A cost too high? The cost-effective analysis (CEA) of our current DMTs


‘Primum non nocere’ – Do no harm; the Hippocratic injunction.

It could be argued that perhaps were are too ready to dose our expectant patients with the next golden ticket in MS. Mayhap, withdrawal of the long list of medications that they are already on, can prove to be just as efficacious?

Yet, I am not a great supporter of masterful inactivity on the part of the physician. I’m equally put out by the currency of living a healthy life. Market statistics and our employers now require us to understand costs of treatment – the lesser of two evils, followed shortly after by a greater evil, restriction of treatment. In my mind, only the blatantly wealthy can afford to take the moral high ground when it comes to this. There is little to loose, when your coffers are overflowing!

In this interesting review, Batcheller and Baker study the cost effectiveness of MS disease modifying therapies (DMTs), trying to make sense of the murky world of list prices (see below) and off setting these against their effectiveness. In their efforts to get usable outcomes, they quickly realise that there are several limitations. But all is not lost, and they do come up with some defining conclusions.

Firstly, the second-line therapies are the most-cost effective, despite the first-line therapies being relatively safe and cheaper.

“Currently, the drugs with the most benefit tend to be those that carry the most risk and the highest price tag”.

Secondly, front-loading the treatment costs in MS may be more cost-effective than paying for continuous long-term treatment. The induction treatments rarely require repeated courses after 1-2years, thus lowering the cost of disease associated complications and cost to society. However, we do not have enough long-term data on how the different treatments pan out.

“CEAs support the idea that it may be worth using more aggressive measures earlier on as front-loading the cost means the cost of long-term disability progression is reduced. It is difficult to say what the long term outcomes of different therapies may be as there is not enough long-term follow-up data”.

List prices for MS DMTs (actual prices may be lower)

Last year several of the Big Pharma agreed to put a freeze of treatment costs after coming under heavy pressure from the Trump administration (probably the only thing that unites both Democrats and Republicans). But, the war on drug price hikes continues, as some pharma companies continue to increase prices on some drugs, while decreasing prices on others.


J Neurol Sci. 2019 Jul 9;404:19-28. doi: 10.1016/j.jns.2019.07.009. [Epub ahead of print]
Cost of disease modifying therapies for multiple sclerosis: Is front-loading the answer?
Batcheller L, Baker D.

There are now over a dozen disease modifying therapies (DMTs) available to treat multiple sclerosis (MS). They vary in efficacy and safety as well as in cost. The literature on the cost effectiveness of these is often confusing and contradictory. There is a lack of quality evidence enabling the comparison of different DMTs. There are scarce randomized controlled trials which look at one DMT compared with another that is not IFN or GA. There is also a lack of systematic reviews comparing the efficacy and safety of different DMTs. This makes it difficult to perform good quality cost-effectiveness analyses (CEAs). Furthermore, CEAs in and of themselves are difficult to interpret or compare due to the variation in methods and cost estimations as well as the use of outcome measures which cannot be proven over a reasonable timeframe. This review looks at the different DMTs available for MS and attempts to draw some conclusions on their cost-effectiveness. It also considers the costs and benefits of front loading the cost of treatment for MS by using more expensive and effective treatment earlier on.

About the author

Neuro Doc Gnanapavan


  • Thanks for the post NDG.

    This statement outlines the absolute absurdity with current MS research and treatments:

    “There is a lack of quality evidence enabling the comparison of different DMTs. There are scarce randomized controlled trials which look at one DMT compared with another that is not IFN or GA. There is also a lack of systematic reviews comparing the efficacy and safety of different DMTs”

    This is why MS research and treatments are in the doldrums. This problem begins and ends with approval bodies, like the EMA or FDA, who appear to be either stupid or conflicted by Pharma.

    Why is the Pharma allowed to get a drug approved when it is not compared to the most efficacious drug on the market? Why do the neurologists involved in the trials put their trusted name behind this? Where is their loyalty to the Hippocratic oath and the patient?

