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Objective: Psoriatic disease remains underdiagnosed and undertreated. We developed and validated a suite of novel, sensor-based smartphone assessments (Psorcast app) that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease., Methods: Participants with psoriasis (PsO) or psoriatic arthritis (PsA) and healthy controls were recruited between June 5, 2019, and November 10, 2021, at 2 academic medical centers. Concordance and accuracy of digital measures and image-based machine learning models were compared to their analogous clinical measures from trained rheumatologists and dermatologists., Results: Of 104 study participants, 51 (49%) were female and 53 (51%) were male, with a mean age of 42.3 years (SD 12.6). Seventy-nine (76%) participants had PsA, 16 (15.4%) had PsO, and 9 (8.7%) were healthy controls. Digital patient assessment of percent body surface area (BSA) affected with PsO demonstrated very strong concordance (Lin concordance correlation coefficient [CCC] 0.94 [95% CI 0.91-0.96]) with physician-assessed BSA. The in-clinic and remote target plaque physician global assessments showed fair-to-moderate concordance (CCC erythema 0.72 [0.59-0.85]; CCC induration 0.72 [0.62-0.82]; CCC scaling 0.60 [0.48-0.72]). Machine learning models of hand photos taken by patients accurately identified clinically diagnosed nail PsO with an accuracy of 0.76. The Digital Jar Open assessment categorized physician-assessed upper extremity involvement, considering joint tenderness or enthesitis (AUROC 0.68 [0.47-0.85])., Conclusion: The Psorcast digital assessments achieved significant clinical validity, although they require further validation in larger cohorts before use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and freely available., (Copyright © 2024 by the Journal of Rheumatology.)

Psoriatic arthritis (PsA) is a systemic chronic inflammatory disease that develops in up to 30% of patients with psoriasis. Mixed data variably support the potential ability to "prevent" and/or delay PsA through use of systemic therapies in psoriasis patients. Though intriguing, almost all of these studies are retrospective in nature, and hold substantial limitations and potential biases that challenge the ability to meaningfully interpretation their results. Thus, the authors believe prospective observational and interventional studies are crucial to understanding our ability to truly modify the transition from psoriasis to psoriatic arthritis and delay or prevent PsA onset., Competing Interests: Disclosures A. Wu has no financial or commercial conflicting interests to disclose. J.U. Scher is a consultant for Bristol-Myers Squibb, Janssen, UCB, and Pfizer. He is a co-PI in the PAMPA study in collaboration with Janssen. A. Ogdie is a consultant and/or investigator for Amgen, AbbVie, Bristol Myers Squibb, Celgene, CorEvitas, Eli Lilly, Gilead, GSK, Happify Health, Janssen, Novartis, Pfizer, and UCB. Christopher Ritchlin is a consultant and/or investigator for Amgen, AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma. J.F. Merola is a consultant and/or investigator for Amgen, Astra-Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Abbvie, Dermavant, Eli Lilly, Incyte, Moonlake, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer, and Leo Pharma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The objective for this study was to evaluate the effects of short chain fatty acids (SCFAs) on arthritic bone remodeling., Methods: We treated a recently described preclinical murine model of psoriatic arthritis (PsA), R26STAT3C stopfl/fl CD4Cre mice, with SCFA-supplemented water. We also performed in vitro osteoclast differentiation assays in the presence of serum-level SCFAs to evaluate the direct impact of these microbial metabolites on maturation and function of osteoclasts. We further characterized the molecular mechanism of SCFAs by transcriptional analysis., Results: The osteoporosis condition in R26STAT3C stopfl/fl CD4Cre animals is attributed primarily to robust osteoclast differentiation driven by an expansion of osteoclast progenitor cells (OCPs), accompanied by impaired osteoblast development. We show that SCFA supplementation can rescue the osteoporosis phenotype in this model of PsA. Our in vitro experiments revealed an inhibitory effect of the SCFAs on osteoclast differentiation, even at very low serum concentrations. This suppression of osteoclast differentiation enabled SCFAs to impede osteoporosis development in R26STAT3C stopfl/fl CD4Cre mice. Further interrogation revealed that bone marrow-derived OCPs from diseased mice expressed a higher level of SCFA receptors than those of control mice and that the progenitor cells in the bone marrow of SCFA-treated mice presented a modified transcriptomic landscape, suggesting a direct impact of SCFAs on bone marrow progenitors in the context of osteoporosis., Conclusion: We demonstrated how gut microbiota-derived SCFAs can regulate distal pathology (ie, osteoporosis) and identified a potential therapeutic option for restoring bone density in rheumatic disease, further highlighting the critical role of the gut-bone axis in these disorders., (© 2023 American College of Rheumatology.)

