Turkeys voting for Christmas

T

Barts-MS rose-tinted-odometer: ★★★ (dollar color Monday hex #6B8068)

Did you know that the effectiveness of high-dose steroids to treat a relapse is small? In reality, there is no difference in outcome at 6 months between relapses treated with steroids and those managed without steroids. In reality, high-dose steroids simply speed up recovery of function by about 2 weeks. So if you are not disabled by your relapse and it has not affected your day-to-day functioning it is better not to have them.

High-dose steroids don’t come without risks, i.e. psychosis, insomnia, depression, avascular necrosis of the hip, hypertension, diabetes, infections, blunted vaccine responses, higher risk of severe COVID-19, etc. So then why do we prescribe them so frequently? Money, money, money!

In many fee-for-service healthcare systems, neurologists and healthcare institutions make money out of admissions and intravenous infusions, which acts as a perverse incentive to prescribe steroids. The good news is that high-dose oral steroids for relapses, taken as an outpatient, work as well. 

The French study below shows how much money could be saved from shifting from inpatient intravenous to outpatient oral steroid use (25 million euros per year in France). I doubt this will change behaviour when there is money to be earned. As the saying goes ‘turkeys voting for Christmas’; not on your life. 

So the next time you are offered inpatient-intravenous steroids for a relapse you should ask for home-oral steroids instead and see what response you get from your HCP.

Michel et al. Cost-utility of oral methylprednisolone in the treatment of multiple sclerosis relapses: Results from the COPOUSEP trial. Rev Neurol (Paris). 2021 Sep 28;S0035-3787(21)00664-0. 

Background: Studies have shown that oral high-dose methylprednisolone (MP) is non-inferior to intravenous MP in treating multiple sclerosis relapses in terms of effectiveness and tolerance. In order to assist with resource allocation and decision-making, its cost-effectiveness must also be assessed. Our objective was to evaluate the cost-utility of per os high-dose MP as well as the cost-savings associated with implementing the strategy.

Methods: A cost-utility analysis at 28 days was carried out using data from the French COPOUSEP multicenter, double-blind randomized controlled non-inferiority trial and the statutory health insurance reimbursement database. Costs were calculated using a societal perspective, including both direct and indirect costs. An incremental cost-effectiveness ratio was calculated and bootstrapping methods assessed the uncertainty surrounding the results. An alternative scenario analysis in which MP was administered at home was also carried out. A budgetary impact analysis was carried at five years.

Results: In the conditions of the trial (hospitalized patients), there was no significant difference in utilities and costs at 28 days. The incremental cost-effectiveness ratio was €15,360 per quality-adjusted life-year gained. If multiple sclerosis relapses were treated at home, oral MP would be more effective, less costly and associated with annual savings up to 25 million euros for the French healthcare system.

Conclusions: Oral MP is cost-effective in the treatment of multiple sclerosis relapses and associated with major savings.

Conflicts of Interest

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice. 

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.

28 comments

  • I was given oral steroids already 15 years ago when I was living in Belgium. Though literally the bitterest pills ever, they worked fine. I guess though that the way of administering high dose steroids wouldn’t make a difference in terms of risks?
    These days indeed if a relapse is not too debilitating, I skip steroids altogether having read a long time ago that it ‘only’ speeds up the recovery.

    • Re: “I guess though that the way of administering high dose steroids wouldn’t make a difference in terms of risks?”

      Believe it or not, some people are allergic to IV formulation and get infusion reactions that can be anaphylactic type reactions; not to the steroids but to the incipients. Otherwise with the oral formulation the liver gets to see much higher doses.

  • What part of the immune system does methylprednisolone target?

    When I was on these steroids (oral) for a relapse. I didn’t get told of any of the side effects or that it could effect covid -19 outcomes. Only online research I found this out. Insomnia was terrible

    • Re: “What part of the immune system does methylprednisolone target?”

      All parts to be honest, but the doses we use to treat relapses is beyond the effect on the immune system and works on membranes and reduces oedema and swelling. We think this is its mode of action in relapses.

