Upbeat Burt team pub on stem cells for MS comes with uneasy back story

Types of Multiple Sclerosis
Types of Multiple Sclerosis and their impact on disability over time. Unmodified Wikimedia open source image by Osmosis.

Stem cells for MS? How promising is that? A new paper gives stronger reason for hope, but unfortunately this story is more complex than it seems on first glance.

New Paper

The idea of using a stem cell-related approach to treat multiple sclerosis (MS) has been around for a long time holding major promise, but there hasn’t been much in the way of high-quality trial data out there in the published literature. A paper this week from the Richard Burt team at Northwestern (NW) and conducted in part at other international sites provides a fresh boost of excitement in this area.

This cross-over study was larger than past published work. It was focused on highly active relapsing-remitting multiple sclerosis. You can see a helpful graphic about the different types of MS and their impact on disability over time at right.

Recipients of hematopoietic stem cell transplants (HSCT) with partial immune ablation fared significantly better in this study, published in JAMA, than recipients of immunosuppression alone. Also, the very large reported differences between those getting HSCT versus standard care suggest a real, meaningful effect.

The short take-home is good news for patients but with some big wrinkles to iron out as discussed below.

Complicated back story including big patient payments

Over the years, I’ve had some concerns about the NW work on HSCT for autoimmune disorders like MS. Some of these issues remain on my mind. For instance, many patients apparently had to pay to enroll. These payments, depending on insurance coverage, could sometimes be very large. It seems unusual to me that some patients would have to pay maybe $100K or more to be enrolled in a trial. That kind of practice could impact the end results of the study too.

What happens to those who cannot pay?

In addition, I don’t see an acknowledgement of patient financial contributions to the HSCT MS study in the new paper itself. Probably JAMA wouldn’t require that (maybe in part because so few studies would require major payments by trial participants). However, in my view, why not give a likely much appreciated hat tip to all the patients who not only took risks to be trial participants, but also financially contributed to the study’s funding?

Patients contributing in big ways to the financials of a study could also impact the results.

Other concerns: portrayal of ongoing trial as curative & off-study experiments on patients

In my opinion there was also a reasonable question as to whether the HSCT trials were being pitched already as curative years ago while they were still ongoing. There was buzz from patients about this as already known to work while the trial was ongoing too. This kind of thing could alter trial outcomes.

Some patients indicated that NW would give certain patients the experimental treatment in an “off-study” fashion, which was concerning to me as well and if confirmed, this would be something I’m still concerned about today. Presumably the off-study patients would still have to find large sums of money to pay toward the trial. Furthermore, the resulting paper(s) wouldn’t include their data. I don’t know if off-study severe adverse events or even deaths would have to be reported to the FDA.

FDA warning to team: any connection to this study?

It’s also a big deal that this team received an FDA warning letter a few years back for a variety of issues including failure to promptly report patient deaths. Unfortunately, we don’t know from the letter whether the deaths mentioned were amongst MS patients who were part of the group reported on in the new paper or were other patients in a different study. The new HSCT-MS paper did not mention the warning letter and it reported no patient deaths.

Numerous other issues were cited by the FDA in the warning letter too and we don’t know if any of those applied to the MS work either. Maybe not, but hard to say. Do JAMA or other journals that publish clinical trials have policies on whether papers in any way connected to warning letters must mention the warnings?

Importantly, the FDA indicated later that the team had addressed the issues in the warning so that’s encouraging.

Older immunosuppressants could have amplified apparent benefit of HSCT

The new study has at least one key limitation in that older immunosuppressant drugs were the focus, while newer drugs in this class work a whole lot better. The big difference in outcomes between HSCT + immunosuppression vs. immunosuppression alone would likely have been smaller in the context of new drugs. The use of older drugs in the study is attributable to the fact that this study simply began a long time ago.

Patient perspectives

Patients including some self-identifying as involved in this or similar studies at NW have had many useful perspectives in their comments on my 3 posts here on The Niche on the NW work (here’s the first¬†post from which you can click on to the second and third). The patients also often let me have it for a variety of things in my posts. They are almost without exception big fans of Dr. Burt.

