GRAPPA 2023: Major Projects, Key Advances, and Milestones.

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, members were updated on a number of ongoing activities during the key project update session. These activities included the Axial Involvement in Psoriatic Arthritis (AXIS) cohort, the Axial Psoriatic Arthritis Molecular and Clinical Characterization study, the Diagnostic Ultrasound Enthesitis Tool (DUET) study, the Sex- and Gender-Based Analysis of the Effectiveness of Advanced Therapies in Psoriatic Arthritis (SAGE-PsA) study, the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES), the GRAPPA slide library, and the GRAPPA treatment recommendations.

GRAPPA 2023 Collaborative Research Network Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Collaborative Research Network (CRN)/research committee met during the GRAPPA 2023 annual meeting. Updates were provided on GRAPPA research projects, including the Axial Involvement in Psoriatic Arthritis (AXIS), Axial Psoriatic Arthritis Molecular and Clinical Characterisation Study, Diagnostic Ultrasound Enthesitis Tool (DUET), and Sex- and Gender-Based Analysis of the Effectiveness of Advanced Therapies (SAGE) studies, as well as the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES) and Elucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium (ELLIPSS) studies. The highlight of the meeting was a presentation and discussion on the use of digital tools to study psoriatic disease.

Introducing New GRAPPA Projects.

Every year at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, new project ideas are presented and discussed with a view to obtaining feedback and support. Arising from previous work, a project proposal was presented at the 2023 meeting; the project aims to improve early diagnosis of psoriatic arthritis (PsA) by comparing a physician-based vs a patient questionnaire-based approach. This project has received the backing of the GRAPPA research committee, but additional funding will be required. A second project, approved by GRAPPA, was presented on delivering an epidemiology training module before the GRAPPA annual meeting in 2024, which will target both established GRAPPA clinicians and trainees. Attendance at such a module would enhance the quality of research in psoriatic disease.

Advances in Psoriatic Disease Research: Insights From GRAPPA Pilot Research Awardees.

Research progress from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) pilot award program was presented and discussed at the GRAPPA 2023 annual meeting. Topics included identification of protein biomarkers associated with enthesitis in psoriatic arthritis (PsA), the role of HLA-B27 on gut microbial dysbiosis in PsA, single-cell profiling of synovial fluid vs psoriatic skin lesions in PsA, and the role of mechanotransduction in hyperactivation of transforming growth factor-ß via αVß6 integrin in psoriatic epidermis.

Prologue: Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 Annual Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting was held on July 13 to 15, 2023, in Dublin, Ireland, and was attended by 285 rheumatologists, dermatologists, trainees, patient research partners (PRPs), representatives of patient organizations, and industry partners. The 20th anniversary of GRAPPA was celebrated with a special presentation and archival video. Ahead of the meeting, the PRP Network met, a workshop was held by the International Dermatology Outcome Measures (IDEOM) group, and there was a workshop in which researchers discussed advancing ultrasound use to improve the management of psoriatic disease (PsD). Young-GRAPPA also held a workshop and business meeting. Multiple presentations highlighted important topics currently influencing PsD, including ensuring that patients are included in advancing research, the role of depression in PsD, the use of magnetic resonance imaging for spinal lesions, and animal models of PsD, among others. Debates focused on whether biologics should be used for mild psoriasis, whether methotrexate should remain the first-line treatment for PsD, and whether PsD is really a primary enthesitis driving joint synovitis. Here we provide an overview of the features of the GRAPPA 2023 annual meeting and introduce the manuscripts published together in this supplement as a meeting report.

Video livestreaming from medical emergency callers' smartphones to emergency medical dispatch centres: a scoping review of current uses, opportunities, and challenges.

