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Objectives Autoantibody seroconversion has been extensively studied in the context of COVID-19 infection but data regarding post-vaccination autoantibody production is lacking. Here we aimed to determine the incidence of common autoantibody formation following mRNA COVID-19 vaccines in patients with inflammatory arthritis (IA) and in healthy controls. Methods Autoantibody seroconversion was measured by serum ELISA in a longitudinal cohort of IA participants and healthy controls before and after COVID-19 mRNA-based immunization. Results Overall, there was a significantly lower incidence of ANA seroconversion in participants who did not contract COVID-19 prior to vaccination compared with those who been previously infected (7.4% vs 24.1%, P  = 0.014). Incidence of de novo anti-CCP seroconversion in all participants was low at 4.9%. Autoantibody levels were typically of low titre, transient, and not associated with increase in IA flares. Conclusions In both health and inflammatory arthritis, the risk of autoantibody seroconversion is lower following mRNA-based immunization than following natural SARS-CoV-2 infection. Importantly, seroconversion does not correlate with self-reported IA disease flare risk, further supporting the encouragement of mRNA-based COVID-19 immunization in the IA population. [ABSTRACT FROM AUTHOR]

RA is a complex multifactorial chronic disease that transitions through several stages. Multiple studies now support that there is a prolonged phase in early RA development during which there is serum elevation of RA-related autoantibodies including RF and ACPAs in the absence of clinically evident synovitis. This suggests that RA pathogenesis might originate in an extra-articular location, which we hypothesize is a mucosal site. In discussing this hypothesis, we will present herein the current understanding of mucosal immunology, including a discussion about the generation of autoimmune responses at these surfaces. We will also examine how other factors such as genes, microbes and other environmental toxins (including tobacco smoke) could influence the triggering of autoimmunity at mucosal sites and eventually systemic organ disease. We will also propose a research agenda to improve our understanding of the role of mucosal inflammation in the development of RA. [ABSTRACT FROM AUTHOR]

Inflammatory epithelial diseases are spurred by the concomitant dysregulation of immune and epithelial cells. How these two dysregulated cellular compartments simultaneously sustain their heightened metabolic demands is unclear. Single-cell and spatial transcriptomics (ST), along with immunofluorescence, revealed that hypoxia-inducible factor 1α (HIF1α), downstream of IL-17 signaling, drove psoriatic epithelial remodeling. Blocking HIF1α in human psoriatic lesions ex vivo impaired glycolysis and phenocopied anti-IL-17 therapy. In a murine model of skin inflammation, epidermal-specific loss of HIF1α or its target gene, glucose transporter 1, ameliorated epidermal, immune, vascular, and neuronal pathology. Mechanistically, glycolysis autonomously fueled epithelial pathology and enhanced lactate production, which augmented the γδ T17 cell response. RORγt-driven genetic deletion or pharmacological inhibition of either lactate-producing enzymes or lactate transporters attenuated epithelial pathology and IL-17A expression in vivo. Our findings identify a metabolic hierarchy between epithelial and immune compartments and the consequent coordination of metabolic processes that sustain inflammatory disease. [Display omitted] • HIF1α is activated in psoriatic epidermis and associated with IL-17A • Ablating epithelial HIF1α curbs vascular, nervous, and immune skin pathology • HIF1α-induced epithelial glycolysis directs multisystemic skin pathology • Lactate, a glycolysis byproduct, potentiates the underlying γδ T17 response How immune and epithelial cells simultaneously fuel their dysfunction in chronic skin diseases is unclear. Subudhi and Konieczny et al. find that IL-17-induced epithelial HIF1α activates glycolysis, which potentiates the γδ T17 response via lactate. This metabolic circuit drives multisystems pathology and can be targeted in inflammatory disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Spondyloarthritis (SpA) is a group of chronic, immune-mediated, inflammatory diseases affecting the bone, synovium, and enthesis. Microbiome, the community of microorganisms that has co-evolved with human hosts, plays a pivotal role in human health and disease. This invisible "essential organ" supplies the host with a myriad of chemicals and molecules. In turn, microbial metabolites can serve as messengers for microbes to communicate with each other and in the cross-talk with host cells. Gut dysbiosis in SpA is associated with altered microbial metabolites, and an accumulated body of research has contributed to the understanding that changes in intestinal microbiota can modulate disease pathogenesis. We review the novel findings from human and animal studies to provide an overview of the contribution of individual microbial metabolites and antigens to SpA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rho-associated kinase 2 (ROCK2) regulates the secretion of proinflammatory cytokines and the development of autoimmunity in mice. Data from a phase 1 clinical trial demonstrate that oral administration of KD025, a selective ROCK2 inhibitor, to healthy human subjects down-regulates the ability of T cells to secrete IL-21 and IL-17 by 90% and 60%, respectively, but not IFN-γ in response to T-cell receptor stimulation in vitro. Pharmacological inhibition with KD025 or siRNA-mediated inhibition of ROCK2, but not ROCK1, significantly diminished STAT3 phosphorylation and binding to IL-17 and IL-21 promoters and reduced IFN regulatory factor 4 and nuclear hormone RAR-related orphan receptor γt protein levels in T cells derived from healthy subjects or rheumatoid arthritis patients. Simultaneously, treatment with KD025 also promotes the suppressive function of regulatory T cells through up-regulation of STAT5 phosphorylation and positive regulation of forkhead box p3 expression. The administration of KD025 in vivo down-regulates the progression of collagen-induced arthritis in mice via targeting of the Th17-mediated pathway. Thus, ROCK2 signaling appears to be instrumental in regulating the balance between proinflammatory and regulatory T-cell subsets. Targeting of ROCK2 in man may therefore restore disrupted immune homeostasis and have a role in the treatment of autoimmunity. [ABSTRACT FROM AUTHOR]

