Dr Joanna Tieu

Recipient:  Dr Joanna Tieu
Intended department: Ken Muirden Fellowship- Addenbrooke’s Hospital, University of Cambridge

Rheumatology Unit  Royal Adelaide Hospital

Project:

 

Molecular Mechanisms and therapeutic effects of Carnosol on collagen-induced arthritis and osteolysis

 

My research has focused on vasculitis, namely anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), and its management. AAV is an umbrella term that encompasses three conditions which share clinical characteristics, and an association with ANCA: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). These are rare autoimmune conditions resulting in inflammation of small blood vessels. Untreated, AAV can have devastating, severe organ and life-threatening consequences. This can involve any organ system, but most commonly affects the kidneys, lungs, nose and sinuses, eyes, skin and joints. The treatment of AAV includes an induction phase for control of disease activity with the aim of achieving disease remission, and maintenance phase for prevention of relapse .Significant advances have been made in the induction of remission of AAV, allowing for better control of the disease. As these advances to induction treatment have been made, an important priority in the long-term management of people with AAV has become the prevention of relapse, which occurs in half of all patients. With each relapse, further disease activity can lead to more organ damage and worse overall outcomes. How to optimally prevent these relapses remains uncertain. Adverse effects of effective agents for treatment of AAV are another major issue, with a difficult balance between the pros and cons of using these treatments. Most importantly, as well as gauging assessments made by health professionals in the treatment of AAV and the adverse outcomes that we see from treatment, the effect of certain characteristics and treatments on quality of life for patients with AAV has been less clear. We have sought to address some of these areas through different studies, with a focus on rituximab, a medication used for the treatment of AAV. To date, there have been trials evaluating the use of rituximab for the maintenance of remission in AAV, and the frequency with which to give rituximab. However, a number of questions remain unanswered. We have worked on developing consensus statements with experts in the field in the United Kingdom to address these gaps and provide guidance on these issues. We plan to evaluate quality of life, specifically in patients with a relapse of AAV, and those with severe kidney or lung involvement from AAV. We hope to learn more about what influences the changes in quality of life and learn more about whether there are specific interventions that will result in better quality of life in patients with AAV. Lastly, we have looked at a group of people with autoimmune disease who have been treated with rituximab at Addenbrooke’s Hospital in Cambridge and have been found to have lower levels of protective antibodies. We have looked at longer term outcomes in these patients, and their infection rates. Further work on why this occurs in some but not all patients who receive rituximab is ongoing. With each of these research projects, we hope to better tailor the treatments that are provided to people with AAV. These projects have been made possible by joining the Vasculitis and Lupus service led by Professor Jayne, the international collaborative network that has been established between vasculitis clinicians and researchers, and the patients who have participated in these studies. With other projects, this work will contribute to a PhD on optimising the management of AAV.