Management of Concomitant Inflammatory Bowel Disease or Uveitis in Patients with Psoriatic Arthritis: An Updated Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Several advanced therapies have been licensed across the related conditions of psoriatic arthritis (PsA), Crohn disease (CD), ulcerative colitis (UC), and noninfectious uveitis. We sought to summarize results from randomized controlled trials (RCTs) investigating the efficacy and safety of advanced therapies for these related conditions in patients with PsA. METHODS: We updated the previous systematic search conducted in 2013 with literature reviews of MEDLINE, Embase, and the Cochrane Library (from February 2013 to August 2020) on this subject; only those new studies are presented here. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The number of RCTs meeting eligibility criteria were 12 for CD, 15 for UC, and 5 for uveitis. The tumor necrosis factor inhibitor (TNFi) class appears to be efficacious and safe across CD, UC, and uveitis, with the exception of etanercept. Interleukin 12/23 inhibitors (IL-12/23i) are efficacious for CD and UC. Phase II and III RCTs of Janus kinase inhibitors (JAKi) and IL-23i in CD and UC are promising in terms of efficacy and safety. IL-17i must be used with great caution in patients with PsA at high risk of inflammatory bowel disease (IBD). RCTs in uveitis have mainly studied adalimumab. CONCLUSION: We have identified 32 recent RCTs in IBD and uveitis and updated recommendations for managing patients with PsA and these related conditions. A multispecialty approach is essential to effectively, safely, and holistically manage such patients. Advanced therapies are not equally efficacious across these related conditions, with dosing regimens and safety varying.

Composite Measures for Clinical Trials in Psoriatic Arthritis: Testing Pain and Fatigue Modifications in a UK Multicenter Study.

OBJECTIVE: To test the addition of pain and fatigue to the Composite Psoriatic Arthritis Disease Activity (CPDAI) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) Composite Exercise (GRACE) composite measures of psoriatic arthritis (PsA). METHODS: Clinical and patient-reported outcome measures were assessed in patients with PsA at 3 consecutive follow-up visits over 6 months in a UK multicenter observational study. A pain visual analog scale and Functional Assessment of Chronic Illness Therapy Fatigue scale were added as modifications to the CPDAI and GRACE composite measures. Original and modified versions were tested against the PsA Disease Activity Score (PASDAS) and the Disease Activity Index for PsA (DAPSA). Discrimination between disease states and responsiveness were tested with t-scores, standardized response means (SRMs), and effect sizes. Data were presented to members at the 2020 annual meeting who then voted on the GRAPPA-recommended composite and treatment targets for clinical trials. RESULTS: One hundred forty-one patients were recruited with a mean PsA disease duration of 6.1 years (range 0-41 yrs). The SRMs for the GRACE and modified GRACE (mGRACE) were 0.67 and 0.64, respectively, and 0.54 and 0.46, respectively, for the CPDAI and modified CPDAI (mCPDAI). The t-scores for the GRACE and mGRACE were unchanged at 7.8 for both, and 6.8 and 7.0 for the CPDAI and mCPDAI, respectively. The PASDAS demonstrated the best responsiveness (SRM 0.84) and discrimination (t-scores 8.3). Most members (82%) agreed the composites should not be modified and 77% voted for the PASDAS as the GRAPPA-recommended composite for clinical trials, with 90% minimal disease activity (MDA) as the target. CONCLUSION: Modifying the CPDAI and GRACE with the addition of pain and fatigue does not enhance responsiveness nor the measures' ability to detect disease status in terms of requiring treatment escalation. GRAPPA members voted for the PASDAS as the composite measure in clinical trials and MDA as the target.

Composite Measures for Routine Clinical Practice in Psoriatic Arthritis: Testing of Shortened Versions in a UK Multicenter Study.

