2023 EULAR recommendations on imaging in diagnosis and management of crystal-induced arthropathies in clinical practice.

OBJECTIVE: To formulate evidence-based recommendations and overarching principles on the use of imaging in the clinical management of crystal-induced arthropathies (CiAs). METHODS: An international task force of 25 rheumatologists, radiologists, methodologists, healthcare professionals and patient research partners from 11 countries was formed according to the EULAR standard operating procedures. Fourteen key questions on the role of imaging in the most common forms of CiA were generated. The CiA assessed included gout, calcium pyrophosphate deposition disease and basic calcium phosphate deposition disease. Imaging modalities included conventional radiography, ultrasound, CT and MRI. Experts applied research evidence obtained from four systematic literature reviews using MEDLINE, EMBASE and CENTRAL. Task force members provided level of agreement (LoA) anonymously by using a Numerical Rating Scale from 0 to 10. RESULTS: Five overarching principles and 10 recommendations were developed encompassing the role of imaging in various aspects of patient management: making a diagnosis of CiA, monitoring inflammation and damage, predicting outcome, response to treatment, guided interventions and patient education. Overall, the LoA for the recommendations was high (8.46-9.92). CONCLUSIONS: These are the first recommendations that encompass the major forms of CiA and guide the use of common imaging modalities in this disease group in clinical practice.

EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update.

OBJECTIVE: New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA. METHODS: Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined. RESULTS: The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed. CONCLUSION: These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.

Validation and incorporation of digital entheses into a preliminary GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis.

OBJECTIVES: The main objective was to generate a GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis and to test its reliability. To this end, we assessed the validity, feasibility and applicability of ultrasound assessment of finger entheses to incorporate them into the scoring system. METHODS: The study consisted of a stepwise process. First, in cadaveric specimens, we identified enthesis sites of the fingers by ultrasound and gross anatomy, and then verified presence of entheseal tissue in histological samples. We then selected the entheses to be incorporated into a dactylitis scoring system through a Delphi consensus process among international experts. Next, we established and defined the ultrasound components of dactylitis and their scoring systems using Delphi methodology. Finally, we tested the interobserver and intraobserver reliability of the consensus- based scoring systemin patients with psoriatic dactylitis. RESULTS: 32 entheses were identified in cadaveric fingers. The presence of entheseal tissues was confirmed in all cadaveric samples. Of these, following the consensus process, 12 entheses were selected for inclusion in GLOUDAS. Ultrasound components of GLOUDAS agreed on through the Delphi process were synovitis, tenosynovitis, enthesitis, subcutaneous tissue inflammation and periextensor tendon inflammation. The scoring system for each component was also agreed on. Interobserver reliability was fair to good (κ 0.39-0.71) and intraobserver reliability good to excellent (κ 0.80-0.88) for dactylitis components. Interobserver and intraobserver agreement for the total B-mode and Doppler mode scores (sum of the scores of the individual abnormalities) were excellent (interobserver intraclass correlation coefficient (ICC) 0.98 for B-mode and 0.99 for Doppler mode; intraobserver ICC 0.98 for both modes). CONCLUSIONS: We have produced a consensus-driven ultrasound dactylitis scoring system that has shown acceptable interobserver reliability and excellent intraobserver reliability. Through anatomical knowledge, small entheses of the fingers were identified and histologically validated.

A multiparametric risk table for loss of clinical remission status in patients with rheumatoid arthritis: A starter study post-hoc analysis.

OBJECTIVE: This post-hoc analysis was carried out on data acquired in the longitudinal Sonographic Tenosynovitis/arthritis Assessment in Rheumatoid Arthritis Patients in Remission (STARTER) study. Its primary aim was to determine the predictive clinical and MSUS features factors for disease flare in RA patients in clinical remission, whilst its secondary aim was to evaluate the probability of disease flare based on clinical and MSUS features. METHODS: The analysis included a total of 389 RA patients in DAS28-defined remission. All patients underwent a MSUS examination according to OMERACT guidelines. Logistic regression and results presented as OR and 95%CI were used for the evaluation of the association between selected variables and disease flare. Significant clinical and MSUS features were incorporated into a risk table to predict disease flare within 12 months in RA remission patients. RESULTS: Within 12 months, 137(35%) RA patients experienced a disease flare. RA patients who experienced a flare disease differed from persistent remission for ACPA positivity (75.9%vs62.3%; p= 0.007), percentage of sustained clinical remission at baseline (44.1%vs68.5%; p= 0.001) and synovium PD signal presence (58.4%vs33.3%; p< 0.001). Based on these results, the three features were considered in a predictive model of disease flare with adjOR 3.064(95%CI 1.728-5.432). Finally, a risk table was constructed including the three significant predictive factors of disease flare within 12 months from the enrolment. CONCLUSION: An adaptive flare prediction model tool, based on data available in outpatient setting, were developed as a multiparametric risk table. If confirmed by the external validation, this tool might support the definition of therapeutic strategies in RA patients in DAS28-defined remission status.