  • Sugarlevel in blood just before prednisolon 5.4
    Couple hours later 19.6

    I’m ADHD.

    ADHD + 19.6 bloodsugar = no sleep for days!

  • A half related question about the severity of a relapse. Should patients take a degree of comfort from a relapse that doesnt particulalry affect them i.e. is it a better prognostic factor in the longer run as the lesion perhaps didn’t affect too many neural pathways?

    • Yes. Motor relapses, disabling relapses, poor recovery from relapse and frequent relapses in the first 2 years are poor prognostic factors.

  • From experience I would have appreciated IV steroids at the hospital, for my first severe relapse instead of tablet version at home. My symptoms keep on coming and I just had to deal with it with no help/care/support. Just a GP called me a week or so later.

    May be something midway would have been helpful, such as an MS nurse home visit, for support when taking tablet steroids for the first time and at home.

    • Yes, when I was trained in South Africa we always had to give the first course of steroids IV to watch how the patient reacted. The worry was psychosis. If they did okay with the first course we used to then give subsequent courses orally. At that time we didn’t have high-dose tablets (100mg) and we used to dispense the IV formulation to be drunk with orange juice. The latter works a trick and is still used a lot all over the world; it is cheaper and a medical hack to keep costs down.

      • Thanks Prof G, I did feel out of control on the steroid tablets. It was a combination of it being my first relapse which was severe, and not knowing what to expect with the steroids. I was also suffering from severe anxiety and insomnia before and during taking steroids.
        I can see why patients might get psychosis.

  • Why do i feel so much better on steroids if all they do is dampen inflamation ? Ive never understood this. Do they do something else ? As someone whos had almost 14grams in the last 18 months, as soon as i come off them i feel like death

    • Yes they do all sorts of things such as knacker your hips and shrink your nads…but to be serious they stop you producing your own steroids because the output from the adrenal is inhibited and therefore you have to taper yourself off them if you have been on them a long time. They give you the fight or flight feeling

      • “As the saying goes ‘turkeys voting for Christmas’”
        “all sorts of things such as knacker your hips ”

        Turkey is Thanksgiving..Ham is Christmas
        World isn’t made of Anglophiles..these were some toughies to get.

        • No chance of either ham or turkey in the UK for the foreseeable with our shower of a government in charge 🙁

        • Sorry forgot to link to slag Try number 3 below

          KNACKERr
          BRITISH
          1. a person whose business is the disposal of dead or unwanted animals, especially those whose flesh is not fit for human consumption.
          2. tire (someone) out.”this weekend has really knackered me”
          3. damage(something) severely. “I knackered my ankle playing on Sunday”

          P.S. Surely the World was made by Anglophiles….:-)

    • Re: “Why do I feel so much better on steroids if all they do is dampen inflammation?”

      It’s not necessarily anti-inflammatory effects that make you feel better. High-dose steroids can lift your mood and give you a buzz. However, they can do the opposite and make you very low.

  • It’s difficult for me to see how giving steroids wouldn’t be neuroprotective in the long run. Surely killing inflammation more quickly results in less tissue damage and more conservation of neurologic reserve? I assume the reason for there being no change in functional recovery at six months in that one study is that relapses happen more frequently in the early stages of the disease and at that point most people probably still have enough neurologic reserve to hit their recovery ceiling no matter what you do. But regular use of steroids in the acute phase of relapses may have an impact on time to transition to SPMS or on long-term (say 5, 10, or 20 years down the line) disability.

    • “But regular use of steroids in the acute phase of relapses may have an impact on time to transition to SPMS or on long-term (say 5, 10, or 20 years down the line) disability.”

      Possibly…but steroids are likely drops in the bucket comapared to the
      disease process. If someone has just had a stroke and lost 1% of their brain
      do you think steroids are going to help..?

      MS damage is 24/7 it doesn’t just happen during
      relapses. And none of the DMT get you down to normal ageing brain atrophy…which is just one reason…ocrevus and tysabri..etc..don’t stop disease progression.

