Persistent neutralizing antibodies to Ifn-B can worsen MS

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Persistent neutralizing antibodies to Ifn-B can worsen MS

Postby NHE » Mon Feb 22, 2010 3:07 am

Clinical Effect of Neutralizing Antibodies to Interferon Beta That Persist Long After Cessation of Therapy for Multiple Sclerosis.
Arch Neurol. 2010 Feb 8.
    OBJECTIVES: To confirm that neutralizing antibodies (NAb) to interferon beta can persist after therapy withdrawal and to evaluate whether persisting NAb are associated with a worse clinical disease course in multiple sclerosis (MS). DESIGN: Retrospective study. SETTING: Tertiary referral center in the Netherlands.Patients A total of 71 patients with relapsing-remitting multiple sclerosis treated with interferon beta in the past. MAIN OUTCOME MEASURES: Persisting NAb after therapy withdrawal were tested using the cytopathic effect assay. Patients with and without persisting NAb were compared on several outcomes: the change in annualized relapse rate from prior to interferon beta treatment initiation to after cessation of treatment, time to sustained disability on the Kurtzke Expanded Disability Status Scale, and the use of disease-modifying treatments after cessation of treatment with interferon beta. RESULTS: Seventeen of 71 patients (24%) tested NAb positive after a median interval of 25 months (interquartile range, 10-51 months) after interferon beta treatment cessation. Eleven of these 17 patients (15%) were high-titer NAb positive (>150 10-fold reduction units per mL). Persisting NAb were associated with an increase in the annualized relapse rate (P = .04) and a reduction in time to reach a sustained Expanded Disability Status Scale score of 6.0, ie, the need for unilateral assistance to walk 100 m (P = .02). Moreover, NAb-positive patients were treated with second-line therapy significantly more often, especially mitoxantrone (P = .006). CONCLUSION: Anti-interferon beta NAb can persist after interferon beta treatment withdrawal and are associated with overt clinical disease activity. This is made apparent by an increase in relapse rate and faster disability progression and is supported by the observed need for more aggressive therapy after interferon beta treatment cessation. Prospective studies are warranted to confirm these results.
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Re: Persistent neutralizing antibodies to Ifn-B can worsen M

Postby euphoniaa » Mon Feb 22, 2010 12:10 pm

NHE wrote: CONCLUSION: Anti-interferon beta NAb can persist after interferon beta treatment withdrawal and are associated with overt clinical disease activity. This is made apparent by an increase in relapse rate and faster disability progression and is supported by the observed need for more aggressive therapy after interferon beta treatment cessation. Prospective studies are warranted to confirm these results.


Thanks for the info, NHE. I guess that, despite the opinions of those who have seriously tried to bully me into taking MS meds by saying, "At least they can't hurt you!!" my suspicions are confirmed.
:( -
Dx'd with MS & HNPP (hereditary peripheral neuropathy) 7/03 but must have had MS for 30 yrs before that. I've never taken meds for MS except 1 yr experiment on LDN. (I found diet, exercise, sleep, humor, music help me the most.)
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Re: Persistent neutralizing antibodies to Ifn-B can worsen M

Postby NHE » Tue Feb 23, 2010 12:28 am

euphoniaa wrote:Thanks for the info, NHE. I guess that, despite the opinions of those who have seriously tried to bully me into taking MS meds by saying, "At least they can't hurt you!!" my suspicions are confirmed.
:( -


For further information, Betaseron has the greatest tendency to elicit neutralizing antibodies. This is due to its being made in bacteria cells. Interferon-beta is a normally glycosylated protein. This means that the natural interferon-beta in our bodies has sugar groups attached to it. These sugar groups can have an important roll in cell signalling. Bacteria don't glycosylate proteins. Therefore, interferon-beta produced in them, i.e., Betaseron, is more likely to be seen as a foreign protein and elicit an antibody response.

In contrast, both Avonex and Rebif are produced in mammalian cells. As such, they will be glycosylated and will be less likely to be seen as a foreign protein and thus less likely to elicit an antibody response.

In one study, patients with high titers of neutralizing antibodies to interferon-beta, Betaseron, were given Avonex after a 3 month wash-out period. The high levels of neutralizing antibodies did not return.
http://www.thisisms.com/ftopicp-69479.html#69479

The presence of persistent neutralizing antibodies was in a small percentage of the patients in the above study. The abstract did not mention which type of interferon-beta they were taking. I suspect that the persistent neutralizing antibodies worsen MS since they will be blocking the affects of the natural interferon-beta in the patients even after the drug has been stopped.

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