ORIGINAL ARTICLE

Remission criteria and activity indices in psoriatic arthritis

M. L. Acosta Felquer & L. Ferreyra Garrott & J. Marin &

E. Catay & M. Scolnik & V. Scaglioni & S. Ruta & J. Rosa &

E. R. Soriano

Received: 25 January 2014 /Revised: 8 April 2014 /Accepted: 10 April 2014# Clinical Rheumatology 2014

Abstract Remission criteria and activity indices used in rheu-matoid arthritis (RA) are often applied in psoriatic arthritis(PsA). Some new indices have been specifically developed forPsA. Our objective was to evaluate the performance of differ-ent remission criteria and activity indices in PsA. This is across-sectional study that includes consecutive patients withPsA. Information necessary to complete the following indiceswas captured: Composite Psoriatic Disease Activity Index(CPDAI), Psoriatic Arthritis Screening and Evaluation(PASE), Disease Activity Index for Psoriatic Arthritis(DAPSA), Disease Activity Score in 28 Joints (DAS28),Simplified Disease Activity Index (SDAI), Clinical DiseaseActivity Index (CDAI), and American College of Rheumatol-ogy and European League Against Rheumatism (ACR/EULAR) Boolean RA remission criteria. Patients were clas-sified according to activity categories (remission, low, medi-um, or high disease activity). Correlation between indices wasestablished. Fifty-five patients were included. Mean age was53 years (SD=12), and 35 (63.6 %) were males. Mean PsAdisease duration was 5.9 years (SD=8.5), and mean psoriasisduration was 15.9 (SD=12.6). We found important differ-ences in the percentage of patients classified as in remissionby applying different remission criteria: DAS28=33 % (95 %confidence interval (CI) 20–45) vs ACR/EULAR=4 % (95 %CI 1–17). Particularly, DAS28 and minimal disease activityseemed to be less stringent in PsA than the other indices. Ofthe specific PsA indices evaluated, CPDAI showed thepoorest correlation with all the other activity measurements,

although differences were not statistically significant in mostcases. Disease activity in PsA is measured by many differentindices. In spite they all showed good correlations betweenthem, they classified different patients in different diseasestatus.

Keywords Minimal disease activity . Psoriatic arthritis .

Remission criteria

Introduction

Psoriatic arthritis (PsA) is a multifaceted disease that involvesperipheral and axial joints, skin and nails, enthesis, anddactylitis. It is important to capture data of all these clinicalfeatures in order to assess disease activity. Composite mea-sures combine several dimensions of disease status often bycombining these different domains into a single score. Suchindices seem to be more efficient than unidimensionalinstruments.

Remission criteria and activity indices used in rheumatoidarthritis (RA) are often applied in PsA [1–3]. The AmericanCollege of Rheumatology Index [4] and the Disease ActivityScore in 28 Joints (DAS28) [5] have historically been used formeasuring PsA in clinical trials [1–3].

Some new indices have been specifically developed forPsA: Composite Psoriatic Disease Activity Index (CPDAI)[6], Disease Activity Index for Psoriatic Arthritis (DAPSA)[7], Psoriatic Arthritis Disease Activity Score (PASDAS) [8],Arithmetic Mean of Desirability Function (AMDF) [8], andminimal disease activity (MDA) criteria in PsA [9].

In the recently published European League Against Rheu-matism (EULAR) recommendations for the management ofpsoriatic arthritis with pharmacological therapies [10], theauthors stated: “The primary goal of treating patients withpsoriatic arthritis is to maximize long-term health-related

M. L. Acosta Felquer : L. Ferreyra Garrott : J. Marin : E. Catay :M. Scolnik :V. Scaglioni : S. Ruta : J. Rosa : E. R. Soriano (*)Rheumatology Section, Medical Services, Hospital Italiano deBuenos Aires, Instituto Universitario Escuela de Medicina HospitalItaliano de Buenos Aires and Fundación Dr. Pedro M Catoggio parael Progreso de la Reumatologia, Peron 4190 (1181), CABA,Buenos Aires, Argentinae-mail: enrique.soriano@hospitalitaliano.org.ar