Objective: To evaluate whether the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a responsive instrument in psoriatic arthritis (PsA) and whether it differentiates between axial and peripheral disease activity in PsA., Methods: Individuals with PsA initiating therapy in a longitudinal cohort study based in the United States were included. Axial PsA (axPsA), most often also associated with peripheral disease, was defined as fulfillment of the Assessment of Spondyloarthritis international Society axial spondyloarthritis classification criteria or presence of axial disease imaging features. Baseline BASDAI, individual BASDAI items, patient global assessment, patient pain, and Routine Assessment of Patient Index Data 3, and score changes following therapy initiation were descriptively reported. Standardized response means (SRMs) were calculated as the mean change divided by the SD of the change., Results: The mean (SD) baseline BASDAI score at the time of therapy initiation was 5.0 (2.2) among those with axPsA (n = 40) and 4.8 (2.0) among those with peripheral-only disease (n = 79). There was no significant difference in patient-reported outcome scores between the groups. The mean change for BASDAI was similar among axial vs peripheral disease (-0.75 vs -0.83). SRMs were similar across axial vs peripheral disease for BASDAI (-0.37 vs -0.44) and the individual BASDAI items., Conclusion: BASDAI has reasonable responsiveness in PsA but does not differentiate between axPsA and peripheral PsA. (ClinicalTrials.gov: NCT03378336)., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: To determine the responsiveness to therapy and minimum clinically important improvement (MCII) for patient-reported outcome measures in psoriatic arthritis (PsA) and to examine the impact of baseline disease activity on the ability to demonstrate change., Methods: A longitudinal cohort study was performed within the PsA Research Consortium. Patients completed several patient-reported outcomes, including the Routine Assessment of Patient Index Data, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Psoriatic Arthritis Impact of Disease 12-item (PsAID12) questionnaire, and others. The mean change in the scores between visits and standardized response means (SRMs) were calculated. The MCII was calculated as the mean change in score among patients who reported minimal improvement. SRMs and MCIIs were compared among subgroups with moderate to highly active PsA and those with lower disease activity., Results: Among 171 patients, 266 therapy courses were included. The mean ± SD age was 51 ± 13.8 years, 53% were female, and the mean swollen and tender joint counts were 3 and 6, respectively, at baseline. SRMs and MCII for all measures were small to moderate, although greater among those with higher baseline disease activity. BASDAI had the best SRM overall and for less active PsA, and the clinical Disease Activity of PsA (cDAPSA) and PsAID12 were best for those with higher disease activity., Conclusion: SRMs and MCII were relatively small in this real-world population, particularly among those with lower disease activity at baseline. BASDAI, cDAPSA, and PsAID12 had good sensitivity to change, but selection for use in trials should consider the baseline disease activity of patients to be enrolled., (© 2023 American College of Rheumatology.)

Competing Interests: AO has received research grants from AbbVie, Novartis, Pfizer, and Janssen to the University of Pennsylvania and from Amgen to the National Databank for Rheumatic Diseases (FORWARD); has research collaborations with GlaxoSmithKline and Harvard Pilgrim; and has received consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, CorEvitas, Gilead, Happify Health, Janssen, Lilly, Novartis, Pfizer, and UCB. JUS has served as a consultant for Janssen, Novartis, Pfizer, Sanofi, Amgen, UCB and AbbVie; and has received funding for investigator-initiated studies from Janssen and Pfizer.

