Neutralizing anti-IFN-β antibodies
2005; Lippincott Williams & Wilkins; Volume: 65; Issue: 1 Linguagem: Inglês
10.1212/01.wnl.0000172080.54415.f1
ISSN1526-632X
AutoresGavin Giovannoni, Andrew Goodman,
Tópico(s)Viral Infections and Immunology Research
ResumoNeutralizing antibodies (NAbs) are a major hurdle to the successful use of biologics in clinical practice. The impact of NAbs is obvious in biologic systems with no redundancy. NAbs induced in response to treatment with recombinant erythropoietin or thrombopoietin cause life-threatening complications of pure red cell aplasia and thrombocytopenia as a direct result of inhibiting the activity of the endogenous hormones. For the type 1 interferons (α and β), NAbs have not yet been shown to have untoward biologic effects. This may relate to the fact that IFNα and IFNβ have overlapping biologic activities or that they are produced locally as autocrine or paracrine mediators and are therefore less likely to be exposed to NAbs. In comparison, the evidence that NAbs interfere with the therapeutic effect of type 1 interferons is much clearer. In subjects with multiple sclerosis (MS), NAbs inhibit the induction of IFNβ-specific gene products and lessen the benefit of IFNβ on both MRI activity and relapse rate. Furthermore, three articles in this issue of Neurology show that NAbs1,2 impact negatively on disease progression and are likely to persist.3 NAbs do not appear until 6 to 24 months after IFNβ is initiated and do not have consistently measurable effects in trials of less than 2 years' duration. In the pivotal IFNβ-1b study (Betaseron/Betaferon), the clinical impact of NAbs on MS relapse rate only became apparent after 18 months of therapy.4 In the subcutaneous IFNβ-1a PRISMS study (Rebif) there were no reported differences in the clinical and MRI endpoints between NAb+ and NAb− patients at 2 years.5 However, in the 4-year extension phase of PRISMS, the relapse rate was 60% greater (0.81 vs 0.50, p = 0.002), the median number of T2 active lesions was five times greater (1.4 vs 0.3, p < 0.01), and …
Referência(s)