Outline Personal profile & research interests Rheumatology research in Ireland Current standing Future plans
Personal profile 1983 MB Queens University 1990-3 ARUK Clinical Research Fellowship 1990-93 Genetics of TNF gene in RA Prof Sir Gordon Duff 1995 PhD 1995-6 ARUK Travelling Fellowship 1995-96 Stanford University, California Effects of TNF genetics on TNF production 1996 Senior Registrar Oxford 1997-13 Professor of Rheumatology University of Sheffield
Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing Voltaire
5 4 TNF (ng/ml/106 cells) 3 2 1 0
Patient stratification: Predicting severity of RA in individual patients Therapeutic targeting: selecting the best drug for the patient personalised medicines
Assessing radiological damage in RA Radiological scoring Modified Larsen score 32 joints of hands & feet Score 0-160 Larsen, A. 1995. J Rheumatol 22:1974-1975
Variability in radiological damage in RA Genetic of Rheumatoid Arthritis (GoRA) study 1,007 patients attending RHH 160 140 120 100 Larsen 80 score 60 40 20 0 0 200 400 600 800 Disease duration (yrs) 1000 1200
Severity of RA is highly variable Year RA diagnosed 1999 X-ray damage score 1988 1998 1999 2005
Biomarkers in rheumatoid arthritis A distinct biological or biologically derived indicator of a event, process or condition DNA SNPs Bone Alkaline Phosphatase Cartilage Hyaluronic acid, cartilage oligomeric protein, aggrecan Inflammation CRP, ESR Immune Rheumatoid Factor and anti-ccp Diagnostic/Prognostic/therapeutic response eg anti-ccp
P=0.04
Patient stratification: Predicting severity of RA in individual patients Therapeutic targeting: selecting the best drug for the patient personalised medicines
Oct 26th 2006 It got to the point where walking was agony, like walking barefoot on a stony beach The rheumatologist diagnosed aggressive rheumatoid arthritis and said some of my joints had permanent damage. I was devastated, I was a fit 23-year-old one minute and next I was in pain, exhausted and could barely walk. There was no history of arthritis in my family, so I was stunned. Doctors first tried a number of different treatments but Stephanie suffered dreadful side-effects including vomiting and mouth ulcers. Finally they found an anti-tnf drug which caused only a mild rash, but brought a real improvement to her symptoms. The difference has been amazing, says Stephanie. Although it is not a cure, I cannot describe the major difference these drugs have made to my life. The good days now outnumber the bad days ten-fold and I am trying to put my life back together. Stephanie Phillips Stephanie is starting medical school next year and she hopes to become a rheumatologist.
Biological treatments for RA Improved Efficacy Good side effect profile Cost Non-response (~30%) Increasing numbers of biologicals TNF inhibitors x5 IL-1ra IL-6R antibody Rituximab (B cells) Abatacept (T cells) Therapeutic targeting
Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) Aim - to identify biomarkers predictive of response to anti-tnf British Society for Rheumatology Biologics Register database used to identify suitable anti-tnf treated patients - Baseline and 6 month DAS score - DNA from >3,500 patients (retrospective) - Prospective study underway (>n=600) Anne Barton (Manchester) Ann Morgan (Leeds) John Isaacs (Newcastle) Gerry Wilson (Sheffield)
Rheumatology Research in Ireland Location Dublin Sheffield Liverpool Publications (n) 82 30 41 Edinburgh Cardiff Belfast 29 45 24 Glasgow 121
Research activity by country
Research plans Next 12 months Appointment of Professor in TCD (Immunology) Centre of Excellence in Rheumatology (Dublin) Patient centred studies in common rheumatic diseases across Dublin & Ireland Research Databases & biological samples
Developing an Arthritis Ireland Centre for Rheumatology Research Autoimmune rheumatology Crystal arthritis Osteoarthritis Clinical cohorts & biorepositories Genomics Transcriptomics Immunology Imaging (Ultrasound/MRI) Statistics Insights into Pathogenic mechanisms Identification of novel therapeutic targets Patient stratification and therapeutic targeting
Developing a Dublin Centre for Rheumatology Develop local, national, international research networks Develop research programmes in rheumatic diseases Research funding SFI, HRB, WT, EU, Industrial EULAR Centre of Excellence Develop training pathways and opportunities Patients
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