Psoriatic Arthritis Disease Activity Score Research Articles

The Role of Chitinase-3-Like Protein 1(YKL-40) as a Biomarker of Psoriatic Arthritis

Background Psoriatic arthritis (PsA) is a chronic multifaceted inflammatory seronegative arthritis. Plasma YKL-40 is an inflammatory biomarker. Objective To evaluate the role of Chitinase-3-like protein 1 (YKL-40) as a diagnostic biomarker in psoriatic arthritis (PsA) patients and determine its value in assessment of disease activity and severity in PsA patients. Patients and Methods This study included twenty five adult patients with clinical evidence of PsA and twenty five healthy matched age and sex as control group. All underwent history, laboratory investigation, clinical examination, assessment of disease activity using Disease Activity in PSoriatic Arthritis (DAPSA) Score and assessment of severity of PsA using Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Leeds Enthesitis Index (LEI) and examination of dactylitis. Results The mean age of patients was 39.72 ± 11.94. Also, The mean age of healthy controls was 42.88 ± 12.11. There was highly statistically significant difference regarding the serum levels of YKL- 40 (P < 0.01) between the patients and the control groups (P < 0.01). The receiver operating characteristic curve (ROC) curve of YKL -40 showed that the sensitivity and the specificity of YKL- 40 in diagnosis of PsA were 96% and 92% respectively. There were statistically significant positive correlations between YKL- 40 levels (μl/mL) and each of PASI score (p = 0.005) (r = 0.539) and DAPSA score (p = 0.007) (r = 0.526). Conclusion YKL- 40 measurement may serve as a diagnostic biomarker for PsA, as it has the potential to contribute to the fundamental processes underlying the pathogenesis of PsA. So, the results of this study suggested that the addition of YKL- 40 as a serological marker has a valuable role in diagnosis of PsA and reflection of disease activity.

Efficacy of tofacitinib on enthesitis in patients with active psoriatic arthritis: analysis of pooled data from two phase 3 studies

BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post hoc analysis assessed tofacitinib efficacy on enthesitis by baseline location and severity, and impact on disease activity and patient-reported outcomes (PROs), in patients with PsA.MethodsData were pooled from two phase 3 studies (NCT01877668/NCT01882439) in patients with PsA receiving tofacitinib 5 or 10 mg twice daily to month (M)6 or placebo to M3. Endpoints were: change from baseline in Leeds Enthesitis Index (LEI) or Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC); proportions of patients with enthesitis, relapsed enthesitis after resolution, de novo enthesitis, low disease activity (LDA) or remission (minimal disease activity/very low disease activity; Psoriatic Arthritis Disease Activity Score; Disease Activity Index for Psoriatic Arthritis, and Composite Psoriatic Disease Activity in Psoriatic Arthritis); and PROs (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] total and arthritis pain Visual Analog Scale scores). Descriptive statistics were generated by visit and treatment. Change from baseline in PROs was evaluated by multivariate linear regression.ResultsSeven hundred ten patients from two studies were included: 479 had LEI > 0; 545 had SPARCC > 0; and 136 had LEI = 0 and SPARCC = 0 at baseline. At baseline, among patients with LEI > 0 or SPARCC > 0, mean LEI and SPARCC across treatments and enthesitis locations/severities ranged from 1.0–4.4 and 1.3–9.4, respectively. Across several baseline enthesitis locations/severities, changes from baseline in LEI and SPARCC up to M3 were greater with tofacitinib (-2.0–0.4 and -3.5–0.2) vs placebo (-‍0.9–‍0.4 and -1.5–1.1). Enthesitis at M6 was more common in patients with greater baseline enthesitis severity. At M6, ≤ 40% of patients with baseline LEI > 0 or SPARCC > 0 whose enthesitis had resolved by M1/M3 experienced a relapse, and < 14% of patients with baseline LEI = 0 and SPARCC = 0 had de novo enthesitis. LDA/remission rates generally increased with tofacitinib over time. Baseline LEI location was significantly associated with change from baseline in arthritis pain score, while baseline SPARCC severity was significantly associated with change from baseline in FACIT-F total and arthritis pain scores.ConclusionTofacitinib treatment resulted in improvements in enthesitis in patients with PsA, regardless of baseline location or severity.Trial registrationNCT01877668;NCT01882439.

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.