    • Loaded questions DJ Harrt, I suspect you already know the answer to them. But, steps have to be taken in the right direction. Makes little sense to be doing placebo-controlled studies outside of Phase II, and we may even move to the first-line orals as comparators (keeping up with the times and all…). Most pharma now have access to their own oral therapies, so not a massive hurdle. Despite, how informative real-life data have been for MS over the years, they still have an intrinsic bias. Only a randomised controlled study will do!

  • Does the analysis factor in additional costs for known adverse effects and the subsequent medications required to treat (e.g. methimazole to treat graves caused by alemtuzumab)?

    I’d love to actually read the article instead of peppering you with questions but it’s locked behind a paywall. Time to fire up BitTorrent and my VPN me thinks…..

    • No, varies from cost effective analysis to cost effective analysis between drugs and changes over the years. They generally look at annualised relapse rates, 3 or 6 month sustained accumulation of disability and cost for any additional monitoring required i.e. direct healthcare related costs. The cost of supplementary treatment costs is difficult to account for from adverse events. Probably the biggest one being PML. Conversely, the cost to society are not included – care costs and indirect costs, such as staying in employment. One of the biggest CEA analysis performed to date is the risk-sharing scheme in the UK for the platform injectables and this highlights the difficulties of picking the correct comparator and model – https://jnnp.bmj.com/content/87/12/e1.161#

      • Mmmm. One would argue that treatment for known and treatment related adverse effects is a direct related healthcare cost. So to your point, all these analysis are flawed and don’t give a truly accurate cost of the drug. I’ve argued for years that industry phase 3 studies should include a CEA (inpatient days, use of concomitant medications, days off work etc) if they want their drug registered. Never gonna happen though.

  • Thank you so much for posting this.
    It was quite shocking to see the difference in treatment costs between the US and the UK – even though I knew there were substantial differences. Do you happen to know the cost of looking after a person with MS per year on the NHS? I have read that in Canada, it’s about CDN$16,000 per year. In the UK, I have heard various numbers such as £1 million pounds over a person with MS life.

    • This is covered in the paper:
      “UK the annual per patient cost to society ranged from £11,400 (€12,800) for mild disease (EDSS 0–3) to £22,700 (€25,400) for the moderate disease group (EDSS 4–6.5) and £36,500 (€40,900) for the severe disease group (EDSS 7–9) [17]. Overall, the average annual cost by disease severity across Europe was €22,800, €37,100 and €57,500 for mild, moderate and severe disease“

  • NDG,

    When neuros / MSologists get together at the various MS conferences I’m guessing there is quite a bit of chat about views on the effectiveness of the various therapies for relapsing MS. Are we missing a trick on gaining real life experience of MS therapies. A survey of MSologists in the U.K. (there’s not that many of them) should be able to provide a ballpark ranking of how effective these therapies are from the experience of the neurologist treating the patients. This would provide a more helpful tool for those starting treatment than research papers containing a range of stats. My friend has breast cancer (bad) and her oncologist told her that in her view therapy x was her best option and the oncologist had patients who were doing well 7 years on. This real life stuff helped my friend to follow her oncologists advice. I wish neuros could learn from this approach rather than just hand out leaflets or point to a website with a toolkit for deciding on which treatment. Cost effectiveness is of little interest to the patient. I’d guess that the vast majority of patients don’t want to become disabled / disabled and a neuro / MSologist should be pointing them to the right treatment to achieve this.

    • Hi Beth, a survey of neurologists has been done already, and not surprisingly opinions differ. MDT decisions have made the variability less and hopefully will moderate both extremes. There is also, and I witnessed this myself, a tendency to recommend a single drug – usually the new kid on the block. But this is also wrong and needs to be tailored to the person. Cost effectiveness aside, highly active induction treatments buy time and make life easier for those on both sides. However, anecdotal data or personal opinions fall quite low on the evidenced based ladder and lead to favourites in drugs and blindness to their limitations. You need to be aware of all of these when you’re prescribing and avoid the pitfalls.