Take home: good news, but still big questions

In the long run, the bottom line is that the data here are very good news, but there were bumps in the road to get here and open questions remain. I hope Dr. Burt and NW can clear things up within the public domain quickly.

A number of other groups are studying HSCT for MS too and there have been preliminary results that seem promising. Looking ahead, could HSCT-related therapies become the standard of care for certain patients with specific kinds of MS? Despite its high cost, could it even become cost-effective when compared to expensive, toxic long-term drug therapies alone? I hope so as this would help thousands of patients.

6 thoughts on “Upbeat Burt team pub on stem cells for MS comes with uneasy back story”

  1. People insurance that are really sick pay for it. Government knows. So if you didn’t live in Chicago you would have to pay hotel. A week of testing. Your getting one sided story. 17 years out. Please start posting positive plus everyone knows they can die. We sign so many papers. So people know we know what can happen. He never his anything from patients. So maybe fda needs to talk to Government that paid for very sick people to get procedure. Selma Blair had private and insurance to pay. He tells you and all studies I know of operate that way. Even for cancer or liver. Look it up

  2. Alex Masters, a journalist, did a big exploration of the “paid for trial” process, the pitfalls, and the opportunities. It seems that with the clever trial design of having the paying participants not in the trial but as separate IND cases a lot of the problems can be avoided.


    Personally, it seems to me that in a world where there is a shortage of money for research and trials, the benefits of this approach outweigh the costs.

  3. Paul, thanks for this account of the back story. It’s very helpful. After reading the paper (and granted, I did not look at any supplementary material), I didn’t sense any reason to question the study or researchers. I found out via Leigh Turner on Twitter about the FDA letter (and had my editor pull a story that I wrote on the study). There is a passing mention in the accompanying editorial by Harold Atkins, MD – “There is concern among some treating physicians about the rigor of HSCT and the risks associated with the procedure.” There is no mention of patient payments or the FDA letter.

    JAMA could have easily added a note or box about the FDA letter and payments in the interest of full disclosure. I’m not sure what else I should have done as a medical reporter. I count on distinguished journals like JAMA to provide an accurate and full picture of the studies that it publishes. Mainstream media did not cover either of these concerns. Nor did well-respected medical and science publications (though their coverage was much deeper and more nuanced). We’ll still publish the article – but I am adding text about patient payments and FDA taking an unusual step in sending a letter. To my mind, not do do so is akin to not mentioning COIs or pharma study support. Maybe none of this makes a difference in the results, but it’s important to have the information nonetheless.

    1. @Kerri,
      I’m glad this was helpful. I wish we knew more conclusively whether the warning letter was related to the JAMA study or not.
      I’m not sure JAMA or any other journal would require disclosure of patient financial contributions to a clinical trial, but maybe they should.
      Interestingly, as a side note on Twitter there was discussion by some with hematopoietic stem cell expertise more broadly about how the approach used in this JAMA study could arguably not really be considered a “stem cell” therapy, but rather the stem cells along with other non-stem cells may simply be viewed as allowing the patient to recover from the primary treatment, which is the immunoablation. Still, I don’t think it’s known for sure whether perhaps the stem cells do have some other roles such as suppression of remaining auto-reactive cells. Paul

  4. This has been on going for 15 years. People need to get on HSCT; or, they pay upwards to 98,000 (yes, that’s right) a year for, in my case, Gilenya. This is a rip-off. Pharma companies have us. The only hope is to do HSCT, readjust your diet and get 3 – 5 days of exercise. You show me whose done that and it not work and I’ll show you a liar.

  5. I know a lady who was treated off study for compassion reasons. She went in a wheel chair. At 6 month checkup she went with a cain and left it with Dr Burt. Walked for 1 year check up.
    At 15 months she severely broke her ankle running down her stairs. She is completely recovered and living a great life
    I was rejected because I had no active lesions and was 60. My insurance was willing to pay 100%.
    Because he turns so many away many are going to Russia and Mexico with same results. Less than 1/2 the cost also

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