Association of inflammatory biomarkers and disease activity with subclinical myocardial dysfunction in psoriatic arthritis

We examined the role of adipokines and pro-inflammatory cytokines in psoriatic arthritis-associated subclinical myocardial dysfunction, and the relationship between these variables and psoriatic arthritis (PsA) disease activity. Fifty-five PsA patients without cardiovascular risk factors and 25 controls underwent standard and speckle tracking echocardiography with global longitudinal strain (GLS) calculated. Standard anthropometric data and Disease Activity in Psoriatic arthritis (DAPSA) scores were recorded, with low disease activity defined as DAPSA ≤ 14 and moderate and high disease activity DAPSA > 14. Standard biochemical tests, adiponectin, resistin, leptin, tumor necrosis factor (TNF) alfa, interleukin 17 A (IL-17A), B lymphocyte chemoattractant (BLC), and monokine induced by intereferon gamma (MIG) were analyzed. Median age was 53.0 (46.0–61.0), median PsA duration 6.0 (4.0–13.0) years and median DAPSA score 25.5 (13.0–41.5). Lower GLS, tricuspid annular plane systolic excursion (TAPSE) and left ventricular ejection fraction (LVEF) were found in moderate and high PsA disease activity compared to low PsA disease activity and controls. PsA patients with GLS < 20 had higher body mass index (BMI), DAPSA score and uric acid levels, and lower adiponectin levels. Although patients with GLS < 20 had higher IL-17A levels, it was not statistically significant (P = 0.056). However, when we included healthy controls and analyzed differences based on a GLS cut-off of 20% in the entire population, the difference in IL-17A became statistically significant, 0.17 pg/mL (0.06–0.32) vs. 0.43 pg/mL (0.23–0.65), P = 0.017. The association between DAPSA score and GLS and IL-17 remained significant in multivariate analysis. Moreover, the association between GLS and IL-17 and adiponectin was significant after adjustment for age and BMI. Patients with moderate and high PsA disease activity have reduced myocardial function, lower adiponectin, and higher IL-17A levels.

Low rates of radiographic progression associated with clinical efficacy following up to 2 years of treatment with guselkumab: results from a phase 3, randomised, double-blind, placebo-controlled study of biologic-naïve patients with active psoriatic arthritis

ObjectiveEvaluate relationship between radiographic progression and clinical outcomes in post hoc analyses of patients with psoriatic arthritis (PsA) receiving up to 2 years of guselkumab therapy in the phase 3,...

Real-World Retention and Clinical Effectiveness of Secukinumab for Psoriatic Arthritis: Results From the Canadian Spondyloarthritis Research Network.

Psoriatic arthritis (PsA) is an immune-mediated disease characterized by pain, stiffness, and swelling of peripheral joints, with an estimated prevalence in Canada of 0.45%. Treatment aims to minimize disease activity, reduce progression of damage, and improve quality of life. Secukinumab (SEC) is a biologic disease-modifying antirheumatic drug (bDMARD) that has demonstrated efficacy and safety for PsA in clinical trials; however, there is limited real-world evidence on its use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC among Canadian patients with PsA. This was an observational cohort study of Canadian patients with PsA, 18 to 65 years of age, who attended a clinic of the CanSpA network and received treatment with SEC. Patients were indexed on the date they first initiated SEC. Retention was assessed at 12 months postindex. Clinical effectiveness was measured as the proportion of patients in remission and change in disease activity from baseline to 12 months using several clinical indices. In total, 213 patients were included. Overall retention was estimated at 73.6% at 12 months (81.8% for bDMARD- or targeted synthetic DMARD-naïve patients). Out of 110 patients, 17 (15.5%) were in remission based on the Disease Activity Index in Psoriatic Arthritis in 28 joints, and 10 out of 70 patients (14.3%) were in remission based on the Psoriatic Arthritis Disease Activity Score at 12 months. The Psoriasis Area and Severity Index improved by 65.8%; the tender joint count in 68 joints and the swollen joint count in 66 joints improved by 65.5% and 73.7%, respectively. This is the first nationwide study that we know of to describe real-world use of SEC in Canada for PsA, and the results support its effectiveness in a Canadian real-world setting. The CanSpA network represents a unique opportunity to build and improve the real-world evidence base for SpA treatment in Canada.

