Annual updates: SpA and PsA SPARCC

27 May 2013

Vinod Chandran

• To understand the utility of a spondyloarthritis database

• Review results of studies conducted using the database

2

Learning Objectives

• Honoraria:• Abbott/Abbvie, Amgen, Bristol-Myers Squibb,

Celgene, Janssen, Pfizer • Advisory Board:

• Abbott/Abbvie, Amgen, Celgene, Janssen, Pfizer

• Research Grants:• Abbvie

Disclosures

• peripheral as well as axial arthritis• radiological sacroiliitis• mucosal and skin inflammation• tendency for familial aggregation • absence of rheumatoid factors• absence of subcutaneous nodules

A group of inflammatory rheumatic diseases with the following common features:

Spondyloarthritis

Ann Rheum Dis 2011;70:1-3.

A trans-disciplinary national research program focusing on Genetic and Pathogenesis Studies and Outcome Measures for Patients with SpA

Established 2003

Funded by The Arthritis Society National Research Initiative Grant 2006-2010

The SPARCC Executive Committee

The three objectives and key elements of the SPARCC research network are • Improved understanding of the biological

basis of SpA • Improved clinical outcomes in SpA• Improved assessment of the impact of SpA

in Canada.

Overall Objective• To improve the health of SpA patients in Canada

by better defining, diagnosing, and predicting the course of AS and PsA

SPARCC Objectives

•Cohort expansion and detailed longitudinal follow up

•Identification and validation of biomarkers •Development of personalized treatments •Development of strategies for early detection •Development of tools and techniques for best practices for clinicians

Areas of focus

SPARCC Research

•Advances in • Genetics and Outcome Measures• Unique Populations

• juvenile SpA• First Nations population

• Access to Care• Social Role Participation measuring the

impact of SpA on quality of life• Knowledge Transfer and Exchange

•Establishment of a common clinical database •Partnership with the Canadian Spondylitis

Association (CSA)

SPARCC Achievements

SPARCC Database

Site AS PsA nXR ReA USpA Total

Toronto 657 1257 40 27 128 2109

St. John’s 233 528 0 0 0 761

Edmonton 836 0 0 0 0 836

Montreal 54 76 0 2 11 143

Winnipeg 39 0 0 0 0 39

Saskatoon 14 13 1 4 3 35

London 46 50 0 0 0 96

Newmarket 53 12 11 0 0 76

Total 1932 1936 52 33 142 4095AS=ankylosing spondylitis; PsA=psoriatic arthritis; nXR=non-radiographic AS; ReA=reactive arthritis; USpA=undifferentiated Spondyloarthritis.

Demographics

SPARCC Database

Disease No. Age Dx F/M(%) %

Caucasian% HLA-B27+

AS1096

31.2 28 / 72 87 80.7

PsA1933

37.9 46 / 54 89 43.5

nXR 52 33.7 60 / 40 92 56.3

ReA 33 35.8 45 / 55 91 73.5

USpA 142 29.9 38 / 62 85 60.1

Extra-articular features at 1st Visit

SPARCC Database

Disease % Uveitis

% Ps vulgaris PASI % Nail

AS 6.1 5.3 0.9 8.7

PsA 0.4 78.0 5.4 63.5

nXR 0 7.3 4.4 8.6

ReA 3.2 8.7 0.4 5.9

USpA 0 2.9 0.2 2.5

Co-morbid conditions

SPARCC Database

Disease % Cardiac

% Diabetes

% Cancer

% Trauma

% Infection

AS 19.1 2.9 2.4 13.8 16.0

PsA 36.9 8.2 5.9 15.1 17.2

nXR 17.0 3.8 1.9 12.2 15.7

ReA 15.0 2.5 0 6.3 63.9

USpA 15.4 3.7 2.5 5.6 20.4

Medication Use 1st Visit

SPARCC Database

Disease % NSAIDs

% DMARDs

% Biologics

AS 71 27 26

PsA 79 55 11

nXR 77 15 13

ReA 51 40 10

USpA 60 30 12

• AS • IL-1 gene cluster, IL-23R, and ERAP-1

• Functional implications of ERAP1

• GWAS and meta-analysis underway• Immunochip analysis with IGAS consortium• CNV analysis

• UGT2B17 gene CNV

• Exome sequencing

• PsA• HLA-Cw6/MICA/TNF-α/KIR alleles,

IL-1 gene cluster, IL-23R• GWAS and meta-analysis underway

• ReA• TLR2

Advances in Genetics

SPARCC Achievements

Ann Rheum Dis 2008;67:1305-9.Arthritis Rheum 2008;58:1020-5.Arthritis Rheum 2009;60:1317-23.Ann Rheum Dis 2010;69:297-300. J Rheumatol 2009;36:137-40.Arthritis Rheum 2008;58:3436-8.

• Multiplex assay of a panel of 58 biomarkers in AS:• identification of high priority candidates for prediction

of structural damage

• Osteocalcin and RANTES higher in AS• Progressor subgroup:

• MMP-9, TGFα, TNFα elevated

• Non-progressor subgroup:• eotaxin, IFNα-2, and MCP-3 elevated

Advances in Biomarkers

SPARCC Achievements

Arthritis Rheum 63(10suppl):S644, 2011.

• INSPIRE study• MRI• SPARCC MRI scoring system

• Impact• Social Role Participation Questionnaire• Work Instability

Advances in Outcome Measures

SPARCC Achievements

J Rheumatol 2007;34:1740-5.J Rheumatol 2007;34:1733-9.Arthritis Rheum2007;57:501-7.Ann Rheum Dis 2011;70:1765-9.Arthritis Rheum 2012;64(Suppl 10):S 595-6

• Paediatric Populations • Validation of outcome measures used in adult

SpA in Juvenile SpA• Whole-body MRI

• First Nations• Access to effective therapeutics amongst SpA

patients from the First Nations peoples in British Columbia

Advances in Unique Populations

SPARCC Achievements

• The CRA/SPARCC Treatment Recommendations for the Management of Spondyloarthritis: A National Multidisciplinary Stakeholder Project

Advances in Access to Care & Guidelines of SPARCC/CRA

SPARCC Achievements

J Rheumatol 2007;34:2273-84.

• Handbook for physicians entitled • Ankylosing Spondylitis: Assessment Scores,

Classification and Diagnostic Criteria• Public Symposia on SpA in collaboration with

the Canadian Spondylitis Association• Web videos (sparcc.ca )

• Spinal mobility measurements• Video archive of all the public patient fora

• Annual Fellows training day

Advances in Knowledge Transfer and Exchange

SPARCC Achievements

• Longitudinal changes in SpA • predictors for progression of joint damage• Compare differences among SpA over time

• Compare quality of life and function among different SpA• Comparison amongst different regions of Canada• Gender effect on disease progression• Drug Response• Economic impact• Co-morbidities• Imaging• Access to Care• Predictive profiles of radiographic progression: Serum

biomarker analysis• SpA in children (novel markers for prognosis and activity)• SpA in First Nations (prevalence, genetic susceptibility,

care gaps)

Future Direction

• Spondyloarthritis not well studied in North America

• SPARCC developed to address need• SPARCC has made important new

observations in SpA and has a significant international profile

• SPARCC will continue to further research, advocacy and education in SpA

Summary