BACKGROUND: Timely dispatch of appropriate emergency medical services (EMS) resources to the scene of medical incidents, and/or provision of treatment at the scene by bystanders and medical emergency lay callers (referred to as 'callers' in this review) can improve patient outcomes. Currently, in dispatch systems worldwide, prioritisation of dispatch relies mostly on verbal telephone information from callers, but advances in mobile phone technology provide means for sharing video footage. This scoping review aimed to map and identify current uses, opportunities, and challenges for using video livestreaming from callers' smartphones to emergency medical dispatch centres. METHODS: A scoping review of relevant published literature between 2007 and 2023 in the English language, searched within MEDLINE; CINAHL and PsycINFO, was descriptively synthesised, adhering to the PRISMA extension for scoping reviews. RESULTS: Twenty-four articles remained from the initial search of 1,565 articles. Most studies were simulation-based and focused on emergency medical dispatchers' (referred to as 'dispatcher/s' in this review) assisted video cardiopulmonary resuscitation (CPR), predominantly concerned with measuring how video impacts CPR performance. Nine studies were based on real-life practice. Few studies specifically explored experiences of dispatchers or callers. Only three articles explored the impact that using video had on the dispatch of resources. Opportunities offered by video livestreaming included it being: perceived to be useful; easy to use; reassuring for both dispatchers and callers; and informing dispatcher decision-making. Challenges included the potential emotional impact for dispatchers and callers. There were also concerns about potential misuse of video, although there was no evidence that this was occurring. Evidence suggests a need for appropriate training of dispatchers and video-specific dispatch protocols. CONCLUSION: Research is sparse in the context of video livestreaming. Few studies have focussed on the use of video livestreaming outside CPR provision, such as for trauma incidents, which are by their nature time-critical where visual information may offer significant benefit. Further investigation into acceptability and experience of the use of video livestreaming is warranted, to understand the potential psychological impact on dispatchers and callers.

Phase 2 Trial of Deucravacitinib in Psoriatic Arthritis: Biomarkers Associated With Disease Activity, Pharmacodynamics, and Clinical Responses.

OBJECTIVE: Our objective was to evaluate the association of serum biomarkers with baseline psoriatic arthritis (PsA) disease activity, pharmacodynamic effects of deucravacitinib on biomarker levels, and the relationship between biomarkers and clinical responses to deucravacitinib. METHODS: The phase 2 trial (ClinicalTrials.gov identifier: NCT03881059) randomly assigned 203 patients with PsA 1:1:1 to placebo, deucravacitinib at 6 mg once daily (QD), or deucravacitinib at 12 mg QD. Serum biomarkers associated with the interleukin 23 (IL-23) pathway (IL-17A, ß-defensin [BD-2], and IL-19), type I interferon pathway, inflammation, and collagen matrix turnover were measured by immunoassay. Clinical responses (≥75% improvement from baseline in the Psoriasis Area and Severity Index [PASI75] and ≥20% improvement from baseline in American College of Rheumatology criteria [ACR20] responses) were measured at week 16. Hematologic variables were also assessed. RESULTS: IL-17A, BD-2, and IL-19 had a modest association with PASI scores (r = 0.4, r = 0.56, and r = 0.5, respectively) at baseline. In deucravacitinib groups, IL-17A, BD-2, IL-19, C-X-C motif ligand 9 (CXCL9), CXCL10, C-reactive protein, matrix metalloproteinase 3, and collagen type 4 degradation marker levels were significantly reduced at week 16 versus baseline (P < 0.01); higher levels of IL-23 pathway-associated biomarkers predicted higher PASI75 and ACR20 response rates in deucravacitinib-treated patients. Significantly higher PASI75 response rates were seen in patients with high baseline IL-17A (odds ratio 15.76) and BD-2 levels (odds ratio 15.41) versus low baseline IL-17A and BD-2 levels. Changes in hematologic variables that are characteristic of JAK inhibition were not observed with deucravacitinib. CONCLUSION: Deucravacitinib significantly impacted biomarkers associated with Tyk2 signaling pathways of key inflammatory cytokines, including IL-23 and type I interferon, and those related to collagen matrix turnover. These biomarkers may predict treatment responses to deucravacitinib.

GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets.

Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To move towards a saturation map of psoriasis susceptibility we meta-analysed 18 GWAS comprising 36,466 cases and 458,078 controls and identified 109 distinct psoriasis susceptibility loci, including 45 that have not been previously reported. These include susceptibility variants at loci in which the therapeutic targets IL17RA and AHR are encoded, and deleterious coding variants supporting potential new drug targets (including in STAP2, CPVL and POU2F3). We conducted a transcriptome-wide association study to identify regulatory effects of psoriasis susceptibility variants and cross-referenced these against single cell expression profiles in psoriasis-affected skin, highlighting roles for the transcriptional regulation of haematopoietic cell development and epigenetic modulation of interferon signalling in psoriasis pathobiology.

Application of clinical and molecular profiling data to improve patient outcomes in psoriatic arthritis.

Achieving a good outcome for a person with Psoriatic Arthritis (PsA) is made difficult by late diagnosis, heterogenous clinical disease expression and in many cases, failure to adequately suppress inflammatory disease features. Single-centre studies have certainly contributed to our understanding of disease pathogenesis, but to adequately address the major areas of unmet need, multi-partner, collaborative research programmes are now required. HIPPOCRATES is a 5-year, Innovative Medicines Initiative (IMI) programme which includes 17 European academic centres experienced in PsA research, 5 pharmaceutical industry partners, 3 small-/medium-sized industry partners and 2 patient-representative organizations. In this review, the ambitious programme of work to be undertaken by HIPPOCRATES is outlined and common approaches and challenges are identified. It is expected that, when completed, the results will ultimately allow for changes in the approaches to diagnosing, managing and treating PsA allowing for better short-term and long-term outcomes.