Because the mechanisms of Helicobacterpylori-induced gastric injury are incompletely understood, we examined the hypothesis that H. pylori induces matrix metalloproteinase-1 (MMP-1) secretion, with potential to disrupt gastric stroma. We further tested the role of CagA, an H. pylori virulence factor, in MMP-1 secretion. Co-incubation of AGS cells with Tx30a, an H. pylori strain lacking the cagA virulence gene, stimulated MMP-1 secretion, confirming cagA-independent secretion. Co-incubation with strain 147C (cagA+) resulted in CagA translocation into AGS cells and increased MMP-1 secretion relative to Tx30a. Transfection of cells with the recombinant 147C cagA gene also induced MMP-1 secretion, indicating that CagA can independently stimulate MMP- 1 secretion. Co-incubation with strain 147A, containing a cagA gene that lacks an EPIYA tyro- sine phosphorylation motif, as well as transfection with 147A cagA, yielded an MMP-1 secretion intermediate between no treatment and 147C, indicating that CagA tyrosine phosphorylation regulates cellular signaling in this model system. H. pylori induced activation of the MAP kinase ERK, with CagA-independent (early) and dependent (later) components. MEK inhibitors UO126 and PD98059 inhibited both CagA-independent and -dependent MMP-1 secretion, whereas p38 inhibition enhanced MMP-1 secretion and ERK activation, suggesting p38 negative regulation of MMP-1 and ERK. These data indicate H. pylori effects on host epithelial MMP-1 expression via ERK, with p38 playing a potential regulatory role. [ABSTRACT FROM AUTHOR]

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.)

Background: Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic for patients with psoriatic arthritis (PsA). Given that many patients with PsA are TNFi inadequate responders (TNF-IR; either inadequate efficacy or intolerance), treatments utilizing alternative mechanisms of action are needed. In phase 3 studies, the fully human interleukin (IL)-23p19 subunit-inhibitor, guselkumab, was efficacious in patients with active PsA, including TNFi-IR. Efficacy was generally consistent between TNFi-naïve and TNFi-experienced cohorts; however, in the latter, higher response rates have been observed with the Q4W dosing regimen relative to the Q8W dosing regimen for some endpoints, suggesting the need to evaluate whether more frequent dosing may provide an incremental clinical benefit for TNFi-IR patients., Methods: The phase 3b SOLSTICE study will assess guselkumab efficacy and safety in TNFi-IR PsA patients. Eligibility criteria include a PsA diagnosis for ≥ 6 months; active disease (≥ 3 swollen, ≥ 3 tender joints, C-reactive protein ≥ 0.3 mg/dL); and inadequate efficacy with, and/or intolerance to, one prior TNFi. Participants will be randomized 1:1:1 to guselkumab Q4W or Q8W or placebo→guselkumab Q4W (at Week 24). The primary endpoint is the proportion of patients achieving ≥ 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 24. Major secondary endpoints include ACR50, ACR70; an Investigator's Global Assessment (IGA) of psoriasis score of 0/1 plus ≥ 2-grade reduction and ≥ 90% improvement in Psoriasis Area and Severity Index (both among patients with ≥ 3% body surface area affected by psoriasis and baseline IGA ≥ 2); minimal/very low disease activity; and changes from baseline in Health Assessment Questionnaire-Disability Index, the 36-item Short-Form Health Survey Physical Component Summary, and Functional Assessment of Chronic Illness Therapy-Fatigue scores. The target sample size (N = 450) is estimated to provide > 90% power in detecting differences between each guselkumab group and the placebo group for the primary endpoint assuming a 2-sided α = 0.05. Cochran-Mantel-Haenszel testing and analyses of covariance will be used to compare efficacy for binary and continuous endpoints, respectively., Discussion: Findings from the phase 3b SOLSTICE study, the design of which was informed by results from previously conducted phase 3 studies, is expected to provide important efficacy and safety information on guselkumab therapy in TNFi-IR patients with PsA., Trial Registration: This trial was registered at ClinicalTrials.gov, NCT04936308, on 23 June 2021., (© 2024. The Author(s).)

