Psoriatic Arthritis Disease Activity Score Research Articles

Wnt signaling as a translational target in rheumatoid and psoriatic arthritis.

Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA) are chronic inflammatory diseases mainly affecting joints. RA primarily targets the synovial joints and is characterized by cartilage and bone erosion, whereas PsA is associated with skin and nail psoriasis and is characterized by erosive bone damage with an exuberant bone formation and soft tissue involvement. Recent evidence described the involvement of the Wnt pathway in the pathogenesis of these diseases. Thus, we aimed to analyze some components of Wnt signaling, i.e. DKK1, Wnt 5a and β-catenin, and their association with disease activity indices, investigating possible differences between the two diseases. Sera from 18 RA patients naïve for biological therapy, 18 PsA patients and 20 matched healthy donors (HD) were tested for DKK1 by ELISA, Wnt 5a and β-catenin by Immunoblotting. Values were correlated with CTX-1, detected by ELISA, and with disease activity indices: Disease Activity Score on 28 joints (DAS28-CRP) for RA and the Disease Activity in Psoriatic Arthritis (DAPSA) score for PsA. This study highlights significant increase in DKK1, Wnt 5a, and β-catenin levels in RA and PsA patients compared to HD, with distinct patterns of correlation with disease activity indices. Indeed, in RA patients, DKK1 levels positively correlated with DAS28-CRP score, whereas in PsA patients, DKK1 levels negatively correlated with DAPSA score. Our findings showed a strong correlation between DKK1 and CTX-1 levels in RA patients, supporting the relationship between DKK1 levels and the presence of joint erosions. Furthermore, a significant positive correlation was found between β-catenin and IL-6 levels in RA, indicating that β-catenin may be involved in the inflammatory cascade. This study compares the involvement of Wnt signaling in RA and PsA, suggesting that Wnt signaling may represent a possible mechanism of disease activity. In particular, it indicates that DKK1 levels are correlated with CTX-1, a marker of bone resorption, and with disease activity in RA patients. These findings underscore the importance of these biomarkers in the potential monitoring of patients, offering insights into disease mechanisms and potential therapeutic targets.

Characteristic of psoriatic arthritis patient with disease activity based on DAPSA score: A literature review

Psoriatic arthritis (PsA) is a chronic inflammation that affects peripheral and axial joints. The prevalence of PsA tends to increase in recent years. As many as 0.1 - 0.2% of the general population suffer from PsA. A study stated that out of 1,442,357 people with PsA, 21,825 deaths occurred. This mortality rate may continue to increase over time. PsA is most common in individuals aged 40 to 50 years with the incidence of PsA in men and women being almost equal. PsA cannot be underestimated and needs proper diagnosis and assessment of disease activity for good management. Early diagnosis is very important in PsA. The diagnosis of PsA can be made based on the Classification Criteria for Psoriatic Arthritis (CASPAR). Assessment of disease activity is essential in the management of PsA. Based on several studies, the most widely and easily used PsA disease activity assessment instrument is Disease Activity in Psoriatic Arthritis (DAPSA) score. Literature reviews on psoriatic arthritis patient with disease activity are still limited. Therefore, researchers are interested in conducting research on the characteristic of psoriatic arthritis patient with disease activity based on DAPSA score. However, further research is needed with more comprehensive variables to explore the characteristic and disease activity of psoriatic arthritis.

Efficacy and safety of tofacitinib in an open-label, long-term extension study in patients with psoriatic arthritis who received adalimumab or tofacitinib in a Phase 3 randomized controlled study: a post hoc analysis

BackgroundData on treatment switching directly from tumor necrosis factor inhibitors to tofacitinib in psoriatic arthritis (PsA) are limited. This post hoc analysis assessed efficacy and safety outcomes in patients with PsA who directly switched to tofacitinib in a long-term extension (LTE) study after receiving adalimumab (ADA) in a Phase 3 study, compared with those who continued to receive tofacitinib.MethodsPatients with active PsA received tofacitinib 5 mg twice daily (BID) or ADA 40 mg once every 2 weeks in a 12-month, randomized, double-blind study (OPAL Broaden) and then continued or switched to tofacitinib 5 mg BID and maintained this dose in an open-label LTE study (OPAL Balance). Efficacy was assessed 3 months before the last visit and at the last visit in the Phase 3 study, and at month 3 (or month 6 for select outcomes) in the LTE study and included rates of ≥ 20/50/70% improvement in American College of Rheumatology response criteria, Psoriasis Area and Severity Index ≥ 75% improvement, Health Assessment Questionnaire-Disability Index (HAQ-DI) response (decrease from baseline ≥ 0.35 for patients with baseline HAQ-DI ≥ 0.35), Psoriatic Arthritis Disease Activity Score ≤ 3.2, and minimal disease activity; and change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue score. Safety was assessed at months 3 and 12 in both studies via incidence rates (patients with first events/100 patient-years).ResultsOverall, 180 patients were included (ADA→tofacitinib 5 mg BID: n = 91; continuing tofacitinib 5 mg BID: n = 89). At Phase 3 baseline, patients in the ADA→tofacitinib 5 mg BID group tended to be younger and have less active disease compared with those continuing tofacitinib. Efficacy was similar between groups in the Phase 3 study, and was maintained to month 3 or 6 in the LTE study. Treatment-emergent adverse events (AEs), serious AEs, and serious infections were generally similar in the Phase 3 and LTE studies, and between groups within each study.ConclusionTofacitinib efficacy and safety were similar in patients with PsA who directly switched from ADA to tofacitinib and those who continued tofacitinib, suggesting that patients can be directly switched from ADA to tofacitinib without any washout period.Trial registrationNCT01877668; NCT01976364

