Is Age the new stopping criteria for MS drugs?

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“Stopping is not the same as giving up” – or at least we’re told that this is the case. The connotations of stopping MS DMTs, on the other hand needs to be handled with kid gloves, and importantly avoid having the discussion spiral into one about value-for-money economics. Because which ever way you slice the latter, you’re guaranteed that someone somewhere will be short-changed. Dr Mark Carney (ex-Governor of the Bank of England) famously said that he still maintains his Canadian citizenship as the value of a Canadian in cost terms is better than that of a British citizen (make what you may of this).

But, ultimately what all this means is that we have become tied into this idea of endless treatment in the world of MS. Some of you may say that this is because there is no cure, but the more widely read of you will have already begun to understand why there is no cure. So with great interest I read this review article by Schweitzer et al. on why you might want to stop MS DMTs on the basis of age. Although I may not agree with all the points stated in this review article, I do buy into the argument of treatment de-escalation (i.e. stepping down to a lesser efficacy drug from a high efficacy treatment as a risk mitigation plan), but only once stability is achieved and we work on a basis of early treatment which allows this to take place in the first place.

Below are there main points outlined by the authors on balancing the benefits and the risks:

(1) Starting/stopping DMTs in patients at the age of 55 years and older: patients should be informed that data on the efficacy of DMTs in this age group largely lacking, and that extrapolation from the studies available suggest that the risks may outweigh the benefits. In particular, these patients should be assessed for disease activity (clinically and on MRI), and only those with evident MS-related activity (e.g., a clinical relapse and corresponding MRI activity) may benefit from commencement of DMTs. Likewise, patients without evidence of disease activity (clinically and MRI) may not benefit from treatment continuation, and stopping DMTs should be discussed. This discussion should include
DMT-specific information on the risk of return of disease activity and of treatment-associated risks, for example, opportunistic infections, malignancies, and autoimmune reactions.


(2) Switching DMTs in patients older than 40 years: available data suggest that DMTs with high efficacy may lose their beneficial effects on disability progression already beyond the age of 40. As such, in patients older than 40 years of age, especially those on high-efficacy DMTs, should be assessed for continuous disease activity (clinically and MRI). In patients without such activity (e.g., for several years) the option of ‘deescalating’ DMTs to a compound with mildto-
moderate efficacy should be discussed, a discussion that again include DMT-specific information on the risk of return of disease activity and of treatment-associated risks.


(3) Early use of high-efficacy DMTs in patients younger than 40 years: recent data support the view that early use of high-efficacy DMTs may reduce disability progression [63&]. Thus, if clear evidence of activity (clinically and on MRI)
is present, early use of high-efficacy drugs should be discussed with the patient, including the above-discussed potential strategies on ‘de-escalating’ DMTs with advancing age.

Abstract

Age and the risks of high-efficacy disease modifying drugs in multiple sclerosis

Schweitzer, Finja; Laurent, Sarah; Fink, Gereon R.; Barnett, Michael H.; Reddel, Stephen; Hartung, Hans-Peter; Warnke, Clemens
Current Opinion in Neurology: June 2019 – Volume 32 – Issue 3 – p 305-312

Purpose of review 

A variety of high-efficacy disease-modifying therapies (DMTs) are available for the treatment of multiple sclerosis (MS). After evaluation and approval by regulatory agencies, DMTs are likely to be administered to patients whose characteristics differ from those enrolled in clinical trials. This may contribute to the emergence of unexpected adverse events observed in the real-world setting. Higher age may be a relevant factor that could change the benefit–risk balance of DMTs, as it may associate with lower efficiency and higher frequency of adverse events.

Recent findings 

The absolute and relative number of patients with MS who reach the age of 55 and higher increases. Growing evidence demonstrates lower efficacy of DMTs in older persons with MS. Specific risks during DMTs for MS, such as the risk of developing progressive multifocal leukoencephalopathy (PML) or the outcome following PML, have been associated with age. It is hypothesized that age-related and therapy-induced alterations to the immune system may have (super)additive effects, resulting in an acceleration of physiological immunosenescence and inflamm-aging.

Summary 

In this article, we review the risks of high-efficacy DMTs in MS with a specific focus on age-related efficacy and risks, including opportunistic infections, malignancies, and autoimmune reactions.