Improving outcomes in Psoriatic Arthritis Psoriatic Arthritis (PsA) is a form of arthritis which is found in approximately 30% of people who have the skin condition, Psoriasis. Frequently debilitating and progressive, achieving a good outcome for a person with PsA is made difficult by late diagnosis, disease clinical features and in many cases, failure to adequately control features of inflammation. Research studies from individual centres have certainly contributed to our understanding of why people develop PsA but to adequately address the major areas of unmet need, multi-centre, collaborative research programmes are now required. HIPPOCRATES is a 5-year, Innovative Medicines Initiative (IMI) programme which includes 17 European academic centres experienced in PsA research, 5 pharmaceutical industry partners, 3 small-/medium-sized industry partners and 2 patient representative organisations (see appendix). In this review, the ambitious programme of work to be undertaken by HIPPOCRATES is outlined and common approaches and challenges are identified. The participation of patient research partners in all stages of the work of HIPPOCRATES is highlighted. It is expected that, when completed, the results will ultimately allow for changes in the approaches to diagnosing, managing and treating PsA allowing for improvements in short-term and long-term outcomes.

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

BACKGROUND: Tofacitinib 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. METHODS: Data 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. RESULTS: Seven 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. CONCLUSION: Tofacitinib treatment resulted in improvements in enthesitis in patients with PsA, regardless of baseline location or severity. TRIAL REGISTRATION: NCT01877668;NCT01882439.

Novel Insights From Basic Science in Psoriatic Disease at the GRAPPA 2022 Annual Meeting.

Recent basic science advances in psoriatic disease (PsD) were presented and discussed at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 annual meeting. Topics included clinical applications of biomarkers, what the future of biomarkers for PsD may hold, the challenges of developing biomarker research to the point of clinical utility, advances in total-body positron emission tomography/computed tomography imaging, and emerging concepts from single-cell studies in PsD.

Proceedings of the GRAPPA 2022 Executive Retreat.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) leadership congregated for a strategic planning meeting before the 2022 GRAPPA annual meeting in New York, USA. Meeting aims were to review GRAPPA's performance in relation to its 2016 goals and identify successes and areas for further improvement, identify key GRAPPA priorities and activities for the next 5 years, and explore committee structures to best support these aims.

Proceedings of the Collaborative Research Network Meeting at the GRAPPA 2022 Annual Meeting.

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 annual meeting, the Collaborative Research Network (CRN) met to present updates on several projects. These included the GRAPPA-Industry biomarker projects, Axial Psoriatic Arthritis Molecular and Clinical Characterisation Study, Axial Involvement in Psoriatic Arthritis Cohort (AXIS) study, and the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES). The meeting concluded with a discussion on pathways to further academia-industry collaboration.

Screening and Referral Strategies for the Early Recognition of Psoriatic Arthritis Among Patients With Psoriasis: Results of a GRAPPA Survey.

OBJECTIVE: This study aimed to explore the experiences of dermatologists and rheumatologists in the early recognition of psoriatic arthritis (PsA) and to identify potential improvements to the current shared-care model. METHODS: A 24-question survey addressing referral strategies was constructed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) project steering committee and sent to all members (n = 927). Questions addressed the use of screening tools, frequency of PsA in patients with psoriasis, therapeutic decision making, and suggestions for earlier PsA recognition and current unmet needs. RESULTS: There were 149 respondents (16.1% response rate), which included 113 rheumatologists from 37 countries and 26 dermatologists from 16 countries. Of the dermatologists, 81% use PsA-specific screening instruments. Conversely, rheumatologists reported that only 26.8% of patients referred to them from all sources had been assessed with screening tools. Although dermatologists reported that a mean of 67% of suspected PsA cases were confirmed, rheumatologists reported a mean of 47.9% of confirmed cases. Both specialties reported similar views regarding optimization of the diagnostic process and indicated that the best approach involved combining patient-reported (ie, screening tools) and physician-confirmed findings. Moreover, both specialties identified the education of primary care physicians (PCPs) and dermatologists as the greatest priority to improve PsA screening. CONCLUSION: The survey indicated the current unmet needs in the early recognition of PsA. Important areas to address include improving the use of screening instruments, increasing the education of community-based dermatologists and PCPs, and using a combination of patient-reported and physician-confirmed findings in the screening approach.