OBJECTIVE: To test shortened versions of the psoriatic arthritis (PsA) composite measures for use in routine clinical practice. METHODS: Clinical and patient-reported outcome measures (PROMs) were assessed in patients with PsA at 3 consecutive follow-up visits in a UK multicenter observational study. Shortened versions of the Composite Psoriatic Arthritis Disease Activity Index (CPDAI) and Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite Exercise (GRACE) measures were developed using PROMs and tested against the Disease Activity Score in 28 joints (DAS28), composite Disease Activity in Psoriatic Arthritis, and Routine Assessment of Patient Index Data (RAPID3). Discrimination between disease states and responsiveness were tested with the t-score, standardized response mean (SRM), and effect size (ES). Data were presented to members at the GRAPPA 2020 annual meeting and members voted on the recommended composite routine practice. RESULTS: The SRM for the GRACE, 3 visual analog scale (VAS), and 4VAS were 0.67, 0.77, and 0.63, respectively, and for CPDAI and shortened CPDAI (sCPDAI) were 0.54 and 0.55, respectively. Shortened versions of the GRACE increased the t-score from 7.8 to 8.7 (3VAS) and 9.0 (4VAS), but reduced the t-score in the CPDAI/sCPDAI from 6.8 and 6.1. The 3VAS and 4VAS had superior performance characteristics to the sCPDAI, DAS28, Disease Activity in Psoriatic Arthritis, and RAPID3 in all tests. Of the members, 60% agreed that the VAS scales contained enough information to assess disease and response to treatment, 53% recommended the 4VAS for use in routine care, and 26% the 3VAS, while leaving 21% undecided. Conclusion. Shortening the GRACE to VAS scores alone enhances the ability to detect status and responsiveness and has the best performance characteristics of the tested composite measures. GRAPPA members recommend further testing of the 3VAS and 4VAS in observational and trial datasets.

Proceedings of the 2020 GRAPPA Collaborative Research Network (CRN) Meeting.

At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Collaborative Research Network (CRN) annual meeting, the GRAPPA-CRN group presented a pilot investigator-initiated study protocol to test electronic case report forms (eCRFs) and proposed Standardized Operating Procedures (SOPs) to evaluate biomarkers of psoriatic arthritis (PsA) associated with axial disease. The progress on 3 studies was also presented: BioDAM PsA (Biomarkers as Predictors of structural DAMage in PsA; to validate soluble biomarkers as predictors of structural damage in PsA), PreventPsA (examining the development of PsA and risk factors among patients with psoriasis and no arthritis), and PredictORPsA (Predicting Treatment respOnse in patients with eaRly PsA; in collaboration with Pfizer using samples from the Oral Psoriatic Arthritis TriaL [OPAL], to identify biomarkers of treatment response). GRAPPA-CRN funding partnerships and applications are also underway with both the Innovative Medicines Initiative (IMI) in Europe and Accelerating Medicines Partnerships (AMP) 2.0 in the USA, and the progress of these applications and associated objectives were presented.

Human osteoarthritic synovial fluid increases excitability of mouse dorsal root ganglion sensory neurons: an in-vitro translational model to study arthritic pain.

OBJECTIVES: Knee OA is a leading global cause of morbidity. This study investigates the effects of knee SF from patients with OA on the activity of dorsal root ganglion sensory neurons that innervate the knee (knee neurons) as a novel translational model of disease-mediated nociception in human OA. METHODS: Dissociated cultures of mouse knee neurons were incubated overnight or acutely stimulated with OA-SF (n = 4) and fluid from healthy donors (n = 3, Ctrl-SF). Electrophysiology and Ca2+-imaging determined changes in electrical excitability and transient receptor potential channel function, respectively. RESULTS: Incubation with OA-SF induced knee neuron hyperexcitability compared to Ctrl-SF: the resting membrane potential significantly increased (F(2, 92) = 5.6, P = 0.005, ANOVA) and the action potential threshold decreased (F(2, 92) = 8.8, P = 0.0003, ANOVA); TRPV1 (F(2, 445) = 3.7, P = 0.02) and TRPM8 (F(2, 174) = 11.1, P < 0.0001, ANOVA) channel activity also increased. Acute application of Ctrl-SF and OA-SF increased intracellular Ca2+ concentration via intra- and extracellular Ca2+ sources. CONCLUSION: Human OA-SF acutely activated knee neurons and induced hyperexcitability indicating that mediators present in OA-SF stimulate sensory nerve activity and thereby give rise to knee pain. Taken together, this study provides proof-of-concept for a new method to study the ability of mediators present in joints of patients with arthritis to stimulate nociceptor activity and hence identify clinically relevant drug targets for treating knee pain.