Sustained response to guselkumab regardless of baseline characteristics in patients with active psoriatic arthritis and inadequate response to TNF inhibitors: results from the phase 3b COSMOS clinical trial

ObjectivesTo prospectively evaluate the effect of guselkumab through 48 weeks across various clinical outcomes in subgroups of patients with psoriatic arthritis (PsA) and inadequate response to tumour necrosis factor inhibitors...

P52 Efficacy of guselkumab in bionaive psoriatic arthritis patients with severe disease activity: post hoc analysis of Phase 3, randomized, double-blind, placebo-controlled study

Abstract The efficacy and safety of guselkumab, a fully human IL-23p19-subunit inhibitor, has been established in DISCOVER-1 and -2 studies. This post hoc analysis evaluates guselkumab efficacy through Week (W)100 in Bionaive psoriatic arthritis (PsA) patients with severe disease activity (DA) based on a range of composite and patient-reported outcomes. In DISCOVER-2, Bionaive adults with active PsA (≥5 swollen and ≥5 tender joints, CRP ≥0.6 mg/dL) received (1:1:1) guselkumab 100 mg every 4W (Q4W); guselkumab 100 mg at W0, W4, Q8W; or placebo with crossover to guselkumab Q4W at W24. Severe DA was defined by clinical DA Index for PsA (cDAPSA >27), PsA DA Score (PASDAS ≥5.4), and patient global assessment (PtGA ≥80 mm) criteria. Least square mean (LSM) changes from baseline were estimated with mixed models for repeated measures, adjusted for treatment group, baseline outcome levels, and study stratification factors (baseline csDMARD use, high-sensitivity serum CRP). Among 739 DISCOVER-2 patients, 648 (88%), 639 (86%), and 218 (29%) met cDAPSA (mean = 49.5), PASDAS (mean = 6.8), and PtGA (mean = 89.0) criteria for severe DA. Baseline characteristics and treatment groups were generally consistent across severe DA cohorts, except guselkumab Q4W group had a higher proportion of males and dactylitis than placebo. In multivariate analyses, irrespective of the severe DA cohort, significantly greater improvements were observed in guselkumab-treated patients vs. placebo in all evaluated endpoints (largest effect observed in severe PtGA cohort). Guselkumab showed clinically meaningful improvements at W2 for cDAPSA (guselkumab Q4W: −5.9; Q8W: −7.2; placebo: −5.0) and W8 for PASDAS (guselkumab Q4W: −1.5; Q8W: −1.5; placebo: −0.9) and PtGA (guselkumab Q4W: −30.0; Q8W: −32.1; placebo: −17.4). The LSM differences between guselkumab Q4W/Q8W and placebo were enhanced through W24 across severe DA cohorts, at which time further improvements with guselkumab occurred, resulting in significant (P < 0.001) differences of −9.8/−9.0 for cDAPSA, −1.1/−1.1 for PASDAS, and −24.0/−20.2 for PtGA. Further improvements were observed through 2 years of guselkumab treatment in all evaluated outcomes (LSM difference from BL: ΔcDAPSA, ∼−36; ΔPASDAS, ∼−3.6; ΔPtGA, ∼−56) representing ∼73%, ∼53%, and ∼63% improvements in joint DA, PsA activity across domains, and patient-reported overall DA. Guselkumab demonstrated rapid (W2 for joint and W8 for overall DA) and clinically meaningful improvements in DA in Bionaive PsA patients with severe DA in a range of joint-focused and multi-domain outcomes; these improvements were further enhanced by W24 and sustained through 2 years. Overall, findings support the use of guselkumab in PsA patients with severe DA.

Persistent Patient-Level Effect of Guselkumab at Consecutive 8-Week Dosing Visits and Over Time in Patients With Active Psoriatic Arthritis: Post Hoc Analysis of a 2-Year, Phase 3, Randomized, Controlled Study.

