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Only a minority of patients with eosinophilic granulomatosis with polyangiitis (EGPA) can be weaned-off glucocorticoids (GC) using conventional treatment strategies. The development of biological agents specifically inhibiting the IL-5 pathway provided the opportunity to treat EGPA by targeting one of the crucial regulators of eosinophils, reducing the GC dose required to control the disease.The anti-IL-5 antibody mepolizumab at the dose of 300 mg/4 weeks has proven to be safe and effective in EGPA. While relapsing patients—who often experience recurrent respiratory manifestations—benefit from this treatment, data are not enough to support its use combined with GC alone in remission induction of severe active forms, or in remission maintenance without conventional immunosuppressants in patients with vasculitic manifestations. Ultimately, the profile of the best candidate for mepolizumab is still unclear.Several real-life reports suggest that mepolizumab at the dose of 100 mg/4 weeks, approved for eosinophilic asthma/chronic rhinosinusitis with nasal polyposis (CRSwNP), effectively maintains remission of EGPA-related asthma and, to a lesser extent, CRSwNP. Preliminary data on the IL-5 pathway-inhibitors benralizumab and reslizumab in EGPA as steroid-sparing agents are also accumulating.Overall, it remains to be proven whether targeting the IL-5 pathway could block progression of organ damage in EGPA, on top of reducing relapses and sparing GC. Other disease-related factors further complicate the understanding of the real anti-IL-5 agent efficacy, such as the lack of a clear definition of remission, of an effective tool to measure disease activity, and of well-defined treat-to-target approaches or goals of treatment.

Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Background/Aims Concerns have been raised about the risk of malignancy with Janus kinase inhibitors (JAKi) following the ORAL Surveillance study, which reported an increased incidence of malignancy with tofacitinib compared with Tumor Necrosis Factor-α inhibitors (TNFi) in people with rheumatoid arthritis (RA) aged over 50 years who had additional cardiovascular risk factors. Our objective was to estimate the risk of malignancy for all licenced JAKi across disease indications, compared with TNFi, methotrexate (MTX), and placebo. Methods A systematic search of electronic databases (Medline, EMBASE, Cochrane) was performed to identify Phase 2/3/4 RCTs and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) in adults with RA, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, or atopic dermatitis. Comparators were placebo, MTX, and TNFi. Random-effects meta-analysis was performed to compare malignancy incidence rates between JAKi and comparators. Our primary outcome measure was the incidence of all malignancies including non-melanomatous skin cancers (NMSC). Secondary outcomes were malignancies excluding NMSC, and NMSC only. Results In 62 eligible RCTs and 14 LTE studies, there were 71,767 person-years of exposure to JAKi; 2,680 to placebo; 7,827 to TNFi; and 1,074 to MTX. Comparing JAKi with placebo arms of RCTs, the incidence rate ratio (RR) for all malignancies including NMSC was not significantly different (RR 0.81; 95% CI 0.52 to 1.26; p = 0.36). Similarly, when comparing JAKi with MTX, no significant differences were observed in the incidence of malignancy (RR 0.73; 95% CI 0.33 to 1.61; p = 0.43). Compared with TNFi, however, administration of JAKi was associated with an increased incidence of malignancy (RR 1.54; 95% CI 1.19 to 2.01; p = 0.001). For all analyses, findings were consistent when excluding NMSC, when analysing NMSC only, and when including LTE data. Conclusion In trial settings, JAKi do not associate with an increased risk of malignancy compared with placebo or MTX, but are associated with an increased risk of malignancy relative to TNFi. Disclosure C. Stovin: None. M.D. Russell: Honoraria; Lilly, Galapagos, Biogen, Menarini. Other; Lilly, Pfizer, Janssen, UCB. E. Alveyn: None. O. Adeyemi: None. V. Patel: None. M.A. Adas: None. F. Atzeni: None. K.K.H. Ng: None. A.I. Rutherford: None. S. Norton: None. A.P. Cope: Consultancies; BMS, Abbvie, GSK/Galvini. Grants/research support; BMS. J.B. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB.

Objective Chronic inflammation and immune dysregulation are crucial mechanisms for atherosclerosis in RA. Recent evidence suggests a link via humoral responses against high-density lipoproteins (HDL). This study aimed to characterize the specificity, clinical relevance and emergence of humoral responses against HDL along disease course, especially during the earliest phases of arthritis. Methods IgG and IgM serum levels of antibodies against HDL (anti-HDL) and apolipoprotein A1 (anti-ApoA1) were measured in 82 early RA patients, 14 arthralgia individuals and 96 controls. Established RA patients (n = 42) were included for validation. Atherosclerosis and vascular stiffness were measured by Doppler ultrasound. Lipoprotein content, particle numbers and size were measured by H-NMR. Cytokines were measured by immunoassays. A cardiometabolic-related protein panel was evaluated using high-throughput targeted proteomics. Results Anti-HDL and anti-ApoA1 responses were increased in early RA compared with controls (both P Conclusion Humoral responses against HDL particles are an early event along the arthritis course, although quantitative and qualitative differences can be noticed among stages. These differences informed distinct capacities as biomarkers and underlying pathogenic circuits.

ObjectivesTo develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD).MethodsAn international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member.ResultsFour overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis againstPneumocystis jiroveciiseems to be beneficial in patients treated with daily doses >15–30 mg of prednisolone or equivalent for >2–4 weeks.ConclusionsThese recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.

Funding Information: The Republic of Turkey Ministry of National Education for the PhD studentship. Publisher Copyright: © 2022 The Author(s) Objectives: To develop evidence-based expert recommendations for non-pharmacological treatments for pain, fatigue, sleep problems, and depression in fibromyalgia. Methods: An international, multidisciplinary Delphi exercise was conducted. Authors of EULAR and the Canadian Fibromyalgia Guidelines Group, members of the American Pain Society and clinicians with expertise in fibromyalgia were invited. Participants were asked to select non-pharmacological interventions that could be offered for specific fibromyalgia symptoms and to classify them as either core or adjunctive treatments. An evidence summary was provided to aid the decision making. Items receiving >70% votes were accepted, those receiving

ObjectivesTo estimate the association of Janus kinase inhibitors (JAKi) with the incidence of malignancy, compared with placebo, tumour necrosis factor (TNF)-α inhibitors (TNFi) and methotrexate.MethodsSystematic searches of databases were performed, to December 2022, to identify phase II/III/IV randomised clinical trials (RCTs) and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) compared with placebo, TNFi or methotrexate, in adults with rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease or atopic dermatitis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy between JAKi and comparators. Bias was assessed using the Cochrane Risk of Bias-2 tool.ResultsIn 62 eligible RCTs and 16 LTE studies, there were 82 366 person-years of exposure to JAKi, 2924 to placebo, 7909 to TNFi and 1074 to methotrexate. The overall malignancy incidence rate was 1.15 per 100 person-years in RCTs, and 1.26 per 100 person-years across combined RCT and LTE data. In network meta-analyses, the incidence of all malignancies including non-melanomatous skin cancers (NMSCs) was not significantly different between JAKi and placebo (IRR 0.71; 95% CI 0.44 to 1.15) or between JAKi and methotrexate (IRR 0.77; 95% CI 0.35 to 1.68). Compared with TNFi, however, JAKi were associated with an increased incidence of malignancy (IRR 1.50; 95% CI 1.16 to 1.94). Findings were consistent when analysing NMSC only and when analysing combined RCT/LTE data.ConclusionsJAKi were associated with a higher incidence of malignancy compared with TNFi but not placebo or methotrexate. Cancers were rare events in all comparisons.PROSPERO registration numberCRD42022362630.

