Friday, 8 March 2013

Research: alemtuzumab allows eye sight to improve

#MSBlog: Is it unrealistic to expect an improvement in your condition with early aggressive treatment? 


BACKGROUND: Alemtuzumab is a monoclonal antibody directed against CD52 that depletes T and B lymphocytes. 

OBJECTIVE: To evaluate the treatment effect of alemtuzumab on low-contrast vision in relapsing-remitting MSers. 

METHODS: This was a pre-defined exploratory analysis within a randomized, rater-blinded trial (CAMMS223) that was run at 49 academic medical centers in the US and in Europe. MSers with untreated, early, RRMS (McDonald, n = 334) were randomized 1:1:1 to subcutaneous interferon beta-1a (IFNB-1a), or alemtuzumab 12 mg or 24 mg. Visual contrast sensitivity was measured for each eye at baseline and quarterly, with Pelli-Robson charts. 

RESULTS: The eyes of MSers in the pooled alemtuzumab group (versus IFNB-1a) had a greater than 2-fold higher rate of both 3-month and 6-month sustained visual improvement, of at least 0.3 log units (2 triplets, 6 letters) (At 3 months the hazard ratio (HR) = 2.26; CI = 1.19 to 4.31; P = 0.013; and at 6 months the HR = 2.44; CI =1.16 to 5.15; P = 0.019), and they had a lower risk of 3- and 6-month sustained worsening of at least 0.15 log units (1 triplet, 3 letters) (At 3 months the HR = 0.58; CI = 0.38 to 0.89; P = 0.012; and at 6 months HR = 0.55; CI=0.35 to 0.87; P = 0.010). Over the 36-month study period, the eyes of MSers in the pooled alemtuzumab group improved in mean contrast sensitivity to a greater extent than those in the IFNB-1a group (0.080 log units versus 0.038 log units; P = 0.0102). 

CONCLUSIONS: Alemtuzumab was associated with a greater chance of improved contrast sensitivity in MSers with RRMS and may delay the worsening of visual function. Contrast sensitivity testing was sensitive to treatment effects, even within an active comparator study design. These results support the validity of low-contrast vision testing as a clinical outcome in MS trials. 

CoI: please note I have multiple conflicts of interest in relation to alemtuzumab and natalizumab as well as other aggressive therapies (cladribine, ocrelizumab, etc.)


"Another clinical outcome that improves post-alemtuzumab. Who says MSers shouldn't expect an improvement with more aggressive therapies. Why is this study important? It is important because the visual outcome measure used is objective. With these and other results in relation to alemtuzumab and natalizumab (it has similar data) I wonder why people question my affinity for early aggressive treatments. Not only does it prevent the accumulation of disability, but a significant number of MSers actually improve with therapy."

"The outstanding qustion with alemtuzumab is the one that will only be answered with extended follow-up. Does it cure some MSers of MS?"
Other posts of interest in relation to the latter point:

12 Feb 2013
#MSBlog: Defining an MS cure. "I have been having several recent discussions with colleagues about whether or not we can cure MS. I think we can, but we need to know what a cure means to do this. We used the opportunity ...
14 Feb 2013
Is there a cure for corporate crime in the drug industry? #MSBlog Pharma behaving badly; when will they learn? We need them to clean up their act! Yet another Pharma bashing Editorial: Courtney Davis. Is there a cure for ...
20 Nov 2012
Research: Antigen-coated beads the New (Old) Cure of the Week. Daniel R Getts, Aaron J Martin, Derrick P McCarthy, Rachael L Terry, Zoe N Hunter, Woon Teck Yap, Meghann Teague Getts, Michael Pleiss, Xunrong Luo, ...
12 Oct 2012
I would say it is half the cure or maybe a third as I will explain. The other half has already been tried in MS and it is safe. If this half is safe, which appears to be the case, you put the two halves together and relapsing MS is ...

01 Feb 2012
The Charcot Project-Towards a Cure for MS. THE CHARCOT PROJECT- TOWARDS A CURE FOR MS. Last weekend at the Research Day Prof Gold (Prof G Down Under) from Team G aired his new vision for the treatment of ...
02 Jun 2011
As usual the stem cell issue is over hyped and clearly creates unrealistic expectations. As scientists we need to manage expectations; not create unrealistic ones. In MS we will not know if we have a cure until we have ...
06 Apr 2012
This is an updated post from the 7th March 2010. I was at a meeting on optic neuritis in central London yesterday (5th April 2012) and we got onto the usual discussion/debate about early aggressive treatment vs. watchful ...
23 Sep 2011
MouseDoctor says 50% reduction IS NOT A CURE, this is bad reporting and over-hyping again creating false expectations... so lets look at the story. This is from a publication. Noorbakhsh F, Ellestad KK, Maingat F, Warren KG ...

