Composite Psoriatic Disease Activity Index Research Articles

Clinical Characteristics of "Severe" Peripheral Psoriatic Arthritis: A Retrospective Analysis of a Longitudinal Cohort.

The concept of severity in a multidomain disease such as psoriatic arthritis (PsA) is still not well defined. The aim of this study was to identify the clinical characteristics of patients with severe peripheral PsA. Retrospective analysis of a longitudinal cohort. Demographic and clinical characteristics of patients with PsA were collected at baseline and at last follow-up. We defined the severe population using the modified Composite Psoriatic Disease Activity Index (mCPDAI); which excludes ankylosing spondylitis quality of life scale). Hence, patients with a score of 3 in at least one domain were defined as having severe PsA. Clinical characteristics of patients fulfilling the definition of severe PsA were compared to those non-severe. We evaluated 177 patients with peripheral PsA (M/F: 98/76). Of these, 64 (36.1%) were identified as severe according to the mCPDAI criteria, at baseline. Eighteen patients (10.1%) at last follow-up still met the definition of severe PsA. At last follow-up visit, severe patients with PsA were only males (18/18, P < 0.01) and have worse outcomes in terms of disease activity, pain, function, and impact of disease. Male sex and the severity of skin involvement at baseline were factors associated with the presence of severe PsA. The agreement between the presence of severe PsA and the absence of minimal disease activity was slight [Cohen's k: 0.174 (0.084-0.264)]. Our study showed that severe patients with PsA had more disease activity, pain, and impact of disease than non-severe patients. Furthermore, we demonstrated that severity and disease activity are not interchangeable concepts.

Serum and Synovial Levels of Cathepsin G and Cathepsin K in Patients with Psoriatic Arthritis and Their Correlation with Disease Activity Indices.

This retrospective case-control study examined the relationship between the serum and synovial levels of cathepsin G (CatG) and cathepsin K (CatK) in patients with psoriatic arthritis (PsA) and their association with disease activity. Methods: This case-control study involved 156 PsA patients, 50 patients with gonarthrosis (GoA), and 30 healthy controls. The target parameters were measured using enzyme-linked immunosorbent assay (ELISA) kits. The serum levels of CatG and CatK were found to be significantly higher in PsA patients compared to both control groups (p < 0.001). Moreover, they could distinguish PsA patients from healthy controls with 100% accuracy. Synovial fluid CatG and CatK were positively associated with the following indicators of disease activity: the VAS (rs = 0.362, rs = 0.391); the DAPSA (rs = 0.191, rs = 0.182); and the mCPDAI (rs = 0.378, rs = 0.313). Our results suggest that serum and synovial fluid CatG and CatK levels could serve as biomarkers for PsA. In PsA patients with synovial fluid crystals, elevated synovial CatG levels demonstrated a sensitivity of 89.54% and a specificity of 86.00% in distinguishing them from PsA patients without crystals. Similarly, elevated synovial CatK levels had a sensitivity of 93.67% and a specificity of 94.34% for distinguishing PsA patients with synovial fluid crystals from those without. Furthermore, the synovial fluid levels of both CatG and CatK showed positive associations with key indicators of disease activity, including the visual analog scale (VAS) (rs = 0.362, rs = 0.391), the disease activity in psoriatic arthritis (DAPSA) (rs = 0.191, rs = 0.182), and the modified composite psoriatic disease activity index (mCPDAI) (rs = 0.378, rs = 0.313). In conclusion, our findings suggest that the serum and synovial fluid levels of CatG and CatK hold promise as potential biomarkers for assessing disease activity in psoriatic arthritis.

Initiating Evaluation of Composite Outcome Measures for Psoriatic Arthritis: 2022 Updates From the GRAPPA-OMERACT Working Group.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) working group-comprising rheumatologists, dermatologists, methodologists, and patient research partners-provided updates at the GRAPPA 2022 annual meeting on its work to evaluate composite outcome measures for PsA. Ten composite outcome measures were considered. Initial steps were to define the population, the purpose of use, and the proposed pros and cons of the 10 candidate composite instruments for PsA. Preliminary Delphi exercises within the working group and GRAPPA stakeholders confirmed high priority for evaluating minimal disease activity (MDA); moderate priority for Disease Activity in PsA (DAPSA), American College of Rheumatology (ACR) response criteria, Psoriatic Arthritis Disease Activity Score (PASDAS), Composite Psoriatic Disease Activity Index (CPDAI), 3 visual analog scale (VAS), and 4VAS; and low priority for Disease Activity Score in 28 joints (DAS28), Psoriatic Arthritis Responder Criteria (PsARC), and Routine Assessment of Patient Index Data 3 (RAPID3). Further appraisal of candidate composite instruments is ongoing.

Comparative performance of composite measures from two phase III clinical trials of ixekizumab in psoriatic arthritis

Background/objectiveThe aim of this study was to evaluate relative performance of composite measures in psoriatic arthritis and assess the impact of structural damage and functional disability on outcomes during ixekizumab...

