1. IMAGING NEURAL CORRELATES OF FATIGUE & PAIN IN PATIENTS WITH RA TREATED WITH TNF INHIBITORS FARHAN BARI SPR RHEUMATOLOGY WARN CONFERENCE 22 ND MAY 2014

2. BACKGROUND RA is an auto-immune, systemic, inflammatory condition causing pain and synovitis in the joints of the hands and feet 1 Repeated flares cause symptoms of pain, fatigue, stiffness and loss of function Fatigue has been identified by RA patients as a key problem, which they consider harder to manage than pain 2 International consensus has been reached that it should be measured in all clinical trial 3

3. FATIGUE IN RA Multiple and complex pathways 4 Tumour necrosis factor inhibitors (TNFi) have been shown in clinical trial to reduce fatigue Major component of fatigue is central in origin i.e. in the brain Similar to pain, fatigue is invisible and subjective fMRI has greatly advanced our understanding of pain processing in the brain Recently, in Chronic Fatigue Syndrome, it has been suggested that fatigue may also be evaluated by fMRI.

4. FUNCTIONAL MRI Functional neuroimaging procedure using MRI technology that measures brain activity by detecting associated changes in blood flow. Cerebral blood flow and neuronal activation are coupled. When an area of the brain is in use, blood flow to that region also increases. Can be used to produce activation maps showing which parts of the brain are involved in a particular mental process.

5. FMRI & FATIGUE Recently, in Chronic Fatigue Syndrome, it has been suggested that fatigue may also be evaluated by fMRI 5. Calcarine fissure Cerebellum Inferior occipital sulcus Occipito-parietal cortex Posterior cingulate gyrus Parahippocampal gyrus

6. THE STUDY CREATE Centre in Cardiff is conducting a clinical trial funded by Erlangen University to evaluate the utility of fMRI to predict response to TNFi and to evaluate the effect of treatment on pain processing. This study aims to build on this opportunity to obtain preliminary data which can be used to assess fatigue in the brain during fMRI imaging in RA patients.

7. METHODOLOGY This is an observational study using fMRI as a tool to assess neural correlates of fatigue. Imaging will be undertaken pre and post TNFi in patients with RA Study duration: 24 weeks Total no. of patients: 16 Recruited from the Rheumatology Department at University Hospital of Wales. fMRI baseline and at 24 weeks, at CUBRIC centre

8. CLINICAL ASSESSMENTS Patient’s Assessment of Arthritis Pain (100mm visual analogue scale [VAS]) Patient’s and Physician’s Global Assessments of Arthritis (100mm VAS) Health Assessment Questionnaire-Disability Index (HAQ-DI) C-reactive protein (CRP) erythrocyte sedimentation rate (ESR) Disease activity score 28 (DAS28) Fatigue will be measured using the Bristol Rheumatoid Arthritis Fatigue Questionnaire.

9. CONTD Mentors: Professor Ernest Choy Professor Richard Wise Dr Ann Taylor LREC and R&D application is currently being prepared THANK YOU

10. REFERENCES 1.Conaghan PG, Green MJ, Emery P. Established rheumatoid arthritis. Baillières Clinical Rheumatology 1999;13:561-575. 2.Hewlett S, Cockshott Z, Byron M, Kitchen K, Tipler S, Pope D et al. Patients' perceptions of fatigue in RA: Overwhelming, uncontrollable, ignored. Arthritis & Rheumatism (Arthritis Care & Research) 2005;53(5):697-702. 3.Kirwan J, Minnock P, Adebajo A, Bresnihan B, Choy E, De Wit M et al. Patient Perspective Workshop: Fatigue as a recommended patient-centred outcome measure in rheumatoid arthritis. Journal of Rheumatology 2007;34:1174-7. 4.Hewlett S, Chalder T, Choy E, Cramp F, Davis B, Dures E, Nicholls C, Kirwan J. Fatigue in rheumatoid arthritis: time for a conceptual model. Rheumatology (Oxford). 2011 Jun;50(6):1004-6. 5.de Lange FP1, Kalkman JS, Bleijenberg G, Hagoort P, van der Werf SP, van der Meer JW, Toni I. Neural correlates of the chronic fatigue syndrome--an fMRI study. Brain. 2004 Sep;127(Pt 9):1948-57. Epub 2004 Jul 7.