Proceedings of the 2019 GRAPPA Collaborative Research Network Meeting.

At the 2019 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis-Collaborative Research Network annual meeting, the group presented its progress in selecting a database platform; items to include in an electronic case report form (eCRF); and standardized operating procedures (SOP) for the collection, processing, storage, and transport of biomaterial. A pilot investigator-initiated study was also proposed that, in addition to addressing an area of unmet need, would allow for the testing of both the eCRF and SOP.

Trajectory of radiographic change over a decade: the effect of transition from conventional synthetic disease-modifying antirheumatic drugs to anti-tumour necrosis factor in patients with psoriatic arthritis.

Objectives: To describe the trajectory of radiographic progression among patients with PsA who transitioned from conventional synthetic DMARDs to anti-TNF-α inhibitors in routine care. Methods: A retrospective sample of patients with PsA (ClASsification criteria for Psoriatic ARthritis) was taken from the Bath longitudinal cohort. All patients had radiographs of the hands and feet taken: 5 years before (T0), at the time of (T1) and 5 years after (T2) commencing anti-TNF treatment. Radiographs were scored blinded using the PsA-modified Sharp-van der Heijde score (mSvdHS) and for osteoproliferation (Psoriatic Arthritis Ratingen Score) by A.Allard, A.Antony and W.T. This sample size was calculated to ensure 90% power to determine the smallest detectable difference of the mSvdHS to a 5% significance level. Cumulative probability plots were used to determine the probability of radiographic progression pre- (T0-T1) and post- (T1-T2) anti-TNF treatment. Results: Eighty-four radiographs from 28 patients were selected for inclusion. The median [interquartile range (IQR)] disease duration at baseline (T0) was 8.5 (0-19.5) years. The interval between T0-T1 and T1-T2 was 4.2 years (3.34-6.65) and 4.9 years (4.25-5.87), respectively. The median mSvdHS at baseline (T0) was 8.5 (IQR 1.75-27.5). The median (IQR) rate of change in mSvdHS per year reduced after commencing anti-TNF, from 2.1 (0.88-3.92) between T0-T1 to 1.0 (IQR 0.05-2.35) between T1-T2 (P = 0.012). Conclusion: The trajectory of damage accumulation over a 10-year period in this observational clinical cohort is low overall. The rate of radiographic damage as measured by the mSvdHS slows following commencement of anti-TNF.

Proceedings of the 2018 GRAPPA Collaborative Research Network Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Collaborative Research Network (CRN) intends to launch and secure funding for 3 pilot projects related to psoriatic disease, psoriatic arthritis (PsA), and cutaneous psoriasis (PsC). The first pilot project, a PsA Biomarkers for Joint Damage (BioDAM) pilot, will seek to determine the independent predictive ability of serum biomarkers for joint damage in PsA. The second pilot project will aim to identify predictors of the development of PsA among patients with PsC. The third pilot project will aim to identify biomarkers that predict treatment response in PsA and PsC. These pilot projects will prompt the development of clinical protocols to operate across participating centers, lead to the development of standard operating procedures for the collection and transport of biosamples across international borders, and begin to establish administrative and managerial structures for the CRN. The CRN hopes that the successful completion and research outputs of these 3 pilot projects will demonstrate the CRN's value to prospective collaborators and sponsors and thereby secure sustainable longterm funding.