Assessment of Crystals in the Synovial Fluid of Psoriatic Arthritis Patients in Relation to Disease Activity.

Background: This study examines the relationship between the presence of crystals in the synovial fluid of patients with psoriatic arthritis (PsA) and disease activity. Methods: The synovial fluid of 156 PsA patients was analyzed and compared to 50 patients with gonarthrosis (GoA). The Leica DM4500P polarization microscope was used for crystal detection. Results: The presence of crystals was observed in 23.71% of PsA patients and none of the GoA patients, p < 0.001. Monosodium urate crystals (67.58%) and calcium pyrophosphate crystals (21.62%) were prevalent. The presence of crystals in the synovial fluid of PsA patients was associated with high disease activity according to the Composite Psoriatic Disease Activity Index (OR = 18.75, 95%; CI: 7.13 to 49.25) and the Disease Activity for Psoriatic Arthritis (OR = 15.96, 95%; CI: 5.76 to 44.23), with severe disability according to the Health Assessment Questionnaire Disability Index (OR = 13.60, 95%; CI: 5.09 to 36.31), and with severe pain on the Visual Analog Scale (OR = 157.25, 95%; CI: 39.50 to 625.94). Conclusion: Our results suggest that synovial fluid examination should be included in the treatment pathway for PsA patients with active disease, to aid in determining whether urate-lowering therapy is required.

Role of ultrasound for assessment of psoriatic arthritis patients with fibromyalgia

ObjectiveTo investigate whether ultrasonography (US), as an objective imaging modality, can optimise the evaluation of disease activity in psoriatic arthritis (PsA) patients with concomitant fibromyalgia syndrome (FMS).MethodsThe study population included...

AB0570 BONE MINERAL DENSITY, TRABECULAR BONE SCORE AND PROXIMAL FEMUR 3D-DXA ANALYSIS IN PSORIATIC DISEASES

Background:current data regarding areal bone mineral density (aBMD) in patients with psoriasis (PsO) or psoriatic arthritis (PsA) are conflicting. Results on Trabecular Bone Score (TBS) in these patients are lacking. 3D-analysis of cortical and trabecular bone from hip DXA is a new method for non-invasive bone structure assessment, providing separate assessment of the cortical layer and trabecular macrostructure.Objectives:Case-control study (NCT02849795)Methods:52 PsO and 52 PsA cases (CASPAR criteria) were each paired to a control subject matched for age, sex and body mass index (BMI). aBMD measurements at (L2-4) lumbar spine (LS), femoral neck (FN) and total hip (TH) were performed using DXA, Lunar GE. TBS was calculated from antero-posterior L2-L4 BMD image using TBS iNsight V1.8 (Med-Imaps, Pessac, France). 3D-SHAPER software (version 2.10, Galgo Medical S.L, Barcelona, Spain) was used to derive a 3D analysis from the hip DXA scans.Results:LS and TH aBMD measurements did not differ between patients with PsO or PsA and their respective controls (Table 1). Left FN BMD was higher in patients with PsO compared to controls (p = 0.028), a difference not observed on the right FN. TBS was similar in PsA patients and their controls while decreased values were observed in PsO patients (p = 0.04). In 3D analysis, none of the parameters differed between patients with PsA and their controls. For patients with PsO, no difference was found with the controls for 3D-DXA parameters from the right FN, while total hip cortical surface BMD (sBMD) of the left FN was higher in PsO compared to their controls (p = 0.037). Similarly, cortical thickness (Cth) of the intertrochanteric and shaft regions of the left FN was also higher in PsO (p = 0.032 and p = 0.033). Finally, analysis by region (neck, intertrochanteric and shaft) showed higher values for cortical sBMD from each region of the left FN in the patients with PsO (all p &lt;0.05).Conclusion:Our results showed comparable aBMD, TBS and 3D proximal femur parameters in patients with PsA and controls. This supports that PsA population is not at increased risk of osteoporosis. In patients with PsO, while LS bone microarchitecture seems impaired, FN displayed better cortical parameters than the controls. Although these results seem marginal, they support the fact that patients with PsO are not at high risk for osteoporosis and hip fracture.Table 1.PsA: psoriatic arthritis; PsO: psoriasis; M: male; F: female; BMI: body mass index; PASI: psoriasis area severity index; CPDAI: composite psoriatic disease activity index; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; aBMD: areal bone mineral density; LS: lumbar spine; FN: femoral neck; TH: total hip; TBS: trabecular bone score; sBMD: surface bone mineral density; Cth: cortical thickness; quantitative data are mean ± standard deviation; * and ***: paired t test comparing patients with psoriatic arthritis or psoriasis alone to their respective controls; * p &lt; 0.05; *** p &lt; 0.001).PsAPsA controlsPsOPsO controlsN52525252Age (years)52.5 ± 11.752.8 ±11.150.5 ± 12.850.7 ± 12.8Sex (M/F)25/2725/2738/1436/16Menopausal women18 (67%)16 (59%)5 (36%)8 (50%)BMI (Kg/m2)27.4 ± 5.927.7 ± 6.428.4 ± 5.828.2 ± 6.1PASI2.4 ± 4.18.4 ± 4.9CPDAI7.4 ± 3.3ESR (mm/h)19.8 ± 16.6 ***6.9 ± 5.810.7 ± 8.8 ***6.4 ± 6.4CRP (mg/L)10.5 ± 11.7 ***3.9 ± 4.86.0 ± 9.04.7 ± 5.5LS (L2-4) aBMD (g/cm2)1.27 ± 0.491.20 ± 0.201.25 ± 0.211.20 ± 0.18FN aBMD (g/cm2) right0.96 ± 0.120.94 ± 0.140.98 ± 0.150.98 ± 0.15 left0.96 ± 0.160.93 ± 0.121.0 ± 0.14 *0.97 ± 0.13TH aBMD (g/cm2)1.01 ± 0.161.00 ± 0.151.11 ± 0.221.06 ± 0.21L2-L4 TBS1.32 ± 0.111.32 ± 0.151.23 ± 0.15 *1.30 ± 0.16Cortical sBMD (left FN) (mg/cm2)169.7 ± 32.8163.1 ± 29.7182.0 ± 31.0 *173.5 ± 30.3Cth intertrochanteric (left FN) (mm)1.91 ± 0.201.94 ± 0.182.03 ± 0.23 *1.97 ± 0.19Cth shaft (left FN) (mm)2.98 ± 0.313.01 ± 0.283.19 ± 0.36 *3.09 ± 0.29Cortical sBMD (left FN) (mg/cm2)neck135.27 ± 26.9129.67 ± 21.9140.29 ± 24.2 *134.6 ± 22.5intertrochanteric162.32 ± 31.1155.34 ± 29.3171.39 ± 29.1 *163.1 ± 28.9shaft cort269.20 ± 49.0257.12 ± 47.3286.2 ± 47.5 *272.7 ± 45.2Disclosure of Interests:ERIC TOUSSIROT: None declared., Renaud Winzenrieth Employee of: GALGO MEDICAL, maxime DESMARETS: None declared., Daniel Wendling: None declared., Francois AUBIN: None declared., Gilles DUMOULIN: None declared.

