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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-β via αVβ6 integrin in psoriatic epidermis., (Copyright © 2024 by The Journal of Rheumatology.)

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., (Copyright © 2024 by The Journal of Rheumatology.)

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., (Copyright © 2024 by The Journal of Rheumatology.)

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., (Copyright © 2024 by The Journal of Rheumatology.)

Study Question: Can we develop a prediction model for the chance of a live birth following the transfer of an embryo created using donated oocytes?, Summary Answer: Three primary models that included patient, past treatment, and cycle characteristics were developed using Australian data to predict the chance of a live birth following the transfer of an embryo created using donated oocytes; these models were well-calibrated to the population studied, achieved reasonable predictive power and generalizability when tested on New Zealand data., What Is Known Already: Nearly 9% of ART embryo transfer cycles performed globally use embryos created using donated oocytes. This percentage rises to one-quarter and one-half in same-sex couples and women aged over 45 years, respectively., Study Design, Size, Duration: This study uses population-based Australian clinical registry data comprising 9384 embryo transfer cycles that occurred between 2015 and 2021 for model development, with an external validation cohort of 1493 New Zealand embryo transfer cycles., Participants/materials, Setting, Methods: Three prediction models were compared that incorporated patient characteristics, but differed in whether they considered use of prior autologous treatment factors and current treatment parameters. We internally validated the models on Australian data using grouped cross-validation and reported several measures of model discrimination and calibration. Variable importance was measured through calculating the change in predictive performance that resulted from variable permutation. The best-performing model was externally validated on data from New Zealand., Main Results and the Role of Chance: The best-performing model had an internal validation AUC-ROC of 0.60 and Brier score of 0.20, and external validation AUC-ROC of 0.61 and Brier score of 0.23. While these results indicate ∼15% less discriminatory ability compared to models assessed on an autologous cohort from the same population the performance of the models was clearly statistically significantly better than random, demonstrated generalizability, and was well-calibrated to the population studied. The most important variables for predicting the chance of a live birth were the oocyte donor age, the number of prior oocyte recipient embryo transfer cycles, whether the transferred embryo was cleavage or blastocyst stage and oocyte recipient age. Of lesser importance were the oocyte-recipient parity, whether donor or partner sperm was used, the number of prior autologous embryo transfer cycles and the number of embryos transferred., Limitations, Reasons for Caution: The models had relatively weak discrimination suggesting further features need to be added to improve their predictive power. Variation in donor oocyte cohorts across countries due to differences such as whether anonymous and compensated donation are allowed may necessitate the models be recalibrated prior to application in non-Australian cohorts., Wider Implications of the Findings: These results confirm the well-established importance of oocyte age and ART treatment history as the key prognostic factors in predicting treatment outcomes. One of the developed models has been incorporated into a consumer-facing website (YourIVFSuccess.com.au/Estimator) to allow patients to obtain personalized estimates of their chance of success using donor oocytes., Study Funding/competing Interest(s): This research was funded by the Australian government as part of the Medical Research Future Fund (MRFF) Emerging Priorities and Consumer Driven Research initiative: EPCD000007. L.R. declares personal consulting fees from Abbott and Merck, lecture fees from Abbott, receipt of an educational grant from Merck, past presidency of the Fertility Society of Australia & New Zealand and World Endometriosis Society and being a minor shareholder in Monash IVF Group (ASX:MVF). G.M.C. declares receipt of Australian government grant funding for the research study and the development and maintenance of the YourIVFSuccess website. O.F., J.N., and A.P. report no conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (Copyright © 2024 by The Journal of Rheumatology.)

The tumor suppressor breast cancer 1 (BRCA1) complexed with BRCA1-associated RING domain 1 (BARD1), a RING-type E3 ligase, facilitates the attachment of ubiquitin onto the substrate protein. Here, we present a protocol for evaluating the E3 ligase activity of BRCA1-BARD1 and its variants by nucleosomal histone ubiquitylation. We describe steps for isolating 147 bp Widom 601 DNA and assembling nucleosome core particles (NCPs). We then detail procedures for the in vitro ubiquitylation of nucleosome histone H2A by BRCA1-BARD1 and its variants. For complete details on the use and execution of this protocol, please refer to Wang et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The licensing step of DNA double-strand break repair by homologous recombination entails resection of DNA ends to generate a single-stranded DNA template for assembly of the repair machinery consisting of the RAD51 recombinase and ancillary factors 1 . DNA end resection is mechanistically intricate and reliant on the tumour suppressor complex BRCA1-BARD1 (ref. 2 ). Specifically, three distinct nuclease entities-the 5'-3' exonuclease EXO1 and heterodimeric complexes of the DNA endonuclease DNA2, with either the BLM or WRN helicase-act in synergy to execute the end resection process 3 . A major question concerns whether BRCA1-BARD1 directly regulates end resection. Here, using highly purified protein factors, we provide evidence that BRCA1-BARD1 physically interacts with EXO1, BLM and WRN. Importantly, with reconstituted biochemical systems and a single-molecule analytical tool, we show that BRCA1-BARD1 upregulates the activity of all three resection pathways. We also demonstrate that BRCA1 and BARD1 harbour stand-alone modules that contribute to the overall functionality of BRCA1-BARD1. Moreover, analysis of a BARD1 mutant impaired in DNA binding shows the importance of this BARD1 attribute in end resection, both in vitro and in cells. Thus, BRCA1-BARD1 enhances the efficiency of all three long-range DNA end resection pathways during homologous recombination in human cells., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

