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Sensitivity and Specificity of the classification of Psoriatic Arthritis Criteria in Early Psoriatic Arthritis
   ARTHRITIS & RHEUMATISMVol. 64, No. 10, October 2012, pp 3150–3155DOI 10.1002/art.34536© 2012, American College of Rheumatology Sensitivity and Specificity of the Classification of Psoriatic Arthritis Criteria in Early Psoriatic Arthritis Laura C. Coates, 1 Philip G. Conaghan, 1 Paul Emery, 1 Michael J. Green, 2 Gamal Ibrahim, 3 Helen MacIver, 3 and Philip S. Helliwell 1 Objective.  To assess the sensitivity and specificityof the Classification of Psoriatic Arthritis (CASPAR)Study Group criteria in early psoriatic arthritis (PsA)and to compare them with the sensitivity and specificityof the Moll and Wright criteria.  Methods.  The CASPAR Study Group criteria wereapplied to patients with early PsA (<24 months symp-tom duration) and to control patients with other new-onset inflammatory arthritides. Both groups were naiveto all disease-modifying antirheumatic drugs. The goldstandard diagnosis was confirmed by the consultingrheumatologist using radiography and magnetic reso-nance imaging where required. Proportions of patientsand control patients meeting the criteria were comparedusing McNemar’s tests.  Results.  We recruited a total of 111 patients withearly PsA and 111 control patients with other forms of inflammatory arthritis (82 with rheumatoid arthritis, 13 with undifferentiated arthritis, 9 with spondylarthritis,4 with inflammatory osteoarthritis, and 3 with crystalarthritis) to the study. The sensitivity of the CASPAR Study Group criteria in classifying early PsA was 87.4%compared to 80.2% for the Moll and Wright criteria.The specificity for both criteria was 99.1%. When con-sidering different cut points for the CASPAR StudyGroup criteria, the best cut point for classificationremained a score of   > 3 as in the original CASPAR Study Group analysis. Considering a score of  > 2 gave ahigher sensitivity of 99.1% but resulted in a drop inspecificity to 94.6%. Regression analysis determinedthat psoriasis and rheumatoid factor negativity werethe most important features that differentiated PsA,followed by nail psoriasis and current or previousdactylitis. Conclusion.  The CASPAR Study Group criteriaare more sensitive than the Moll and Wright criteria inclassifying early PsA. Although their sensitivity for earlyPsA is lower than that for established disease, theCASPAR Study Group criteria are valid for use asinclusion criteria for trials in early PsA. The Classification of Psoriatic Arthritis (CASPAR)Study Group criteria were developed as new classifica-tion criteria for psoriatic arthritis (PsA) using a largecohort of patients with PsA and controls with otherinflammatory arthritides. They include characteristicfeatures of PsA and have been shown to have highsensitivity and specificity in a population with estab-lished disease (1). However, one of the limitations of theCASPAR Study Group criteria is that they have notbeen validated in early disease. A retrospective survey of the Toronto database found that the CASPAR StudyGroup criteria had high sensitivity for identifying earlydisease within their PsA clinic population (2). However,that study included only patients referred to a specialisttertiary referral clinic; therefore, there is a significantrisk of overestimating the sensitivity of the criteria.Studies in Italy and Sweden have also investigated the Dr. Coates was recipient of a Clinical Research Fellowshipfrom Arthritis Research UK (grant number 18364). 1 Laura C. Coates, MBChB, PhD, MRCP, Philip G.Conaghan, MBBS, PhD, FRCP, FRACP, Paul Emery, MA, MD,FRCP, Philip S. Helliwell, MA, DM, PhD: University of Leeds andNIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK; 2 Michael J. Green, MBChB, MRCP: York Teaching Hospital NHSFoundation Trust, York, and Harrogate and District NHS FoundationTrust, Harrowgate, UK;  3 Gamal Ibrahim, ABMS, MSc, FRCP, HelenMacIver, MBChB, MRCP: St. Luke’s Hospital and Bradford TeachingHospital NHS Foundation Trust, Bradford, UK.Dr. Emery has received consulting fees, speaking fees, and/orhonoraria from Pfizer, MSD, Abbott, Roche, UCB, Celgene, andBristol-Myers Squibb (less than $10,000 each). Address correspondence to Philip S. Helliwell, DM, PhD,Division of Musculoskeletal and Rheumatic Diseases, Chapel AllertonHospital, Chapeltown Road, Leeds LS7 4SA, UK. for publication July 15, 2011; accepted in