A Novel Bioassay for the Determination of Neutralizing Antibodies to IFNβ1b

Püngor, E.; Files, James G.; Gabe, Jeffrey D.; Linh, Trần Mỹ; Foley, Wayne; Gray, Julia L.; Nelson, Jim; Nestaas, Eirik; Taylor, Jerry; Grossberg, Sidney E.

doi:10.1089/jir.1998.18.1025

Cited by 99 publications

(48 citation statements)

References 9 publications

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“…The detected neutralizing activity was not characterized further by the presence of immunoglobulin in our study. As non-IgG-mediated neutralizing activity is known to occur in very few samples [14], if none from patients treated with IFN-b-1b [18], we referred as NAb + any serum where some neutralizing activity was found. However, one cannot exclude the fact that in our low titred samples, other components from the drug manufacture may have contributed in determining the antagonizing effect to IFN-b-1b.…”

Section: Discussionmentioning

confidence: 99%

“…Neutralizing activity detected in our samples was not characterized further as immunoglobulin (Ig)-mediated. However, as in previous work performed using this assay, non-Ig-mediated neutralizing activity contributed in very few samples [14] for this study, we referred as NAb + any serum where some neutralizing activity was found.…”

Section: Neutralizing Antibodiesmentioning

confidence: 99%

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A case study on the effect of neutralizing antibodies to interferon beta 1b in multiple sclerosis patients followed for 3 years with monthly imaging

Chiu

Ehrmantraut

Richert

et al. 2007

Clinical and Experimental Immunology

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Section: Discussionmentioning

confidence: 99%

Section: Neutralizing Antibodiesmentioning

confidence: 99%

A case study on the effect of neutralizing antibodies to interferon beta 1b in multiple sclerosis patients followed for 3 years with monthly imaging

Chiu

Ehrmantraut

Richert

et al. 2007

Clinical and Experimental Immunology

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“…Anti-IFNβ neutralizing antibody titers were measured in duplicate using the MxA protein production neutralization assay [5,16]. A serum sample with a NAb titer ≥ 20 NU/mL was considered to be positive and NAb positive status was defined by two consecutive NAbpositive titers.…”

Section: ■ Measurement Of Neutralizing Antibodiesmentioning

confidence: 99%

The OPTimization of Interferon for MS Study: 375 μg interferon beta-1b in suboptimal responders

et al. 2008

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We aimed to evaluate the safety and MRI efficacy of interferon beta-1b (IFNbeta-1b) 375 microg (subcutaneously [sc] every other day [eod]) in relapsing-remitting multiple sclerosis (RRMS) patients with a suboptimal response to IFNbeta-1b 250 microg, i.e., with MRI activity or relapses. The OPTimization of Interferon for MS (OPTIMS) study was a prospective multicenter randomized phase 2 trial comprising a 6-month run-in phase (to identify suboptimal responders) and a 6-month randomized phase of open-label clinical and blinded MRI follow-up. During run-in all patients were treated with IFNbeta-1b 250 microg sc eod; during the study phase suboptimal treatment responders were randomized either to IFNbeta-1b 250 or 375 microg sc eod. Primary outcome was the proportion of patients without MRI activity during study Months 9-12 according to the intention-to-treat principle. 216 RRMS patients entered the study: 83 suboptimal responders were identified and randomized, 7 refused to continue treatment, 76 were included in the analysis. More patients treated with 375 microg had no MRI activity at Months 9-12 (30/36 vs.16/40; relative risk, 0.28; 95 % confidence interval, 0.08-0.47; p = 0.0001). Sensitivity analysis ("worst case scenario") confirmed the results. No new or unexpected adverse events were observed, but there was a trend towards more withdrawals in the 375 microg group. Increasing the dose of IFNbeta-1b from 250 microg to 375 microg is a successful strategy for reducing subclinical signs of disease activity in RRMS patients. Further studies are needed to show whether this dose may also improve clinical efficacy.

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“…The most common assay utilises the antiviral effect of IFN β and, more recently, the ability of IFN β to induce the MxA protein [10]. The former is the current method recommended by the World Health Organisation (WHO) [11], and is based on the measurement of the virus-induced cytopathic effect -the so-called CPE assay.…”

Section: Nab Assaysmentioning

confidence: 99%

Optimising MS disease-modifying therapies: antibodies in perspective

Giovannoni

2004

J Neurol

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A proportion of people with multiple sclerosis (MS) treated with interferon (IFN) a develop neutralising anti-IFN beta antibodies (NABs). The immunogenicity of the available commercial compounds relates to the genetic structure of the IFN beta molecule, its mode of production, glycosylation status, aggregate formation, commercial formulation, potency, dose, frequency and, possibly, route of administration. At present, it is not possible to predict who will develop NABs usually appear within the first 2 years of starting therapy. In patients treated with IFN beta in whom NABs persist for a significant period of time, their presence is associated with a reduction in both the biological effects and clinical efficacy. Approximately one third of NAB-positive patients with a titre > 20 NU/mL will revert to NAB-negative status with long-term follow-up. The persistence of NABs appears to be linked to the type of IFN beta treatment as well as the titre of antibodies. The overall efficacy of IFN beta and, hence, of any biological disease-modifying treatment (DMT) would be substantially improved if the development of NABs could be prevented or reversed. Although the overall efficacy of IFN beta in MS is relatively modest, the efficacy in individuals who remain NAB-negative is considerably better than in those who become persistently NAB-positive. One could argue that when comparing the 'true' clinical efficacy of different IFN beta products, the comparisons should be limited to the cohorts that remain NAB-negative. As a corollary, the therapeutic efficacy of IFN beta could be maximised if patients who tolerate higher-dose preparations could be prevented from developing persistent NABs. Strategies employed to prevent or reverse the development of NABs with other biological compounds (e. g. insulin, factor VIII, IFN beta, recombinant human erythropoietin) include improvements in the manufacturing process, immunosuppression, induction of tolerance and deimmunisation, and these should be considered in relation to biological DMT therapy as part of future clinical studies.

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A Novel Bioassay for the Determination of Neutralizing Antibodies to IFNβ1b

Cited by 99 publications

References 9 publications

A case study on the effect of neutralizing antibodies to interferon beta 1b in multiple sclerosis patients followed for 3 years with monthly imaging

A case study on the effect of neutralizing antibodies to interferon beta 1b in multiple sclerosis patients followed for 3 years with monthly imaging

The OPTimization of Interferon for MS Study: 375 μg interferon beta-1b in suboptimal responders

Optimising MS disease-modifying therapies: antibodies in perspective

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