Objective: Individuals of racially and ethnically diverse backgrounds are underrepresented in psoriatic arthritis (PsA) research/clinical trials, despite evidence that their disease presentation, severity and course may be distinct. Here we aim to describe how race, ethnicity and other socioeconomic factors inform disease characteristics in PsA., Methods: 817 consecutive patients with PsA from a large, diverse metropolitan area, were enrolled in an observational, longitudinal registry. Demographics, medical history, medication use, and psoriatic disease phenotype and activity were all recorded and analyzed., Results: The population was 77.4% non-Hispanic White, 2.2% Black, 7.1% Asian, and 9.9% identified as other races or multiracial, and 11.8% identified as Hispanic. Hispanic and non-White individuals had higher tender joint counts (p= 0.033) with similar swollen joint counts (p= 0.308) and medication use (p= 0.171). They also had high rates of radiographic axial disease. Hispanic individuals were significantly more likely to have higher tender joint counts (p= 0.029), higher RAPID3 scores (p= 0.004), and moderate-severe psoriasis (p= 0.010) compared with non-Hispanic White individuals., Conclusion: In this diverse cohort, 22.6% of patients identified as underrepresented racial and/or ethnic groups, mostly Asian or Hispanic. Despite similar swollen joint counts and medication use, non-white individuals have higher tender joint counts compared with white individuals. Phenotypically, they also were more likely to have radiographic axial involvement. These findings may reflect differences in PsA presentation, experience and outcomes in individuals of various racial and ethnic groups, which need to be taken into consideration in clinical care and research design., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.)

Background: Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized., Objective: To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic., Methods: This prospective cohort analysis evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients., Results: One thousand thirty-nine patients were analyzed (490 GR [47.2%], 65 MBF [6.3%]). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter 2 variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was Tumor necrosis factor-α inhibitor to IL-17 inhibitor use., Limitations: Biologic adherence between visits was not evaluated., Conclusion: Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up., Competing Interests: Conflicts of interest J.Q.J. has received research grant funding from the National Psoriasis Foundation and institutional funding from the University of California, San Francisco. A.C., C.R.T., and R.R.M. are employees of CorEvitas, LLC. E.B.W. has served as an investigator for Pfizer and Target RWE. S.R has served as an advisor for UCB, Novartis, Amgen, Fresenius Kabi, Abbvie, and Janssen. G.H. has received honoraria or research grants from AbbVie, Amgen, Arcutis, Athenex, Bausch Health, Boehringer Ingelheim, Bond Avillion, Bristol Myers Squibb, Celgene Corporation, Dermavant, DermTech, Eli Lilly and Company, EPI Health, Janssen Pharmaceuticals, LEO Pharma, MC2 Therapeutics, Novartis, Ortho Dermatologics, PellePharm, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, SUN Pharmaceutical Industries Ltd, and UCB. J.U.S. has received research grant funding from the National Psoriasis Foundation, Pfizer and Janssen and has served as a consultant for Janssen, Abbvie, Novartis, Sanofi, UCB and BMS. A.W.A. has served as a research investigator and/or scientific advisor to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, Dermavant, Dermira, EPI, Incyte, Janssen, Leo, Lilly, Modmed, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun and UCB. T.B. has received research grant funding from Novartis and Regeneron and is a principal investigator for trials sponsored by Abbvie, Castle, CorEvitas, Dermavant, Galderma, Mindera, and Pfizer. T.B. has served as an advisor for Abbvie, Arcutis, Boehringer-Ingelheim, Bristol Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, Sun, and UCB. W.L. has received research grant funding from Abbvie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and TRex Bio. The remaining authors have nothing to disclose., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Backgroud: Psoriatic arthritis (PsA) is a chronic, inflammatory arthritis that, when left untreated, can lead to erosions, deformities and decrease in quality of life. PsA is known to be associated with multiple comorbidities, including cardiovascular, metabolic and mental health syndromes, all of which can increase its overall morbidity and mortality., Objective: To characterize a cohort of patients with PsA and understand the impact of depression on PsA outcome measures., Methods: 527 consecutive patients with PsA were enrolled in an observational, longitudinal registry that followed them prospectively at standard of care visits. Demographics, medical history, medication use, and clinical exam were all recorded., Results: Depression was reported in 22.8% of the population, anxiety in 18%, and attention deficit hyperactivity disorder in 4%. Depression was more common in female participants (P < .001). At baseline, individuals with PsA and concomitant depression had similar tender and swollen joint counts and RAPID3 compared to those without depression, and had lower body surface area affected by psoriasis (P = .04). At year one, all patients had improvement in clinical outcomes. However, patients with depression had a significantly higher tender joint count compared to those without depression (P = .001), despite similar swollen joint count and body surface area., Conclusion: In patients with depression, there is a discrepancy between improvement in physician assessed measures and patient reported outcomes. These observations underscore the importance of addressing depression and psychological distress as part of PsA treatment outcomes and points towards the need to address residual pain through co-adjuvant approaches., Competing Interests: Declaration of Conflicting Interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RHH has served as a consultant for Janssen and UCB. 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. SR has served as a consultant for AbbVie/Abbott, Amgen, Novartis, Janssen, Pfizer. SA has received grants from Johnson and Johnson. 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.

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.)

Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context and systemic impact remain poorly understood. We thus profiled human psoriasis (PsO) as a prototypic immune-mediated condition with a high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses of 25 healthy, active lesion, and clinically uninvolved skin biopsies and integration with public single-cell transcriptomics data revealed marked differences in immune microniches between healthy and inflamed skin. Tissue-scale cartography further identified core disease features across all active lesions, including the emergence of an inflamed suprabasal epidermal state and the presence of B lymphocytes in lesional skin. Both lesional and distal nonlesional samples were stratified by skin disease severity and not by the presence of systemic disease. This segregation was driven by macrophage-, fibroblast-, and lymphatic-enriched spatial regions with gene signatures associated with metabolic dysfunction. Together, these findings suggest that mild and severe forms of PsO have distinct molecular features and that severe PsO may profoundly alter the cellular and metabolic composition of distal unaffected skin sites. In addition, our study provides a valuable resource for the research community to study spatial gene organization of healthy and inflamed human skin.

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.)

Objectives: Autoantibody seroconversion has been extensively studied in the context of COVID-19 infection but data regarding post-vaccination autoantibody production is lacking. Here we aimed to determine the incidence of common autoantibody formation following mRNA COVID-19 vaccines in patients with inflammatory arthritis (IA) and in healthy controls., Methods: Autoantibody seroconversion was measured by serum ELISA in a longitudinal cohort of IA participants and healthy controls before and after COVID-19 mRNA-based immunization., Results: Overall, there was a significantly lower incidence of ANA seroconversion in participants who did not contract COVID-19 prior to vaccination compared with those who been previously infected (7.4% vs 24.1%, P = 0.014). Incidence of de novo anti-CCP seroconversion in all participants was low at 4.9%. Autoantibody levels were typically of low titre, transient, and not associated with increase in IA flares., Conclusions: In both health and inflammatory arthritis, the risk of autoantibody seroconversion is lower following mRNA-based immunization than following natural SARS-CoV-2 infection. Importantly, seroconversion does not correlate with self-reported IA disease flare risk, further supporting the encouragement of mRNA-based COVID-19 immunization in the IA population., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.)

Case: This case describes a 45-year-old man with documented history of untreated bilateral lower extremity psoriasis of equal severity who sustained a closed left tibial-fibular shaft fracture. After operative fixation with an intramedullary nail under a regional nerve block, the left lower extremity circumferential psoriatic plaque resolved throughout 1 year of follow-up with persistence of the contralateral limb disease., Conclusion: This case describes a rare outcome for a patient with bilateral leg psoriasis who experienced resolution of psoriatic plaques on the operated leg only after surgery. It is unknown which process: injury, anesthetic, surgery, or fracture healing mediated this unique finding., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B960)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Competing Interests: AS, AJE, JPB, and PMI contributed equally to this work. AS, AJE, NF, RMC, JPB, and PMI conceived the study. AS, BB, GHa, and PMI performed the literature search. AS, AJE, BB, GHa, NF, DZ, MM, GHo, JL, PR, C-ET, HMB, RMC, JPB, and PMI performed data collection. AS, AJE, JPB, and PMI created the figures and wrote the original draft. All authors performed interpretation and analysis of data, reviewed or edited the manuscript, approved the final version for publication, and agree to be accountable for all aspects of the work. AS, AJE, and PMI verified the underlying data. AS, AJE, JPB, and PMI had final responsibility for the decision to submit for publication. AS has received consulting fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, and Kezar Life Sciences. RHH has received consulting compensation from Janssen. JUS has served as a consultant for Janssen, Amgen, Pfizer, Sanofi, UCB, Bristol-Myers Squibb, and Abbvie; and has received funding for investigator-initiated studies from Pfizer and Janssen. RMC has received consulting fees from Momenta–Janssen. JPB has received consulting fees and served on data and safety monitoring boards for Momenta–Janssen, Ventus, Equillium, and GlaxoSmithKline. PMI has received consulting fees from GlaxoSmithKline and Momenta–Janssen. All other authors declare no competing interests. Deidentified participant data will be made available upon request by email to the corresponding author. This work was supported by the National Institutes of Health–National Institute of Arthritis and Musculoskeletal and Skin Diseases (P50 AR07059) to JPB and PMI and Bloomberg Philanthropies COVID-19 Response Initiative Grant to JUS and PMI. The funders of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit for publication.

Rheumatoid arthritis is a chronic systemic immune-mediated disease caused by genetic and environmental factors. It is often characterized by the generation of autoantibodies that lead to synovial inflammation and eventual multi-joint destruction. A growing number of studies have shown significant differences in the gut microbiota composition of rheumatoid arthritis (RA) patients compared to healthy controls. Environmental factors, and changes in diet and nutrition are thought to play a role in developing this dysbiosis. This review aims to summarize the current knowledge of intestinal dysbiosis, the role of nutritional factors, and its implications in the pathogenesis of rheumatoid arthritis and autoimmunity. The future direction focuses on developing microbiome manipulation therapeutics for RA disease management.

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.)

