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.

Understanding the impact of bioactive coating materials for human mesenchymal stromal cells and implications for manufacturing.

Bioactive materials interact with cells and modulate their characteristics which enable the generation of cell-based products with desired specifications. However, their evaluation and impact are often overlooked when establishing a cell therapy manufacturing process. In this study, we investigated the role of different surfaces for tissue culture including, untreated polystyrene surface, uncoated Cyclic Olefin Polymer (COP) and COP coated with collagen and recombinant fibronectin. It was observed that human mesenchymal stromal cells (hMSCs) expanded on COP-coated plates with different bioactive materials resulted in improved cell growth kinetics compared to traditional polystyrene plates and non-coated COP plates. The doubling time obtained was 2.78 and 3.02 days for hMSC seeded in COP plates coated with collagen type I and recombinant fibronectin respectively, and 4.64 days for cells plated in standard polystyrene treated plates. Metabolite analysis reinforced the findings of the growth kinetic studies, specifically that cells cultured on COP plates coated with collagen I and fibronectin exhibited improved growth as evidenced by a higher lactate production rate (9.38 × 105 and 9.67 × 105 pmol/cell/day, respectively) compared to cells from the polystyrene group (5.86 × 105 pmol/cell/day). This study demonstrated that COP is an effective alternative to polystyrene-treated plates when coated with bioactive materials such as collagen and fibronectin, however COP-treated plates without additional coatings were found not to be sufficient to support cell growth. These findings demonstrate the key role biomaterials play in the cell manufacturing process and the importance of optimising this selection.

Densified HKUST-1 Monoliths as a Route to High Volumetric and Gravimetric Hydrogen Storage Capacity.

We are currently witnessing the dawn of hydrogen (H2) economy, where H2 will soon become a primary fuel for heating, transportation, and long-distance and long-term energy storage. Among diverse possibilities, H2 can be stored as a pressurized gas, a cryogenic liquid, or a solid fuel via adsorption onto porous materials. Metal-organic frameworks (MOFs) have emerged as adsorbent materials with the highest theoretical H2 storage densities on both a volumetric and gravimetric basis. However, a critical bottleneck for the use of H2 as a transportation fuel has been the lack of densification methods capable of shaping MOFs into practical formulations while maintaining their adsorptive performance. Here, we report a high-throughput screening and deep analysis of a database of MOFs to find optimal materials, followed by the synthesis, characterization, and performance evaluation of an optimal monolithic MOF (monoMOF) for H2 storage. After densification, this monoMOF stores 46 g L-1 H2 at 50 bar and 77 K and delivers 41 and 42 g L-1 H2 at operating pressures of 25 and 50 bar, respectively, when deployed in a combined temperature-pressure (25-50 bar/77 K → 5 bar/160 K) swing gas delivery system. This performance represents up to an 80% reduction in the operating pressure requirements for delivering H2 gas when compared with benchmark materials and an 83% reduction compared to compressed H2 gas. Our findings represent a substantial step forward in the application of high-density materials for volumetric H2 storage applications.

GRAPPA Patient Research Partner Network: Update to the GRAPPA 2020 Annual Meeting.

Eleven patient research partners (PRPs) attended the virtual Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2020 Annual Meeting. PRPs fully participated in the panel discussion at the 2020 GRAPPA Annual Meeting on the topic of the coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2). The members of the PRP group have been involved in many GRAPPA projects over the last year, including work on the GRAPPA-Outcome Measures in Rheumatology (OMERACT) Core Set, GRAPPA's 2020 Treatment Guidelines update project, and GRAPPA's Collaborative Research Network project.

