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Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
ClASsification criteria for the diagnosis of Psoriatic ARthritis: The CASPAR Study
Taylor W4, Helliwell P1, Gladman D3, Mease P5, Mielants H6, Marchesoni A2, for the CASPAR
investigators .1Academic Unit of Musculoskeletal Medicine, University of Leeds, UK; 2Istitutio Ortopedico G. Pini, Milan, Italy;
3University of Toronto, Canada; 4University of Otago, Wellington, New Zealand; 5Seattle Rheumatology Associates, USA; 6University of Ghent, Belgium.
Wellington Regional Rheumatology Unit, Hutt Hospital, Wellington, New Zealand
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
The CASPAR investigators
Australia: M Lassere; Belgium: H Mielants, M Van de Berghe, H Zmierczak, K de Vlam; Canada: A Russell, D Gladman; France: B Fournie, M Dougados, E Dernis, L Gossec, D Zerkak; Ireland: D Veale, O Fitzgerald, M O’Rouke; Morocco: N Hajjaj-Hassouni, N Bentalha; New Zealand: W Taylor, P Healy; Italy: A Marchesoni, C Salvarani, P Macchioni, E Lubrano, I Olivieri; South Africa: A Kalla, J Potts, G Mody, N Patel; Spain: J Torre Alonso; Sweden: B Svensson, U Lindqvist, G Holmstrom, E Theander, S Dahlqvist, G Alenius, K Ek; United Kingdom: A Isdale, D McGonagle, J Holdsworth, H Sharlala, A Adebajo, L Kay, N McHugh, J Lewis, P Owen, N Barkham, V Bejarano, P Emery, P Helliwell, G Ibrahim; United States: C Ritchlin, L Espinoza, L Candia, P Mease, L Wang, L Gunter.
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Background
• Classification criteria for distinguishing between groups of PsA and non-PsA
• There are 7 proposed classification criteria for the diagnosis of PsA
• Only 1 has been derived from observed data
• None have been adequately validated
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
• Moll & Wright (1973)
• Bennett (1979)
• Vasey & Espinoza (1984)
• Gladman (1987)
• ESSG (1991)
• McGonagle (1999)
• Fournie (1999)
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
RF
negative
Inflamm
atory arthritis
Clinical sacroiliitis
Clinical spondylitis
Clinical enthesitis
Dactylitis
Xray features
HL
A
Evidence of skin
disease
Family history
Other features
Moll and Wright
Bennett
DIP, nodules, asymmetry, synovial tissue and fluid analysis
Vasey and Espinoza
DIP disease
Gladman Excluding other defined diseases
ESSG Asymmetrical lower limb
McGonagle DIP, rare associated conditions
Fournie DIP involvement
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Background
• There are 7 proposed classification criteria for the diagnosis of PsA
• Only 1 has been derived from observed data
• None have been adequately validated
• In 2001, CASPAR arose from a collaborative effort determined to address this problem
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Aim
• To compare the test performance characteristics of existing classification criteria
• To determine whether new criteria derived from observed data would be more accurate than existing criteria
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Design
• Prospective, observational study of consecutive clinic patients with PsA and other inflammatory arthritis
• Target sample size of 1012 in total• 30 clinics in 13 countries• Gold-standard of diagnosis based on
physician’s opinion• Data collected between Feb 02 to Mar 04
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Methods
• Data collected included:– Clinical and examination features– Xrays of spine, sacroiliac joints, hands and feet– Rheumatoid factor, [HLA], anti-CCP, stored blood
• Xrays were read centrally by 2 readers in tandem, blinded to diagnosis
• Clinical gold-standard validated by quality control and Latent Class Analysis (statistical modelling)
• New criteria developed using CART and logistic regression
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Characteristics of the cohort
PsA (n=588) Controls (n=536)
Disease (%)RA (70), AS (13), UA (7),
CTD (3), other (5)
Age, yrs (mean, SE) 50.3 (0.54) 55.2 (0.62)*
Disease duration, yrs (mean, SE)
12.5 (0.40) 13.3 (0.46)
Male (%) 52.0 37.0*
RF positive (%) 4.6 57.3*
Anti-CCP positive (%) 7.6 54.5*
PASI (median, range) 2.15 (0 to 54)
* p<0.001
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
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Gladman McGonagle Fournie ESSG Moll and Wright Bennett Vasey andEspinoza
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R (log scale)
Not able to be classified Sensitivity Specificity DOR
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
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Gladman McGonagle ESSGMoll &Wright Bennett
Vasey &Espinoza
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Worse specificity
Better specificity
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
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Gladman McGonagle ESSGMoll &Wright Bennett
Vasey &Espinoza
Fa
lse
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Od
ds
ra
tio