Competing Interests: JUS reports consultancy fees from Janssen, Novartis, Pfizer, Sanofi, UCB, AbbVie, and Amgen, and funding for investigator-initiated studies from Pfizer, Sanofi, and Janssen. MJM reports laboratory research and clinical trials contracts with Lilly, Pfizer, and Sanofi, and personal fees for scientific advisory board service from Merck, Meissa Vaccines, and Pfizer. PMI reports consulting fees from GlaxoSmithKline and Momenta/Janssen. RHH reports consulting fees from Janssen. SA reports grant support from Johnson & Johnson. GS reports consulting fees from AbbVie. DPH reports consultancy fees from AbbVie, Bristol Myers Squibb, Janssen, Takeda, UCB, and Pfizer, and reports research support from Janssen and Pfizer. JEA reports consultancy fees from BioFire Diagnostics and Janssen; research grant support from BioFire Diagnostic; and holds US patent 2012/0052124A1. SCh reports consulting fees from AbbVie, Pfizer, and Bristol Myers Squibb. AS reports consulting fees from Lilly, GlaxoSmithKline, AstraZeneca, and Kezar. ALN reports consultancy fees from Janssen, UCB, AbbVie, and Bristol Myers Squibb, and her immediate family member owns shares of stock in Johnson & Johnson, Eli Lilly, AbbVie, and Pfizer. All other authors declare no competing interests. RHH, SU, and JEA contributed equally to this paper. DPH and JUS contributed equally to this paper. All data relevant to the study are included in the article or uploaded as supplementary information. Further de-identified data can be made available upon request via email to the corresponding author. This study was funded by US National Institutes of Health (NIH)–National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR074500 to Scher, T32-AR-069515 to RHH and JUS), NIH–National Institute of Diabetes and Digestive and Kidney Diseases (K23DK124570 to JEA), NIH–National Institute of Allergy and Infectious Diseases (AI082630 and AI158617 to SH), Rheumatology Research Foundation (Scientist Development Award to RHH), Bloomberg Philanthropies, Pfizer COVID-19 Competitive Grant Program, The Beatrice Snyder Foundation, The Riley Family Foundation, Crohn's and Colitis Foundation (to JEA), and the Judith and Stewart Colton Center for Autoimmunity (to JEA). No authors are employed by the NIH. We are grateful to our patients and their families for participating in this study and to our colleagues who referred patients to use. We thank Luz Alvarado, Rhina Medina, Parvathi Girija, and Jyoti Patel for coordinating and for data entry efforts.

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of mature T-cell neoplasms characterized by the accumulation of clonal malignant CD4+ T cells in the skin. The most common variant of CTCL, mycosis fungoides (MF ), is confined to the skin in early stages but can be accompanied by extracutaneous dissemination of malignant T cells to the blood and lymph nodes in advanced stages of disease. Sézary syndrome (SS), a leukemic form of disease, is characterized by significant blood involvement. Little is known about the transcriptional and genomic relationship between skin- and blood-residing malignant T cells in CTCL. To identify and interrogate malignant clones in matched skin and blood from patients with leukemic MF and SS, we combine T-cell receptor clonotyping with quantification of gene expression and cell surface markers at the single cell level. Our data reveal clonal evolution at a transcriptional and genetic level within the malignant populations of individual patients. We highlight highly consistent transcriptional signatures delineating skin- and blood-derived malignant T cells. Analysis of these 2 populations suggests that environmental cues, along with genetic aberrations, contribute to transcriptional profiles of malignant T cells. Our findings indicate that the skin microenvironment in CTCL promotes a transcriptional response supporting rapid malignant expansion, as opposed to the quiescent state observed in the blood, potentially influencing efficacy of therapies. These results provide insight into tissue-specific characteristics of cancerous cells and underscore the need to address the patients' individual malignant profiles at the time of therapy to eliminate all subclones., (© 2021 by The American Society of Hematology.)

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.)

