Neutralizing antibodies in interferon beta treated patients with multiple sclerosis: knowing what to do now

Menge, Til; Hartung, Hans‐Peter; Kieseier, Bernd C.

doi:10.1007/s00415-011-5941-0

Cited by 4 publications

(2 citation statements)

References 39 publications

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“…[13–17] In comparison, neutralizing antibodies occur in ∼2% to 6% of patients treated with Avonex, 12% to 28% in those treated with Rebif, and in 28% to 47% of patients on Betaferon. [18,19] Pharmacological forms of beta interferons differ in their immunogenicity; therefore, there is a different proportion of patients with elevated levels of antibodies for different formulations. [18,20] …”

Section: Discussionmentioning

confidence: 99%

The cross-reactivity of binding antibodies with different interferon beta formulations used as disease-modifying drugs in multiple sclerosis patients

et al. 2016

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Interferon beta (IFNb) preparations are commonly used as first-line therapy in relapsing-remitting multiple sclerosis (RRMS). They are, however, characterized by limited efficacy, partly due to the formation of anti-IFNb antibodies in patients.In this pilot study, we assessed with the ELISA method the presence of the binding antibodies (BAbs) against interferon beta after 2 years of therapy with subcutaneous interferon beta 1a (Rebif) in 49 RRMS patients. Antibody levels were established again within 1 year after treatment withdrawal. We used 3 interferons that are commercially available for MS therapy, namely Avonex (Biogen Idec Limited), Rebif (Merck Serono), and Betaferon (Bayer Pharma AG), as antigens.BAbs reacting with Rebif were found in 24.4% to 55% of patients, depending on the units of their expression. The levels of anti-Rebif antibodies remained high in 8 patients and in 4 patients they dropped significantly. Strong correlations were obtained in all assays (anti-Rebif-anti-Avonex, anti-Rebif-anti-Betaferon, and anti-Betaferon-anti-Avonex) and the existence of cross-reactivity in the formation of antibodies against all the tested formulations of interferon beta was confirmed. The levels of BAbs remain significant in the clinical context, and their assessment is the first choice screening; however, methods of BAbs evaluation can be crucial for further decisions. More studies are needed to confirm our results; specifically it would be of interest to evaluate methods of neutralizing antibodies identification, as we only assessed the binding antibodies. Nevertheless, our results support the concept that in interferon nonresponders, that are positive for binding antibodies, switching the therapy to alternative disease-modifying agent (for example glatiramer acetate, fingolimod, or natalizumab) is justified, whereas the switch to another interferon formulation will probably be of no benefit.

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Section: Discussionmentioning

confidence: 99%

The cross-reactivity of binding antibodies with different interferon beta formulations used as disease-modifying drugs in multiple sclerosis patients

et al. 2016

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“…The production of neutralizing antibodies in IFNbtreated MS patients is actually a cause of IFNb inefficacy. In this context, Menge et al[25] revised current knowledge on this topic in a commentary.…”

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confidence: 97%

Progress in multiple sclerosis research in the last year

Galimberti

Scarpini

2012

J Neurol

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Alemtuzumab: eine weitere Chance zur Therapie der Multiplen Sklerose

et al. 2011

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Alemtuzumab is a humanized monoclonal therapeutic antibody that targets the CD52 antigen which s expressed on most cells of the lymphoid lineage, exclusive of precursors. Alemtuzumab rapidly depletes CD52(+) cells from the peripheral blood. This depletion is long-lasting, and cells repopulate in a specific pattern with B cells and regulatory T cells peaking first. Alemtuzumab was examined for clinical utility in two open-labelled intervention trials in multiple sclerosis (MS). Because of very promising results its clinical efficacy was further explored in a clinical phase-II trial using s.c. interferon beta-1a as the active comparator. Severe or opportunistic infections were surprisingly rare given the long-term lymphopenia. However, up to 30% of patients developed some antibody-mediated autoimmunity. The thyroid gland was the most frequently affected organ. Immune-mediated thrombocytopenic purpura and Goodpasture's syndrome were additionally observed. This review summarizes the pre-clinical and clinical development of alemtuzumab and discusses potential modes of action as well as the pathogenetic link to the treatment emergent autoimmune phenomena.

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Neutralizing antibodies in interferon beta treated patients with multiple sclerosis: knowing what to do now

Cited by 4 publications

References 39 publications

The cross-reactivity of binding antibodies with different interferon beta formulations used as disease-modifying drugs in multiple sclerosis patients

The cross-reactivity of binding antibodies with different interferon beta formulations used as disease-modifying drugs in multiple sclerosis patients

Progress in multiple sclerosis research in the last year

Alemtuzumab: eine weitere Chance zur Therapie der Multiplen Sklerose

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