Objectives: To investigate the cutaneous microbiome spanning the entire psoriatic disease spectrum, and to evaluate distinguishing features of psoriasis (PsO) and psoriatic arthritis (PsA)., Methods: Skin swabs were collected from upper and lower extremities of healthy individuals and patients with PsO and PsA. Psoriatic patients contributed both lesional (L) and contralateral non-lesional (NL) samples. Microbiota were analysed using 16S rRNA sequencing., Results: Compared with healthy skin, alpha diversity in psoriatic NL and L skin was significantly reduced (p<0.05) and samples clustered separately in plots of beta diversity (p<0.05). Kocuria and Cutibacterium were enriched in healthy subjects, while Staphylococcus was enriched in psoriatic disease. Microbe-microbe association networks revealed a higher degree of similarity between psoriatic NL and L skin compared with healthy skin despite the absence of clinically evident inflammation. Moreover, the relative abundance of Corynebacterium was higher in NL PsA samples compared with NL PsO samples (p<0.05), potentially serving as a biomarker for disease progression., Conclusions: These findings show differences in diversity, bacterial composition and microbe-microbe interactions between healthy and psoriatic skin, both L and NL. We further identified bacterial biomarkers that differentiate disease phenotypes, which could potentially aid in predicting the transition from PsO to PsA., Competing Interests: Competing interests: RHH: received consulting fees from Janssen ALN: served as a consultant for Janssen, UCB, AbbVie and Bristol-Myers Squibb; has an immediate family member who owns shares of stock in J&J, Eli Lilly, AbbVie and Pfizer JUS: served as a consultant for Janssen, Abbvie, Novartis, Sanofi, UCB and BMS., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Psoriatic arthritis (PsA) is a complex, immune-mediated disease associated with skin psoriasis that, if left untreated, can lead to joint destruction. Up to 30% of patients with psoriasis progress to PsA. In most cases, psoriasis precedes synovio-entheseal inflammation by an average of 5-7 years, providing a unique opportunity for early and potentially preventive intervention in a susceptible and identifiable population. Guselkumab is an effective IL-23p19 inhibitor Food and Drug Administration (FDA-approved for treatment of moderate-to-severe psoriasis and PsA. The Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort (PAMPA) study aims to evaluate the efficacy of guselkumab in preventing PsA and decreasing musculoskeletal power Doppler ultrasound (PDUS) abnormalities in a population of patients with psoriasis who are at-increased risk for PsA progression., Methods and Analysis: The PAMPA study is a multicentre, randomised, double-blind, placebo-controlled, interventional, preventive trial comparing PDUS involvement and conversion to PsA in patients with psoriasis at-increased risk for progression treated with guselkumab compared with non-biological standard of care. The study includes a screening period, a double-blind treatment period (24 weeks) and an open-label follow-up period (72 weeks). At baseline, 200 subjects will be randomised (1:1) to receive either guselkumab 100 mg (arm 1) or placebo switching to guselkumab 100 mg starting at week 24 (arm 2). Arm 3 will follow 150 at-risk psoriasis patients who decline biological therapy and randomisation. Changes from baseline in the PDUS score at week 24 and the difference in proportion of patients transitioning to PsA at 96 weeks will be examined as the coprimary endpoints., Ethics and Dissemination: Ethics approval for this study was granted by the coordinating centre's (NYU School of Medicine) Institutional Review Board (IRB). Each participating site received approval through their own IRBs. The findings will be shared in peer-reviewed articles and scientific conference presentations., Trial Registration Number: NCT05004727., Competing Interests: Competing interests: KAM, SC, ZU, RBB, JS, JH, RC, KQ, FT have nothing to disclose. RHH has served as a consultant for Janssen. MT has served as a consultant for Horizon. VP has received honoraria for speaker and/or advisory board member roles from AbbVie, Almirall, Celgene, Janssen, Kyowa Kirin, LEO Pharma, Novartis, Pfizer, Sanofi, UCB and Union Therapeutics. In his role as Department Division Director of Dermatology at the University of Toronto. VP has received departmental support in the form of unrestricted educational grants from AbbVie, Bausch Health, Celgene, Janssen, LEO Pharma, Lilly, L’Oréal, NAOS, Novartis, Pfizer, Pierre-Fabre, Sandoz and Sanofi in the past 36 months. JY has served as a speaker, consultant, honoraria, and/or trialist for Abbvie, Amgen, Anacor, Astellas, Bausche, Baxalta, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, Janssen, Leo, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, Xenon. ALN declares that she has served as a consultant for Janssen, UCB, AbbVie, BMS and her immediate family member owns shares of stock in J&J, Eli Lilly, AbbVie and Pfizer. WG has received grants and research support from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer and honorari for ad boards, invited talks, or consultation from AbbVie, Actelion, Amgen, Arylide, Bausch Health, Boehringer, Celgene, Cipher, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, PeerVoice, Pfizer, Sanofi-Genzyme, Tribute, UCB, Valeant. Other: Clinical trials (study fees): AbbVie, Asana Biosciences, Astellas, Boerhinger-Ingleheim, Celgene, Corrona/National Psoriasis Foundation, Devonian, Eli Lilly, Galapagos, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, UCB. RGT has served as a consultant for Novartis, Bioclinica. JFM has served as a consultant and/or investigator for Amgen, Bristol-Myers Squibb, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Sanofi, Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma. AO has received esearch grants from AbbVie, Novartis, and Pfizer to University of Pennsylvania and Amgen to FORWARD/NDB; has research collaborations with GSK and Harvard Pilgrim; and has received consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, CorEvitas, Gilead, Happify Health, Janssen, Lilly, Novartis, Pfizer, and UCB; royalties from Novartis (to spouse).PR has received esearch grants from Janssen and Novartis and speaker and consulting fees from Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and Pfizer. LE has received grants from Novartis, Eli Lily, UCB, Pfizer, Abbvie, Sandoz, Janssen and consulting fees from Janssen, Abbvie, Pfizer, UCB, Eli Lily, Novartis. CTR has served as a consultant for Abbvie, Amgen, UCB, Novartis, Lilly, Janssen, MoonLake, Pfizer. JUS has served as a consultant for Janssen, Novartis, Pfizer, Sanofi, Amgen, UCB and AbbVie; and has received funding for investigator-initiated studies from Janssen and Pfizer. CG and SDC are employees of Janssen Scientific Affairs, LLC and shareholders in Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly owned subsidiary., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate secukinumab (SEC) 300 mg and 150 mg vs placebo in a United States-only population of biologic-naïve patients with psoriatic arthritis (PsA)., Methods: CHOICE was a double-blind, randomized controlled trial conducted in the US. Biologic-naïve patients with PsA and psoriasis (PsO) were randomized 2:2:1 to SEC 300 mg (n = 103), SEC 150 mg (n = 103), or placebo (n = 52). The primary objective was to show superiority of SEC 300 mg vs placebo in American College of Rheumatology 20% (ACR20) response at week 16. Additional objectives included the effect of SEC on dactylitis, enthesitis, PsO, and safety., Results: ACR20 response rates at week 16 were higher with SEC 300 mg than with placebo (51.5% vs 23.1%; odds ratio 3.51 [95% CI 1.65-7.45]; P = 0.001). SEC 300 mg also led to greater ACR50/70 responses and improvements in other variables vs placebo. Responses were generally sustained over time. Patients with inadequate response to SEC 150 mg at weeks 16, 28, or 40 who received dose escalation to 300 mg experienced improved clinical response after uptitration. The most common adverse events were upper respiratory tract infections and diarrhea. No inflammatory bowel disease was reported or new safety signals observed., Conclusion: SEC 300 mg led to rapid and significant improvements over placebo in symptoms of PsA in this heavier population of US-only, biologic-naïve patients. Findings were consistent with previous studies and suggest that SEC 300 mg is a safe and efficacious first-line biologic treatment for patients with PsA. [ClinicalTrials.gov: NCT02798211]., (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 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.)