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, β-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., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

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., (© 2024. The Author(s).)

Objective: To assess whether using ultrasound (US) in addition to clinical information versus only clinical information in a treat-to-target (T2T) strategy leads to more clinical remission and to less radiographic progression in RA., Methods: Patients with RA from the 2-year prospective BIODAM cohort were included. Clinical and US data (US7-score) were collected every 3 months and hands and feet radiographs every 6 months. At each visit, it was decided whether patients were treated according to the clinical definition of T2T with DAS44 remission as benchmark (T2T-DAS44). T2T-DAS44 was correctly applied if: (i) DAS44 remission had been achieved or (ii) if not, treatment was intensified. A T2T strategy also considering US data (T2T-DAS44-US) was correctly applied if: (i) both DAS44 and US remission (synovitis-score < 2, Doppler-score = 0) were present; or (ii) if not, treatment was intensified. The effect of T2T-DAS44-US on attaining clinical remission and on change in Sharp-van der Heijde score compared to T2T-DAS44 was analysed., Results: A total of 1016 visits of 128 patients were included. T2T-DAS44 was correctly followed in 24% of visits and T2T-DAS44-US in 41%. DAS44 < 1.6 was achieved in 39% of visits. Compared to T2T-DAS44, using the T2T-DAS44-US strategy resulted in a 41% lower likelihood of DAS44 remission [OR (95% CI): 0.59 (0.40;0.87)] and had no effect on radiographic progression [β(95% CI): 0.11 (- 0.16;0.39)] assessed at various intervals up to 12 months later., Conclusion: Our results do not suggest a benefit of using the US7-score in addition to clinical information as a T2T benchmark compared to clinical information alone. Key Points • Ultrasound has a valuable role in diagnostic evaluation of rheumatoid arthritis, but it is unclear whether adding ultrasound to the clinical assessment in a treat-to-target (T2T) strategy leads to more patients achieving remission and reduction in radiographic progression. • Our data from a real-world study demonstrated that adding information from ultrasound to the clinical assessment in a T2T strategy led to a lower rather than a higher likelihood of obtaining clinical remission as compared to using only clinical assessment. • Our data demonstrated that adding ultrasound data to a T2T strategy based only on clinical assessment did not offer additional protection against radiographic progression in patients with RA. • Adding US to a T2T strategy based on clinical assessment led to far more treatment intensifications (with consequences for costs and exposure to adverse events) without yielding a meaningful clinical benefit., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Study Question: What is the association between a country's level of gender equality and access to ART, as measured through ART utilization?, Summary Answer: ART utilization is associated with a country's level of gender equality even after controlling for the level of development., What Is Known Already: Although gender equality is recognized as an important determinant of population health, its association with fertility care, a highly gendered condition, has not been explored., Study Design, Size, Duration: A longitudinal cross-national analysis of ART utilization in 69 countries during 2002-2014 was carried out., Particpants/materials, Setting, Methods: The Gender Inequality Index (GII), Human Development Index (HDI), and their component indicators were modelled against ART utilization using univariate regression models as well as mixed-effects regression methods (adjusted for country, time, and economic/human development) with multiple imputation to account for missing data., Main Results and the Role of Chance: ART utilization is associated with the GII. In an HDI-adjusted analysis, a one standard deviation decrease in the GII (towards greater equality) is associated with a 59% increase in ART utilization. Gross national income per capita, the maternal mortality ratio, and female parliamentary representation were the index components most predictive of ART utilization., Limitations, Reasons for Caution: Only ART was used rather than all infertility treatments (including less costly and non-invasive treatments such as ovulation induction). This was a country-level analysis and the results cannot be generalized to smaller groups. Not all modelled variables were available for each country across 2002-2014., Wider Implications of the Findings: Access to fertility care is central to women's sexual and reproductive health, to women's rights, and to human rights. As gender equality improves, so does access to ART. This relation is likely to be reinforcing and bi-directional, with progress towards global, equitable access to fertility care also improving women's status and participation in societies., Study Funding/competing Interest(s): External funding was not provided for this study. G.D.A. declares consulting fees from Labcorp and CooperSurgical. G.D.A. is the founder and CEO of Advanced Reproductive Care, Inc., as well as the Chair of the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) and the World Endometriosis Research Foundation, both of which are unpaid roles. G.M.C. is an ICMART Board Representative, which is an unpaid role, and no payments are received from ICMART to UNSW, Sydney, or to G.M.C. to undertake this study. O.F., S.D., F.Z.-H., and E.K. report no conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (Copyright © 2023 by the Journal of Rheumatology.)

