Nearly all biopharmaceuticals induce antibodies. Although the impact of these antibodies varies widely, it is clear that the immunogenicity of biopharmaceuticals may hamper optimum treatment strategies. The effectiveness of interferon beta (IFNb) is well established in relapsing-remitting multiple sclerosis (MS). Nevertheless, the use of this drug in clinical practice is complex, especially because it may induce neutralising antibodies (NABs). These NABs cause a reduction in IFNb bioavailability as measured by reduced levels of biomarkers. Moreover, there is evidence that persistent NABs reduce therapeutic efficacy. Because a standardised assay is lacking, the relevant clinical and biological level of NABs has not yet been defined. We here propose to setup a European wide network to provide standardised testing and to define the titres which are clinically relevant. We also want to develop in-vitro and in-vivo assays and models that predict immunogenicity, allowing strategies to prevent or modulate the induction of NABs. This project will increase the efficient use of IFNb in MS and safe money (approximately 100 million Euros per year) for the EU health systems by avoiding the use of this expensive treatment in patients in whom the drug is not effective. We want to achieve these goals by: 1 Validation and standardisation of a recently CHMP approved common assay for the detection of NABs. 2 Developing new assays. 3 Evaluating clinical effects in large cohorts of patients. 4 Studying bio-activity markers. 5 Studying immunogenicity. This research may lead to an evidence-based approach for dealing with the clinical problems of NABs and to improve care of MS patients by deciding what a clinically significant level of NABs is and recommending a strategy that will reduce clinical sequelae. Moreover, these studies may lead to data that can be applied more generally on the induction of antibodies by other biopharmaceuticals.
Call for proposal
See other projects for this call
Funding SchemeSTREP - Specific Targeted Research Project