Besides the huge benefits that come with the use of biologics, there is one major limitation that arises when using these therapeutics: anti-drug antibodies (ADAs)
Since biologics are proteins, they can be recognized by the immune system as foreign molecules, and so the body can mount an immune response against them in the form of ADAs. Some ADAs neutralize the biological drugs and decrease the drug’s efficacy and increase its clearance, resulting in patient secondary unresponsiveness, leading to worsening of their disease.
Although these new biologic therapies have now been prescribed to many patients, there remains a lack of routine clinical assessment of the drug levels and immunogenicity in serum. We provide an accessible way of assessing drug efficacy and immunogenicity.
Immunogenicity is the ability of therapeutic proteins to provoke an antibody response targeting themselves, since they contain unique sequences that can elicit an immune response. Clinical trials with Remicade (infliximab) showed that 10-51 % of treated patients developed anti-drug antibodies (ADA) against Remicade (Vincent 2013).
The anti-Remicade antibodies were analyzed by an ELISA method which measures binding ADA, and cannot determine whether these factors have functional significance, i.e. if the ADA neutralizes the effect of the drug.
Depending on how the methods are built, there is a risk of false negative and false positive results.
Today, authorities require estimations of immunogenicity in the clinical trial programs (Phase I through Phase IV) for new biological drugs (EMA 2007 and 2012 and the FDA draft 2009). According to EMA and FDA, tests for neutralizing anti-drug antibodies (NAbs) with a biological activity assay should be included where it is relevant.