Avonex v/s Copaxone in SPMS
Posted: Thu Apr 27, 2006 1:49 pm
I've been Googling all day. I'm not finding much. If you can point me in the right direction, I'd love to have some links. Our Neuro is recommending getting off Avonex and onto Copaxone and maybe adding Novantrone. Right now I'm mainly interested in trying to weigh Avonex v/s Copaxone. I'm not interested in side effects, the goal is walking. Problem is Secondary Progressive MS.
Here's what I've found so far:
1) Avonex is generally less agressive than Rebif and Betaseron. Glatiramer Acetate is generally less agressive than the Interferons.
2) Interferons can become less effective over time because of neutalizing antibodies. Copaxone is good to switch to if you have the NAB problem.
3) TEVA says Copaxone may protect from axonal injury, but I cannot find the original article anywhere to get the details.
I can't find the medical journal article that recommends copaxone in SPMS. I'd also like to know which cytokines both of these drugs act on. If you have links, I'd love to look. Thanks in advance! napay
Update 4/28/06
I followed up on the post about the 5 year study. It's from the 2005 conference so the info is not as new as I'd like it to be. I have some new info:
1) Copaxone double dose trials are looking positive. But this would be in the future if we got it.
2) I found a very expensive book at the bookstore and took some notes. Book is McAlpines Multiple Sclerosis.
The current thinking on INF {beta} is:
Inhibits INF {gamma} expression of MHC class II
Increases IL-10 and IL-4 and MRNA Levels
Decreases IL-12
Decreases TNF {alpha} and INF {gamma}
Suppresses Th1 and Upregulates IL-10
Enhanced Shedding of VCAM-1 from Endothelium
Decreases T cell Migration
Decreases integrin gene expression
Inhibits MRNA for MIP 1a RANTES and CCRS
Decreases IL-2 Stimulated secretion of MMP
Reduced MMP-a in PPMS
Enhanced TIMP-1 in RRMS
Reduced secretion of TNF {alpha} and IL-1
The current thinking on Glatiramer Acetate is:
Modulates T-cell activation and or proliferation
Competes for binding sites for MHC class II Antigens
May Modify Denderitic cell costimulation processes or act as weak /partial T-cell receptor agonist
Reduces proliferation of MBP reactive T cells
Activates both Th1 and Th2 cells
Increases ratio of anti-inflammatory (Th2) to proinflammatory (Th1) cytokines
Increases IL-10, IL-4 and IL-6 Production and Decreases IL-12 production
Increases then Decreases IFN {gamma} secretion with repeated antigen stimulation
Upregulates CD8+ T-cell responses
Induce regulatory Th2/3 cells that penetrate CNS and express anti inflamatory cytokines and neurotrophic factors in situ in animal models of MS
Induces TNF {alpha} and INF {gamma} Production
Enhances Production of Brain Derived Nerve Growth Factor
Reduces monocyte and antigen presenting cell function
I might have some errors in the IFN {beta} ones. I'm going to try to find the abstracts and link them. I wrote this all down on a small scrap of paper and I don't think the bookshop folks liked me referencing their expensive books. I bought McAlpine's Multiple Sclerosis and I've cleaned up the GA items (this is a fantastic book albeit expensive). So when I find abstracts for the above I will link them blue and make corrections. Of course I still have no idea what the merits are of this regimen change. napay
UPDATE 5/10/06
I think we're going with Copaxone/Novantrone. In large part because IFN {beta}'s don't have a very solid history in SPMS. I was able to access the articles for these two abstracts: Results from a 3-year controlled study and A combined analysis of the two trials . Basically, as I read them here's the statement that stands out the most (from the first one listed above:
Here's what I've found so far:
1) Avonex is generally less agressive than Rebif and Betaseron. Glatiramer Acetate is generally less agressive than the Interferons.
2) Interferons can become less effective over time because of neutalizing antibodies. Copaxone is good to switch to if you have the NAB problem.
3) TEVA says Copaxone may protect from axonal injury, but I cannot find the original article anywhere to get the details.
I can't find the medical journal article that recommends copaxone in SPMS. I'd also like to know which cytokines both of these drugs act on. If you have links, I'd love to look. Thanks in advance! napay
Update 4/28/06
I followed up on the post about the 5 year study. It's from the 2005 conference so the info is not as new as I'd like it to be. I have some new info:
1) Copaxone double dose trials are looking positive. But this would be in the future if we got it.
2) I found a very expensive book at the bookstore and took some notes. Book is McAlpines Multiple Sclerosis.
The current thinking on INF {beta} is:
Inhibits INF {gamma} expression of MHC class II
Increases IL-10 and IL-4 and MRNA Levels
Decreases IL-12
Decreases TNF {alpha} and INF {gamma}
Suppresses Th1 and Upregulates IL-10
Enhanced Shedding of VCAM-1 from Endothelium
Decreases T cell Migration
Decreases integrin gene expression
Inhibits MRNA for MIP 1a RANTES and CCRS
Decreases IL-2 Stimulated secretion of MMP
Reduced MMP-a in PPMS
Enhanced TIMP-1 in RRMS
Reduced secretion of TNF {alpha} and IL-1
The current thinking on Glatiramer Acetate is:
Modulates T-cell activation and or proliferation
Competes for binding sites for MHC class II Antigens
May Modify Denderitic cell costimulation processes or act as weak /partial T-cell receptor agonist
Reduces proliferation of MBP reactive T cells
Activates both Th1 and Th2 cells
Increases ratio of anti-inflammatory (Th2) to proinflammatory (Th1) cytokines
Increases IL-10, IL-4 and IL-6 Production and Decreases IL-12 production
Increases then Decreases IFN {gamma} secretion with repeated antigen stimulation
Upregulates CD8+ T-cell responses
Induce regulatory Th2/3 cells that penetrate CNS and express anti inflamatory cytokines and neurotrophic factors in situ in animal models of MS
Induces TNF {alpha} and INF {gamma} Production
Enhances Production of Brain Derived Nerve Growth Factor
Reduces monocyte and antigen presenting cell function
I might have some errors in the IFN {beta} ones. I'm going to try to find the abstracts and link them. I wrote this all down on a small scrap of paper and I don't think the bookshop folks liked me referencing their expensive books. I bought McAlpine's Multiple Sclerosis and I've cleaned up the GA items (this is a fantastic book albeit expensive). So when I find abstracts for the above I will link them blue and make corrections. Of course I still have no idea what the merits are of this regimen change. napay
UPDATE 5/10/06
I think we're going with Copaxone/Novantrone. In large part because IFN {beta}'s don't have a very solid history in SPMS. I was able to access the articles for these two abstracts: Results from a 3-year controlled study and A combined analysis of the two trials . Basically, as I read them here's the statement that stands out the most (from the first one listed above:
more to come, napay... leading to the conclusion that IFN{beta}-1b provides therapeutic benefit on disability progression only in those patients who remain in the inflammatory phase of their disease.