The Novel OMERACT Ultrasound Scoring System for Salivary Gland Changes in Patients With Sjögren Syndrome Is Associated With MRI and Salivary Flow Rates.

OBJECTIVE: To assess the construct validity of the novel Outcome Measures in Rheumatology (OMERACT) ultrasound (US) semiquantitative scoring system for morphological lesions in major salivary glands by comparing it with magnetic resonance imaging (MRI) and unstimulated whole salivary flow rates (U-WSFRs) in patients with primary Sjögren syndrome (pSS). METHODS: Nine sonographers applied the OMERACT 0-3 grayscale scoring system for parotid (PGs) and submandibular glands (SMGs) in 11 patients with pSS who also had MRIs performed. These were evaluated by 2 radiologists using a semiquantitative 0-3 scoring system for morphological lesions. The agreement between US and MRI and the association between U-WSFRs and imaging structural lesions was determined. A score ≥ 2 for both US and MRI was defined as gland pathology. RESULTS: The prevalence of US morphological lesions in 11 patients with a score ≥ 2 was 58% for PGs and 76% for SMGs, and 46% and 41% for PGs and SMGs, respectively, for MRI. The agreement between OMERACT US scores and MRI scores was 73-91% (median 82%) in the right PG and 73-91% (median 91%) in the left PG, 55-91% (median 55%) in the right SMG and 55-82% (median 55%) in the left SMG. When relations between the presence of hyposalivation and an US score ≥ 2 were examined, agreement was 91-100% (median 83%) in both PGs and 55-91% (median 67%) in both SMGs. CONCLUSION: There is moderate to strong agreement between the OMERACT US and MRI scores for major salivary glands in patients with pSS. Similar agreement ratios were observed between the higher OMERACT US scores and presence of hyposalivation.

Comorbidities in the Spondyloarthritis GISEA Cohort: an average treatment effect analysis on patients treated with bDMARDs.

OBJECTIVES: We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis. METHODS: SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance. RESULTS: The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities. CONCLUSIONS: Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.

Points to consider: EULAR-UEMS standards for the training of European rheumatologists.

BACKGROUND: Postgraduate rheumatology training programmes are already established at a national level in most European countries. However, previous work has highlighted a substantial level of heterogeneity in the organisation and, in part, content of programmes. OBJECTIVE: To define competences and standards of knowledge, skills and professional behaviours required for the training of rheumatologists. METHODS: A European Alliance of Associations for Rheumatology (EULAR) task force (TF) of 23 experts, including two members of the European Union of Medical Specialists (UEMS) section of rheumatology, was convened. The mapping phase consisted of the retrieval of key documents on specialty training in rheumatology and other related specialties across a broad set of international sources. The content of these documents was extracted and represented the foundation for the document draft that underwent several rounds of online discussion within the TF, and afterwards was also distributed to a broad group of stakeholders for collecting feedback. The list of generated competences was voted on during the TF meetings, while the level of agreement (LoA) with each statement was established by anonymous online voting. RESULTS: A total of 132 international training curricula were retrieved and extracted. In addition to the TF members, 253 stakeholders commented and voted on the competences through an online anonymous survey. The TF developed (1) an overarching framework indicating the areas that should be addressed during training, (2) 7 domains defining broad areas that rheumatology trainees should master by the end of the training programme, (3) 8 core themes defining the nuances of each domain and (4) 28 competences that trainees should acquire to cover each of the areas outlined in the overarching framework. A high LoA was achieved for all competences. CONCLUSION: These points to consider for EULAR-UEMS standards for the training of European rheumatologists are now defined. Their dissemination and use can hopefully contribute to harmonising training across European countries.

