Interferon neutralizing antibodies

Neutralizing Antibodies Antibodies to beta interferons can form over time and reduce the clinical effect of beta interferons.40 The clinical effect of neutralizing antibodies is seen 18 to... 

Many issues surrounding neutralizing antibodies remain such as standardization of the neutralizing antibody assay, testing recommendations, and treatment recommendations for positive tests 41 Neutralizing antibodies may disappear even with continued treatment. Neutralizing antibodies exhibit cross-reactivity with the other beta interferons.41... 

Choosing Therapy There is no consensus on the best medication for initial therapy. Comparative beta interferon trials indicate better efficacy with more frequent and/or higher dosing.37 This consideration must be balanced with neutralizing antibody development and patient acceptance and tolerance. 

Hartung HP, Munschauer F, Schellekens H. Significance of neutralizing antibodies to interferon beta during treatment of multiple sclerosis expert opinions based on the Proceedings of an International Consensus Conference. Eur J Neurol 2005 12 588-601. 

Immunogenicity Nine percent of patients treated with peginterferon alfa-2a with or without ribavirin tablets developed binding antibodies to interferon alfa-2a, as assessed by an ELISA assay. The clinical and pathological significance of the appearance of serum neutralizing antibodies is unknown. 

Immunogenicity Approximately 2% of patients receiving peginterferon alfa-2b or interferon alfa-2b with or without ribavirin capsules developed low-titer (160 or less) neutralizing antibodies to peginterferon alfa-2b or interferon alfa-2b. 

Deisenhammer F, Schellekens H, Bertolotto A. Measurement of neutralizing antibodies to interferon beta in patients with multiple sclerosis. J Neurol. 2004 251(suppl 2) II31—1139. 

Recombinant aldesleukin-binding antibodies were detected in the half of 205 patients with metastatic cancer but there were neutralizing antibodies in only 7% (113). No significant difference in incidence was found between subcutaneous and continuous intravenous administration. In another study, none of the patients receiving aldesleukin alone developed neutralizing antibodies, whereas 18% of patients treated with aldesleukin and interferon alfa-2b had antibodies (114). Whatsoever, the clinical relevance of recombinant aldesleukin-neutralizing antibodies has not been accurately evaluated and a loss of response was apparently documented in only one patient (115). 

Both binding and neutralizing antibodies to interferon alfa can be detected in interferon alfa-treated patients, and the incidence or clinical significance of these antibodies is the subject of continuous controversy, which has been addressed in a number of studies or general reviews (SED-13, 1096) (SEDA-20, 330) (SEDA-21, 373) (156,323-325). 

Antonelli G, Current M, Turriziani O, Dianzani F. Neutralizing antibodies to interferon-alpha relative frequency in patients treated with different interferon preparations. J Infect Dis 1991 163(4) 882-5. 

Pastore G. Neutralizing antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection. Liver 1993 13(3) 146-50. 

Russo D, Candoni A, Zuffa E, Minisini R, Silvestri F, Fanin R, Zaja F, Marline Hi G, Tura S, Botta G, Baccarani M. Neutralizing anti-interferon-alpha antibodies and response to treatment in patients with Ph-f chronic myeloid leukaemia sequentially treated with recombinant (alpha 2a) and lymphoblastoid interferon-alpha. Br J Haematol 1996 94(2) 300-5. 

In multiple sclerosis, neutralizing antibodies to recombinant interferon beta occurred in 12-38% of patients treated for 2-3 years (3-5,70). There were no adverse consequences in patients who developed antibodies to interferon beta-la (4), but there was reduced therapeutic efficacy in terms of clinical relapse rate or magnetic resonance imaging in several patients who had neutralizing antibodies to interferon beta-lb (SEDA-20, 332) (5,71). 

The IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-lb experience during the first three years. Neurology 1996 47(4) 889-94. 

Deisenhammer F, Reindl M, Harvey J, Gasse T, Dilitz E, Berger T. Bioavailability of interferon beta lb in MS patients with and without neutralizing antibodies. Neurology 1999 52(6) 1239 3. 

Khan OA, Dhib-Jalbut SS. Neutralizing antibodies to interferon beta-la and interferon beta-lb in MS patients are cross-reactive. Neurology 1998 51(6) 1698-702. 

Rice GP, Paszner B, Oger J, Lesaux J, Paty D, Ebers G. The evolution of neutralizing antibodies in multiple sclerosis patients treated with interferon beta-lb. Neurology 1999 52(6) 1277-9. 

Fierlbeck G, Schreiner T. Incidence and chnical significance of therapy-induced neutralizing antibodies against interferon-beta. J Interferon Res 1994 14(4) 205-6. 

McKay F, Schibeci S, Heard R et al (2006) Analysis of neutralizing antibodies to therapeutic interferon-beta in multiple sclerosis patients a comparison of three methods in a large Australasian cohort. J Immunol Methods 310 20-29... 

If a patient taking interferon decompensates and has neutralizing antibodies in the blood, most practitioners will stop the medication. In this situation it is controversial whether to rechallenge the patient at a later date with interferon therapy. Many clinicians will only rechallenge with interferon therapy if the patient does not do well on other therapies. 

Bertolotto A. Neutralizing antibodies to interferon beta Implications for the management of multiple sclerosis. Curr Opin Neurol 2004 17 241-246. 

Giovannoni, G., Munschauer, F.E., and Deisenhammer, F. (2002) Neutralizing antibodies to interferon beta during the treatment of multiple sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry, 73, 465 469. 

Bertolotto, A., Sala, A., Caldano, M., Capobianco, M., Malucchi, S., Mametto, F., and Gilli, F. (2007) Development and validation of a real time PCR based bioassay for quantification of neutralizing antibodies against human interferon beta. Journal of... 

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