Psoriatic Arthritis Core Research Articles

Plain Radiographic Instruments for Structural Damage in Peripheral Joints in Psoriatic Arthritis: A Report 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) Core Set working group is focused on the development of a core set of instruments used to assess the domains described in the 2016 PsA Core Domain Set. At the 2021 annual meeting, the group presented an update on the domain of structural damage. In this report, we discuss the steps taken to assess the domain match and feasibility of plain radiographic instruments in the assessment of structural damage in PsA.

Articular and Extra-Articular Benefits in ACR20 Non-responders at Week 104 Treated With Apremilast: Pooled Analysis of Three Randomized Controlled Trials.

IntroductionPALACE 1, 2, and 3 were phase 3 studies aimed to evaluate apremilast efficacy and safety in patients with active psoriatic arthritis (PsA) despite prior treatment with conventional disease-modifying anti-rheumatic drugs and/or biologics. The pooled analysis reported here further characterized the clinical outcomes associated with long-term apremilast exposure in patients failing to achieve ≥ 20% improvement in the American College of Rheumatology response criteria (ACR20) at Week 104.MethodsPatients randomized to apremilast 30 mg twice daily at baseline and classified as ACR20 non-responders (ACR20NRs) or ACR20 responders (ACR20Rs) at Week 104 were included. Efficacy outcomes included change from baseline to Week 104 in ACR core components and other endpoints.ResultsAt Week 104, a total of 109 patients were ACR20NRs and 193 were ACR20Rs. As expected, the ACR20R group had improvements in all indices assessed. The ACR20NR group demonstrated substantial mean improvements from baseline in swollen joint count (SJC; − 58%), tender joint count (TJC; − 42%), and Physician’s Global Assessment of Disease Activity (PhGA; − 44%); resolution of enthesitis (34%) and dactylitis (68%); and achievement of ≥ 75% reduction from baseline Psoriasis Area and Severity Index scores (among patients with psoriasis involving ≥ 3% of the body surface area) (36%).ConclusionDespite not fulfilling a formal ACR20 response at Week 104, ACR20NRs experienced sustained improvements in several PsA core domains, including SJC, TJC, enthesitis, dactylitis, and psoriasis, as well as the PhGA (visual analog scale) scores, with apremilast treatment.Trial RegistrationClinicalTrials.gov identifier: NCT01172938, NCT01212757, and NCT01212770.

Secukinumab Efficacy on Psoriatic Arthritis GRAPPA-OMERACT Core Domains in Patients with or Without Prior Tumor Necrosis Factor Inhibitor Use: Pooled Analysis of Four Phase3 Studies.

BackgroundPsoriatic arthritis (PsA) is a chronic, heterogeneous, immune-mediated disease manifesting as a spectrum of possible inflammatory signs and symptoms. Clinicians need therapeutic choices that work across all active PsA disease domains, as well as practical information about efficacy of available treatments for individual domains in specific groups of patients. The objective of this study was to evaluate the effect of prior tumor necrosis factor inhibitor (TNFi) exposure on the efficacy of secukinumab across PsA core domains.MethodsData were pooled from 2049 participants with PsA in four phase 3 studies (FUTURE 2–5). Efficacy at week 16 was evaluated for each GRAPPA-OMERACT PsA core domain using nonresponder imputation for musculoskeletal disease activity and Psoriasis Area and Severity Index scores or as-observed data for other outcomes. For each measure, comparisons with placebo were made separately in the TNFi-naive and TNFi-inadequate responder/intolerant (TNF-IR) cohorts.ResultsTreatment with secukinumab improved PsA disease activity across all disease domains regardless of previous TNFi use, although TNFi-naive patients experienced numerically greater benefits in most outcomes. Among patients treated with secukinumab 300 mg, 41.5% and 24.4% of TNFi-naive patients (P < 0.05 vs placebo) and 18.6% and 9.0% of TNF-IR patients (nonsignificant vs placebo) experienced resolution in 66 swollen and 68 tender joint counts, respectively; additionally, 37.2% of TNFi-naive patients and 24.2% of TNF-IR patients achieved complete resolution of psoriasis at week 16 (all P < 0.05 vs placebo). Secukinumab effect sizes were generally larger in TNFi-naive vs TNF-IR patients for musculoskeletal and patient-reported domains.ConclusionsSecukinumab demonstrated efficacy vs placebo across GRAPPA-OMERACT PsA core domains. Higher responses among TNFi-naive vs TNF-IR patients suggest that secukinumab should be considered for first-line use in PsA.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00337-5.

