Glucocorticoid Toxicity
Clinicians struggle with management of GCA, particularly in terms of the difficult balance between the clinical knowledge of the long-term cumulative toxicity of glucocorticoid (steroid) therapy against the fact that glucocorticoids suppress inflammation and enable patients to continue their everyday functions.
Background
For many years, Leeds has played an important role in phenotyping GCA patients, which demands considerable clinical acumen [Bird et al., 1979; Leeb and Bird, 2004; Pease et al., 2005; Mackie et al., 2010]. Although prednisolone tablets are inexpensive, the real healthcare costs of long-term steroid therapy are immense. In addition, there are well-known consequences including obesity, diabetes, cardiovascular disease, and osteoporosis, and less well-characterised consequences including adrenal suppression, glucocorticoid-related myopathy and impaired wound healing. These toxicities interact with age-related co-morbidity resulting in devastating and costly patient outcomes, including falls, fractures and dependency.
In Western healthcare systems, overall lifespan is not curtailed in GCA compared to the general population, so healthcare costs of the disease are high. Patient engagement activities have demonstrated that the adverse effects of glucocorticoids therapy can dominate the lives of patients, far more than is usually appreciated by their doctors and often far more than the original disease. While the disease is treatable, large doses of glucocorticoids are needed for many patients with relapsing disease, however, many of the glucocorticoid-related adverse effects are irreversible and continue long after they are stopped. There is therefore a real unmet need in GCA for an alternative to prednisolone that has a more favourable side-effect profile without substantial loss of efficacy. There is a paucity of clinical trial data to support the use of alternative immunosuppressants compared to other autoimmune disease, although promising data is emerging for some biological therapies, particularly Tocilizumab. Once available for routine use in the NHS, these newer treatments would have an enormous impact for patients, and would be likely to reduce overall healthcare costs.
Projects
Epidemiology of Glucocorticoid Toxicity
- Glucocorticoid dose-response relationship with infection (Dr Mar Pujades Rodriguez; Professor Ann Morgan; Dr Jianhua Wu, Lecturer in Medical Statistics and Biostatistics, University of Leeds; Professor Christian Mallen, NIHR Professor of General Practice, Keele University)
- Glucocorticoid dose-response relationship with adrenal dysfunction and death (Dr Mar Pujades Rodriguez; Professor Ann Morgan; Professor Paul Stewart, Professor of Medicine and Consultant Endocrinologist, University of Leeds; Dr Teumzghi Mebrahtu, Post-doctoral researcher, University of Leeds)
- Glucocorticoid dose-response relationship with cardiovascular diseases (Dr Mar Pujades Rodriguez; Dr Jianhua Wu; Professor Ann Morgan)
- Glucocorticoid dose-response relationship with hypertensive disease (Dr Mar Pujades Rodriguez; Dr Teumzghi Mebrahtu; Professor Ann Morgan; Professor Paul Stewart)
- Glucocorticoid dose-response relationship with diabetes (Dr Mar Pujades Rodriguez; Dr Sarah Mackie; Lana Lai PhD student, University of Leeds; Professor Robert West, Professor of Biostatistics and Chartered Statistician, University of Leeds)
Assessment of Glucocorticoid Toxicity
- Glucocorticoid-induced skin disease (Ana Tiganescu, Independent Research Fellow and Professor Paul Stewart, University of Leeds)
Patient-reported outcome measures of glucocorticoid toxicity
- Development and validation of a patient reported outcome measure for Giant Cell Arteritis (Dr Joanna Robson, Consultant Senior Lecturer in Rheumatology, UWE Bristol)