Clin RheumatolDOI 10.1007/s10067-014-2626-y

quality of life, through control of symptoms, prevention ofstructural damage, normalization of function and social par-ticipation; abrogation of inflammation, targeted at remission,is an important component to achieve these goals” [11]. Whileno remission criteria have been standardized for PsA, datafrom several clinical series [12–15] and from the SwedishEarly Psoriatic Arthritis Register [16, 17] reported a frequencyof clinical remission (using different remission criteria) rang-ing from 17.6 to 58 %, with the highest rate observed inpatients treated with anti-TNF-α agents [14, 15]. This widerange may be partly explained by the absence of validatedcriteria for remission in PsA, which has led to the use ofdifferent sets for remission assessment as well as the differentmethods of selecting patients [18, 19]. Our objective was toevaluate the performance of different remission criteria andactivity indices in PsA.

Methods

Study design This is a cross-sectional study. This study wasapproved by the Hospital Italiano Ethical Committee.

Patients

Consecutive patients with PsA fulfilling CASPAR criteria[20] seen at the Rheumatology Section of Hospital Italianode Buenos Aires between March and June 2012, who accept-ed to participate, were included. At study entry, the followingindices (see below) were collected: CPDAI, DAPSA, Psoriat-ic Arthritis Screening and Evaluation (PASE), MDA, DAS28,Simplified Disease Activity Index (SDAI), Clinical DiseaseActivity Index (CDAI), and American College of Rheumatol-ogy (ACR)/EULAR Boolean RA remission criteria [21, 22].We also included the following: Health Assessment Question-naire (HAQ), Bath Ankylosing Spondylitis Disease ActivityIndex (BASDAI), Bath Ankylosing Spondylitis FunctionalIndex (BASFI), and Psoriatic Assessment of Skin Index(PASI). The treating rheumatologist also recorded his/herintention to change treatment.

All indices were applied to all patients and were classifiedaccording to activity categories (remission, low, moderate, orhigh disease activity). Percentage of patients in remission usingACR/EULAR criteria and with MDAwas also calculated.

Assessment instruments

All assessments were done by the same rheumatologist(MLAF).

– In CPDAI [6], disease involvement is assessed in up tofive domains: peripheral joints [swollen joint count (SJC)

of 66 and tender joint count (TJC) of 68], skin (PASI),enthesitis (number of tendons/fascia insertion sites show-ing enthesitis scored from 0 to 4, based on palpation ofAchilles tendon and bilateral plantar fasciae insertion),dactylitis (a simple count of each digit involved), andspinal manifestations [BASDAI and ASQol (AnkylosingSpondylitis Quality of Life)]. Domains are scored from 0to 3, giving a CPDAI score range of 0–15. For axialinvolvement, BASDAI and ASQol were calculated onlyin patients who had inflammatory low back pain for morethan 3 months and/or X-ray evidence of axial involve-ment. Otherwise, they received a score of 0 for axialinvolvement. Recently, the cutoff values for low and highdisease activity have been established at four and eightpoints, respectively (Helliwell, personal communication).A modified CPDAI (mCPDAI), as previously described[23] including only four domains (without axial domain),was also calculated.

– DAPSA [7] score is a simple arithmetic sum of thefollowing: (1) patient-reported pain and global assess-ment on a 0–10 scale; (2) joint involvement, signifiedbest by 66 swollen joint counts and 68 tender joint countsas main variables; and (3) acute phase response, repre-sented by CRP (mg/dl). DAPSA=66 SJC+68 TJC+PtGA+pain+CRP. Cutoff values for low and high dis-ease activity have been set at 18.5 and 45.1 points(Helliwell, personal communication).

– PASE [24] is a patient self-administered questionnairethat consists of 15 questions divided into two subscales:symptoms subscale with seven questions and functionsubscale with eight questions. The scoring system pro-vides a numeric scale; those individuals who are morelikely to have PsA will score higher than individualswithout PsA. We used the validated Spanish version[25]. Although this is a screening questionnaire, it has afunction subscale and has proved to be sensitive tochange after initiation of therapy [26] and might be usefulas an activity index.

