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    Improving Imaging Modalities in Early Psoriatic Arthritis: The Role of Ultrasound in Early Diagnosis of Psoriatic Arthritis. Gudu Tania,Ng Beverly,Jethwa Hannah,Graham Catherine,Kudva Veda,Rammanohar Jashmitha,Zhang Chen,Sapsford Mark,Jadon Deepak R Frontiers in medicine Despite recent advances, early diagnosis of psoriatic arthritis (PsA) remains a challenge in clinical practice. Ultrasound (US) could be a useful tool for the diagnosis and management of PsA. The objective of this review was to determine the role of US in early diagnosis of PsA. We have performed a literature review aiming to evaluate studies on US findings in psoriasis and their predictive value of progression to PsA, as well as studies on US features specific for PsA in comparison with other conditions. A total of 40 studies were included. Sixteen studies assessed US findings in psoriasis, of which only 3 prospectively evaluated the role of US in predicting progression to PsA. Patients with PsA had a greater frequency of US abnormalities, in particular enthesitis and Power Doppler(PD) signal compared to patients with psoriasis only. In the longitudinal studies, psoriatic patients with higher enthesopathy scores at baseline were more likely to progress to PsA. Twenty-four studies evaluated US abnormalities in PsA and compared them to other conditions. Most specific US features that distinguish PsA from psoriasis were PD signal and erosions in joints and entheses. Extra-synovial changes, including peri-tendinous dermal soft tissue oedema with associated PD signal and flexor tendon enthesopathy, as well as thickening of the pulleys in the flexor tendons were highly characteristic for PsA, as they were frequently found in PsA patients, but in none of the RA patients. US-detected entheseal abnormalities in particular erosions and PD signal were more frequent in patients with PsA compared to fibromyalgia. Despite the wide use of US in PsA, more research is needed to identify predictive factors of progression to PsA in patients with psoriasis, as well as to determine most specific US features that differentiate PsA from other conditions. 10.3389/fmed.2021.804695
    Characterising axial psoriatic arthritis: correlation between whole spine MRI abnormalities and clinical, laboratory and radiographic findings. Diaz Pamela,Feld Joy,Eshed Iris,Eder Lihi RMD open OBJECTIVE:To describe the prevalence of inflammatory and structural lesions using whole spine MRI in patients with psoriatic disease, and to assess their correlation with clinical features and with axial spondyloarthritis (axSpA) classification criteria. METHODS:This retrospective analysis included patients with whole spine and sacroiliac joints (SIJ) MRI, selected from 2 populations: (1) active psoriatic arthritis (PsA), irrespective of axial symptoms; (2) psoriasis with confirmed or suspected PsA and axSpA symptoms. MRI spondylitis and/or sacroiliitis (MRI-SpA) was defined according to Assessment of Spondyloarthritis International Society (ASAS) consensus and by radiologist impression. Agreement between MRI-SpA and different inflammatory back pain (IBP) definitions (Berlin/ASAS/rheumatologist criteria) and the axSpA classification criteria were calculated considering MRI as gold standard. Logistic regression determined MRI-SpA-associated factors. RESULTS:93 patients were analysed (69.9% PsA; 30.1% psoriasis). Back pain was present in 81.7%, defined as IBP in 36.6%-57%. MRI-SpA was found in 9.7% of patients by ASAS definition and in 12.9% by radiologist impression, of which 25% had isolated spondylitis.Low agreement was found between the three IBP definitions and MRI-SpA. Rheumatologist criteria was the most sensitive (50%-55.6%) while ASAS and Berlin criteria were the most specific (61.9%-63%). axSpA criteria had poor sensitivity for MRI-SpA (22.2%-25%). Late onset of back pain or asymptomatic patients accounted for most cases with MRI-SpA not meeting axSpA or IBP criteria. Male sex was associated with MRI-SpA (OR 6.91; 95% CI 1.42 to 33.59) in multivariable regression analysis. CONCLUSION:Prevalence of MRI-defined axSpA was low and showed poor agreement with IBP and axSpA criteria. 10.1136/rmdopen-2021-002011
    The incidence and risk factors for venous thromboembolic events in patients with psoriasis and psoriatic arthritis. Damian Andreea C,Colaco Keith,Rohekar Sherry,Boyd Tristan,Chandran Vinod,Gladman Dafna D,Cook Richard,Eder Lihi Seminars in arthritis and rheumatism 10.1016/j.semarthrit.2022.151950
    Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. Smerilli Gianluca,Cipolletta Edoardo,Destro Castaniti Giulia Maria,Di Matteo Andrea,Di Carlo Marco,Moscioni Erica,Francioso Francesca,Mashadi Mirza Riccardo,Grassi Walter,Filippucci Emilio The Journal of rheumatology OBJECTIVE:To explore the association of the OMERACT ultrasound (US) entheseal abnormalities with the presence of US joint bone erosions in psoriatic arthritis (PsA). METHODS:Consecutive PsA patients were included in this cross-sectional study. Demographic and clinical parameters were collected. A bilateral US assessment was carried out at the following entheses: plantar fascia, quadriceps, patellar (proximal and distal) and Achilles tendons. The following US entheseal abnormalities were registered: hypoechogenicity, thickening, Doppler signal <2mm from the bony cortex, calcification/enthesophyte, bone erosion. The presence of US joint bone erosions was investigated at the 2nd and 5th metacarpophalangeal (MCP) joints, ulnar head and 5th metatarsophalangeal (MTP) joint, bilaterally, as well as at the level of the most inflamed joint on physical examination. Multiple linear regression analysis was performed to identify clinical and/or US variables associated with US-detected joint bone erosions. RESULTS:A total of 104 PsA patients were enrolled. At least one joint bone erosion was found in 47/104 patients (45.2%). Bone erosions were most frequently detected at 5th MTP joint level (42/208 joints, 20.2 %; 32/104 patients, 30.8%). In the multivariate model, only PD signal at the enthesis (P<0.001, standardized β=0.51), bone erosions at the enthesis (P=0.02, standardized β=0.2), PsA disease duration (P=0.04, standardized β=0.17) and greyscale joint synovitis (P=0.03, standardized β=0.42) were associated with US-detected joint bone erosions. CONCLUSION:PD signal and bone erosions at the enthesis represent sonographic biomarkers of a more severe subset of PsA in terms of US-detected joint erosive damage. 10.3899/jrheum.210974
    Cardiovascular Diseases in the Patients With Psoriatic Arthritis. Akhlaq Anum,Ali Huma Fatima,Sheikh Abu Baker,Muhammad Hafiz,Ijaz Sardar Hassan,Sattar Muhammad Hassaan,Nazir Salik,Ud Din Mian Tanveer,Nasir Usama,Khan Muhammad Zia,Muslim Muhammad Osama,Wazir Muhammad Hisham Khan,Dani Sourbha S,Fudim Marat,Minhas Abdul Mannan Khan Current problems in cardiology There are limited data regarding the burden and trend of cardiovascular diseases (CVD) in psoriatic arthritis (PsA). We analyzed the National Inpatient Sample database from January 2005 to December 2018 to examine the hospitalization trends amongst adults with PsA primarily for heart failure (HF), acute myocardial infarction (AMI), and stroke. The primary outcomes of interest included in-hospital mortality, length of stay (LOS), and inflation-adjusted cost. The age-adjusted percentage of HF hospitalizations among PsA patients decreased from 2.5% (2005/06) to 1.4% (2011/12; P-trend 0.013) and subsequently increased to 2.0% (2017/18; P-trend 0.044). The age-adjusted percentage of AMI hospitalizations among PsA patients showed a non-statistically significant decreasing trend from 2.1% (2005/06) to 1.7% (2011/12; P-trend 0.248) and showed a non-statistically significant increase to 2.3% (2017/18; P-trend 0.056). The age-adjusted stroke hospitalizations increased from 1.1% (2005/06) to 1.3% (2017/18; P-trend 0.036). Apart from a decrease in adjusted inflation-adjusted cost among heart failure hospitalizations, there was no significant change in inpatient mortality, length of stay or hospital cost, during the study period. We found an increasing trend of cardiovascular hospitalizations in patients with PsA. These findings will raise awareness and inform further research and clinical practice for PSA patients with CVD. 10.1016/j.cpcardiol.2022.101131
    Implementation of the OMERACT Psoriatic Arthritis Magnetic Resonance Imaging Scoring System in a randomized phase IIb study of abatacept in psoriatic arthritis. Østergaard Mikkel,Bird Paul,Pachai Chahin,Du Shuyan,Wu Chun,Landis Jessica,Fuerst Thomas,Ahmad Harris A,Connolly Sean E,Conaghan Philip G Rheumatology (Oxford, England) OBJECTIVES:Investigate if the OMERACT Psoriatic Arthritis MRI Scoring System (PsAMRIS), including a novel total inflammation score, shows sensitivity to change with an agent (abatacept) known to impact clinical outcomes in PsA. METHODS:Post hoc analysis of randomized phase IIb study of abatacept in patients with PsA and inadequate DMARD response. Participants received one of three abatacept dosing regimens (ABA3, ABA10 or ABA30/10 mg/kg [30 mg/kg switched to 10 mg/kg after two doses]) or placebo until day (D)169, then ABA10 through D365. MRIs at baseline, D85, D169 and D365 were centrally evaluated by two readers blinded to chronological order and treatment arm. Synovitis, osteitis, tenosynovitis, periarticular inflammation, bone erosions, joint space narrowing and bone proliferation were assessed using PsAMRIS. A novel total inflammation score was tested. RESULTS:MRIs for 123 patients were included. D169: ABA10 and ABA30/10 significantly reduced MRI synovitis and tenosynovitis, respectively, vs placebo (differences -0.966 [p = 0.039] and -1.652 [p = 0.014], respectively). Synovitis in the placebo group increased non-significantly from baseline to D169; total inflammation and tenosynovitis decreased non-significantly; all measures improved significantly after switch to ABA10 (-1.019, -0.940, -2.275 [p < 0.05], respectively, D365 vs D169). Structural outcomes changed minimally across groups. CONCLUSION:Adults with PsA receiving ABA10 and ABA30/10 demonstrated significant resolution of inflammatory components of disease, confirmed by MRI, with synovitis and tenosynovitis improvements consistent with previously reported clinical responses for these doses. Results indicate that reduction in OMERACT PsAMRIS inflammation scores may provide proof of tissue-level efficacy in PsA clinical trials. CLINICALTRIALS.GOV REGISTRATION:ClinicalTrials.gov, https://clinicaltrials.gov, NCT00534313. 10.1093/rheumatology/keac073
    Long-term Safety of Secukinumab Over Five Years in Patients with Moderate-to-severe Plaque Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis: Update on Integrated Pooled Clinical Trial and Post-marketing Surveillance Data. Acta dermato-venereologica Secukinumab, a selective interleukin (IL)-17A inhibitor, is approved for use in adult and paediatric psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. The aim of this study was to report the long-term safety of secukinumab in pooled data from 28 clinical trials and a post-marketing safety surveillance in psoriasis, psoriatic arthritis and ankylosing spondylitis patients. Analyses included 12,637 secukinumab-treated patients, corresponding to 15,063, 5,985 and 3,527 patient-years of exposure in psoriasis, psoriatic arthritis and ankylosing spondylitis patients, respectively. Incidences of serious adverse events were low, with no identifiable patterns across indications. Active tuberculosis or latent tuberculosis infections were rare. The incidence of opportunistic infections was < 0.2/100 patient-years, the incidence of malignancy was ≤ 1/100 patient-years, and the incidence of major adverse cardiovascular events was < 0.7/100 patient-years, with no apparent increases over time. Secukinumab demonstrated a favourable safety profile for up to 5 years of treatment across the 3 indications, and no new safety signals were identified. 10.2340/actadv.v102.563
