Neutralizing Antibodies to Interferon β-1b are not Associated with Disease Worsening in Multiple Sclerosis

Goodin, D. S.; Hurwitz, Barrie J.; Noronha, Avertano

doi:10.1177/147323000703500202

Cited by 30 publications

(31 citation statements)

References 39 publications

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“…Fortunately, expanding knowledge of interferon-regulated genes is still in process [2,22,35,41]. The clinical significance of differential appearance of neutralizing antibodies directed against rIFN-β in specificity and quantity are under scrutiny [23]. Reder at al.…”

Section: ■ Kinetics and Effects Of Ifn-β Therapy In Msmentioning

confidence: 98%

Monitoring of multiple sclerosis immunotherapy

2008

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Applying microarray technology to identify new diagnostic and prognostic markers in peripheral blood cells (PBC) after therapeutic intervention opens great perspectives regarding patient subclassification. Three recombinant products of the pleiotropic agent interferon beta (rIFN-beta) are available for disease modifying therapy of relapsing remitting multiple sclerosis (RRMS), a complex inflammatory autoimmune disease that targets the central nervous system. They differ according to formulation, route of administration and dosage regimens. The currently, only partially understood mechanism of action of injected rIFN-beta into human organisms needs provision with accessory key molecules; in addition, the significance of established clinical IFN-beta response criteria that distinguish responding from non-responding patients remain unclear.With respect to these major questions, we discuss promising candidates on the gene transcription level, attained from scientific MS literature that included a longitudinal aspect. Reviewed studies were in part carried out with distinct gene interrogating platforms (GeneArrays; RT-PCR), settings (in vitro; ex vivo), and study designs (drug formulations and regimen; inclusion criteria and clinical endpoints), hampering meaningful meta-analysis. Nevertheless, PBC from therapy-naïve MS patients, rIFN-beta treated MS patients, and healthy controls served to characterize facets of both the disease and its treatment. Hence, the field of MS transcriptomics in immunomodulatory therapy is (by far) not adequately understood and should be embedded into systems biology disciplines, yielding multi-layer analyses that deliver timely identification of MS subjects who will profit from applied rIFN-beta therapy.

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Section: ■ Kinetics and Effects Of Ifn-β Therapy In Msmentioning

confidence: 98%

Monitoring of multiple sclerosis immunotherapy

2008

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“…10,14,16,25,28 However, in a recent survey of 6,698 patients with MS on IFN␤-1b therapy, 54 the seroprevalence of NAbs (defined as a single positive test with a titer Ն20 NU/mL) in two clinically deteriorating cohorts (21% in North America and 28% in Europe) was significantly lower (p Ͻ 10…”

Section: Are Nabs To Ifn␤ Associated With An Increase In the Activitymentioning

confidence: 99%

Neutralizing antibodies to interferon beta: Assessment of their clinical and radiographic impact: An evidence report: [RETIRED]

et al. 2007

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Abstract-The clinical and radiologic impact of developing neutralizing antibodies (NAbs) to interferon beta (IFN␤) while on this therapy for multiple sclerosis (MS) is assessed. On the basis of Class II and III evidence, it is concluded that treatment of patients with MS with IFN␤ (Avonex, Betaseron, or Rebif) is associated with the production of NAbs (Level A). NAbs in the serum are probably associated with a reduction in the radiographic and clinical effectiveness of IFN␤ treatment (Level B). In addition, the rate of NAb production is probably less with IFN␤-1a treatment than with IFN␤-1b treatment, although the magnitude and persistence of this difference is difficult to determine (Level B). Finally, it is probable that there is a difference in seroprevalence due to variability in the dose of IFN␤ injected or in the frequency or route of its administration (Level B). Regardless of the explanation, it seems clear that IFN␤-1a (as it is currently formulated for IM injection) is less immunogenic than the current IFN␤ preparations (either IFN␤-1a or IFN␤-1b) given multiple times per week subcutaneously (Level A). However, because NAbs disappear in some patients even with continued IFN␤ treatment (especially in patients with low titers), the persistence of this difference is difficult to determine (Level B). Although the finding of sustained high-titer NAbs (Ͼ100 to 200 NU/mL) is associated with a reduction in the therapeutic effects of IFN␤ on radiographic and clinical measures of MS disease activity, there is insufficient information on the utilization of NAb testing to provide specific recommendations regarding when to test, which test to use, how many tests are necessary, or which cutoff titer to apply (Level U).

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“…Although it has been shown in numerous trials that patients who develop antibodies against IFNb have higher relapse rates, increased number of lesions detected by MRI, and higher rates of disease progression [Francis et al 2005;Kappos et al 2005], the significance of antiIFNb ADAs remains controversial [Goodin et al 2007]. This is due to the difficulty in establishing a temporal correlation between the presence of antiIFNb ADAs and the loss of drug efficacy due to the variable nature of the disease, the partial effectiveness of the drug, the delay between initiation of treatment and the detection of an effect of the drug on the course of the disease, and the difference in the immunogenicity of different IFNb products.…”

Section: Therapeutic Advances In Drug Safety 2 (3)mentioning

confidence: 99%

Immunogenicity and other problems associated with the use of biopharmaceuticals

Tovey¹,

Lallemand

2011

Therapeutic Advances in Drug Safety

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Biopharmaceuticals are used widely for the treatment of cancer, chronic viral hepatitis, inflammatory, and autoimmune diseases. Biopharmaceuticals such as interferons are well tolerated for the most part with the most common adverse events observed being 'flu-like' symptoms that resolve rapidly after initial treatment. Prolonged treatment is associated, however, with more serious adverse events including leucopenia, thrombocytopenia, and neuropsychiatric effects, which may necessitate dose reduction or even cessation of treatment in some patients. Recombinant growth factors, such as erythropoietin (EPO), granulocyte colony-stimulating factor, or granulocyte macrophage colony-stimulating factor, are for the most part well tolerated, although severe complications have been reported in patients with cancer or chronic kidney disease treated with EPO. Similarly, treatment of patients with cancer with high doses of interleukin-2 is associated with significant toxicity. Treatment of chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis, and Crohn's disease, with antitumor necrosis factor-alpha monoclonal antibodies is associated with an increased risk of granulomatous infections and, in particular, tuberculosis. The monoclonal antibody, natalizumab, that targets alpha4 integrins is effective in the treatment of multiple sclerosis but is associated with the activation of JC virus and development of progressive multifocal leukoencephalopathy. Repeated administration of recombinant proteins can cause a break in immune tolerance in some patients resulting in the production of a polyclonal antibody response that can adversely affect pharmacokinetics and clinical response. In addition, neutralizing antibodies that cross react with nonredundant essential proteins such as EPO can cause severe autoimmune reactions.

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Neutralizing Antibodies to Interferon β-1b are not Associated with Disease Worsening in Multiple Sclerosis

Cited by 30 publications

References 39 publications

Monitoring of multiple sclerosis immunotherapy

Monitoring of multiple sclerosis immunotherapy

Neutralizing antibodies to interferon beta: Assessment of their clinical and radiographic impact: An evidence report: [RETIRED]

Immunogenicity and other problems associated with the use of biopharmaceuticals

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