QUESTION ABOUT NABS.

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QUESTION ABOUT NABS.

Postby HUTTO » Tue Aug 22, 2006 12:43 pm

what are they trying to say. that the intreferon could be bad for the people using it? i know its a dumb question but im new to the lingo and research. thanks for your help..
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Postby Axiom » Tue Aug 22, 2006 1:15 pm

Yes I think it's pretty universally accepted that if a patient develops NABs to interferon treatment then that treatment will be less effective and other options may need to be explored (from Teva's perspective Copaxone would be the obvious choice)

I guess I'm one of the cynical sort since I think this study is very much about what is best for Teva and only secondarily about what is best for the MS patient.

But I will concede that bringing attention to the problem of NABs developing and the need for more routine testing is a good thing.
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Postby amelia » Tue Aug 22, 2006 1:31 pm

When you develop NABS, the interferons are worthless. Or that was the case with Gary. He was on Betaseron and did okay with it. But after about 2 years, he went into a series of attacks. When he stopped the Betaseron altogether, he went into high gear with attacks. Bad ones every 4-6 weeks.
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Question about NABs

Postby NHE » Wed Aug 23, 2006 2:15 am

Amelia wrote:When you develop NABS, the interferons are worthless. Or that was the case with Gary. He was on Betaseron and did okay with it. But after about 2 years, he went into a series of attacks. When he stopped the Betaseron altogether, he went into high gear with attacks. Bad ones every 4-6 weeks.

Perhaps I've misunderstood what you've written, but it seems that there may have been some positive effect from the interferon-beta as the attacks were worse after stopping it. Have you considered another interferon? For further discussion, Betaseron appears to have the highest tendency to produce neutralizing antibodies out of the three different interferon-beta preparations. I've discussed the reasons for this in an earlier thread and the principle factor is likely to be due to the fact that Betaseron is produced in bacteria. Here's a link to a research article which discusses the difference in neutralizing antibody response between the different interferon-betas.
NABs developed during the first three months of treatment and continued to develop until month 18. Over 18 months of treatment, the risk of being persistent NAB+ was 31% for Betaferon, 15% for Rebif, and 2% for Avonex (Betaferon versus Avonex, p = 0.001; Betaferon versus Rebif, p = 0.19; Rebif versus Avonex, p = 0.04). In all patients with one or more NAB+ samples, the risk of becoming NAB+ was 38% for Betaferon, 18% for Rebif, and 7% for Avonex (Betaferon versus Avonex, p = 0.0007; Betaferon versus Rebif, p = 0.10; Rebif versus Avonex, p = 0.07). At month 18, the prevalence of persistent NAB+ patients was 31.6% for Betaferon, 18.7% for Rebif, and 4% for Avonex.

Given this information, you may wish to consult with your doctor to see if Avonex might be an option in Gary's case. While there have been several reports in the PubMed database of cross reactivity in neutralizing antibodies, I have read one paper (which I apologize for not being able to locate in PubMed) which demonstrated that patients with neutralizing antibodies to Betaseron produce no neutralizing antibodies upon switching to Avonex after a months abstention from Betaseron. I know that I have this paper on file, but I'm away from my journal database right now and will post it later once I return.

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Last edited by NHE on Wed Aug 30, 2006 1:17 pm, edited 1 time in total.
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Postby amelia » Wed Aug 23, 2006 6:39 am

No, he had a rough time with the Betaseron. He went on Copaxon for several years with better results and NO side effects. With Copaxon he did not have to have the blood work as much. He is now off of Copaxon and awaiting his approval for Tysabri. His attacks did not worsen in strength after the Betaseron, just in numbers, but with the same intesity. While on Betaseron, his attacks put him flat on his back, paralyzed from the upper waist down. :?
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How about "new" research?

Postby Chris55 » Wed Aug 23, 2006 6:46 am

I don't understand why they would conduct a very large, expensive trial just to better their chances of having their drug used. The CRAB drugs "were" great for what they did--it is time to MOVE FORWARD TO BETTER DRUGS! Why not spend this money on new research? And I know I am a cynic!
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Postby bromley » Wed Aug 23, 2006 7:35 am

Chris,

I think of the four CRAB manufacturers as a cartel. Each is producing a drug with pretty much the same level of efficacy - c.30% reduction in relapses. Each of the four maunfacturers has done pretty well for a relatively long period of time. The demand for these drugs has increased as (i) they are being prescribed at the first attack and (ii) some are being precribed when the patient moves to the SP stage.

This cosy and profitable set-up is at risk from drugs such as Tysabri (much better efficacy but with higher risks) and drugs in the pipeline such as FTY720 (and other oral MS drugs). The four know their time is up. But they won't go down fighting - there are various combos being used or in trial e.g. mitoxantrone and copaxone, betaferon and copaxone, copaxone and minocycline, beta-interferon and doxycycline. Also in trial are double strength beta-interferon and new formula Rebif.

The NAB study is another which is probably aimed at extending the lives of the DMDs. Once the new drugs are available, the CRAB manufacturers will claim that they have reduced the impact of NABs. It's interesting that Tysabri is only to be used if the patient does not do well on the current DMDs - can anyone really do well on a drug with an average of 30% efficacy? There have been a number of studies published showing the 'effectiveness' of the DMDs over the last 15ish years or the effectiveness at delaying the move from CIS to definite MS. The data from these various studies of the DMDs never disclose the real questions we are interested in i.e did the drug keep the patient from needing a wheelchair, keep the patient employed etc etc. All the publicity for the DMDs show users on racing bikes, competing in marathons etc but the data we see is about relapse or gd enhancing lesions.

