Antidrug Antibodies Against Biological Treatments for Multiple Sclerosis

AbstractThe development of antidrug antibodies (ADAs) is a major problem in several recombinant protein therapies used in the treatment of multiple sclerosis (MS). The etiology of ADAs is multifaceted. The predisposition for a breakdown of immune tolerance is probably genetically determined, and many factors may contribute to the immunogenicity, including structural properties, formation of aggregates, and presence of contaminants and impurities from the industrial manufacturing process. ADAs may have a neutralizing capacity and can reduce or abrogate the bioactivity and therapeutic efficacy of the drug and cause safety issues. Interferon (IFN)- β was the first drug approved for the treatment of MS, and—although it is generally recognized that neutralizing antibodies (NAbs) appear and potentially have a negative effect on therapeutic efficacy—the use of routine measurements of NAbs and the interpretation of the presence of NAbs has bee n debated at length. NAbs appear after 9–18 months of therapy in up to 40% of patients treated with IFNβ, and the frequency and titers of NAbs depend on the IFNβ preparation. Although all pivotal clinical trials of approved IFNβ products in MS exhibited a detrimental effect of NAbs after prolon ged therapy, some subsequent studies did not observe clinical effects from NAbs, which led to the claim that NAbs did not matter. However, it is now largely agreed that persistently high titers of NAbs indicate an abrogation of the biological r...
Source: CNS Drugs - Category: Neurology Source Type: research