Group-level analyses from the phase 3 DISCOVER-2 trial of guselkumab demonstrated robust and durable improvements across psoriatic arthritis (PsA) domains. To specifically evaluate continuous disease control in individual patients, persistence of clinically relevant improvements was assessed, both at consecutive guselkumab dosing visits and over time. Post hoc analyses included biologic-naïve patients randomized to 100 mg of guselkumab at week 0, week 4, and then every 8 weeks (Q8W). Improvements in joint (minimal clinically important improvement [MCII] in Disease Activity Index for PsA [DAPSA; ≥7.25], clinical DAPSA [cDAPSA; ≥5.7]), skin (Investigator's Global Assessment [IGA] 0/1), and overall disease activity (patient global assessment of arthritis and psoriasis [PtGA Arthritis+Psoriasis; MCII ≥ 15 mm], PsA Disease Activity Score [PASDAS; MCII ≥ 0.8]) were assessed. Proportions of patients with maintenance of DAPSA and cDAPSA MCII at consecutive Q8W guselkumab dosing visits (ie, at weeks 4 and 12, weeks 12 and 20, etc through week 52) and patient-level durability of response through week 100 (Kaplan-Meier) were determined. Among 248 patients randomized to guselkumab Q8W, 93% to 99% maintained clinical improvement in joint disease at consecutive Q8W dosing visits through week 52 across time periods. Among guselkumab patients achieving MCII by week 24, estimated probabilities of maintenance of clinical improvement 100 weeks post achievement ranged from 68% (IGA 0/1) to 89% (PASDAS MCII). Median times to loss of improvement were not reached; estimated mean weeks of maintenance of improvement were 58.6, 52.4, 75.7, 83.6, and 76.7, respectively, for DAPSA, cDAPSA, IGA, PtGA Arthritis+Psoriasis, and PASDAS. Guselkumab provided highly durable patient-level improvements, both at consecutive Q8W dosing visits for joint disease activity and over time across PsA domains according to physician- and patient-driven assessments.

Multi-domain effectiveness of guselkumab evaluated via composite indices through 1 year in patients with PsA and inadequate response to TNFi: post hoc analysis of COSMOS.

Evaluate guselkumab efficacy, an anti-interleukin-23p19-subunit antibody, in patients with active psoriatic arthritis (PsA) and inadequate response to 1-2 tumour necrosis factor inhibitors (TNFi-IR), utilizing composite indices assessing disease activity across disease domains. In the Phase IIIb COSMOS trial, 285 adults with TNFi-IR PsA were randomized (2:1) to receive guselkumab 100 mg or placebo at Week (W)0, W4, then every 8 weeks through W44. Patients receiving placebo crossed over to guselkumab at W24. In this post-hoc analysis, composite indices evaluated included the Disease Activity Index for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Disease Activity Score (PASDAS), GRAPPA Composite score (GRACE), modified Composite Psoriatic Disease Activity Index (mCPDAI), minimal disease activity (MDA) and very low disease activity (VLDA). Through W24, treatment failure rules were applied. Through W48, non-responder imputation was used for missing data. Greater proportions of guselkumab- than placebo-randomized patients achieved composite index endpoints relating to low disease activity (LDA; 14.8-52.4% vs 3.1-28.1%) or remission (3.7-5.3% vs 0.0-2.1%) at W24. Among guselkumab-randomized patients, LDA rates increased to W48 (DAPSA, 44.4%; DAS28, 47.8%; PASDAS, 34.4%; GRACE, 33.3%; mCPDAI, 40.2%), and 27.0% and 64.0% achieved MDA and a PsARC response, respectively. In the placebo→guselkumab crossover group, W48 response rates were similar to the guselkumab-randomized group. Guselkumab treatment provided substantial benefits across multiple disease domains, with increasing proportions of patients achieving LDA/remission over 1 year, highlighting the effectiveness of guselkumab despite previous inadequate response to TNFi.

Early Improvements with Guselkumab Associate with Sustained Control of Psoriatic Arthritis: Post hoc Analyses of Two Phase 3 Trials.

Patterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA). Post hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4or8weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve). Achievement of MCII in clinical Disease Activity Index for PsA (cDAPSA), patient global assessment (PtGA) of arthritis, PtGA of psoriasis, patient-reported pain, Functional Assessment of Chronic Illness Therapy-Fatigue, Health Assessment Questionnaire-Disability Index, 36-item Short-Form Health Survey Physical Component Summary score, PtGA Arthritis + Psoriasis, and PsA Disease Activity Score (PASDAS) was compared between the guselkumab and placebo groups using Cox regression. Logistic regression adjusting for baseline factors evaluated associations between early (W4/W8) MCII achievement and stringent response (≥%50/%70 improvement in American College of Rheumatology response criteria, cDAPSA low disease activity [LDA], PASDAS LDA, and minimal disease activity) at W24/W52 among guselkumab-randomized patients. Among patients with highly active PsA (baseline cDAPSA = 44.1-45.0, PASDAS = 6.4-6.5), times to MCII were significantly faster for guselkumab vs. placebo (hazard ratios 1.3-2.5; P < 0.05). Across measures, at first timepoint assessed, MCII rates were significantly higher with guselkumab (Q4W/Q8W 28-68%/29-65%) vs. placebo (19-47%; both P < 0.05). Early (W4/W8) MCII with guselkumab associated with higher odds of achieving stringent responses at W24/W52 (odds ratios 1.4-17.2/1.4-5.4). In a mixed PsA population, significant proportions of patients treated with guselkumab achieved early (W4/W8) MCII across clinical and PRO measures, which associated with ahigher likelihood of attaining clinically relevant improvements and low levels of disease activity at W24/W52. DISCOVER-1 (NCT03162796). DISCOVER-2 (NCT03158285).