revisedform May 3, 2012.3150  sensitivity of the criteria in early PsA (3,4), but as yet nostudies have been completed with a control populationto address the sensitivity and specificity of the CASPARStudy Group criteria in early disease. The criteria cannotcurrently be recommended for use in studies of earlyPsA.The other key issue raised with the CASPARStudy Group criteria is the entry criterion that statesthat the patients must have “inflammatory articulardisease (joint, spine, or entheseal).” Particularly in earlyPsA, the pattern of disease may be evolving and may bedifferent from that of established disease.This study aimed to emulate the methodology of the srcinal CASPAR study and to recruit both patients with early PsA and control patients with other inflam-matory arthritides to allow calculation of the sensitivityand specificity of the criteria in this population of patients with early PsA. The Moll and Wright criteria, which state that patients have PsA if they have inflam-matory arthritis, psoriasis, and (usually) are negative forrheumatoid factor (RF) (5), were used for compar-ison. In addition, an assessment of arthritis, enthesitis,and axial involvement was included to investigate thepattern of disease in treatment-naive patients with earlyarthritis. PATIENTS AND METHODS Patient and control selection.  Patients and controls were recruited from Early Arthritis Clinics and from newreferrals to rheumatology clinics in 4 hospitals based in theYorkshire region. Consecutive clinic attendees newly diag-nosed as having PsA were enrolled in the study. All PsA patients were required to have active inflammatory musculo-skeletal disease comprising arthritis and/or enthesitis and/ordactylitis. For each patient enrolled, a consecutive controlpatient with new-onset inflammatory musculoskeletal disease was also enrolled. The gold standard diagnosis was confirmedby the consulting rheumatologist using radiography and mag-netic resonance imaging (MRI) where required. All patientsand controls were required to have disease duration of    2 years (from onset of symptoms) and to be disease-modifyingantirheumatic drug naive. Data collection.  Data were recorded on standardizedforms that included demographics, date of onset of arthritis,duration of early morning stiffness, activity of arthritis/ enthesitis and axial disease, and application of the CASPARStudy Group criteria. Activity of arthritis and enthesitis wasassessed using clinical examination. All patients underwent aswollen joint count (66 joints), a tender joint count (68 joints),and clinical assessment of entheses, including the enthesealsites required for the Leeds Enthesitis Index (6), the Maas-tricht Ankylosing Spondylitis Enthesitis Score (MASES) (7),and sites used in the Infliximab Multinational Psoriatic Arthri-tis Controlled Trial (IMPACT) and IMPACT 2 clinical trials(bilateral Achilles tendon and plantar fascia) (8,9). Entheses were considered to have active enthesitis if they were tenderand/or swollen. The presence of axial involvement was assessedclinically by questioning the patient about inflammatory backpain using the Calin criteria (10). All patients underwent plain radiography of the handsand feet and additional imaging as deemed clinically necessaryby the treating physician. Patients with symptoms suggestive of inflammatory back pain underwent radiography and MRI asclinically indicated. Results of all relevant investigations wererecorded, including levels of inflammatory markers, IgM-RFand anti–cyclic citrullinated peptide antibodies, presence orabsence of typical PsA-like periosteal new bone formation onradiographs, and evidence of axial involvement identified withradiographs or MRI by consensus of radiologists and thereferring rheumatologist in each center (11).When considering patterns of arthritis, oligoarthritis was defined as  5 joints with active disease and polyarthritis as  5 joints with active disease. Small joints were defined astemporomandibular joints, sternoclavicular joints, acromiocla- vicular joints, carpometacarpal joints, metacarpal joints, prox-imal and distal interphalangeal (DIP) joints, metatarsophalan-geal joints, and interphalangeal joints of the toes (total of 58 joints). Large joints were defined as the glenohumeral joints,elbows, hips, knees, and ankle joints (total of 10 joints). Thesymmetry number was calculated as the number of joints assymmetric pairs/total number of joints involved. Symmetry was defined as a symmetry number of    0.5 as previouslydescribed (12). Statistical analysis.  