Prologue: 2020 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) held its annual meeting in 2020 in an online format due to travel restrictions during the coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2) pandemic. The virtual meeting was attended by 351 rheumatologists, dermatologists, representatives of biopharmaceutical companies, and patient research partners. Similar to previous years, GRAPPA's annual meeting focused on the 3 overlapping missions of education, research, and clinical care of psoriatic disease. Trainee sessions this year included the annual trainee symposium and a grant-writing workshop. Plenary sessions included updates on COVID-19 and psoriatic disease from multispecialty and patient perspectives, and updates on pustular psoriasis and associated musculoskeletal manifestations. Progress on research and updates were presented for the following groups: Collaborative Research Network, Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis Working Group, International Dermatology Outcome Measures, Composite Measures, Education Committee, and Treatment Guidelines. New this year were 3 concurrent workshops on ultrasound assessment of joints and entheses, magnetic resonance imaging of psoriatic arthritis, and pustular psoriasis efficacy endpoints; 6 "Meet the Expert" sessions; and facilitated "poster tours." In our prologue, we introduce the papers that summarize this meeting.

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.

Outcomes of the 2019 GRAPPA Workshop on Continuous Composite Indices for the Assessment of Psoriatic Arthritis and Membership-recommended Next Steps.

OBJECTIVE: Improving the assessment of psoriatic arthritis (PsA) is a key purpose of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA). Herein, we report the proceedings of the GRAPPA composites workshop at the 2019 GRAPPA annual meeting and the membership's recommended next steps. METHODS: A review of continuous composite measures was conducted in an introductory workshop, followed by 10 breakout group sessions and a final plenary session for feedback and voting. RESULTS: Participants included 154 members: 87 rheumatologists, 18 dermatologists, 2 rheumatologist/dermatologists, 12 patient research partners, 14 academics, 1 methodologist, and 20 industry members. Of voting members, 88.8% agreed a need exists for a continuous composite measure for routine practice, but only 62% were currently using a composite measure. Of these, 27% were using the 28-joint count Disease Activity Score (DAS), which is not a PsA-specific measure; 20% were using a PsA-specific measure such as PsA DAS (PASDAS), Composite Psoriatic Disease Activity Index (CPDAI), or Disease Activity Index for PsA (DAPSA). Members agreed that the existing measures were not feasible in their current forms (CPDAI 83%, PASDAS 82%, and DAPSA 47%) and that modification should be tested. The majority (76%) agreed that disease effect should be measured separately from disease activity. CONCLUSION: The GRAPPA membership supports the need for a continuous composite measure of disease activity for use in routine clinical care, the separate measurement of disease effect and activity, and the testing of modifications to candidate instruments rather than the development of new measures.

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.

GRAPPA 2019 Project Report.

At the 2019 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members received updates on several ongoing efforts. Among them were updates on research, including the trainee symposium, pilot research grants, and the Collaborative Research Network; GRAPPA's patient research partners; education, including the slide collection; treatment recommendations; and additional work related to advancing the understanding of disease aspects, including the Outcome Measures in Rheumatology (OMERACT)-GRAPPA outcome measure, axial involvement, and ultrasound enthesitis projects; as well as the early psoriatic disease systematic literature review and magnetic resonance imaging.

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 Patient Research Partner Network Matures: A Report from the GRAPPA 2017 Annual Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has reached the third of 5 stages of organizational maturity regarding incorporating patient research partners (PRP) into psoriatic arthritis (PsA) and psoriasis research and educational efforts. Herein, we report the involvement of PRP at the GRAPPA 2017 annual meeting and plans for future PRP engagement.

GRAPPA 2017 Project Report.

At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members received updates on several ongoing educational and research efforts. Among them were updates on GRAPPA's continued education efforts; GRAPPA's continued research efforts, including the Biomarker Project, a collaborative research effort to identify and study biomarkers of joint damage; treatment recommendations, including recommendations and core principles related to biosimilars; efforts to update GRAPPA's Website and to create a GRAPPA smart-phone application (app); and the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network.

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.

Developing evidence-based patient-focused learning materials to support health behaviour change for people living with psoriatic arthritis.