)
Worse specificity
Better specificity
Better sensitivity
Worse sensitivity
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Validation of ‘gold-standard’
• Data control committee closely examined the data for 124 randomly selected subjects (only 1 control reclassified as PsA)
• Latent Class Anlaysis used to reclassify subjects on the basis of modelling using the agreement pattern between existing criteria: very close agreement with clinical diagnosis (kappa >0.9)
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Latent class model fitted to the data (n=949)
Criteria Sensitivity Specificity Probability of a positive response, given
subject is in class-3
McGonagle 0.99 1.00 0.93
Vasey & Espinoza
1.00 1.00 0.24
Moll & Wright 0.95 1.00 0.003
ESSG 0.76 1.00 0.69
Gladman 0.95 1.00 0.08
Bennett 0.53 1.00 0.002
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Vasey & EspinozaIn: Calin A, editor. Spondyloarthropathies. Orlando, Florida: Grune & Stratton; 1984. p. 151-185
Psoriatic skin or nail involvement [current psoriasis, history of psoriasis, or nail disease]
PLUS One of these 2
(a) Peripheral pattern (any of):
1/ DIP involvement [finger DIP swollen]
2/ Asymmetry or dactylitis
3/ Symmetry in absence of RF and nodules
4/ Pencil-in-cup deformity, whittling of terminal phalanges, fluffy periostitis and bony ankylosis [radiographic osteolysis, tuft erosion, ankylosis, or juxta-articular new bone formation]
(b) Axial pattern (any of):
1/ Spinal pain and stiffness with the restriction of motion present for over 4 weeks
2/ Grade 2 symmetric sacroiliitis according to the New York criteria
3/ Grade 3 or 4 unilateral sacroiliitis
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
CART analysis
• Iterative partitioning of the dataset using most discriminating variables to produce the most ‘pure’ groups; progressive pruning back of the tree to balance complexity with accuracy
• CART selected only 2 variables: – history of psoriasis and current psoriasis
– surrogates: nail dystrophy, family history, dactylitis, RF
– specificity 96.8%; sensitivity 96.1%
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Discrimination of clinical, laboratory and xray items
Univariate analysis Multivariate analysis
Sensitivity Specificity OR (95% CI) p-value
RF negative 95.1 60.2 27.8 (6.5-125.0) <0.001
Current dactylitis
History of dactylitis
53.6 94.617.9 (5.2-62.1)
6.0 (1.9-19.0)<0.001
History of psoriasis 93.6 97.6 102.6 (37.8-278.5) <0.001
Family history of psoriasis
46.7 91.3 5.6 (2.3-13.3) <0.001
Current psoriasis 88.3 97.8 22.5 (8.5-59.1) <0.001
Juxta-articular new bone formation
18.7 95.4 4.6 (1.3-16.9 <0.001
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
0.0 0.2 0.4 0.6 0.8 1.0
1 - Specificity
0.0
0.2
0.4
0.6
0.8
1.0S
ensi
tiv
ity
Selected cutpoint, sens 0.93 spec 0.987
ROC Curve
Area under the curve 0.990 (95% CI 0.984 to 0.995)
1. Current psoriasis
2. History of psoriasis (if current psoriasis not present)
3. Family history of psoriasis (if neither history nor current psoriasis is present)
4. Psoriatic nail dystrophy
5. RF negative
6. Current dactylitis
7. History of dactylitis (if current dactylitis not present)
8. Xray signs of juxta-articular new bone formation
(3 or more items)
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
CASPAR criteriaInflammatory musculoskeletal disease (joint, spine, or entheseal)
With 3 or more of the following:
1. Current psoriasis Psoriatic skin or scalp disease present today as judged by a rheumatologist
2. Personal history of psoriasis (if current psoriasis not present)
A history of psoriasis that may be obtained from patient, family doctor, dermatologist or rheumatologist
3. Family history of psoriasis (if personal history of psoriasis or current psoriasis is not present)
A history of psoriasis in a first or second degree relative according to patient report
4. Psoriatic nail dystrophyTypical psoriatic nail dystrophy including onycholysis, pitting and hyperkeratosis observed on current physical examination
5. A negative test for rheumatoid factorBy any method except latex but preferably by ELISA or nephlemetry, according to the local laboratory reference range
6. Current dactylitis Swelling of an entire digit
7. History of dactylitis (if current dactylitis is not present)
A history of dactylitis recorded by a rheumatologist
8. Radiological evidence of juxta-articular new bone formation
Ill-defined ossification near joint margins (but excluding osteophyte formation) on plain xrays of hand or foot
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Conclusion
• Robust design (large sample, many centres, unselected subjects, validation of gold-standard, large number of items examined, convergence of separate statistical approaches)
• Results not applicable to early disease or to non-rheumatic populations (e.g. general population)
• CASPAR criteria are simple, highly specific, and derived from observed patient data: a new standard for the case-definition of PsA?