Evaluation of CD4+ CD25+/high CD127low/- Regulatory T-Cells in Different Stages of Psoriatic Arthritis Patients.

Psoriatic arthritis (PsA) is a systemic auto-immune condition characterized by diverse and distinctive inflammation, affecting both musculoskeletal and extra-articular systems. This study aims to investigate the role of regulatory T-cells (Tregs), specifically the CD4+CD25+/high CD127-/low subset, in PsA pathogenesis, and their potential as biomarkers and therapeutic targets. In a case-control study involving 40 PsA patients and 25 healthy individuals, CD4+ CD25+/high CD127-/low Tregs were analyzed in peripheral blood mononuclear cells (PBMCs) using flow cytometry. Disease activity was assessed using the Disease Activity in Psoriatic Arthritis (DAPSA) score. We observed a significant positive correlation between Treg levels and the DAPSA score (P = 0.02) in non-treated PsA patients. Additionally, patient age showed a significant positive correlation with erythrocyte sedimentation rate in the same group (P = 0.04), emphasizing the potential influence of Tregs on disease activity and age-related effects on inflammatory markers in PsA. While not revealing significant differences in Treg populations, our research underscores the importance of considering specific Treg subsets in PsA. These subsets may respond differently to disease micro-environments and treatments, affecting disease progression. This study contributes to the broader comprehension of immune dysregulation in auto-immune diseases and suggests that further investigation into Treg subsets' function and count is warranted. Such insights may lead to more tailored therapeutic approaches for PsA patients.

Comparing DAPSA, DAPSA28, and DAS28-CRP in Patients With Psoriatic Arthritis Initiating a First Tumor Necrosis Factor Inhibitor Across Nine European Countries.

Because 66/68 joint counts are not always performed in routine care, we aimed to determine which of the modified 28-joint disease activity index for psoriatic arthritis (DAPSA28) or 28-joint disease activity score with C-reactive protein (DAS28-CRP) should be preferred for monitoring disease activity in psoriatic arthritis (PsA) when the original DAPSA (66/68 joints) is not available. Prospectively collected real-world data of European bionaive patients with PsA initiating a first tumor necrosis factor inhibitor were pooled. Remission and response status were evaluated at 6 months by remission (DAPSA ≤ 4, DAPSA28 ≤ 4, and DAS28-CRP < 2.6), response (75% improvement for DAPSA and DAPSA28), and combined EULAR good/moderate responses for DAS28-CRP. Logistic regression analyses on multiple imputed data were used to identify baseline predictors. Remission and response cohorts included 3,159 and 1,866 patients, respectively. The 6-month proportions achieving remission/response were DAPSA (27%/44%), DAPSA28 (28%/44%), and DAS28-CRP (59%/80%). Of 14 possible baseline predictors, 11 predicted both DAPSA and DAPSA28 remission (8 of which also predicted their response, indicated by "*"): longer disease duration*, male sex*, and higher CRP* were positive, whereas older age*, higher body mass index*, patient fatigue*, and global, physician global, health assessment questionnaire score*, and tender and swollen* joint counts were negative predictors. Eight and five of these predicted DAS28-CRP remission and response, respectively. In patients with PsA, DAPSA28 should be preferred over DAS28-CRP as a substitute for DAPSA when 66/68 joint counts are not available because of the large overlap in remission and response status and in predictors between DAPSA and DAPSA28.

