#ECTRIMS2021: a potential cure?

Barts-MS rose-tinted-odometer: ★★★★★★★
A 7-Starred Bright Pink Sunday Special #ff007f

Some asked about the 10-year alemtuzumab follow-up data. Here are the headline results:

  1. 60% of subjects are free of disability worsening.

2. 50% had confirmed improvement in disability.

3. Annualized brain volume loss consistently below 0.2% (essentially normal).

4. Tragically, the trial subjects who were randomised to interferon-beta for the first 2-years never catch up; time really is brain and spinal cord.

As you will see these results are clouded by a 40% drop-out rate and hence may be enriched for responders. However, these results still support hitting MS early and hard with an IRT will result in a significant number of pwMS going into long-term remission. 

I did the TOPAZ exit assessments of a large number of study subjects for both the CARE-MS1 and CARE-MS2 cohorts and I have never seen so many people with MS living normal lives with no disability in long-term remission, but still carrying around the label of having MS.

Wouldn’t it be great to be able to tell some of these pwMS you are cured? 


Knowing what MS can do to people and seeing these results who wouldn’t want to be treated with, or at least offered the option of being treated with, alemtuzumab or another IRT when they are diagnosed? 

Giovannoni et al. Early treatment with alemtuzumab maintains its efficacy on clinical and MRI disease activity outcomes, including slowing of brain volume loss, over 10 years in RRMS patients: CARE-MS II follow-up (TOPAZ Study). ECTRIMS 2021, P722.

Introduction: In CARE-MS II (NCT00548405), alemtuzumab (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved clinical/MRI outcomes versus SC IFNB-1a over 2 years (y) in RRMS patients with inadequate response to prior therapy and further minimised disease in a 4-y extension study (NCT00930553). Further follow-up was available in an additional 5-y extension, TOPAZ (NCT02255656).

Aims: Evaluate the efficacy and safety of alemtuzumab in CARE-MS II patients over 10 y.

Methods: At investigator discretion, patients in TOPAZ can receive additional alemtuzumab as needed for disease activity (≥12 months apart) or other disease-modifying therapy (DMT) at any time.

Results: Proportions of patients remaining on study after 10 y were 62% (271/435) among those treated initially with alemtuzumab in the core study and 73% (107/146) among those treated with SC IFNB-1a for 2 y before switching to alemtuzumab in the extensions. In the extension studies, 39% of the alemtuzumab group did not receive further treatment (alemtuzumab or other DMT). Among the alemtuzumab group over the combined core and extension studies, 71% of patients had stable/improved EDSS scores, the mean change in EDSS score was +0.34, 58% of patients were free of 6-month confirmed disability worsening, and 49% achieved 6-month confirmed disability improvement. In Y10, the annualised relapse rate was 0.11, 71% of patients were free of MRI disease activity, 92% were free of new gadolinium-enhancing lesions, and 72% were free of new/enlarging T2 hyperintense lesions. The median annual brain volume loss was ≤0.19% each year over Y3–10. Alemtuzumab had a consistent safety profile over 10 y, with the incidence of overall adverse events (AEs) and infections declining through Y10. Cumulative incidence of thyroid AEs was 44% and immune thrombocytopaenia was 4%. Efficacy and safety in SC IFNB-1a–treated patients from the core study who switched to alemtuzumab in the extension were consistent with those treated with alemtuzumab in both the core and extension.

Conclusions: Early treatment efficacy with alemtuzumab on clinical, MRI lesion, and brain volume outcomes was maintained over 10 y in CARE-MS II patients, with 62% remaining on study and 39% receiving no additional courses or other DMTs through Y10. Safety remained consistent and manageable over 10 y, with declining AE incidences over time, including a consistent reduction in autoimmune AE occurrence after Y3.

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.

24 thoughts on “#ECTRIMS2021: a potential cure?”