The Benefits and Challenges of Setting Up a Longitudinal Psoriatic Arthritis Database.

The members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) have shown great interest in developing a common GRAPPA database. To address this interest, GRAPPA included a symposium at its 2017 annual meeting to examine the concepts of registries and databases. At this symposium, examples of existing databases were reviewed, and their challenges and achievements were discussed.

Proceedings of the 2017 GRAPPA Collaborative Research Network Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Collaborative Research Network (CRN) is an endeavor that aims to address gaps in the knowledge of the etiopathogenesis and management of psoriatic disease by best using the large community of experienced investigators who are already collecting rich clinical phenotype data and biologic samples using validated techniques. Exemplar rheumatology and dermatology projects will inform strategies to implement the CRN, while input and funding from government organizations, charities, and industry will shape the CRN. The key immediate priorities to establish the CRN are discussed herein and include (1) strategies for building infrastructure to collect and store biosamples and associated clinical data, (2) best practices for sample collection and storage, (3) approaches to engage the GRAPPA community of investigators and industry to collaborate most effectively on shared priorities, and (4) agreement on a funding strategy. The following 4 CRN candidate flagship research areas were identified: (1) predictors of treatment response in psoriatic arthritis (PsA) and cutaneous psoriasis (PsC) to permit personalized and stratified medicine approaches; (2) predictors of structural damage and disease severity, linking with the existing PsA BioDAM project; (3) predictors of PsC progressing to PsA to enable earlier intervention and possibly halt progression to PsA; and (4) comorbidity prevalence and effect on clinical outcomes in psoriatic disease. The collaboration and momentum provided by a GRAPPA-CRN will offer more than the sum of its individual contributing centers. A CRN will permit high-quality research that can more effectively address questions pertinent to patients, clinicians, scientists, industry, and governments.

Axial Disease in Psoriatic Arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis.

OBJECTIVES: To compare the prevalence, clinical and radiographic characteristics of psoriatic spondyloarthritis (PsSpA) in psoriatic arthritis (PsA), with ankylosing spondylitis (AS). METHODS: A prospective single-centre cross-sectional observational study recruited consecutive PsA and AS cases. Participants completed outcome measures, and underwent clinical examination, axial radiographic scoring and HLA-sequencing. Multivariable analyses are presented. RESULTS: The 402 enrolled cases (201 PsA, 201 AS; fulfilling classification criteria for respective conditions) were reclassified based upon radiographic axial disease and psoriasis, as: 118 PsSpA, 127 peripheral-only PsA (pPsA), and 157 AS without psoriasis (AS) cases. A significant proportion of patients with radiographic axial disease had PsSpA (118/275; 42.91%), and often had symptomatically silent axial disease (30/118; 25.42%). Modified New York criteria for AS were fulfilled by 48/201 (23.88%) PsA cases, and Classification of Psoriatic Arthritis criteria by 49/201 (24.38%) AS cases. pPsA compared with PsSpA cases had a lower frequency of HLA-B*27 (OR 0.12; 95% CI 0.05 to 0.25). Disease activity, metrology and disability were comparable in PsSpA and AS. A significant proportion of PsSpA cases had spondylitis without sacroiliitis (39/118; 33.05%); they less frequently carried HLA-B*27 (OR 0.11; 95% CI 0.04 to 0.33). Sacroiliac joint complete ankylosis (adjusted OR, ORadj 2.96; 95% CI 1.42 to 6.15) and bridging syndesmophytes (ORadj 2.78; 95% CI 1.49 to 5.18) were more likely in AS than PsSpA. Radiographic axial disease was more severe in AS than PsSpA (Psoriatic Arthritis Spondylitis Radiology Index Score: adjusted incidence risk ratio 1.13; 95% CI 1.09 to 1.19). CONCLUSIONS: In a combined cohort of patients with either PsA or AS from a single centre, 24% fulfilled classification criteria for both conditions. The pattern of axial disease was influenced significantly by the presence of skin psoriasis and HLA-B*27.