– DAS28 [5, 27] score considers 28 tender and swollenjoint counts and general health [GH; patient assessmentof disease activity using a 100-mm visual analog scale(VAS) with 0=best and 100=worst], plus levels of anacute phase reactant [either ESR (mm/h) or CRP (mg/l)].DAS28 values were calculated as follows:

DAS28 ESRð Þ ¼ 0:56�ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi

TJC28ð Þ þ 0:28p

�ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi

SJC28ð Þ þ 0:014p

� GH

þ 0:70� In ESRð Þ;

Remission was defined if DAS28 score is ≤2.6, lowdisease activity (LDA) with a score of >2.6 and ≤3.2,MDA with a score of >3.2 and ≤5.1, and high diseaseactivity (HDA) with a score of >5.1.

Clin Rheumatol

– SDAI [28] is the simple sum of the tender joint count(using 28 joints), swollen joint count (using 28 joints),patient global assessment (0–10 scale), physician globalassessment (0–10 scale), and CRP level (mg/dl). Cutoffvalues used were as follows: remission ≤3.3, LDA >3.3and ≤11, MDA >11 and ≤26, and HDA >26.

– CDAI is the same as the SDAI, except that CRP is notincluded. Cutoff values used were as follows: remis-sion ≤2.8, LDA >2.8 and ≤10, MDA >10 and ≤22, andHDA >22.

– ACR/EULAR remission criteria [21, 22], are defined bythe presence of all of the following: (1) tender jointcount≤1, (2) swollen joint count≤1, (3) CRP≤1 mg/dl,and (4) PGA≤1 (on a 0–10 scale).

– MDA [9] is defined by the presence of five of seven of thefollowing criteria: (1) tender joint count ≤1, (2) swollencount ≤1, (3) PASI ≤1 or BSA ≤3 %, (4) patient pain VAS≤15, (5) patient global activity VAS ≤20, (6) HAQ ≤0.5,and (7) tender entheseal points ≤1.

– HAQ [29] is a measure that contains 20 itemsdivided into eight domains: dressing and grooming,arising, eating, walking, hygiene, reach, grip, andcommon daily activities. Subjects rate the degree of

difficulty they have had in the past week on a four-point scale, ranging from 0 (no difficulty) to 3(unable to do). The highest scores in each categoryare summed (0–24) and divided by the number ofcategories scored to yield a score from 0 to 3.

Statistical analysis

Descriptive statistics were expressed as means and standarddeviations or percentages, where appropriate.

Percentage of patients in each level of disease activitywas calculated with their 95 % confidence intervals (CIs)using the preselected cutoff values. In order to explorewhether the same patients are classified as in remissionby different criteria, we assessed an agreement betweenremission measures by the kappa statistic and alsoshowed them with a Venn diagram.

Pearson correlation coefficients were calculated betweenDAS28, CDAI, SDAI, CPDAI, PASE, DAPSA, HAQ,BASDAI, and modified CPDAI.

A receiver operating characteristic (ROC) curve wasconstructed to investigate the discriminative ability ofeach one of the composite activity indices for treatmentchange. The area under the curve (AUC) provided ameasure of the overall discriminative ability of thedifferent activity indices.

P values less than 0.05 were considered statisticallysignificant.

Results

Fifty-five patients were included. Patients’ characteristics areshown in Table 1. Mean age was 53 years (SD=12), and 64%

Table 1 Patients’ characteristics

PsA patients (n=55)

Male, n (%) 35 (63.6)

Mean age, years (SD) 53 (12)

Mean PsA duration, years (SD) 5.9 (8.5)

Mean psoriasis duration, years (SD) 15.9 (12.6)

Mean tender joint count (SD) 4.3 (6)

Mean swollen joint count (SD) 2.4 (3)

Mean PASI (SD) 1.9 (2.7)