Effect of tofacitinib on dactylitis and patient-reported outcomes in patients with active psoriatic arthritis: post-hoc analysis of phase III studies

BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post-hoc analysis of two phase III studies in patients with PsA treated with tofacitinib assessed dactylitis by location, and the impact on patient-reported outcomes (PROs).MethodsPatients received tofacitinib 5 or 10 mg twice daily (BID), or placebo. Endpoints included change from baseline in Dactylitis Severity Score (DSS), proportions of patients with dactylitis, Psoriatic Arthritis Disease Activity Score (PASDAS), and PROs (Health Assessment Questionnaire-Disability Index [HAQ-DI]; Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]; Short Form-36 Health Survey [SF-36] Physical Component Summary [PCS], Mental Component Summary [MCS], and physical functioning [PF]; arthritis pain; and Work Limitations Questionnaire [WLQ]). Descriptive statistics were generated by visit and treatment. Change from baseline in PROs were evaluated by multivariate linear regression.ResultsThe analysis included 373/337 patients with baseline DSS > 0/DSS = 0. Regardless of location, DSS improvements in patients with DSS > 0 were greater from month 1 with tofacitinib (10 mg BID) versus placebo. For patients with DSS > 0/DSS = 0, both doses of tofacitinib led to mean dactylitis presence ≤ 15%/< 2% for all digits at month 6, and PASDAS (by dactylitis location) was lower versus placebo at month 3. Dactylitis location was not significantly associated with change from baseline in PROs.ConclusionTofacitinib resulted in sustained improvements in dactylitis irrespective of location, with minimal emergence of new dactylitis.Trial registration NCT01877668; NCT01882439.

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...

Minimal disease activity and remission in patients with psoriatic arthritis with elevated body mass index: an observational cohort study in the Swiss Clinical Quality Management cohort

ObjectiveTo assess the impact of elevated body mass index (BMI) in the achievement of minimal disease activity (MDA) and several definitions of remission in patients with psoriatic arthritis (PsA) in...

Determinants of work and social participation in patients with psoriatic arthritis in the Netherlands: an observational study

BackgroundPsoriatic arthritis can cause pain, disability, and permanent joint damage. This can lead to impairments in work and social participation. Little is known about the extent of these impairments in routine practice. With this study, we aim to examine the extent of work and activity impairment in (subgroups of) Dutch patients with psoriatic arthritis (PsA), and to examine determinants associated with this impairment.MethodsThis is an observational study using data collected from the electronic health records of PsA patients treated at the Sint Maartenskliniek, the Netherlands. Data about work and activity impairment were collected via the Work Productivity and Activity Impairment questionnaire. To compare our PsA-cohort with the Dutch general population, we used age- and sex-matched data derived from the Central Bureau of Statistics. Regression analyses were performed to examine determinants of work and activity impairment.ResultsIn total, 246 patients were included, of which 126 (51.2%) were female. Mean age (S.D.) was 55.7 (13.2) years. Compared with the Dutch general population, work for pay (WFP) was significantly lower in PsA (52.9% versus 62.6%, P < 0.001). In PsA, younger age and better physical function were associated with WFP status (P < 0.05). Higher disease activity, worse physical function, and worse mental health-related quality of life were associated with both more work and activity impairment (P < 0.05). Furthermore, reaching low disease activity status (LDA) according to Psoriatic ArthritiS Disease Activity Score (PASDAS; ≤ 3.2) was associated with less work and activity impairment than reaching LDA according to DAS28-CRP (≤ 2.9) (P < 0.05).ConclusionsIn PsA patients, worse physical function was associated with a lower likelihood of having WFP, and higher work and activity impairment. PASDAS LDA as a goal for treat to target, compared to DAS28-CRP, appears to favour the reduction of work and activity impairment.

Impact of clinical domains other than arthritis on composite outcomes in psoriatic arthritis: comparison of treatment effects in the SEAM-PsA trial

ObjectiveWe used the Study of Etanercept And Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) data set to examine the impact of presence of enthesitis, dactylitis,...

Predictive Value of Monocyte Chemoattractant Protein-1 in the Development of Diastolic Dysfunction in Patients with Psoriatic Arthritis.

We aimed to evaluate the diagnostic accuracy of the proinflammatory monocyte chemotactic protein-1 (MCP-1) in the diagnosis of asymptomatic diastolic dysfunction (DD) in patients with psoriatic arthritis (PsA). The disease activity in psoriatic arthritis (DAPSA) was determined using clinical and laboratory parameters, and echocardiography was performed to estimate DD. Serum MCP-1 concentrations were elevated in PsA patients with DD diagnosed with ultrasound (median (25th percentile, 75th percentile): 366.6 pg/mL (283, 407.1 pg/mL) vs. 277.5 pg/mL (223.5, 319.1 pg/mL) in controls; P < 0.0017). PsA patients with serum MCP-1 concentration higher than the cut-off value of 347.6 pg/mL had a 7.74-fold higher chance of developing DD than PsA patients with lower serum MCP-1 concentrations (controls), with a specificity of 86.36% and sensitivity of 55%, as verified using ultrasound. The group with MCP-1 concentrations above the cut-off value also showed a higher late peak diastolic mitral inflow velocity, A-wave value (P = 0.000005), E/E′ ratio (P = 0.00005), and a lower E/A ratio (P = 0.000002), peak systolic left atrial reservoir strain, SA value (P = 0.0066), early peak diastolic displacement of the mitral septal annulus, E′ wave value (P = 0.003), than controls. Systolic blood pressure (P = 0.01), LDL cholesterol concentration (P = 0.012), glucose concentration (P = 0.011), and DAPSA (P = 0.0000) increased in the PsA group with higher MCP-1 concentrations, although there were no differences in comorbidities and therapy between the groups compared. Thus, the serum MCP-1 concentration was a significant and independent prognostic indicator for asymptomatic DD in PsA patients (area under the curve = 0.730, P = 0.001). The DAPSA score in PsA patients might indicate the need for echocardiography and adjustment of anti-inflammatory treatment in terms of DD prevention.