EULAR points to consider for the definition of clinical and imaging features suspicious for progression from psoriasis to psoriatic arthritis.

BACKGROUND: The transition from psoriasis (PsO) to psoriatic arthritis (PsA) and the early diagnosis of PsA is of considerable scientific and clinical interest for the prevention and interception of PsA. OBJECTIVE: To formulate EULAR points to consider (PtC) for the development of data-driven guidance and consensus for clinical trials and clinical practice in the field of prevention or interception of PsA and for clinical management of people with PsO at risk for PsA development. METHODS: A multidisciplinary EULAR task force of 30 members from 13 European countries was established, and the EULAR standardised operating procedures for development for PtC were followed. Two systematic literature reviews were conducted to support the task force in formulating the PtC. Furthermore, the task force proposed nomenclature for the stages before PsA, through a nominal group process to be used in clinical trials. RESULTS: Nomenclature for the stages preceding PsA onset, 5 overarching principles and 10 PtC were formulated. Nomenclature was proposed for three stages towards PsA development, namely people with PsO at higher risk of PsA, subclinical PsA and clinical PsA. The latter stage was defined as PsO and associated synovitis and it could be used as an outcome measure for clinical trials evaluating the transition from PsO to PsA. The overarching principles address the nature of PsA at its onset and underline the importance of collaboration of rheumatologists and dermatologists for strategies for prevention/interception of PsA. The 10 PtC highlight arthralgia and imaging abnormalities as key elements of subclinical PsA that can be used as potential short-term predictors of PsA development and useful items to design clinical trials for PsA interception. Traditional risk factors for PsA development (ie, PsO severity, obesity and nail involvement) may represent more long-term disease predictors and be less robust for short-term trials concerning the transition from PsO to PsA. CONCLUSION: These PtC are helpful to define the clinical and imaging features of people with PsO suspicious to progress to PsA. This information will be helpful for identification of those who could benefit from a therapeutic intervention to attenuate, delay or prevent PsA development.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update.

OBJECTIVES: To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field. METHODS: An international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item. RESULTS: The task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3-6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations. CONCLUSIONS: These updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.

The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

The provisional OMERACT ultrasonography score for giant cell arteritis.

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.

Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update.

BACKGROUND: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. METHODS: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. RESULTS: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, Castleman's disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. CONCLUSIONS: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.

Relationship between the prevalence of subclinical tenosynovitis and treatment in patients with RA in clinical remission: STARTER study.

OBJECTIVE: This study is a sub-analysis from the patient cohort of the STARTER (Sonographic Tenosynovitis Assessment in RheumaToid arthritis patiEnts in Remission) study. The aim was to evaluate differences in ultrasound-detected joint and/or tendon involvement between patients receiving therapies based on a combination of conventional synthetic DMARDs (csDMARDs) and biologic DMARDs (bDMARDs) and those who were treated with either csDMARDs or bDMARDs in monotherapy. MATERIAL AND METHODS: Four hundred and twenty-seven consecutive patients with a diagnosis of RA were recruited between October 2013 and June 2014. They were divided into three subgroups based on their therapy at baseline: patients with bDMARD in monotherapy, patients with csDMARD in monotherapy and patients in combination therapy (csDMARD + bDMARD). At baseline, 6 months and 12 months, a clinical examination (28 joint count) and an ultrasound evaluation were performed in each patient. A score of grey-scale (GS) and power Doppler (PD) synovitis and tenosynovitis was calculated based on the OMERACT scoring systems. RESULTS: Two hundred and fifty-six patients completed the observation period: 48 patients from the bDMARD group (18.75%), 152 patients from the csDMARD group (59.38%) and 56 patients from csDMARD + bDMARD group (21.88%). The analysis showed that GS tenosynovitis and PD tenosynovitis are better controlled in combination therapy than they are with csDMARD alone (P = 0.025 and P = 0.047, respectively); for PD synovitis, there was a better response in those who were treated with the combination therapy when compared with the patients receiving csDMARD (P = 0.01) or bDMARD (P = 0.02) alone. CONCLUSIONS: The analysis showed a lower prevalence of subclinical inflammatory manifestations detected with ultrasound imaging in those patients treated with the combination therapy than in those in monotherapy.