About the author

Neuro Doc Gnanapavan

30 comments

  • On the other hand..know of someone near 60 w/pp ms. Went to Russia for hsct..mri right before chemo showed a new lesion. 2 years post hsct edss went from 5.5 to 2. He now walks miles a day in Australia Outback.

    Another woman late diagnosis just turning spms in early 70’s went to Russia hsct..Her u.k. doctor told her she was wasting her money and being selfish for not giving it to her grandson. She said it was her money to do
    what she wanted with and none of his business.

    • What chance for a 75 yr old getting HSTC here? (Edss 6.5), formerly very fit, no known co morbidities

      • About the same as me being struck by an Elvis-shaped meteorite whilst clutching a jackpot-winning lottery ticket.

        • Funny you should say that, my wife’s mother was just talking to a friend whose neighbour’s aunt’s postman’s daughter had been chatting to someone in the queue at the Post Office whose cousin’s driving instructor’s partner had experienced exactly the same thing. Except, in her case it wasn’t Elvis but Mick Jagger and she hadn’t yet bought her lottery ticket. And, I don’t know if she said meteorite. Still, quite a coincidence!

  • Maybe a weak IRT before going off maintenance therapies? But I guess when a neuro wants to discuss stopping with pwMS it is unsuitable to take even a weak IRT by then.

    • Not sure a weak IRT will have the same effect as a highly active IRT that achieves a few years of remission.

  • People should be on DMT to avoid brain loss…which increases in older ages.

    “We had a very nasty rule in Slovakia until 2008: no single MS patient over the age of 45 was to receive DMDs!
    The health insurance system here is semi-open, so there are lots of general rules and regulations which apply to all insurers. Slovak MS community launched a campaign in 2007 and mostly thanks to being an EU member this regulation has been almost lifted. Almost means, that if somebody gets their MS diagnosis after the age of 45, they still will not receive any DMDs…
    PS: Speaking of ancient rules: PPMS is still officially considered here as untreatable, so good doctors never declare a new patient to be PP anymore . . .”

  • The only people w/ms who make it walking in old age are the ones who’s rr didn’t turn into spms.

    “Am now 90 yrs. & one of those who is getting perfunctory care. Was diagnosed at age 36, about 3 troublesome years but was greatly helped with acthar gel injections. Went into remission 40 + years but had a relapse in mid-eighties. Now find treatments suggested are result of my direct question of how to manage my symptoms of primarily vertigo & fatigue. Am now on only supplements which are beneficial. On my own I make sincere efforts to eat well, get rest & on arm chair exercises. Do my walking at local large Target store. Walking the periphery of the store is about 1/2 mile.
    Like to be more engaged with my neurologist who dismisses me with “you are doing well.”
    Well then why do I feel like hell so often ???”

  • Please could you explain the following
    “The absolute and relative number of patients with MS who reach the age of 55 and higher increases.”

    Does that mean that we are quite likely to croak it before hitting 55???!!

    • Take it easy – the global prevalence of MS is on the rise; better diagnostic tools and guidelines; increasing global population and more people avoiding fatal complications from MS with high-efficacy treatments.

      • “Take it easy – the global prevalence of MS is on the rise; better diagnostic tools and guidelines”

        That’s just feel good mumbo/jumbo…still no real treatment for ppms which is the real ms the so called smoldering ms you read about here.

    • “Does that mean that we are quite likely to croak it before hitting 55???!!

      Michelle Obama’s father had ms and was gone at 58…she never mentioned ms..her issue was gardens/eating fresh vegetables. Very little Alemtuz/Lemtrada in u.s. as cost is $200,000 in u.s….No hsct…I mean they do it in Bulgaria now.

  • Age is too arbitrary of a measure.
    Each Individual needs to be Evaluated and Treated to their best ability.
    A Doctor and a Patient working together on their challenges.
    Payment is too arbitrary of a measure.
    Unfortunately, healthcare systems use age and payment stresses to arbitrarily assign
    Value to these ages. Yesterday I was defending using daily Glatopa shots as my DMT. Now, at 63, it may be my safest option. I’ll talk it over with my Doctors 😎

    • Yes you’re right it’s a discussion with your neuro on what you think would be helpful for you at a certain disease stage. Age is an easy think to assign a cut off at but harder to justify at an individual basis. But, hopefully the insurance companies do not jump on this band wagon.