OBJECTIVES: In psoriatic arthritis (PsA), self-management is important for patient function and quality of life. Behaviour change can be difficult, patients could benefit from high-quality support to initiate change. Our aim was to codesign the project as theory-informed, evidence-based, patient-focused, materials supporting healthy lifestyle changes for patients diagnosed with PsA. METHODS: Development of the materials was overseen by a steering group of patients with PsA, psychologists, rheumatologists, a design team and researchers. First, a literature review was performed to establish the evidence base for behaviours and potential interventions in PsA, including diet, weight, alcohol, smoking, exercise, anxiety, depression and stress. An initial roundtable of patients with PsA prioritised areas and content ideas. Draft materials including a website and downloadable materials were produced. A second roundtable of patients with PsA collected feedback on the draft content and design. A third roundtable was held with patients with PsA and a fourth with clinicians to refine the materials and ensuring that they were evidence based, accessible, interesting, and helpful to initiate and maintain change. A final evaluation survey was performed to review the draft website before launching the final materials. RESULTS: 15 candidate topics were prioritised. A website and set of postcards summarising the topics were developed by the design team and refined following feedback from the roundtable groups. CONCLUSION: This project created patient-focused resources to support behaviour change. It addresses common concerns of patients with PsA about how they may optimise their health by providing practical and brief interventions to challenge and support them to make changes.

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

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

Lifestyle Modifications and Nonpharmacologic Interventions to Improve Outcomes in Psoriatic Arthritis: A Systematic Review.

PURPOSE: Psoriatic arthritis (PsA) is a multisystem inflammatory disorder associated with significant mortality and morbidity, including functional impairment and psychological disability. Although evidence-based treatment recommendations are available for the use of drug treatments in PsA, there is little guidance for health professionals on nonpharmacologic and psychological interventions that may be useful in PsA. The objective of this systematic review (SR) was to identify how lifestyle modifications and the use of nonpharmacologic and psychological interventions may improve the outcomes of patients with PsA. METHODS: Studies were included if they evaluated adults diagnosed with PsA and included exposure to nonpharmacologic interventions, psychological interventions, and lifestyle modifications. The outcomes used needed to have been validated in PsA. A systematic literature search was run on May 28, 2021, in the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), EMBASE, Global Health, MEDLINE, and PsycINFO databases to identify articles related to lifestyle modifications and nonpharmacologic or psychological interventions for adults with PsA published between 2010 and 2021. Two review authors independently screened and selected full-text studies for inclusion in the SR. Risk of bias was assessed with either the Risk of Bias 2 (ie, RoB 2) tool or Critical Appraisal Skills Program checklist depending on the study type. FINDINGS: The search strategy identified 26,132 references. Eight studies examining lifestyle modifications and the effect on PsA were eligible to be included in the SR. Three of the 8 studies were randomized controlled trials, and 5 were nonrandomized studies. Three studies assessed physical activity, 3 assessed diet, 1 study assessed smoking, and another study assessed mud bath therapy. There was large heterogeneity between studies, and the measures of disease activity, and psychological and functional outcomes varied widely between studies. IMPLICATIONS: Although this SR identified 8 relevant studies, these studies did not provide high-quality evidence to guide patients for non-drug treatments of PsA. The effectiveness of these interventions has therefore not been established. We found that physical activity seems to have a positive impact on disease activity and psychological well-being. Further well-designed research studies are needed to develop treatment recommendations. PROSPERO identifier: CRD42021257404.

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

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

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

Basic Science Session 1. Biomarkers for Psoriatic Arthritis Treatment Response and Joint Damage Progression: An Update on 2 Industry-GRAPPA Projects.

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.

GRAPPA Treatment Recommendations: 2021 Update.

Since its inception, one of the central missions of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has been the development of treatment recommendations for patients with psoriatic arthritis (PsA). The initial guidelines, developed in 2009, were updated in 2015. Because of the abundance of new data concerning the therapeutic approach to PsA, GRAPPA members have been working throughout 2020-2021 to once again update the recommendations. At the GRAPPA 2021 annual meeting, the full committee presented proposals from each of the treatment domain groups, including the comorbidities and related conditions groups, based on previous systematic literature reviews. Overarching principles and summary evidence tables were presented, including results from a GRAPPA membership survey of patients and clinicians to assess levels of agreement. A draft of the figure for the treatment recommendations was presented and discussed with the wider membership.

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.