AbstractGolimumab was approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of moderate-to-severe ulcerative colitis in 2013 and was the third anti-tumour necrosis factor therapy, after adalimumab, and infliximab, licensed for this indication. These approvals were granted based on evidence generated by a large-scale, randomised controlled trial programme (PURSUIT) that demonstrated significant benefit compared with placebo during both induction and maintenance treatment. However, despite the efficacy demonstrated in PURSUIT, several aspects regarding the use of golimumab remained to be studied. These included its effectiveness in ‘real-world’ clinical practice, the exposure-response relationship associated with its use and the role that therapeutic drug monitoring may have to play in terms of treatment optimisation. In addition, as part of ascertaining a clearer understanding of the pharmacokinetics (PK) and pharmacodynamics (PD) of any drug, it is crucial that techniques used to measure serum concentrations are appropriately validated and verified.
This thesis provides an original contribution to knowledge, firstly by evaluating clinical outcomes of golimumab-treated patients as part of a retrospective observational study. Secondly, a prospective, phase IV, therapeutic drug monitoring study (GO-LEVEL) was designed to identify therapeutic thresholds for golimumab serum concentrations during induction and maintenance therapy. Finally, samples collected as part of GO-LEVEL were analysed to validate and verify use of a commercially available assay for measurement of serum golimumab and anti-golimumab antibody concentrations.
|Date of Award
|1 Feb 2023
|Peter Irving (Supervisor) & Jeremy Sanderson (Supervisor)