Values for sensitivity and specific-ity for the CASPAR Study Group criteria in establisheddisease are 0.91 and 0.99, respectively. Prior to the develop-ment of the CASPAR Study Group criteria, the Moll andWright criteria were traditionally used, and the values forsensitivity and specificity for the Moll and Wright criteria inthe CASPAR study were 0.99 and 0.92, respectively. Assumingthat in early case definition the emphasis is on specificity, thenull hypothesis is that the specificity for the CASPAR StudyGroup criteria will be equivalent to that for the Moll andWright criteria (H  A     H O , respectively). The alternativehypothesis is that the specificity for the CASPAR Study Groupcriteria differs from that for the Moll and Wright criteria(H  A     H O ). According to Obuchowski (13), the number of patients required to test the alternative (2-tailed) hypothesis with an alpha value of 0.05 and a beta value of 0.20 is 111.Therefore, 111 patients and 111 consecutive control patients were required.Sensitivity and specificity of the CASPAR StudyGroup criteria and Moll and Wright criteria were comparedusing McNemar’s tests for paired variables. Receiver operatingcharacteristic (ROC) curves were used to estimate the areaunder the curve (AUC) for both criteria and the optimal cutpoint for the CASPAR Study Group criteria for the diagnosisof early PsA. Univariate and multivariate forward stepwisebinary logistic regression was used to identify which featuresincluded in the CASPAR Study Group criteria were indepen-dently associated with PsA. Significance testing was performed USE OF CASPAR CRITERIA IN EARLY PsA 3151  using McNemar’s tests for categorical variables and Mann-Whitney U tests for continuous variables. RESULTS We recruited a total of 111 patients with earlyPsA and 111 control patients with other forms of inflammatory arthritis (82 with rheumatoid arthritis[RA], 13 with undifferentiated arthritis, 9 with spondy-larthritis, 4 with inflammatory osteoarthritis, and 3 withcrystal arthritis) to the study. The baseline features of these patients are shown in Table 1. The sensitivity of the CASPAR Study Group criteria (score  3) in classi-fying early PsA was 87.4% compared to 80.2% for theMoll and Wright criteria (  P   0.008). The specificity forboth criteria was 99.1%, with only 1 control patientfulfilling both criteria for PsA.Using ROC analysis, the AUC for the CASPARStudy Group criteria was 0.991 compared to 0.896 forthe Moll and Wright criteria (Figure 1). When consid-ering different cut points for the CASPAR Study Groupcriteria, the best cut point for classification remained ascore of    3 as in the srcinal CASPAR Study Groupanalysis (Table 2). Considering a score of    2 gave ahigher sensitivity but resulted in a drop in specificity that would not be ideal for classification criteria.When considering the individual components of the CASPAR Study Group criteria, 96.4% of PsA patients had current or previous psoriasis or a familyhistory of psoriasis with 84% having current psoriasis.Dactylitis and nail psoriasis were highly discriminatory,as only 1 control patient each had these features.Univariate binary logistic regression analysis determinedthat all of the features of the CASPAR Study Groupcriteria, with the exception of radiographic evidence of new bone formation, were significant in distinguishing Table 1.  Baseline features of the PsA patients and control patientsrecruited to the CASPAR study * PsA patients(n  111)Controlpatients(n  111) Age, median (IQR) years 44 (34–55) 52 (38–66)Disease duration, median (IQR) months 8 (5–14) 5 (3–9.25)Consultant diagnosis, no. of patientsPsA 111 0RA 0 82UA 0 13SpA 0 9ReA 0 6IBD related 0 2 Axial SpA 0 1Inflammatory OA 0 4Crystal arthritis 0 3 Arthritis, % 100 99Enthesitis, % 67† 52 Axial symptoms, % 5 1Early morning stiffness, median (IQR)minutes60 (20–120) 60 (30–120)Fulfilling Moll and Wright criteria forPsA, %80† 1Fulfilling CASPAR Study Group criteriafor PsA, %87† 1* PsA   psoriatic arthritis; CASPAR  Classification of Psoriatic Ar-thritis; IQR  interquartile range; RA   rheumatoid arthritis;UA   undifferentiated arthritis; SpA   spondylarthritis; ReA   reac-tive arthritis; IBD  inflammatory bowel disease; OA   osteoarthri-tis.†  P   0.05 versus control patients. Figure 1.  