Transcript Ankylosing Spondylitis

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
Axial SpA
(HLA-B27)
Tag B27 SNP (rs116488202)
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
Biomarker
Gene/gene
interaction
Genetic Screen for Axial SpA
Gene/Allele
Tag-SNP
HLA-B*2705
HLA-B*3801
HLA-B*3905
HLA-B*3906
HLA-B*4402
HLA-B*4403
HLA-B*4404
HLA-B*4405
HLA-B*0801
HLA-C*0602
rs116488202
rs2734331
rs3131382
rs9468859
rs3130501
rs12526186
rs2524180
rs2516683
rs6457374
rs887466
IL23R
ERAP1
IL12B
CARD9
CARD15
TRAF3IP2
TNFAIP3
FBXL19
rs11209026
rs27434
rs6556416
rs10781500
rs2066845
rs33980500
rs33980500
rs10782001
Weighted Genetic Risk Score
MSK Risk Tool
Chronic low back in patient
less than 45 years of age
Accelerated Rheumatologist
Consult within 2 wks of
referral
Primary
Care
Allied
Health:
Screening
Questionnaires
for Axial SpA
Positive
Screen for
SpA
Negative
Screen for
SpA
All consult with
APC within 2
wks of primary
screening
10% randomly
selected to
consult with
APC within 2
wks of primary
screening
Community
APC
Assessment
[Clinical, Labs,
X-ray]
[Biomarker
sampling]
High
Probability
IA
Intermediate
Probability
IA
Rheumatology
Consult
Within
Consult
3 months
Low
Probability
IA
Placed on regular wait list
Consult and Shared Care Tools
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
APC – Advanced Practice Clinicians: physiotherapists and chiropractors with 12 days of advanced training in IA; co-located in
networked PCP communities.
IA - Inflammatory Arthritis
MSK Risk Tool
Epigenetic Study of Advanced Ankylosis in
Patients with Ankylosing Spondylitis
Variability in Radiographic Progression
in AS
Baraliakos X, J Rheumatol 2009;36:997–1002
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
Acknowledgements
•
•
•
•
•
•
•
•
•
•
Yuhua Zhang
Zhiwei Gao
Nayef Al-Ghanim
Rose Ardern
Donna Hackett
Sean Hamilton
Dianne Codner
Amanda Dohey
Guangju Zhai
Darren O’Rielly
Dafna Gladman
Vinod Chandran
Remy Pollock
Lihi Eder
Nigil Haroon
Robert Inman
Mohammed Uddin