    Defining Imaging Sub-phenotypes of Psoriatic Arthritis: Integrative Analysis of Imaging Data and Gene Expression in a PsA Patient Cohort. Eder Lihi,Li Quan,Rahmati Sara,Rahman Proton,Jurisica Igor,Chandran Vinod Rheumatology (Oxford, England) OBJECTIVES:To define imaging sub-phenotypes in patients with psoriatic arthritis (PsA); determine their association with whole blood gene expression, and identify biological pathways characterizing the sub-phenotypes. METHODS:55 patients with PsA ready to initiate treatment for active disease were prospectively recruited. We performed musculoskeletal ultrasound assessment of the extent of inflammation in the following domains: synovitis, peritenonitis, tenosynovitis, and enthesitis. Peripheral whole blood was profiled with RNAseq, and gene expression data were obtained. First, unsupervised cluster analysis was performed to define imaging sub-phenotypes that reflected the predominant tissue involved. Subsequently, principal component analysis was used to determine the association between imaging-defined sub-phenotypes and peripheral blood gene expression profile. Pathway enrichment analysis was performed to identify underlying mechanisms that characterize individual sub-phenotypes. RESULTS:Cluster analysis revealed three imaging sub-phenotypes: 1) Synovitis predominant (N = 31 [56%]); 2) Enthesitis predominant (N = 13 [24%]); 3) Peritenonitis predominant (N = 11 [20%]). The peritenonitis-predominant sub-phenotype had the most severe clinical joint involvement whereas the enthesitis-predominant sub-phenotype had the highest tender entheseal count. Unsupervised clustering of gene expression data identified three sub-phenotypes that partially overlapped with the imaging sub-phenotypes suggesting biological and clinical relevance of these sub-phenotypes. We therefore characterized enriched differential pathways, which included: immune system (innate system, B cells and neutrophil degranulation), complement system, platelet activation and coagulation function. CONCLUSIONS:We identified three sub-phenotypes based on the predominant tissue involved in patients with active PsA. Distinct biological pathways may underlie these imaging sub-phenotypes seen in PsA, suggesting their biological and clinical importance. 10.1093/rheumatology/keac078
    Plain Radiographic Instruments for Structural Damage in Peripheral Joints in Psoriatic Arthritis: A Report From the GRAPPA-OMERACT Working Group. The Journal of rheumatology The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group is focused on the development of a core set of instruments used to assess the domains described in the 2016 PsA Core Domain Set. At the 2021 annual meeting, the group presented an update on the domain of structural damage. In this report, we discuss the steps taken to assess the domain match and feasibility of plain radiographic instruments in the assessment of structural damage in PsA. 10.3899/jrheum.211322
    Controversies in rheumatology: Imaging of enthesitis in spondyloarthritis - does it mean anything for treatment decisions? Balint Peter V,Poddubnyy Denis Rheumatology (Oxford, England) Enthesitis is considered a hallmark manifestation of spondyloarthritis including axial spondyloarthritis and psoriatic arthritis. Detection of enthesitis might be challenging in both diagnostic and classification processes. In this debate, we discuss the controversy on the role of imaging in the detection of enthesitis including the relevance for treatment decisions in spondyloarthritis. 10.1093/rheumatology/keac116
    The clinical and molecular cardiometabolic fingerprint of an exploratory psoriatic arthritis cohort is associated with the disease activity and differentially modulated by methotrexate and apremilast. Journal of internal medicine OBJECTIVES:(1) To evaluate clinical and molecular cardiovascular disease (CVD) signs and their relationship with psoriatic arthritis (PsA) features and (2) to identify a clinical patient profile susceptible to benefit from methotrexate (MTX) and/or apremilast regarding CVD risk. METHODS:This cross-sectional study included 100 patients with PsA and 100 age-matched healthy donors. In addition, an exploratory cohort of 45 biologically naïve patients treated for 6 months with apremilast, MTX or combined therapy according to routine clinical practice was recruited. Extensive clinical and metabolic profiles were obtained. Ninety-nine surrogate CVD-related molecules were analysed in plasma and peripheral blood mononuclear cells (PBMCs). Hard cluster analysis was performed to identify the clinical and molecular phenotypes. Mechanistic studies were performed on adipocytes. RESULTS:Cardiometabolic comorbidities were associated with disease activity and long-term inflammatory status. Thirty-five CVD-related proteins were altered in the plasma and PBMCs of PsA patients and were associated with the key clinical features of the disease. Plasma levels of some of the CVD-related molecules might distinguish insulin-resistant patients (MMP-3, CD163, FABP-4), high disease activity (GAL-3 and FABP-4) and poor therapy outcomes (CD-163, LTBR and CNTN-1). Hard cluster analysis identified two phenotypes of patients according to the rates of cardiometabolic comorbidities with distinctive clinical and molecular responses to each treatment. CONCLUSIONS:(1) Novel CVD-related proteins associated with clinical features could be emerging therapeutic targets in the context of PsA and (2) the pleiotropic action of apremilast could make it an excellent choice for the management of PsA patients with high CVD risk, targeting metabolic alterations and CVD-related molecules. 10.1111/joim.13447
    Secukinumab demonstrates high and sustained efficacy in nail psoriasis: post hoc analysis from phase III trials in patients with psoriatic arthritis. The British journal of dermatology Secukinumab showed consistent and sustained efficacy in clearing nail psoriasis in patients with psoriatic arthritis, with or without axial manifestations, irrespective of severity of nail involvement. Reduction of nail disease was also associated with response across all musculoskeletal and skin manifestations of psoriatic arthritis. 10.1111/bjd.21233
    Association of Cardiac Biomarkers With Cardiovascular Outcomes in Patients With Psoriatic Arthritis and Psoriasis: A Longitudinal Cohort Study. Arthritis & rheumatology (Hoboken, N.J.) OBJECTIVE:In patients with psoriatic disease (PsD), we determined whether cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with carotid plaque burden and the development of cardiovascular events independent of the Framingham Risk Score (FRS). METHODS:Among 1,000 patients with PsD, carotid total plaque area (TPA) was measured in 358 participants at baseline. Cardiac troponin I and NT-proBNP were measured using automated clinical assays. The association between cardiac biomarkers and carotid atherosclerosis was assessed by multivariable regression after adjusting for cardiovascular risk factors. Improvement in the prediction of cardiovascular events beyond the FRS was tested using measures of risk discrimination and reclassification. RESULTS:In univariate analyses, cTnI (β coefficient 0.52 [95% confidence interval (95% CI) 0.3, 0.74], P < 0.001) and NT-proBNP (β coefficient 0.24 [95% CI 0.1, 0.39], P < 0.001) were associated with TPA. After adjusting for cardiovascular risk factors, the association remained statistically significant for cTnI (adjusted β coefficient 0.21 [95% CI 0, 0.41], P = 0.047) but not for NT-proBNP (P = 0.21). Among the 1,000 patients with PsD assessed for cardiovascular risk prediction, 64 patients had incident cardiovascular events. When comparing a base model (with the FRS alone) to expanded models (with the FRS plus cardiac biomarkers), there was no improvement in predictive performance. CONCLUSION:In patients with PsD, cTnI may reflect the burden of atherosclerosis, independent of traditional cardiovascular risk factors. Cardiac troponin I and NT-proBNP are associated with incident cardiovascular events independent of the FRS, but further study of their role in cardiovascular risk stratification is warranted. 10.1002/art.42079
    Secukinumab Drug Survival in Psoriasis and Psoriatic Arthritis Patients: A 24-Month Real-Life Study. Ortolan Augusta,Lorenzin Mariagrazia,Leo Giovanni,Pampaloni Francesca,Messina Francesco,Doria Andrea,Piaserico Stefano,Ramonda Roberta Dermatology (Basel, Switzerland) BACKGROUND:Secukinumab effectiveness has been demonstrated in both psoriasis (PsO) and psoriatic arthritis (PsA). However, it is unknown whether patients with arthritis may carry a risk factor for withdrawal. OBJECTIVE:To identify predictors of secukinumab survival, including the presence of arthritis, in PsO and PsA. METHODS:Consecutive PsO and PsA patients initiating secukinumab were enrolled and followed up every 6 months, up to 24 months or discontinuation. Medical history, disease activity indices and body mass index (BMI) were collected. Kaplan-Meier curves and log-rank test were used to analyze differences in drug survival according to sex, BMI, biological therapy line in the whole population (psoriatic disease), and separately for PsO/PsA. A multivariable Cox regression model was built to assess whether presence of arthritis (main independent variable) may influence drug survival by having time to secukinumab discontinuation as outcome. Results were expressed as hazard ratio and 95% confidence interval. RESULTS:Sixty-two PsO and 90 PsA patients were enrolled. Retention rate at 12 and 24 months, respectively, was 85% and 61% for PsO and 68% and 57% for PsA. In the whole population, naïve patients had a higher chance of drug survival (log-rank = 4.06; p = 0.04); in PsA, obese patients had a significantly higher chance to discontinue secukinumab (log-rank = 5.25; p = 0.021). The multivariable Cox regression showed that arthritis was independently associated with a higher risk of secukinumab discontinuation (hazard ratio 2.43; 95% confidence interval 1.06-5.55, p = 0.035) after adjusting for age, sex, gender, BMI, therapy line and PsO severity at baseline. CONCLUSIONS:Our data confirmed a very good response to secukinumab in both PsO and PsA patients. However, presence of arthritis might affect drug survival. 10.1159/000522008
    Janus Kinase Inhibitors: Safety in Patients With Psoriatic Arthritis. The Journal of rheumatology Janus kinase inhibitors (JAKi; or Jakinibs) have become widely prescribed around the world for a variety of immune-mediated inflammatory diseases, including psoriatic arthritis. A previous noninferiority surveillance study of patients aged > 50 years with rheumatoid arthritis and ≥ 1 additional cardiac risk factor raised a number of safety concerns. This review focuses on available safety data from peer-reviewed publications, as well as the most recent presentations from major conferences highlighting JAKi-associated adverse effects. The safety data for several types of JAKi are reviewed. The latest available safety data for tofacitinib, upadacitinib, filgotinib, deucravacitinib, and brepocitinib is presented. In addition, the findings from the oral surveillance study will be discussed to put safety concerns into context. 10.3899/jrheum.211329
    What Constitutes a Positive MRI for Clinical Trial Recruitment of Psoriatic Arthritis Patients With Axial Involvement? The Journal of rheumatology There has been a resurgence of interest in defining the axial inflammation component of psoriatic arthritis (PsA) since recent randomized controlled trials (RCTs) raised the possibility that this entity may respond differentially to therapeutics compared to patients with axial spondyloarthritis. A workshop was conducted during the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis annual meeting to review the literature on diagnosing PsA and to determine which criteria might be most appropriate. There was quite strong agreement that magnetic resonance imaging (MRI) had an important role to play in helping to define axial inflammation in PsA and that a data-driven methodology for generating optimal MRI quantitative cut-offs for lesions in the sacroiliac joints and/or spine that reflect imaging typical of axial inflammation in PsA would be most desirable. 10.3899/jrheum.211340
    Toward a Sonographic Composite Index for Diagnosis in Psoriatic Arthritis: Highlights From the GRAPPA Ultrasound Workshop. The Journal of rheumatology The ability to visualize musculoskeletal structures with high-resolution ultrasound is an asset to understanding the complexity of psoriatic arthritis (PsA). During the 2021 Annual Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) meeting, 3 topics were presented and discussed in the ultrasound workshop: (1) the progress on the Diagnostic Ultrasound Enthesitis Tool (DUET) project; (2) the sonographic evaluation of joints in PsA-GRAPPA joint project; and (3) extrasynovial lesions in PsA. The ultrasound group aims to develop sonographic tools that are feasible and can be used in standard care to diagnose PsA early. The discussions around these topics will shape the group's work toward developing a composite index to diagnose PsA early. 10.3899/jrheum.211339