Diagnosis of COVID-19 associated arthritis in patients with or without underlying rheumatic and musculoskeletal disease supported by musculoskeletal ultrasound: a case series from three European centres.

OBJECTIVES: The coronavirus disease 19 (COVID-19) pandemic concerns the field of rheumatology in many ways. Arthritis in conjunction with COVID-19 is increasingly reported. However, clinical data are still limited and there is lack of a detailed characterisation of COVID-19 associated arthritis by musculoskeletal ultrasound (MSUS). This case series reports different forms of COVID-19 associated arthritis supported by MSUS in patients with or without underlying rheumatic and musculoskeletal disease (RMD). METHODS: From March 2020 to July 2021, adult patients (n=10) with arthritis timely related to COVID-19 were assessed in three European centres by clinical and laboratory values and additionally MSUS. RESULTS: In the group without underlying RMD (n=6), two patients presented with polyarticular arthralgia during severe COVID-19, swelling was rarely seen and MSUS demonstrated arthritis only in a few joints affected. The other four patients showed arthritis four to 16 weeks after mild or moderate COVID-19 (without hospitalisation): polyarthritis (n=1), oligoarthritis of the upper and lower limb (n=2), and in one case, late-onset rheumatoid arthritis (LORA) was newly diagnosed. In the group with an underlying RMD (n=4), an increase of disease activity was reported by MSUS during mild and mild-moderate COVID-19. In general, MSUS often presented power Doppler (PD) positive synovitis and tenosynovitis. CONCLUSIONS: In our patients without underlying RMD, arthritides associated with COVID-19 are comparable to the clinical picture of a reactive arthritis (ReA) or other virus-related arthritides (e.g. parvovirus B19). New onset or flares of RMD possibly triggered by COVID-19 are noteworthy.

Adherence to therapy in people with rheumatic and musculoskeletal diseases in Italy and the role of the digital health: results of an expert Delphi consensus survey.

OBJECTIVES: To present the results of a Delphi consensus survey among Italian rheumatologists on adherence to therapy in people with rheumatic and musculoskeletal diseases (RMDs) in Italy and the role of digital health. METHODS: A taskforce of 12 rheumatologists comprehensively discussed the applicability of the 2020 EULAR Points to Consider (PtCs) for Italian rheumatology practice and formulated 44 new country-specific statements. Through an on-line survey, the panellists voted on their level of agreement with the statements using a 10-point Likert scale (0: no agreement; 10: total agreement). A combination of two distinct criteria, a mean agreement level ≥8 and a percentage of at least 75% of responses with a value ≥8, was deemed acceptable. RESULTS: The consensus threshold was reached for 43 of the 44 country-specific statements. The following were acknowledged among the barriers to applicability of the recommendations: visit time too short; lack of resources; lack of a clear operational flow-chart; lack of communication skills and poor knowledge of techniques to improve patient adherence by healthcare professionals (HCPs). CONCLUSIONS: This consensus initiative helps contribute to more widespread implementation of EULAR PtCs in Italian rheumatology practice. Optimisation of visit time, greater availability of resources, specific training, use of standardised and validated protocols, and active involvement of patients represent the main goals. Digital health can provide valuable support for the application of PtCs and, more generally, in improving adherence. A collaborative effort between HCPs, patients and their associations, scientific societies, and policymakers is strongly advocated to overcome some of the barriers.

Association between Patient Acceptable Symptom State and disease activity in psoriatic arthritis is disrupted by confounders, including comorbid fibromyalgia.

OBJECTIVES: Due to the prevalence of fibromyalgia in psoriatic arthritis (PsA) patients, any evaluation about PsA-specific patient-reported outcomes (PROs) should take in account the possible bias related to this comorbidity. Patient acceptable symptom state (PASS) is a patient-reported measure evaluating the acceptable and/or satisfactory level of symptoms in rheumatic diseases, which has been proposed as a disease activity index, in patients with PsA. Thus, this study was designed to analyse if the association between PASS and PsA disease activity may be biased by the presence of comorbid fibromyalgia. METHODS: A multi-centre, cross-sectional, observational study enrolling consecutive PsA participants has been conducted from July 2021 to November 2021. The Disease Activity for Psoriatic Arthritis (DAPSA) was collected; the following formulation of PASS question: 'Think about all the ways your PsA has affected you during the last 48 hours. If you were to remain in the next few months as you were during the last 48 hours, would this be acceptable to you?', was submitted to our participants. RESULTS: Multivariable logistic regressions, adjusted for the presence of fibromyalgia, did not show any significant association between PASS and DAPSA low disease activity, DAPSA as nominal variable (remission, low disease activity, moderate disease activity, high disease activity) and DAPSA as continuous variable. CONCLUSIONS: Our data suggest that fibromyalgia influences the patient's perception of the disease and has a negative impact on PASS status independently of disease activity, thus limiting the utility of this Patient reported outcome in real world clinical practice.