The risk of cardiovascular disease is increased in patients with rheumatoid arthritis compared with the general population owing to the influence of traditional and non-traditional risk factors. Inflammation has a pivotal contribution and can accelerate the atherosclerotic process. Although dampening inflammation with DMARDs should theoretically abrogate this process, evidence suggests that these drugs can also promote atherosclerosis directly and indirectly, hence adding to an increased cardiovascular burden. However, the extent and direction of the effects largely differ across drugs. Understanding how these drugs influence endothelial damage and vascular repair mechanisms is key to understanding these outcomes. NSAIDs and glucocorticoids can increase the cardiovascular risk. Conversely, conventional, biologic and targeted DMARDs control inflammation and reduce this risk, although some of these drugs can also aggravate traditional factors or thrombotic events. Given these data, the fundamental objective for clinicians should be disease control, in an individualized approach that considers the most appropriate drug for each patient, taking into account joint and cardiovascular outcomes. This Review provides a comprehensive analysis of the effects of DMARDs and other approved drugs on cardiovascular involvement in rheumatoid arthritis, from a clinical and mechanistic perspective, with a roadmap to inform the research agenda. Various drugs used in rheumatoid arthritis management have anti-inflammatory effects that can hinder atherosclerosis development and progression. However, these drugs can also concurrently have different pro-atherogenic effects, complicating the relationship between these drugs and cardiovascular involvement in rheumatoid arthritis.

Objectives To ascertain if the use of hydroxychloroquine(HCQ)/cloroquine(CLQ) and other conventional DMARDs (cDMARDs) and rheumatic diseases per se may be associated with COVID-19-related risk of hospitalization and mortality. Methods This case–control study nested within a cohort of cDMARD users was conducted in the Lombardy, Veneto, Tuscany and Lazio regions and Reggio Emilia province. Claims databases were linked to COVID-19 surveillance registries. The risk of COVID-19-related outcomes was estimated using a multivariate conditional logistic regression analysis comparing HCQ/CLQ vs MTX, vs other cDMARDs and vs non-use of these drugs. The presence of rheumatic diseases vs their absence in a non-nested population was investigated. Results A total of 1275 patients hospitalized due to COVID-19 were matched to 12 734 controls. Compared with recent use of MTX, no association between HCQ/CLQ monotherapy and COVID-19 hospitalization [odds ratio (OR) 0.83 (95% CI 0.69, 1.00)] or mortality [OR 1.19 (95% CI 0.85, 1.67)] was observed. A lower risk was found when comparing HCQ/CLQ use with the concomitant use of other cDMARDs and glucocorticoids. HCQ/CLQ was not associated with COVID-19 hospitalization as compared with non-use. An increased risk for recent use of either MTX monotherapy [OR 1.19 (95% CI 1.05, 1.34)] or other cDMARDs [OR 1.21 (95% CI 1.08, 1.36)] vs non-use was found. Rheumatic diseases were not associated with COVID-19-related outcomes. Conclusion HCQ/CLQ use in rheumatic patients was not associated with a protective effect against COVID-19-related outcomes. The use of other cDMARDs was associated with an increased risk when compared with non-use and, if concomitantly used with glucocorticoids, also vs HCQ/CLQ, probably due to immunosuppressive action.

ObjectiveFibromyalgia (FM) is a chronic musculoskeletal pain syndrome of unknown aetiopathogenesis. Its development and maintenance are related to the interplay of biological, psychological, and contextual factors. Among the contextual factors, sociodemographic aspects are poorly elucidated. This study aimed to evaluate the relationships between sociodemographic/ clinical factors and symptom severity measures using a web-based registry of patients with FM.MethodsAdult patients with an ACR 2010/2011 diagnosis of FM underwent a clinical evaluation and were asked to complete questionnaires covering their sociodemographic data (gender, age, marital status, educational level), and disease-specific measures (the revised Fibromyalgia Impact Questionnaire (FIQR), and the Polysymptomatic Distress Scale (PDS)).ResultsData relating to 3,221 patients (3001 women and 220 men) was collected. The ANOVA showed significant difference in mean FIQR scores when the five marital conditions (cohabiter, married, separated/divorced, single, widowed) were compared ( F 3.321, p< 0.01). While males and females were found to have comparable FIQR scores, the interaction between gender and marital status indicated that separated/divorced males have higher FIQR scores (F 5.684, p=0.001). The multiple regression analysis demonstrated that patients who reported lower educational level experienced more severe FM symptoms, as scored with FIQR (p

ObjectiveTo develop recommendations for cardiovascular risk (CVR) management in gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).MethodsFollowing European League against Rheumatism (EULAR) standardised procedures, a multidisciplinary task force formulated recommendations for CVR prediction and management based on systematic literature reviews and expert opinion.ResultsFour overarching principles emphasising the need of regular screening and management of modifiable CVR factors and patient education were endorsed. Nineteen recommendations (eleven for gout, vasculitis, SSc, MCTD, myositis, SS; eight for SLE, APS) were developed covering three topics: (1) CVR prediction tools; (2) interventions on traditional CVR factors and (3) interventions on disease-related CVR factors. Several statements relied on expert opinion because high-quality evidence was lacking. Use of generic CVR prediction tools is recommended due to lack of validated rheumatic diseases-specific tools. Diuretics should be avoided in gout and beta-blockers in SSc, and a blood pressure target ConclusionThese recommendations can guide clinical practice and future research for improving CVR management in rheumatic and musculoskeletal diseases.

