More long-term alemtuzumab data


Do you want your brain to age well? The choice may be yours. #MSBlog #MSResearch

“In response to a discussion yesterday around the open-label alemtuzumab data from Cambridge I am re-posting the 5-year extension data from the phase 2 Alemtuzumab trial. As you can see MSers treated with Alemtuzumab do a lot better than those treated with interferon over 5 years. As always this comes with a price, namely the risk of secondary autoimmunity.”

“A delegate at the Top Seminars meeting in Sorrento confronted me with the argument that the FDA used when they turned down Alemtuzumab in the US, that there is no evidence alemtuzumab is better than Rebif in drug-naive MSers. You may recall that there was not statistically significant difference between those with sustained progression on the CARE-MS 1 trial. I said that is fine if you are only prepared to look at the tip of the iceberg and even then alemtuzumab was superior to Rebif in relapse reduction. However, when you dive under the surface and look at end-organ damage you will see that the rate of brain volume loss in year 2 was 0.25% on alemtuzumab and 0.5% on Rebif (slide 16 below).  Please remember that normal people lose between  0.1% and 0.4% of their brain volume per year after the age of 35.”

“Which drug, alemtuzumab or interferon-beta, is preventing end-organ damage? Which drug will keep your brain healthy for old age? People always see what they want to see in the data.”

“The natural conclusion of moving the therapeutic goal posts in MS to preventing end-organ damage is that you need to get on to the most effective DMTs as soon as possible in the course of the disease. I have tried to illustrate this in slides 50 to 56 below; only early highly-effective treatments can protect your brain sufficiently to give you a chance in old age.

Coles AJ, et al. Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 Clinical Trial. Neurology. 2012 Apr 3;78(14):1069-78.

OBJECTIVE: To report the long-term safety and efficacy results from CAMMS223 comparing alemtuzumab with interferon β-1a in early, active relapsing-remitting multiple sclerosis (RRMS). What are the long-term effects of alemtuzumab treatment, received 36 to 48 months previously, on relapse and disability in early, active RRMS? This study provides evidence of the effectiveness of alemtuzumab in reducing the relapse rate and accumulation of disability compared with interferon β-1a (IFNβ-1a) through extended follow-up (up to 60 months from baseline).

METHODS: Of 334 MSers originally randomized, 198 participated in the extension phase (151 [68%] alemtuzumab and 47 [42%] IFNβ-1a). Disability, relapses, and safety were assessed as in the original study period. Efficacy outcomes were analyzed from baseline of the original trial period to 60 months. Safety data extended beyond 60 months.

RESULTS: Over 5 years, alemtuzumab lowered the risk of sustained accumulation of disability by 72% and the rate of relapse by 69% compared with IFNβ-1a (both p < 0.0001). The annualized relapse rate from baseline to month 60 was 0.11 for alemtuzumab and 0.35 for IFNβ-1a. Complete safety follow-up reflected 988 and 376 person-years for alemtuzumab and IFNβ-1a patients, respectively. Serious infections were seen in 7% of alemtuzumab patients and 3% of IFNβ-1a patients, and thyroid disorders were seen in 30% of alemtuzumab patients vs 4% of IFNβ-1a patients. Immune thrombocytopenia (autoimmune attack of platelets) occurred in 3% of alemtuzumab patients and 0.9% of IFNβ-1a patients during the initial study period; no additional events were reported during the extension phase. One alemtuzumab-treated MSer developed Goodpasture disease 39 months after the second annual cycle of alemtuzumab.

CONCLUSIONS: Through extended follow-up, alemtuzumab remained significantly more efficacious than IFNβ-1a, with a safety profile consistent with previous reports.

CoI: Multiple

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.


  • Re " People always see what they want to see in the data."

    Are you not also guilty of this, Prof G? The jury is still highly sceptical of alemtuzamab's efficacy.

    • Re: "Are you not also guilty of this, Prof G? The jury is still highly sceptical of alemtuzamab's efficacy."

      Which jury? The FDA? Alemtuzumab has licenses in most markets; I suspect the FDA will recapitulate and give it a license in the US as well. I sincerely hope so for MSers living in the US. We all have a worldview and the diffusion of any innovation takes time. I have tried to explain it in this post:

      You also need to be aware that unless Genzyme, and we the community, sort out the secondary autoimmunity then Alemtuzmab will have a very brief time in the sun. The anti-CD20 therapies may prove to be as effective as alemtuzumab with a better side effect profile; the first anti-CD20 therapy may on the market as soon as 2016. I would like to reiterate that the early highly-effective treatment strategy, to prevent end-organ damage, is not about specific agents, it is about a treatment philosophy. You can get there via many routes.