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., (Copyright © 2023 by the Journal of Rheumatology.)

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., (Copyright © 2023 by the Journal of Rheumatology.)

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., (Copyright © 2023 by the Journal of Rheumatology.)

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., (Copyright © 2023 by the Journal of Rheumatology.)

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., (Copyright © 2023 by the Journal of Rheumatology.)

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., (Copyright © 2023 by the Journal of Rheumatology.)

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., (Copyright © 2023 by the Journal of Rheumatology.)

The tumor-suppressor breast cancer 1 (BRCA1) in complex with BRCA1-associated really interesting new gene (RING) domain 1 (BARD1) is a RING-type ubiquitin E3 ligase that modifies nucleosomal histone and other substrates. The importance of BRCA1-BARD1 E3 activity in tumor suppression remains highly controversial, mainly stemming from studying mutant ligase-deficient BRCA1-BARD1 species that we show here still retain significant ligase activity. Using full-length BRCA1-BARD1, we establish robust BRCA1-BARD1-mediated ubiquitylation with specificity, uncover multiple modes of activity modulation, and construct a truly ligase-null variant and a variant specifically impaired in targeting nucleosomal histones. Cells expressing either of these BRCA1-BARD1 separation-of-function alleles are hypersensitive to DNA-damaging agents. Furthermore, we demonstrate that BRCA1-BARD1 ligase is not only required for DNA resection during homology-directed repair (HDR) but also contributes to later stages for HDR completion. Altogether, our findings reveal crucial, previously unrecognized roles of BRCA1-BARD1 ligase activity in genome repair via HDR, settle prior controversies regarding BRCA1-BARD1 ligase functions, and catalyze new efforts to uncover substrates related to tumor suppression., Competing Interests: Declaration of interests D.N.I. is a co-founder and a shareholder of E3 Bioscience LLC, a commercial entity that manufactures FRET-active E2∼Ub conjugates used in this study., (Published by Elsevier Inc.)

The Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) is a nonprofit organization whose mission is to optimize the clinical care of patients with psoriatic disease through multidisciplinary collaboration models. The PPACMAN 2021 Annual Meeting was held virtually on December 11, 2021. In all, 50 stakeholders participated in the meeting including dermatologists, rheumatologists, cardiologists, clinical researchers, patient advocacy representatives, and industry representatives. During the opening session of the meeting, presenters provided an update of several research projects dedicated to predicting and preventing psoriatic arthritis (PsA) such as the Psorcast, PAMPA, HIPPOCRATES, and the ELLIPSS studies. The second session centered around novel approaches to deliver multidisciplinary care in psoriatic disease. PPACMAN leadership introduced its wellness program and invited speakers to discuss new advances in cardiovascular disease, sleep disturbance, mental health problems, and dietary interventions in psoriatic disease. The final session of the meeting focused on how to improve patient engagement in their disease and care., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Carly Grant, BS: has no relevant disclosures. Joseph F. Merola, MD, MMSc: JFM is a consultant and/or investigator for Dermavant, Eli Lilly, UCB, Sun Pfizer and Leo Pharma. Daniel Webster, PhD: As of this writing, Dan Webster is employed at AbbVie. Jose U. Scher, MD: Janssen, Abbvie, UCB, Sanofi, Novartis, Lilly, BMS, and Pfizer. Oliver FitzGerald, MD: receive support in the form of grants and/or honoraria from Novartis, UCB, Pfizer, BMS, AbbVie, Janssen, Lilly and Biogen. Christopher Ritchlin, MD: Consultant for Abbvie, UCB, Novartis, Janssen, BMS, and Pfizer. Research for UCB, Janssen, BMS, and UCB. Vinod Chandran, MD, PhD: has received honoraria from Amgen, AbbVie, Eli Lilly, Janssen, Novartis and Pfizer; research grants from AbbVie; spouse is an employee of AstraZeneca. Alexis Ogdie, MD: has consulted for Abbvie, Amgen, BMS, Celgene, CorEvitas, Gilead, GSK, HappifyHealth, Janssen, Novartis, Pfizer and UCB and received grants from Abbvie, Amgen, Novartis and Pfizer. Lourdes Perez-Chada, MD, MMSc: has no relevant disclosures. Brittany Weber, MD: has no relevant disclosures Michael Garshick, MD: Consultant fee from Abbvie Pharmaceuticals. Cheryl F. Rosen, MD: has no relevant disclosures. Soumya Reddy, MD: Consulted for Amgen, Abbvie, Novartis, Janssen, Fresnius-Kabi, Pfizer Rebecca H. Haberman, MD: has received consulting fees from Janssen. Lihi Eder, MD, PhD: Grants and consultation fees from Abbvie, UCB, Janssen, Pfizer, Eli Lilly, Fresenius Kabi, Novartis, Sandoz., (© The Author(s) 2023.)