    Altered Fecal Metabolomics and Potential Biomarkers of Psoriatic Arthritis Differing From Rheumatoid Arthritis. Frontiers in immunology Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, and the diagnosis is quite difficult due to the unavailability of reliable clinical markers. This study aimed to investigate the fecal metabolites in PsA by comparison with rheumatoid arthritis (RA), and to identify potential diagnostic biomarkers for PsA. The metabolic profiles of the fecal samples from 27 PsA and 29 RA patients and also 36 healthy controls (HCs) were performed on ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). And differentially altered metabolites were screened and assessed using multivariate analysis for exploring the potential biomarkers of PsA. The results showed that 154 fecal metabolites were significantly altered in PsA patients when compared with HCs, and 45 metabolites were different when compared with RA patients. A total of 14 common differential metabolites could be defined as candidate biomarkers. Furthermore, a support vector machines (SVM) model was performed to distinguish PsA from RA patients and HCs, and 5 fecal metabolites, namely, α/β-turmerone, glycerol 1-hexadecanoate, dihydrosphingosine, pantothenic acid and glutamine, were determined as biomarkers for PsA. Through the metabolic pathways analysis, we found that the abnormality of amino acid metabolism, bile acid metabolism and lipid metabolism might contribute to the occurrence and development of PsA. In summary, our research provided ideas for the early diagnosis and treatment of PsA by identifying fecal biomarkers and analyzing metabolic pathways. 10.3389/fimmu.2022.812996
    Combined Single Cell Transcriptome and Surface Epitope Profiling Identifies Potential Biomarkers of Psoriatic Arthritis and Facilitates Diagnosis Machine Learning. Frontiers in immunology Early diagnosis of psoriatic arthritis (PSA) is important for successful therapeutic intervention but currently remains challenging due, in part, to the scarcity of non-invasive biomarkers. In this study, we performed single cell profiling of transcriptome and cell surface protein expression to compare the peripheral blood immunocyte populations of individuals with PSA, individuals with cutaneous psoriasis (PSO) alone, and healthy individuals. We identified genes and proteins differentially expressed between PSA, PSO, and healthy subjects across 30 immune cell types and observed that some cell types, as well as specific phenotypic subsets of cells, differed in abundance between these cohorts. Cell type-specific gene and protein expression differences between PSA, PSO, and healthy groups, along with 200 previously published genetic risk factors for PSA, were further used to perform machine learning classification, with the best models achieving AUROC ≥ 0.87 when either classifying subjects among the three groups or specifically distinguishing PSA from PSO. Our findings thus expand the repertoire of gene, protein, and cellular biomarkers relevant to PSA and demonstrate the utility of machine learning-based diagnostics for this disease. 10.3389/fimmu.2022.835760
    Characteristics of Patients with Generalized Pustular Psoriasis and Psoriatic Arthritis: A Retrospective Cohort Study. Manone-Zenke Yukari,Ohara Yuri,Fukui Sho,Kobayashi Daiki,Sugiura Kazumitsu,Ikeda Shigaku,Arai Satoru Acta dermato-venereologica 10.2340/actadv.v102.2226
    Long-term Persistence of First-line Biologics for Patients With Psoriasis and Psoriatic Arthritis in the French Health Insurance Database. JAMA dermatology Importance:Treatment options for psoriasis (PsO) and psoriatic arthritis (PsA) have evolved significantly throughout the era of biologics. Clinical trials are inadequate to assess the relative long-term efficacy of biologics and are often insufficient regarding safety. Objectives:To assess the long-term persistence of different biologic classes to treat PsO and PsA. Design, Setting, and Participants:This nationwide cohort study involved the administrative health care database of the French health insurance scheme linked to the hospital discharge database. All adults with PsO and PsA who were new users of biologics (not in the year before the index date) from January 1, 2015, to May 31, 2019, were included and followed up through December 31, 2019. Patients hospitalized for PsA in the PsO cohort and for PsO in the PsA cohort in the year before the index date were excluded. Data were analyzed from June 1 to October 31, 2021. Main Outcomes and Measures:Persistence was defined as the time from biologic therapy initiation to discontinuation and was estimated using the Kaplan-Meier method. Comparison of persistence by biologic class involved using propensity score-weighted Cox proportional hazards regression models and adjustment on specific systemic nonbiologics (time-dependent variables). Results:A total of 16 892 patients with PsO were included in the analysis (mean [SD] age, 48.5 [13.8] years; 9152 men [54.2%] men). Of these, 10 199 patients (60.4%) started therapy with a tumor necrosis factor (TNF) inhibitor; 3982 (23.6%), with an interleukin 12 and interleukin 23 (IL-12/23) inhibitor; and 2711 (16.0%), with an interleukin 17 (IL-17) inhibitor. An additional 6531 patients with PsA (mean [SD] age, 49.1 [12.8] years; 3565 [54.6%] women) were included; of these, 4974 (76.2%) started therapy with a TNF inhibitor; 803 (12.3%), with an IL-12/23 inhibitor; and 754 (11.5%), with an IL-17 inhibitor. Overall 3-year persistence rates were 40.9% and 36.2% for PsO and PsA, respectively. After inverse probability of treatment weighting and adjustment, the IL-17 inhibitor was associated with higher persistence compared with the TNF inhibitor for PsO (weighted hazard ratio [HR], 0.78 [95% CI, 0.73-0.83]) and PsA (weighted HR, 0.70 [95% CI, 0.58-0.85]) and compared with the IL-12/23 inhibitor for PsA (weighted HR, 0.69 [95% CI, 0.55-0.87]). No difference between the IL-17 inhibitor and IL-12/23 inhibitor for PsO was noted. The IL-12/23 inhibitor was associated with higher persistence than the TNF inhibitor for PsO (weighted HR, 0.76 [95% CI, 0.72-0.80]), with no difference observed for PsA. Conclusions and Relevance:The findings of this cohort study suggest that IL-17 inhibitors are associated with higher treatment persistence than the TNF inhibitor for PsO and PsA. Interleukin 17 inhibitors were also associated with higher persistence than the IL-12/23 inhibitor for PsA, with no difference for PsO. However, the persistence rates of all biologics remained globally low at 3 years. 10.1001/jamadermatol.2022.0364
    Peripheral γδ T cells regulate neutrophil expansion and recruitment in experimental psoriatic arthritis. Nguyen Cuong Thach,Furuya Hiroki,Das Dayasagar,Marusina Alina I,Merleev Alexander A,Ravindran Resmi,Jalali Zahra,Khan Imran H,Maverakis Emanual,Adamopoulos Iannis E Arthritis & rheumatology (Hoboken, N.J.) OBJECTIVE:This study was undertaken to identify the mechanistic role of γδ T cells in the pathogenesis of experimental psoriatic arthritis (PsA). METHODS:In this study, we perform IL-23 gene transfer in WT and TCR δ deficient mice and perform tissue phenotyping in the joint, skin, and nails to characterize the inflammatory infiltrate. We further perform detailed flow cytometry, immunofluorescence, RNAseq, T cell repertoire analysis and in vitro T -cell polarization assays to identify regulatory mechanisms of γδ T cells. RESULTS:We demonstrate that γδ T cells support systemic granulopoiesis which is critical for murine PsA-like pathology. Briefly, γδ T cell ablation inhibited the expression of neutrophil chemokines CXCL-1, CXCL-2 and neutrophil CD11b Ly6G accumulation in the aforementioned PsA-related tissues. Although a significantly reduced expression of GM-CSF and IL-17A was detected systemically in TCR mice, no GM-CSF /IL-17A γδ T cells were detected locally in the inflamed skin and/or bone marrow in WT mice. Our data demonstrate that non-resident γδ T cells regulate the expansion of an CD11b Ly6G neutrophil population and their recruitment to joint and skin tissues, where they develop hallmark pathologic features of human PsA. CONCLUSION:Our findings do not support that tissue-resident γδ T cells are initiating the disease but demonstrate a novel role of γδ T cells in neutrophil regulation that can be exploited therapeutically in PsA patients. 10.1002/art.42124
    Targeted systemic therapies for psoriatic arthritis: a systematic review and comparative synthesis of short-term articular, dermatological, enthesitis and dactylitis outcomes. RMD open INTRODUCTION:Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis (PsA); few have compared them head to head. OBJECTIVES:To compare the efficacy and safety of all evaluated DMARDs for active PsA, with a special focus on biological DMARDs (bDMARDs) licensed for PsA or psoriasis. METHODS:A systematic review identified RCTs and Bayesian network meta-analysis (NMA) compared treatments on efficacy (American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, resolution of enthesitis and dactylitis) and safety (patients discontinuing due to adverse events (DAE)) outcomes. Subgroup analyses explored ACR response among patients with and without prior biological therapy exposure. RESULTS:The NMA included 46 studies. Results indicate that some tumour necrosis factor inhibitors (anti-TNFs) may perform numerically, but not significantly, better than interleukin (IL) inhibitors on ACR response but perform worse on PASI response. Few significant differences between bDMARDs on ACR response were observed after subgrouping for prior bDMARD exposure. Guselkumab and IL-17A or IL-17RA inhibitors-brodalumab, ixekizumab, secukinumab-were best on PASI response. These IL-inhibitors and adalimumab were similarly efficacious on resolution of enthesitis and dactylitis. Infliximab with and without methotrexate, certolizumab 400 mg every 4 weeks and tildrakizumab showed the highest rates of DAE; abatacept, golimumab and the IL-inhibitors, the lowest. CONCLUSIONS:Despite similar efficacy for ACR response, IL-17A and IL-17RA inhibitors and guselkumab offered preferential efficacy to anti-TNFs in skin manifestations, and for enthesitis and dactylitis, thereby supporting drug selection based on predominant clinical phenotype. 10.1136/rmdopen-2021-002074
    Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: post hoc analysis of three randomised clinical trials. RMD open OBJECTIVE:Evaluate the effect of upadacitinib on pain outcomes in patients with active psoriatic arthritis (PsA) or ankylosing spondylitis (AS) across 3 randomised trials (SELECT-PsA 1 and 2 for PsA; SELECT-AXIS 1 for AS). METHODS:Patients were randomised to upadacitinib 15 mg once daily or placebo (all 3 studies), or adalimumab 40 mg every other week (SELECT-PsA 1 only). Pain outcomes included proportion of patients achieving ≥30%, ≥50% and ≥70% reduction from baseline in patient global assessment of pain and other end points. RESULTS:A higher proportion of patients receiving upadacitinib versus placebo achieved ≥30%, ≥50% and ≥70% reduction in pain end points as early as week 2; these improvements with upadacitinib were generally sustained or increased through year 1 (PsA 1/2 studies: 64%/48%, 58%/42% and 38%/22%, respectively; SELECT-AXIS 1 study: 76%, 72% and 54%). Results were similar with adalimumab in PsA 1 (59%, 49% and 32%). Patients who switched from placebo to upadacitinib 15 mg were able to reach a similar level of improvement as the continuous upadacitinib groups by year 1 (PsA 1/2 studies: 46%-60%, 35%-49% and 15%-34%; AS study: 83%, 72% and 46%). Results were similar with other pain end points. CONCLUSION:Rapid and sustained improvements in pain outcomes across several end points were consistently shown with upadacitinib over 1 year in patients with active PsA or AS who had either inadequate response to prior non-biologic or biologic disease-modifying antirheumatic drugs (PsA studies) or were biologic-naïve with inadequate response to non-steroidal anti-inflammatory drugs (AS study). 10.1136/rmdopen-2021-002049
