This Is MS Multiple Sclerosis Community: Knowledge & Support

Found this artical regarding high neurtralizing antibodies blocking the effect of interferons. My neuro tested me for this after 6 months of use of Betaseron when my 6 month MRI showed break through lesions. My blood test came back very high so he switched my medicine. I found this article because I am battling my insurance company to approve IVIg since I cannot take the interferons and I am allergic to copaxone. Just thought I would share this with everyone just in case others are in a similar situation as I am.


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javaneen

This is interesting. I had never heard before that there is a marker for interferon-beta activity.

Several journal articles have reported that Betaseron (Ifn-B1b) is more antigenic than either Avonex or Rebif (Ifn-B1a). This is partly due to the fact that Ifn-B1b is produced in bacteria cells. Ifn-B is a normally glycosylated protein. This means that when our cells produce it they attached sugar groups to it. Bacteria do not glycosylate proteins. As a result, Ifn-B1b produced in bacteria will look more like a foreign protein to the immune system and will be more likely to elicit neutralizing antibodies (NAB). The journal article below shows that with patients on Ifn-B1b and with high levels of NAB, a short wash-out period eliminated the NAB and they did not return after switching over to Ifn-B1a.

I hope that this is helpful for you, NHE



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 said...



Thanks for the info NHE. Can you tell me what it means by wash-out period? My doctor didn't seem to think switching to the other interferons would do anything to protect me therefore he switched me to once monthly IV steroid and IVIg. So far it seems to be working fine except getting the insurance company to cover the IVIg.

Thanks again for your help!

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javaneen

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In this study, the wash-out period was 3 months with no Betaseron usage. After this time period, the NAB levels dropped to zero. The patients were then switched to Avonex. The NAB levels were detectable but only at trace levels and were certainly not statistically significant. Here's the data plot from the full paper. I was not able to find a pdf version.






No problem. I'm happy to share what I can.

NHE