Objective: Blood glucose measurements in the intensive care unit (ICU) are typically made at irregular intervals. This presents a challenge in choice of forecasting model. This article gives an overview of continuous time autoregressive recurrent neural networks (CTRNNs) and evaluates how they compare to autoregressive gradient boosted trees (GBT) in forecasting blood glucose in the ICU., Methods: Continuous time autoregressive recurrent neural networks (CTRNNs) are a deep learning model that account for irregular observations through incorporating continuous evolution of the hidden states between observations. This is achieved using a neural ordinary differential equation (ODE) or neural flow layer. In this manuscript, we give an overview of these models, including the varying architectures that have been proposed to account for issues such as ongoing medical interventions. Further, we demonstrate the application of these models to probabilistic forecasting of blood glucose in a critical care setting using electronic medical record and simulated data and compare with GBT and linear models., Results: The experiments confirm that addition of a neural ODE or neural flow layer generally improves the performance of autoregressive recurrent neural networks in the irregular measurement setting. However, several CTRNN architecture are outperformed by a GBT model (Catboost), with only a long short-term memory (LSTM) and neural ODE based architecture (ODE-LSTM) achieving comparable performance on probabilistic forecasting metrics such as the continuous ranked probability score (ODE-LSTM: 0.118 ± 0.001; Catboost: 0.118 ± 0.001), ignorance score (0.152 ± 0.008; 0.149 ± 0.002) and interval score (175 ± 1; 176 ± 1)., Conclusion: The application of deep learning methods for forecasting in situations with irregularly measured time series such as blood glucose shows promise. However, appropriate benchmarking by methods such as GBT approaches (plus feature transformation) are key in highlighting whether novel methodologies are truly state of the art in tabular data settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Both blood glucose and lactate are well-known predictors of organ dysfunction and mortality in critically ill patients. Previous research has shown that concurrent adjustment for glucose and lactate modifies the relationship between these variables and patient outcomes, including blunting of the association between blood glucose and patient outcome. We aim to investigate the relationship between ICU admission blood glucose and hospital mortality while accounting for lactate and diabetic status. Across 43,250 ICU admissions, weighted to account for missing data, we assessed the predictive ability of several logistic regression and generalised additive models that included blood glucose, blood lactate and diabetic status. We found that inclusion of blood glucose marginally improved predictive performance in all patients: AUC-ROC 0.665 versus 0.659 (p = 0.005), with a greater degree of improvement seen in non-diabetics: AUC-ROC 0.675 versus 0.663 (p < 0.001). Inspection of the estimated risk profiles revealed the standard U-shaped risk profile for blood glucose was only present in non-diabetic patients after controlling for blood lactate levels. Future research should aim to utilise observational data to estimate whether interventions such as insulin further modify this effect, with the goal of informing future RCTs of interventions targeting glycaemic control in the ICU., (© 2023. Springer Nature Limited.)

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., Competing Interests: OF has received grants from AbbVie, Bristol Myers Squibb, Janssen, Eli-Lilly, Novartis, Pfizer and UCB. DS has received grants from AbbVie, Janssen, Eli-Lilly and Novartis. SK is an employee of and has stocks or stock options in Bristol Myers Squibb. LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer and UCB; worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli-Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB and has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli-Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB. FB and MK have received grants/research support from AbbVie, Amgen, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer and UCB; worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli-Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB and has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli-Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB. AB has received grants/research support from Pfizer, Bristol Myers Squibb, Galapagos and Schiper Medicine and received speaker fees from Chugai-Roche. AV, MKl and JMS – no conflicts of interest to declare. CSG has received grants/research support from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim Pharmaceuticals, Eli-Lilly, Istesso, Janssen, MedAnnex, MiroBio, Pfizer, UCB; worked as a consultant for AstraZeneca, Bristol Myers Squibb, Janssen, MedAnnex, MiroBio; and has been paid as a speaker for AbbVie and UCB. BBD was an employee and then a consultant of Novartis Pharma AG. CH is an employee of Novartis Pharma AG. SS has received institutional research support from Amgen (previously Celgene), Boehringer Ingelheim, Bristol Myers Squibb, Eli-Lilly, GSK, Janssen and UCB; consultancy/speaker fees from AbbVie, Amgen, AstraZeneca, Eli-Lilly, GSK, Janssen and UCB. MdW: Over the last 3 years Stichting Tools has received fees for lectures or consultancy provided by Maarten de Wit from Celgene, Eli-Lilly, Pfizer and UCB., (© The Author(s), 2023.)