Fibromyalgia is characterized by chronic widespread pain, fatigue, sleep disturbances and functional symptoms. The etiopathogenesis, diagnostic criteria and classification criteria of fibromyalgia are still debated and, consequently, so are the strategies for treating this condition. Fibromyalgia is the third most frequent musculoskeletal condition, and its prevalence increases with age. However, although diagnosis has improved with the evolution of more accurate diagnostic criteria, a considerable proportion of physicians still fail to recognize the syndrome. Many factors contribute to the development of fibromyalgia in a unique manner: genetic predisposition, personal experiences, emotional-cognitive factors, the mind-body relationship and a biopsychological ability to cope with stress. The multiple components of the pathogenesis and maintenance of the condition necessitate a multi-modal treatment approach. Individually tailored treatment is an important consideration, with the increasing recognition that different fibromyalgia subgroups exist with different clinical characteristics. Consequently, although an evidence-based approach to fibromyalgia management is always desirable, the approach of physicians is inevitably empirical, and must have the aim of creating a strong alliance with the patient and formulating shared, realistic treatment goals.

The revised Fibromyalgia Impact Questionnaire (FIQR) is a widely used fibromyalgia severity assessment tool that was introduced in 2009 prior to the publication of the American College of Rheumatology (ACR) preliminary fibromyalgia criteria in 2010 and its revision in 2016. In 2020, the modified Fibromyalgia Assessment Scale (FASmod) was published. The Polysymptomatic Distress scale (PSD) of the fibromyalgia criteria and FASmod include assessments of pain location severity and can be used for diagnosis as well as in non-fibromyalgia patients. The aim of this study is to provide equations for the conversion of the FIQR scores to PSD and FASmod as an aid to understanding and sharing fibromyalgia severity information.3089 patients with fibromyalgia, diagnosed according to the ACR 2010/2011 criteria and belonging to the Italian Fibromyalgia Registry completed FIQR, FASmod and PSD questionnaires. Pearson's correlation coefficient was used to test the correlations between indices. The least square regression approach was used to produce predictive equations for each scale based on the remaining scales.FIQR was correlated with PSD (r=0.714) and FASmod (r=0.801); PSD and FASmod showed the highest correlation (r=0.897), expected since they assess the same constructs. Predictive equations showing a linear model were effective in producing mean cohort values, but individual predictions deviated substantially, precluding prediction in the individual patient.Conversion equations that allow for interconversion of multiple scales fibromyalgia severity assessment scales are produced. These can be useful in obtaining mean values for cohorts but are not accurate enough for use in individual patients.

Fibromyalgia (FM) is a syndrome of unknown aetiology characterised by chronic widespread musculoskeletal pain and associated with high rates of psychiatric comorbidities, mainly mood and anxiety disorders.This study aims to determine the age at onset (AAO) and temporal sequencing patterns of FM and its frequent and distinguishable psychiatric comorbidities, the major depressive episode/s (MDE), and panic disorder (PD).Diagnosis of MDE and PD were assigned using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV). The AAO of FM, MDE, and PD was defined using the event history calendar. All patients completed a sociodemographic data form, self-report questionnaires measuring FM-related symptoms and function, and the Childhood Trauma Questionnaire-28 (CTQ-28).98 (83%) of the 118 recruited patients with FM had at least one psychiatric comorbidity. Two main temporal patterns were identified among the 83 patients (70.3 %) who could reliably report the age at onset of FM and psychiatric comorbidities. In the concurrent comorbidity pattern (CCP), MDE and/or PD co-occurred with the onset of FM. In the sequential pattern (SP), the patients first developed PD, then MDE, and finally FM. FM patients with SP are overweight and younger than those with a CCP (FM concurrent with MDE and PD) and reported more childhood adversities, mainly sexual abuse. AAO of psychiatric comorbidities significantly differed between the two patterns.The presence of different temporal comorbidity patterns may suggest prevention/early treatment interventions, especially in patients with childhood adversities and early-onset PD.

ObjectiveThe role of age in influencing the severity of fibromyalgia (FM) is still controversial. The aim of this study is to define the contribution of age in the severity of FM from data from a large national database.MethodsThis cross-sectional study included adult patients with FM diagnosed according to the 2010/2011 American College of Rheumatology criteria. Disease severity was assessed with the revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FAS 2019mod). Patients were grouped into five age categories (between 18-40 years, between 41- 50 years, between 51-60 years, between 61-70 years, and =71 years). Differences in disease severity between groups were assessed by one-way analysis of variance (ANOVA).ResultsThe study included 2889 patients (199 males and 2690 females), mean age of 52.58 (+/- 11.82) years, with a mean FIQR score of 59.22 (+/- 22.98) and a mean FAS 2019mod of 25.50 (+/- 8.66). Comparing the mean values of the various indices between age categories, there were no statistically significant differences between the groups for FIQR total score and FAS 2019mod. However, the 60-70 years category showed the lowest scores for both scales. The main difference emerged for the FIQR physical function subscale, where the =71 years category showed significantly higher scores (p

Objective In this study, we aimed to describe the clinical characteristics, life-threatening complications occurrence, and mortality of adult-onset Still's disease (AOSD) patients with elderly onset. Methods A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was performed. Results Out of 221 assessed patients, 37 (16.7%) had an onset of the disease aged over 60 years. When compared with younger patients, these were characterised by a higher prevalence of pericarditis (p=0.008), comorbidities (p < 0.0001), and mortality (p=0.023). Age predicted the presence of serositis in both univariate (HR: 1.02, 95%CI: 1.01-1.03, p=0.007) and multivariate analyses (HR: 1.02, 95%CI: 1.01-1.04, p=0.007). Age was also a significant predictor of parenchymal lung disease in both univariate (HR: 1.03, 95%CI: 1.01-1.05, p=0.017) and multivariate analyses (HR: 1.03, 95%CI: 1.00-1.05, p=0.048). Furthermore, age resulted to be a negative predictor of polycyclic pattern only in univariate analysis (HR: 0.99, 95%CI: 0.97-1.00, p=0.048). Finally, age significantly predicted the mortality in both univariate (HR: 1.03, 95%CI: 1.00-1.06, p=0.034) and multivariate analyses (HR: 1.05, 95%CI: 1.01-1.08, p=0.012). Conclusion Clinical features of AOSD patients in the elderly were described in our cohort. Although the main clinical characteristics were similar comparing older and younger patients, patients aged over 60 years at disease onset were characterised by an increased prevalence of serositis, comorbidities, mostly cardiometabolic, and a higher mortality rate. Age predicted the presence of parenchymal lung disease and mortality, and it could be considered a negative prognostic factor in AOSD.

Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81–0·84 for cutaneous only vs 0·84, 0·82–0·85 for antibody only vs 0·84, 0·83–0·86 for combined) or for progression-free survival (0·70, 0·69–0·71 vs 0·71, 0·70–0·72 vs 0·71, 0·70–0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46–0·71 for antibody only vs 0·29, 0·19–0·39 for cutaneous only) and disease progression (0·36, 0·29–0·46 vs 0·21, 0·14–0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70–0·74 for antibody only vs 0·66, 0·64–0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75–0·77 vs 0·71, 0·70–0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation.