Fig. 1 Percentage of patients inremission and different levels ofactivity according to differentindices. LDA low disease activity,MDA moderate disease activity,HDA high disease activity,DAS28 Disease Activity Score in28 Joints, CDAI Clinical DiseaseActivity Index, SDAI SimplifiedDisease Activity Index, CPDAIComposite Psoriatic DiseaseActivity Index, DAPSA DiseaseActivity Index for PsoriaticArthritis, MDA minimal diseaseactivity

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were males. Mean PsA disease duration was 5.9 (SD=8.5)years, and mean psoriasis duration was 15.9 (SD=12.6).Sixteen patients (30 %) had axial involvement, of whom nine(35 %) had a radiologic evidence of sacroiliitis. In 33 patients(60 %), the treating rheumatologist indicated an initiation (21patients) or change in DMARD treatment.

Figure 1 and Table 2 shows the percentage of patients ineach disease activity status for the different indices. DAS28was the index that classified the major number of patients as inremission, while SDAI was the one that classified the lowernumber in that status. Twenty-nine percent of patients wereconsidered to be in minimal disease activity.

Table 3 shows the Pearson correlation coefficients betweenthe different indices, with their 95 % confidence intervals. Asseen in the table, activity indices, taking into account onlyjoint disease (DAS28, CDAI, SDAI, and DAPSA), showedvery good correlation between each other. PASE, although notdeveloped as an activity index, showed very good correlationwith DAPSA (r=0.65), HAQ (r=0.84), DAS28 (r=0.75),CDAI (r=0.75), tender joint count (r=0.71), patient globalactivity (r=0.71), and BASDAI (r=0.84); correlation wasmoderate with CPDAI (r=0.43) and swollen joint count(r=0.47). CPDAI correlation coefficients were in generallower, although the only significant difference were the cor-relation with PASE, compared with the correlation of PASEwith CDAI, and compared with the correlation of PASE withDAS28; and the correlation between CPDAI with DAPSA,when compared with the correlation between DAPSA andDAS28, and DAPSA with SDAI (Table 3). The modifiedCPDAI score (without the axial domain), seemed to correlatebetter with all the other indices than the original CPDAI,although the differences were not significant.

Similar cross-sectional probabilities do not necessarilymean that the same patients are identified by the differentcriteria. To investigate agreement, we applied kappa statistics

Table 2 Percentage of patients in remission and different levels ofactivity according to the different indices

Index Percentage inremission(95 % CI)

Low diseaseactivity(95 % CI)

Moderatediseaseactivity(95 % CI)

High diseaseactivity(95 % CI)

DAS28 33 (20–45) 11 (4–22) 43 (30–58) 13 (5–24)

SDAI 4 (0.4–14) 34 (21–49) 36 (23–51) 26 (15–40)

CDAI 9 (1–17) 36 (24–50) 35 (22–48) 20 (10–33)

CPDAI 78 (65–88) 5 (0.01–15)

ACR/EULAR(Boolean)

9 (1–17) – – –

MDA 29 (18–43) – – –

DAS28 Disease Activity Score in 28 Joints, SDAI Simplified DiseaseActivity Index,CDAIClinical Disease Activity Index,CPDAICompositePsoriatic Disease Activity Index, MDA minimal disease activity T

able3

Pearsoncorrelationcoefficientsbetweendifferentindices

(95%

confidence

intervals)

Index

DAS2

8CDAI

SDAI

CPDAI

PASE

HAQ

BASD

AI

mCPDAI

DAPSA

DAS28

10.83

0.75

0.60

0.75

0.71

0.68

0.73

0.78

CDAI

0.83

(0.7–0.9)

10.76

0.57

0.75

0.70

0.63

0.75

0.70

SDAI

0.75

(0.6–0.85)

0.76

(0.6–0.85)

10.42

0.61

0.61

0.52

0.55

0.96

CPDAI

0.60

(0.4–0.7)

0.57

(0.35–0.7)

0.42

(0.14–0.6)

10.44

0.53

0.38

0.86

0.41

PASE

0.75

(0.6–0.85)

0.75

(0.6–0.85)

0.61

(0.4–0.8)

0.44

(0.18–0.6)

