[Immunogenicity of biopharmaceuticals: Which consequences during the treatment of rheumatoid arthritis?]

The biopharmaceuticals used in rheumatology are monoclonal antibodies, chimeric (-ximab), humanized (-zumab) or fully human (-[m]umab), or fusion proteins. The immunogenicity, that is the ability to develop an immune response towards biopharmaceuticals and leading to the production of anti-drug antibodies (ADA), may be observed in nearly 30% of patients with monoclonal antibodies, more rarely with fusion proteins. The immunogenicity may lead to an increase of clearance, a reduction of half-life and serum concentration of biopharmaceuticals, a decrease of clinical response and therapeutic maintenance, as well as the occurrence of immuno-allergic reactions. However, we must relativize the importance of this phenomenon because in registers with anti-TNFα, the survival curve of monoclonal antibodies is much closed to that of fusion proteins. The immunogenicity is only one of the factors allowing to explain the clinical response, or the lack of response, with biopharmaceuticals. This phenomenon may explain some clinical situations (secondary failures, adverse reactions), but other factors (weight, inflammatory activity, combination with an immunosuppressive agent, etc.) may influence, more importantly than immunogenicity, the dose-response relationship with biopharmaceuticals.