The Development and Validation of a Novel Training Infographic for the Physician Global Visual Analog Scale in Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a heterogenous condition with musculoskeletal and skin manifestations. The physician global visual analog scale (VAS) is an important component of many composite scores used in clinical trials and observational studies. Currently, no training material exists to standardize this assessment. The Psoriatic Arthritis Validation of Physician Global VAS (PAVLOVAS) project describes the development of a novel training infographic with stakeholder involvement, which was then evaluated in a Latin square design in which 20 patients with PsA were assessed by 10 clinicians. For each group of 10 patients, 5 assessors conducted traditional assessment (consisting of 66/68-joint count, body surface area, Leeds Enthesitis Index, and dactylitis and nail counts) and 5 assessors conducted a standardized, thorough general examination informed by the infographic. Assessors switched assessment type between groups. The 3-item (3VAS) and 4VAS informed by traditional and infographic methods were compared, alongside other composite scores. There was strong agreement between traditional and infographic physician global VAS (intraclass correlation coefficient [ICC] 0.69, P = 0.01). This improved to very strong agreement when incorporated into the 3VAS (ICC 0.99, P < 0.001) and 4VAS (ICC 0.99, P < 0.001). The duration of assessment was significantly less for the infographic vs traditional groups (6.5 vs 7.8 mins, P < 0.001). There was moderately high agreement between the 3VAS and 4VAS categories of disease activity, with the same categories defined by Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for Psoriatic Arthritis (DAPSA; χ2 17.0, P = 0.049). Our group developed and validated a novel training infographic that informs a briefer assessment of the physician global VAS than traditional assessments. This tool has potential applications in training and routine clinical practice.

Association Between Achievement of Clinical Disease Control and Improvement in Patient-Reported Outcomes and Quality of Life in Patients With Psoriatic Arthritis in the Phase 3 SELECT-PsA 1 and 2 Randomized Controlled Trials.

We explored the relationship between achievement of clinical disease control and improvements in and normative values for patient-reported outcomes (PROs), including quality of life (QoL) measures, in patients with psoriatic arthritis (PsA). This was a post hoc analysis of 104-week data from the SELECT-PsA 1 and 2 trials in adults with PsA and inadequate response to one or more conventional synthetic (SELECT-PsA 1) or biologic (SELECT-PsA 2) disease-modifying antirheumatic drug. Patients were initially randomized to upadacitinib 15 mg once daily (QD) to placebo switched to upadacitinib 15 mg QD at week 24 or to adalimumab 40 mg every other week (SELECT-PsA 1 only), and data were pooled across treatments and analyzed. We evaluated several clinical disease control measures (minimal disease activity [MDA]; very low disease activity [VLDA]; and low disease activity [LDA] and/or remission by Disease Activity in Psoriatic Arthritis [DAPSA], Psoriatic Arthritis Disease Activity Score [PASDAS], and Routine Assessment of Patient Index Data 3 [RAPID3]) and examined their associations with improvements and normative values for various PROs. A total of 1,069 and 317 patients were analyzed for SELECT-PsA 1 and 2, respectively. In both studies, responders (patients who achieved MDA or VLDA, and DAPSA, PASDAS, and RAPID3 LDA or remission) at week 104 achieved more marked changes from baseline, and more responders achieved normative values in PROs compared with nonresponders (most nominal P < 0.0001). Furthermore, numerically larger proportions of responders achieved minimal clinically important differences across PROs compared with nonresponders in both studies. In addition, patients who achieved MDA or VLDA were more likely to achieve DAPSA, PASDAS, and RAPID3 LDA or remission (all nominal P < 0.0001) for upadacitinib 15 mg QD and when treatment arms were pooled. Patients with PsA who achieve clinical disease control are more likely to achieve improvements and normative values in PROs and QoL measures, which reinforces disease control as a treatment target.

Durable control of psoriatic arthritis with guselkumab across domains and patient characteristics: post hoc analysis of a phase 3 study.

Evaluate patterns of stringent disease control with 2 years of guselkumab across key disease-identified domains and patient-reported outcomes (PROs) in subgroups of patients with psoriatic arthritis (PsA) defined by baseline characteristics. This post hoc analysis of DISCOVER-2 (Clinicaltrials.gov NCT03158285) evaluated biologic-naïve PsA patients (≥ 5 swollen/ ≥ 5 tender joints, C-reactive protein [CRP] ≥ 0.6 mg/dL) randomized to guselkumab every4weeks (Q4W); guselkumab at Weeks0and 4, thenQ8W; or placebo with crossover to guselkumab Q4W at Week24. Achievement of American College of Rheumatology 50/70% improvement (ACR50/70), Investigator's Global Assessment (IGA) 0, dactylitis/enthesitis resolution, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue response (≥ 4-point improvement), HAQ-Disability Index (HAQ-DI) response (≥ 0.35-point improvement), PsA Disease Activity Score (PASDAS) low disease activity (LDA), and minimal disease activity (MDA) was assessed at Weeks 24, 52, and 100 in subgroups defined by sex and baseline medication use, body mass index, PsA duration, swollen/tender joints, CRP, and psoriasis severity/extent. Patients with missing categorical response data were considered nonresponders. 442/493 (90%) guselkumab-randomized patients completed treatment through Week 100. Significant multi-domain efficacy of guselkumab versus placebo was shown across adequately sized patient subgroups. A pattern of continuous improvement was observed across key PsA domains and PROs within patient subgroups: 65%-85% of guselkumab-randomized patients had enthesitis/dactylitis resolution, 50%-70% achieved complete skin clearance, 60%-80% reported meaningful improvements in function/fatigue, 40%-65% achieved PASDAS LDA, and 35%-50% achieved MDA at Week100. Patients with active PsA receiving guselkumab demonstrated durable achievement of stringent endpoints associated with disease control across key PsA domains and PROs, regardless of baseline characteristics. Key Points • Among biologic-naïve patients with highly active psoriatic arthritis (PsA), efficacy of guselkumab across stringent disease endpoints and patient-reported outcomes (PROs) at Week 24 was consistent regardless of baseline demographics and disease characteristics. • Within guselkumab-randomized PsA patient subgroups, major improvements in joint disease activity, complete skin clearance, dactylitis/enthesitis resolution, clinically meaningful improvements in PROs, and achievement of low overall disease activity were maintained through Week 100. • Durable stringent endpoint achievement indicating disease control was observed with guselkumab, regardless of baseline patient or disease characteristics.