Study Question: Does a public online IVF success prediction calculator based on real-world data help set patient expectations?, Summary Answer: The YourIVFSuccess Estimator aided consumer expectations of IVF success: one quarter (24%) of participants were unsure of their estimated IVF success before using the tool; one half changed their prediction of success after using the tool and one quarter (26%) had their expectations of IVF success confirmed., What Is Known Already: Several web-based IVF prediction tools exist worldwide but have not been evaluated for their impact on patient expectations, nor for patient perceptions of usefulness and trustworthiness., Study Design, Size, Duration: This is a pre-post evaluation of a convenience sample of 780 online users of the Australian YourIVFSuccess Estimatorhttps://yourivfsuccess.com.au/ between 1 July and 31 November 2021., Participants/materials, Setting, Methods: Participants were eligible if they were over 18 years of age, Australian residents, and considering IVF for themselves or their partner. Participants filled in online surveys before and after using the YourIVFSuccess Estimator., Main Results and the Role of Chance: The response rate of participants who completed both surveys and the YourIVFSuccess Estimator was 56% (n = 439). The YourIVFSuccess Estimator aided consumer expectations of IVF success: one quarter (24%) of participants were unsure of their estimated IVF success before using the tool; one half changed their prediction of success after using the tool (20% increased, 30% decreased), bringing their predictions in line with the YourIVFSuccess Estimator, and one quarter (26%) had their IVF success expectations confirmed. One in five participants claimed they would change the timing of IVF treatment. The majority of participants found the tool to be at least moderately trustworthy (91%), applicable (82%), and helpful (80%), and would recommend it to others (60%). The main reasons given for the positive responses were that the tool is independent (government funded, academic) and based on real-world data. Those who did not find it applicable or helpful were more likely to have had a worse-than-expected prediction, or to have experienced non-medical infertility (e.g. single women, LGBTQIA+), noting that at the time of evaluation the Estimator did not accommodate these patient groups., Limitations, Reasons for Caution: Those who dropped out between the pre- and post-surveys tended to have a lower education status or have been born outside of Australia or New Zealand, therefore there may be issues with generalizability., Wider Implications of the Findings: With consumers demanding increasing levels of transparency and participation in decisions around their medical care, public-facing IVF predictor tools based on real-world data are useful for aligning expectations about IVF success rates. Given differences in patient characteristics and IVF practices internationally, national data sources should be used to inform country-specific IVF prediction tools., Study Funding/competing Interest(s): The YourIVFSuccess website and evaluation of the YourIVFSuccess Estimator are supported by the Medical Research Future Fund (MRFF) Emerging Priorities and Consumer Driven Research initiative: EPCD000007. BKB, ND, and OF have no conflicts to declare. DM holds a clinical role at Virtus Health. His role did not influence the analysis plan or interpretation of results in this study. GMC is an employee of the UNSW Sydney, and Director of the UNSW NPESU. UNSW receives research funding on behalf of Prof Chambers from the MRFF to develop and manage the Your IVF Success website. Grant ID: MRFF Emerging Priorities and Consumer Driven Research initiative: EPCD000007., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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.

Objective: We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations., Methods: A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings., Results: The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain., Conclusion: Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations., (Copyright © 2023 by the Journal of Rheumatology.)