POS1048 SAFETY AND EFFICACY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR, IN PATIENTS WITH PSORIATIC ARTHRITIS: 52-WEEK RESULTS FROM A RANDOMISED PHASE 2 TRIAL

BackgroundDeucravacitinib (DEUC) is a novel, oral, selective, allosteric inhibitor of tyrosine kinase 2 (TYK2) that acts by binding to the unique TYK2 regulatory domain, thereby suppressing signalling of key cytokines (eg, IL-23) involved in skin psoriasis and psoriatic arthritis (PsA) pathogenesis. Results from the initial 16-week (wk), placebo (PBO)-controlled period (Part A) of a 52-wk, blinded Phase 2 trial in PsA showed that DEUC was significantly more efficacious than PBO.1 The Psoriatic Arthritis Disease Activity Score (PASDAS), a validated comprehensive measure assessing a variety of PsA clinical domains, was used to assess efficacy of DEUC up to 52 wks.ObjectivesEvaluate the safety and efficacy of DEUC in Part B (Wks 16-52) in the Phase 2 PsA trial.MethodsPatients (pts) with PsA were randomised 1:1:1 to PBO, DEUC 6 mg once daily (QD), or 12 mg QD. After Wk 16 (Part A), pts could enrol in an optional, double-blind period until Wk 52 (Part B). In Part B, pts receiving DEUC who had achieved minimal disease activity (MDA) at Wk 16 continued DEUC treatment and those who had not achieved MDA were switched to ustekinumab (UST) at the approved PsA dose. All pts treated with PBO in Part A switched to UST in Part B. Pts were assessed up to 52 wks for adverse events (AEs) and exploratory efficacy endpoints including change in PASDAS. Analyses were descriptive using data as observed.ResultsOf 203 pts randomised in Part A, 180 (89%) completed 16 wks of treatment and 173 (96%) of these pts chose to enrol in Part B. Of 118 pts initially randomised to DEUC, 25% (29/118; 6 mg QD, 22% [13/60]; 12 mg QD, 28% [16/58]) achieved MDA at Wk 16 and continued at the same dose. All other pts switched to UST in Part B: PBO, 100% (55/55; including 5 pts who had achieved MDA at Wk 16); DEUC 6 mg QD, 78% (47/60); DEUC 12 mg QD, 72% (42/58). The safety profile of DEUC in Part B (Table 1) was consistent with that in Part A, and all AEs were mild or moderate except 2 AEs in 1 pt with severe cataract/macular fibrosis. There were no opportunistic infections, herpes zoster, malignancy, thrombotic events, or treatment-related serious AEs reported in pts who remained on DEUC. Decreases in mean PASDAS score observed at Wk 16 were maintained at Wk 52 in pts who continued on DEUC (Figure 1). Improvements in other outcomes, including ACR components, PASI, and FACIT-Fatigue, were also sustained at Wk 52 in pts who continued DEUC treatment. Pts who had not achieved MDA on DEUC at Wk 16 showed a decrease in mean PASDAS score at Wk 52 after switching to UST.Table 1.Overall summary of safety in Part B (Weeks 16 to 52)AE, n (%)aDEUC 6 mg QD n = 13DEUC 12 mg QD n = 16DEUC 6 mg QD →UST n = 47DEUC 12 mg QD → UST n = 42PBO → UST n = 55Total AEs11 (84.6)8 (50.0)26 (55.3)26 (61.9)30 (54.5)Deaths001 (2.1)d1 (2.4)d0SAE1 (7.7)b03 (6.4)4 (9.5)0Treatment-related SAE00000Discontinued due to AE01 (6.3)c02 (4.8)c,e0Includes all treated patients in Part B. Medical Dictionary for Regulatory Activities version 23.0 was used. an is the number of patients who experienced an event. bOne patient had SAEs of psoriatic arthropathy in 1 joint and peripheral neuropathy. cPatient had an AE of COVID-19 infection leading to discontinuation. dDeaths in UST arms were due to car accident and sudden death in a 71-year-old patient with hypertension. ePatient had an AE of urinary tract infection leading to discontinuation.AE, adverse event; DEUC, deucravacitinib; PBO, placebo; QD, once daily; SAE, serious adverse event; UST, ustekinumab.ConclusionIn the 16- to 52-wk blinded Part B of a Phase 2 study in pts with PsA, no new safety signals were observed with continuous DEUC treatment vs the earlier Part A period. Efficacy in PASDAS, as well as other key efficacy measures, was maintained with continued DEUC treatment through Wk 52.

