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Traditional NSAIDs and some selective cyclooxygenase (COX)-2 inhibitors used to treat patients with osteoarthritis (OA) have adverse effects. However, traditional NSAIDs remain first-line therapy for some patients. The toxicities (eg, renal and GI effects) mostly are the result of COX inhibition. Earlier, it was suggested that the ideal NSAID would inhibit COX-2 while sparing COX-1. The mechanisms for increased COX-2 cardiovascular toxicity remain less than fully understood. The recent accumulation of knowledge about NSAIDs probably will yield valuable insights in the next few years. Several conservative strategies may help primary care physicians use these agents effectively and safely. OA therapies under investigation (eg, inhibition of prostaglandin E syntheses and disease-modifying osteoarthritis drugs) may render NSAIDs and COX-2 inhibitors obsolete. [ABSTRACT FROM AUTHOR]

NSAIDs have been a mainstay of treatment for patients with osteoarthritis (OA), but toxicity may be a problem and cyclooxygenase-2 inhibitors may increase cardiovascular risk. Current OA treatments combine several approaches to alleviate symptoms. Patient education and physical and occupational therapy are valuable components. Support appliances help stabilize joints and improve function. Weight loss is recommended in patients who have a high body mass index. Studies of complementary and alternative medicine therapies are inconclusive. Surgery may be indicated. Acetaminophen is considered first-line pharmacologic therapy for mild to moderate OA. Opioid analgesics are useful in patients with moderate to moderately severe pain. Intra-articular corticosteroids can relieve pain and reduce effusions. Topical NSAIDs and capsaicin may reduce OA-related pain. [ABSTRACT FROM AUTHOR]

Objectives: To identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting., Methods: In the multicentre PsA Research Consortium (PARC) study, we applied factor analysis of mixed data to reduce dimensionality and collinearity, followed by hierarchical clustering on principal components. We then evaluated the transition of PsA clusters and their response to new immunomodulatory therapy and tumour necrosis factor inhibitor (TNFi)., Results: Among 627 patients with PsA, three clusters were identified: mild PsA and psoriasis only (PsO) (Cluster 1, 47.4%), severe PsA and mild PsO (Cluster 2, 34.3%) and severe PsA and severe PsO (Cluster 3, 18.3%). Among 339 patients starting or changing, significant differences in response were observed (mean follow-up of 0.7 years, SD 0.8), with Cluster 3 showing the largest improvements in cDAPSA and PsAID. No differences were found among those starting TNFi (n=218). cDAPSA remission and PsAID patient acceptable symptom state were achieved in 10% and 54%, respectively. Clusters remained stable over time despite treatment changes, though some transitions occurred, notably from Cluster 3 to milder clusters., Conclusion: Data-driven clusters with distinct therapy responses identified in this real-world study highlight the extensive heterogeneity in PsA and the central role of psoriasis and musculoskeletal severity in treatment outcomes. Concurrently, these findings underscore the need for better outcome measures, particularly for individuals with lower disease activity., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RBB has no conflicts to declare. RRN has no conflicts to declare. JUS has served as a consultant for Janssen, Novartis, Pfizer, Sanofi, Amgen, UCB, BMS, and AbbVie; and has received funding for investigator-initiated studies from Janssen and Pfizer.

Objective: Individuals of racially and ethnically diverse backgrounds are underrepresented in 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: A total of 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 analysed., 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 (Routine Assessment of Patient Index Data 3) 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.)

The increasing prevalence of autoimmune and immune-mediated diseases (AIMDs) underscores the need to understand environmental factors that contribute to their pathogenesis, with the microbiome emerging as a key player. Despite significant advancements in understanding how the microbiome influences physiological and inflammatory responses, translating these findings into clinical practice remains challenging. This viewpoint reviews the progress and obstacles in microbiome research related to AIMDs, examining molecular techniques that enhance our understanding of microbial contributions to disease. We discuss significant discoveries linking specific taxa and metabolites to diseases such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis, highlighting the role of gut dysbiosis and host-microbiome interactions. Furthermore, we explore the potential of microbiome-based therapeutics, including faecal microbiota transplantation and pharmacomicrobiomics, while addressing the challenges of identifying robust microbial targets. We advocate for integrative, transdisease studies and emphasise the need for diverse cohort research to generalise findings across populations. Understanding the microbiome's role in AIMDs will pave the way for personalised medicine and innovative therapeutic strategies., (Copyright © 2024 European Alliance of Associations for Rheumatology (EULAR). Published by Elsevier B.V. All rights reserved.)

