Hopkins, Ashley Mark,2025-12-172025-12-172016https://hdl.handle.net/11541.2/1226931 ethesis (xxiv, 275 pages) :illustrations (some colour)Includes bibliographical references (pages 155-171)Historically, leflunomide has been a second-line disease modifying anti-rheumatic drug (DMARD), initiated in those who fail to respond to methotrexate-based therapies. Nowadays, those who fail to respond to leflunomide tend to progress to expensive biological agents. Leflunomide’s therapeutic effects occur through the inhibition of the mitochondrial enzyme dihydro-oroate dehydrogenase within T-lymphocytes by its active metabolite, teriflunomide. Given teriflunomide has highly variable pharmacokinetics between individuals (that may be influenced by pharmacogenetic variants), relatively consistent within individual pharmacokinetic variability and there is a documented concentration-response relationship, leflunomide appears to be an ideal candidate for personalised dosing strategies. The aim of this thesis was to review leflunomide’s place in therapy and assist the development of individualisation strategies for leflunomide dosing in rheumatoid arthritis (RA) patients, thereby minimising the wide variability in response and toxicity to therapy. To achieve this, qualitative and pharmacoepidemiological studies were conducted to investigate treatment strategies employed by Australian rheumatologists, while novel variants and pharmacometric modelling techniques were explored to assist the development of individualisation strategies for leflunomide.enLeflunomideRheumatoid arthritisthesis