Composite Outcome Measures for Psoriatic Arthritis: OMERACT and 3 and 4 Visual Analog Scale Progress in 2023.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) psoriatic arthritis (PsA) working group provided updates at the GRAPPA 2023 annual meeting on its work to evaluate composite outcome measures for PsA. An ongoing systematic literature review is in progress to evaluate psychometric measurement properties using the OMERACT filter 2.2 for a list of candidate composite outcome measures, which include minimal disease activity (MDA), Disease Activity for Psoriatic Arthritis (DAPSA), American College of Rheumatology (ACR) response criteria, Psoriatic Arthritis Disease Activity Score (PASDAS), Composite Psoriatic Disease Activity Index (CPDAI), 3 visual analog scale (3VAS), and 4VAS. The performance of the 3VAS and 4VAS in clinical practice and a synthesis of new data were presented, including estimates for minimal clinically important differences and thresholds of meaning, discrimination and construct validity, and longitudinal construct validity. Numeric rating scale (NRS) versions of the VAS have also been tested. Performance characteristics and psychometric properties are similar to the ASSESS study, a UK multicenter study, indicating that the VAS scales may be feasible tools for routine clinical care with a preference for the 4VAS because of superior face validity and clinical utility.

Filling the "GAP" in Real-World Assessment of Psoriatic Arthritis Disease Activity: Performance Characteristics of a Global/Pain Composite Endpoint.

Some retrospective data sources, such as electronic health records in the USA, report composite outcome measures not fully validated in psoriatic arthritis (PsA). However, they often contain global assessments, such as a Physician Global Assessment (PhGA) and Patient Global Assessment (PatGA), along with patient-reported pain scores, which individually are considered validated in PsA. This research described the performance characteristics of a 3-item global assessment and pain (GAP) composite endpoint using data from the ixekizumab phase3 PsA clinical trial program. Discrimination of GAP was assessed by comparing placebo to active treatment arms. The magnitude of treatment effect and responsiveness were compared to Disease Activity Index for PsA (DAPSA), clinical DAPSA, DAPSA28, and Psoriatic Arthritis Disease Activity Score (PASDAS) using effect size (ES) and standardized response mean (SRM), respectively. Construct validity was evaluated through correlation among the composite endpoints, and with other physician- and patient-reported outcomes. Change in GAP was compared in patients who reached low disease activity (LDA) levels based on DAPSA, cDAPSA, and PASDAS vs those who did not. GAP discriminated between active treatment and placebo with statistically significant separation as early as week1. The largest ES/SRM was seen with GAP (2.29/1.74) and PASDAS (2.47/1.68). GAP had the strongest correlation with PASDAS (0.81-0.92) and showed moderate correlations with patient-assessed physical function, low correlations with physician-assessed skin and nail psoriasis, and low to moderate correlation with physician-assessed enthesitis. A significantly greater improvement in GAP was seen in the groups achieving LDA states compared to those not (p < 0.001). The GAP composite, an abbreviated endpoint comprising measures common in electronic health records, has promising performance characteristics and could be used to address important clinical questions regarding outcomes and impact of PsA in existing datasets. CLINTRIALS. NCT01695239; NCT02349295.