Background: Although genetic factors have been identified in the pathogenesis of rheumatoid arthritis (RA), the concordance rate in monozygotic (MZ) twins is low, suggesting that other features contribute to disease development. Further, the relative contribution of such non-genetic elements in identical twins have not been characterized. Here, we aimed to measure differentiating host and microbial biomarkers of RA by studying MZ twins discordant for disease using a multi-omics approach., Methods: Eight pairs of MZ twins discordant for RA (n=16) were enrolled. Gut microbiome was assessed using shotgun metagenomic sequencing. Autoantibodies, cytokines, and other plasma proteins were measured in both plasma and feces. Levels of short and medium-chain fatty acids from serum and feces were quantified using gas chromatography mass spectrometry (GC-MS)., Results: While overall microbiome diversity and composition did not significantly differ between twins, we observed a decrease in Blautia faecis in affected twins. Affected twins had higher concentrations of both fecal and plasma citrullinated and non-citrullinated autoantibodies, as well as significantly lower concentrations of fecal butyrate and propionate., Conclusion: Multi-omics biomarkers differentiate MZ twins discordant for RA. Blautia faecis , which is associated with reduced inflammatory cytokine expression, was decreased in RA twins. Similarly, short-chain fatty acids, known to have immune modulatory effects, were decreased in affected twins, suggesting further bi-directional interactions between inflammation at the gut barrier and disease state. If confirmed in other cohorts, exhaustive multi-omics approaches may improve our understanding of RA pathogenesis and potentially contribute to novel diagnostics and co-adjuvant therapies., Competing Interests: Competing interests: RBB, KB, WC, IC, AH, RH, RRN, JH, AC, JL, JS, LL, CU, JCC, have no conflicts to declare. JUS has served as a consultant for Janssen, Novartis, Pfizer, Sanofi, Amgen, UCB, BMS, and AbbVie; and has received funding for investigator-initiated studies from Janssen and Pfizer.

Psoriasis is a chronic inflammatory skin disease that often precedes the development of psoriatic arthritis. Advances over the past 10 years have deepened our understanding of the transition from skin inflammation to joint inflammation, revealing various phases during which genetic, environmental, and immunological factors can affect this transition. In 2023, a European Alliance of Associations for Rheumatology task force outlined key considerations for identifying individuals with subclinical disease from those with clinically stabilised disease. Discerning between subclinical psoriatic arthritis and very early disease is crucial and raises doubts and questions about when an individual transitions from being at risk to having established psoriatic arthritis. Labelling this stage as very early psoriatic arthritis rather than subclinical disease might have substantial clinical and therapeutic implications. This Viewpoint highlights the importance of precisely identifying the different stages of progression of psoriatic arthritis for timely interventions and better outcomes for patients., Competing Interests: Declaration of interests FC reports consulting fees from Eli Lilly, AbbVie, Novartis, and Janssen; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Eli Lilly, AbbVie, Alfasigma, Fresenius, GSK, Bristol Myers Squibb, Pfizer, Galapagos, UCB, and Janssen. SG reports consulting fees from Janssen and Boehringer Ingelheim; and support for attending meetings or travel from AbbVie, Novartis, and Pfizer. RC reports consulting fees from AbbVie, Alfasigma, and Eli Lilly; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Alfasigma, Eli Lilly, Pfizer, UCB, Fresenius, Galapagos, and Janssen; and participation on a data safety monitoring board or advisory board for Alfasigma and Galapagos. JUS reports consulting fees from Bristol Myers Squibb, Janssen, and UCB; and leadership or fiduciary roles in other board, society, committee, or advocacy groups, paid or unpaid, from the US National Psoriasis Foundation., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

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.)

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., Competing Interests: Declaration of interests I. Subudhi, P.K., and S.N. have filed a provisional patent for HIF1α inhibition in inflammatory skin diseases (U.S. serial number 63/540,794, filed September 27, 2023). N.A. is a consultant for Immunitas, 23 and me, Cellino Pharmaceuticals, and Janssen and serves on the SAB of Shennon Bio. S.N. is on the SAB of Seed Inc., is a consultant for BiomX, and receives funding from Takeda Pharmaceuticals. This activity is not relevant to the content of this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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: 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.)

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.

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

Objective: 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: None declared.

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.)

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.)

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.

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.)

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.)

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.)

Objective: To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multiethnic/multiracial cohort of patients with systemic lupus erythematosus (SLE)., Methods: Ninety SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; interferon-γ (IFNγ) production was measured by enzyme-linked immunospot (ELISpot) assay in order to assess T cell responses. Disease activity was measured by the hybrid SLE Disease Activity Index (SLEDAI), and flares were identified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index., Results: Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD compared to fully vaccinated controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-double-stranded DNA antibody level prior to vaccination were associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and correlated with antigen-specific IFNγ production determined by ELISpot. In a subset of patients with poor antibody responses, IFNγ production was similarly diminished. Pre- and postvaccination SLEDAI scores were similar in both groups. Postvaccination flares occurred in 11.4% of patients; 1.3% of these were severe., Conclusion: In a multiethnic/multiracial study of SLE patients, 29% had a low response to the COVID-19 vaccine which was associated with receiving immunosuppressive therapy. Reassuringly, severe disease flares were rare. While minimal protective levels remain unknown, these data suggest that protocol development is needed to assess the efficacy of booster vaccination., (© 2021, American College of Rheumatology.)

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.)

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.)

Objective: To investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment., Methods: Established patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response., Results: Although healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination., Conclusions: In two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines., Competing Interests: Competing interests: JUS declares that he has served as a consultant for Janssen, Novartis, Pfizer, Sanofi, UCB and Abbvie and has received funding for investigator-initiated studies from Novartis, Sanofi and Janssen. GS has served as a consultant for Abbvie, BMS, Eli Lilly, Gilead, GSK Novartis, Janssen and Roche and has received funding for investigator-initiated studies from BMS, Eli Lilly, GSK, Novartis and UCB. MM declares grants from Eli Lilly, Pfizer and Sanofi and personal fees from Meissa Vaccines. PI has received consulting fees from GSK. RHH has received consulting from Janssen. SA reports grant support from Johnson and Johnson. GS declares consulting fees from AbbVie., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)