Objective: To update guidance regarding the management of psoriatic disease during the COVID-19 pandemic., Study Design: The task force (TF) includes 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation staff. Clinical questions relevant to the psoriatic disease community were informed by inquiries received by the National Psoriasis Foundation. A Delphi process was conducted., Results: The TF updated evidence for the original 22 statements and added 5 new recommendations. The average of the votes was within the category of agreement for all statements, 13 with high consensus and 14 with moderate consensus., Limitations: The evidence behind many guidance statements is variable in quality and/or quantity., Conclusions: These statements provide guidance for the treatment of patients with psoriatic disease on topics including how the disease and its treatments affect COVID-19 risk, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 (including novel vaccination), and what they should do if they develop COVID-19. The guidance is a living document that is continuously updated by the TF as data emerge., Competing Interests: Conflicts of interest Dr Gelfand has served as a consultant for Bristol Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Janssen Biologics, Novartis Corp, Regeneron, UCB (Data Safety and Monitoring Board), Sanofi, and Pfizer, receiving honoraria; has received research grants (to the Trustees of the University of Pennsylvania) from AbbVie, Janssen, Novartis Corp, Sanofi, Celgene, OrthoDermatologics, and Pfizer; has received payment for continuing medical education work related to psoriasis that was supported indirectly by Eli Lilly and Company and Ortho Dermatologics; is a copatent holder of resiquimod for treatment of cutaneous T-cell lymphoma; and is a deputy editor for the Journal of Investigative Dermatology, receiving honoraria from the Society for Investigative Dermatology. Dr Armstrong has served as a research investigator and/or scientific advisor to Leo, AbbVie, UCB, Incyte, Janssen, Lilly, Novartis, Ortho Dermatologics, Sun, Dermavant, Bristol Myers Squibb, Sanofi, Regeneron, Dermira, and Modmed. Dr Bell is an employee of the National Psoriasis Foundation. Dr Anesi is supported by the Agency for Healthcare Research and Quality (K12HS026372) and has received fees from UpToDate for authoring COVID-19 clinical reference material. Dr Blauvelt has served as a scientific advisor and/or clinical study investigator for AbbVie, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB Pharma. Dr Calabrese is a speaker for Sanofi-Regeneron and consultant for AbbVie. Dr Feldman has received research, speaking, and/or consulting support from Galderma, GlaxoSmithKline/Stiefel, Almirall, Alvotech, Leo Pharma, Bristol Myers Squibb, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Ortho Dermatology, AbbVie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate, and National Psoriasis Foundation; has consulted for others through Guidepoint Global, Gerson Lehrman, and other consulting organizations; is the founder and majority owner of www.DrScore.com; and is a founder and part owner of Causa Research, a company dedicated to enhancing patients' adherence to treatment. Dr Gladman is a consultant for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, and UCB and has received grants from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Dr Kircik has served either as an investigator, consultant, or speaker for AbbVie, Almirall, Amgen, Arcutis, Bausch Health Canada, Bristol Myers Squibb, Boehringer Ingelheim, Cellceutix, Celgene, Coherus, Dermavant, Dermira, Eli Lilly, Leo, MC2, Maruho, Novartis, Ortho Dermatologics, Pfizer, Dr Reddy's Laboratories, Sun Pharma, UCB, Taro, and Xenoport. Dr Lebwohl is an employee of Mount Sinai; receives research funds from AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen Research and Development, Leo Pharmaceuticals, Ortho Dermatologics, Pfizer, and UCB; and is a consultant for Aditum Bio, Allergan, Almirall, Arcutis, Avotres Therapeutics, BirchBioMed, BMD Skincare, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr Reddy's Laboratories, Serono, Theravance, and Verrica. Dr Martin is a consultant for Almirall, Athenex, Bristol Meyers Squibb, Celgene, Eli Lilly, LEO, Ortho Dermatologic, Pfizer, and UCB and a scientific advisor for Almirall, Athenex, Bristol Meyers Squibb, Celgene, Eli Lilly, Janssen, LEO, Ortho Dermatologic, Pfizer, and UCB. Dr Merola is a consultant and/or investigator for Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Sun Pharma, Pfizer, and EMD Serono. Dr Scher is a consultant for UCB, Janssen, AbbVie, Pfizer, Novartis, Bristol Myers Squibb, and Sanofi and is supported in part by the Riley Family Foundation and the Beatrice Snyder Foundation. Dr Schwartzman is a speaker for AbbVie, Genentech, Janssen, Lilly, Novartis, Pfizer, and UCB; owns stock in Amgen, Boston Scientific, Gilead, Medtronic, and Pfizer; is a consultant for AbbVie, Myriad, Janssen, Gilead, Lilly, Novartis, and UCB; is a scientific advisory board member for Myriad; and is a board member of the National Psoriasis Foundation. Dr Van Voorhees has been an investigator for Celgene, Lilly, and AbbVie and an advisor/consultant for AbbVie, Allergan, AstraZeneca, Celgene, Dermira, Merck, Novartis, Pfizer, UCB, and Valeant. Dr Syed is supported by a grant from Pfizer. Authors Gondo, Heydon, and Koons are employees of the National Psoriasis Foundation. Dr Ritchlin reports personal fees from AbbVie, Amgen, Janssen, Novartis, UCB, and Boehringer Ingelheim, as well as grants from Amgen, UCB, and AbbVie outside the submitted work. Drs Dommasch, Lo Re, Treat, Ellebrecht, Fenner, Ocon, and Weinstein have no conflicts of interest to declare., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Psoriasis is associated with increased cardiovascular risk that is not captured by traditional proinflammatory biomarkers., Objective: To investigate the relationship between Psoriasis Area and Severity Index, circulating proinflammatory biomarkers, and vascular health in psoriasis., Methods: In patients with psoriasis and in age and sex-matched controls, 273 proteins were analyzed with the Proseek Multiplex Cardiovascular disease reagents kit and Inflammatory reagents kit (Olink Bioscience), whereas vascular endothelial inflammation and health were measured via direct transcriptomic analysis of brachial vein endothelial cells., Results: In psoriasis, chemokine ligand 20 (CCL20), interleukin (IL) 6, and IL-17A were the top 3 circulating proinflammatory cytokines. Vascular endothelial inflammation correlated with CCL20 (r = 0.55; P < .001) and less so with IL-6 (r = 0.36; P = .04) and IL-17A (r = 0.29; P = .12). After adjustment for potential confounders, the association between CCL20 and vascular endothelial inflammation remained significant (β = 1.71; P = .02). In nested models, CCL20 added value (χ 2  = 79.22; P < .001) to a model already incorporating the Psoriasis Area and Severity Index, Framingham risk, high-sensitivity C-reactive protein, Il-17A, and IL-6 (χ 2  = 48.18; P < .001) in predicting vascular endothelial inflammation., Limitations: Our study was observational and did not allow for causal inference in the relationship between CCL20 and cardiovascular risk., Conclusion: We demonstrate that CCL20 expression has a strong association with vascular endothelial inflammation, reflects systemic inflammation, and may serve as a potential biomarker of impaired vascular health in psoriasis., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

