TPMI Research Day Proton Rahman

Burden of Musculoskeletal Diseases MSDs is the second leading cause of disability Overall annual socioeconomic burden of MSD in Canada is estimated to be $22.3 billion 3% of Canada’s GDP

(HLA-B27) Axial SpA

Tag B27 SNP (rs ) 99.6% accurate in NL

Cost savings Current clinical test – The total cost per sample of direct HLA-B locus testing by PCR-SSO is $55.09 New test – The total cost per sample using TaqMan® tag-SNP genotyping assay was $4.09 – A 13.5-fold cost reduction – Will save EH 25K/year

Risk of axial SpA in B27 positive patients with inflammatory back pain

Epidemiology Clinical Gene/gene interaction Biomarker

Genetic Screen for Axial SpA Gene/AlleleTag-SNP HLA-B*2705rs HLA-B*3801rs HLA-B*3905rs HLA-B*3906rs HLA-B*4402rs HLA-B*4403rs HLA-B*4404rs HLA-B*4405rs HLA-B*0801rs HLA-C*0602rs IL23Rrs ERAP1rs27434 IL12Brs CARD9rs CARD15rs TRAF3IP2rs TNFAIP3rs FBXL19rs

Weighted Genetic Risk Score

MSK Risk Tool Chronic low back in patient less than 45 years of age

Consult Within 3 months Primary Care Allied Health: Screening Questionnaires for Axial SpA Community APC Assessment [Clinical, Labs, X-ray] [Biomarker sampling] High Probability IA Rheumatology Consult All consult with APC within 2 wks of primary screening Positive Screen for SpA Accelerated Rheumatologist Consult within 2 wks of referral Step 1 Primary Care Provider Screening using validated questionnaires Step 2 Assessment by Advanced Practice Clinicians (physiotherapists, chiropractors) at PCP centre Step 3 Rheumatology consult & shared-care tools Placed on regular wait list APC – Advanced Practice Clinicians: physiotherapists and chiropractors with 12 days of advanced training in IA; co-located in networked PCP communities. IA - Inflammatory Arthritis Consult and Shared Care Tools Negative Screen for SpA 10% randomly selected to consult with APC within 2 wks of primary screening Intermediate Probability IA Low Probability IA

MSK Risk Tool

Epigenetic Study of Advanced Ankylosis in Patients with Ankylosing Spondylitis

Baraliakos X, J Rheumatol 2009;36:997–1002 Variability in Radiographic Progression in AS

Multivariate Analysis: Interaction between Smoking, Epigenetics and Radiographic Progression Among smokers, low total methylation score was significantly associated with more radiographic progression β=2.01; 95%CI (0.75 to 3.26 p=0.0017) No such association was observed among non-smokers. (p=0.55)

Targeted therapy

Yuhua Zhang Zhiwei Gao Nayef Al-Ghanim Rose Ardern Donna Hackett Sean Hamilton Dianne Codner Amanda Dohey Guangju Zhai Darren O’Rielly Acknowledgements Dafna Gladman Vinod Chandran Remy Pollock Lihi Eder Nigil Haroon Robert Inman Mohammed Uddin