Secondary progression conversion is low after alemtuzumab

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This is a paper that may be of interest to people who have taken alemtuzumab in the past few years.

It looks at the conversion rate to SPMS.

Sadly I think an error has been made from relegating alemtuzmab from being the the easiest drug to prescribe first line to being a drug that has been thrown on the maggot-pile by the regulators to be essentially third line. The risk is yours not theirs.

Proportion of alemtuzumab-treated patients converting from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis over 6 years.Horáková D, Boster A, Bertolotto A, Freedman MS, Firmino I, Cavalier SJ, Jacobs AK, Thangavelu K, Daizadeh N, Poole EM, Baker DP, Margolin DH, Ziemssen T; CARE-MS I, CARE-MS II, and CAMMS03409 Investigators.Mult Scler J Exp Transl Clin. 2020 Dec 18;6(4):2055217320972137

Background: Few data exist concerning conversion to secondary progressive MS in patients treated with disease-modifying therapies.

Objective: Determine the proportion of alemtuzumab-treated patients converting from relapsing-remitting to secondary progressive MS during the CARE-MS core and extension studies.

Methods: Patients (N = 811) were analyzed post hoc for secondary progressive MS conversion. Optimal conversion definition: Expanded Disability Status Scale (EDSS) score ≥4, pyramidal functional system score ≥2, and confirmed progression over ≥3 months including confirmation within the functional system leading to progression, independent of relapse.

Results: Over 6.2 years median follow-up, 20 alemtuzumab-treated patients converted (Kaplan-Meier estimate, 2.7%; 95% confidence interval, 1.8%-4.2%). Sensitivity analysis accounting for dropouts showed similar results (3%), as did analyses using alternative definitions with different EDSS thresholds and/or confirmation periods, and analysis of core study subcutaneous interferon beta-1a-treated patients who received alemtuzumab in the extension. Patients converting to secondary progressive MS were older, and had higher EDSS scores and greater brain lesion volumes at baseline, but did not need additional alemtuzumab or other therapies.

Conclusions: The 6-year conversion rate to secondary progressive MS was low for alemtuzumab-treated patients, supporting further study of the role alemtuzumab may play in reducing risk of secondary progression.ClinicalTrials.gov identifiers: NCT00530348NCT00548405NCT00930553

This suggests that the regulators are going to limit the benefit that has to offer by using it late.

However there is an experiment to be done to see how quick you need to get onto high efficacy DMT.

The trials were beta interferon or alemtuzumab and then after 2 years everyone goes on alemtuzumab

MS CARE I = treatment naive treatment within 2 years of onset (a) Alemtuzumab = 1 year (b) Beta interferon for 2 years then alemtuzumab for 1 year

CARE_MS II trial = treatment in within 4 years in people taking beta interferon.a) Beta intereferon for 2 years then Alemtuzumab = 1 year (b) Beta interferon for 2 years then beta interferon for 2 years then alemtuzumab for 1 year

so you have alemtumab, beta interferon 2 year then alemtuzumab and beta interferon 4 years and then alemtuzumab then ask when secondary progression occurred.

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MouseDoctor

16 comments

    • The problem is that that MS is being labelled as a chronic disease and as such they you to relapse. Like ProfG and MD said, its slowly moving from reduction of relapses to NEDA and now the big focus will be brain atrophy + NEDA.

  • So the conversion rate to SP status of these patients on Alemtuzumab was ~ 2.7% over 6 yrs.

    The authors say the rate is low.

    Low compared to what ?

  • “I want to be your sledgehammer
    Why don’t you call my name
    Oh let me be your sledgehammer”

    “I want to be your sledgehammer
    Why don’t you call my name
    You’d better call the sledgehammer
    Put your mind at rest”

    🙂

    Nice post

  • Thanks for this post MD – potentially good news for those of us who’ve received Alem, even if I am one of the Olds!

    Talking of which I’ve been Googling today searching for info concerning my sore and inflamed toes.
    I have mild eczema and have previously had it on my feet…🤔
    Most likely chilblains, though haven’t had those since before the days of central healing – showing my age! …🤔 Side effects of Alem…🤔
    So, I’ve barely typed in the search when up comes COVID TOES 😳

    Perhaps ProfG might kindly let me know (thereby others who’ve received treatment) whether any correlation should be drawn with the potential side effects of Alem.

    Actually any advice that assists with distinguishing between Covid more unusual symptoms and MS/DMT symptoms/side effects will be helpful, especially when the reports of COVID TOES state you may well be a symptomatic otherwise.

  • Secondary autoimmunity? Humanization part I, II, III…….?

    Agree on efficacy; however, there is a zero probability the regulators are going to approve Alem plus a anti-CD20 to reduce the risk of secondary autoimmunity. I asked my Neuro at a major university hospital and was told NO WAY! Too much liability.

    Sad, as it could have significantly helped my MS disease course. My only option left is Clad.

    • And not a bad option

      The regulators wont approve combinations, virtually everybody taking medicines have some form of polypharmacy (two or more drugs), these combinations are selectd by your neuro and not the regulators. The key issue to know is how they may interact e.g does one drug cause or block the breakdown of others and that may be very important when the the drug it stops working is a contraceptive pill for example.

      The neuro said no way and liability because the manufacturers have no done this, had the manufacturrs done this when we went to pitch the idea to them, they would have had the answer long before ocrelizumab came around and alemtuzumab would have been used earlier in the states and then the cardiac issues may not have been a new liability. With enough data there would have been adoption if it worked. Will anyone risk supplementing alemtuzumab with regulatory cells…I suspect not. I suspect there was a window of opportunity until 2017 (ocrelizumab appeared) and now it has largely been shut unless someone from the manufactureres has a risky urge. I doubt it as alemtuzumab mark II was shelved years ago.

      • Dam shame, given alemtuzumab seems equal to aHsct in efficacy…… without the additional risk associated with the cocktail of chemo they use in aHsct.

        Also happy with my option 😉

  • How does that compare to untreated group after 6.5 years? And to other dmt such as tender, Ocrelizumab etc. This study leads to more questions then answers. Completely pointless without comparator.

      • Hi Prof G. Your preaching to the converted. My question was much more abou5 how much more effective is Alemtuzumab than other DMTs and Placebo. Also what happens at 20 years? Etc. I just want to know how much more quality of life does it add! Not HSCt fan until it becomes safe, perhaps use crisp instead of radiation. Also there are people who won’t wear mask or take the COVID vacine without educational background to justify their stances. I guess natural selection is at work.

    • Pointless without a comparator, but it sets a bench mark….The atrophy data is miles better than with ocrelizumab and cladribine…I would argue that the key difference is starting with active drug early but you need to do the study

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