10.84

0.84

0.60

0.65

HAQ

0.71

(0.5–0.8)

0.70

(0.5–0.8)

0.61

(0.4–0.8)

0.53

(0.3–0.7)

0.84

(0.7–0.9)

10.76

0.65

0.63

BASD

AI

0.68

(0.45–0.8)

0.63

(0.4–0.8)

0.52

(0.3–0.7)

0.38

(0.1–0.6)

0.84

(0.7–0.9)

0.76

(0.6–0.85)

10.54

0.55

mCPD

AI

0.73

(0.6–0.8)

0.75

(0.6–0.8)

0.55

(0.3–0.7)

0.86

(0.8–0.9)

0.60

(0.4–0.75)

0.65

(0.5–0.8)

0.54

(0.3–0.7)

10.41

DAPS

A0.78

(0.6–0.8)

0.70

(0.5–0.8)

0.96

(0.7–0.99)

0.41

(0.06–0.6)

0.65

(0.5–0.8)

0.63

(0.4–0.8)

0.55

(0.4–0.8)

0.41

(0.03–0.6)

1

The

numbersin

italicsrepresentp

erfectagreem

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DAS28Disease

Activity

Scorein28

Joints,C

DAIClin

icalDisease

Activity

Index,SD

AISim

plifiedDisease

Activity

Index,CPDAICom

positePsoriaticDisease

Activity

Index,PA

SEPsoriaticArthritis

ScreeningandEvaluation,HAQHealth

Assessm

entQ

uestionnaire,B

ASD

AIB

athAnkylosingSp

ondylitisDisease

Activity

Index,mCPDAIm

odifiedCom

positePsoriatic

Disease

Activity

Index,DAPSA

Disease

Activity

IndexforPsoriatic

Arthritis

Clin Rheumatol

(Table 4). There was only moderate to poor agreement beyondchance between the different indices. The best agreement wasbetween CDAI and ACR/EULAR Boolean criteria, and thelower agreement was between SDAI and DAS28 and betweenSDAI and MDA.

This is also shown in Venn diagram (Fig. 2). As can beseen, only four patients (7 %) were classified as in remissionby ACR criteria and DAS28 and considered to be in MDA,while only five patients (9%) were considered in remission byboth ACR and DAS28 criteria.

All indices showed a good discriminative power for achange in treatment in the ROC curve (Fig. 3): PASE–AUC=0.78 (95 % CI 0.65–0.9), CPDAI–AUC=0.81 (95 % CI 0.7–0.9), DAPSA–AUC=0.78 (95%CI 0.65–0.91), DAS28–AUC=0.92 (95 % CI 0.89–1), CDAI–AUC=0.93 (95 % CI 0.87–0.99), and SDAI–AUC=0.89 (95 % CI 0.79–0.9).

Discussion

Most of the instruments currently used to assess treatmentresponse in PsA are derived from studies in rheumatoid

arthritis. These measures have proven useful in separat-ing active treatment from placebo, but they appear lesseffective when two similar, active treatments are com-pared [11]. The measures are largely measures of jointinflammation only; other components of PsA includingskin, entheseal, dactylitic, axial, and nail responses arenot included. A number of new, composite measures ofdisease activity have recently been proposed, but thereis very scarce information of how these measures com-pare between each other in PsA patients outside clinicaltrials. In a disease with involvement of multiple differ-ent structures, it is logical to define remission as theabsence of activity in all the domains involved. In thatline, Group for Research and Assessment of Psoriasisand Psoriatic Arthritis (GRAPPA) has been working inthe development and validation of composite measuresof disease activity [30]. As a result of that, two com-posite indices PASDAS and AMDF have been devel-oped and validated, and it was agreed at the lastOMERACT meeting that further exploration and valida-tion of all of these composite measures was appropriateto continue to investigate [30].

