Outline. Personal profile & research interests. Rheumatology research in Ireland. Current standing. Future plans

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2 Outline Personal profile & research interests Rheumatology research in Ireland Current standing Future plans

3 Personal profile 1983 MB Queens University ARUK Clinical Research Fellowship Genetics of TNF gene in RA Prof Sir Gordon Duff 1995 PhD ARUK Travelling Fellowship Stanford University, California Effects of TNF genetics on TNF production 1996 Senior Registrar Oxford Professor of Rheumatology University of Sheffield

4 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 5 4 TNF (ng/ml/106 cells)

6 Patient stratification: Predicting severity of RA in individual patients Therapeutic targeting: selecting the best drug for the patient personalised medicines

7 Assessing radiological damage in RA Radiological scoring Modified Larsen score 32 joints of hands & feet Score Larsen, A J Rheumatol 22:

8 Variability in radiological damage in RA Genetic of Rheumatoid Arthritis (GoRA) study 1,007 patients attending RHH Larsen 80 score Disease duration (yrs)

9 Severity of RA is highly variable Year RA diagnosed 1999 X-ray damage score

10 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

11 P=0.04

12 Patient stratification: Predicting severity of RA in individual patients Therapeutic targeting: selecting the best drug for the patient personalised medicines

13 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.

14 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

15 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)

16

17 Rheumatology Research in Ireland Location Dublin Sheffield Liverpool Publications (n) Edinburgh Cardiff Belfast Glasgow 121

18 Research activity by country

19 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

20 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

21 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

22 ?

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