  • “Some of you may say that this is because there is no cure, but the more widely read of you will have already begun to understand why there is no cure”

    Can you embellish on this a little please Doc. I am assuming because a cure = no customers

    • The cause is multifactorial (small changes here and there that lead to MS over 10-15years), there is a potential for considering prevention but again this is not the same as a cure (i.e. treating once the disease is present). This is why we talk about no evidence of disease activity (or NEDA) which is long-term remission but not the same as a cure. We have been successful on focusing on the latter and has improved MS disability outcomes, and just need to keep pushing this and tweaking it.

  • A curve ball really, but do you mind telling us more about Listeriosis, condidiasis and nocardiosis with alemtizumuba?
    Does the incidence increase with patient treated when older than 55 or all patients when they reach 55 regardless of when they were treated?
    Thank you

    • Infections which are only present in an immunocompromised host like listeria, nocardia can occur at any age, but the outcome is poorer if you’re older. Whilst HSV increases with age primarily due to senescence of the immune system with age.

  • This is really scary to consider. I have had this discussion with my neurologist. I have been on Tysabri for 15 years and am now JCV+. If I choose to go off this med, I will never be allowed to start it again per insurance. I agree with Neuro Doc G, that we need older patients in the trials. Prof G believes in starting with highly active DMT. If that is the case, so many of us will be NEDA2 at least for many years which was the goal. In the case of Tysabri there is the real fear of rebound as patients come off the med. What happens then??? As I now move through menopause that adds another level of unknown. Honestly coming off all meds is just not acceptable with out far more data.

    I for one do not plan on letting my MS dictate my life right now.

  • Well as a RRMS person who was first diagnosed at 44 doesn’t make a lot of sense to me. I thought live expectancy for people for ms was only slightly less than the average, which is way more than 55! These days we just seem to receive more and more conflicting posts.

    • agreed, I’m astounded to hear the numer 55, as I am nearly 49!
      Like you say, it’s said a lot that PWMS will live only slightly less than anyone else.
      Should we be out and about having our last hurrah then if that is a load of cobblers?

  • This premise is not something I can support as it isn’t without some key flaws:

    Inadequate studies data is lacking on the efficacy and safety of DMTs in those over age 55. This isn’t a valid reason for any PwMS to be deprived of the possible benefits.

    Secondly, Mary is correct in saying that age is too arbitrary a measure to use as a marker as to whether or not someone is given access to DMTs, including the more highly efficacy treatments.

    All this also ignores the increase in late onset MS – according to a report in Neurology in 2018 it has nearly doubled in women age 50-64.

    Finally there’s the risk of rebound: think I recall ProfG mentioning in a recent post a woman who came off of a DMT after which her disease struck with a vengeance and within 12 months she has gone from walking to being in a wheelchair.

    I’m aware some of what informs my reaction is that I wasn’t diagnosed until age 51 and that I’m so grateful to the neuro at one of the London centres who approved my receiving Alem. I’m not quite four years post the second round of infusions and, as mentioned in my reply to ProfG post, I’ve seen only very slight improvement. However, I’m no worse and according the the 2020 mri report there was no evidence of any further BVL from my 2019 scan.

    I also watched the Aaron Boster vid where he gives his arguments for not stopping DMTs and found his rationale makes sense.

    There’s a reason for why a large number focus on associated risks with regards to treatment in a considerably different way – being focussed on the devil you’re already living with and less so on possible/maybes.

    Very sadly due to restrictions and criteria there’s already too little access to DMTs. Added to which it would seem a degree of mismanagement of switching to another therapy. So therefore adding a blanket age factor to this whole situation appears to risk PwMS health, not positively, but negatively.

    • These discussions will flare up from time to time with neurologists and patients alike trying to quash these types of decision making around DMTs. We need to at least push the goal posts of clinical trials up to 60 so that it starts to cover our ageing population as the treatments work. This makes scientific sense. What has likely resurged the discussion about age is the risk of infections in the older age group, especially in the current COVID era.

      • Your assertion that studies should include those up to age 60 is so very pertinent – as you say: with an ageing population. I hope we will see this happening before very long.

  • It makes sense to ease up on immuno-suppression as you age. You immune system itself weakens and you also have to worry about malignant neoplasm.

    I am 36 and on DMF and stable. Perhaps DMF is neuroprotective, perhaps not. But does lower my white blood cell count quite a bit.

    Do I stay on this permanently? Reduce dose? Switch to maybe teriflunomide? Especially if MS has a viral component?

    I don’t want cancer, particular the blood cancers, but I also don’t want active MS.

    Fun times.

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