Aims: Observational studies indicate U-shaped associations of blood pressure (BP) and incident dementia in older age, but randomized controlled trials of BP-lowering treatment show mixed results on this outcome in hypertensive patients. A pooled individual participant data analysis of five seminal randomized double-blind placebo-controlled trials was undertaken to better define the effects of BP-lowering treatment for the prevention of dementia., Methods and Results: Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, and presence of prior stroke. Mediation analysis was used to quantify the contribution of trial medication and changes in systolic and diastolic BP on risk of dementia. The total sample included 28 008 individuals recruited from 20 countries. After a median follow-up of 4.3 years, there were 861 cases of incident dementia. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval: 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4 mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age or sex. Mediation analysis confirmed the greater fall in BP in the actively treated group was associated with a greater reduction in dementia risk., Conclusion: The first single-stage individual patient data meta-analysis from randomized double-blind placebo-controlled clinical trials provides evidence to support benefits of antihypertensive treatment in late-mid and later life to lower the risk of dementia. Questions remain as to the potential for additional BP lowering in those with already well-controlled hypertension and of antihypertensive treatment commenced earlier in the life-course to reduce the long-term risk of dementia., Classification of Evidence: Class I evidence in favour of antihypertensive treatment reducing risk of incident dementia compared with placebo., Competing Interests: Conflict of interest: The authors report no targeted funding. R.P. is funded by the Australian National Health and Medical Research Centre Australian Dementia Centre for Research Collaboration, and Neuroscience Research Australia; Y.X. is funded by NHMRC Project Grant (APP1160373); M.W. and C.S.A. are supported by Investigator Grants (APP1174120 and GNT1175861 respectively) from the National Health and Medical Research Council (NHMRC) of Australia, and together with J.C. receive funding from an NHMRC Program Grant (APP1149987); M.W. is a consultant to Amgen, Kyowa Kirin, and Freeline; J.C. has received research grants from Servier, and from the NHMRC for both PROGRESS and ADVANCE, and honoraria from Servier for speaking about them at Scientific meetings; C.S.A. has received research grants from Penumbra, Takeda, Credit, and Genesis paid to his institution., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The definitive diagnosis and early treatment of many immune-mediated inflammatory diseases (IMIDs) is hindered by variable and overlapping clinical manifestations. Psoriatic arthritis (PsA), which develops in ~30% of people with psoriasis, is a key example. This mixed-pattern IMID is apparent in entheseal and synovial musculoskeletal structures, but a definitive diagnosis often can only be made by clinical experts or when an extensive progressive disease state is apparent. As with other IMIDs, the detection of multimodal molecular biomarkers offers some hope for the early diagnosis of PsA and the initiation of effective management and treatment strategies. However, specific biomarkers are not yet available for PsA. The assessment of new markers by genomic and epigenomic profiling, or the analysis of blood and synovial fluid/tissue samples using proteomics, metabolomics and lipidomics, provides hope that complex molecular biomarker profiles could be developed to diagnose PsA. Importantly, the integration of these markers with high-throughput histology, imaging and standardized clinical assessment data provides an important opportunity to develop molecular profiles that could improve the diagnosis of PsA, predict its occurrence in cohorts of individuals with psoriasis, differentiate PsA from other IMIDs, and improve therapeutic responses. In this review, we consider the technologies that are currently deployed in the EU IMI2 project HIPPOCRATES to define biomarker profiles specific for PsA and discuss the advantages of combining multi-omics data to improve the outcome of PsA patients.

Objectives: Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models., Methods: Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)-based heritability estimate (h 2 SNP ) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation., Results: We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10 -9 ), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10 -45 ) and Wnt signaling (adjusted P = 9.5 × 10 -58 ). The heritability of PsA in this cohort was found to be moderate (h 2 SNP  = 0.63), which was similar to the heritability of PsC (h 2 SNP  = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data., Conclusion: Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post-hoc analysis of two phase III studies in patients with PsA treated with tofacitinib assessed dactylitis by location, and the impact on patient-reported outcomes (PROs)., Methods: Patients received tofacitinib 5 or 10 mg twice daily (BID), or placebo. Endpoints included change from baseline in Dactylitis Severity Score (DSS), proportions of patients with dactylitis, Psoriatic Arthritis Disease Activity Score (PASDAS), and PROs (Health Assessment Questionnaire-Disability Index [HAQ-DI]; Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]; Short Form-36 Health Survey [SF-36] Physical Component Summary [PCS], Mental Component Summary [MCS], and physical functioning [PF]; arthritis pain; and Work Limitations Questionnaire [WLQ]). Descriptive statistics were generated by visit and treatment. Change from baseline in PROs were evaluated by multivariate linear regression., Results: The analysis included 373/337 patients with baseline DSS > 0/DSS = 0. Regardless of location, DSS improvements in patients with DSS > 0 were greater from month 1 with tofacitinib (10 mg BID) versus placebo. For patients with DSS > 0/DSS = 0, both doses of tofacitinib led to mean dactylitis presence ≤ 15%/< 2% for all digits at month 6, and PASDAS (by dactylitis location) was lower versus placebo at month 3. Dactylitis location was not significantly associated with change from baseline in PROs., Conclusion: Tofacitinib resulted in sustained improvements in dactylitis irrespective of location, with minimal emergence of new dactylitis. Trial registration NCT01877668; NCT01882439., (© 2022. The Author(s).)