EULAR recommendations for the management and vaccination of people with rheumatic and musculoskeletal diseases in the context of SARS-CoV-2: the November 2021 update.

The first EULAR provisional recommendations on the management of rheumatic and musculoskeletal diseases (RMDs) in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), largely based on expert opinion, were published in June 2020. Since then, an unprecedented number of clinical studies have accrued in the literature. Several SARS-CoV-2 vaccines have been approved for population-wide vaccination programmes in EULAR-affiliated countries. Studies regarding vaccination of patients with (inflammatory) RMDs have released their first results or are underway.EULAR found it opportune to carefully review to what extent the initially consensus expert recommendations stood the test of time, by challenging them with the recently accumulated body of scientific evidence, and by incorporating evidence-based advice on SARS-CoV-2 vaccination. EULAR started a formal (first) update in January 2021, performed a systematic literature review according to EULAR's standard operating procedures and completed a set of updated overarching principles and recommendations in July 2021. Two points to consider were added in November 2021, because of recent developments pertaining to additional vaccination doses.

Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study.

OBJECTIVES: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.

Musculoskeletal ultrasound may narrow the gap between patients and physicians in the assessment of rheumatoid arthritis disease activity.

OBJECTIVES: To investigate the association between patient-physician discordance in the assessment of disease activity and residual US synovitis/tenosynovitis in a cohort of patients with RA in clinical remission. METHODS: A post hoc analysis of the STARTER study, promoted by the Musculoskeletal-US (MSUS) Study Group of the Italian Society for Rheumatology, was performed using data from 361 consecutive patients with RA in clinical remission. The global assessment of disease activity by each patient (PGA) and evaluator/physician (EGA) was recorded on a 100-mm visual analogue scale. The PGA-EGA discordance was classified as positive (PGA>EGA) or negative (PGA

Cytokine profile, ferritin and multi-visceral involvement characterize macrophage activation syndrome during adult-onset Still's disease.

OBJECTIVES: To multidimensionally characterize macrophage activation syndrome (MAS) complicating adult-onset Still's disease (AOSD) considering cytokine profile, inflammatory markers and multi-visceral involvement of the disease. To perform a high-dimensional phenotypic analysis of circulating immune cells in AOSD patients with and without MAS. To assess interferon (IFN)-related pathways in AOSD synovial tissues by a bulky RNA sequencing. METHODS: Clinical and biologic data were collected and compared in AOSD patients with and without MAS. Sera biomolecules were analysed by Luminex multiplexing technology. Mass cytometry (CyTOF) was used to characterize circulating immune cells. A bulky RNA sequencing was performed in AOSD synovial tissues. RESULTS: Forty consecutive AOSD patients were assessed, 14 complicated with MAS. Paralleling with increases of systemic score and ferritin, MAS patients showed higher levels of IL-1α, IL-1ß, IL-1Ra, IL-2Ra, IL-6, IL-10, IL-17A, IFN-γ, G-CSF, MCP-1, MIP-1α and SCF. Combining the discriminatory ability of these data in identifying MAS, the best model was composed by systemic score, ferritin, IFN-γ and IL-10. By CyTOF analysis, MAS patients showed an increase of circulating 'classical monocytes' and a reduction of total NK cells. Our assessment showed 3477 IFN-related genes (IRGs) were differently expressed in AOSD synovial tissues. CONCLUSIONS: A multidimensional characterization of AOSD patients suggested that IFN-γ, IL-10, ferritin and systemic score discriminated the occurrence of cytokine storm syndrome associated with MAS. The inflammatory milieu of AOSD and MAS may be related to a signature of circulating immune cells. Finally, our results about IRGs reinforced the role of IFN-γ in these patients.