Objective To compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still’s disease (AOSD). Methods The clinical charts of consecutive patients with sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered. Results A total of 166 patients (median age at diagnosis 5 years) with sJIA and 194 patients with AOSD (median age at diagnosis 41 years) were included. The frequency of fever, rash, arthralgia, abdominal pain, MAS, parenchymal lung disease and increased acute phase reactants and ferritin were comparable between the two cohorts. Patients with sJIA had a higher prevalence of arthritis, whereas patients with AOSD had experienced leucocytosis and extra-articular organ involvement more frequently. Patients with AOSD were given more commonly low-dose corticosteroids, whereas biologic DMARDs were administered first-line more frequently in patients with sJIA. Conclusion We found remarkable disparities in the prevalence of clinical manifestations between the two illnesses, which may partly depend on their classification by different criteria.

Objective To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. Methods The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. Results The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P 65 years, P Conclusion The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

Objective To compare the concordance of the three diagnostic criteria, respectively the 2011 ACR criteria (ACR 2011 Cr), the ACR 2016 criteria (ACR 2016 Cr) and the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION)-APS Pain Taxonomy criteria (AAPT Cr), and to explore the performance of an additional set of criteria, the modified Fibromyalgia Assessment Status (FAS 2019 modCr), in the diagnosis of FM syndrome. Methods Consecutive patients with chronic widespread pain, referred by the primary care setting, underwent rheumatologic assessment that established the presence or not of FM and were investigated through the four sets of proposed criteria. For the FAS 2019 modCr, discriminant validity to distinguish patients with FM and non-FM was assessed with receiver operating characteristic curve analysis. Results A total of 732 (405 with FM and 327 with other common chronic pain problems) patients were evaluated. Against the clinical diagnosis of FM, the sensitivity, specificity and correct classification were, respectively: 79.8, 91.7 and 85.1% for ACR 2011 Cr; 78, 90.5 and 83.6% for the ACR 2016 Cr; and 73.8, 91.7 and 81.8% for the AAPT Cr. The alternative set, proposed on the FAS 2019 modCr, provided a maximal diagnostic accuracy with a score ≥20 (Youden’s index), with a sensitivity of 84.2%, specificity 89.0% and positive likelihood ratio 7.65. Conclusion There is a considerable agreement between criteria-based diagnoses of FM, although the AAPT Cr perform least well in terms of percentage of correct classification. The FAS 2019 modCr had comparable characteristics.

Objective.To evaluate the prevalence and factors associated with the neuropathic pain features in a cohort of patients with psoriatic arthritis (PsA).Methods.A cross-sectional evaluation was conducted in consecutive patients having PsA with prevalent peripheral joint involvement, referred to 3 rheumatological centers. For each patient, a comprehensive assessment of disease activity, physical function, and disease effect was carried out. The presence of comorbid fibromyalgia syndrome (FMS) was evaluated. Acute-phase reactants were also recorded. The neuropathic pain features were investigated through the PainDETECT Questionnaire (PDQ). A logistic regression analysis was therefore conducted using the PDQ as the dependent variable.Results.The final evaluation included 118 patients. A comorbid FMS was detectable in 30 of the 118 patients with PsA (25.4%). Probable characteristics of neuropathic pain (PDQ ≥ 19) were found in 30 (25.4%) patients overall, ambiguous (PDQ > 12 and < 19) in 21 (17.8%) patients, and unlikely (PDQ ≤ 12) in 67 (56.8%) patients. Using logistic regression analysis, the only independent variable among those investigated that could explain the neuropathic pain features was the presence of a comorbid FMS (p = 0.0127). Excluding patients with comorbid FMS, an association with disability (measured by Health Assessment Questionnaire–Disability Index) emerges (p = 0.0489). In patients with PsA and comorbid FMS, PDQ scores were significantly higher than in patients without comorbid FMS.Conclusion.Neuropathic pain features are common in patients with PsA, and the presence of pain sensitization (comorbid FMS) seems to be its main predictor.

The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still’s disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, smokers showed higher values of systemic score (6.4 ± 2.2 vs 5.4 ± 1.8, p = 0.004), an increased rate of macrophage activation syndrome (MAS) (28.9% vs 6.4%, p < 0.0001) and of parenchymal lung disease (17.7% vs 12.6%, p = 0.035). Although not significant, these patients more frequently experienced a poor prognosis (13.3% vs 4.3%, p = 0.074). Smoking habit predicted MAS occurrence in both univariate (HR: 5.98, 95% CI: 2.45–14.57, p < 0.0001) and multivariate regression models (HR: 6.21, 95% CI: 2.46–15.70, p < 0.0001). Smokers had a significant higher risk of parenchymal lung disease in both univariate (HR: 3.97, 95% CI: 1.43–11.02, p = 0.008) and multivariate regression models (HR: 3.90, 95% CI: 1.36–11.23, p = 0.012). Smoking habit also increased the risk of mortality in univariate regression model (HR: 4.25, 95% CI: 1.33–13.55, p = 0.015). Smoking habit resulted to be a negative prognostic factor on AOSD patients. Smokers were characterised by a higher frequency of serositis and higher values of systemic score. Additionally, these patients were more frequently burdened by MAS and parenchymal lung disease associated with a poor prognosis.Key points•Smoking habit resulted to be a negative prognostic factor on AOSD.•Smokers were characterised by an increased frequency of serositis and higher values of systemic score.•Cigarette exposure was associated with MAS and parenchymal lung disease in AOSD.

Objectives: The recent introduction of direct-acting antiviral agents (DAAs) which can eliminate Hepatitis C virus (HCV) had revolutionized the treatment of HCV infections also in a complex clinical setting such as the patients with rheumatoid arthritis (RA). HCV elimination is also opportune due to the availability of more efficient immunosuppressive drugs, whose effect on the course of HCV infection is largely unknown. Methods: Consensus process was endorsed by the Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) to review the available evidence and produce practical, hospital-wide recommendations. The consensus panel consisted of 18 infectious diseases consultants, 20 rheumatologists and one clinical epidemiologist, who used the criteria of the Oxford Centre for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations. Results: A core-set of statements about management of patients with RA and infection by HCV have been developed to help clinicians in their clinical practice. Conclusions: A screening for HCV should be performed in all RA patients and it is mandatory before starting an immunosuppressive therapy. Finally, a DAA treatment should be considered in all HCV-infected patients.Significance and Innovations HCV antibodies should be investigated at the time of diagnosis of RA and, in any case, before starting immunosuppressive therapy with disease-modifying antirheumatic drugs (DMARDs). HCV eradication with DAA should be attempted as soon as possible, depending on patient conditions allowing a continuous oral treatment lasting 8–12 weeks Conventional and biological DMARDs are allowed in patients with HCV infection, but they should be used cautiously in presence of advanced liver disease.