OP0224 CONTINUOUS COMPOSITE MEASURES FOR ROUTINE CARE IN PSORIATIC ARTHRITIS: THRESHOLDS OF MEANING AND CLINICALLY IMPORTANT DIFFERENCE ESTIMATES FOR THE 3 AND 4 VAS SCALES FROM A UK MULTICENTRE STUDY

Background:There is a recognised need for a continuous composite measure of disease activity for the assessment of Psoriatic Arthritis (PsA) in routine clinical settings to allow objective assessment of response and implementation of treat to target.1 Longer multidimensional measures are considered less feasible in routine care and a number of shorter measures have been proposed including, the Disease Activity Score for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), the 3 Visual Analogue Scale (VAS) (comprising physician global VAS, patient global VAS and patient skin VAS) or 4 VAS (comprising physician global VAS, patient pain VAS, joint VAS and patient skin VAS). Testing of these measures in clinical trial datasets has been suggested but thresholds of meaning have not been established.2Objectives:To estimate clinically relevant thresholds of disease activity and improvement for composite measures for routine clinical practice in PsA.Methods:Clinical and patient reported outcome measures were assessed in patients fulfilling CASPAR criteria for PsA at three consecutive follow up visits in a UK multicentre observational study. Participants underwent clinical assessment and completed patient reported measures including health anchor questions. Estimates for Minimal Detectible Change (MDC) were derived using 1.96*2*Standard Error of the Mean (SEM). Minimal Clinically Important Difference (MCID) for improvement were derived using the health anchor method and two distribution methods (Table 1). Thresholds for low, moderate and high disease activity were triangulated from established cut-off values for the patient global VAS, PASDAS and DAPSA.Table 1.Minimal Clinically Important Difference (MCID) and Minimal detectable change (MDC)ANCHOR (MEDIAN)DISTRIBUTION#1DISTRIBUTION #2MDCCPDAI0.51.491.54.16GRACE0.260.60.772.18PASDAS1.220.640.761.58DAS280.20.850.621.463VAS1.131.160.913.124VAS1.110.960.942.45DAPSA7.259.0910.4035.63Disease Activity Score for Psoriatic Arthritis (DAPSA); Psoriatic Arthritis Disease Activity Score (PASDAS); Composite Psoriatic Arthritis Disease Activity Index (CPDAI); Disease Activity Score 28 (DAS28).Distribution #1: Baseline standard deviation (sd) * √ 1 – Cronbach’s alphaDistribution #2: 0.5 * baseline sdMinimal detectable change (MDC): 1.96*2*SEM where SEM = baseline sd √1 - ICCResults:139 subjects were recruited (59 male, 80 female, mean (range) age (years) 52.7 (19 – 83), mean (range) duration of psoriasis (years) 21.9 (2 – 71), mean (range) duration of psoriatic arthritis (years) 6.1 (0 – 41). Cut-off values for low, moderate and high disease activity were 1.3, 2.4, and 4.8 for the 3 Vas and 1.6, 2.8 and 5.0 for the 4 VAS (Figure 1). Estimates for the MCID and MDC for the continuous composite measures and are reported in Table 1.Conclusion:We report estimates of clinically relevant improvements for continuous composite measures in PsA and estimates of low, moderate and high disease activity for the 3 and 4 VAS scales. The thresholds of meaning can now be tested in independent observational and clinical trial datasets.

