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Title: Determining outcomes and prognostic factors in ANCA associated vasculitis as a platform for the evaluation of newer treatments
Author: Flossmann, Oliver
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2013
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Anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis (AAV) is a multisystem disease with substantial morbidity and mortality despite modem treatment. Longer-term patient outcomes are inadequately defined and new safe therapies arc needed. The aims o[this thesis were to investigate long-term outcomes of patients with AAV, compare two different damage assessment scores and the study of a novel immune-suppressant, deoxyspcrgualin (DSG), in the treatment of relapsing and refractory disease. Survival was studied in 535 newly diagnosed patients recruited to four randomised controlled trials. After a median of 5.2 years 25% deaths occurred with a mortality rate ratio of 2.6 (95% Confidence Interval (Cl) 2.2-3.1 ) compared to an age and sex matched general population. Multivariable analysis showed severely impaired kidney function, advancing age, higher disease activity and white cell count and lower haemoglobin were significant negative prognostic factors. In the same cohort, 38% experienced a relapse. Higher risk for relapse was independently associated with anti-proteinase 3 (anti-PR3) antibodies and cardiovascular involvement whereas impaired kidney function conferred a lower risk. A comparison between the Vasculitis Damage Index (VDI) and the Combined Damage Assessment Index (CDA) showed good correlation between both indices. The CDA was more complex but captured more detail. An international expert panel developed recommendations for the conduct of clinical studies and therapeutic trials in AA V. The following areas were covered: disease definitions, disease activity states, outcome measures, eligibi lity criteria, trial design including relevant end-points and biomarkers. Areas for further research were identified. A prospective open label study in 44 patients with refractory or relapsing granulomatosis with polyangiitis (GPA) treated for six months with DSG showed that 95% achieved either partial Of complete remission. Adverse events were common but rarely led to treatment discontinuation. Prolonged administration of DSG in eleven patients was effective III the majority without the occurrence of unexpected toxicity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available