Clinical Controversies in Psoriatic Disease: The Use of IL-17i/IL-23i Versus TNFi as First-line Advanced Therapy in Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a complex, heterogeneous disease, with disease activity in various domains. In recent years, many novel treatments with diverse mechanisms of action have been introduced into the clinical setting. Numerous factors go into the choice and sequencing of different therapies for individual patients. At the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, a point/counterpoint debate was held addressing therapeutic choices. Specifically, the question addressed was whether interleukin (IL)-17/IL-23 inhibitors or tumor necrosis factor inhibitors are the appropriate initial therapy for patients with PsA.

The role of the multidisciplinary team in the management of psoriatic arthritis.

Psoriatic arthritis (PsA) has a heterogenous clinical phenotype with manifestations in a number of different organs and systems. Whilst PsA is typified by enthesitis, synovitis and psoriasis (skin and nail); innate and adaptive immune system dysfunction often results in concomitant conditions. These include inflammatory bowel disease, uveitis, metabolic syndrome, metabolic bone disease and mental health issues. All of which have the potential to impact on quality of life, daily function, employment, family life and social activities. Through a collection of clinical vignettes, we describe the importance of multi-disciplinary and multi-speciality involvement in the care of people with PsA.

Proceedings of the 2021 GRAPPA-Collaborative Research Network (CRN) Meeting.

At the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Collaborative Research Network (CRN) annual meeting, the GRAPPA-CRN group presented a number of project updates, including a pilot investigator-initiated study to evaluate liquid and tissue biomarkers associated with axial involvement in psoriatic arthritis (PsA). The GRAPPA-CRN session updated progress made with 3 parallel international research initiatives based on 3 previously defined unmet needs in PsA. The Health Initiatives in Psoriasis and PsOriatic arthritis ConsoRTium European States (HIPPOCRATES) is a European research consortium formed to address unmet clinical needs in PsA. The Preventing Arthritis in a multicenter Psoriasis At-Risk Population (PAMPA) is a US-based organization that has defined consensus terminology for preclinical phases of PsA and is interested in the transition process from psoriasis to PsA. An overview of the Accelerating Medicines Partnership Autoimmune and Immune-Mediated Diseases (AMP AIM) program 2.0, a consortium including GRAPPA-CRN members that addressed these 3 unmet needs in PsA, was also presented.

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021.

Since the second version of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations were published in 2015, therapeutic options for psoriatic arthritis (PsA) have advanced considerably. This work reviews the literature since the previous recommendations (data published 2013-2020, including conference presentations between 2017 and 2020) and reports high-quality, evidence-based, domain-focused recommendations for medication selection in PsA developed by GRAPPA clinicians and patient research partners. The overarching principles for the management of adults with PsA were updated by consensus. Principles considering biosimilars and tapering of therapy were added, and the research agenda was revised. Literature searches covered treatments for the key domains of PsA: peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis; additional searches were performed for PsA-related conditions (uveitis and inflammatory bowel disease) and comorbidities. Individual subcommittees used a GRADE-informed approach, taking into account the quality of evidence for therapies, to generate recommendations for each of these domains, which were incorporated into an overall schema. Choice of therapy for an individual should ideally address all disease domains active in that patient, supporting shared decision-making. As safety issues often affect potential therapeutic choices, additional consideration was given to relevant comorbidities. These GRAPPA treatment recommendations provide up-to-date, evidence-based guidance on PsA management for clinicians and people with PsA.

Biomarkers predictive of treatment response in psoriasis and psoriatic arthritis: a systematic review.

