully gets people who are still unsure about starting treatment off the fence.

In a large review of administrative health databases in Canada amounting to 35,894 MS cases from 1996-2017 exposure to MS disease modifying drugs (DMDs) was found to lower the risk of mortality by 26% (see Figure below). Whilst, a 33% lowering of mortality was seen with the second-generation DMDs. The other subgroups studied, however, were not large enough to calculate similar risk associations and found to be not significant. In the case of DMF there were a few deaths which lead to the wide confidence intervals that you see.

Figure: DMD Use for Multiple Sclerosis and Hazard of All-Cause Mortality

When they studied the larger group of individuals on first-line DMDs, dividing them according to whether they started DMD ‘very early’, ‘early’ vs ‘late’, staring treatment very early was better (see Figure below).

“For example, very early initiation (i.e., first exposure at year 2 postindex date) was associated with a 62%–63% lower hazard of mortality at 2 years of follow-up (i.e., close to DMD initiation), decreasing to 44%–45% at 5 years of follow-up (i.e., 3 years after first exposure), and 24%–28% at 10 years of follow-up (i.e., 8 years after first exposure), the latter of which reached significance for glatiramer acetate only. At 15 years of follow-up, this diminished even further, to a 9%–13% lower hazard of mortality. Although ‘late’ initiation (i.e., first exposure at year 10 postindex date) of beta-interferon and glatiramer acetate was also associated with a lower hazard, findings did not reach significance”.

Figure: The Association Between Exposure to a First-Generation DMD and All-Cause Mortality by Timing of Drug Initiation (Very Early, Early, or Late) and Duration of Follow-Up

After 15 years, however, this trend was no longer significant and probably reflects the diminished effect of anti-inflammatory agent on progressive disease with ageing for the first line agents.

About the author

Neuro Doc Gnanapavan

14 comments

  • I read these data as DMD has no real impact on mortality rate, anything about mortality rate with less than 10 years follow up doesnt describe MS as a chronic disease well. I guess qos is improved before that point.

    • Every treatment including cancer treatments have a finite action, and 10 years is generally the accepted cut off. Pretty much what this paper is showing is that you’re slowing down the rate at which you reach these defined milestones with a proportion of individuals reaching maybe one milestone but not the subsequent ones that has a greater impact on overall mortality.

      • Sure, but I think you are comparing apples and oranges – 2 diseases one with an early age onset and one with decades later average onset. 10 years for MS doesnt make sense.

  • “For example, very early initiation (i.e., first exposure at year 2 postindex date) was associated with a 62%–63% lower hazard of mortality at 2 years of follow-up (i.e., close to DMD initiation), decreasing to 44%–45% at 5 years of follow-up (i.e., 3 years after first exposure), and 24%–28% at 10 years of follow-up (i.e., 8 years after first exposure), the latter of which reached significance for glatiramer acetate only.“

    NDG, would you really expect that some MSers would die (of MS related causes) just 2, 5, 10 years of diagnosis / starting treatment? The various MS charity websites always claim that MSers have a near normal lifespan or a “slightly” (c.8 years) reduced lifespan.

    What is really of interest to MSers is to have some stats in the form of average life expectancy stats eg the average life expectancy for a woman in the U.K. is 84 and for a man is 81 ie what is the average life expectancy for MSers, and for MSers who were on a DMT.

    From reading various papers, it appears to me that an MSer lives, on average, for 30-40 years after diagnosis. Not great if you get diagnosed in your 20s. I don’t hear of many MSers who have had MS for 50-60 years ie MSers in their 80s and 90s. There’s also a big issue about “survival”. EDSS 8 and 9 are really about existing rather than living.

    • There are quite a few factors involved in this aside from treatment. For example, age at diagnosis (older age has worse prognosis), race. But, in general the main contributing factor is probably other all cause mortality i.e. smoking, chest infections, UTIs. This then leads to a 10y survival of 90%.

      And yes, mortality is not the same as quality of survival and beyond an EDSS 8.0 this is very very poor.

  • This is very ghoulish anxiety producing for someone like me. I was Dx twenty years ago, and became bed bound five years ago—basically EDSS 8 / 8.5. I constantly develop UTIs and it have to be cathetered twice a day every day to make sure my bladder is completely empty so that I don’t develop more UTIs and have to be hospitalized once again. The UTIs have caused so much further damage that I only have the use of my left hand where all other limbs are useless. All of my days are composed of just keeping on top of all the things I need to do to stay stable, and stay on the people around me I need to help me, since their default tendency is to slack off. Really… reading information like this… what am I to gather that will help me? What kind of hope does this give me? I am still fairly young and have spent a good portion of my best years fighting to staunch progression of my disease. I mean… what the heck do I have to look forward to?

    • Christopher,
      Nothing is the truthful answer. MS is a chronic progressive disease so always gets worse. The EDSS shows you where you are and where you are heading. The damage is irreversible. That’s why I’ve always been a cynic on this blog – despite all the claims of research progress the destination for MSers is the same, although DMTs slow the progression and push it to the right. If MS research had really moved on in the last 25 years, we wouldn’t have cases like yours or the two women with MS in their mid 30s living in care homes who my GP looks after. MS research had to do one thing – stop progression / destruction of CNS tissue. The Mouse Doctors, Prof G and the numerous other Profs at Barts should be visiting people like you to get a real world view of what MS does and how the research / therapies are not addressing the real MS.

      • Here you go again sniping at us, because you have a platform, enjoy it while you can. Do you think any of your treasured Neuros/Profs are any different or are they a different breed at Barts….and surely the Profs at Barts are dealing with the Real World…However I would indeed say they are different but not what you imply

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