12 comments:

  1. So what? Alem suppressed the inflammation quicker and the optic nerves had more time to heal themselves. This is no proof that it did something to the cause of damage of contrast sensitivity.

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    1. Predictable response there VV. If alemtuzumab can positively affect neural recovery (as it seems to in this study)that is to be celebrated not dismissed with carping comments.

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    2. I agree with VV in this matter, though I am no fan of his. I do get the sense that Prof G very much champions drugs he has actively consulted on but I get the sense that he may be inflated the miracles he claims they can perform. If alemtuzumab and natalizumab are so brilliant then they will also have an affect on progressive MS, but they don't. If alemtuzumab and natalizumab work so well then NICE would've been jumping through hoops of fire to give them to us in order to minimise disability claims and maximise employment contributions through taxes, but NICE isn't convinced.

      I have no faith in what's being said. Prof G last winter said that he didn't believe that DMTs are actually able to prevent progression because none of the DMTs impact on those mechanisms eroding nerve cells.

      Until a drug can fix progressive damage then it's all hot air. It's like someone saying eat more bread and you'll stave off disability. DMTs and MS progression are disconnected.

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    3. Firstly your impression is completely wrong no matter that Prof G has consulted on pretty much every drug for MS there is!
      Secondly, it is still too early to say whether the new DMTs such as alemtuzumab will have a long term effect on progression but at this stage the omens are very favourable, which may be due that they are much more effective at suppressing relapses than the old first line DMTs.
      However, it is important to remember that once progression has taken hold, purely anti-inflammatory treatments will be much less effective if at all, which is why we need neuroprotectants as an adjunct and neuroprotectants probably need to be a first line therapy for primary progressive MS.

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  2. Anon 3.40 is wrong I believe. Just because a drug does not work on prog. MS it doesn't follow that it is no good. It may prevent RRMSers ever becoming progressive, which is surely to be hoped for. Then maybe all the research will go into prog MS. Nataluzimab is licensed through NICE as tysabri, although maybe consideration should be given to making it available earlier in the course of MS. Alemtuzumab can't be licensed yet as the EMA hasn't given its ruling on its safety and efficacy following phase 3 results. Then NICE will have to consider it and its cost. Unfortunately NICE does not seem to take in the long term financial effects of disability.

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    1. Unfortunately, NICE is not that well informed re disability progression. They base their decisions on the EDSS and we know how flawed that measure is in early MS. They also base their modeling on direct medical costs only; i.e. how much is this going to cost the NHS. The don't take indirect or societal costs into account. This however will change in the future; I am confident that this will give induction therapies, such as alemtuzumab a better chance.

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  3. This drug is dangerous and has killed

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    1. Agreed. All the drugs mentioned are very dangerous and have devastating side-effects. The majority of clinicians and health policy people are dubious of both alemtuzumab and natalizumab. They will never become first line early treatments. Relapses and progression are entirely different things. DMTs only work on the former and NICE knows that.

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    2. Don't forget how dangerous MS is; you simply have to read this blog to appreciate how bad MS can be! Choose your poison; MS vs. the drugs that treat it? I know what camp I am in. The sooner we MSers get access to Alemtuzumab the better.

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  4. The problem is that some people that have been treated with alemtuzumab and natalizumab have gone on to develop SPMS. These drugs aren't a cure, it seems.

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    1. It's a question of treating early enough. If you treat well down the line when the train is well on the way to progession then the outlook is not as good as if you treted much earlier. Data now coming out particularly where alemtuzumab is concerned suggests that those treated very early are doing much better. Of course these patients will have to be followed up for many years to see if progression really has been halted but so far it is very encouraging.

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  5. Anon 8:26 My understanding is that none of the long-time MS researchers think of any current drug as a broad cure for anyone. But many say that some drugs are cures for some people. I think that's what Prof. G says above. That's why from time to time researchers talk about the promise of personalized medicine.

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