Background: Occupational therapy self-management groups aim to assist individuals to incorporate health-promoting behaviours and management strategies into their daily routines to promote wellbeing. The Lifestyle Management for Arthritis Group (LMAG) is a 2-h-long, occupational therapy educational-behavioural group intervention adapted from the evidence-based Lifestyle Management for Arthritis Programme (Hammond & Rayner, 2013) and was delivered to inpatients with inflammatory and degenerative arthritis separately., Aim: The aim of this study was to evaluate the effectiveness of this intervention in an inpatient Rheumatology Rehabilitation setting., Method: This was an observational study with a pretest-posttest design using multiple methods. A knowledge of joint protection survey was gathered at three intervals. In-depth semi-structured phone interviews were undertaken 6 weeks post intervention. The quantitative data was analysed using IBM SPSS version 25, whilst thematic analysis was used to analyse the interviews., Results: The results confirmed that the 36 participants who completed the study had increased joint protection knowledge immediately after LMAG and continued to retain that knowledge 6 weeks post intervention. The majority of participants evaluated the intervention as excellent whilst empowerment emerged as the core concept from the qualitative analysis., Conclusion: These study findings suggest that the LMAG intervention can have a beneficial effect inimproving the self-management skills and confidence levels of patients with inflammatory and degenerative arthritis., (© 2021 John Wiley & Sons Ltd.)

Background: COVID-19 mass vaccination programs place an additional burden on healthcare services. We aim to model the queueing process at vaccination sites to inform service delivery., Methods: We use stochastic queue network models to simulate queue dynamics in larger mass vaccination hubs and smaller general practice (GP) clinics. We estimate waiting times and daily capacity based on a range of assumptions about appointment schedules, service times and staffing and stress-test these models to assess the impact of increased demand and staff shortages. We also provide an interactive applet, allowing users to explore vaccine administration under their own assumptions., Results: Based on our assumed service times, the daily throughput for an eight-hour clinic at a mass vaccination hub ranged from 500 doses for a small hub to 1400 doses for a large hub. For GP clinics, the estimated daily throughput ranged from about 100 doses for a small practice to almost 300 doses for a large practice. What-if scenario analysis showed that sites with higher staff numbers were more robust to system pressures and mass vaccination sites were more robust than GP clinics., Conclusions: With the requirement for ongoing COVID-19 booster shots, mass vaccination is likely to be a continuing feature of healthcare delivery. Different vaccine sites are useful for reaching different populations and maximising coverage. Stochastic queue networks offer a flexible and computationally efficient approach to simulate vaccination queues and estimate waiting times and daily throughput to inform service delivery., (© 2022. The Author(s).)

Introduction: Guselkumab, a novel interleukin-23p19 subunit monoclonal antibody, has been shown to effectively improve the diverse manifestations of active psoriatic arthritis (PsA) in two phase 3 trials (DISCOVER-1, DISCOVER-2). Serum concentrations of extracellular matrix (ECM) biomarkers at baseline and following treatment with guselkumab were evaluated in patients with active PsA, and the relationship of these biomarkers with baseline PsA characteristics and clinical response to guselkumab treatment was explored., Methods: Serum samples were collected at weeks 0, 4, 24, and 52 from a selected subset (N = 260) of the 739 biologic-naïve patients with PsA treated with guselkumab 100 mg every 4 or 8 weeks or placebo in DISCOVER-2. Demographically matched healthy controls (N = 76) were used for comparison. The samples were analyzed for ECM biomarkers associated with collagen degradation (C1M, C2M, C3M, C4M, C6M, C10C) and collagen formation (PRO-C1, PRO-C2, PRO-C3, PRO-C4, PRO-C6)., Results: Baseline concentrations of collagen degradation biomarkers C1M, C3M, C4M, and C6M and collagen formation biomarkers PRO-C3 and PRO-C6 were significantly higher (i.e., ≥ 1.25-fold and false discovery rate adjusted p < 0.05) in PsA patients than in healthy controls. Serum C1M, C3M, C4M, and C6M levels declined from baseline in guselkumab-treated patients in both dosing regimens. In addition, guselkumab-treated ACR20 responders (≥ 20% improvement in American College of Rhematology response criteria) had significantly lower C1M levels than ACR20 nonresponders., Conclusion: These data demonstrate that serum collagen biomarkers are elevated in patients with PsA compared with healthy controls and that treatment with guselkumab decreases levels of C1M, C3M, C4M, and C6M. Importantly, C1M serves as a biomarker that associates with improvement of joint signs and symptoms., Trial Registration: ClinicalTrials.gov identifier: NCT03158285., (© 2022. The Author(s).)