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Acknowledgements
Funding: EULAR, Barnsley District NHS Trust, Groote Schuur Hospital (Cape Town), Department of Medical Sciences (University Hospital, Uppsala), Krembil Foundation, St. Vincent’s University Hospital Radiology Department (Dublin), Inkosi Albert Luthuli Central Hospital (Durban), El Ayachi Hospital (Morocco), National Psoriasis Foundation (USA), The Foundation for Scientific Research of the Belgian Society of Rhumatology, Arthritis New Zealand.
Data Quality Committee: Dennis McGonagle, Philip Helliwell, Mike Green, Leeds; Deborah Symmons, Manchester, UK
Radiology: Guy Porter, Keighly, UKCCP analysis: Neil McHugh, Pat Owen, Bath, UKStatistical analysis: John Horwood, Christchurch, NZ
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Discussion• Is better specificity worth the trade-off with
sensitivity?• Construction of CASPAR criteria
– Dependent nature of some items– Meaning of the initial mandatory criterion (note that
1.6% of dataset had no involved joints)?– Should some degree of chronicity be required?
• Practical application of CASPAR criteria– Should dactylitis be excluded from the initial
mandatory criterion (“double-dipping”)?– Hands and feet xrays required
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Statistical comparison of sensitivity and specificity.
OR (95% CI) for classifying cases as PsA (true positive rate) and classifying controls as PsA (false positive rate) compared to Vasey
& Espinoza (red means significantly different)
Rule True positive rate (value of more than 1 means
better sensitivity)
False positive rate
(value of less than 1 means better specificity)
Gladman 0.36 (0.20-0.64) 0.72 (0.29-1.81)
McGonagle 1.72 (0.8-3.81) 3.65 (1.85-7.23)
ESSG 0.11 (0.07-0.19) 3.14 (1.57-6.28)
Moll & Wright 0.38 (0.21-0.68) 0.36 (0.11-1.13)
Bennett 0.04 (0.02-0.06) 0.04 (0.003-0.76)
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Anti-CCP performance
0.0 0.2 0.4 0.6 0.8 1.0
1 - Specificity
0.0
0.2
0.4
0.6
0.8
1.0
Sen
siti
vity
Sens 0.51, spec 0.96 (>40)
Sens 0.54, spec 0.92 (>20)
ROC Curve
AUC 0.76 (95% CI 0.72 to 0.79)
Rehabilitation Teaching & Research Unit, Wellington School of Medicine & Health Sciences, University of Otago
Item (frequency, N) Sens. Spec.
Normal acute phase reactant (279) 31.8 80.3
RF negative (727) 95.1 60.2
Anti-CCP negative (483) 90.4 56.8
Any tender enthesis (436) 53.2 76.8
Chest wall pain (239) 25.2 83.0
Diffuse enthesis pain (122) 14.0 92.5
Inflammatory heel pain (335) 39.4 80.7
Inflammatory LBP (408) 46.0 74.4
Lumbar stiffness (481) 53.0 51.0
Inflammatory neck pain (407) 38.4 66.2
Neck stiffness (695) 69.0 31.0
Inflammatory thoracic spinal pain (180) 19.6 87.9
Thoracic stiffness (176) 17.0 84.0
Clinical sacroiliitis (263) 30.6 84.4
Absence of subcutaneous nodules (1039) 99.8 15.7
Iritis (62) 4.6 93.4
Dactylitis (338) 53.6 94.6
Nail dystrophy (352) 57.9 97.7
History of psoriasis (538) 93.6 97.6
Item (frequency, N) Sens. Spec.
Family history of psoriasis (318) 46.7 91.3
Current psoriasis on exam (532) 88.3 97.8
Less than 4 MCP involved (628) 65.7 55.0
Any DIP involved (202) 28.9 94.0
Any toe DIP involved (168) 23.3 94.2
Symmetry of joint involvement (924) 79.8 15.1
All joints of a single ray involved (90) 11.2 95.5
Interphalangeal bony ankylosis (74) 11.9 97.0
Bilateral sacroiliitis (111) 11.0 87.0
DIP erosive disease (170) 61.9 89.0
Entheseal erosion (76) 6.7 90.0
Entheseal bony proliferation (143) 15.8 85.0
Juxtaarticular new bone formatn (116) 18.7 95.4
Marginal syndesmophytes (56) 4.5 91.4
Non-marginal syndesmophytes (87) 10.0 90.2
Joint osteolysis (102) 12.6 91.5
Ray involvement (37) 6.1 98.6
Tuft osteolysis (22) 4.3 100.0
Unilateral sacroiliitis (34) 5.38 98.4
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