AIMS: The ability to predict response to treatment remains a key unmet need in psoriatic disease. We conducted a systematic review of studies relating to biomarkers associated with response to treatment in either psoriasis vulgaris (PsV) or psoriatic arthritis (PsA). METHODS: A search was conducted in PubMed, Embase and the Cochrane library from their inception to 2 September 2020, and conference proceedings from four major rheumatology conferences. Original research articles studying pre-treatment biomarker levels associated with subsequent response to pharmacologic treatment in either PsV or PsA were included. RESULTS: A total of 765 articles were retrieved and after review, 44 articles (22 relating to PsV and 22 to PsA) met the systematic review's eligibility criteria. One study examined the response to methotrexate, one the response to tofacitinib and all the other studies to biologic disease-modifying antirheumatic drugs (DMARDs). Whilst several studies examined the HLA-C*06 allele in PsV, the results were conflicting. Interleukin (IL)-12 serum levels and polymorphisms in the IL-12B gene show promise as biomarkers of treatment response in PsV. Most, but not all, studies found that higher baseline levels of C-reactive protein (CRP) were associated with a better clinical response to treatment in patients with PsA. CONCLUSION: Several studies have identified biomarkers associated with subsequent response to treatment in psoriatic disease. However, due to the different types of biomarkers, treatments and outcome measures used, firm conclusions cannot be drawn. Further validation is needed before any of these biomarkers translate to clinical practice.

Axial involvement in psoriatic arthritis: An update for rheumatologists.

Psoriatic arthritis (PsA) is a heterogenous, chronic, inflammatory musculoskeletal disease that can lead to peripheral and axial damage and loss of function. Axial involvement occurs in 25% to 70% of patients with PsA, varying greatly depending on its definition, with the key manifestations being sacroiliitis and/or spondylitis. However, there are no agreed-upon classification or diagnostic criteria for axial involvement in PsA and no consensus on treatment paradigms, which complicates management of PsA. There have only been a few studies assessing biologics in patients with PsA with axial involvement, and most treatment plans are based on evidence from patients with axial spondyloarthritis. Rheumatologists therefore face many challenges in the management of axial PsA, including diagnosis, differential diagnosis, and choice of appropriate treatment. In this review, we summarize the clinical presentation, imaging characteristics, differential diagnoses, treatment options, and prognosis of axial PsA, with the aim of increasing rheumatologists' knowledge of this phenotype of PsA and thereby aiding its optimal management.

Prevalence of axial spondyloarthritis in patients with inflammatory bowel disease using cross-sectional imaging: a systematic literature review.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an excess burden of axial spondyloarthritis (axSpA), which, if left untreated, may significantly impact on clinical outcomes. We aimed to estimate the prevalence of axSpA, including previously undiagnosed cases, in IBD patients from studies involving cross-sectional imaging and identify the IBD features potentially associated with axSpA. METHODS: PubMed, Embase and Cochrane databases were searched systematically between 1990 and 2018. Article reference lists and key conference abstract lists from 2012 to 2018 were also reviewed. All abstracts were reviewed by two authors to determine eligibility for inclusion. The study inclusion criteria were (a) adults aged 18 years or above, (b) a clinical diagnosis of IBD and (c) reporting identification of sacroiliitis using cross-sectional imaging. RESULTS: A total of 20 observational studies were identified: 12 used CT, 6 used MR and 2 utilised both computed tomography (CT) and magnetic resonance (MR) imaging. Sample sizes ranged from 25 to 1247 (a total of 4096 patients); 31 studies were considered to have low selection bias, 13 included two or more radiology readers, and 3 included rheumatological assessments. The prevalence of sacroiliitis, the most commonly reported axSpA feature, ranged from 2.2% to 68.0% with a pooled prevalence of 21.0% [95% confidence interval (CI) 17-26%]. Associated IBD features include increasing IBD duration, increasing age, male sex, IBD location, inflammatory back pain and peripheral arthritis. No significant difference in the prevalence of sacroiliitis between Crohn's disease and ulcerative colitis was identified. Study limitations include variability in the individual study sample sizes and patient demographics. CONCLUSION: This review highlights the need for larger, well-designed studies using more sensitive imaging modalities and multivariable modelling to better estimate the prevalence of axSpA in IBD. An improved knowledge of the IBD phenotype(s) associated with axSpA and use of cross-sectional imaging intended for IBD assessment to screen for axSpA may help clinicians identify those patients most at risk.