AB0891 Deucravacitinib Efficacy in Psoriatic Arthritis by Baseline DMARD Use: Exploratory Analysis From a Phase 2 Study

BackgroundPsoriatic arthritis (PsA) treatment guidelines recommend that patients (pts) inadequately responding to conventional synthetic DMARDs (csDMARDs) can be treated with targeted synthetic DMARDs with or without background use of csDMARDs. Deucravacitinib (DEUC) is a novel, oral, selective, allosteric inhibitor of tyrosine kinase 2 (TYK2) that binds to the unique TYK2 regulatory domain, thereby suppressing signaling of key cytokines (eg, IL-23) involved in PsA pathogenesis. In a Phase 2 trial in pts with active PsA, DEUC was well tolerated and significantly more efficacious than placebo (PBO) after 16 weeks of treatment.1ObjectivesThis analysis further evaluated the effect of DEUC in this Phase 2 trial in pts treated with and without background csDMARDs for 16 weeks.MethodsThis double-blind trial (NCT03881059) enrolled pts with active PsA who had either failed or were intolerant to ≥1 nonsteroidal anti-inflammatory drug, corticosteroid, csDMARD, and/or 1 TNF inhibitor (TNFi; up to 30%). Pts were randomised 1:1:1 to DEUC 6 mg once daily (QD) or 12 mg QD, or PBO. A post hoc subgroup analysis in pts with and without background csDMARD use assessed improvements in select clinical outcomes (ACR 20 response, and change from baseline in ACR components, Psoriasis Area and Severity Index total score, and Psoriatic Arthritis Disease Activity Score) at Week 16.ResultsBaseline (BL) demographics, clinical characteristics, and disease activity were generally similar among pts with and without background csDMARD use. At BL, background csDMARD use was 64.3%, 64.2%, and 66.7% and methotrexate use was 50.0%, 55.2%, and 59.1% in the DEUC 6 mg QD, 12 mg QD, and PBO groups, respectively. Pts with and without background csDMARD use showed similar improvements at Week 16 with DEUC treatment versus PBO on most clinical measures, pt-reported outcomes, and composite measures (Table 1 and Figure 1). No clinically meaningful differences in adverse events (AEs) were observed in pts with or without background csDMARD use.Table 1.Adjusted mean (SE) change from baseline at Week 16 in clinical outcomes by csDMARD usePBO w/o csDMARD (n=22)PBO w csDMARD (n=44)DEUC 6 mg QD w/o csDMARD (n=25)DEUC 6 mg QD w csDMARD (n=45)DEUC 12 mg QD w/o csDMARD (n=24)DEUC 12 mg QD w csDMARD (n=43)Swollen joint count-4.7 (1.4)-5.0 (0.9)-7.4 (1.4)-6.8 (0.9)-8.4 (1.3)-7.7 (1.0)Tender joint count-5.3 (2.2)-6.6 (1.3)-6.4 (2.2)-11.3 (1.3)-11.5 (2.0)-11.6 (1.4)Physician’s Global Assessment of Disease Activity-20.6 (5.6)-20.6 (3.7)-29.1 (5.8)-32.6 (3.5)-30.1 (5.3)-32.1 (3.9)Patients’ Global Assessment of Disease Activity-14.9 (5.8)-13.4 (3.9)-23.0 (5.9)-28.4 (3.8)-28.2 (5.4)-24.9 (4.2)Pain-14.7 (5.6)-14.6 (3.9)-22.7 (5.7)-26.2 (3.7)-25.5 (5.3)-25.5 (4.2)HAQ-DI-0.23 (0.11)-0.04 (0.09)-0.31 (0.11)-0.38 (0.08)-0.48 (0.10)-0.34 (0.09)hsCRP12.0 (5.3)-4.4 (2.1)-10.1 (5.3)-13.3 (2.0)-4.9 (4.9)-10.0 (2.2)PASI total score2.5 (1.4)-2.3 (0.7)-3.7 (1.4)-4.0 (0.6)-4.0 (1.3)-4.9 (0.7)PASDAS-0.9 (0.4)-1.2 (0.3)-1.8 (0.4)-2.1 (0.2)-2.2 (0.3)-2.1 (0.3)The number of patients with data available for individual endpoints may vary.csDMARD, conventional synthetic disease-modifying antirheumatic drug; DEUC, deucravacitinib; HAQ-DI, Health Assessment Questionnaire-Disability Index; hsCRP, high-sensitivity C-reactive protein; PASDAS, Psoriatic Arthritis Disease Activity Score; PASI, Psoriasis Area and Severity Index; PBO, placebo; QD, once daily; SE, standard error; w, with; w/o, without.ConclusionThese analyses demonstrate that the efficacy of DEUC for the treatment of PsA was similar in pts with and without background csDMARD use. The AE profile of DEUC treatment with and without csDMARD use was consistent with findings from the overall Phase 2 PsA trial population.