    Advanced neural networks for classification of MRI in psoriatic arthritis, seronegative, and seropositive rheumatoid arthritis. Folle Lukas,Bayat Sara,Kleyer Arnd,Fagni Filippo,Kapsner Lorenz A,Schlereth Maja,Meinderink Timo,Breininger Katharina,Tacilar Koray,Krönke Gerhard,Uder Michael,Sticherling Michael,Bickelhaupt Sebastian,Schett Georg,Maier Andreas,Roemer Frank,Simon David Rheumatology (Oxford, England) OBJECTIVES:To evaluate whether neural networks can distinguish between seropositive rheumatoid arthritis (RA), seronegative RA and psoriatic arthritis (PsA) based on inflammatory patterns from hand MRI and to test how psoriasis patients with subclinical inflammation fit into such patterns. METHODS:ResNet neural networks were utilized to compare (i) seropositive RA vs. PsA, (ii) seronegative RA vs. PsA and (iii) seropositive vs. seronegative RA with respect to hand MRI data. Results from T1 coronal, T2 coronal, T1 coronal and axial fat suppressed contrast-enhanced (CE) and T2 fat suppressed axial sequences were used. The performance of such trained networks was analyzed by the area-under-the-receiver-operating-characteristic curve (AUROC) with and without presentation of demographic and clinical parameters. Additionally, the trained networks were applied to psoriasis patients without clinical arthritis. RESULTS:MRI scans from 649 patients (135 seronegative RA, 190 seropositive RA, 177 PsA, 147 psoriasis) were fed into ResNet neural networks. AUROC was 75% for seropositive RA vs. PsA, 74% for seronegative RA vs. PsA and 67% for seropositive vs. seronegative RA. All MRI sequences were relevant for classification, however, when deleting contrast agent-based sequences the loss of performance was only marginal. The addition of demographic and clinical data to the networks did not provide significant improvements for classification. Psoriasis patients were mostly assigned to PsA by the neural networks, suggesting that a PsA-like MRI pattern may be present early in the course of psoriatic disease. CONCLUSION:Neural networks can be successfully trained to distinguish MRI inflammation related to seropositive RA, seronegative RA, and PsA. 10.1093/rheumatology/keac197
    Multimodal imaging of the distal interphalangeal-joint synovio-entheseal complex in psoriatic arthritis (MIDAS): a cross-sectional study on the diagnostic accuracy of different imaging modalities comparing psoriatic arthritis to psoriasis and osteoarthritis. RMD open OBJECTIVE:Can ultrasound (US), MRI and X-ray applied to the distal interphalangeal (DIP)-joint and synovio-entheseal complex (SEC) discriminate between patients with psoriatic arthritis (PsA), skin psoriasis (PsO) and hand osteoarthritis (OA)? METHODS:In this prospective, cross-sectional study, patients with DIP-joint PsA and nail involvement (n=50), PsO with nail involvement (n=12); and OA (n=13); were consecutively recruited. Risk ratios (RR) were calculated for US, MRI and X-ray findings of the DIP-joint and SEC between diagnoses. RESULTS:New bone formation (NBF) in US and MRI was a hallmark of OA, reducing the risk of having PsA (RR 0.52 (95% CI 0.43 to 0.63) and 0.64 (95% CI 0.56 to 0.74). The OA group was different from PsA and PsO on all MRI and X-ray outcomes reflected in a lower RR of having PsA; RR ranging from 0.20 (95% CI 0.13 to 0.31) for MRI bone marrow oedema (BMO) to 0.85 (95% CI 0.80 to 0.90) in X-ray enthesitis. No outcome in US, MRI or X-ray was significantly associated with a higher risk of PsA versus PsO, although there was a trend to a higher degree of US erosions and NBF in PsA. 82% of PsA and 67% of PsO was treated with disease modifying antirheumatic drugs which commonly reflects the clinical setting. CONCLUSION:High grade of US, MRI and X-ray NBF reduce the RR of having PsA compared with OA. In PsA versus PsO patients, there was a trend for US to demonstrate more structural changes in PsA although this did not reach significance. 10.1136/rmdopen-2021-002109
    Smoking, alcohol consumption and disease-specific outcomes in rheumatic and musculoskeletal diseases (RMDs): systematic reviews informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs. RMD open BACKGROUND:A EULAR taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). The aim of this paper was to review the literature on the relationship between smoking and alcohol consumption with regard to RMD-specific outcomes. METHODS:Two systematic reviews were conducted to identify systematic reviews and meta-analyses, published between 2013 and 2018, related to smoking and alcohol consumption in seven RMDs: osteoarthritis (OA), rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), systemic sclerosis (SSc) and gout. Two additional systematic reviews were performed to identify original longitudinal studies on smoking and alcohol consumption and disease-specific outcomes. RESULTS:Nine reviews and 65 original studies on smoking as well as two reviews and 14 original studies on alcohol consumption met the inclusion criteria. While most studies were moderate/poor quality, smoking was significantly associated with poorer outcomes: cardiovascular comorbidity; poorer response to RA treatment; higher disease activity and severity in early RA; axSpA radiographic progression. Results were heterogeneous for OA while there was limited evidence for PsA, SSc and gout. Available studies on alcohol mainly focused on RA, reporting a positive association between alcohol intake and radiographic progression. Five studies assessed alcohol consumption in gout, reporting a significant association between the number and type of alcoholic beverages and the occurrence of flares. CONCLUSION:Current literature supports that smoking has a negative impact on several RMD-specific outcomes and that moderate or high alcohol consumption is associated with increased risk of flares in RA and gout. 10.1136/rmdopen-2021-002170
    Effects of physical exercise and body weight on disease-specific outcomes of people with rheumatic and musculoskeletal diseases (RMDs): systematic reviews and meta-analyses informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs. RMD open BACKGROUND:A European League Against Rheumatism (EULAR) taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). This paper reviews the literature on the effects of physical exercise and body weight on disease-specific outcomes of people with RMDs. METHODS:Three systematic reviews were conducted to summarise evidence related to exercise and weight in seven RMDs: osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis (axSpA), psoriatic arthritis, systemic sclerosis and gout. Systematic reviews and original studies were included if they assessed exercise or weight in one of the above RMDs, and reported results regarding disease-specific outcomes (eg, pain, function, joint damage). Systematic reviews were only included if published between 2013-2018. Search strategies were implemented in the Medline, Embase, Cochrane Library of systematic reviews and CENTRAL databases. RESULTS:236 articles on exercise and 181 articles on weight were included. Exercise interventions resulted in improvements in outcomes such as pain and function across all the RMDs, although the size of the effect varied by RMD and intervention. Disease activity was not influenced by exercise, other than in axSpA. Increased body weight was associated with worse outcomes for the majority of RMDs and outcomes assessed. In general, study quality was moderate for the literature on exercise and body weight in RMDs, although there was large heterogeneity between studies. CONCLUSION:The current literature supports recommending exercise and the maintenance of a healthy body weight for people with RMDs. 10.1136/rmdopen-2021-002168
    Basic Science Session 1. Biomarkers for Psoriatic Arthritis Treatment Response and Joint Damage Progression: An Update on 2 Industry-GRAPPA Projects. The Journal of rheumatology The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has identified several priority areas for biomarker development, including biomarkers to predict at baseline which patients may progress to develop joint damage and whether a patient will respond to a specific targeted therapy. Two industry-GRAPPA projects were initiated in 2020 on these biomarker research areas: (1) the Pfizer-GRAPPA project, focused on biomarkers of treatment response to tofacitinib in the Oral Psoriatic Arthritis TriaL program; and (2) the Lilly-GRAPPA project, focused on biomarkers of damage in the ixekizumab SPIRIT-P1 randomized controlled trial. Preliminary results from these 2 projects were presented by the GRAPPA team, with both studies showing promising initial results. Data from these studies will be published when the studies have been completed. Large-scale validation studies are required and are under discussion. 10.3899/jrheum.211320
    Psoriatic arthritis: prospects for the future. Hackett Simon,Ogdie Alexis,Coates Laura C Therapeutic advances in musculoskeletal disease Psoriatic arthritis (PsA) is a form of chronic inflammatory arthritis associated with psoriasis and a multitude of other symptoms, most commonly arthritis, dactylitis, enthesitis and axial involvement. PsA is significantly heterogeneous, with a highly variable clinical course of PsA. Patients may experience significant or mild skin and joint symptoms, with some patients developing rapidly progressing joint destruction and skin symptoms. Despite the range of symptom severity, PsA is frequently associated with significantly impaired quality of life from joint destruction, as well as chronic pain and a range of comorbidities such as depression and cardiovascular disease. Currently, there are no definitive diagnostic tests for PsA, with diagnosis remaining challenging owing to the heterogeneous presentation and course of the disease. Presently, the CASPAR criteria are often used to aid rheumatologists in distinguishing PsA from other inflammatory arthritides. Treatment options for patients have been expanded over the last two decades with the emerging clinical utility of biological therapies. However, early identification and diagnosis of patients and effective disease control remain unmet medical needs within the PsA community. In addition, predicting response to treatment also remains a challenge to rheumatologists. This review highlights the current hurdles faced by healthcare professionals in the diagnosis and management of PsA patients and provides future action points for consideration by the members of the multidisciplinary team who treat PsA patients. 10.1177/1759720X221086710
    All-cause and cause-specific mortality in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis: a nationwide registry study. Kerola Anne M,Kazemi Amirhossein,Rollefstad Silvia,Lillegraven Siri,Sexton Joseph,Wibetoe Grunde,Haavardsholm Espen A,Kvien Tore K,Semb Anne Grete Rheumatology (Oxford, England) OBJECTIVES:To explore mortality and causes of death among Norwegian patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) compared with the general population by conducting a nationwide registry-based cohort study. METHODS:Patients with RA, PsA and axSpA were identified from the Norwegian Patient Registry based on ICD-10-codes between 2008 and 2017. Using age as the time variable, all-cause and cause-specific mortality were estimated between 2010 and 2017 with the Kaplan-Meier estimator and the cumulative incidence competing risk method, respectively. Sex-, education level-, health region- and age group-adjusted HRs for mortality were estimated using Cox regression models. RESULTS:We identified 36 095 RA, 18 700 PsA, and 16 524 axSpA patients (70%, 53%, and 45% women, respectively). RA and axSpA were associated with increased all-cause mortality (HR 1.45 [95% CI, 1.41-1.48] and HR 1.38 [95% CI, 1.28-1.38], respectively). Women but not men with PsA had a slightly increased mortality rate (HR 1.10 [95% CI, 1.00-1.21] among women and 1.02 [95% CI 0.93-1.11] among men). For all patient groups as well as for the general population, the three leading causes of death were cardiovascular diseases, neoplasms and respiratory diseases. RA patients had increased mortality from all of these causes, while axSpA patients had increased mortality from cardiovascular and respiratory diseases. CONCLUSION:Even in the era of modern treatments for IJDs, patients with RA and axSpA still have shortened life expectancy. Our findings warrant further attention to the prevention and management of comorbidities. 10.1093/rheumatology/keac210
