The Epidemiology and Patient Perspectives of Glucocorticoid Use in Rheumatoid Arthritis and Other Inflammatory Diseases

Abstract

The overarching theme is to improve understanding of oral glucocorticoid (GC) use, including the benefits and harms of GC treatment in inflammatory rheumatic diseases, with an emphasis on rheumatoid arthritis (RA). The introduction summarises inflammation as a normal physiological process, and its contribution to chronic inflammatory diseases, commonly treated with GCs. It further describes GCs in detail, identifying three key areas where the literature is lacking and/or conflicting that are addressed as the thesis aims. The first section of the thesis explores how GCs are used in RA and the influence of patient and prescriber factors in two large databases in the United Kingdom (UK) and Australia. In Chapter 2, primary care data from clinical practice research datalink (CPRD) demonstrated that half of patients with incident RA received GCs in primary care, with an average GC use of 7.5 mg (prednisolone equivalent daily dose, PEQ) for 25% of the time. GCs were prescribed more commonly in certain high-risk populations. In Chapter 3, data from Australian Rheumatology Association Database (ARAD), found the probability of GC use has decreased over time. In contrast to CPRD, GC use in ARAD RA patients was less likely with increasing age, with older patients being less likely to commence GCs, but also less likely to cease GCs. The second section of the thesis explores the patient perspective of the benefits and harms of GC use, and the need for a patient reported outcome measure (PRO). A crosssectional survey administered to GC users with rheumatic diseases in Australia and United States (US) demonstrated that most patients with rheumatic diseases feel that GCs are effective treatments and that the benefits of GC use, outweigh the harms. Many adverse effects important to patients, cannot be easily measured, such as skin thinning/easy bruising, sleep disturbance, mood disturbance, and change in facial shape. This chapter also discusses the role of Outcome Measures in Rheumatology (OMERACT) in developing a PRO for GC use, describing additional work by the author contributing to both this thesis and the OMERACT GC working group. The final section of the thesis focuses on cataract and glaucoma, as two important potential harms of GC use. Chapter 5 presents a published manuscript reporting the results of a systematic literature review and meta-analysis, concluding that although the current literature suggests a possible association between GC use and the development of cataract, this risk cannot be accurately quantified in RA from the available evidence. In addition, there was insufficient evidence to determine the risk of GC use and the development of glaucoma. To address this gap in the literature, analyses of different models of GC exposure in CPRD were performed to quantify the risk of developing cataracts and glaucoma in RA patients. The results demonstrated that current GC exposure is associated with a twofold increased risk of developing cataracts and 60% increased risk of developing glaucoma in patients with RA. For cataracts, cumulative doses greater than 1000mg PEQ are associated with increased risk, more so at doses above 4000mg PEQ, whereas for glaucoma, the risk is seen only with higher cumulative doses greater than 4000mg. The results of these three sections of work expand current knowledge about GC use, with opportunities for the findings to be directly translated and improve clinical care.