      • that’s the point though isn’t it? The patient is told to visit the MS Decisions website and told to make a choice which one they want to have…..I mean come on, how the heck is someone whose head is reeling minutes after being diagnosed supposed to know what one to choose?

        The specialist is supposed to be just that, a specialist, who should know far more about treatments than the MS decisions website page.

        Do doctors for other ailments do it that way? Are cancer patients told to do it that way as well?

        Are the specialists trying to absolve themselves of any responsibility in terms of being sued or something?

        • Yes you’re all correct there are differences between cancer management and MS. There’s huge pressure to be not paternalistic with MS with great emphasis on patient choice. The MS Trust site and similar DMT decision sites were developed to aid this decision making process. But, as the treatments have become more complicated this is starting change. Ergo, the requirement for MDT decision making processes for second-line drugs or all treatments. The PwMS is then given a choice between the most suitable for them. In our centre, we base it on clinical presentation, MRI findings and neurofilament readings.

      • I suspect some neurologists select the drug with the least monitoring requirements (for them and the patient). I certainly found this was the case with the first neurologist my wife saw. We kicked him to the curb and purposely sort out a neurologist who was willing to treat aggressively. In hindsight, that was actually not that hard (in Australia where all DMTs are currently available first line including alemtuzumab).

    • That last sentence is spot on….do other specialists make their patients chose their treatment this way? (I genuinely do not know).

      If someone is seeing a specialist for something as serious as MS, pointing them to a website and telling them to make their choice from the list is scandalous.

      They must have patients on lots of treatments, surely they could use their specialist knowledge and experience of how people do on different ones to make an informed choice and guide the patient?

  • Thanks for summarizing the current fee schedule for MS DMT meds in the USA and UK.
    As a patient, and former neurological nurse in the 1980’s, Before all these drugs,
    I appreciate having any one of them. They are all better that the way it used to be, The Dwindling Steady Dive into Nothingness. Now at least I am Less Disabled by Fatigue, Pain, And an Aging body.
    But Multiple Sclerosis has so many more layers than keeping me going with a daily shot costing $60-80 Thousand Dollars a year. I want more than the pat on the back I can do the Ten Peg test or the 25 foot dash. A Psychologist referral Nobody calls me back to schedule. The PT/OT exercise pamphlets sitting on my dresser, the Pain I cannot treat with THC because I don’t live in the right state, the secret Hell my husband sees but no one else does. The pile of paperwork I have to fill out to say I can’t, I can’t, I can’t. The neurologist says, You’re doing pretty well. My insistence that Gadolinium contrast, injected over and over, accumulated in every cell in my body and I only get skeptical glances (don’t groan, please). The MRI’s that look like Swiss Cheese And Doctor says, You’re doing pretty well. I say all this because I want the Big Quality of Life Study. The Big Risk/Cost vs. outcome analysis. The Long Term Study, Lifetime, even. My Total history, bad habits and all. I want My chart of My Daily Life, My Husband’s Too, to be analyzed so My Neuro Team can See, in a snapshot, anytime, more than my easily said “i’m fine” in my 6 month clinic visits. I want more for all the young people who don’t understand how or why take DMT’s, or that their struggles may or may not be blamed on the MonSter I know so intimately, from being a Caregiver and being cared for. I hope this makes sense.

    • Hi Mary it makes sense. The brain is sacrosanct and a disorder that takes bits of it takes everything away. The generation pre-DMT bear the brunt of this. It’s difficult how to approach this in clinic slots. The burden to the population from neurological disorders, including MS, Parkinson’s, ALS as it ages is increasing. There is a tendency to have an ostrich effect when it comes down to it.

  • Congrats to Dr mouse and coleages
    It would be nice to study also some
    Generic therapy like rituximab
    And also Hsct (maybe the most cost efective of them all)

    • This was an essay from one of the medical students, I gave a little guidance. However we have been there with regard generic therapy. Please see Moa et al. We compared the price of the MS drug UK and US price price and included cladribine azothioprine cyclophosphamide etc.
      I can’t rember if HSCT was included. This was another student project by Dr Doctor…yep their real.name now



Recent Posts

Recent Comments