Resume Objectif Determiner l’incidence du cancer chez des patients atteints de spondyloarthrite (SpA) traites par inhibiteurs du TNF (anti-TNF) enregistres dans le registre GISEA et identifier les facteurs associes a l’apparition du cancer. Methodes Cette etude observationnelle a inclus une cohorte ouverte de 3321 patients atteints de SpA figurant dans le registre GISEA en vue de collecter des donnees cliniques reelles concernant les patients atteints de PR ou de SpA et recevant un traitement biologique. Les parametres demographiques et cliniques ont ete enregistres a l’inclusion. L’incidence generale des tumeurs a ete comparee a celle observee dans la population generale, selon l’association italienne d’oncologie medicale. Resultats Sur les 3321 patients atteints de SpA (1731 hommes, 52,2 % ; âge moyen 47 ± 13 ans ; duree mediane de la maladie trois ans, intervalle interquartile [IQR] 0–8), 50 ont developpe au moins l’un de 56 cancers pendant la periode de suivi de 12 ans du traitement par anti-TNF. L’incidence globale etait de 6,3/1000 annees–patient de suivi (intervalle de confiance [IC95 % : 4,7–8,2]), soit 7,3/1000 annees–patient (IC95 % : 4,1–11,8) sous ADA, 6,1/1000 annees–patient (IC95 % : 3,8–9,4) sous ETN et 5,8/1000 annees–patient (IC95 % 3,5–9,1) sous INF, contre 5,1/1000 annees–patient dans la population generale. L’analyse univariee a montre que l’âge a l’instauration du traitement anti-TNF (p = 0,001), la presence (p = 0,012) et le nombre (p Conclusions L’incidence du cancer chez les patients atteints de SpA traites par les trois anti-TNF etait plus elevee que dans la population generale ; un antecedent de cancer solide est predictif de l’apparition d’un nouveau cancer.

Fibromyalgia (FM) is a syndrome of unknown aetiology characterised by chronic pain, fatigue, and disturbed sleep. This review presents and summarises the 2020 literature on FM by retrieving all articles indexed in PubMed between 1 January 2020 and 31 December 2020. The attention of the scientific community towards FM is constantly growing, and this year's review is focused on the diagnostic, pathogenetic and therapeutic aspects of this syndrome. In particular, the treatment options for FM, both pharmacological and non-pharmacological, have been extensively studied.

Objective Various studies have shown that overweight and obesity are central features of FM, but the real impact of a high BMI on clinical severity in patients with FM is still controversial. The aim of this study was to analyse the relationships between BMI categories and measures of symptom severity and functional impairment using data from a Web-based registry of patients with FM. Methods Adult patients with an ACR 2010/2011 diagnosis of FM underwent a complete physical examination and laboratory tests and were asked to complete a package of questionnaires covering their sociodemographic and treatment details, in addition to the following disease-specific questionnaires: the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Status questionnaire (ModFAS) and the Polysymptomatic Distress Scale (PDS). Results A total of 2339 patients were recruited and divided into two weight categories, underweight/normal (U/N, n = 1127, 48.2%) and overweight/obese (O/O, n = 1212, 51.8%). The total and subscales of FIQR, ModFAS and PSD scores were significantly higher in the O/O patients, as were all the mean scores of the individual FIQR items (P Conclusion Our findings demonstrate that O/O patients with FM are significantly more impaired than U/N patients in all the symptomatological and functional domains as measured using the FIQR, ModFAS and PDS, thus suggesting that being O/O has an additional effect on symptoms and function.

Objective To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity. Methods Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: ‘In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?’—which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach. Results The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th–75th percentiles) were respectively 61.16 (41.16–77.00), 27.00 (19.00–32.00) and 19.0 (13.00–24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0–23 for remission, 24–40 for mild disease, 41–63 for moderate disease, 64–82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0–12 for remission, 13–20 for mild disease, 21–28 for moderate disease, 29–33 for severe disease and >33 for very severe disease; PDS: 0–5 for remission, 6–15 for mild disease, 16–20 for moderate disease, 21–25 for severe disease and >25 for very severe disease. Conclusions Disease severity cut-offs can represent an important improvement in interpreting FM.

Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. ‘Repurposing’ immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patients.

OBJECTIVES: To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjögren's syndrome (pSS). METHODS: By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression. RESULTS: There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of 95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R2 0.87) and the frequency of abnormal oral tests (adjusted R2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase). CONCLUSIONS: The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.

Objectives To stratify adult-onset Still’s disease (AOSD) patients in distinct clinical subsets to be differently managed, by using a multi-dimensional characterization. Methods AOSD patients were evaluated by using a hierarchical unsupervised cluster analysis comprising age, laboratory markers systemic score and outcomes. The squared Euclidean distances between each pair of patients were calculated and put into a distance matrix, which served as the input clustering algorithm. Derived clusters were descriptively analysed for any possible difference. Results Four AOSD patients clusters were identified. Disease onset in cluster 1 was characterized by fever (100%), skin rash (92%) and arthritis (83%), with the highest ferritin levels [mean (S.D.) 14 724 (6837) ng/ml]. In cluster 2, the onset was characterized by fever (100%), arthritis (100%) and liver involvement (90%), together with the highest CRP levels [288.10 (46.01) mg/l]. The patients in cluster 3 presented with fever (100%), myalgia (96%) and sore throat (92%). The highest systemic score values [8.88 (1.70)] and the highest mortality rate (54.2%) defined cluster 3. Fever (100%) and arthritis (90%) were the symptoms at the onset in cluster 4, which was characterized by the lowest ferritin and CRP levels [1457 (1298) ng/ml and 54.98 (48.67) mg/l, respectively]. Conclusion Four distinct phenotypic subgroups in AOSD could be suggested, possibly associated with different genetic background and pathogenic mechanisms. Our results could provide the basis for a precision medicine approach in AOSD in an attempt to find a clinical and laboratory multidimensional stratification and characterization, which would drive a tailored therapeutic approach in these patients.

