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Abstract

Introduction: This thesis comprises three studies examining treatment persistence with tumour necrosis factor alpha (TNFα) antagonists in rheumatoid arthritis (RA) patients. Persistence, also commonly known as duration of treatment, has been suggested as an indirect measure that balances benefit and harm, and it is important for cost-effectiveness analysis and budget planning. Previous research has examined the effect of drug and patient characteristics on persistence with TNFα antagonists. Objectives: 1) To estimate pairwise comparative persistence with TNFα antagonists infliximab, adalimumab and etanercept in RA patients; 2) To evaluate the impact of investigator factors (methods) and of prescriber factors (propensity for discontinuation and preference for prescribed drug) on comparative persistence estimates with TNFα antagonists in RA patients . Methods: To address these objectives, three population-based studies of an RA cohort were conducted in British Columbia patients using survival analysis methodology. Results: 1) In RA patients similar persistence was observed with infliximab, adalimumab and etanercept, with median persistence equaling approximately 3.5 years; 2) The length of ‘drug-free interval’ used to ascertain drug discontinuation influences the observed magnitude and significance of comparative persistence estimates; 3) Physician factors (prescribing habits) are predictors and possible confounding factors in studies of persistence and comparative persistence. Conclusions: This thesis provides evidence showing that researchers and physicians can influence estimated and actual comparative persistence on TNFα antagonists in RA patients. The role of researchers and physicians in affecting estimates of persistence may explain heterogeneity in these estimates across different studies. Improved methodology in conducting comparative persistence research is needed to establish a high quality body of evidence for the use of patients, clinicians, researchers and policy makers.