Tuesday, 6 September 2016

ResearchSpeak: Interferon vs. Alemtuzumab

There is still life in the old dog; interferon-beta does better than expected. #ResearchSpeak #MSBlog

"Is there life in the old dog yet? The old dog being interferon-beta-1a. As you can see from the MRI paper below comparing the impact of alemtuzumab vs. interferon-beta-1a on MRI metrics of disease activity that alemtuzumab beats IFNbeta on average. What the study hides is responder vs. non-responder data. responders to interferon-beta do as well as MSers treated with alemtuzumab. If only we could select the responders up front then we wouldn't have to expose so many pwMS to the risks associated with alemtuzumab to derive the benefits."

"To be honest, I and others, were surprised at how well MSers did on interferon-beta-1a in both the CARE-MS 1&2 studies; they did much better than expected. The proportion of interferon-treated subjects who progressed in the CARE-MS 1 study was about half of what was expected. I suspect the MSers did so well because they were naive to  treatment and were enrolled very early in the disease course and most of the subjects randomised to Rebif in this study received the new formulation of the drug, which is almost certainly better than the old formulation. For one RNF (Rebif New Formulation) has a lower NAB rate when compared to the old formulation. Rebifers did not do as well in the CARE-MS 2 study as they had to be failing on an existing DMT to be eligible for the trial; in other words treatment failures, or 'suboptimal responders' found themselves being randomised back onto Rebif. In the CARE-MS 2, or non-naive , study the Rebif-treated subjects behaved as expected."

"One thing that is very impressive with alemtuzumab is its impact on end-organ damage, i.e. it 'normalises' or 'pseudo-normalises' brain volume loss, which doesn't happen on average with interferon-beta. Now that we are  treating-to-target and moving non-responders off interferons, and other platform therapies, sooner rather than later a large proportion of pwMS are choosing the safer option. Why take the risks of alemtuzumab if you don't have to? They hedge their bets and keep alemtuzumab in reserve for later. I have no problem with this strategy, but still worry that our biomarkers for monitroing MS are not good enough, which is why we are subjecting more and more of our patients to having lumbar punctures to measure CSF neurofilament levels to see how well they are doing, or not, despite being relapse and MRI-activity free. It is kind of a hedge against alemtuzumab first-line and keeping the more effective, riskier drugs, in reserve. All these arguments will become superfluous if we have a very high-efficacy frugal that was safe. Who wouldn't choose the latter? It all depends if the latter offered long-term remission or a potential cure or not.  It is only when you start discussing the scenarios and how they play out do you realise how complex the treatment landscape has become in MS. This is even before the first crop of drugs targeting progressive MS are launched."


Epub: Arnold et al. Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon β-1a in MS. Neurology. 2016 Sep 2. pii: 10.1212/WNL.0000000000003169.

Background: To describe detailed MRI results from 2 head-to-head phase III trials, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study I (CARE-MS I; NCT00530348) and Study II (CARE-MS II; NCT00548405), of alemtuzumab vs subcutaneous interferon β-1a (SC IFN-β-1a) in patients with active relapsing-remitting multiple sclerosis (RRMS).

METHODS: The impact of alemtuzumab 12 mg vs SC IFN-β-1a 44 μg on MRI measures was evaluated in patients with RRMS who were treatment-naive (CARE-MS I) or who had an inadequate response, defined as at least one relapse, to prior therapy (CARE-MS II).

RESULTS: Both treatments prevented T2-hyperintense lesion volume increases from baseline. Alemtuzumab was more effective than SC IFN-β-1a on most lesion-based endpoints in both studies (p < 0.05), including decreased risk of new/enlarging T2 lesions over 2 years and gadolinium-enhancing lesions at year 2. Reduced risk of new T1 lesions (p < 0.0001) and gadolinium-enhancing lesion conversion to T1-hypointense black holes (p = 0.0078) were observed with alemtuzumab vs SC IFN-β-1a in CARE-MS II. Alemtuzumab slowed brain volume loss over 2 years in CARE-MS I (p < 0.0001) and II (p = 0.012) vs SC IFN-β-1a.

CONCLUSIONS: Alemtuzumab demonstrated greater efficacy than SC IFN-β-1a on MRI endpoints in active RRMS. The superiority of alemtuzumab was more prominent during the second year of both studies. These findings complement the superior clinical efficacy of alemtuzumab over SC IFN-β-1a in RRMS.

CLINICALTRIALSGOV IDENTIFIER: NCT00530348 and NCT00548405.

CoI: multiple

9 comments:

  1. Replies
    1. All depends on which league you want to play in, or are forced to play in. My neurologist is not prepared to prescribe alemtuzumab because he feels it is too risky. The sad fact of life is that there is only room for 20 teams in the premiership.

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  2. Prof G,

    I had my first alememtuzumab infusion 10 years ago and my second infusion 9 years ago. My annual MRI shows no disease activity. I have experienced no relapses. My EDSS has remained unchanged at 3. Would there be any benefit in asking my neuro to check my neurofilament level/s or is this only available at your clinic? Thanks.

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    Replies
    1. Hi Anon, sorry I can't answer your question for you but I just wanted to say thank you for posting your background with alemtuzumab, because as a recent inductee to "Club MS" I really like reading stories from people who are years down the line and enjoying long-term remission. It makes it seem a little more real and achievable for me too. :)

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    2. Any secondary autoimmunity such as Grave's since your treatment?

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    3. Graves disease. Radio-active iodine treatment to kill off thyroid (no problem) and I take one tiny tablet once a day for the rest of my life. A good exchange compared to the disabling relapses before Alemtuzumab. My only regret is not getting the Alemtuzumab earlier. No relapes + stability = priceless. COI = none. JAMES - others I met during Alemtuzumab treatment have had a similar experience. Best wishes.

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    4. Thanks for that IRON. As you say a pretty reasonable trade off.
      Now if only we can achieve the same result without the development of secondary autoimmunities such as Graves. MD and DrK are on the case.
      All the best
      MD2

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  3. Shame for people who discover that they were not actually 'responders' after considerable time on interferon. So until true 'responders' can be identified from the start, it's a gamble. Given that the risks associated with Lemtrada are mitigated (& treatable) with monitoring and early detection, I'll hedge my bets with the treatment most likely to save my brain.

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  4. I'm only 8 months post-alemtuzumab, no relapses, or other side effects at this point. Today i feel like before diagnosis, I'm able to play rugby and surf like all that happened 1 year ago was a bad dream (onset + 2 relapses within 5 months). Sad thing is that at my 1 relapse I knew exactly what was going on as I had been studying neurology recently for a national exam, went straight to the Neuro ward, got an MRI and LP, (had 4 lesions on the spine and some more on the brain, including 1 on the posterior fossa) I knew I had a poor prognosis profile and wanted either alemtuzumab or a BMT frllom day 1 and got turned down, then relapsed twice in the next months and then I was cleared for alemtuzumab (on Spain its not 1 line). My advice is that if you want an aggressive treatment and your Neuro its not for it, switch, one can live with your own mistakes, but its harder to live with someone else's, I can't even blame him, his hands were and continue to be tied, I was mad for a while.

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