Diffuse Idiopathic Skeletal Hyperostosis (DISH) is considered a metabolic condition, characterized by new bone formation affecting mainly at entheseal sites. Enthesitis and enthesopathies occur not only in the axial skeleton but also at some peripheral sites, and they resemble to some extent the enthesitis that is a cardinal feature in spondyloarthritis (SpA), which is an inflammatory disease. We review the possible non-metabolic mechanism such as inflammation that may also be involved at some stage and help promote new bone formation in DISH. We discuss supporting pathogenic mechanisms for a local inflammation at sites typically affected by this disease, and that is also supported by imaging studies that report some similarities between DISH and SpA. Local inflammation, either primary or secondary to metabolic derangements, may contribute to new bone formation in DISH. This new hypothesis is expected to stimulate further research in both the metabolic and inflammatory pathways in order to better understand the mechanisms that lead to new bone formation. This may lead to development of measures that will help in earlier detection and effective management before damage occurs.

Background:Fibromyalgia (FM) patients report chronic widespread pain, fatigue, cognitive difficulties and sleep disturbances, often associated with anxiety and/or depression (1). FM syndrome more frequently affects women and many papers describe gender-related differences in the perception, description and expression of pain (2), but up to now, the impact of gender on the clinical severity of FM is still a controversial topic.Objectives:The aim of this study was to analyse the data from a web-based registry of FM patients in order to detect a relationship between gender and disease severity.Methods:Adult patients with FM, diagnosed on the basis of the 2010/2011 American College of Rheumatology (ACR) diagnostic criteria (3), were recruited at 19 Italian rheumatology centres between November 2018 and April 2019. Those affected by other conditions that could interfere with the assessment of FM, e.g. psychiatric disorders, were excluded from the study. The severity of the disease was evaluated by validated FM-specific questionnaires: the revised Fibromyalgia Impact Questionnaire (FIQR) (4), the modified Fibromyalgia Assessment Status (ModFAS) questionnaire (5), and the Polysymptomatic Distress Scale (PDS) (6). The data obtained were collected in the Italian Fibromyalgia Registry, an online registry created with the support of the Italian Society of Rheumatology (SIR).Results:We analyse data from 2.381 patients affected by FM, 2.184 females (91.7%) and 197 males. No significant differences in mean age, disease duration, or BMI between the two genders were reported. The women expressed greater disease burden as indicated by higher scores for each completed test: higher mean ModFAS score (25.23 ± 8.83 Vs 23.37 ± 9.22; p = 0.005), mean FIQR score (58.62 ± 23.22 Vs 51.68 ± 23.06; p Figure 1.Mean scores for each FIQR item by gender.Conclusion:Our findings demonstrate that women with FM are globally more impaired than men (even if some psychological aspects of the disease are comparable), thus reinforcing the idea that gender plays a role in symptoms and functional impairments associated with the disease.References:[1]Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014;311:1547-55.[2]Nascimento, et al. Gender role in pain perception and expression: an integrative review. BrJP. 2020; 3: 58-62[3]Wolfe F, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: A modification of the ACR preliminary diagnostic criteria for fibromyalgia. J Rheumatol 2011;38:1113–22.[4]Burckhardt CS, et al. The fibromyalgia impact questionnaire: development and validation. J Rheumatol 1991;18:728–33.[5]Salaffi F, et al. Diagnosis of fibromyalgia: comparison of 2011/2016 ACR and AAPT criteria and validation of the modified Fibromyalgia Assessment Status. Rheumatol 2020; 0:1-8.[6]Wolfe F, et al. Fibromyalgia prevalence, somatic symptom reporting, and the dimensionality of polysymptomatic distress: results from a survey of the general population. Arthritis Care Res. 2013; 65:777–85Disclosure of Interests:None declared.

SARS-CoV-2 is a novel coronavirus that was first isolated from a group of patients hospitalized with pneumonia in China at the end of 2019, and, in February 2020, the syndrome it caused was named coronavirus disease 2019 (COVID-19) by the World Health Organization. In the absence of specific antiviral treatments capable of neutralizing the etiological agent, one therapeutic approach is to control the cytokine storm responsible for the most severe forms of the disease. The characteristic cytokine profile of severely affected patients is increased levels of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor alpha (TNF-α).This article discusses the pathogenesis of COVID-19 as a rationale for using the biological and targeted synthetic drugs used in rheumatology (anti-TNF, anti-IL-1 and anti-IL-6 agents and baricitinib) to treat the disease, and provides key information concerning their potential benefits and adverse effects.Interleukin inhibition seems to be a promising means of treating COVID-19 patients when respiratory function declines (or even earlier) if there are laboratory data indicating the presence of a cytokine storm because the interleukins are key drivers of inflammation. However, it is important to consider the risks and benefits of biological agents carefully, and critically analyze the evidence concerning their use in COVID-19 patients.

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterised by calcification and ossification of ligaments and entheses. The condition usually affects the axial skeleton, in particular, at the thoracic segment, though also other portions of the spine are often involved. DISH often involves also peripheral tendinous and/or entheseal sites either alone, or in association with the involvement of peripheral joints. At times, new bone formation involves the bone itself, but sometimes it involves joints not usually affected by osteoarthritis (OA) which result in bony enlargement of the epiphysis, joints space narrowing and a reduced range of motion. Because of the entheseal involvement, DISH can be mistaken for seronegative spondyloarthropathies or for a "simple" OA. Furthermore, other implications for the recognition of DISH include spinal fractures, difficult intubation and upper endoscopies, decreased response rates in DISH with concomitant spondyloarthritides, and increased likelihood to be affected by metabolic syndrome and cardiovascular diseases. This Atlas is intended to show the imaging finding in DISH in patients diagnosed with the condition by the Resnick classification criteria.

Post-marketing surveillance activities are essential to detect the risk/benefit profile of biologic disease-modifying antirheumatic drugs (bDMARDs) in inflammatory arthritis. The aim of this study was to evaluate adverse events (AEs) in patients treated with bDMARDs in rheumatology during a prospective pharmacovigilance study from 2016 to 2018. Descriptive statistical analyses were performed to evaluate bDMARDs-related variables of patients without AEs/failures vs patients with AEs and failures. The risk profile among biologics was assessed by comparing patients treated with each bDMARD to patients treated with etanercept. A total of 1155 patients were enrolled, mostly affected by rheumatoid arthritis (46.0%). AEs and failures were experienced by 8.7% and 23.3%, respectively. The number of comorbidities significantly influenced the onset of AEs, while anxiety-depressive, gastrointestinal disease, and fibromyalgia influenced onset of failures. The probability of developing an AE was significantly lower in patients treated with secukinumab, while the probability of developing treatment failure was significantly lower in patients treated with golimumab, secukinumab and tocilizumab. A total of 216 AEs were reported (25.5% serious), mostly regarding infections (21.8%), musculoskeletal (17.6%) and skin (16.2%) disorders. Serious AEs included neutropenia (12.7%), lymphocytosis (9.1%) and uveitis (7.3%). The obtained results revealed known AEs but real-world data should be endorsed for undetected safety concerns.