Introduction: Low disease activity (LDA)/remission is the target of treatment in patients with psoriatic arthritis (PsA). We assessed the proportions of patients with PsA receiving upadacitinib who achieved LDA/remission over 1 year., Methods: This was a post hoc analysis of the double-blind, placebo-controlled SELECT-PsA 1 (also adalimumab-controlled) and SELECT-PsA 2 trials. Treatment targets assessed included LDA/remission defined by Disease Activity in Psoriatic Arthritis (≤ 14/ ≤ 4) and Psoriatic Arthritis Disease Activity Scores (≤ 3.2/ ≤ 1.9), as well as minimal disease activity (MDA)/very low disease activity (VLDA) states (5/7 and 7/7 components, respectively, of MDA criteria). Targets were assessed at 24 and 56 weeks. For binary outcomes, non-responder imputation was used for missing data. Data from patients receiving upadacitinib 30 mg was not included in the analysis., Results: Overall, 1386 patients were analyzed. Disease control (i.e., LDA/MDA) was achieved at 24 weeks in upadacitinib 15 mg-treated patients across both studies: LDA/MDA was achieved by 25-48% of patients receiving upadacitinib 15 mg versus 2-16% of patients receiving placebo, and remission/VLDA rates were 7-14% with upadacitinib 15 mg versus 0-4% with placebo. The proportions of patients achieving treatment targets were numerically similar to upadacitinib 15 mg and adalimumab. All responses were sustained at 56 weeks., Conclusions: Remission and LDA are feasible targets with upadacitinib treatment in patients with PsA., Trial Registration: ClinicalTrial.gov identifiers NCT03104400 (SELECT-PsA 1) and NCT03104374 (SELECT-PsA 2)., (© 2022. The Author(s).)

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., (© 2022. Springer Nature Limited.)

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis hosted a Meet the Experts session at its 2021 virtual meeting. Dermatology and rheumatology experts held 5 sessions that broadly centered on psoriasis and psoriatic arthritis., (Copyright © 2022 by The Journal of Rheumatology.)

The second basic science session at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting focused on 2 recent publications that have increased our understanding of the pathogenesis of psoriatic arthritis (PsA). Data from the first publication, presented by Prof. Erik Lubberts, showed that interleukin (IL)-17A is produced by CD4+ and not CD8+ T cells in PsA synovial fluid following T cell receptor activation. These findings contrast with previously published data, which had suggested that CD8+ T cells are a prominent source of IL-17A. In further experiments, they showed that when CD8+ T cells were stimulated with paramethoxyamphetamine/ionomycin, relatively high levels of IL-17A were detected. Prof. Jose Scher presented work on the role of the microbiome in PsA and more specifically, on pharmacomicrobiomics. He demonstrated the baseline collection of genomes and genes from the microbiota community (the metagenome) can be used as predictor for future treatment response in early rheumatoid arthritis and also likely in PsA., (Copyright © 2022 by The Journal of Rheumatology.)

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has identified several priority areas for biomarker development, including biomarkers to predict at baseline which patients may progress to develop joint damage and whether a patient will respond to a specific targeted therapy. Two industry-GRAPPA projects were initiated in 2020 on these biomarker research areas: (1) the Pfizer-GRAPPA project, focused on biomarkers of treatment response to tofacitinib in the Oral Psoriatic Arthritis TriaL program; and (2) the Lilly-GRAPPA project, focused on biomarkers of damage in the ixekizumab SPIRIT-P1 randomized controlled trial. Preliminary results from these 2 projects were presented by the GRAPPA team, with both studies showing promising initial results. Data from these studies will be published when the studies have been completed. Large-scale validation studies are required and are under discussion., (Copyright © 2022 by The Journal of Rheumatology.)

At the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, a summary of the research conducted by the recipients of the 2020 GRAPPA Research Awards was presented by the awardees. The summary of the 4 presentations is provided here., (Copyright © 2022 by The Journal of Rheumatology.)

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., (Copyright © 2022 by The Journal of Rheumatology.)

The Australian Government began to roll out the national COVID-19 vaccination program in late February 2021, with the initial aim to vaccinate the Australian adult population by the end of October 2021. The task of vaccinating some 20 million people presents considerable logistic challenges, but a rapid rollout is essential to allow for the reopening of borders and is especially urgent as new more transmissible variants arise. Here, we run a series of projections to estimate how long it will take to vaccinate the Australian population under different assumptions about the rate of vaccine administration, the schedule for vaccine eligibility and prevalence of vaccine hesitancy. Our analysis highlights the number of vaccine doses that can be administered per day as the key factor determining the duration of the vaccine rollout. A rate of 200,000 doses per day would achieve 90% population coverage by the end of 2021; 80,000 doses a day would see the rollout extended until mid-2023. Vaccine hesitancy has the potential to greatly slow down the rollout and becomes the main limiting factor when the supply of vaccine doses is high. Speed is of the essence when it comes vaccinating populations against COVID-19: a rapid rollout will minimise the risk of sporadic and costly lockdowns and the potential for small, local clusters getting out of control and sparking new epidemic waves. In order to achieve rapid population coverage, the Australian government must ramp up vaccine administration to at least 200,000 doses per day as quickly as possible, while also promoting vaccine willingness in the community through clear public health messaging, especially to known hesitant demographics., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Raina MacIntyre has been on an advisory board for COVID-19 vaccine for Seqirus and consulted or done speaking engagements on COVID-19 vaccines for Janssen and Astra Zeneca]., (Copyright © 2021 Elsevier Ltd. All rights reserved.)