E072 The psoriatic arthritis disease activity score demonstrates excellent test-retest reliability in early, untreated psoriatic arthritis

Abstract Background/Aims Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterised by heterogenous clinical features including peripheral arthritis, spondylitis, enthesitis, dactylitis, skin and nail disease. Historically, outcome measures in PsA trials focused on the articular manifestations of disease, with a recent emphasis in composite tools. The Psoriatic Arthritis Disease Activity Score (PASDAS) is a validated, composite measure with defined cut-off and excellent responsiveness when compared with other PsA-specific and non-specific composite measures. Although PASDAS is one of the recommended GRAPPA measures for research trials, data on its test-retest reliability are limited particularly in PsA of short disease duration. Aims and Objectives - To assess the test-retest reliability of the PASDAS composite index in a cohort of early, untreated PsA patients. Methods Data were collected from a subset of participants recruited to the GOLMePsA clinical trial (EudraCT Number: 2013-004122-28), after a minor protocol amendment enabling additional data collection at the screening visit. The test-retest reliability of PASDAS was performed by calculating the intraclass correlation coefficient (ICC) between measurements collected at screening and baseline time-points (maximum 4 weeks apart, by protocol). Table 1 details the sample size calculation. Baseline variables collected in the GOLMePsA trial were described by absolute numbers, percentages, means, medians, absolute and inter-quartile ranges (IQR). Results The PASDAS test-retest reliability was assessed in 37 consecutive participants. Average time between the two time-points was 1.9 weeks (range 0.4 to 4.0). Baseline characteristics of test-retest subset compared to all GOLMePsA participants were similar (table 1). The ICC was 0.85 (95% confidence interval 0.73-0.92). The observed ICC was identical to the value assumed in the sample size calculation for this analysis, yielding an acceptably narrow confidence interval around the estimate. There was no substantial correlation between the means of the two measurements and the differences between them (Pearson’s r=-0.26). The Bland-Altman limits of agreement were -0.11 ± 1.24 (-1.35 to 1.13). Conclusion These results confirm the excellent test-retest reliability of PASDAS in early, untreated PsA, supporting its use as an outcome measure in interventional studies in newly diagnosed disease of short-duration. Disclosure G. De Marco: Consultancies; Janssen, Novartis. E.M.A. Hensor: None. D.G. McGonagle: Consultancies; AbbVie, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB. Grants/research support; AbbVie, BMS, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB. A. Tan: None. L.C. Coates: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB. Honoraria; AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB. Grants/research support; AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB. P. Emery: None. P.S. Helliwell: None. H. Marzo Ortega: Consultancies; AbbVie, Celgene, Eli-Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB. Grants/research support; Janssen, Novartis and UCB.

Autoimmune thyroiditis in psoriatic disease

Objectives. To assess autoimmune thyroiditis prevalence in subclinical and clinical psoriatic arthritis (PsA). Materials and methods. 45 female adult Egyptian patients with psoriatic disease were classified into 3 equal groups: PsA, subclinical PsA, and psoriasis. A full assessment was done including Health Assessment Questionnaire, Psoriasis Area Severity Index (PASI), Leeds Enthesitis Index (LEI), PsA disease activity score (DAPSA), MAdrid Sonographic Enthesitis Index (MASEI), thyroid hormones (TSH, FT4, and FT3), thyroglobulin and thyroid peroxidase antibodies (Tg and TPO Abs), and thyroid ultrasound. Results. Thyroid abnormalities prevalence was: 33.3% with subclinical hypothyroidism, 80% with positive TPO Ab, and 46.7% with positive Tg Ab in PsA group, 26.7% with subclinical hypothyroidism, 60% with positive TPO Ab, and 33.3% with positive Tg Ab in subclinical PsA group and none in psoriasis group. PsA patients had higher TPO Ab levels compared to psoriasis patients with high statistical significant difference and lower FT3 levels compared to psoriasis patients with statistical significant difference. In subclinical PsA group, MASEI was positively correlated with TPO Ab with high statistical significance and with FT3 and Tg Ab with statistical significance, FT4 was negatively correlated with LEI with high statistical significance, and FT4 was correlated with PASI with statistical significance. In PsA group, TPO Ab was correlated with DAPSA with statistical significance. Conclusions. Autoimmune thyroiditis is more common in PsA than subclinical PsA patients. PsA patients are advised to be tested for TPO and Tg Abs. Musculoskeletal ultrasound is a screening tool to detect enthesitis in psoriasis patients.

Guselkumab provides durable improvement across psoriatic arthritis disease domains: post hoc analysis of a phase 3, randomised, double-blind, placebo-controlled study

ObjectiveEvaluate long-term guselkumab effectiveness across Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognised domains/related conditions of psoriatic arthritis (PsA).MethodsPost hoc analyses used data from DISCOVER-2 (NCT03158285) biologic/Janus-kinase...