AB0737 MEASUREMENT PROPERTIES OF RADIOGRAPHIC OUTCOME MEASURES IN PSORIATIC ARTHRITIS: A SYSTEMATIC REVIEW FROM THE GRAPPA-OMERACT INITIATIVE

Background:Structural damage was identified as an important outcome domain in the Psoriatic Arthritis (PsA) Core Domain Set and should be assessed at least once in the development of a new therapeutic.Objectives:To conduct a systematic literature review (SLR) to identify studies addressing the measurement properties (MPs) for ROIs and appraise the evidence through the OMERACT Filter 2.1 Framework Instrument Selection Algorithm (OFISA). [1]Methods:An SLR was conducted in EMBASE and MEDLINE to identify full-text English studies developing or assessing MPs of ROIs in PsA. Determination of eligibility, data extraction and methodology asssessment were performed by 2 reviewers. MPs were rated according to the ‘Provisional Standards’ and assigned a Red/Amber/White/Green (RAWG) rating (Figure 1). [1, 2]Results:3621 references were screened, 531 full-text articles reviewed, and 12 were included (Figure 2). Nine instruments assessing peripheral radiographs and six assessing axial radiographs were identified (Table 1). Three of the nine peripheral radiographic instruments had adequate evidence for reliability and some evidence for construct validity: the modified Steinbrocker, Ratingen, and modified Sharp van der Heijde scores. There was scant evidence for reliability, construct validity and responsiveness for the axial ROIs, compounded by the lack of a standardized definition of axial PsA.Conclusion:This SLR summarizes the MPs of ROIs and identifies relevant knowledge gaps that need to be addressed prior to endorsement of an instrument for the PsA Core Domain Set.

Effect of Secukinumab on the Different GRAPPA-OMERACT Core Domains in Psoriatic Arthritis: A Pooled Analysis of 2049 Patients.

To compare the efficacy of secukinumab with that of placebo across the updated Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and Outcome Measures in Rheumatology (GRAPPA-OMERACT) individual psoriatic arthritis (PsA) core domains using pooled data from 4 phase III PsA studies and 1 phase III ankylosing spondylitis (AS) study. Data were pooled from 2049 patients with PsA participating in 4 on-label phase III PsA studies (FUTURE 2-5), and the efficacy of each GRAPPA-OMERACT PsA core domain (musculoskeletal disease activity, skin disease activity, pain, patient's global assessment, physical function, health-related quality of life, fatigue, and systemic inflammation) was assessed using multiple measures and definitions specific to each domain. The MEASURE 2 study, a phase III clinical trial in patients with AS, was used to assess improvement in spine symptoms at Week 16. Treatment with secukinumab demonstrated robust and consistent efficacy across all GRAPPA-OMERACT PsA core domains, with secukinumab 300 mg showing the greatest response rates across most PsA core domains compared with placebo at Week 16. Notably, among patients treated with secukinumab 300 mg, 34.3% and 19.5% achieved complete resolution of swollen and tender joint counts, respectively; 53.2% and 61.5% achieved complete resolution of enthesitis and dactylitis, respectively; and 33.2% achieved 100% improvement in Psoriasis Area and Severity Index (all p < 0.05 vs placebo); similar improvements were shown for all other core domains. This analysis suggests that secukinumab can benefit people with PsA across the clinical phenotypic spectrum commonly encountered in this disease.

Endorsement of the 66/68 Joint Count for the Measurement of Musculoskeletal Disease Activity: OMERACT 2018 Psoriatic Arthritis Workshop Report.

The Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials and longitudinal observational studies has recently been updated. The joint counts are central to the measurement of the peripheral arthritis component of the musculoskeletal (MSK) disease activity domain. We report the Outcome Measures in Rheumatology (OMERACT) 2018 meeting's approaches to seek endorsement of the 66/68 swollen and tender joint count (SJC66/TJC68) for inclusion in the PsA Core Outcome Measurement Set (COS). Using the OMERACT Filter 2.1 Instrument Selection Process, the SJC66/TJC68 was assessed for (1) domain match, (2) feasibility, (3) numerical sense (construct validity), and (4) discrimination (test retest reliability, longitudinal construct validity, sensitivity in clinical trials, and thresholds of meaning). A protocol was designed to assess the measurement properties of the SJC66/TJC68 joint count. The results were summarized in a Summary of Measurement Properties table developed by OMERACT. OMERACT members discussed and voted on whether the strength of the evidence supported that the SJC66/TJC68 had passed the OMERACT Filter as an outcome measurement instrument for the PsA COS. OMERACT delegates endorsed the use of the SJC66/TJC68 for the measurement of the peripheral arthritis component of the MSK disease activity domain. Among patient research partners, 100% voted for a "green" endorsement, whereas among the group of other stakeholders, 88% voted for a "green" endorsement. The SJC66/TJC68 is the first fully endorsed outcome measurement instrument using the OMERACT Filter 2.1 and the first instrument fully endorsed within the PsA COS.

Using Acute-phase Reactants to Inform the Development of Instruments for the Updated Psoriatic Arthritis Core Outcome Measurement Set.

Systemic inflammationˆ is assessed through measurement of acute-phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). With few exceptions, most randomized controlled trials (RCT) have assessed acute-phase reactants (CRP and ESR) as part of the American College of Rheumatology (ACR) 20 response criteria. As part of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) working group, we performed a systematic review of the literature to assess the performance of inflammatory biomarkers in psoriatic arthritis (PsA). A systematic search of PubMed and Embase was performed. The search included peer-reviewed articles and scientific meeting abstracts about RCT and longitudinal observational studies that assessed systemic inflammation using acute-phase reactants in PsA. Studies were assessed following the components of the OMERACT filter including construct validity, responsiveness, and predictive validity. There were 2764 articles retrieved, and 71 articles were included for this systematic review. Twenty-eight articles reported CRP and/or ESR separately, and the remaining articles reported CRP and/or ESR as part of the ACR response criteria. Studies assessing OMERACT responsiveness provided conflicting reports. Inflammatory biomarkers had construct validity for more active disease. Evidence suggests that an elevation of ESR predicts cardiovascular outcomes. Data regarding assessment of systemic inflammation using acute-phase reactants (CRP and ESR) are limited. There is only weak evidence to support normalization of these biomarkers in predicting good clinical outcomes/remission criteria. The predictive value for cardiovascular outcomes was generally good. Further studies to assess systemic inflammation in PsA using acute-phase reactants and other laboratory biomarkers are needed.

Content and Face Validity and Feasibility of 5 Candidate Instruments for Psoriatic Arthritis Randomized Controlled Trials: The PsA OMERACT Core Set Workshop at the GRAPPA 2017 Annual Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group is in the process of selecting core instruments for PsA clinical trials. During a 2-h workshop and breakout group discussions at the GRAPPA 2017 annual meeting in Amsterdam, the Netherlands, participants discussed the first set of candidate instruments to be taken through the OMERACT Filter 2.1 instrument selection process: 66/68 swollen/tender joint count (66/68JC), Spondyloarthritis Consortium of Canada (SPARCC) enthesitis index, patient's global assessment (GRAPPA and OMERACT formulations), Health Assessment Questionnaire-Disability Index (HAQ-DI), Psoriatic Arthritis Impact of Disease (PsAID) questionnaires 9 and 12, and Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue. Based on the assessment of domain match (content and face validity) and feasibility according to the OMERACT instrument selection criteria, the working group recommends continuing with appraisal of construct validity and discrimination for 66/68JC, SPARCC, PsAID 9 and 12, HAQ-DI, and FACIT-Fatigue. In addition, it recommends repeating the OMERACT Filter 2.1 process for patient global instruments because of insufficient votes. Additional sets of candidate instruments for the PsA core instrument set will be evaluated in a similar process.