O13 Which composite measure best reflects disease activity and predicts treatment change in psoriatic arthritis?

Abstract Background/Aims  Multiple composite measures of disease activity are available and used in psoriatic arthritis (PsA) research; however, poor agreement remains amongst clinicians on the optimal measure of disease activity. Research to date has focused on polyarticular PsA, despite oligoarticular disease accounting for around half of cases in clinical practice. We aim to compare the ability of Composite Psoriatic Disease Activity Index (CPDAI), Psoriatic ArthritiS Disease Activity Score (PASDAS), Disease Activity score for PSoriatic Arthritis (DAPSA), GRAppa Composite scorE (GRACE) and Disease Activity Score 28 CRP (DAS28-CRP) to assess disease activity and predict treatment change, amongst usual care patients with oligoarticular and polyarticular psoriatic disease. Methods  The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise (GRACE) dataset was utilised. Oligoarthritis was defined as &amp;lt; 5 active joints. Reference measures were clinician and patient opinions on disease control and whether treatment was escalated. Patients with baseline data for all composite measures were included. The ability of each composite measure to predict treatment change and capture disease activity was compared using the Mann-Whitney U test. Results  Data were available for 271 patients (152 oligoarthritis, 119 polyarthritis). The mean age, duration of PsA and psoriasis were similar for both groups. A higher proportion of oligoarticular patients were male. Patients with polyarticular disease had higher disease activity in skin, enthesitis and dactylitis. Using both patient and physician definitions of disease control, all composite measures were able to differentiate between patients with active and quiescent disease, regardless of disease subtype (p &amp;lt; 0.05). PASDAS demonstrated the largest differentiation in score. Differences between active and inactive disease scores were more pronounced in oligoarticular disease. PASDAS demonstrated the greatest ability to predict treatment change in both oligoarticular and polyarticular disease. Interestingly, DAPSA could not predict treatment change in polyarticular patients, p = 0.074 (Table 1). Conclusion  This is the first study to compare composite measures, in oligoarticular and polyarticular PsA in a multinational cohort. All composite measures of disease activity were able to differentiate between active and inactive disease in both subtypes. PASDAS demonstrated the largest discrimination in both polyarticular and oligoarticular disease, suggesting greatest clinical and research utility. Disclosure  L. Tucker: None. P. Helliwell: None. L. Coates: None.

Comparison of Composite Measure Remission Targets in Psoriatic Arthritis.

To identify (1) which composite measure is the most stringent target of remission; and (2) which disease component target proves the most difficult to achieve in the different states of minimal disease activity (MDA), Composite Psoriatic Disease Activity Index (CPDAI), Disease Activity Index for Psoriatic Arthritis (DAPSA), and clinical DAPSA (cDAPSA) in patients with psoriatic arthritis (PsA). There were 258 patients with PsA recruited. Disease remission was evaluated comparing 4 different composite measures and using remission cutoffs as previously proposed (very low disease activity [VLDA], CPDAI ≤ 2, DAPSA ≤ 4, cDAPSA ≤ 4). Patients met VLDA criteria (MDA 7/7) in 9.0% of visits, DAPSA remission in 19.8%, cDAPSA remission in 23.4% and CPDAI remission in 30.2%. Of 258 patients, MDA criteria (≥ 5/7) were fulfilled in 46.5%. Of those in MDA, VLDA criteria were reached in 25.0%. Patients met the pain visual analog scale (VAS) target in 57.5% of visits when they were in MDA, 43.3% when in low disease activity (MDA 5-6/7), and 44.8% when in CPDAI remission. Multivariate regression analysis revealed that pain VAS was the least likely target to be achieved. Patients with inflammatory-type back pain had significantly higher pain scores; further, a significant relationship was seen between Bath Ankylosing Spondylitis Disease Activity Index and pain VAS. Based on our analysis, VLDA proved the most stringent target of disease remission in PsA compared to CPDAI, DAPSA, and cDAPSA. The pain VAS target of ≤ 1.5 cm was the most difficult component to achieve. CPDAI ≤ 2 was found to be the least stringent remission target; however, measurements of axial involvement, which contributed to the elevated pain VAS score in patients not achieving VLDA, were included as a domain in CPDAI only.

Evaluation and Validation of a Patient-completed Psoriatic Arthritis Flare Questionnaire.