Effectiveness of Tofacitinib in Patients Initiating Therapy for Psoriatic Arthritis: Results from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

Randomized controlled trials have demonstrated tofacitinib efficacy for psoriatic arthritis (PsA); however, real-world effectiveness data are limited. This real-world analysis assessed baseline demographics/disease characteristics and tofacitinib effectiveness in patients with PsA in the CorEvitas PsA/Spondyloarthritis Registry. This study (NCT05195814) included patients with PsA initiating tofacitinib from December 2017-December 2021, as monotherapy or with oral small molecules (methotrexate/leflunomide/sulfasalazine/apremilast), pre-existing use, or initiated concurrently. mean change from baseline in disease activity/patient-reported outcomes, proportion of patients achieving low disease activity (LDA)/remission at 6 ± 3 months, and discontinuation rates. Of 222 patients with PsA who initiated tofacitinib (60.8% as monotherapy), 123 patients had 6 ± 3months of follow-up. At initiation, 59.7% were female, 92.3% were White, mean age was 56.3 years, PsA duration since diagnosis was 8.2 years, and 25.7% were biologic disease-modifying antirheumatic drug (bDMARD)-naïve. Improvements to 6 ± 3months were observed with tofacitinib for Clinical Disease Activity Index for PsA (cDAPSA), DAPSA, PsA Disease Activity Score (PASDAS), Clinical Disease Activity Index, body surface area (BSA), tender/swollen joint count, patient fatigue, pain, Patient Global Skin Assessment, and Health Assessment Questionnaire-Disability Index. At 6 ± 3months, 25.0%/7.8% of patients treated with tofacitinib achieved cDAPSA-defined LDA/remission, 18.2% achieved minimal disease activity, 30.8%had PASDAS ≤ 3.2, 42.9%/29.4% had resolved enthesitis/dactylitis, and 22.5% achieved BSA = 0%. Tofacitinib discontinuation occurred in 51.2% of patients (51.6% of monotherapy initiators) at/prior to 6 ± 3months (27.6%/23.6%), 57.1% of whom switched to tumor necrosis factor/interleukin-17 inhibitors. Reasons for discontinuation were not reported in 85.3%/79.3% of patients who discontinued at/prior to 6 ± 3 months. This real-world US cohort analysis described patients with PsA newly initiating tofacitinib; most were bDMARD-experienced or receiving monotherapy treatment. In patients who remained on therapy (48.8%), tofacitinib was effective across multiple PsA domains at 6 ± 3 months. Limitations included small patient numbers at follow-up and potential selection bias. ClinicalTrials.gov identifier, NCT05195814.

Correlation of changes in inflammatory and collagen biomarkers with durable guselkumab efficacy through 2 years in participants with active psoriatic arthritis: results from a phase III randomized controlled trial.

Guselkumab (human monoclonal antibody) selectively inhibits the interleukin (IL)-23p19 subunit. Assess the longer-term pharmacodynamic effects of guselkumab and explore associations between such effects and clinical responses in patients with active psoriatic arthritis (PsA). DISCOVER-2 randomized 739 biologic-naïve patients with active PsA (swollen/tender joint counts each ⩾5, C-reactive protein (CRP) ⩾0.6 mg/dL) to guselkumab (100 mg every 4 weeks (Q4W) or at Weeks 0, 4, and then Q8W) or placebo. Guselkumab-randomized participants with available serum biomarker data (randomly selected to reflect demographic and disease characteristics of the DISCOVER-2 population) comprised inflammatory (N = 100) and collagen (N = 178) biomarker cohorts. Pharmacodynamic effects of guselkumab through 2 years on inflammatory and collagen biomarker levels (general linear model) and associations between biomarkers and improvements in composite measures of joint, skin, and overall disease activity (Spearman linear regression) through 2 years were assessed. The relationship between the pharmacodynamic effects of guselkumab and achieving ⩾50% improvement in the American College of Rheumatology response criteria (ACR50) was assessed using a general linear model. With guselkumab, pharmacodynamic effects on inflammatory (CRP, IL-6, serum amyloid A (SAA), IL-17A, IL-17F, IL-22, and beta-defensin 2 (BD-2)) and collagen (matrix metalloproteinase-degradation type I, III, IV, and VI collagen (C1M, C3M, C4M, and C6M)) biomarker levels were sustained or enhanced through Week 100. Throughout follow-up timepoints (Week 24/52/100), decreases in CRP, IL-6, C1M, and C6M levels correlated (r = 0.26-0.30; p < 0.05) with improved joint disease activity (Disease Activity in Psoriatic Arthritis); decreases in IL-17A, IL-17F, IL-22, and BD-2 levels correlated (r = 0.34-0.58; p < 0.05) with improved skin disease (Psoriasis Area and Severity Index); and decreases in C1M, C3M, C4M, and C6M correlated (r = 0.27-0.31; p < 0.05) with improved overall disease activity (Psoriatic Arthritis Disease Activity Score). Significantly (p < 0.05) greater reductions from baseline at Week 100 in CRP, IL-6, SAA, and C1M levels were observed in participants improving from Week 24 ACR50 nonresponse to Week 100 ACR50 response and were accompanied by a significant decrease in C1M from Week 24 to Week 100 versus nonresponders at both Weeks 24 and 100. In biologic-naïve participants with active PsA, guselkumab elicited substantial and enduring reductions in biomarkers that were associated with durable improvements in joint, skin, and overall disease activity through 2 years of DISCOVER-2. NCT03158285 (clinicaltrials.gov identifier).