There is some concern with the concept of a com-posite score combining very different elements of onedisease into a single score that may not respond simi-larly to a single therapy [30]. Disease activity in differ-ent domains of PsA may be unrelated; for example,arthritis may flare when skin psoriasis is controlled orvice versa, and there are obviously different treatmentimplications depending on what element of the diseaseis active [30]. This study would not help to solve thisconcern, as only one composite measure was included.This study was done in patients seen in routine clinicalpractice. There are some feasibility issues with theproposed composite measures in daily clinical practice.The first one is related to the complexity of calculating

Table 4 Agreement in percentages of patients in remission amongdifferent indices using kappa statistics

Index DAS28 CDAI SDAI ACR/EULAR MDA

DAS28 1 0.34 0.14 0.34 0.41

CDAI 0.34 1 0.55 0.78 0.28

SDAI 0.14 0.55 1 0.25 0.17

ACR/EULAR 0.34 0.78 0.25 1 0.28

MDA 0.41 0.28 0.17 0.28 1

The numbers in italics represent perfect agreement

DAS28 Disease Activity Score in 28 Joints, CDAI Clinical DiseaseActivity Index, SDAI Simplified Disease Activity Index, MDA minimaldisease activity

Fig. 2 Venn diagramrepresenting the number ofpatients meeting differentremission criteria

Clin Rheumatol

the PASDAS and AMDF scores once all of the assess-ments have been done. Both of these require statisticaltransformations of all of the variables with complexequations. Although all of these could be done usinga calculator such as that used for the DAS28, it requirestime in a busy routine consultation. The second feasi-bility issue, and perhaps the most important, is thenecessity to perform different articular and non-articular outcome assessments to allow calculation ofthe scores. These assessments include the physical com-ponent of the SF36 that needs a license for clinical useand the Psoriatic Arthritis Quality of Life index(PsAQol) that, for example, has not been validated inSpanish. These issues partially explain why we have notincluded these measures in our study.

In spite of not helping to solve the discussion ofthe usefulness of composite measures in the assess-ment of PsA, there is still some valuable informationin our study. We found that there were importantdifferences, not only in the percentage of patientsclassified as in remission by the different remissioncriteria but also in which patients would be includedin each category as well. Particularly, DAS28 andMDA seemed to be less stringent in PsA than theother indices. Among the composite indices, studiedCPDAI showed the poorest correlation with all theother activity measurements, probably reflecting thefact that CPDAI not only assess peripheral arthritis,but the skin, enthesis, and dactylitis as well, althoughthe differences were not statistically significant inmost cases. Probably, a larger sample size would havebeen needed to show differences.

If remission would be our target, there is a need tohave an accepted definition of the state of remission inPsA. Even more, a treat-to-target (T2T) approach similarto the one currently used in rheumatoid arthritis isgoing to be pushed forward in PsA [31]. Coates et al.have made progress regarding a definition of MDA [9],but as shown in our study, this definition might not bestringent enough. One of the problems that have notbeen addressed in this study is whether control ofcomposite disease activity delays or halts disease pro-gression or improves long-term outcome or survival, sothis study did not attempt to choose the best remissioncriteria.

In our study, it was shown, however, that all indices have agood discriminative power to detect patients that would re-ceive a change in therapy because of disease activity.

In summary, we have shown that different indicesproposed and used in PsA performed differently, classi-fying different percentages and different patients in thedifferent diseases stages. If remission would be ourtarget and T2T approach is going to be taken forward,there is an urgent need to define and agree with aremission definition in PsA.

Conflict of interest The authors declare no conflict of interests.

Funding There was no funding for this study.

Ethical approval The study was conducted according to the Declara-tion of Helsinki and local regulations. Ethical approval for the study wasobtained from the hospital local ethics committee, and informed consentwas obtained from all patients.

Fig. 3 Receiver operatingcharacteristic (ROC) curve ofdifferent indices for a change intreatment. DAS28 DiseaseActivity Score in 28 Joints, CDAIClinical Disease Activity Index,SDAI Simplified Disease ActivityIndex, CPDAI CompositePsoriatic Disease Activity Index,DAPSA Disease Activity Indexfor Psoriatic Arthritis, PASEPsoriatic Arthritis Screening andEvaluation

Clin Rheumatol

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