Immunogenicity of therapeutics in inflammatory joint- and bowel diseases

Abstract

Immunogenicity of therapeutics impact their effectiveness Foreign substrates may trigger an immune response in the human body. This immune response can be desirable or undesirable, dependent on the substrate. Vaccines rely on strong immune responses to be effective, while immune responses against biologic drugs may compromise their treatment effect. The aim of this thesis was to explore the immunogenicity of COVID-19 vaccines and the biologic drug adalimumab in patients with inflammatory joint- and bowel diseases. Data from two observational studies were used, the Norwegian Study of Vaccine Response to COVID-19 (Nor-vaC) and the The Norwegian Antirheumatic Drug Registry (NOR-DMARD). Patients with inflammatory joint- and bowel diseases treated with a wide range of immunosuppressive medication had reduced antibody responses to two COVID-19 vaccine doses compared to healthy controls. An additional dose was beneficial in these patients. Patients using the biologic drug rituximab had poor antibody responses even after repeated vaccination. However, a third COVID-19 vaccine provided cellular immune responses in all patients. Adalimumab is the most widely used biologic drug in the world. It has indications across inflammatory joint diseases and is prescribed in a one dose fits all manner. Jyssum and co-workers found that 10% of patients with inflammatory joint diseases treated with adalimumab had developed neutralizing anti-drug antibodies at 3 months. This was associated with poorer treatment outcomes. Further, higher serum adalimumab levels were associated with better response to treatment. These findings can contribute to algorithms for personalized treatment of patients using adalimumab.