    Profiling Blood Serum Extracellular Vesicles in Plaque Psoriasis and Psoriatic Arthritis Patients Reveals Potential Disease Biomarkers. International journal of molecular sciences Psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) are inflammatory diseases with unresolved pathophysiological aspects. Extracellular vesicles (EVs) play an important role in intercellular communication. We compared the miRNA contents and surface proteome of the EVs in the blood serum of PsV and PsA patients to healthy controls. Size-exclusion chromatography was used to isolate EVs from the blood serum of 12 PsV patients, 12 PsA patients and 12 healthy control subjects. EV samples were characterized and RNA sequencing was used to identify differentially enriched EV-bound miRNAs. We found 212 differentially enriched EV-bound miRNAs present in both PsV and PsA groups-a total of 13 miRNAs at FDR ≤ 0.05. The predicted target genes of these miRNAs were significantly related to lesser known but potentially disease-relevant pathways. The EV array revealed that PsV patient EV samples were significantly enriched with CD9 EV-marker compared to controls. Analysis of EV-bound miRNAs suggests that signaling via EVs in the blood serum could play a role in the pathophysiological processes of PsV and PsA. EVs may be able to fill the void in clinically applicable diagnostic and prognostic biomarkers for PsV and PsA. 10.3390/ijms23074005
    Challenges in the Diagnosis and Assessment of Psoriatic Arthritis. The Journal of rheumatology Each year, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) holds a trainee symposium adjacent to the GRAPPA annual meeting. The target audience for this meeting includes trainees in rheumatology, dermatology, and related fields. The 2021 GRAPPA Trainee Symposium focused on challenges in the diagnosis and assessment of psoriatic arthritis (PsA). During the meeting, speakers focused on identification of psoriasis (PsO), the differential diagnosis for both PsO and PsA, diagnostic errors and pitfalls, physical examination in PsA, patient-reported outcomes and composite measures in the assessment of PsA, and the patient perspective on diagnosis and assessment, followed by a panel discussion. This paper summarizes the content discussed at the meeting. 10.3899/jrheum.211337
    Effectiveness of 6-month Use of Secukinumab in Patients With Psoriatic Arthritis in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. The Journal of rheumatology OBJECTIVE:To evaluate clinical and patient-reported outcomes (PROs) at 6 months after secukinumab initiation in US patients with psoriatic arthritis (PsA). METHODS:Patients with PsA in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry who initiated secukinumab between April 1, 2017, and December 2, 2019, and maintained secukinumab at their 6-month follow-up visit were included. Achievement of minimal disease activity (MDA) among patients not in MDA at initiation; resolution (ie, no evidence) of tender and swollen joint counts, enthesitis, and dactylitis among patients with ≥ 1 of these at initiation; and change in disease activity and PROs were evaluated at 6 months in all patients and in patients who received secukinumab as a first-line biologic. RESULTS:Of the 100 eligible patients included, most (83.0%) were biologic experienced and 17.0% initiated secukinumab as a first-line biologic. At initiation, 75/90 patients (83.3%) with available data were not in MDA; 26/71 (36.6%) with follow-up data achieved MDA at 6 months. Further, 28/68 patients (41.2%) with ≥ 1 tender joint, 24/54 (44.4%) with ≥ 1 swollen joint, 17/28 (60.7%) with enthesitis, and 9/12 (75.0%) with dactylitis at initiation achieved resolution at 6 months. Improvements in clinical manifestations, PRO measures, and work productivity and activity were observed after 6 months among patients with PsA who initiated and maintained secukinumab. CONCLUSION:In this real-world population, patients with PsA who received and maintained secukinumab for 6 months achieved MDA in proportions consistent with clinical trials and demonstrated improvements in clinical manifestations and PROs. 10.3899/jrheum.211033
    Potential Impact of Sex and BMI on Response to Therapy in Psoriatic Arthritis: Post Hoc Analysis of Results From the SEAM-PsA Trial. The Journal of rheumatology OBJECTIVE:In this post hoc analysis, we examined the potential impact of sex and BMI on response in the Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) trial (NCT02376790), a 48-week, phase III, randomized controlled trial that compared outcomes with methotrexate (MTX) monotherapy, etanercept (ETN) monotherapy, and MTX+ETN combination therapy in patients with psoriatic arthritis (PsA) who were naïve to MTX and biologics. METHODS:We evaluated key outcomes at week 24 stratified by sex (male vs female) and BMI (kg/m ≤ 30 vs > 30), including the American College of Rheumatology 20 (ACR20) criteria, minimal disease activity (MDA), very low disease activity (VLDA), and Psoriatic Arthritis Disease Activity Score (PASDAS). We analyzed data using descriptive statistics, normal approximation, logistic model, and analysis of covariance. RESULTS:A total of 851 patients completed the SEAM-PsA trial. Higher proportions of men than women who received MTX+ETN combination therapy achieved ACR20 (71.5% vs 58.3%; = 0.02), MDA (45.8% vs 25.2%; = 0.0003), and VLDA (19.1% vs 9.5%; = 0.03), and men achieved better PASDAS (-3.0 vs -2.3; = 0.0004). Patients with BMI ≤ 30 generally had better outcomes than those with BMI > 30 in some treatment arms for ACR20, MDA, VLDA, and PASDAS; however, there was no consistent pattern regarding the treatment arm in which the difference occurred. CONCLUSION:Improved outcomes were observed more in men than in women for MDA and PASDAS with MTX+ETN combination therapy. Patients with BMI ≤ 30 had better outcomes than those with BMI > 30, with no clear pattern regarding treatment received. These findings suggest that contextual factors such as sex and BMI may affect response to PsA therapy. 10.3899/jrheum.211037
    Baseline Disease Activity Predicts Achievement of cDAPSA Treatment Targets With Apremilast: Phase III Results in DMARD-naïve Patients With Psoriatic Arthritis. The Journal of rheumatology OBJECTIVE:The probability of achieving Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) treatment targets (remission [REM], low disease activity [LDA]) was evaluated following apremilast monotherapy in disease-modifying antirheumatic drug (DMARD)-naïve patients with psoriatic arthritis (PsA) based on baseline disease activity. METHODS:This post hoc probability analysis of PALACE 4, a phase III, multicenter, randomized, placebo-controlled study, evaluated shifting across cDAPSA categories from baseline to week 52 and included DMARD-naïve patients receiving apremilast 30 mg BID with available baseline cDAPSA data. Changes in articular/extraarticular manifestations were evaluated in patients with week 52 cDAPSA components. cDAPSA treatment target achievement was assessed in a subgroup with baseline extraarticular PsA manifestations (skin involvement, enthesitis, dactylitis). RESULTS:Of 175 apremilast-treated patients in the probability analysis, 66.3% were in high disease activity (HDA) and 31.4% in moderate disease activity (ModDA) at baseline. Approximately twice as many patients in ModDA at baseline reached REM/LDA at week 52 vs those in HDA (61.7% vs 28.2%). Achieving cDAPSA treatment targets was associated with reductions in articular (swollen/tender joints) and extraarticular (skin involvement, enthesitis, dactylitis, functional disability) disease activity. Similar treatment target achievement rates were observed in the subgroup with ≥ 1 extraarticular PsA manifestation (n = 126; ModDA: 66.7%, HDA: 32.2%). CONCLUSION:Apremilast-treated patients with baseline ModDA had higher probability of achieving cDAPSA treatment targets than patients with HDA. Resolution and/or near resolution of articular and/or extraarticular PsA manifestations was achieved by patients in REM/LDA at week 52. Consistent treatment target achievement was observed in patients with 1 or multiple extraarticular manifestations of active PsA. 10.3899/jrheum.210906
    Secukinumab in United States Biologic-Naïve Patients With Psoriatic Arthritis: Results From the Randomized, Placebo-Controlled CHOICE Study. The Journal of rheumatology 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]; = 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]. 10.3899/jrheum.210912
    Strong site-specific association of pharyngeal cultures with the onset of psoriatic arthritis and psoriasis, regardless of pathogen. Thrastardottir Telma, Meer Elana, Hauksdottir Arna, Gudbjornsson Bjorn, Kristinsson Sigurdur Yngvi, Ogdie Alexis, Love Thorvardur Jon OBJECTIVES: To evaluate the association of culture site, culture result, and pathogen with incident psoriatic arthritis (PsA) and psoriasis. METHODS: Records of all samples sent for culture from a large population during a three-year period were linked with nationwide registry data on diagnoses and death over a 15-year period. The main outcomes of interest were incident diagnoses of PsA and psoriasis, defined by ICD codes. The effect of culture site, culture result (positive vs negative), and pathogen (streptococcus vs negative culture) on the risk of developing PsA and psoriasis was calculated using cox proportional hazards models adjusted for age and gender. RESULTS: A total of 313,235 bacterial cultures from 128,982 individuals were analyzed. Comparing individuals with pharyngeal cultures to those with urine cultures the HR for incident PsA was 8.78 (95% CI 3.23-23.91) and 8.00 (95% CI 5.28-12.12) for incident psoriasis. Most of the risk was concentrated in the first 50 days after culture date. Increased risk was also found when comparing individuals with cultures from the pharynx to those with cultures from nasopharynx and blood. An association with streptococci was not found, neither in the pharynx nor at any other site. A positive bacterial culture from any site was associated with reduced risk for both PsA and psoriasis. CONCLUSION: There is a strong site-specific association between pharyngeal culture samples and an increased risk of PsA and psoriasis, regardless of the pathogen. This may indicate that the site of infection, rather than the pathogen, is associated with increased risk. 10.1093/rheumatology/keac253
    Related Risk Factors and Treatment Management of Psoriatic Arthritis Complicated With Cardiovascular Disease. Frontiers in cardiovascular medicine Psoriatic arthritis (PsA) is a chronic autoimmune inflammatory joint disease related to psoriasis (PsO). The risk of PsA patients with cardiovascular disease (CVD) is significantly higher than that of the general population. At present, the relevant mechanism is not clear, chronic inflammation and traditional cardiovascular risk factors are the most important factors for the increased risk of CVD in PsA patients. Early assessment of the risk of PsA patients with CVD, and active control of the disease activity of PsA patients and intervention of traditional cardiovascular risk factors can delay the progression of CVD risk. This article reviews the epidemiology and pathogenesis between PsA and CVD, and reviews the latest developments in the risk assessment and management of CVD in PsA patients. 10.3389/fcvm.2022.835439
    Is there still a place for methotrexate in severe psoriatic arthritis? Therapeutic advances in musculoskeletal disease The management of psoriatic arthritis (PsA) has long been equated with that of rheumatoid arthritis (RA), particularly because methotrexate (MTX) was found efficient in RA in the 1990s. However, results of collective evidence-based medicine, included and argued in this narrative review, do not currently support the use of MTX as first-line therapy in severe PsA. A recent Cochrane systematic review examining the efficacy of MTX in PsA concluded that low-dose MTX was only slightly more effective than placebo. Questions about a structural effect of MTX in PsA remains non-elucidated. Even if tolerance data on MTX are more consensual and adverse events generally non-severe, subjective side effects such as fatigue might lead to MTX withdrawal based on the patient's decision. PsA patients with axial disease, radiographic lesions, and extensive and disabling skin or joint involvement should receive early treatment with targeted therapy and no longer with MTX. Finally, the usefulness of MTX combined with targeted therapies is limited. MTX does not affect efficacy but only seems to increase the therapeutic maintenance of monoclonal TNF inhibitors. This narrative review may help clarify the place of MTX in PsA management. It allows for reflection on the evolution of current concepts and practices. 10.1177/1759720X221092376