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.)

Psoriatic arthritis (PsA) is part of a group of closely related clinical phenotypes ('psoriatic disease') that is defined by shared molecular pathogenesis resulting in excessive, prolonged inflammation in the various tissues affected, such as the skin, the entheses or the joints. Psoriatic disease comprises a set of specific drivers that promote an aberrant immune response and the consequent development of chronic disease that necessitates therapeutic intervention. These drivers include genetic, biomechanical, metabolic and microbial factors that facilitate a robust and continuous mobilization, trafficking and homing of immune cells into the target tissues. The role of genetic variants involved in the immune response, the contribution of mechanical factors triggering an exaggerated inflammatory response (mechanoinflammation), the impact of adipose tissue and altered lipid metabolism and the influence of intestinal dysbiosis in the disease process are discussed. Furthermore, the role of key cytokines, such as IL-23, IL-17 and TNF, in orchestrating the various phases of the inflammatory disease process and as therapeutic targets in PsA is reviewed. Finally, the nature and the mechanisms of inflammatory tissue responses inherent to PsA are summarized., (© 2022. Springer Nature Limited.)

Objective: To examine the association of biologic therapy use for psoriasis with incident psoriatic arthritis (PsA) diagnosis., Methods: A retrospective cohort study was conducted in the OptumInsights Electronic Health Record Database between 2006 and 2017 among patients with psoriasis between the ages of 16 and 90 initiating a therapy for psoriasis (oral, biologic or phototherapy). The incidence of PsA was calculated within each therapy group. Multivariable Cox models were used to calculate the HR for biologic versus oral or phototherapy using biologics as a time-varying exposure and next in a propensity score-matched cohort., Results: Among 1 93 709 patients with psoriasis without PsA, 14 569 biologic and 20 321 cumulative oral therapy and phototherapy initiations were identified. Mean age was lower among biologic initiators compared with oral/phototherapy initiators (45.9 vs 49.8). The incidence of PsA regardless of therapy exposure was 9.75 per 1000 person-years compared with 77.26 among biologic users, 61.99 among oral therapy users, 26.11 among phototherapy users and 5.85 among those without a prescription for one of the target therapies. Using a multivariable adjustment approach with time-varying exposure, adjusted HR (95% CI) for biologic users was 4.48 (4.23 to 4.75) compared with oral or phototherapy users. After propensity score matching, the HR (95% CI) was 2.14 (2.00 to 2.28)., Conclusions: In this retrospective cohort study, biologic use was associated with the development of PsA among patients with psoriasis. This may be related to confounding by indication and protopathic bias. Prospective studies are needed to address this important question., Competing Interests: Competing interests: No commercial entities provided support for the work in the submitted manuscript. Dr. Gelfand served as a consultant for Abcentra, Abbvie, BMS, Boehringer Ingelheim, Cara (DSMB), GSK, Lilly (DMC), Janssen Biologics, Novartis Corp, UCB (DSMB and Mindera Dx, receiving honoraria; and receives research grants (to the Trustees of the University of Pennsylvania) from Abbvie, Boehringer Ingelheim, Janssen, Novartis Corp, Celgene, Ortho Dermatologics, and Pfizer Inc; Dr Gelfand is a Deputy Editor for the Journal of Investigative Dermatology receiving honoraria from the Society for Investigative Dermatology, is Chief Medical Editor for Healio Psoriatic Disease (receiving honoraria) and is a member of the Board of Directors for the International Psoriasis Council, receiving no honoraria. Thorvardur Love has received reimbursement from Celgene for speaking about guidelines for the treatment of psoriatic arthritis. Alexis Ogdie has served as a consultant for Abbvie, Amgen, BMS, Celgene, Corrona, Global Health Living Foundation, Janssen, Lilly, Novartis, Pfizer, and Takeda and has received grants to the University of Pennsylvania from Pfizer and Novartis and to Forward from Amgen. Her husband has received royalties from Novartis. The remaining authors have no COI to report., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Psoriatic arthritis (PsA) is a complex inflammatory disease with heterogeneous clinical features, which complicates psoriasis in 30% of patients. There are no diagnostic criteria or tests available. Diagnosis is most commonly made by identifying inflammatory musculoskeletal features in joints, entheses or the spine in the presence of skin and/or nail psoriasis and in the usual absence of rheumatoid factor and anti-cyclic citrullinated peptide. The evolution of psoriasis to PsA may occur in stages, although the mechanisms are unclear. In many patients, there may be little or no relationship between severity of musculoskeletal inflammation and severity of skin or nail psoriasis. The reason for this disease heterogeneity may be explained by differences in genotype, especially in the HLA region. New targeted therapies for PsA have been approved with additional therapies in development. These developments have substantially improved both short-term and long-term outcomes including a reduction in musculoskeletal and skin manifestations and in radiographic damage. With efforts underway aimed at improving our understanding of the molecular basis for the heterogeneity of PsA, a personalized approach to treating PsA may become possible., (© 2021. Springer Nature Limited.)

The coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2) pandemic has affected the healthcare system on a global scale, and we utilized the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2020 annual meeting to examine how COVID-19 might affect patients with psoriatic disease (PsD) and the clinicians who care for them. Pressing issues and concerns identified included whether having psoriasis increased the risk of acquiring COVID-19, vaccine safety, and the acceptability of telehealth. The general message from rheumatologists, dermatologists, infectious disease specialists, and patient research partners was that data did not suggest that having PsD or its treatment significantly increased risk of infection or more severe disease course, and that the telehealth experience was a success overall., (Copyright © 2021 by The Journal of Rheumatology.)

Objectives: Physical function is a core outcome in PsA. We examined the construct validity and responsiveness of three commonly used instruments to assess physical function in PsA: HAQ disability index (HAQ-DI), MultiDimensional HAQ (MDHAQ) and the Patient-Reported Outcomes Measurement Information System (PROMIS®) Global-10., Methods: Between 2016 and 2019, patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium longitudinal cohort study in the USA. Correlations were calculated at baseline and among change scores using Spearman's correlation coefficient. Standardized response means were calculated. Agreement with the 20% improvement cut-off was used to determine the potential effect of using MDHAQ or the PROMIS Global-10 physical health (GPH) subscore in place of HAQ-DI when assessing the ACR20., Results: A total of 274 patients were included in the analysis. The mean age of patients was 49 years and 51% were male. At baseline, the mean HAQ-DI was 0.6 (s.d. 0.6; range 0-3), the mean MDHAQ was 1.8 (s.d. 1.6; range 0-10) and the mean GPH T-score was 43.4 (s.d. 9.3; range 0-100). All three instruments were strongly correlated at baseline (rho 0.75-0.85). Change scores were moderately correlated (rho 0.42-0.71). Among therapy initiators, the mean change between two visits in HAQ-DI, MDHAQ and GPH was -0.1 (s.d. 0.4), -0.2 (s.d. 1.2) and 2.5 (s.d. 6.1), respectively. The standardized response means were 0.18, 0.16 and 0.41, respectively., Conclusion: The three instruments tested are not directly interchangeable but have overall similar levels of responsiveness., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The concept of psoriatic arthritis (PsA) prevention is gaining increased interest owing to the physical limitation, poor quality of life and low remission rates that are achieved with current therapies for PsA. The psoriasis-to-PsA transition offers a unique opportunity to identify individuals at increased risk of developing PsA and to implement preventive strategies. However, identifying individuals at increased risk of developing PsA is challenging as there is no consensus on how this population should be defined. This Consensus Statement puts forward recommended terminology from the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) for defining specific subgroups of individuals during the preclinical and early clinical phases of PsA to be used in research studies. Following a three-round Delphi process, consensus was reached for three terms and definitions: 'increased risk for PsA', 'psoriasis with asymptomatic synovio-entheseal imaging abnormalities' and 'psoriasis with musculoskeletal symptoms not explained by other diagnosis'. These terms and their definitions will enable improved identification and standardization of study populations in clinical research. In the future, as increasing evidence emerges regarding the molecular and clinical features of the psoriasis-to-PsA continuum, these terms and definitions will be further refined and updated.

Objective: To characterize the hospitalization and death rates among patients with inflammatory arthritis (IA) affected by coronavirus disease 2019 (COVID-19) and to analyze the associations of comorbidities and immunomodulatory medications with infection outcomes., Methods: Data on clinical and demographic features, maintenance treatment, disease course, and outcomes in individuals with IA (rheumatoid arthritis and spondyloarthritis) with symptomatic COVID-19 infection were prospectively assessed via web-based questionnaire followed by individual phone calls and electronic medical record review. Baseline characteristics and medication use were summarized for hospitalized and ambulatory patients, and outcomes with the different medication classes were compared using multivariable logistic regression., Results: A total of 103 patients with IA were included in the study (80 with confirmed COVID-19 and 23 with high suspicion of COVID-19). Hospitalization was required in 26% of the participants, and 4% died. Patients who were hospitalized were significantly more likely to be older (P < 0.001) and have comorbid hypertension (P = 0.001) and chronic obstructive pulmonary disease (P = 0.02). IA patients taking oral glucocorticoids had an increased likelihood of being admitted for COVID-19 (P < 0.001), while those receiving maintenance anticytokine biologic therapies did not., Conclusion: Among patients with underlying IA, COVID-19 outcomes were worse in those receiving glucocorticoids but not in patients receiving maintenance anticytokine therapy. Further work is needed to understand whether immunomodulatory therapies affect COVID-19 incidence., (© 2020, American College of Rheumatology.)

Objective: To examine the construct validity of Routine Assessment of Patient Index Data 3 (RAPID3) and Psoriatic Arthritis Impact of Disease (PsAID) in patients with psoriatic arthritis (PsA). In examining construct validity, we also addressed scores among subgroups with severe psoriasis, poly articular disease, enthesitis, and dactylitis, and evaluated influences of sociodemographic factors and comorbidities (contextual factors) on these patient-reported outcomes (PRO)., Methods: Patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium (PARC) between 2014 and 2016. PARC is a longitudinal observational cohort study conducted at 4 US institutions. In this cross-sectional study, construct validity was assessed by examining Spearman correlation coefficients for RAPID3 and PsAID with physician-reported disease activity measures and other PRO [e.g., Medical Outcomes Study Short Form-12 physical component summary/mental component summary (SF-12 PCS/MCS), Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F)]. Contextual factors and disease subgroups were assessed in multivariable linear regression models with RAPID3 or PsAID12 as outcomes of interest and the hypothesized contextual factors as covariates., Results: Among 401 patients enrolled in PARC, 347 completed RAPID3 or PsAID12. Of these, most were white females with a mean age of 51.7 years (SD 14.02). RAPID3 and PsAID were highly correlated (r = 0.90). These measures were also correlated with the SF-12 PCS (r = -0.67) and FACIT-F (r = -0.77). Important contextual factors and disease subgroups included enthesitis, joint counts, education, insurance type, and depression., Conclusion: RAPID3 and PsAID12 have excellent construct validity in PsA and are strongly correlated despite differing items. Contextual factors (i.e., the presence of depression and obesity) should be considered when interpreting raw scores of the RAPID3 and PsAID12.

