Friday, 5 September 2014

Alemtuzumab and Progressive MS..It doesn't stop it once it has started

Coles AJ, Wing MG, Molyneux P, Paolillo A, Davie CM, Hale G, Miller D, Waldmann H, Compston A.Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis.Ann Neurol. 1999 Sep;46(3):296-304.

The elective treatment of patients with multiple sclerosis, using a humanized anti-leukocyte (CD52) monoclonal antibody (Campath-1H), has illuminated mechanisms that underlie the clinical course of the disease. Twenty-seven patients were studied clinically and by magnetic resonance imaging (MRI) before and for 18 months after a single pulse of Campath-1H. The first dose of monoclonal antibody was associated with a transient rehearsal of previous symptoms caused by the release of mediators that impede conduction at previously demyelinated sites; this effect remained despite selective blockade of tumor necrosis factor-alpha. Disease activity persisted for several weeks after treatment but thereafter radiological markers of cerebral inflammation were suppressed for at least 18 months during which there were no new symptoms or signs. However, about half the patients experienced progressive disability and increasing brain atrophy, attributable on the basis of MRI spectroscopy to axonal degeneration, which correlated with the extent of cerebral inflammation in the pretreatment phase. These data support the formulation that inflammation and demyelination are responsible for relapses of multiple sclerosis; that inflammatory mediators, but not tumor necrosis factor-alpha, cause symptomatic reactivation of previously demyelinated lesions; and that axonal degeneration, conditioned by prior inflammation but proceeding despite its suppression, contributes to the progressive phase of disability. These results provide evidence supporting the emerging view that treatment in multiple sclerosis must be given early in the course, before the consequences of inflammation are irretrievably established.


A comment yesterday wondering what SPMSers wanting to try Alemtuzumab should do. 

I would the say the jury is not completely out on what exactly would happen, but what I think we can say is that it will not stop progressive MS. In the studies above the vast majority of MSers got worse and it may have not impact on progression at all.  As such I doubt NICE would consider it to be cost-effective without more supportive evidence. However, what is "active MS"?

So far current immunosuppressives have not had a major impact on progressive MS and so would alemtuzumab be any different? 

The question that has not been adequately addressed is whether Alemtuzumab could change the rate of progression. I suspect not, but would happily change that view if the ASCEND trial in progressive MS shows a positive effect. There large enough numbers of people are being studied to get an answer.

Again, I doubt that it will stop progression completely if started later in the disease course, once progression has taken hold, as there are a number of people using tysabri that I have seen who have progressed. However, will it change the trajectory. This can't be known until the data is seen. 

There is no doubt in my mind that inflammation is ongoing in progressive MS and if you are having progressive MS with gadolinium enhancing lesions this aspect would probably get cleared up with treatments like tysabri and alemtuzumab and fingolimod etc. Could enough alemtuzumab get into the brain to affect the inflammation that drives progressive MS...I am not sure.

I suspect quite a few progressive MSers without gadolinium-enhancing lesions will give this a try. Remember your old lesions can reactivate when you first get the drug. The more advanced MS the more lesions you probably have. Steroids may help solve this but be warned.  Are  you less likely to get autoimmunities...probably not...you will be seriously out of pocket and your progression may be unaffected. Those starting this type of treatment have most to gain if started early after diagnosis...when will it start to have limited effect... I don't know

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