Saturday, 30 July 2011

Alemtuzumab - risks of developing other autoimmune diseases

Study objectives: To define the rate, timing, and clinical risk factors for the development of autoimmune disease after alemtuzumab treatment in MS'ers.

"What is alemtuzumab? You may know the drug as Campath-1h. This is a powerful immuno-modulator that is given as a course of intravenous infusions. It depletes the immune system and allows it to recover. I refer to it as an immune system rebooter. Short of bone marrow transplantation it is probably the most effective MS disease-modifying therapy in late stage development."

"What is an autoimmune disease? Autoimmunity refers to a family of related diseases in which the body's immune system goes awry and attacks itself. For every organ system in the body there is an autoimmune disease. Please see Wikipedia's article on the subject for more information; autoimmunity"

Methods: The data on 248 MS'ers treated with alemtuzumab, with a median follow-up of 34.3 months (range 6.7-107.3), was analysed.
Results
  1. Novel autoimmune disease developed in 22.2%. 
  2. Thyroid autoimmune disease was the most frequent (15.7%). 
  3. A range of blood, kidney, and skin autoimmune disease were also observed as was the development of asymptomatic autoantibodies. 
  4. Autoimmune disease was seen from 2 weeks after initial treatment and was most frequent 12-18 months after first treatment. 
  5. No new cases of autoimmune disease were identified after 60 months after initial treatment. 
  6. The risk of autoimmune disease was not linked to the dose or interval of alemtuzumab treatments. 
  7. Established risk factors for autoimmune diseases including sex and age had no impact on autoimmune disease frequency. 
  8. In this study MS'ers with a family history of an autoimmune disease were 7.3x more likely to develop an autoimmune disease, compared to MS'ers without a family history. 
  9. MS'ers with a personal smoking history were 3x more likely to develop autoimmune disease, compared to non-smokers. 
Conclusions: Individual risk of autoimmune disease post-alemtuzumab is modified by smoking and family history, which should be incorporated into the counseling process prior to treatment. 


"This is a very useful study and allows us to assess the risk of developing autoimmunity after alemtuzumab therapy. Some MS'ers may find this risk too high and others may find the risk acceptable. The good news is that the risk falls off after 5 years. This will help us as it means we may not need to monitor for these complications beyond this time."

"More data on how bad smoking is for MS'ers; time to give up?"

"Are you prepared to take the risk?"

Conflicts of interest: multiple

Additional reading: autoimmunity, autoantibody, alemtuzumab

Please see other posts on this blog in relation to Alemtuzumab:

18 Jul 2011
"This was not a negative study; Alemtuzumab is still a very promising disease-modifying therapy! The patients in this trial were less active than previously therefore the trial lacked power to detect a difference in ...
12 Jul 2011
More on the Alemtuzumab trial. The previous post is simply the headline results; we need to wait for the full results that will be presented at the ECTRIMS/ACTRIMS meeting from the 19 – 22 October 2011, in Amsterdam, ...
11 Jul 2011
A press release on the headline results of the Alemtuzumab vs. Interferon-beta-1a trial: "Sanofi said Lemtrada worked better than an older drug, Rebif, in preventing relapses, as patients treated with Lemtrada were 55 ...
17 Jan 2011
Wow! Let's hope it is not too expensive for the NHS. Click here to read the press release!

Etc. Please use search term "alemtuzumab"

6 comments:

  1. "This is a very useful study and allows us to assess the risk of developing autoimmunity after alemtuzumab therapy...."

    As a recipient of Alemtuzumab I did develop an auto-immune disease (Graves' disease). However, I've never smoked and there is no history of thyroid diseases / other auto-immune disease in my family. So, as ever, assessing the risk is never straightforward.

    I much prefer an assessment based on the benefits - I was having disabling relapses and Alemtuzumab stopped them dead (5 years out). The auto-immune disease I got is treatable with tablets and radio-acive iodine (permanent solution).

    PS how does smoking increase the risk of getting MS or contribute to MS worsening?

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  2. First reaction: No, not prepared to take the risk, with a family history of various auto-immune diseases going back to at least great-great-grandparents (Before that we don't know).

    But after reading the previous comment I'm not so sure. It depends on what sort of diseases could develop and whether they are all treatable.
    For example, if there's a risk of getting Type 1 Diabetes then no amount of MS improvement benefit is worth it

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  3. Why/how does rebooting the immune system lead to new autoimmune disease?

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  4. Regarding risk - I saw enough of the risk (of MS) every time I spent time in the neuro's waiting room. EDSS scale sets out the risk nicely. There are some grim statistics for MS patients regarding retaining a job, remaining n a relationship, developing depression etc etc. Average life expectancy reduced by c.10 years. Anyone considering these higher risk treatments should also really reflect on the risks with MS. Unfortunately, a decision on whether to take a more effective treatment (which comes with more risks) has to be taken early in the course of MS (when disability may be minimal). Any decision should be very carefully thought through and discussed with your neuro.

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  5. Re: "Why/how does rebooting the immune system lead to new autoimmune disease?"

    The million dollar question. It may relate to a subset of cells call T regulatory cells that are responsible for keeping autoimmunity at bay. Another factor relates to one of the cytokines or immune messages that is very high in MS'ers who get autoimmune disease. Then there is the B cell theory. I beginning to realise that this will need a separate set of posts.

    More on this later ....

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  6. Re: “There are some grim statistics for MS patients regarding retaining a job, remaining in a relationship, developing depression etc etc.”

    • retaining a job: Got made redundant months after getting diagnosed with progressive MS. Never was able to find work as condition got worse.

    • remaining in a relationship: Got divorced at 31 years of age. Partner said it was too much for them to deal with.

    • developing depression: I’ve been down in the dumps but never depressed. One can always figure a way around these things.

    I was never given the choice of so-called “high risk” treatments as my MS is a special kind of disease and won’t respond to medicines. However, I was put on Mitoxantrone and for all the good it did me I might as well have not bothered.

    Progressive MS almost feels like game over, but I try not to think like that. I hope something good will come along soon enough to make it all seem worthwhile. If progressive MS ever becomes a treatable disease then there will be so many profoundly grateful individuals who I’m sure will go on to live their lives in a maximised way, taking full advantage of every opportunity that was beyond them previously.

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