This Is MS Multiple Sclerosis Knowledge & Support Community

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:

... 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.

more to come, napay

This might be the study on which your neuro is basing the suggestion of copaxone and novantrone. This study was presented at last years AAN meeting.

FYI, and apologies to Arron for recommending going outside of ThisIsMS, but if anybody is really stuck on digging up information about MS therapies, I suggest looking at the Braintalk forums (see link below). In particular one user, XO, seems to have every study ever conducted on an MS therapy at his fingertips (that's where the info below came from) -- and even more amazing, he seems to understand what they're saying in all of those studies too.



5 Year Retrospective Study of the Use of Mitoxantrone and Glatiramer Acetate Combination in Patients with Very Active Relapsing Remitting Multiple Sclerosis

Jason Ramtahal, Anu Jacob, Kumar Das, Mike Boggild, Liverpool, United Kingdom

OBJECTIVE: To examine the safety and effectiveness of Mitoxantrone and Glatiramer Acetate used in combination in patients with RRMS.

DESIGN/METHODS: For twenty-seven (27) patients with early active RRMS received sequential treatment with MX / GA from October 1999 – September 2004 (60 months). Treatments were overlapped for 3-7 months in the first 10 patients, to cover one or two pulses of Mx. A standardised protocol was used for the remaining 17 patients who had an overlap period of 5 months.

Patients were followed up using 6 monthly EDSS and Annual Relapse Rate as outcome measures and adverse events for safety profile. In 9 of the first 10 patients contrast enhanced MRI brain has been recently undertaken.

RESULTS: No unanticipated adverse effects were experienced with this novel combination. Therapy related acute leukaemia (TRAL) occurred in one patient who developed acute promyelocytic leukaemia seven months after stopping MX.

The leukaemia is in remission after treatment and the patient remains relapse free to date. One patient stopped GA after 11 months due to recurrent erythematous injection site reactions. This patient has remained relapse free, off all treatment, for a further 20 months.

Only seven relapses have occurred after initiation of treatment, six occurring while on Mx alone and one occurring 4 months after initiation of GA. At most recent follow-up EDSS was stable or improved in all patients and no patients have progressed clinically on continued follow-up which now extends to a mean of 33 months (range 10-60).

MRIs were undertaken in 9 out of the first ten patients at a mean of 42 months from initiation of treatment. There has been a substantial reduction in T2 lesion load compared to (non-standardised) pre-treatment scans. More importantly no enhancing lesions were identified on current imaging.

CONCLUSIONS: Clinical outcomes in this series of patients with very active RRMS and high risk of early disability are encouraging, with no unanticipated side effects from this novel drug combination. We believe the results may reflect a synergistic effect of this combination. GA appears a safe and effective option for continuing disease modification in those patients with RRMS who have received MX.

http://brain.hastypastry.net/forums/sho ... t=copaxone

Dignan, no worries! Those are great resources for this issue.

MRIs were undertaken in 9 out of the first ten patients at a mean of 42 months from initiation of treatment. There has been a substantial reduction in T2 lesion load compared to (non-standardised) pre-treatment scans. More importantly no enhancing lesions were identified on current imaging.

In view of the previous thread questioning MRI accuracy, I wonder how much credibility can be given to results obtained using MRIs?

Harry

Dignan's post mentioned Mike Boggild a UK neurologist based in Liverpool. Whenever I've seen posts about him on other sites his patients always rate him very highly. Here is the transcript of a presentation he gave in 2004 about combination tratements and he covers the various types of MS.

Ian

http://www.mssociety.org.uk/document.rm?id=77