Evaluation of a psoriatic arthritis (PsA), multidimensional, patient-completed disease flare questionnaire (FLARE). The FLARE questionnaire was administered to 139 patients in a prospective observational study. The "gold standard" of flare was based on patient opinion. Test-retest reliability was evaluated by intraclass correlation coefficient (ICC). Disease activity was measured by the Psoriatic Arthritis Disease Activity Score (PASDAS), Group for Research and Assessment of Psoriasis and PsA (GRAPPA) Composite Exercise (GRACE), Composite Psoriatic Disease Activity Index (CPDAI), and Disease Activity Index for Psoriatic Arthritis (DAPSA). The most common symptoms of a PsA flare were musculoskeletal, followed by fatigue, frustration, loss of function, and an increase in cutaneous symptoms. The test-retest ICC for the FLARE questionnaire was 0.87 (95% CI 0.72-0.94). The optimum cut-off to identify a flare of disease was 4/10 (sensitivity 0.82, specificity 0.76; area under the curve 0.85). For those patients scoring ≥ 4, the mean score for the composite measures was as follows (score for those not reporting a flare in parentheses): PASDAS 5.3 ± 1.3 (3.1 ± 1.6); GRACE 4.5 ± 1.2 (2.2 ± 1.4); CPDAI 8.9 ± 2.5 (4.7 ± 3.1); and DAPSA 38.2 ± 20.3 (16.8 ± 14.9). In a new flare, the increase in composite measure score was calculated as follows: 1 for PASDAS and GRACE, 2 for CPDAI, and 7 for DAPSA. Agreement between the definition of flare using the cut-off of 4 from the questionnaire, and that indicated by the subject in a separate, standalone question was 0.57 (Cohen κ). A PsA flare displays escalation of symptoms and signs across multiple domains. The FLARE questionnaire has external validity in terms of both composite disease activity and overall patient opinion about the state of their condition.

Assessment of subclinical atherosclerosis with ankle-brachial index in psoriatic arthritis: A case-control study.

Objectives This study aims to evaluate subclinical atherosclerosis using the Ankle-Brachial Index (ABI) in patients with psoriatic arthritis (PsA). Patients and methods This case-control study included 51 PsA patients (24 males, 27 females; median age 47; range, 41 to 52 years) recruited at our hospital’s outpatient clinics between October 2016 and January 2017 and 50 healthy controls (24 males, 26 females; median age: 48.5; range, 40.7 to 56 years). Anthropomorphic measurements and laboratory results were recorded. In patients, the 66 swollen/68 tender joints count, dactylitis score, Leeds Enthesitis Index, Health-related Quality of Life, the Psoriasis Area and Severity Index, and Dermatology Life Quality Index were evaluated. Ankylosing Spondylitis Quality of Life and Bath Ankylosing Spondylitis Disease Activity Index were applied to patients with axial disease. Then, Composite Psoriatic Disease Activity Index was determined. A Doppler probe and a standard blood pressure cuff were used to calculate the ABI values for each participant.Results Patients had lower right ABI (median, 1.05 vs. 1.1, p<0.01), lower left ABI (1.04 vs. 1.09, p<0.01) and lower overall ABI (1.03 vs. 1.09, p<0.01) compared with healthy subjects. Twelve (23.5%) patients had borderline ABI, but none of the controls (p<0.01). Patients with borderline ABI had a longer duration of psoriasis (25 vs. 15 years, p=0.03). The distribution of borderline ABI value was statistically significant between patients with axial disease and peripheral disease only (42.1% vs. 12.5%, p=0.02). Disease activity was found as an independent risk factor for borderline ABI in a binary logistic regression (odds ratio 6.306, 95% confidence interval 1.185 to 33.561, p=0.031).ConclusionLower ABI was found in PsA patients than healthy controls even in those matched with traditional cardiovascular risk factors. All participants with borderline ABI were in the patient group. Borderline ABI was associated with disease activity and disease duration.

Outcomes of the 2019 GRAPPA Workshop on Continuous Composite Indices for the Assessment of Psoriatic Arthritis and Membership-recommended Next Steps.

Improving the assessment of psoriatic arthritis (PsA) is a key purpose of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA). Herein, we report the proceedings of the GRAPPA composites workshop at the 2019 GRAPPA annual meeting and the membership's recommended next steps. A review of continuous composite measures was conducted in an introductory workshop, followed by 10 breakout group sessions and a final plenary session for feedback and voting. Participants included 154 members: 87 rheumatologists, 18 dermatologists, 2 rheumatologist/dermatologists, 12 patient research partners, 14 academics, 1 methodologist, and 20 industry members. Of voting members, 88.8% agreed a need exists for a continuous composite measure for routine practice, but only 62% were currently using a composite measure. Of these, 27% were using the 28-joint count Disease Activity Score (DAS), which is not a PsA-specific measure; 20% were using a PsA-specific measure such as PsA DAS (PASDAS), Composite Psoriatic Disease Activity Index (CPDAI), or Disease Activity Index for PsA (DAPSA). Members agreed that the existing measures were not feasible in their current forms (CPDAI 83%, PASDAS 82%, and DAPSA 47%) and that modification should be tested. The majority (76%) agreed that disease effect should be measured separately from disease activity. The GRAPPA membership supports the need for a continuous composite measure of disease activity for use in routine clinical care, the separate measurement of disease effect and activity, and the testing of modifications to candidate instruments rather than the development of new measures.