Potential Impact of Sex and BMI on Response to Therapy in Psoriatic Arthritis: Post Hoc Analysis of Results From the SEAM-PsA Trial

In this post hoc analysis, we examined the potential impact of sex and BMI on response in the Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) trial (NCT02376790), a 48-week, phase III, randomized controlled trial that compared outcomes with methotrexate (MTX) monotherapy, etanercept (ETN) monotherapy, and MTX+ETN combination therapy in patients with psoriatic arthritis (PsA) who were naïve to MTX and biologics. We evaluated key outcomes at week 24 stratified by sex (male vs female) and BMI (kg/m2; ≤ 30 vs > 30), including the American College of Rheumatology 20 (ACR20) criteria, minimal disease activity (MDA), very low disease activity (VLDA), and Psoriatic Arthritis Disease Activity Score (PASDAS). We analyzed data using descriptive statistics, normal approximation, logistic model, and analysis of covariance. A total of 851 patients completed the SEAM-PsA trial. Higher proportions of men than women who received MTX+ETN combination therapy achieved ACR20 (71.5% vs 58.3%; P = 0.02), MDA (45.8% vs 25.2%; P = 0.0003), and VLDA (19.1% vs 9.5%; P = 0.03), and men achieved better PASDAS (-3.0 vs -2.3; P = 0.0004). Patients with BMI ≤ 30 generally had better outcomes than those with BMI > 30 in some treatment arms for ACR20, MDA, VLDA, and PASDAS; however, there was no consistent pattern regarding the treatment arm in which the difference occurred. Improved outcomes were observed more in men than in women for MDA and PASDAS with MTX+ETN combination therapy. Patients with BMI ≤ 30 had better outcomes than those with BMI > 30, with no clear pattern regarding treatment received. These findings suggest that contextual factors such as sex and BMI may affect response to PsA therapy.

Comparing methotrexate monotherapy with methotrexate plus leflunomide combination therapy in psoriatic arthritis (COMPLETE-PsA): a double-blind, placebo-controlled, randomised, trial.

Conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) are the preferred first-line treatment in patients with psoriatic arthritis, although there is a paucity of evidence for the efficacy of conventional synthetic DMARDs and especially their combination. We aimed to investigate whether a combination of methotrexate plus leflunomide is superior to methotrexate monotherapy at improving disease activity in patients with psoriatic arthritis. This single centre, investigator-initiated, double-blind, randomised, placebo-controlled trial was conducted at Sint Maartenskliniek in the Netherlands (locations included Boxmeer, Geldrop, Woerden, and Nijmegen). Patients aged 16 years or older with a clinical diagnosis of psoriatic arthritis and active disease (defined as two or more swollen joints; dactylitis counting as one swollen joint) were included. Patients were randomly allocated (1:1) and stratified by high disease activity (psoriatic arthritis disease activity score [PASDAS] ≥5·4) to either methotrexate plus leflunomide (combination therapy) or methotrexate plus placebo (monotherapy), using computer-generated stratified variable block randomisation. In both groups, patients received oral methotrexate 15 mg per week for the first 4 weeks and 25 mg per week thereafter combined with two leflunomide 10 mg tablets once per day or two placebo tablets. During the study period, the patients, nurses, researchers, and treating physicians were all masked to treatment allocation. The primary outcome was the difference in mean PASDAS at week 16, adjusted for baseline PASDAS, between the combination and monotherapy groups, assessed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register (NL7404) on Dec 3, 2018. Between Feb 19, 2019, and March 11, 2021, 82 patients were screened for eligibility. Four patients were ineligible and 78 were enrolled and randomly assigned to either methotrexate plus leflunomide (n=39) or methotrexate plus placebo (n=39). 50 (64%) of 78 patients were male, 28 (36%) were female, and the median age of patients was 55·0 years (IQR 42·0-64·0). Methotrexate plus leflunomide combination therapy was superior to methotrexate monotherapy at week 16 (PASDAS 3·1 [SD 1·4] vs 3·7 [SD 1·3]; treatment difference -0·6, 90% CI -1·0 to -0·1; p=0·025). There were no study deaths. The most frequently occurring adverse events were nausea or vomiting (17 [44%] of 39 patients in the methotrexate plus leflunomide group vs 11 [28%] of 39 in the methotrexate plus placebo group), tiredness (9 [23%] vs 13 [33%]) and elevated alanine aminotransferase (12 [31%] vs 7 [18%]. Generally, the incidence of mostly mild adverse events was higher in the methotrexate plus leflunomide group than in the methotrexate plus placebo group. Methotrexate plus leflunomide combination therapy results in greater improvement in disease activity according to PASDAS in patients with psoriatic arthritis. However, methotrexate plus leflunomide combination therapy is less well tolerated than methotrexate monotherapy. Regional Junior Researcher Grant from the Sint Maartenskliniek.