A growing body of evidence suggests the usability of biologic disease-modifying anti-rheumatic drugs (bDMARDs) in treating adult-onset Still's disease (AOSD). In a multicentre "real-life" cohort, the physicians' prescribing motivations and patients' predictive characteristics of being treated with bDMARDs were assessed. Patients with AOSD, who were included in GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort and treated with bDMARDs, were retrospectively assessed. Relevant data were collected by a review of clinical charts. Forty-four patients treated with bDMARDs were analysed, with slight male preponderance (52.3%) and a mean age of 39.3 ± 15.2years. All patients were treated with corticosteroids (CCSs) (38.6% with low dosage) and 93.2% were treated with synthetic DMARDs (sDMARDs). Regarding the effectiveness of the first-line bDMARD, 65.6% of patients experienced a complete remission, defined as complete disappearance of both systemic and joint symptoms and normalisation of laboratory evidence of disease. The physicians' prescribing motivations for bDMARDs were inadequate response to CCSs and/or sDMARDs, CCS-sparing effect and occurrence of macrophage activation syndrome (MAS). Analysing patients' characteristics, chronic disease course (OR 3.09; 95%CI 1.22-7.80, p = 0.017), defined as disease with persistent symptoms, was predictive of being treated with bDMARDs, whereas age (OR 0.97, 95%CI 0.93-0.99, p = 0.048) was negatively associated, suggesting younger age as a further predictive factor. Patients with AOSD were treated with bDMARDs for inadequate response to CCSs and/or sDMARDs, CCS-sparing effect and MAS occurrence. Younger age and chronic disease course were patients' predictive characteristics of being treated with bDMARDs.

Biological drugs, such as proteins and immunogens, are increasingly used to treat various diseases, including tumors and autoimmune diseases, and biological molecules have almost completely replaced synthetic drugs in rheumatology. Although biological treatments such as anti-tumor necrosis factor (TNF) drugs seem to be quite safe, they cause some undesirable effects, such as the onset of infections due to weakening of the immune system. Given the biological nature of these drugs, they might be recognized as extraneous; this would induce an immune reaction that neutralizes their effectiveness or lead to more serious consequences. Laboratories play a pivotal role in appropriate therapeutic management. The aim of this review was to underline the production of anti-drug antibodies during treatment with biological drugs and highlight the role of laboratories in ensuring appropriate use of these drugs.

Marco A Cimmino,1 Massimiliano Parodi,1 Francesca Barbieri,1 Stefano Bombardieri,2 Giuseppe Zampogna,1 Annamaria Iagnocco,3 Alberto Batticciotto,4 Luca Maria Sconfienza,5,6 Luigi Sinigaglia,7 Fabrizio De Benedetti,8 Fabiola Atzeni,9 Piercarlo Sarzi-Puttini10 1Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; 2Rheumatology Unit, Santa Chiara Hospital, University of Pisa, Pisa, Italy; 3Academic Rheumatology Centre, Università degli Studi di Torino, Turin, Italy; 4Rheumatology Unit ASST-Settelaghi, Ospedale di Circolo – Fondazione Macchi, Varese, Varese, Italy; 5IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; 6Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy; 7Rheumatology Unit, G. Pini Hospital, Milan, Italy; 8Division of Rheumatology, IRCCS, Bambin Gesù Paediatric Hospital, Rome, Italy; 9Rheumatology Unit, University of Messina, Messina, Italy; 10Rheumatology Unit, L. Sacco University Hospital, Milan, ItalyCorrespondence: Piercarlo Sarzi-PuttiniReumatology Department, L. Sacco University Hospital, ASST Fatebenefratelli – Sacco, Via G.B. Grassi, 74, Milan 20157, ItalyTel +39 02 39042208Email piercarlo.sarziputtini@gmail.comObjective: This open-label study evaluated the effects of combined tocilizumab (TCZ) and disease-modifying antirheumatic drugs (DMARDs) on magnetic resonance imaging (MRI) changes in synovial membrane enhancement, bone marrow edema (BME), and erosions in the wrist and hand joints of rheumatoid arthritis (RA) patients inadequately responding to DMARDs alone.Methods: The efficacy of intravenous TCZ 8 mg/kg administered every four weeks for 48 weeks was evaluated on six occasions. The primary endpoints were the changes in the extent and degree of wrist synovitis as measured using the RA MRI Score (RAMRIS) and dynamic, gadolinium-enhanced 0.2T MRI (DCE-MRI). A number of different parameters of DCE-MRI were evaluated.Results: Fifty-eight patients were treated, eight of whom (13.8%) discontinued the study prematurely. The mean RAMRIS significantly decreased after two weeks and the decrease was maintained for up to 48 weeks. By week 4, the mean RAMRIS synovitis score had significantly decreased from baseline (− 0.804± 1.575; p=0.018), but not the mean early enhancement (REE) or relative enhancement (RE). However, there were significant decreases in RE at week 24, in REE and Ntotal (total number of enhancing voxels)*IRE (initial rate of enhancement) at weeks 12, 24 and 48, and in Ntotal*ME (maximal enhancement) at weeks 24 and 48. Mean BME decreased from baseline to week 48, and bone erosions did not progress. The patients’ clinical parameters significantly improved from baseline until week 48.Conclusion: TCZ in combination with DMARDs improved wrist synovitis, BME and clinical parameters, without any progression in bone erosions. The RAMRIS for synovitis rapidly improved from as early as two weeks after the first TCZ infusion. (Funded by F. Hoffmann–La Roche; ACTRACE EudraCT No. 2009 012185-32).Keywords: tocilizumab, rheumatoid arthritis, wrist, synovitis, low-field MRI, dedicated MRI

BackgroundPatients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression.MethodsThis was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient’s lifetime.ResultsThe analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p p p ConclusionsHAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc.