P277 Assessment of disease activity using RAPID3 and evaluation of treatment effect of guselkumab in patients with PsA: results from a randomised placebo-controlled Phase 2 clinical trial

Abstract Background To evaluate the effect of guselkumab (GUS) on Routine Assessment of Patient Index Data 3 (RAPID3) in patients with psoriatic arthritis (PsA). Methods In a Phase 2 trial, patients with active PsA and ≥3% body surface area of plaque psoriasis despite current or previous treatment with standard-of-care therapies, including anti-TNFα agents, were randomized 2:1 to receive GUS 100 mg (n = 100) or placebo (PBO, n = 49) subcutaneously at weeks 0, 4, and every 8 weeks (q8w) thereafter through W44. At W16, patients from either group with &amp;lt;5% improvement from baseline in both swollen and tender joint counts were eligible for early escape to open label ustekinumab. At W24, all remaining PBO patients crossed over to receive GUS 100 mg, and then received GUS at W28 and q8w thereafter through W44. RAPID3 (0-30) is derived from the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) and numerical rating scales (0-10) for pain and patient global assessment. A change of 5.1 in RAPID3 score was identified as the minimally important difference (MID) in PsA, and RAPID3 ≤3.0 was used to define PsA remission. Change in RAPID3 and proportion of patients achieving MID were compared between treatments. Correlations of RAPID3 scores with the PsA Disease Activity Score (PASDAS), GRACE index, Disease Activity in Psoriatic Arthritis (DAPSA), and Modified Composite Psoriatic Disease Activity Index (mCPDAI) were evaluated using Spearman correlation. Results The mean (SD) RAPID3 score at baseline was 16.9 (5.19). At W24, patients in the GUS group (n = 100) achieved statistically significantly greater decrease from baseline (improvement) in RAPID3 (-5.81 ± 6.0) than the PBO group (n = 49) (-0.57 ± 5.1, p &amp;lt; 0.001), and 50% of patients in the GUS group vs 20.4% in the PBO group achieved an MID (p &amp;lt; 0.001). Higher RAPID3 remission rate in the GUS than the PBO group (14.0% vs 2.4%, p = 0.022) was observed. The mean ± SD decrease from baseline in RAPID3 was -6.36 ± 6.2 at W24, and -7.48 ± 6.3 at W44 in those who continued GUS (n = 86). Among patients who switched from PBO to GUS at W24 (n = 28), mean ± SD change from baseline (improvement) in RAPID3 was -2.28 ± 5.2 at W24 while on placebo and -7.60 ± 6.6 at W44 after switching to GUS. The RAPID3 score was highly correlated with PASDAS (r = 0.84, p &amp;lt; 0.001), GRACE index (r = 0.89, p &amp;lt; 0.001), DAPSA (r = 0.77 p &amp;lt; 0.001) and mCPDAI (r = 0.65, p &amp;lt; 0.001) at W16. Conclusion GUS-treated PsA patients demonstrated significant improvement in RAPID3 compared to PBO. RAPID3 is simple and feasible to use in routine clinical care, and it correlates well with other comprehensive PsA-specific disease activity measures. Disclosures A. Deodhar: Other; A.D. has been a study investigator for Janssen. B. Kirkham: Other; B.K. has been a study investigator for Janssen. P. Rahman: Other; P.R. has been a study investigator for Janssen. P. Helliwell: Other; P.H. has been a study investigator for Janssen. A.B. Gottlieb: Other; A.G. has been a study investigator for Janssen. W. Boehncke: Other; W.B. has been a study investigator for Janssen. X.L. Xu: Other; X.X. is a Janssen employee. P.C. Gorecki: Other; P.G. is a Janssen employee. C. Han: Other; C.H. is a Janssen employee.

Plasma gelsolin levels in patients with psoriatic arthritis: a possible novel marker.

Psoriatic arthritis (PsA) is an inflammatory disorder affecting the joints of psoriatic patients. Gelsolin regulated the actin assembly and disassembly. Reduction in plasma gelsolin levels was detected in tissue damages, including trauma, sepsis, and chronic inflammatory disorders. The study aims to investigate the potential role of gelsolin in PsA and to determine the association between gelsolin and the disease activity. Plasma gelsolin levels were measured in 76 PsA patients in comparison with 40 patients having psoriasis only and 40 age- and sex -matched healthy controls. Plasma gelsolin levels were decreased in PsA patients compared to controls and psoriasis-only patients (p˂0.0001). The optimal cutoff point of gelsolin was 172.5mg/L. Gelsolin showed 92.1% sensitivity and 95% specificity in detecting PsA. But, it had 92.1% sensitivity and 80% specificity in differentiating between psoriasis and PsA. Plasma gelsolin showed a significant negative correlation with inflammatory markers as C-reactive protein and erythrocyte sedimentation rate (p < 0.0001 and p = 0.039; respectively). A significant negative correlation between plasma gelsolin and PsA activity was detected (p < 0.0001). The PsA activity was defined by the Disease Activity for Psoriatic Arthritis Score and the Composite Psoriatic Disease Activity Index. The plasma gelsolin levels were decreased in PsA patients, suggesting that gelsolin may be implicated in the chronic joint inflammation process. Plasma gelsolin seems to be a useful predictive biomarker for diagnosing PsA and monitoring the disease activity.Key Points• This study introduces an unprecedented focus within which the relationship between the levels of plasma gelsolin and PsA is investigated• The study examines the potential role of gelsolin in PsA, and detects the association between gelsolin and the arthritis activity.• There were decreased plasma gelsolin levels in PsA patients. So, gelsolin can constitute a role in the chronic joint inflammation process.• Gelsolin may be a useful biomarker for diagnosing of PsA and monitoring the disease activity.