Vaccination for SARS-CoV-2 in Patients With Psoriatic Arthritis: Can Therapy Affect the Immunological Response?

BackgroundA few studies on vaccination in patients with rheumatic diseases, including arthritis, connective tissue diseases, vasculitis, and psoriatic arthropathy (PsA), demonstrated reduced production of neutralizing antibodies to SARS-CoV-2 Spike RBD (receptor-binding domain contained in the N-terminal of the S1 globular head region) when compared to the general population.ObjectiveThe aim of our study was to observe whether different therapies for PsA [methotrexate, anti-TNF antibodies, soluble TNF receptor (etanercept) or IL-17 inhibitors] have a different impact on SARS-CoV-2 vaccination in a homogeneous population of patients.MethodsWe enrolled 110 PsA patients in remission, assessed with Disease Activity in PSoriatic Arthritis (DAPSA). Of these: 63 were in treatment with anti-TNF-α therapy (26 etanercept, 15 certolizumab, 5 golimumab, 17 adalimumab); 37 with anti-IL17 secukinumab; 10 with methotrexate. All patients underwent vaccination for SARS-CoV-2 with mRNA BNT162b2 vaccine. Assessment of absolute and percentage lymphocyte subsets and anti-SARS-CoV-2 Spike RBD IgG antibody value 3 weeks after the second vaccine dose were performed. In addition, the serum antibody levels of 96 healthy healthcare workers (HCW) were analyzed.ResultsThe mean disease activity assessed with DAPSA score was 2.96 (SD = 0.60) with no significant differences between patients under different medications (p = 0.779). Median levels of neutralizing antibodies to SARS-CoV-2 Spike RBD were 928.00 binding antibody unit (BAU)/mL [IQR 329.25, 1632.0]; 1068.00 BAU/ml [IQR 475.00, 1632.00] in patients taking MTX, 846.00 BAU/ml [IQR 125.00, 1632.00] in patients taking etanercept, 908.00 BAU/mL [IQR 396.00, 1632.00] in patients taking anti-IL17 and 1148.00 BAU/ml [IQR 327.00, 1632.00] in patients taking TNF-α inhibitors, without statistically significant differences between these groups. Mean serum antibody level of HCW group was 1562.00 BAU/ml [IQR 975.00, 1632.00], being significantly higher than in the patient group (p = 0.000816). Absolute and percentage count of lymphocyte subsets were not statistically different between the subgroups under different treatments and when compared with HCW.ConclusionsAs for other rheumatic diseases on immunomodulatory treatment, our data showed a reduced humoral response in PsA patients compared to the control group. However, antibody response did not significantly differ between groups treated with different medications.

Defining the minimal important change (MIC) and meaningful change value (MCV) for the Psoriatic Arthritis Disease Activity Score (PASDAS) in a routine practice cohort of patients with psoriatic arthritis.