Improving Imaging Modalities in Early Psoriatic Arthritis: The Role of Ultrasound in Early Diagnosis of Psoriatic Arthritis.

Objective: Despite recent advances, early diagnosis of psoriatic arthritis (PsA) remains a challenge in clinical practice. Ultrasound (US) could be a useful tool for the diagnosis and management of PsA. The objective of this review was to determine the role of US in early diagnosis of PsA. Methods: We have performed a literature review aiming to evaluate studies on US findings in psoriasis and their predictive value of progression to PsA, as well as studies on US features specific for PsA in comparison with other conditions. Results: A total of 40 studies were included. Sixteen studies assessed US findings in psoriasis, of which only 3 prospectively evaluated the role of US in predicting progression to PsA. Patients with PsA had a greater frequency of US abnormalities, in particular enthesitis and Power Doppler(PD) signal compared to patients with psoriasis only. In the longitudinal studies, psoriatic patients with higher enthesopathy scores at baseline were more likely to progress to PsA. Twenty-four studies evaluated US abnormalities in PsA and compared them to other conditions. Most specific US features that distinguish PsA from psoriasis were PD signal and erosions in joints and entheses. Extra-synovial changes, including peri-tendinous dermal soft tissue oedema with associated PD signal and flexor tendon enthesopathy, as well as thickening of the pulleys in the flexor tendons were highly characteristic for PsA, as they were frequently found in PsA patients, but in none of the RA patients. US-detected entheseal abnormalities in particular erosions and PD signal were more frequent in patients with PsA compared to fibromyalgia. Conclusion: Despite the wide use of US in PsA, more research is needed to identify predictive factors of progression to PsA in patients with psoriasis, as well as to determine most specific US features that differentiate PsA from other conditions.

Composite Measures for Clinical Trials in Psoriatic Arthritis: Testing Pain and Fatigue Modifications in a UK Multicenter Study.

OBJECTIVE: To test the addition of pain and fatigue to the Composite Psoriatic Arthritis Disease Activity (CPDAI) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) Composite Exercise (GRACE) composite measures of psoriatic arthritis (PsA). METHODS: Clinical and patient-reported outcome measures were assessed in patients with PsA at 3 consecutive follow-up visits over 6 months in a UK multicenter observational study. A pain visual analog scale and Functional Assessment of Chronic Illness Therapy Fatigue scale were added as modifications to the CPDAI and GRACE composite measures. Original and modified versions were tested against the PsA Disease Activity Score (PASDAS) and the Disease Activity Index for PsA (DAPSA). Discrimination between disease states and responsiveness were tested with t-scores, standardized response means (SRMs), and effect sizes. Data were presented to members at the 2020 annual meeting who then voted on the GRAPPArecommended composite and treatment targets for clinical trials. RESULTS: One hundred forty-one patients were recruited with a mean PsA disease duration of 6.1 years (range 0-41 yrs). The SRMs for the GRACE and modified GRACE (mGRACE) were 0.67 and 0.64, respectively, and 0.54 and 0.46, respectively, for the CPDAI and modified CPDAI (mCPDAI). The t-scores for the GRACE and mGRACE were unchanged at 7.8 for both, and 6.8 and 7.0 for the CPDAI and mCPDAI, respectively. The PASDAS demonstrated the best responsiveness (SRM 0.84) and discrimination (t-scores 8.3). Most members (82%) agreed the composites should not be modified and 77% voted for the PASDAS as the GRAPPA-recommended composite for clinical trials, with 90% minimal disease activity (MDA) as the target. CONCLUSION: Modifying the CPDAI and GRACE with the addition of pain and fatigue does not enhance responsiveness nor the measures' ability to detect disease status in terms of requiring treatment escalation. GRAPPA members voted for the PASDAS as the composite measure in clinical trials and MDA as the target.