Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Johan Rönnelid, Uppsala University, Sweden
- Second opponent: Professor Inger Gjertsson, University of Gothenburg, Sweden
- Third member and chair of the evaluation committee: Associate Professor Mimi Stokke Opdal, University of Oslo
Chair of the Defence
Professor II Marianne Grønlie Guren, University of Oslo
Principal Supervisor
MD, PhD Nils Bolstad, Oslo University Hospital
Summary
Antibody-based biopharmaceuticals have revolutionised treatment of inflammatory joint diseases in the last two decades. However, a considerable proportion of patients fail to achieve, or lose response. Individualised dosing based on serum concentration measurements, therapeutic drug monitoring (TDM), has been proposed as a strategy to optimise treatment with tumour necrosis factor alpha (TNF) inhibitors. Knowledge on therapeutic target concentrations and immunogenicity is necessary for validation of TDM as a tool in research and clinical practice.
In this thesis, Gehin and colleagues investigated therapeutic target concentrations, and incidence and clinical consequences of neutralising anti-drug antibodies (ADAb), for TNF inhibitors in patients with inflammatory joint diseases.
Therapeutic target concentrations were identified for the TNF inhibitors certolizumab pegol and golimumab. ADAb formation was associated with lower serum concentrations and lack of clinical effect. This indicated a rationale for TDM in treatment with these drugs. In contrast to other TNF inhibitors, no therapeutic target concentration could be identified for etanercept and no ADAb were observed.
Implementation of TDM in clinical practice requires reliable assays. As immunoassays use animal antibodies for detection, rheumatoid arthritis patients constitute a high-risk population with regard to interference from Fc-reactive rheumatoid factors. This thesis revealed a high occurrence of rheumatoid factors with anti-animal IgG reactivity that was associated with interference in commercial immunoassays.
This thesis provides novel knowledge to improve treatment with TNF inhibitors in patients with inflammatory joint diseases. In addition, it highlights the importance of considering risk of rheumatoid factor interference when designing immunoassays and interpreting immunoassay results.
Additional information
Contact the research support staff.