Serum Interleukin 23 in Psoriatic Arthritis Patients: Relation to disease activity, physical function and health related quality of life

AbstractObjective To assess interleukin 23 (IL-23) levels in the sera of psoriatic arthritis (PsA) patients and to determine the relationship of IL-23 with different disease activity indices, physical function and quality of life (QoL).Methods Fifty PsA patients and 46 matched healthy controls were included in this study. Data including a detailed history, a thorough clinical examination, skin severity based on the Psoriasis Area and Severity Index (PASI), the Disease Activity index for Psoriatic Arthritis (DAPSA) and the Composite Psoriatic Disease Activity Index (CPDAI) were obtained for all patients. Physical function was assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI) and health-related QoL was assessed using the Short Form Health Survey (SF-36), Psoriatic Arthritis Quality of Life (PsAQoL) and the Dermatology Life Quality Index (DLQI) were also assessed. Serum IL-23 levels were measured in the studied groups.Results The study included 23(46%) females and 27 (54%) males with a mean age of 42.78±12.33 years. The mean serum IL-23 level was significantly higher in PsA patients (50.89±13.86 pg/ml) than in controls (43.88±6.34 pg/ml) (p=0.006). There were significant correlations between serum IL-23 levels and different grades of DAPSA activity (p=0.007) and PASI (p=0.015). No significant correlations could be detected between serum IL-23 levels and (HAQ-DI, DLQI, SF-36 or PsAQoL). CPDAI and DAPSA were significantly correlated with DLQI, SF-36 and PsAQoL.Conclusion IL-23 is a useful biomarker for identifying joint activity or skin severity but not QoL or physical function.

Mediterranean diet and Psoriatic Arthritis activity: a multicenter cross-sectional study.

Diet is a modifiable factor implicated in chronic systemic inflammation, and the mediterranean dietary pattern is considered to be a healthy model in terms of morbidity and mortality. The main aim of this study was to evaluate the adherence to the mediterranean diet in patients with Psoriatic Arthritis (PsA) and its impact on disease activity. A cross-sectional observational study was conducted in a cohort of 211 consecutive PsA patients. We evaluated PsA activity by disease activity index for PSoriatic Arthritis (DAPSA) and composite psoriatic disease activity index (CPDAI). The NCEP-ACT III criteria were used to identify subjects with MetS, and in each subject, we evaluated body mass index (BMI). A validated 14-item questionnaire for the assessment of adherence to the mediterranean diet (PREDIMED) was recorded for all the enrolled subjects. Patients showed a median age of 55 (48-62) and disease duration was 76 (36-120) months. 27.01% of patients were classified as having MetS. The median of the mediterranean diet score (MDS) was 7 (6-9). A moderate adherence to mediterranean diet was found in 66.35% of the entire cohort; 15.64% and 18.01% of the patients showed low- and high adherence to the dietary pattern, respectively. We found a negative association between DAPSA and adherence to mediterranean diet (B = -3.291; 95% CI -5.884 to -0.698). DAPSA was positively associated with BMI (B = 0.332; 95% CI 0.047-0.618) and HAQ ( B= 2.176; 95% CI 0.984-3.368). Results from our study evidenced that in PsA patients, higher levels of disease activity as measured by DAPSA correlated with low adherence to mediterranean diet, suggesting potential benefit of antinflammatory properties of this dietary pattern.

Research in Brief.

A comparison of composite indices could help to inform future trial design in psoriatic arthritis. In an analysis of secondary outcomes of an international phase 2 trial, the Psoriatic Arthritis Disease Activity Score (PASDAS) and Grappa Composite score (GRACE) were more sensitive than the modified Composite Psoriatic Disease Activity Index (mCPDAI) and Disease Activity index for PSoriatic Arthritis (DAPSA) tools in distinguishing the treatment effect of the IL-23p19 inhibitor guselkumab over placebo. In the original trial, patients with psoriatic arthritis were randomised (2:1) to receive guselkumab 100 mg (n=100) or placebo (n=49) once every eight weeks for 44 weeks. All of the indices distinguished the treatment effect of guselkumab from placebo at week 24, but significantly more patients who received guselkumab achieved low disease states or remission according to PASDAS (35·0% vs 4·1% for placebo) and GRACE (29·6% vs 2·1%) than according to mCPDAI (45·9% vs 10·4%) or DAPSA (40·0% vs 12·2%; all p<0·001). Residual non-articular disease activity was more common in patients achieving DAPSA low disease activity than those achieving low disease according to the other indices.