      “Brain atrophy, the gradual loss of brain volume, is quite extensive in MS, nearly 0.5–1.35% per year, far off the limits of normal aging [5, 6]. It arises early in the course of the disease, accelerates with disease progression”

      https://www.google.com/search?q=yearly+brain+atrophy+in+ms&rlz=1CATQWC_enUS898&oq=yea&aqs=chrome.0.69i59j0i433i512j0i512j69i57j46i433i512j46i175i199i512j0i512j46i131i433i512j0i433i512l2.7637j0j15&sourceid=chrome&ie=UTF-8&safe=active&ssui=on

      • I agree that it would only be a drop in the bucket, but if you can get a 1% gain here and add it to a whole bunch of other 1% gains from other small-effect interventions, you might make a big difference overall (the marginal gains philosophy, in other words). Even HSCT is not going to be a cure unless you do it really early and get lucky, so I would prefer to maximize my chances of aging normally in every way possible.

    • Maybe the swelling damage recovers nicely, and steroids have little to no effect on the scarring types of damages.

  • IV STEROIDS CAN BE GIVEN IN ANY DOCTOR’S OFFICE NOT A HOSPITAL. IN ADDITION WITH ORAL OR IV IT MAKES A DIFFERENCE FOR ANY MS PERSON (ME). ORAL STEROIDS HAVE MINIMAL IMPACT WITH SUCH LOW AMOUNTS ENTERING YOUR BLOOD TO MAKE A DIFFERENCE. AFTER 5 DAYS OF IV STEROIDS I WAS WALKING WITHOUT MY WALKER. I WISH DOCTOR’S WOULD CONCENTRATE ON #CURE4MS” AND OR ANY DRUG (NOT ANY OF THE DMD’S ON THE MARKET TODAY THAT COME WITH VERY RISKY SIDE EFFECTS INCLUDING CANCER. THE BEST OPTION FOR ALL OF MY 2.9M FRIENDS WORLDWIDE IS HSCT. IT’S NOT A CURE AS WE ALL ARE AWARE, BUT WE ARE IN REMISSION. JANET SCHLESSER WARK TIMES UP #CURE4MS. **HSCT JAN 2017 BY DR. RICHARD BURT. CURRENTLY IN REMISSION. THANK GOD!!

    • For sure it’s important to weigh cost vs benefit of steroids for particular person and specific flare. I feel the doctor and pwms need to be responsible in same way we are with antibiotics. But I’m afraid Your comment, “ So if you are not disabled by your relapse and it has not affected your day-to-day functioning it is better not to have them.” might have been too brief a sentiment on this point.. I quickly deteriorated and my ability to function at all was disappearing in a matter of days from an aggressive flare. Hospitalization and Use of Iv steroids wasn’t really optional. In fact, the doctors considered what other more powerful drugs could be used if I didn’t respond to the steroids. And what’s the general rule about tapers? My taper was too short and I still remember how it made me feel. If you’re on high dose oral, how is it tapered down?

      • Randomised trials have not shown a difference in outcome between steroids vs. placebo and between IV and oral. Also, trials have shown that oral tapers make no difference, but add to the adverse events.

  • Dear Prof G.,

    Concerning the equal effectiveness of IV and oral cortisone, I would have 2 remarks/objections:

    – While it is massively requested that several studies should be conducted to validate a scientific hypothesis, in this particular case only one was conducted, with the impossibility of double-blindness. If we reason by applying the standards of Evidence Based Medicine, then the level of proof provided by this French study is low, isn’t?

    – My neurologist told me, after having spoken with other neurologists who have made the same observations as his, that for quite a high number of patients oral steroids are much less effective than intravenous infusions. These neurologists (unofficially) question the validity of the study methodology and continue to prescribe outpatient IV steroids to increase the chances of patient relief.

    So, this time, money may not be the main criteria, at least for some very capable neurologists!

By Prof G

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