Purpose of Review: To provide a general overview of the organizations dedicated to advance clinical and translational research in the field of psoriatic disease and to describe the current and future opportunities for team science approaches to overcome unmet needs in the field. Descriptions of initiatives from the NPF, PPACMAN, and GRAPPA are summarized., Recent Findings: Program projects have recently identified areas of knowledge gaps in diagnosis, treatment, and prevention of psoriasis and psoriatic arthritis (PsA). NPF's Psoriasis Prevention Initiative aims to identify interventions that can prevent the onset and relapse of psoriatic disease or related comorbidities. The Psorcast Study is a joint venture between PPACMAN and Sage Bionetworks based on patient-generated smartphone measurements of psoriatic disease. Similarly, GRAPPA is involved in a number of projects related to axial PsA, enthesitis prevalence, and biomarker discoveries. As important initiatives bring new targets for diagnosis and therapeutics in psoriatic disease, supra-endeavors such as the NIH-Accelerating Medicines Partnership (AMP) and the European Innovative Medicines Initiative (IMI) are promising public-private partnerships that can significantly catapult the field forward.

Precision medicine, propelled by advances in multi-omics methods and analytics, aims to revolutionize patient care by using clinically-actionable molecular markers to guide diagnostic and therapeutic decisions. We describe the applications of precision medicine in risk stratification, drug selection, and treatment response prediction in psoriatic arthritis, for which targeted, personalized approaches are steadily emerging., (Copyright © 2020. Published by Elsevier Inc.)

Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease hypothesized to promote inflammation via cleavage of protease-activated receptor 1 (PAR1) and PAR2. KLK6 levels are elevated in multiple inflammatory and autoimmune conditions, but no definitive role in pathogenesis has been established. Here, we show that skin-targeted overexpression of KLK6 causes generalized, severe psoriasiform dermatitis with spontaneous development of debilitating psoriatic arthritis-like joint disease. The psoriatic skin and joint phenotypes are reversed by normalization of skin KLK6 levels and attenuated following genetic elimination of PAR1 but not PAR2. Conservation of this regulatory pathway was confirmed in human psoriasis using vorapaxar, an FDA-approved PAR1 antagonist, on explanted lesional skin from patients with psoriasis. Beyond defining a critical role for KLK6/PAR1 signaling in promoting psoriasis, our results demonstrate that KLK6/PAR1-mediated inflammation in the skin alone is sufficient to drive inflammatory joint disease. Further, we identify PAR1 as a promising cytokine-independent target in therapy of psoriasis and psoriatic arthritis.

Objective: To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome in psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients., Methods: Fecal samples from PsA/SpA patients pre- and posttreatment with tumor necrosis factor inhibitors (TNFi; n = 15) or an anti-interleukin-17A monoclonal antibody inhibitor (IL-17i; n = 14) underwent sequencing (16S ribosomal RNA, internal transcribed spacer and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL-17i (n = 5) were analyzed for expression of IL-23/Th17-related cytokines, IL-25/IL-17E-producing cells, and type 2 innate lymphoid cells (ILC2s)., Results: There were significant shifts in abundance of specific taxa after treatment with IL-17i compared to TNFi, particularly Clostridiales (P = 0.016) and Candida albicans (P = 0.041). These subclinical alterations correlated with changes in bacterial community co-occurrence, metabolic pathways, IL-23/Th17-related cytokines, and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL-25/IL-17E-producing tuft cells and ILC2s (P < 0.05), compared to pre-IL-17i treatment levels., Conclusion: In a subgroup of SpA patients, the initiation of IL-17A blockade correlated with features of subclinical gut inflammation and intestinal dysbiosis of certain bacterial and fungal taxa, most notably C albicans. Further, IL-17i-related CD was associated with overexpression of IL-25/IL-17E-producing tuft cells and ILC2s. These results may help to explain the potential link between inhibition of a specific IL-17 pathway and the (sub)clinical gut inflammation observed in SpA., (© 2019, American College of Rheumatology.)