Evaluating current definitions of low disease activity in psoriatic arthritis using ultrasound.

To evaluate low disease activity (LDA) cut-offs in psoriatic arthritis (PsA) using ultrasound. Eighty-three PsA patients underwent clinical and ultrasound examinations at two visits. LDA was assessed using the Disease Activity index for Psoriatic Arthritis (DAPSA ⩽ 14), the Psoriatic ArthritiS Disease Activity Score (PASDAS ⩽ 3.2), the Composite Psoriatic Disease Activity Index ⩽ 4, the DAS28-CRP ⩽ 2.8 and the minimal disease activity criteria. Ultrasound was performed at 68 joints and 14 entheses. Minimal ultrasound disease activity (MUDA-j/e) was defined as a Power Doppler score ⩽ 1, respectively at joints, paratendinous tissue, tendons and entheses. A global ultrasound score was calculated by summing Grey Scale and Power Doppler information (GUIS-j/e). LDA was present in 33.7-65.0% at baseline and in 44.3-80.6% at follow-up, depending on the criteria used. MUDA-j/e was observed in 16.9% at baseline and in 30% at follow-up. GUIS-j/e was significantly higher in patients with moderate/high disease activity vs LDA according to DAPSA and PASDAS at baseline and DAPSA, PASDAS, Composite Psoriatic Disease Activity Index and minimal disease activity at follow-up. Patients in moderate/high disease activity had MUDA-j/e in 8.1-21.4% at baseline and in 8.3-20.0% at follow-up, depending on the applied clinical composite. MUDA-j/e patients with moderate/high disease activity had higher levels of pain and pain-related items than those with LDA. The LDA cut-offs of DAPSA, PASDAS, Composite Psoriatic Disease Activity Index, minimal disease activity, but not DAS28-CRP are capable of distinguishing between high and low ultrasound activity. Pain and pain-related items are the main reason why PsA patients without signs of ultrasound inflammation are classified with higher disease activity.

Disease-specific composite measures for psoriatic arthritis are highly responsive to a Janus kinase inhibitor treatment that targets multiple domains of disease

BackgroundThe multiple disease domains affected in psoriatic arthritis (PsA) may make composite endpoints appropriate for assessing changes in disease activity over time. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Data from two phase 3 studies of patients with PsA were used to evaluate the effect of tofacitinib on composite endpoints.MethodsOral Psoriatic Arthritis triaL (OPAL) Broaden was a 12-month study of tumor necrosis factor inhibitor (TNFi)-naïve patients with an inadequate response to at least one conventional synthetic disease-modifying anti-rheumatic drug; OPAL Beyond was a 6-month study of patients with inadequate response to TNFi. Patients with active PsA received tofacitinib 5 or 10 mg doses twice daily (BID), adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL Broaden only), or placebo advancing at month 3 to tofacitinib 5 or 10 mg BID. The disease-specific composites were Psoriatic Arthritis Disease Activity Score (PASDAS), Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis (DAPSA), and Composite Psoriatic Disease Activity Index (CPDAI). Change from baseline in composite endpoints was also assessed for minimal disease activity (MDA) responders versus non-responders.ResultsOverall, 422 patients from OPAL Broaden and 394 patients from OPAL Beyond were treated. The mean changes from baseline to month 3 for tofacitinib 5 mg BID, tofacitinib 10 mg BID (standard error; effect size) were OPAL Broaden: PASDAS, −2.0 (0.14; 1.73), −2.4 (0.14; 2.4); DAPSA, −20.2 (1.72; 0.9), −24.4 (1.73; 1.23); and CPDAI, −2.9 (0.34; 1.03), −4.2 (0.36; 1.53); OPAL Beyond: PASDAS, −1.9 (0.14; 1.53), −2.1 (0.14; 1.84); DAPSA, −22.5 (1.67; 0.81), −21.0 (1.70; 0.84); and CPDAI, −3.3 (0.31; 1.41), −3.4 (0.31; 1.45). Greater changes from baseline to month 3 (P ≤0.05) were seen with both doses of tofacitinib versus placebo for all endpoints except CPDAI for tofacitinib 5 mg BID in OPAL Broaden. Effect sizes generally increased from 3 to 6 months. Mean changes from baseline were greater in MDA responders than MDA non-responders for all composite endpoints across all time points and treatments.ConclusionsThis analysis suggests that disease-specific composite measures are appropriate for evaluating treatment efficacy on multiple disease domains in PsA.Trial registrationOPAL Broaden: ClinicalTrials.gov Identifier: NCT01877668, first posted June 12, 2013; OPAL Beyond: ClinicalTrials.gov Identifier: NCT01882439, first posted June 20, 2013.