    • Prof G, my neurologist says that natalizumab is just as effective as alemtuzamab, though, he doubts either is curative A second neurologist in presence agreed with that premise. All this crosswire information is confusing me.

    • Natalizumab is as effective at stopping relapses as alemtuzumab. The differences are the way that you take the agents one every month for ever or the other one a year for two years. The other is the side effect profiles. We know that if you stop natilizumab and do not switch to another drug then relapses occur with high frequency so it is clearly not a cure but a sticky plaster. For alemtuzumab you get NEDA in about 50% of people is this a cure I don't honestly know.

      We will need to wait until people die before we can really see what is happening to their brains, but as far as I know this thankfully has not happened.

      If you start Alemtuzumab and Natiluzimab too late, it is not a cure and disease worsens, Is the rate of worsening changed is not clear.

      How quick is quick to start again we don't know the precise answer, we know time is brain so the earlier you start effective treatment the better.

  • Prof G – I already have an under-active thyroid (and possibly Hashimoto) – if I were to take Alem what would you think happen – the thyroid getting even worse or a secondary autoimmunity would develop in another organ (which could that be?). Thanks

    • Re: "… already have an under-active thyroid (and possibly Hashimoto)…"

      If you have hypothyroidism then you already have end-organ thyroid disease and need thyroid replacement therapy. Alemtuzumab is unlikely to make any difference to your thyroid gland. However, you will still be at risk of the other autoimmune complications of the drug and would need to be monitored. What we don't know is whether, or not, you would be at increased risk of another autoimmune disease because you already have hypothyroidism.

    • Prof G- Thank you.

      You mention the 'other autoimmune complications of the drug' – what would the other complications be?

      Any data on that?

      Still, I tend to think that I might risk taking Alem – I don't have much time left to wait.

    • There has been ITP which is a platelet disease and Good pasteurs syndrome, which is a kidney disease and others

    • Looks like most of the autoimmunities emerged after the second pulse of the alemz. Just wondering, what is the rationale behind giving every person at least two pulses?


    • They say occurrence is 5/87 in 12 months, 13/87 in 24 months and the same again in 36 months from the first exposure.
      But why they give everyone at least two courses?
      Also I have r read somewhere that there was a group of SPMSers in the very first trial, who had given Campath only once for 5 days фnd never again. Did they have the same rate of autoimmunities? I can't find the paper shame for me. 🙁 Would be grateful if you got the link or answer. Thanks Prof Mouse.

    • Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis.Coles AJ, Wing M, Smith S, Coraddu F, Greer S, Taylor C, Weetman A, Hale G, Chatterjee VK, Waldmann H, Compston A.Lancet. 1999 Nov 13;354(9191):1691-5.

      In this study it was a third in the trials it was about a third also

    • As to drug dosing why are MS taken forever when a pulse therapy can work? Cash to the company and selling product… Good example would be anti-CD20 data which suggests that it can be an induction therapy, but why would a certain company waste time doing a trial on subcutaneous verse intra venous injection if they were not planning a repeated injection?

  • I'll share my Alemtuzumab experience. Had my first infusions 8 years ago and my second 7 years ago. No relapses since my first infusion (I was diagnosed with quite aggressive MS and Rebif had little effect i.e. bad relapses when on it). I've had regular MRIs and no activity or new lesions – last was MRI was two months ago. The thyroid condition was picked up by the excellent monitoring and I now take thyroid replacement – 1 small tablet a day. I work fulltime and am fairly active (for a 50 year old). Best decision I made. Dr Coles and his team are excellent. Alemtuzumab prevented me from accumulating any further disability (edss is stable). Still hoping for a repair therapy in the next 5 years. I know of two other men who have had the same experience. A therapy which should be considered following discussion with your neuro and

  • "There was a significant slowing in brain atrophy on alemtuzumab vs. IFNβ-1a ; brain volume change -1.5% IFNβ-1a vs -0.8% alemtuzumab."

    Clearly, the brain atrophy rates are all over the map. If these measurments are not performed on the same equipment by the same blinded evaluators as well as the same methods, the results can be thrown in the garbage. Short term dehydration is a known factor that causes brain atrophy on MRI measurements. This seems to be more of a marketing campaign.

    • Re: "Clearly, the brain atrophy rates are all over the map.."