  1. I find this bitter sweet reading. Up until 5 months ago I genuinely thought I was one of those very lucky people in long term remission from this horrendous illness. I had been treated, off label, just over 10 years ago with alemtuzumab literally within a couple of weeks of a quick diagnosis and had been able to get on with life with just some residual numbness in left leg.
    To my utter shock, I experienced a brainstem relapse this May. I am still wondering if the covid vaccine had anything to do with it as relapse occurred a few weeks following second vaccine. My haematologist, who treats my ITP, thinks most probably. I am still trying desperately to recover from this relapse – speech OK now, but still problems with walking & right arm and hand.
    However, my point is that following the first massive attack, paralyzed from chest down, I still remain hugely grateful for those 10 years of near normality. I hope the other people in long term remission continue to do well, but I do think a cure and some treatment to help with remylination is years overdue.
    I sometimes wonder, based on the two huge attacks experienced, if I have aggressive ms only kept in check my the alemtuzumab. My current neurologist is not as forward thinking, or as passionate, as my first one. I would be OK to go for the big guns treatment again, but it isn’t an option on the table.
    I honestly do not want to put a dampener on this article based on my recent experience. I still hope for improvement in my symptoms & a return to near normality. Thank you to all involved in this blog for the work that you do & for sharing information with us.

    1. Sorry to hear this. I wish we could have a predictor or predictors to be able to offer people like additional treatments or another course of alemtuzumab to prevent late disease reactivation. This is why an induction-maintenance treatment strategy makes so much sense to me.

    2. Hi there. Sorry to read this but I’m in very similar situation after AHSCT. Great results for almost 5 years and relapsed two years ago. Since this episode I feel that disease is slowly progressing (smouldering?) but fortunatelly not in that aggresive form as it was before the IRT. I’m considering a follow-up treatment of Ocrelizumab…
      ps. I’m the EBV positive, had mono at teenage.

  2. Why weren’t the Cambridge team involved in this research (Alemtuzumab was their baby)?

    How does the MOA of Alemtuzumab fit with the view that EBV is the cause / driver of MS?

    Alemtuzumab is excellent at addressing relapses / focal inflammation, but is it addressing smouldering MS in the CNS? Any evidence of oligoclonal bands disappearing?

    I’d wait 20 years post second infusion before declaring victory a cure! Alot can happen in years 11-20.

    1. Do we know why such a large percentage of people dropped out of the study? This must impact results.

      1. Many reasons, tired of having to come up for consultation, moving to another region or country, centres closing down, etc.

  3. It would be great if everyone could be offered it as an option for first line treatment. Surely if this works the cost outweighs the benefit as the person is not likely to need further treatment. Unfortunately cost seems to stop a lot…. is there similar data on the other irts? I have tried to look but data I find is a couple of years old. If someone could point me in the direction I’d appreciate it (or maybe the data just isn’t therr, but don’t know why it wouldn’t be).. thanks for all your work

  4. More good news!

    Any chance to produce a similar CDW curve for cladribine? Failing a head to head, it would give at least some sense whether effect is comparable…

    1. Sadly not as part of the trial. After the CLARITY extension study, the trial subjects were never followed up. The CLASSIC-MS study however suggests that a proportion of cladribine-treated will do as well.

  5. Thanks for this very interesting post. I have some questions :
    Why the curve in chart 1 does not flatten? If there is no other confounding factor this could indicate that the disease is still not cured and something is still going on.
    For point number 3 why the first alemtuzumab year after IFN has a different BPF with respect to year 1 in alemtuzumab only study?
    The results are anyway remarkable, unfortunately alemtuzumab is not given so often now 🙁

    1. Yes, every year a few more people have recurrent disease activity. The question is when will it flatten and how many treated people will never have any further disease activity.

      1. Is there a relationship between time since disease onset to treatment and likelihood of staying stable? How strong is it? Is there evidence of a window of opportunity?

  6. Brilliant. Fantastic. I am so happy my neurologist fought my insurance company and got them to pay for alemtuzumab.

    1. I’m so happy that I live in a country where treatment comes at no additional cost and alemtuzumab is accessible as first line therapy. Australia isn’t perfect but they are top of the list when it comes to DMT access!

      1. Interesting to note that New Zealand, right next door, is probably one of the worst countries in the world for access to DMTs. From what I understand the only high-efficacy DMT available there is natalizumab and only a tiny percentage of patients get it. Everyone else gets either no treatment or a CRAB drug. You’d think their medical establishments would be more in sync.

      2. I did not realise that was the case. I suspect the problem is Pharmac not listing the drug for reimbursement. I could be wrong though.

      3. So the experiment has been set in motion to see where people are in x number of years progression wise

  7. What does this study say about someone 20 years out from diagnosis? Too late to switch to this drug and see disability improvement?
    What about with primary progressive MS?

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