Project Highlights From the GRAPPA 2022 Annual Meeting: Education Initiatives and Axial Involvement in Psoriatic Arthritis.

A core mission of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) is to provide education about psoriasis and psoriatic arthritis globally. This is a multifaceted endeavor involving in-person and virtual lectures, discussions, podcasts, and archived videos directed toward clinicians and researchers who are involved with psoriatic disease (PsD) care. In partnership with patient service leagues, we also aim to provide education to patients with PsD. At the 2022 annual meeting, an update of the ongoing and expected educational initiatives was presented. A project with a high educational and research value is the Axial Involvement in Psoriatic Arthritis (AXIS) cohort established in collaboration with the Assessment of Spondyloarthritis international Society (ASAS). Here we summarize the status of the project.

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.

Prologue: Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 Annual Meeting.

The 2022 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was held from July 14 to 17, 2022, in New York City, New York, USA, and was attended by 420 rheumatologists, dermatologists, basic scientists, allied health professionals, patient research partners, and industry partners from 31 countries. A GRAPPA executive retreat, a Trainee Symposium, and the Patient Research Partners Network meeting were held prior to the annual meeting. Presentations included updates in basic research, focusing on biomarkers, personalization of treatments, and the promise of single-cell omics, elucidating the pathogenesis of psoriatic disease (PsD). Presentations also highlighted guttate and plaque psoriasis (PsO), the impact of coronavirus disease 2019 (COVID-19) and its treatments on patients with PsD globally, and the effects of sex and gender in PsD. Reports of ongoing projects included an update on the recently published treatment recommendations, educational initiatives, and the Diagnostic Ultrasound Enthesitis Tool (DUET) study. A session on early identification of psoriatic arthritis (PsA) among patients with PsO included an update on PsA screening tools. Debates were held on whether early intervention for PsO will reduce PsA, whether interleukin (IL)-17 or IL-23 inhibition is a better treatment for PsO and PsA, similarities and differences between axial PsA and axial spondyloarthritis with PsO, and data affecting the understanding of guttate and plaque PsO. Reports from the International Dermatology Outcome Measures (IDEOM) and Young GRAPPiAns concurrent sessions were presented in addition to reports of several other partner groups. Here, we highlight features of the annual meeting and introduce the manuscripts published together as a meeting report.

GRAPPA 2021 Pilot Grant Award Reports.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) pilot grant awards help support young researchers starting their careers while also encouraging them to develop a focus on psoriatic disease. In this brief report, winners of the 2020 and 2021 awards present the results of their pilot projects.

Stricter treat-to-target in RA does not result in less radiographic progression: a longitudinal analysis in RA BIODAM.

OBJECTIVES: To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. METHODS: Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. RESULTS: In total, 511 patients were included [mean (s.d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: -0.04, 0.33) for 2 vs 0 visits; and +0.08 units (-0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. CONCLUSIONS: In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.

Differentiating patients with psoriasis from psoriatic arthritis using collagen biomarkers.

OBJECTIVES: Around 30% of patients diagnosed with cutaneous psoriasis (PsC) will go on to develop psoriatic arthritis (PsA) which includes inflammation of the joints. Collagens are core proteins in all tissues, which are involved in the inflammatory process in both PsC and PsA. The aim of this study is to investigate collagen biomarkers and their potential use in separating the three patient groupings: PsC, PsA and healthy donors. METHODS: Healthy donors (n=41), patients with PsC (n=30) and patients with PsA (n=30) were recruited. Clinical disease parameters were recorded. Collagen remodelling was measured using ELISA immunoassays which detect the serological anabolic biomarkers quantifying formation of type I, III and IV collagen (PRO-C1, PRO-C3 and PRO-C4 respectively), and the catabolic biomarkers measuring degradation of type I, II, III, IV and X collagen (C1M, C2M, C3M, C4M and C10C respectively). RESULTS: Patients with PsC and PsA presented lower levels of PRO-C1 and C3M compared to healthy controls (p<0.05-p<0.0001), C1M was higher in PsA compared to healthy controls (p<0.0001) and C2M was all elevated in PsC and PsA compared to healthy controls (p=0.0002 and p=0.0004 respectively), reflecting alterations in the tissues. In addition, C1M was able to separate between PsC and PsA patients with an AUROC=0.664, indicating that this biomarker may be a biomarker of joint involvement. CONCLUSIONS: This work provides evidence that serum collagen biomarkers are dysregulated in PsC and PsA, as compared to healthy controls. C1M was able to differentiate patients with PsC from PsA and could be a potential biomarker of inflammatory systemic musculoskeletal involvement.