This Is MS Multiple Sclerosis Community: Knowledge & Support

Periodically, discussions arise regarding the danger and prevelance of NABs (neutralizing antibodies)for those patients who use the interferons. The drug companies usually have a tendancy to minimize the concern for NAbs, stating they don't normally effect very many patients. I've also read that some patients on these drugs don't get their NAB levels tested and their docs have never mentioned them.
This study in Switzerland followed patients for 4 years and discovered the problem could be much larger than we are lead to believe.

Harry

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Neurology. 2005 Jul 12;65(1):48-55. Related Articles, Links


Interferon beta-1a in MS: results following development of neutralizing antibodies in PRISMS.

Francis GS, Rice GP, Alsop JC; PRISMS Study Group.

Serono International, Geneva, Switzerland. gordon.francis@gmail.com

BACKGROUND: Debate continues concerning the relevance of neutralizing antibody (NAb) development on the efficacy of interferon (IFN) therapy in patients with multiple sclerosis (MS). The PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study of subcutaneous IFNbeta-1a showed significant benefit on all efficacy outcomes with no significant impact from NAb development on relapses at 2 years. The 2-year extension permitted longer observation following NAb development. METHODS: Exploratory post-hoc analyses of pharmacodynamic response and clinical and MRI outcomes were performed on data from 368 patients with relapsing MS treated with IFN from study start, based on NAb status. RESULTS: Persistent NAbs, above 20 NU/mL, were present in 14% of the 44-microg three times weekly (TIW) and 24% of the 22-microg TIW group over 4 years. NAb development was associated with reduced pharmacodynamic marker induction at 1 year. Over the entire 4 years of study, relapse and disability measures were similar between NAb+ and NAb- patients. However, once NAbs developed, significant differences were noted between NAb+ and NAb- groups, particularly on MRI and relapse measures. The presence of binding antibodies alone did not affect outcome. CONCLUSION: Neutralizing antibody development in interferon-treated patients is correlated with reduced efficacy and is a potential cause for renewed disease activity.

Just came across another study that recommends all patients who have started on the interferons be tested for NABs.

Harry

Neurology. 2005 Jul 12;65(1):33-9. Epub 2005 May 11. Related Articles, Links


Appearance and disappearance of neutralizing antibodies during interferon-beta therapy.

Sorensen PS, Koch-Henriksen N, Ross C, Clemmesen KM, Bendtzen K; Danish Multiple Sclerosis Study Group.

Copenhagen MS Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark. pss@rh.dk

BACKGROUND: Neutralizing antibodies (NABs) occur frequently in patients receiving interferon (IFN)-beta for multiple sclerosis (MS), but it is unclear whether occurrence of NABs is predictive for the persistence of NABs during continued IFN-beta therapy. METHODS: The authors used an antiviral neutralization bioassay to measure NABs blindly from 6 months up to 78 months in patients with MS who were followed for at least 24 months during treatment with IFN-beta. Patients were classified into three groups: 1) persistently NAB-negative patients, defined as patients without any positive samples at any time; 2) definitely NAB-positive patients, defined as patients who had at least two consecutive positive samples; and 3) patients with fluctuating NAB-positive and NAB-negative samples. RESULTS: A total of 455 patients were included in the study. Overall, 52.3% of the patients were persistently NAB-negative, 40.9% became definitely NAB-positive, and the remaining 6.8% were fluctuating. More patients treated with IFN-beta-1a (Avonex) remained NAB-negative (p < 0.0001), whereas there was no difference between IFN-beta-1b (Betaferon) and IFN-beta-1a (Rebif). Patients who have remained NAB-negative during the first 24 months of therapy rarely developed NABs. On the contrary, the majority of patients, who had been NAB-positive from 12 through 30 months after start of therapy, remained NAB-positive. CONCLUSIONS: NABs should be measured in all patients treated with IFN-beta. If patients have been persistently NAB-negative for 24 months, measurements can be discontinued. Patients who have been NAB-positive for a period of 18 months or more usually remain NAB-positive for a long time.