We engineered a machine learning approach, MSHub, to enable auto-deconvolution of gas chromatography-mass spectrometry (GC-MS) data. We then designed workflows to enable the community to store, process, share, annotate, compare and perform molecular networking of GC-MS data within the Global Natural Product Social (GNPS) Molecular Networking analysis platform. MSHub/GNPS performs auto-deconvolution of compound fragmentation patterns via unsupervised non-negative matrix factorization and quantifies the reproducibility of fragmentation patterns across samples.

Enormous progress has been made in the field of rheumatology in the past several decades, historically led by publicly funded academic innovators but in more recent times with much greater involvement of the pharmaceutical industry. This shift in resources has created a complex new model for reinvestment in the medical community in which the vast majority of private funds are redirected towards influencing the prescription behaviour of practitioners through 'key opinion leaders', with the main purpose of enhancing and perpetuating profit rather than innovation and critical thinking, and often at the expense of partnerships with scientists (that is, basic and translational researchers) and academic collaborations. This new episteme brings multiple opportunities to rethink approaches to sustaining long-term critical research in the field, ultimately maximizing the return on investment: scientific knowledge for the benefit of patients and society. Central to such strategies should be the rebalancing of academia-industry partnerships towards academic research and the involvement of 'innovation and knowledge leaders', rather than mostly key opinion leaders.

Objective: To provide guidance about management of psoriatic disease during the coronavirus disease 2019 (COVID-19) pandemic., Study Design: A task force (TF) of 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care was convened. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation (NPF) staff. Clinical questions relevant to the psoriatic disease community were informed by questions received by the NPF. A Delphi process was conducted., Results: The TF approved 22 guidance statements. The average of the votes was within the category of agreement for all statements. All guidance statements proposed were recommended, 9 with high consensus and 13 with moderate consensus., Limitations: The evidence behind many guidance statements is limited in quality., Conclusion: These statements provide guidance for the management of patients with psoriatic disease on topics ranging from how the disease and its treatments impact COVID-19 risk and outcome, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 and what they should do if they develop COVID-19. The guidance is intended to be a living document that will be updated by the TF as data emerge., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Patients with psoriasis have impaired vascular health and increased cardiovascular disease (CVD). Platelets are key players in the pathogenesis of vascular dysfunction in cardiovascular disease and represent therapeutic targets in cardiovascular prevention. The object of this study was to define the platelet phenotype and effector cell properties on vascular health in psoriasis and evaluate whether aspirin modulates the platelet-induced phenotype. Approach and Results: Platelets from psoriasis patients (n=45) exhibited increased platelet activation (relative to age- and gender-matched controls, n=18), which correlated with psoriasis skin severity. Isolated platelets from psoriasis patients demonstrated a 2- to 3-fold ( P <0.01) increased adhesion to human aortic endothelial cells and induced proinflammatory transcriptional changes, including upregulation of IL 8 (interleukin 8), IL1β , and Cox (cyclooxygenase)-2 Platelet RNA sequencing revealed an interferon signature and elevated expression of COX-1 , which correlated with psoriasis disease severity ( r =0.83, P =0.01). In a randomized trial of patients with psoriasis, 2 weeks of 81 mg low-dose aspirin, a COX-1 inhibitor, reduced serum thromboxane (Tx) B 2 and reduced brachial vein endothelial proinflammatory transcript expression >70% compared with the no-treatment group ( P <0.01). Improvement in brachial vein endothelial cell inflammation significantly correlated with change in serum TxB 2 ( r =0.48, P =0.02)., Conclusions: In patients with psoriasis, platelets are activated and induce endothelial cell inflammation. Low-dose aspirin improved endothelial cell health in psoriasis via platelet COX-1 inhibition. These data demonstrate a previously unappreciated role of platelets in psoriasis and endothelial cell inflammation and suggests that aspirin may be effective in improving vascular health in patients with psoriasis. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03228017.