A systematic review of measurement properties of patient reported outcome measures in psoriatic arthritis: A GRAPPA-OMERACT initiative.

An updated psoriatic arthritis (PsA) core outcome set (COS) for randomized controlled trials (RCTs) was endorsed at the Outcome Measures in Rheumatology (OMERACT) meeting in 2016. To synthesize the evidence on measurement properties of patient reported outcome measures (PROMs) for PsA and thereby contribute to development of a PsA core outcome measurement set (COMS) as described by the OMERACT Filter 2.0. A systematic literature search was performed in EMBASE, MEDLINE and PsycINFO on Jan 1, 2017 to identify full-text articles with an aim of assessing the measurement properties of PROMs in PsA. Two independent reviewers rated the quality of studies using the COnsensus based standards for the Selection of health Measurement INstruments (COSMIN) checklist, and performed a qualitative evidence synthesis. Fifty-five studies were included in the systematic review. Forty-four instruments and a total of 89 scales were analyzed. PROMs measuring COS domains with at least fair quality evidence for good validity and reliability (and no evidence for poor properties) included the Stockerau Activity Score for PsA (German), Psoriasis Symptom Inventory, visual analogue scale for Patient Global, 36 Item Short Form Health Survey Physical Function subscale, Health Assessment Questionnaire Disability Index, Bath Ankylosing Spondylitis Functional Index, PsA Impact of Disease questionnaire, PsA Quality of Life questionnaire, VITACORA-19, Functional Assessment of Chronic Illness Therapy Fatigue scale and Social Role Participation Questionnaire. At least one PROM with some evidence for aspects of validity and reliability was available for six of the eight mandatory domains of the PsA COS.

Defining Outcome Measures for Psoriatic Arthritis: A Report 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) Core Set working group recently published the updated 2016 psoriatic arthritis (PsA) core domain set, a set of disease features that should be measured in all clinical trials. At the GRAPPA annual meeting in July 2016, the PsA working group presented the updated PsA core domain set endorsed by 90% of participants at OMERACT in May 2016 and drafted a roadmap for the development of the PsA core outcome measurement set. In this manuscript, we review the development process of the PsA core domain set and the ongoing and proposed work streams for development of a PsA core measurement set.

Updating the Psoriatic Arthritis (PsA) Core Domain Set: A Report from the PsA Workshop at OMERACT 2016.

To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS). At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants. We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries representing 5 continents to identify patient domains. We achieved consensus through 2 rounds of separate surveys with 50 patients and 75 physicians, and a nominal group technique meeting with 12 patients and 12 physicians. We conducted a workshop and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient's global assessment, physical function, health-related quality of life, and systemic inflammation, which were recommended for all RCT and LOS. These were important, but not required in all RCT and LOS: economic cost, emotional well-being, participation, and structural damage. Independence, sleep, stiffness, and treatment burden were on the research agenda. The updated PsA Core Domain Set was endorsed at OMERACT 2016. Next steps for the PsA working group include evaluation of PsA outcome measures and development of a PsA Core Outcome Measurement Set.

International patient and physician consensus on a psoriatic arthritis core outcome set for clinical trials

ObjectiveTo identify a core set of domains (outcomes) to be measured in psoriatic arthritis (PsA) clinical trials that represent both patients' and physicians' priorities.MethodsWe conducted (1) a systematic literature review...