    Risks of Comorbidities in Patients With Palmoplantar Pustulosis vs Patients With Psoriasis Vulgaris or Pompholyx in Korea. JAMA dermatology Importance:Palmoplantar pustulosis (PPP) has been reported to be accompanied by systemic conditions. However, the risks of comorbidities in patients with PPP have rarely been evaluated. Objective:To assess the risks of comorbidities in patients with PPP compared with patients with psoriasis vulgaris or pompholyx. Design, Setting, and Participants:This nationwide population-based cross-sectional study used data from the Korean National Health Insurance database and the National Health Screening Program collected from January 1, 2010, to December 31, 2019. Data were analyzed from July 1, 2020, to October 31, 2021. Korean patients diagnosed with PPP, psoriasis vulgaris, or pompholyx who visited a dermatologist between January 1, 2010, and December 31, 2019, were enrolled. Exposures:Presence of PPP. Main Outcomes and Measures:The risks of comorbidities among patients with PPP vs patients with psoriasis vulgaris or pompholyx were evaluated using a multivariable logistic regression model. Results:A total of 37 399 patients with PPP (mean [SD] age, 48.98 [17.20] years; 51.7% female), 332 279 patients with psoriasis vulgaris (mean [SD] age, 47.29 [18.34] years; 58.7% male), and 365 415 patients with pompholyx (mean [SD] age, 40.92 [17.63] years; 57.4% female) were included in the analyses. Compared with patients with pompholyx, those with PPP had significantly higher risks of developing psoriasis vulgaris (adjusted odds ratio [aOR], 72.96; 95% CI, 68.19-78.05; P < .001), psoriatic arthritis (aOR, 8.06; 95% CI, 6.55-9.92; P < .001), ankylosing spondylitis (aOR, 1.91; 95% CI, 1.61-2.27; P < .001), type 1 diabetes (aOR, 1.33; 95% CI, 1.16-1.52; P < .001), type 2 diabetes (aOR, 1.33; 95% CI, 1.29-1.38; P < .001), Graves disease (aOR, 1.25; 95% CI, 1.11-1.42; P < .001), Crohn disease (aOR, 1.63; 95% CI, 1.11-2.40; P = .01), and vitiligo (aOR, 1.87; 95% CI, 1.65-2.12; P < .001) after adjusting for demographic covariates. The risks of ankylosing spondylitis (aOR, 1.37; 95% CI, 1.16-1.62; P < .001) and Graves disease (aOR, 1.40; 95% CI, 1.23-1.58; P < .001) were significantly higher among patients with PPP vs psoriasis vulgaris. However, the risks of psoriatic arthritis (aOR, 0.54; 95% CI, 0.47-0.63; P < .001), systemic lupus erythematosus (aOR, 0.67; 95% CI, 0.46-0.97; P = .04), Sjögren syndrome (aOR, 0.70; 95% CI, 0.50-0.96; P = .03), systemic sclerosis (aOR, 0.29; 95% CI, 0.11-0.77; P = .01), vitiligo (aOR, 0.53; 95% CI, 0.47-0.60; P < .001), and alopecia areata (aOR, 0.88; 95% CI, 0.81-0.95; P = .001) were significantly lower among those with PPP vs psoriasis vulgaris. Conclusions and Relevance:The results of this cross-sectional study suggest that patients with PPP have an overlapping comorbidity profile with patients with psoriasis vulgaris but not patients with pompholyx. However, the risks of comorbidities among patients with PPP may be substantially different from those among patients with psoriasis vulgaris. 10.1001/jamadermatol.2022.1081
    What is peripheral spondyloarthritis? Identifying proportion, phenotype and burden in post hoc analysis of the ASAS-PerSpA study. Seminars in arthritis and rheumatism BACKGROUND:Little is known about the prevalence, phenotype, and burden of peripheral spondyloarthritis (pSpA). The objective of the study is to compare the phenotype and burden of disease of pure pSpA to that of pure psoriatic arthritis (PsA), pure axial SpA (axSpA), and combined forms of SpA. METHODS:This is a post hoc analysis of 4,185 patients from the cross-sectional ASAS-Peripheral involvement in SpA (PerSpA) study. Patients were approached in 2 ways: the first approach was based on the rheumatologist's diagnosis (diagnostic approach) and the second one was based on the fulfillment of ASAS or CASPAR classification criteria (classification criteria approach). Demographics, disease phenotype, and burden were compared among pure pSpA, PsA, axSpA, and the combined forms. FINDINGS:The proportion of pSpA was 31.5% of SpA using the classification criteria approach and 10.3% using the diagnostic approach. pSpA was pure (i.e. without axSpA or PsA) in 16.8% of pSpA using the criteria, and in 62.3% using the diagnostic approach. Using classification criteria and diagnostic approach, respectively, pure pSpA patients had a high prevalence of peripheral joint disease (86 and 96%), synovitis (76 and 91%), and enthesitis (57 and 55%), a positive HLA-B27 in 65 and 59%, a high C-Reactive Protein level in 51% and inflammatory back pain in 52 and 42%. However, compared to pure PsA and pure axSpA, they had a significantly higher disease burden, but lower use of biologics using both approaches. INTERPRETATION:The proportion of pSpA varies when using the classification criteria or the diagnostic approach. pSpA occurred in a pure form less frequently than PsA and axSpA and had intermediate features but a higher disease burden. FUNDING:The PerSpA main study has been conducted under the umbrella of ASAS thanks to unrestricted grants from PFIZER, LILLY, ABBVIE, NOVARTIS, UCB, JANSSEN, MERCK. 10.1016/j.semarthrit.2022.152012
    Comparative genetic analysis of psoriatic arthritis and psoriasis for the discovery of genetic risk factors and risk prediction modelling. Arthritis & rheumatology (Hoboken, N.J.) OBJECTIVES:Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. The objective was to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models. METHODS:Genome-wide meta-analyses were conducted separately in 5,065 PsA cases vs. 21,286 controls and in 4,340 PsA cases vs. 6,431 PsC separately. The heritability of PsA was calculated and biological pathways that differentiate PsA from PsC were identified using the Priority Index software. The generalisability of published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation. RESULTS:We identified a novel genome-wide significant susceptibility locus for PsA on chromosome 22q11 (rs5754467, p-value=1.61x10 ), and key pathways that differentiate PsA from PsC including NF-kB signalling ( p-value=1.4x10 ) and WNT signalling ( p-value=9.5x10 ). The heritability of PsA was found to be 0.63, similar to PsC (0.61). Modest performance of published classification pipelines (max AUC 0.61) was observed with similar performance for a risk model derived from the current data. CONCLUSION:Key biological pathways associated with PsA were identified but the investigation of risk classification revealed modest utility in the available datasets, possibly because a large number of the PsC patients were receiving treatments that are also effective in PsA; future predictive models of PsA should be tested in PsC patients recruited from primary care. 10.1002/art.42154
    Disparities in healthcare in psoriatic arthritis: an analysis of 439 patients from 13 countries. RMD open OBJECTIVES:Patient care can vary substantially by country. The objective was to explore differences in psoriatic arthritis (PsA) across countries for disease activity, impact and treatments. METHODS:A cross-sectional analysis of 13 countries from the Remission/Flare in PsA study (NCT03119805) of consecutive adult patients with definite PsA was performed. Countries were classified into tertiles by gross domestic product (GDP)/capita. Disease activity (Disease Activity in PsA, DAPSA and Minimal Disease Activity, MDA) and their components, disease impact (patient-reported outcomes) and biological disease-modifying antirheumatic drugs (bDMARDs) were analysed per country and compared between the three tertiles of GDP/capita by parametric and non-parametric tests. We also explored the percentage of patients with significant disease activity (DAPSA >14) and no ongoing bDMARD prescription. RESULTS:In 439 patients (50.6% male, mean age 52.3 years, mean disease duration 10.1 years), disease activity and disease impact were higher in the lowest GDP/capita countries. DAPSA remission and MDA were attained in the lowest tertile in 7.0% and 18.4% patients, vs 29.1% and 49.5% in the middle tertile and 16.8% and 41.3% in the high tertile, respectively (all p<0.001). bDMARDs use was similar in the tertiles (overall mean 61%). The overall rate of patients with DAPSA >14 and no bDMARDs was 18.5%, and was higher in lower GDP/capita countries (p=0.004). CONCLUSION:PsA patients from countries with the lowest GDP/capita, despite similar use of bDMARDs, were more likely to have high disease activity and worse disease impact. There is a need for more equity in healthcare. 10.1136/rmdopen-2021-002031
    Increased erythrocyte mean corpuscular volume by methotrexate predicts clinical response in psoriatic arthritis. Rheumatology (Oxford, England) 10.1093/rheumatology/keac276
    Conventional Synthetic Disease-Modifying Anti-rheumatic Drugs for Psoriatic Arthritis: Findings and Implications From a Patient Centered Longitudinal Study in Brazil. Frontiers in pharmacology Conventional synthetic disease-modifying antirheumatic drugs are the first-line treatment to inhibit the progression of psoriatic arthritis. Despite their widespread clinical use, few studies have been conducted to compare these drugs for psoriatic arthritis. a longitudinal study was carried out based on a centered patient national database in Brazil. Market share of drugs, medication persistence, drug costs, and cost per response were evaluated. a total of 1,999 individuals with psoriatic arthritis were included. Methotrexate was the most used drug (44.4%), followed by leflunomide (40.6%), ciclosporin (8.2%), and sulfasalazine (6.8%). Methotrexate and leflunomide had a greater market share than ciclosporin and sulfasalazine over years. Medication persistence was higher for leflunomide (58.9 and 28.2%), followed by methotrexate (51.6 and 25.4%) at six and 12 months, respectively. Leflunomide was deemed the most expensive drug, with an average annual cost of $317.25, followed by sulfasalazine ($106.47), ciclosporin ($97.64), and methotrexate ($40.23). Methotrexate was the drug being the lowest cost per response. Methotrexate had the best cost per response ratio, owing to its lower cost and a slightly lower proportion of persistent patients when compared to leflunomide. Leflunomide had a slightly higher medication persistence than methotrexate, but it was the most expensive drug. 10.3389/fphar.2022.878972
    Validation of the Physician's Global Assessment of Fingernail Psoriasis by Rheumatologists Treating Psoriatic Arthritis. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research OBJECTIVES:This study aimed to assess the content validity and reliability of the Physician's Global Assessment of Fingernail Psoriasis (PGA-F) by rheumatologists treating patients with psoriatic arthritis. METHODS:There were 3 stages of analyses with 3 clinician cohort groups. Stage 1 (concept confirmation) included rheumatologist qualitative data (cohort 1) to establish content validity, acceptability, utility, and feasibility of the PGA-F in assessing nail severity. Quantitative information regarding the response category utilization in nail abnormalities was assessed by photographs. Stage 2 (inter-rater reliability) involved quantitative analysis of PGA-F data from study investigators, including rheumatologists, involved in a phase III clinical study (cohort 2) and a cohort of newly recruited rheumatologists (cohort 3). Stage 3 included known-groups validity. RESULTS:Qualitative analyses identified consensus that the PGA-F severity levels are comprehensive of real-world patient symptoms and the instrument is simple to use and understand. Psychometric analyses support the PGA-F as a clinical outcome assessment tool. Inter-rater reliability showed rheumatologist agreement across the fingernail psoriasis severity spectrum. They were monotonically ordered by the hypothesized severity structure with excellent fit to the clinicians who evaluated them. Agreement on the rank order of the severity of the photographs in this target rheumatologist population was consistent with previous reports by dermatologists. CONCLUSIONS:The PGA-F was shown to be usable by rheumatologists to measure patients along the full range of the fingernail psoriasis severity spectrum, have a strong relationship with a conceptually similar reference measure, differentiate among patients based on fingernail psoriasis severity, and detect category severity change over a 24-week period. 10.1016/j.jval.2022.04.1727