Receiver operating characteristic curve for the Classifica-tion of Psoriatic Arthritis (CASPAR) Study Group criteria and theMoll and Wright criteria predicting psoriatic arthritis diagnosis. Table 2.  Receiver operating characteristic curve analysis of the Molland Wright criteria and the CASPAR Study Group criteria*Criteria Score Sensitivity SpecificityMoll and Wright Positive 80.2 99.1CASPAR Study Groupcriteria score  1 100 42.3  2 99.1 94.6  3 87.4 99.1  4 42.3 100  5 15.3 100* CASPAR  Classification of Psoriatic Arthritis.3152 COATES ET AL   PsA patients from control patients. Multivariate forwardstepwise logistic regression determined that current orprevious psoriasis, RF negativity, nail psoriasis, familyhistory of psoriasis, and current or previous dactylitis were all associated with PsA. Table 3 shows in moredetail the proportion of patients fulfilling each individ-ual aspect of the CASPAR Study Group criteria.When considering the diagnosis of inflammatoryarticular disease (joint, spine, or entheseal) required forthe first aspect of the CASPAR Study Group criteria,there were some minor differences between the PsA patients and control patients. Nearly all patients hadarthritis. Enthesitis was significantly more frequent inPsA patients than in control patients (67% versus 52%;  P     0.029). There was a trend toward higher enthesitiscounts in PsA patients compared to control patients, butthis was not significant. When considering the 3 clinicalindices for enthesitis (MASES, Leeds Enthesitis Index,and IMPACT) individually, there was again a trendtoward higher enthesitis scores in PsA patients com-pared to control patients, but this was only significant when using the IMPACT tool (  P     0.022). There wereno individual entheseal sites or other combinations of entheseal sites that could distinguish PsA patients fromcontrol patients. Spondylitis appeared more frequentlyin PsA patients, but the difference was not significantdue to small numbers (5% versus 1%;  P   0.055).Further analysis examined the pattern of arthritisseen in PsA patients and patients with other inflamma-tory arthritides (Table 4). The average tender andswollen joint counts and the proportions of people witholigoarticular and polyarticular disease did not differsignificantly between PsA patients and control patients.Involvement of large and small joints was also similar when comparing PsA patients to all control patients.The 82 control patients with RA were found to havesignificantly higher joint counts (  P   0.008), principallydue to an increased number of small joints involved.More than 60% of RA patients had predominantly small joint disease. However, DIP joint involvement was sig-nificantly more common in PsA patients than in allcontrol patients (32% versus 16%;  P   0.007) and more Table 3.  Proportion of PsA patients and control patients fulfillingeach aspect of the CASPAR Study Group criteria*PsA patients(n  111)Controlpatients(n  111) Any psoriasis 96† 12Current psoriasis 84† 4Previous psoriasis 6† 1Family history of psoriasis 18† 8Nail psoriasis 38† 1Rheumatoid factor negative 96† 47Current or previous dactylitis 28† 1Radiographic evidence of new bone formation 2 0* Values are the percent of patients. See Table 1 for definitions.†  P   0.05 versus control patients. Table 4.  Disease patterns in PsA patients, all patient controls, and RA patient controls*PsA patients(n  111) All patient controls(n  111)RA patient controls(n  82)Proportion with arthritis, % 100 99 100Oligoarthritis, % 30 24 15Polyarthritis, % 70 76 85DIP joint involvement, no. (%) 35 (32)†‡ 18 (16) 15 (18)Tender joint count, median (IQR) 7 (3–16)‡ 8 (4–19) 12 (6–22)Swollen joint count, median (IQR) 5 (2–9)‡ 5 (3–12) 7 (3–14)Joints with active disease, median (IQR) 9 (4–17)‡ 10 (5–20) 12.5 (7–23)Predominantly small joint arthritis, no. (%) 59 (54) 59 (54) 50 (62)Predominantly large joint arthritis, no. (%) 51 (46) 50 (45) 31 (38)Small joints involved, median (% of total) 7 (12)‡ 9 (16) 11.5 (20)Large joints involved, median (% of total) 1 (10) 1 (10) 1.5 (15)Symmetry number, median (IQR) 0.5 (0–0.78)†‡ 0.67 (0.29–0.86) 0.73 (0.49–0.89)Symmetric disease, no. (%) 58 (52)‡ 72 (65) 62 (76)Proportion with enthesitis, % 67† 52 52Enthesitis count, median (IQR) 2 (0–4) 1 (0–3) 1 (0–4)Proportion with spondylitis, % 5 1 0* DIP  distal interphalangeal (see Table 1 for other definitions).†  P   0.05 versus all control patients.‡  P   0.05 versus RA control patients.USE OF CASPAR CRITERIA IN EARLY PsA 3153
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