      Not true; this is group data done in a randomised trial and analysed at one MRI centre. It is pretty robust data hence the highly significant p-values. What you are referring to is individual scans done serially. These criticisms are not relevant to group data as randomization and the power (number of subjects) gets rid of the variability. This has nothing to do with marketing; brain atrophy is a integrator of end-organ damage and alemtuzumab is only one of several DMTs that impacts on this outcome; the others are fingolimod, natalizumab and BMT.

      You are also referring to data over 2 years. Most of us in the field use year 2 data and beyond. This gets rid of the pseudo-atrophy that occurs in year 1. The following post goes into that in more detail:

    • Anon Monday May 26,10:02am,

      are you the same anon that consistently complains about the alemtuzumab data on this site?

      I don't see concerted anonymously posted negative comments about other drugs on this site (though flavour of the year on here is alemtuzumab).

      If you are the same person, I wonder if you could enlighten us as to your background – are you a person with MS, a person with an interest in neurology, or drug company employee?

      I'm posting anonymously as it's not currently in my interests to leave an online trail of comments relating to this unfortunately stigmatising disease.

      I don't disagree with scepticism at all, but some of the persistent anon comments on here make me think they're from the same person, and their framing makes me question the motives behind them.

  • AnonymousMonday, May 26, 2014 3:02:00 pm,

    Yes, I'm a person with MS, but I'm probably the least vocal here with concerns about the way alemtuzumab is being pushed on this site. My major concern is that Giovannoni keeps changing the bar of what this drug is supposed to do. First it was a touted as a "highly effective" therapy that is going to halt disease if treated early, but it looks like there is no statistical difference between the compared interferon as far as the primary endpoint. Now Giovannoni is touting that this drug is far superior to the other drugs as far as atrophy rates, but again was this measured in a legitimate way, instead of just "trust me, it
    works. I'm not blinded but my results are valid". The fact of the matter is using atrophy reduction as the most beneficial aspect of this drug is shakey at best based on the data collected so far.

    If you really want to see if this drug has an effect an atrophy, you need to conduct it in a legitimate way such as Dr Khan has demonstrated:

    If alemtuzumab halts brain atrophy, this would be great. If you want to have a convincing argument, you are going to have to try harder.

    So what's your beef, AnonymousMonday, May 26, 2014 3:02:00 pm?

    • In the CARE-MS 1 trial alemtuzumab was statistically significant on one of the primary outcomes, relapse rate. There was a trend on disability progression. In the CARE-MS 2 trial alemtuzumab was superior to Rebif on both outcomes. Alemtuzumab was also superior to Rebif on all the secondary outcomes. You are being disingenuous to claim otherwise. Atrophy measurements were done blinded and according to a strict trial protocol; the results are therefore robust. Alemtuzumab is superior to Rebif. Professor Giovannoni right to shift the goal posts and focus on brain atrophy; in long-term studies brain atrophy correlates very well with clinical outcomes. Therefore, it is only natural to want to prevent brain atrophy as a treatment outcome in MS.

      I have a conflict in that I participated in the CARE-MS 2 trial.

    • I agree with anon 4:13. Also I think it discourteous of anon 11:59 to talk about Giovannoni. Give him his prefix of Prof, or even Prof G if it's too much to type. If I thought that's just the way you talk about everyone I wouldn't be bothered, but you manage to give Dr. Khan his title. I don't expect you to agree with Prof G, and healthy debate is always useful, but it makes me less willing to look at anon 11.59's arguments if I think there's a touch of malice there.

  • Approve new treatments for MS. Approve alemtuzumab as a choice for MS patients because it is safe and effective.

    Multiple Sclerosis (MS) is a progressive disorder impacting the central nervous system (CNS). Given the severity of the disorder and the fact that there is no known cure, it is critical for physicians to have additional options for treating their patients. This petition requests the expedited approval for innovative new treatments for MS. Specifically, we ask that MS patients get to choose whether or not to take alemtuzumab because it is a safe and effective treatment option for some people suffering from MS. Existing therapies are not meeting the needs of current patients. These patients do not want to wait for either future therapies or the completion of additional trials for alemtuzumab.

    Alemtuzumab should be approved so MS doctors and their patients have a new treatment choice.

    I want to let you know about a new petition I created on We the People, a new feature on, and ask for your support. Will you add your name to mine? If this petition gets 100,000 signatures by August 29, 2014, the White House will review it and respond. We the People allows anyone to create and sign petitions asking the Obama Administration to take action on a range of issues. If a petition gets enough support, the Obama Administration will issue an official response.

    You can view and sign the petition here:

By Prof G



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