    The 2022 British Society for Rheumatology guideline for the treatment of psoriatic arthritis with biologic and targeted synthetic DMARDs. Rheumatology (Oxford, England) 10.1093/rheumatology/keac295
    Apremilast Use in Oligoarticular Psoriatic Arthritis. The Journal of rheumatology We read with interest the article published in by Ogdie et al in which apremilast monotherapy showed more benefit in a specific subset of the psoriatic arthritis (PsA) population (oligoarticular pattern), compared to methotrexate (MTX) and biologic disease-modifying antirheumatic drugs (bDMARDs). The authors collected baseline and follow-up data (6-month period) regarding the clinical response to either MTX, apremilast, or bDMARD, all in monotherapy. 10.3899/jrheum.211227
    Active Disease in Psoriatic Arthritis: An Assessment of Spondyloarthritis International Society Health Index (ASAS-HI)-based Analysis. The Journal of rheumatology Psoriatic arthritis (PsA) is a chronic inflammatory arthritis that affects one-third of patients with psoriasis (PsO). PsA is a relatively common condition in rheumatology clinics. In fact, the prevalence of PsA increased to approximately 0.6% of the general population in a recent epidemiological study carried out in Spain.. 10.3899/jrheum.210887
    Effects of diet on the outcomes of rheumatic and musculoskeletal diseases (RMDs): systematic review and meta-analyses informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs. RMD open BACKGROUND:A EULAR taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). In this paper, the literature on the effect of diet on the progression of RMDs is reviewed. METHODS:Systematic reviews and meta-analyses were performed of studies related to diet and disease outcomes in seven RMDs: osteoarthritis (OA), rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis, psoriatic arthritis, systemic sclerosis and gout. In the first phase, existing relevant systematic reviews and meta-analyses, published from 2013 to 2018, were identified. In the second phase, the review was expanded to include published original studies on diet in RMDs, with no restriction on publication date. Systematic reviews or original studies were included if they assessed a dietary exposure in one of the above RMDs, and reported results regarding progression of disease (eg, pain, function, joint damage). RESULTS:In total, 24 systematic reviews and 150 original articles were included. Many dietary exposures have been studied (n=83), although the majority of studies addressed people with OA and RA. Most dietary exposures were assessed by relatively few studies. Exposures that have been assessed by multiple, well conducted studies (eg, OA: vitamin D, chondroitin, glucosamine; RA: omega-3) were classified as moderate evidence of small effects on disease progression. CONCLUSION:The current literature suggests that there is moderate evidence for a small benefit for certain dietary components. High-level evidence of clinically meaningful effect sizes from individual dietary exposures on outcomes in RMDs is missing. 10.1136/rmdopen-2021-002167
    Impact of psoriasis remains important in psoriatic arthritis patients with low musculoskeletal disease activity. Clinical and experimental rheumatology OBJECTIVES:Achieving low disease activity (LDA) is important in patients with psoriatic arthritis. It is of value to know if health-related quality of life (HRQoL) of patients who reached musculoskeletal low disease activity can be further improved by additionally achieving remission of their psoriasis. So, the aim of this study was to assess HRQoL in patients with active psoriasis who reached disease activity in psoriatic arthritis (DAPSA) LDA after one year of follow-up. METHODS:Data were collected from the Dutch south west Psoriatic Arthritis cohort. Musculoskeletal disease activity was measured using DAPSA. Patients who reached DAPSA-LDA after one year were divided based on reaching psoriasis remission (Psoriasis Area and Severity Index [PASI] <1). HRQoL and work productivity were compared between both groups. RESULTS:After one year, 230 (44%) patients with active psoriasis at baseline reached DAPSA-LDA, of which 108 (47%) patients achieved psoriasis remission. The group of patients with active psoriasis (n=122, 53%) contained more men (p=0.023) and scored lower on the 12-item Psoriatic Arthritis Impact of Disease questionnaire (p=0.012). On the Skindex-17 psychosocial subscale, 31% experienced moderate to high impairment and on the symptoms subscale 28% experienced a lot of symptoms. Work productivity did not differ between both groups. CONCLUSIONS:The majority of patients with DAPSA-LDA and active psoriasis after one year has a good HRQoL. However, a proportion of these patients still experiences considerable skin burden. We recommend rheumatologists to continue assessing and treating psoriasis to reduce skin burden in PsA patients who achieved musculoskeletal low disease activity. 10.55563/clinexprheumatol/q8fh0a
    Effectiveness of Disease Modifying Anti-Rheumatic Drugs for Enthesitis in a Prospective Longitudinal Psoriatic Arthritis Cohort. The Journal of rheumatology OBJECTIVE:Our objective was to assess the effectiveness of conventional and targeted disease modifying anti-rheumatic drugs (cDMARDs and tDMARDs, respectively) in treating enthesitis in PsA. METHODS:Patients with active enthesitis, defined as ≥1 tender entheses (of 29 sites included in the spondyloarthritis research consortium of Canada enthesitis index, the Leeds enthesitis index, and the Maastricht ankylosing spondylitis enthesitis score), enrolled in a large PsA cohort were included. Medications at baseline were classified into 3 mutually exclusive categories: 1.'no treatment/non-steroidal anti-inflammatory drugs (NSAIDs)', 2. 'cDMARDs±NSAIDs' and 3.'tDMARDs±cDMARDs/NSAIDs'. Complete resolution of enthesitis (no tender entheseal site) at 12 months was the primary outcome. Logistic regression models were developed to determine the association between medication category and enthesitis resolution. RESULTS:Of the 1270 patients studied, 628(49.44%) had enthesitis; 526 patients (51.71% males; mean age (standard deviation, s.d.) - 49.02(13.12) years; mean enthesitis score (s.d.) 2.13(2.16) with adequate follow-up were analysed. Complete resolution of enthesitis was noted in 453(86%) patients, within a mean period of 8.73 months from baseline. In the regression analysis, though not significant, DMARDs (Categories 2 and 3) had higher odds ratio compared to category 1 for resolution of enthesitis. Enthesitis resolution was associated with lower joint activity (OR 0.97; 95% CI 0.95 - 0.99; p = 0.01) and male sex (OR 1.66; 95% CI 0.97 - 2.84; p = 0.06). CONCLUSION:Resolution of enthesitis was observed in 86% of patients in an observational setting regardless of the medication used. Future effectiveness studies may warrant evaluation of enthesitis using advanced imaging. 10.3899/jrheum.211231
    A practical guide for assessment of skin burden in patients with psoriatic arthritis. The Journal of rheumatology OBJECTIVE:Rheumatologists play a pivotal role in the management of patients with Psoriatic Arthritis (PsA). Due to time constraints, the skin may not receive the attention that is needed for optimal patient outcome. Therefore, the aim of this study was to select a set of core questions that can help rheumatologists to identify PsA patients with a high skin burden in daily rheumatology clinical practice. METHODS:Baseline data from patients included in the Dutch south west Psoriatic Arthritis cohort were used. Questions were derived from the Skindex-17 and Dermatology Life Quality Index (DLQI) questionnaires. Underlying clusters of questions were identified with an exploratory principal component analysis (PCA) with varimax rotation, after which a 2-parameter logistic model was fitted per cluster. Questions were selected based on their discrimination and difficulty. Subsequently, two flowcharts were made with categories of skin burden severity. Clinical consideration were specified per category. RESULTS:In total, 413 patients were included. The PCA showed 2 underlying clusters; a psychosocial domain and a domain assessing physical symptoms. We selected these 2 domains. The psychosocial domain contains 3 questions and specifies 4 categories of skin burden severity. The physical symptoms domain contains 2 questions and categorizes patients in one out of 3 categories. CONCLUSION:We have selected a set of maximum 5 questions which rheumatologists can easily implement in their consult to assess skin burden in PsA patients. This practical guide makes assessment of skin burden more accessible to rheumatologists and can aid in clinical decision making. 10.3899/jrheum.210550
    Reply to comment by Gorman et al. on Pregnancy outcomes in women with psoriatic arthritis with respect to presence and timing of antirheumatic treatment. Arthritis & rheumatology (Hoboken, N.J.) 10.1002/art.42254
    Risk of major adverse cardiovascular events in patients initiating biologics/apremilast for psoriatic arthritis: a nationwide cohort study. Rheumatology (Oxford, England) OBJECTIVE:Several biological DMARDs (bDMARDs) have demonstrated anti-inflammatory effects in PsA. However, their comparative cardiovascular safety profiles remain unknown. We evaluated the risk of major adverse cardiovascular events (MACEs) in PsA patients on therapy with different classes of bDMARDs and apremilast. METHODS:This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database. All adults with PsA who were new users of bDMARDs/apremilast (neither in the year before the index date) during 2015-19 were included. Patients with previous cardiovascular diseases were excluded. End of follow-up was 31 December 2019. The primary endpoint was an occurrence of MACEs in a time-to-event analysis with propensity score-weighted Cox and Fine-Gray models. RESULTS:Between 2015 and 2019, we included 9510 bDMARD new users [mean age 48.5 (s.d. 12.7) years; 42% men], including 7289 starting a TNF inhibitor, 1058 an IL-12/23 inhibitor and 1163 an IL-17 inhibitor, with 1885 apremilast new users [mean age 54.0 (s.d. 12.5) years; 44% men]. MACEs occurred in 51 (0.4%) patients. After propensity score weighting, the risk of MACEs was significantly greater with IL-12/23 (weighted hazard ratio 2.0, 95% CI 1.3, 3.0) and IL-17 (weighted hazard ratio 1.9, 95% CI 1.2, 3.0) inhibitors than TNF inhibitors, with no significant increased risk with apremilast (weighted hazard ratio 1.3, 95% CI 0.8, 2.2). Similar results were observed with the Fine-Gray competing risks survival model. CONCLUSION:Analysis of a large database revealed a small overall number of MACEs, and the risk of MACEs was greater for PsA new users of IL-12/23 and IL-17 vs TNF inhibitors. 10.1093/rheumatology/keab522
    Confounders contributing to explain the association between sex and disease impact in patients with recent-onset psoriatic arthritis. Clinical and experimental rheumatology OBJECTIVES:To evaluate the effect of potential confounders on the association between sex and disease impact in recent-onset psoriatic arthritis. METHODS:We performed a multicentre observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. The dataset was generated using data for each patient at the 3 visits (baseline, first year, and second year of follow-up) matched with the PsAID values at each of the 3 visits. Once variables associated with both PsAID ≥4 and sex were selected, those that led to a difference of >10% between the adjusted and crude estimations were identified as potential confounders in the association between sex and PsAID. Lastly, the final multivariate logistic regression model estimating the association between sex and PsAID was defined. RESULTS:The dataset contained 418 observations (158 at baseline, 135 at the first follow-up visit, and 125 at the second visit). The confounders identified in the multivariate model were HAQ, global pain, level of physical activity, and joint pattern at diagnosis. After adjustment for these variables, no statistically significant association was observed between female sex and PsAID ≥4. CONCLUSIONS:The association between female sex and greater disease impact could be explained by the influence of other variables, specifically higher HAQ score, greater intensity of pain, differences in the level of physical activity and in the joint pattern at diagnosis (lower frequency of the spondylitis pattern in women). 10.55563/clinexprheumatol/077ul6