Background: Dual neutralisation of interleukin 17A (IL17A) and interleukin 17F (IL17F) is a potential novel therapeutic approach in psoriatic arthritis. We assessed bimekizumab, a monoclonal antibody that selectively neutralises IL17A and IL17F, in patients with active psoriatic arthritis., Methods: BE ACTIVE was a randomised, double-blind, placebo-controlled, dose-ranging phase 2b study done at 41 sites in the Czech Republic, Germany, Hungary, Poland, Russia, and the USA. Eligible patients aged 18 years or older with active adult-onset psoriatic arthritis and symptoms for at least 6 months were randomly assigned (1:1:1:1:1) to placebo, 16 mg bimekizumab, 160 mg bimekizumab, 160 mg bimekizumab with a one-off 320 mg loading dose, or 320 mg bimekizumab, which were administered as subcutaneous injections every 4 weeks for 12 weeks. After 12 weeks, patients assigned to the placebo and 16 mg bimekizumab groups were randomly reassigned (1:1) to either 160 mg or 320 mg bimekizumab, and all other patients remained on their originally assigned initial dose up to 48 weeks. Both participants and researchers were blinded to treatment allocation in the first 12 weeks, and blinded to the dose of bimekizumab thereafter. The primary endpoint was the proportion of patients with at least 50% improvement in the American College of Rheumatology response criteria at week 12, which was assessed in all patients who received at least one dose of study treatment and had a valid measurement of the primary efficacy endpoint at baseline. The trial, including all follow-up, has been completed. This trial is registered with ClinicalTrials.gov, NCT02969525., Findings: Between Oct 27, 2016, and July 16, 2018, 308 patients were screened, and 206 were randomly assigned: 42 to the placebo group, and 41 each to the four bimekizumab groups. At 12 weeks, compared with the placebo group, significantly more patients in the 16 mg bimekizumab (odds ratio [OR] 4·2 [95% CI 1·1-15·2]; p=0·032), 160 mg bimekizumab (8·1 [2·3-28·7]; p=0·0012), and 160 mg (loading dose) bimekizumab (9·7 [2·7-34·3]; p=0·0004) groups achieved an ACR50 response. At 12 weeks, 24 (57%) of 42 patients in the placebo group and 68 (41%) of the 164 patients in the bimekizumab groups reported treatment-emergent adverse events. Most of these adverse events were mild or moderate. Serious treatment-emergent adverse events occurred in nine patients, eight of whom were receiving bimekizumab. No deaths or cases of inflammatory bowel disease were reported., Interpretation: Bimekizumab doses of 16 mg and 160 mg (with or without a 320 mg loading dose) were associated with significant improvements in ACR50 compared with placebo, with an acceptable safety profile. Our results support phase 3 investigation of bimekizumab as a treatment for psoriatic arthritis., Funding: UCB Pharma., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose of Review: The therapeutic response to biologic agents in psoriasis is significantly higher than observed in psoriatic arthritis (PsA). In this review, specific actions to improve treatment outcomes in PsA are discussed., Recent Findings: Increased understanding of disease pathogenesis derived from improved preclinical models and advances in cell-based and molecular technologies provide new tools to identify therapeutic targets. In addition to the important contributions of metabolic comorbidities, chronic pain and the lack of a diagnostic biomarker signal the need for new strategies to improve outcomes. Potential strategies include the following: (1) discover a novel pathway or cellular subset, (2) apply stratification biomarkers to individualize therapy, (3) preclinical intervention, (4) combination therapy, (5) lifestyle modification, (6) address chronic pain and fatigue, and (7) multidisciplinary care. The future holds great promise for enhanced treatment responses in PsA based on improved understanding of individual variation in disease pathophysiology coupled with comprehensive and integrated treatment programs.

Psoriasis is one of the most common chronic inflammatory skin diseases, affecting 3% of the world's population, and approximately one-third of patients with psoriasis will eventually transition to having psoriatic arthritis (PsA). The evolution from cutaneous to synovio-entheseal inflammation in these patients presents an opportunity to investigate the critical events linked to arthritis development. The events responsible for progression to PsA are currently unclear. Genetic and clinical-demographic risk factors (most notably familial aggregation and psoriasis sub-phenotypes) provide relevant insights into the variables that promote transition. The specific underlying molecular and cellular mechanisms, however, remain poorly defined. Intriguingly, although targeting the IL-23-IL-17 axis substantially improves psoriasis outcomes, this strategy is not more effective than TNF inhibitors in improving musculoskeletal symptoms in PsA. Major unmet needs in the field of PsA include defining those patients with psoriasis at increased risk of developing arthritis, improving our understanding of the natural history of disease and characterizing the immune, environmental and molecular subclinical events preceding PsA onset. Improving our knowledge of this transition is essential for designing clinical trials with treatments that can delay, attenuate or even prevent the development of PsA in patients with psoriasis.

Objective: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF)., Methods: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations., Results: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment., Conclusion: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA., (© 2018, American College of Rheumatology.)

The microbiome is a known and established immunomodulator of many inflammatory disorders, including psoriasis and psoriatic arthritis. Microbes co-evolved with their human hosts and provide them with nutritional, metabolic, and immunologic support. An accumulating body of evidence has revealed that psoriatic diseases are characterized by a state of intestinal dysbiosis, which has been linked to a decrease in beneficial commensals and fatty acids. This has been shown in both animal models and human samples, and multiple studies have addressed the physiological and potentially pathogenic role of intestinal and cutaneous microbes in human health and disease. In this review, we discuss state-of-the-art literature in the field of the microbiome in psoriatic diseases that was presented during the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2017 annual meeting, with a special emphasis on synovio-entheseal inflammation. A better understanding of these microbe-host interactions can lead to novel diagnostic and therapeutic targets.