In the past three decades, extraordinary advances have been made in the understanding of the pathogenesis of, and treatment options for, inflammatory arthritides, including rheumatoid arthritis and spondyloarthritis. The use of methotrexate and subsequently biologic therapies (such as TNF inhibitors, among others) and oral small molecules have substantially improved clinical outcomes for many patients with inflammatory arthritis; for others, however, these agents do not substantially improve their symptoms. The emerging field of pharmacomicrobiomics, which investigates the effect of variations within the human gut microbiome on drugs, has already provided important insights into these therapeutics. Pharmacomicrobiomic studies have demonstrated that human gut microorganisms and their enzymatic products can affect the bioavailability, clinical efficacy and toxicity of a wide array of drugs through direct and indirect mechanisms. This discipline promises to facilitate the advent of microbiome-based precision medicine approaches in inflammatory arthritis, including strategies for predicting response to treatment and for modulating the microbiome to improve response to therapy or reduce drug toxicity.

Background: Chronic inflammatory diseases (CIDs; ankylosing spondylitis [AS], psoriatic arthritis [PsA], psoriasis [PsO], or rheumatoid arthritis [RA]) and inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) are associated with substantial economic burden. The relative increased costs among patients with CIDs and concomitant IBD compared to those without IBD is an important consideration when deciding on the clinical management of patient symptoms. Given the increasing use of novel agents for the treatment of CIDs, including those that may increase the risk of IBD in patients with CIDs, the objective of the study was to describe the incidence of IBD and to quantify healthcare resource utilization (HRU) and costs associated with IBD among patients with CIDs., Methods: The IBM MarketScan® Research Databases (1/2010-7/2017) were used to identify adult patients with ≥2 claims with a diagnosis of either AS/PsA/PsO/RA (index date was a random claim for AS/PsA/PsO/RA). The one-year incidence rate of IBD was calculated following the index date. HRU and healthcare costs were compared between patients developing and not developing IBD in the year following the index date, adjusting for baseline characteristics., Results: A total of 537,450 patients with CIDs (mean age = 54.0 years; 63.1% female) were included in the study. The 1-year incidence rate of IBD was 0.52% (range = 0.39% in patients with PsO but without PsA to 1.73% in patients with AS). Patients who developed IBD ( N  = 2778) had significantly higher rates of inpatient, outpatient, and emergency room visits (incidence rate ratios [IRR] = 2.91, 1.35, 1.81; all P  < 0.0001), compared to patients without IBD ( N  = 534,672). Patients who developed IBD had $18,500 ( P  < 0.0001) higher total costs per year, including $15,121 ( P  < 0.0001) higher medical costs and $3380 higher pharmacy costs ( P  < 0.0001)., Conclusion: Higher HRU and costs were observed in patients with concomitant CID and IBD compared to patients with CID alone. Consideration should be given to treatment decisions that adequately manage CID and IBD to ensure optimal clinical and economic outcomes., Competing Interests: Competing interestsBE and PL are employees of Analysis Group, Inc., a consulting company which provided paid consulting services to Janssen Scientific Affairs, LLC for the conduct of this study. SDC, LAE, and KS are employees of Janssen Scientific Affairs, LLC and shareholders of Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly-owned subsidiary. DPH reports the following affiliations: Janssen (consulting), Takeda (consulting), AbbVie (consulting), Salix (consulting), and Pfizer (consulting and research support). JUS reports the following affiliations: Janssen (consulting), UCB (consulting), Novartis (consulting and research support), Amgen (consulting and research support [via NIH Target]), and Pfizer (research support)., (© The Author(s) 2020.)

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.)

Objective: In these studies, we examined the association of single nucleotide polymorphisms (SNPs) of the IL1RN gene with radiographic severity of symptomatic knee osteoarthritis (SKOA) and the risk of incident OA. We also explored these genetic polymorphisms in patients with new onset rheumatoid arthritis (RA)., Methods: Over 1000 subjects who met American College of Rheumatology criteria for tibiofemoral OA were selected from three independent, National Institute of Health (NIH)-funded cohorts. CTA and TTG haplotypes formed from three SNPs of the IL1RN gene (rs419598, rs315952, rs9005) were assessed for association with radiographic severity, and risk for incident radiographic OA (rOA) in a nested case-control cohort. These IL1RN haplotypes were also assessed for association with disease activity (DAS28) and plasma inflammatory markers in patients with RA., Results: Carriage of the IL1RN TTG haplotype was associated with increased odds of more severe rOA compared with age-matched, sex-matched and body mass index-matched individuals. Examination of the osteoarthritis initiative Incidence Subcohort demonstrated that carriage of the TTG haplotype was associated with 4.1-fold (p=0.001) increased odds of incident rOA. Plasma IL-1Ra levels were lower in TTG carriers, while chondrocytes from TTG carriers exhibited decreased secretion of IL-1Ra. In patients with RA, the TTG haplotype was associated with increased DAS28, decreased plasma IL-1Ra and elevations of plasma inflammatory markers (hsCRP, interleukin 6 (IL-6))., Conclusion: Carriage of the IL1RN TTG haplotype is associated with more severe rOA, increased risk for incident OA, and increased evidence of inflammation in RA. These data suggest that the IL1RN TTG risk haplotype, associated with decreased IL-1Ra plasma levels, impairs endogenous 'anti-inflammatory' mechanisms., Competing Interests: Competing interests: MA and SBA have one provisional patent application and another approved patent for the use of inflammatory and genetic biomarkers in predicting at-risk knee OA patients., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

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.