    Non-invasive metabolic profiling of inflammation in joints and entheses by multispectral optoacoustic tomography. Rheumatology (Oxford, England) OBJECTIVE:To explore the metabolic characteristics of arthritis and enthesitis using multispectral opto-acoustic tomography (MSOT), a technology using near-infrared multispectral laser to stimulate tissues and detect the emitted acoustic energy, enabling non-invasive quantification of tissue components in vivo based on differential absorbance at multiple wavelengths. METHODS:We performed a cross sectional study in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and healthy controls (HC). Participants underwent clinical, ultrasonographic and MSOT examination of metacarpophalangeal and wrist joints as well as the entheses of the common extensor tendon at the lateral humeral epicondyles and of the patellar, quadriceps and Achilles tendon. MSOT-measured haemoglobin, oxygen saturation, collagen and lipid levels were quantified and scaled mean differences (SMD) between affected and unaffected joints and entheses were calculated as defined by clinical examination or ultrasonography using linear mixed effects models. RESULTS:We obtained 1535 MSOT and 982 ultrasonography scans from 87 participants (34 PsA, 17 RA, 36 HC). Entheseal tenderness was not associated with significant metabolic changes, whereas enthesitis-related sonographic changes were associated with increased total haemoglobin, oxygen saturation and collagen content. In contrast, presence of arthritis-related clinical and sonographic findings showed increased haemoglobin levels, reduced oxygen saturation and reduced collagen content. Synovial hypertrophy was associated with increased lipid content in the joints. CONCLUSION:MSOT allows determination of distinct metabolic differences between arthritis and enthesitis in a non-invasive setting in humans in vivo. 10.1093/rheumatology/keac346
    Improved patient-reported outcomes in patients with psoriatic arthritis treated with risankizumab: analysis of the Phase 3 trial KEEPsAKE 2. RMD open OBJECTIVES:Determine the impact of 24-week risankizumab (RZB) versus placebo (PBO) on patient-reported outcomes (PROs) in patients with psoriatic arthritis (PsA) and inadequate response to one or two biologics (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). METHODS:Patients in the Phase 3 trial, KEEPsAKE 2, were randomised (1:1) to RZB 150 mg or PBO by subcutaneous injection. PROs assessed: 36-Item Short-Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Patient's Assessment of Pain by visual analogue scale (VAS), Patient's global assessment of disease activity (PtGA), EuroQoL-5 Dimension-5 Level (EQ-5D-5L) and Work Productivity and Activity Impairment-PsA (WPAI-PsA). Least squares mean change from baseline at week 24 was compared between RZB versus PBO by mixed-effects repeated regression modelling. RESULTS:At week 24, RZB versus PBO treatment resulted in significant differences (95% CIs) in mean change from baseline in ranked secondary endpoints SF-36 physical component summary score (3.9 (2.4 to 5.3); p<0.001) and FACIT-Fatigue (2.2 (0.6 to 3.9); p=0.009) and improvements in pain (-8.1 (-12.8 to -3.5)), PtGA (-8.8 (-13.5 to -4.2)) and EQ-5D-5L index (0.08 (0.04 to 0.11)) and VAS (5.9 (1.9 to 9.8)) (all nominal p<0.01). More RZB-treated versus PBO-treated patients reported improvements from baseline at week 24 in 7 of 8 SF-36 subdomains (nominal p<0.05). At week 24, more RZB-treated versus PBO-treated patients reported improvements in 3 of 4 WPAI-PsA domains (nominal p≤0.01). CONCLUSION:Overall, RBZ treatment resulted in improvements in pain, fatigue, health-related quality of life and ability to perform work in Bio-IR and/or csDMARD-IR patients with PsA. TRIAL REGISTRATION NUMBER:NCT03671148. 10.1136/rmdopen-2022-002286
    Persistence and effectiveness of the IL-12/23 pathway inhibitor ustekinumab or tumour necrosis factor inhibitor treatment in patients with psoriatic arthritis: 1-year results from the real-world PsABio Study. Annals of the rheumatic diseases OBJECTIVE:We evaluated real-world treatment persistence and effectiveness at 1 year following initiation of IL-12/23 inhibitor ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis (PsA). METHODS:PsABio (NCT02627768), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or TNFi. Drug persistence, effectiveness (achievement of clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very low disease activity (MDA/VLDA)), and safety were assessed every 6 months. In addition to descriptive statistics, propensity score (PS)-adjusted comparisons across cohorts were performed. RESULTS:At 1 year, overall persistence was similar in the ustekinumab (n=317/438, 72.4%) and TNFi (n=321/455, 70.5%) groups. PS-adjusted HR (95% CI) for stopping/switching ustekinumab versus TNFi was 0.82 (0.60; 1.13). cDAPSA LDA (including remission)/remission was achieved in 55.9%/22.1% of ustekinumab-treated and 67.1%/31.7% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.80 (0.57; 1.10) for cDAPSA LDA and 0.73 (0.49; 1.07) for remission. MDA/VLDA was achieved in 34.2%/11.9% of ustekinumab-treated and 43.1%/12.6% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.89 (0.63; 1.26) for MDA and 0.90 (0.54; 1.49) for VLDA. The safety profiles were similar in both groups. CONCLUSION:In the real-world PsABio Study, after 1 year of treatment, although unadjusted persistence was numerically slightly higher for ustekinumab versus TNFi and unadjusted effectiveness was numerically slightly higher for TNFi versus ustekinumab, the PS-adjusted comparisons demonstrated comparable overall persistence, effectiveness and safety for both modes of action in PsA. 10.1136/annrheumdis-2021-221640
    EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases. Annals of the rheumatic diseases OBJECTIVE:To develop EULAR points-to-consider for therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases (RMDs). METHODS:The points-to-consider were developed in accordance with EULAR standardised operation procedures by a multidisciplinary task force from eight European countries, based on a systematic literature review and expert consensus. Level of evidence and strength of the points-to-consider were determined, and mean levels of agreement among the task force were calculated using a 10-point rating scale. RESULTS:Six overarching principles and 13 points-to-consider were formulated. The level of agreement among the task force for the overarching principles and points-to-consider ranged from 8.4 to 9.9.The overarching principles define TDM and its subtypes, and reinforce the underlying pharmacokinetic/pharmacodynamic principles, which are relevant to all biopharmaceutical classes. The points-to-consider highlight the clinical utility of the measurement and interpretation of biopharmaceutical blood concentrations and antidrug antibodies in specific clinical scenarios, including factors that influence these parameters. In general, proactive use of TDM is not recommended but reactive TDM could be considered in certain clinical situations. An important factor limiting wider adoption of TDM is the lack of both high quality trials addressing effectiveness and safety of TDM and robust economic evaluation in patients with RMDs. Future research should focus on providing this evidence, as well as on further understanding of pharmacokinetic and pharmacodynamic characteristics of biopharmaceuticals. CONCLUSION:These points-to-consider are evidence-based and consensus-based statements for the use of TDM of biopharmaceuticals in inflammatory RMDs, addressing the clinical utility of TDM. 10.1136/annrheumdis-2022-222155
    2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases. Gwinnutt James M,Wieczorek Maud,Balanescu Andra,Bischoff-Ferrari Heike A,Boonen Annelies,Cavalli Giulio,de Souza Savia,de Thurah Annette,Dorner Thomas E,Moe Rikke Helene,Putrik Polina,Rodríguez-Carrio Javier,Silva-Fernández Lucía,Stamm Tanja,Walker-Bone Karen,Welling Joep,Zlatković-Švenda Mirjana I,Guillemin Francis,Verstappen Suzanne M M Annals of the rheumatic diseases OBJECTIVES:A European League Against Rheumatism taskforce was convened to review the literature and develop recommendations on lifestyle behaviours for rheumatic and musculoskeletal diseases (RMDs). METHODS:Six lifestyle exposures (exercise, diet, weight, alcohol, smoking, work participation) and seven RMDs (osteoarthritis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, systemic lupus erythematosus, systemic sclerosis, gout) were considered. The taskforce included health professionals in rheumatology, geriatricians, epidemiologists, public health experts, people with RMDs and exposure domain experts. Systematic reviews were conducted to gather available evidence, from which recommendations were developed. RESULTS:Five overarching principles and 18 specific recommendations were defined based on available evidence. The overarching principles define the importance of a healthy lifestyle, how lifestyle modifications should be implemented, and their role in relation to medical treatments. Exercise recommendations highlight the safety and benefits of exercise on pain and disability, particularly among people with osteoarthritis and axial spondyloarthritis. The diet recommendations emphasise the importance of a healthy, balanced diet for people with RMDs. People with RMDs and health professionals should work together to achieve and maintain a healthy weight. Small amounts of alcohol are unlikely to negatively affect the outcomes of people with RMDs, although people with rheumatoid arthritis and gout may be at risk of flares after moderate alcohol consumption. Smokers should be supported to quit. Work participation may have benefits on RMD outcomes and should be discussed in consultations. CONCLUSIONS:These recommendations cover a range of lifestyle behaviours and can guide shared decision making between people with RMDs and health professionals when developing and monitoring treatment plans. 10.1136/annrheumdis-2021-222020
    Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure. Deodhar Atul A,Combe Bernard,Accioly Ana P,Bolce Rebecca,Zhu Danting,Gellett Amanda M,Sprabery Aubrey Trevelin,Burmester Gerd-Rüdiger R Annals of the rheumatic diseases OBJECTIVES:Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A (IL-17A), has shown significant efficacy in the treatment of psoriatic arthritis (PsA) and sustained long-term clinical response without unexpected new safety outcome for an IL-17A inhibitor. Here, we report the updated safety profile of ixekizumab up to 3 years in patients with PsA. METHODS:This is an integrated safety analysis from four clinical trials in patients with PsA who received at least one dose of ixekizumab. Treatment-emergent adverse events (TEAEs) and selected adverse events (AEs) exposure-adjusted incidence rates (EAIRs) per 100 patient-years up to 3 years of exposure are reported. RESULTS:A total of 1401 patients with a cumulative ixekizumab exposure of 2247.7 patient-years were included in this analysis. The EAIR of patients with ≥1 TEAE was 50.3 per 100 patient-years and most TEAEs were mild to moderate in severity. Serious AEs were reported by 134 patients (EAIR=6.0). The most reported TEAEs were nasopharyngitis (EAIR=9.0) and upper respiratory tract infection (EAIR=8.3). Infections in general and injection site reactions were the most common TEAEs; the incidence rates of serious cases were low (EAIR ≤1.2). The EAIRs of malignancies (EAIR=0.7), inflammatory bowel disease (EAIR=0.1) including ulcerative colitis and Crohn's disease, depression (EAIR=1.6), and major adverse cerebro-cardiovascular events (EAIR=0.5) were low. As assessed, based on year of exposure, incidence rates were decreasing or constant over time. CONCLUSIONS:In this analysis, the overall safety profile and tolerability of ixekizumab are consistent with the known safety profile in patients with PsA. No new or unexpected safety events were detected. TRIAL REGISTRATION NUMBER:NCT01695239, NCT02349295, NCT02584855, NCT03151551. 10.1136/annrheumdis-2021-222027
    Sequential interleukin-17/interleukin-23 inhibition in treatment-refractory psoriatic arthritis. Annals of the rheumatic diseases 10.1136/annrheumdis-2022-222415
    Guselkumab for treating immune checkpoint inhibitor-induced psoriatic arthritis. Annals of the rheumatic diseases 10.1136/annrheumdis-2022-222628