The aim of the study was to determine the Minimal Important Change (MIC) values and Meaningful Change (MCV) values for the Psoriatic Arthritis Disease Activity Score (PASDAS) and the Standard Error of Measurement (s.e.m.) of the PASDAS. The routine practice data for 544 patients with PsA was available for analysis. An anchor-based method using linear regression analyses was used to determine the MICs and MCVs for the PASDAS. With this anchor-based method, we compared changes in the PASDAS score with an external reference (anchor). The anchor question inquired whether the patient's well-being had changed since their previous visit. It consisted of a 7-point Likert scale (range: very much improved to very much deteriorated). Interperiod correlation matrix analysis was performed to determine the s.e.m. The overall MIC and MCV for the PASDAS were 0.67 (95% CI: 0.55, 0.79) and 1.34 (95% CI: 1.21, 1.46), respectively. Results for improvement and deterioration were 0.65 (95% CI: 0.46, 0.83) and 0.71 (95% CI: 0.49, 0.93) for the MIC, respectively, and 1.29 (95% CI: 1.11, 1.48) and 1.42 (95% CI: 1.19, 1.64) for the MCV, respectively. The s.e.m. was determined at 0.81. The MIC for the PASDAS is a tool for physicians treating patients with PsA enabling them to give context to the patient's perspective of disease activity, while the MCV might aid the use of the PASDAS in PsA clinical trials.

Clinical Characteristics of Psoriatic Arthritis in Chinese Patients: A Cross-Sectional Study.

IntroductionThe clinical features of psoriatic arthritis (PsA) varied in different studies from different countries, nevertheless rarely reported from China. We aimed to show the portraits of Chinese PsA patients.MethodsDemographics as well as clinical and laboratory data at the first visit of a PsA cohort were collected. Joints and entheses were further assessed by imaging techniques. The correlation between psoriasis severity index (PASI) and disease activity in PsA (DAPSA) was analyzed. The metabolic comorbidities were also explored among patients with different disease activity.ResultsThree hundred patients with definite PsA were enrolled in this study; 159 (53.0%) of them were male. Their median age was 39 (31, 51) years with disease duration of 3 (0.6, 7) years; 15.6% patients were HLA-B27-positive, and 37.8% patients reported a family history of psoriasis or PsA. Among 300 patients, psoriasis presented earlier than arthritis in most of them (214, 74.0%), while 48 (16.6%) patients presented with arthritis before psoriasis. Articular involvement was found in 293 (97.7%) patients. Polyarticular type was most common, with proximal interphalangeal as most frequently involved joints. Axial joint involvement was found in 45 (15.4%) patients. Dactylitis was observed in 94 (31.3%) patients, most often at the second, third, and fourth toes. Enthesitis was found in 18 (6.0%) patients by physical examination, however in 129/227 (56.8%) patients by ultrasound. The DAPSA score was correlated with PASI (r = 0.22, p = 0.021). A variety of comorbidities were more often observed in patients with moderate/high disease activity comparing with those in remission/low-disease activity, especially type 2 diabetes with statistically significant difference (19.1 vs. 4.1%, p = 0.023). However, further logistic regression analysis showed diabetes was not independently associated with moderate/high disease activity. The most frequently prescribed medication was methotrexate (101, 66.4%). Biological agents were applied in 25 (16.4%) patients.ConclusionsPolyarticular involvement was most common in Chinese PsA patients. Ultrasound dramatically increased the identification of peripheral enthesitis. Active PsA patients were more likely to have comorbidities.

Performance of 3 Composite Measures for Disease Activity in Peripheral Spondyloarthritis.

To investigate concurrent validity and discrimination of the Disease Activity Index for Psoriatic Arthritis (DAPSA) score, Psoriatic Arthritis Disease Activity Score (PASDAS), and Ankylosing Spondylitis Disease Activity Score (ASDAS) in peripheral spondyloarthritis (pSpA) in clinical practice. Data from a Dutch registry for SpA (SpA-Net) were used. Predefined hypotheses on concurrent validity of the composite measures with 15 other outcome measures of disease activity, physical function, and health-related quality of life were tested. Concurrent validity was considered acceptable if ≥ 75% of the hypotheses were confirmed. Discrimination was assessed by stratifying patients in DAPSA, PASDAS, and ASDAS predefined disease activity states and studying mean differences in health outcomes by 1-way ANOVA. Further, the concordance in disease activity states was determined. All analyses were repeated in subgroups with and without psoriasis (PsO). DAPSA, PASDAS, and ASDAS scores were available for 191, 139, and 279 patients with pSpA, respectively. The concurrent validity and discrimination of all composite measures were acceptable, as the strength of correlations were as hypothesized in ≥ 75% of the studied correlations. With increasing disease activity states, scores in nearly all outcome measures worsened significantly. The DAPSA, PASDAS, and ASDAS classified 22%, 56%, and 48% of the patients, respectively, in the 2 highest disease activity states. Stratified analyses for concomitant PsO revealed no relevant subgroup differences. The performance of DAPSA, PASDAS, and ASDAS in pSpA was acceptable, and independent of concomitant PsO. Due to discrepancy in classification, the validity of existing thresholds for disease activity states warrants further study in pSpA.