Objective: To introduce a novel preclinical animal model of psoriatic arthritis (PsA) in R26Stat3C stopfl/fl CD4Cre mice, and to investigate the role of Th17 cytokines in the disease pathogenesis., Methods: We characterized a novel murine model of Th17-driven cutaneous and synovio-entheseal disease directed by T cell-specific expression of a hyperactive Stat3 allele. By crossing R26Stat3C stopfl/fl CD4Cre mice onto an interleukin-22 (IL-22)-knockout background or treating the mice with a neutralizing antibody against IL-17, we interrogated how these Th17 cytokines could contribute to the pathogenesis of PsA., Results: R26Stat3C stopfl/fl CD4Cre mice developed acanthosis, hyperkeratosis, and parakeratosis of the skin, as well as enthesitis/tendinitis and periarticular bone erosion in different joints, accompanied by osteopenia. T cell-specific expression of a hyperactive Stat3C allele was found to drive the augmented Th17 response in these animals. Careful characterization of the mouse bone marrow revealed an increase in osteoclast progenitor (OCP) and RANKL-producing cells, which contributed to the osteopenia phenotype observed in the mutant animals. Abrogation of the Th17 cytokines IL-17 or IL-22 improved both the skin and bone phenotype in R26Stat3C stopfl/fl CD4Cre mice, revealing a central role of Th17 cells in the regulation of OCP and RANKL expression on stromal cells., Conclusion: Perturbation of the IL-23/Th17 axis instigates Th17-mediated inflammation in R26Stat3C stopfl/fl CD4Cre mice, leading to cutaneous and synovio-entheseal inflammation and bone pathologic features highly reminiscent of human PsA. Both IL-17A and IL-22 produced by Th17 cells appear to play critical roles in promoting the cutaneous and musculoskeletal inflammation that characterizes PsA., (© 2018, American College of Rheumatology.)

Optimal management of patients with both psoriasis and psoriatic arthritis (PsA) necessitates collaboration among dermatologists and rheumatologists. In this manuscript, we discuss challenges and opportunities for dual care models for patients with psoriasis and PsA and the results of a survey of combined clinics based in North America.

Programmed death-1 (PD-1) is an inhibitory co-receptor that is highly expressed in T lymphocytes that has been shown to downregulate inflammatory responses in several inflammatory diseases including systemic lupus erythematosus and rheumatoid arthritis. Yet, the role of PD-1 in psoriatic arthritis (PsA) has not been studied. In order to fill this gap, we measured the expression levels of PD-1 in peripheral T cells from patients with active disease. Twenty patients and fifteen age-matched healthy control subjects were recruited. The percentage of CD3(+)PD-1(+) T cells was measured by flow cytometry. Despite normal concentration of peripheral T cells, the expression levels of PD-1 were significantly higher in patients compared to healthy controls. Interestingly, among the patients, the expression levels inversely correlated with disease activity measured by disease activity scores (DAS28). PD-1 expression levels strongly correlated with the number of tender and swollen joints, but not with C-reactive protein (CRP) levels or psoriasis area and severity index (PASI). Functionally, in vitro ligation of PD-1 receptor in PsA T cells inhibited interleukin-2 (IL-2) secretion, Akt phosphorylation, and Rap1 activation. These findings suggest that PD-1 might serve as a biomarker for disease activity in PsA and highlight the need for additional studies in order to establish the role of PD-1 in PsA pathogenesis.

Objective: To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA)., Methods: High-throughput 16S ribosomal RNA pyrosequencing was utilized to compare the community composition of gut microbiota in patients with PsA (n = 16), patients with psoriasis of the skin (n = 15), and healthy, matched control subjects (n = 17). Samples were further assessed for the presence and levels of fecal and serum secretory IgA (sIgA), proinflammatory proteins, and fatty acids., Results: The gut microbiota observed in patients with PsA and patients with skin psoriasis was less diverse when compared to that in healthy controls. This could be attributed to the reduced presence of several taxa. Samples from both patient groups showed a relative decrease in abundance of Coprococcus species, while samples from PsA patients were also characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA levels and decrease in RANKL levels. Analysis of fatty acids revealed low fecal quantities of hexanoate and heptanoate in both patients with PsA and patients with psoriasis., Conclusion: Patients with PsA and patients with skin psoriasis had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had a lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that previously described in patients with inflammatory bowel disease and was associated with changes in specific inflammatory proteins unique to this group, and distinct from that in patients with skin psoriasis and healthy controls. Thus, the role of the gut microbiome in the continuum of psoriasis-PsA pathogenesis and the associated immune response merits further study., (Copyright © 2015 by the American College of Rheumatology.)

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. About a quarter of patients with psoriasis of the skin will develop PsA, although it is currently challenging-if not impossible-to determine a priori which individuals will progress. Identification of biomarkers for screening, disease activity, joint damage, treatment response and comorbidities are therefore perceived as important clinical needs in the field. Over the last few years, several lines of investigation have advanced our knowledge of new markers for PsA and its outcomes, including genomic, proteomic, cellular and tissue studies. Imaging studies utilizing ultrasonography have been applied to better understand the natural history of the disease. Novel biomarkers, such as soluble proteins and microbiomics, are also being described. Although no biomarker has yet been validated for use in clinical practice, discovery studies are in progress and validation cohorts are being designed. In this report, we review the latest progress in biomarker research in PsA and its potential implications in pathogenesis, diagnosis and therapy.