So I think this study of NABs is a sign of desperation. If FTY720 makes it to market and shows that it is more effective and safe, then the DMDs will be dead in the water. Would anyone really continue self-injecting if there was a better oral drug? I'm guessing the Tysabri will also start eating up the market share of the DMDs as (hopefully) it delivers more benefits and more is known about the risks.

The CRAB drugs are the Model T Fords - a big breakthrough but have had their day.

Ian
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Postby amelia » Wed Aug 23, 2006 8:48 am

Ian,
Don't forget the irreversable liver damage that can come from the interfersons. They fuss about Tysabri with PML, but the C"RABs", leaving Copaxon out, only states under their breath that you could have some series liver damage, if not complete failure from using the interferons. I don't think many people go on living without a liver! Oh, and the ads with all those ACTIVE people? HA It rates up there with Fat people clothes on skinny models. (I can say that 'cause I am overweight!)
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Postby Ronnie » Wed Aug 23, 2006 9:49 am

Dear Amelia and Ian, and all the others:
Yeah, even in the NMSS publications when you turn the cover to the first page, there is someone hiking or riding a bike or competing in marathons or some such thing, and they always have some cheery slogan about one of the CRABs; which makes me feel like I must be an anomoly or at least genetically flawed! Everybody seems to do so WELL on every kind of therapy!

Until you read the actual articles.

I was on Betaseron for several years when I suddenly realized that I couldn't think straight, had terrible leg cramps at night, had another attack of ON, and lots of problems I hadn't had before. My neurologist changed me to Copaxone at that time, then I was on Novantrone, then Rebif, then Tysabri, then woops! Copaxone again, and now I am champing at the bit for Tysabri again.

I can think much better now, but still have problems with word retrieval, and there are some parts of my life which disappeared. Did you ever see "The Eternal Sunshine of the Spotless Mind"? Sometimes it feels like that.

It is good that they are investigating the NABs, for whatever their motivation may be, because it would be good if people didn't have to keep switching medications or suffer sudden onslaughts of heaploads of exacerbations with no warning!

That is what I think, for whatever it is worth (and like I say, sometimes I can't think straight, so I don't trust my judgement anymore),
Ronnie
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I know I read it somewhere

Postby notasperfectasyou » Thu Aug 24, 2006 9:50 am

I can't find it. But I had a journal article about NAB's that siad that they come and go and the appreance and disapperance of them was normal. I remember that the study showed that NAB's only effected folks on Rebif and BetaS and not Avonex.

BTW, we switched out to Copaxone a month ago and it's going well.The daily 5 minutes of stinging, is greatly preferred to the post-shot day slump with Avonex. napay
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Re: Question about NABs

Postby NHE » Wed Aug 30, 2006 1:14 pm

NHE wrote:I have read one paper (which I apologize for not being able to locate in PubMed) which demonstrated that patients with neutralizing antibodies to Betaseron produce no neutralizing antibodies upon switching to Avonex after a months abstention from Betaseron. I know that I have this paper on file, but I'm away from my journal database right now and will post it later once I return.

As promised, here's the paper I was referring to above.
    Interferon-beta (INF-beta) antibodies in interferon-beta1a- and interferon-beta1b-treated multiple sclerosis patients. Prevalence, kinetics, cross-reactivity, and factors enhancing interferon-beta immunogenicity in vivo.
    Eur Cytokine Netw. 2001 Mar;12(1):56-61.

    We analysed the role of dosage, route and frequency of administration of clinical grade interferon-beta (IFN-beta) preparations in inducing anti-IFN-beta antibodies (IFN-beta-Abs) in 5 groups of relapsing-remitting multiple sclerosis (RRMS) patients who were respectively treated as follows: 1) weekly intramuscular (i.m.) injections of 30 mg of recombinant IFN-beta1a (Avonex), 2) subcutis (s.c.) injections of 250 mg IFN-beta1b (Betaferon) every other day, 3) weekly i.m. injections of 250 mg IFN-beta1b (Betaferon), 4) s.c. injections of 22 mg of IFN-beta1a (Rebif) three times a week, and 5) i.m. injections of 22 mg of IFN-beta1a (Rebif) twice a week. IFN-beta-Abs were determined by ELISA. IFN-beta1b was more immunogenic than IFN-beta1a not only when administered s.c. every other day, but also when administered i.m. at a lower weekly dose; i.m. injection, however, significantly delayed the appearance, and induced lower serum levels of IFN-beta-Abs. In patients treated with s.c. IFN-beta1b, Ab levels peaked 3 to 9 months after therapy initiation, and then slowly, but progressively, declined to pre-therapy levels that in some patients were reached after three years. Patients treated with i.m. or s.c. IFN-beta1a only rarely developed IFN-beta-Abs, and then at very low titers. Overall, the i.m. weekly administration of IFN-beta1a was the less immunogenic treatment. In IFN-beta1b-treated patients, a wash-out period of two/three months was sufficient to bring the IFN-beta-Ab levels below the cut-off. Our findings suggest that the immunogenicity of IFN-beta1a is low, regardless of the route of administration and the dosage, while that of IFN-beta1b is high, and is significantly, but not completely reduced by i.m. administration. As IFN-beta-Abs are cross-reactive, a wash-out period is suggested when the preparation is changed from IFN-beta1b to IFN-beta1a in order to maintain the clinical benefits of the therapy.

NHE
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