Report of the GRAPPA-OMERACT Psoriatic Arthritis Working Group from the GRAPPA 2015 Annual Meeting

The GRAPPA-OMERACT psoriatic arthritis (PsA) working group is in the process of updating the PsA core domain set to improve and standardize the measurement of PsA outcomes. Work streams comprise literature reviews of domains and outcome measurement instruments, an international qualitative research project with PsA patients to generate domains important to patients, outcome measurement instrument assessment, conduct of domain consensus panels with patients and physicians, and evidence-based selection of instruments. Patient research partners are involved in each of the projects. The working group will present findings and seek endorsement for the new PsA core domain set, outcome measurement set, and research agenda at the OMERACT meeting in May 2016.

Review of the Psoriatic Arthritis Working Group at OMERACT 12: A Report from the GRAPPA 2014 Annual Meeting

At the 2014 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the psoriatic arthritis (PsA) working group of OMERACT (Outcome Measures in Rheumatology) presented a review of the progress made at the OMERACT 12 meeting, held in 2014. Members of the PsA OMERACT working group presented work from the Patient Involvement in Outcome Measures for PsA initiative to improve the incorporation of patient research partners in PsA outcomes research, the results of discussions within the OMERACT breakout groups, and finally the voting results. The OMERACT 12 participants had endorsed the need to update the PsA core set according to the Filter 2.0 framework. The breakout group discussions identified potential opportunities for revising the core set, including consolidating existing redundancy within the core set, improving incorporation of the patient perspective, and including disease effects such as fatigue as a core criterion. GRAPPA members of the OMERACT working group now have a program of research to update the core set with the goal of seeking endorsement at OMERACT 13, to be held in 2016.

Enhanced Patient Involvement and the Need to Revise the Core Set - Report from the Psoriatic Arthritis Working Group at OMERACT 2014.

To discuss the need for revision of the "core set" of domains to be included for assessment in psoriatic arthritis (PsA) randomized controlled trials and longitudinal observational studies, review work undertaken since the 2012 meeting of Outcome Measures for Rheumatology 11 (OMERACT 11) to include patient perspectives in this revision, and reassess proposed composite measures in the context of new research data and the OMERACT Filter 2.0 framework. The OMERACT 12 (2014) PsA working group presented work completed over the last 2 years to incorporate patient involvement in PsA outcomes research, review the endorsed PsA core set based on the patient perspective as well as new research findings, and further develop PsA responder indices. Breakout groups then discussed 2 topics: (1) the need to revise the PsA core set, and opportunities to add, move, or merge existing domains to improve existing redundancy; and (2) how to incorporate the core set in a composite index. Breakout groups fed back to the working group before participant voting. Meeting participants endorsed the need to revise the PsA core set according to the OMERACT Filter 2.0 framework (100%), and the inclusion of disease impact (94%) and fatigue (72%) in the inner circle. Breakout group feedback suggested the core set revision was an opportunity to consolidate pathophysiologic aspects such as arthritis, enthesitis, dactylitis, spondylitis as "inflammatory musculoskeletal disease," and nail and skin psoriasis as "psoriasis activity." Future work will focus on updating the PsA core set and development of responder indices with ongoing, meaningful involvement of patient research partners.

Limbic hyperconnectivity in the vegetative state

To investigate functional connectivity between the default mode network (DMN) and other networks in disorders of consciousness. We analyzed MRI data from 11 patients in a vegetative state and 7 patients in a minimally conscious state along with age- and sex-matched healthy control subjects. MRI data analysis included nonlinear spatial normalization to compensate for disease-related anatomical distortions. We studied brain connectivity data from resting-state MRI temporal series, combining noninferential (independent component analysis) and inferential (seed-based general linear model) methods. In DMN hypoconnectivity conditions, a patient's DMN functional connectivity shifts and paradoxically increases in limbic structures, including the orbitofrontal cortex, insula, hypothalamus, and the ventral tegmental area. Concurrently with DMN hypoconnectivity, we report limbic hyperconnectivity in patients in vegetative and minimally conscious states. This hyperconnectivity may reflect the persistent engagement of residual neural activity in self-reinforcing neural loops, which, in turn, could disrupt normal patterns of connectivity.