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

Background:Fibromyalgia syndrome (FM) is characterised by a complex symptom spectrum, dominated by the presence of chronic widespread pain, fatigue and unrefreshing sleep. FM affects between 2 and 3% of the general population. It is a condition that mainly involves middle-aged women, although it is increasingly being diagnosed in younger people. The severity of symptoms can vary greatly between individual patients, and is influenced by many factors (e.g. sex, body mass index) [1]. To date, there is little information about changes in severity in accordance with patient age.Objectives:The aim of this study was to investigate variations in symptom severity in FM patients according to age categories.Methods:A cross-sectional study of adult FM patients diagnosed according to the American College of Rheumatology 2010/2011 criteria was performed. The case series was included from an Italian national registry [2]. Patients were grouped according to five age categories: 18-40 years, 41-50 years, 51-60 years, 61-70 years, over 71 years. Symptom severity was assessed through the revised Fibromyalgia Impact Questionnaire (FIQR) and domains, including FIQR physical function (items 1-9), FIQR health status (items 10-11), and FIQR symptoms (items 12-21). Between-group characteristics were analysed using one-way analysis of variance (ANOVA).Results:This study included a total of 2889 patients, 403 aged 18-40 years, 756 aged 40-50 years, 1035 aged 50-60 years, 528 aged 60-70 years, and 167 over 70 years, respectively. The mean (standard deviation [SD]) score of the total FIQR was 52.68 (11.82). Total FIQR and individual domains all showed a normal distribution. Analysing the data by age category, there were statistically significant differences between the categories for the total FIQR (p = 0.030). The age categories with the highest disease severity were those above 71 years (FIQR 62.14, SD 22.45), and between 51-60 years (FIQR 60.31, SD 22.89) (Table 1). Significant differences between age categories were also found for the domains physical function (p = 0.006) and health status (p = 0.012), but not for the domain symptoms (p = 0.164).Table 1.Mean values of FIQR total score and domains according to age categories.FIQR and domains18-40 years41-50 years51-60 years61-70 years≥71 yearsp*FIQR total, mean (SD)57.90 (21.76)59.25 (23.30)60.31 (22.89)57.13 (23.59)62.14 (22.45)0.030FIQR physical function, mean (SD)15.51 (7.56)16.44 (7.77)16.77 (7.51)15.96 (7.82)17.68 (7.26)0.006FIQR health status, mean (SD)11.19 (5.85)11.24 (5.99)11.49 (5.93)10.57 (6.11)12.21 (5.97)0.012FIQR symptoms, mean (SD)31.32 (10.48)31.56 (11.32)32.10 (11.01)30.68 (11.47)32.24 (11.34)0.164Abbreviations and legend. FIQR = revised Fibromyalgia Impact Questionnaire; SD = standard deviation; * = one-way analysis of variance (ANOVA).Conclusion:Distinguishing the disease severity in FM patients according to age categories, a bimodal distribution emerges, with the disease severity being greatest in patients over 71 years and in the 51-60 years decade. The main differences in severity, according to what can be detected through the FIQR, are attributable to the domains physical function and health status, which show higher scores in the two classes with higher severity.References:[1]Sarzi-Puttini P et al., Fibromyalgia: an update on clinical characteristics, aetiopathogenesis and treatment. Nat Rev Rheumatol 2020; 16: 645–660.[2]Salaffi F et al., The Italian Fibromyalgia Registry: a new way of using routine real-world data concerning patient-reported disease status in healthcare research and clinical practice. Clin Exp Rheumatol 2020; Suppl 123: 65-71.Acknowledgements:Società Italiana di Reumatologia (SIR) and Italian Ministry of HealthDisclosure of Interests:None declared

Background:Rheumatoid arthritis (RA) is associated with an increased risk of atherosclerotic cardiovascular disease (CVD). The Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA) estimates the 10-year risk of myocardial infarction, stroke or CVD-related death based on conventional and RA-specific (clinical disease activity index, CDAI, disease duration, glucocorticoid use) risk factors (1).Objectives:We evaluated the associations between ERS-RA 10-year risk of CVD, high-sensitivity C-reactive protein (hs-CRP) concentrations, and pharmacological treatment in 1,251 RA patients collected by the “Cardiovascular Obesity and Rheumatic Disease Study (CORDIS)” group of the Italian Society of Rheumatology (SIR).Methods:We assessed independent associations between ERS-RA risk score and each relevant variable using multivariate regression (ENTER approach; listwise deletion analysis). Given the relatively high number of missing hs-CRP data (n=385), regression analysis was also performed using multiple imputation (10 sets, Stata 16.1). Regression models were not adjusted for independent variables included in the ERS-RA score.Results:Among 1,251 RA patients [mean (SD) age 60.4(9.3), range (40-80) years; 78% female; mean (SD) disease duration, 11.6(8) years; mean (SD) CDAI, 9(9); mean (SD) HAQ, 0.77(0.7); mean (SD) hs-CRP, 6.8(12) mg/L] the estimated 10-year CVD risk was 11.6(0.9) % [mean (SD)]. Regarding treatment, 539(43%) received glucocorticoids, 676(54%) a biological or targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) (n missing=1), and 885(81%) at least one conventional synthetic DMARD (csDMARD). Ninety-three (7.4%) patients did not receive any treatment. After adjusting for the use of b/tsDMARD and csDMARD, hs-CRP concentrations were significantly associated with 10-year risk of CVD both in standard multiple regression (n=865; coefficient=0.005 for each 10 mg/L hs-CRP increment, 95% confidence interval (0.000-0.100), p=0.043) and after multiple imputation (n=1,251; coefficient=0.005 for each 10 mg/L hs-CRP increment, 95% confidence interval (0.000-0.114), p=0.035) (Table 1). This corresponds to an increase of 10-year CV risk of 1% for every 20 mg/L increase in hs-CRP concentrations.Conclusion:In a large cohort of RA patients, we observed a significant, positive, and independent association between hs-CRP concentrations and 10-year CV risk estimated by ERS-RA. The cross-sectional design of the study did not allow to establish a cause-effect relationship between hs-CRP and CV risk. Given that conventional CV risk factors and inflammation-related variables are accounted for in the ERS-RA risk score, other, unexplored, mechanisms may underlie the observed association between hs-CRP and CV risk.References:[1]Solomon, D. H., et al. “Derivation and internal validation of an expanded cardiovascular risk prediction score for rheumatoid arthritis: a Consortium of Rheumatology Researchers of North America Registry Study.” Arthritis & rheumatology 67.8 (2015): 1995-2003.Table 1.Multiple regression modelsModel 1n= 865Model 2n= 1, 251ERS-RA scoreCoefficient95% CI, pCoefficient95% CI, phs-CRP, every 10 mg/L increment0.0050.000 to 0.100, 0.0430.0050.000 to 0.011, 0.035b/tsDMARD use-0.002-0.005 to 0.001, 0.199-0.000-0.002 to 0.002, 0.963csDMARD use0.002-0.003 to 0.007, 0.3940.002-0.002 to 0.006, 0.371Prob >F, model with only CRP0.030.03Prob >F, full model0.070.08A multiple linear regression (ENTER method) was performed for the dependent variable ERS-RA score using a listwise deletion analysis (Model 1) and a multiple imputation analysis (Model 2).Disclosure of Interests:None declared

Fibromyalgia (FM) is difficult to diagnose and manage chronic pain condition whose symptoms have no clear pathophysiological cause, although it is thought that patient hypersensitivity to a range of stimuli may give rise to mechanical hyperalgesia as a result of altered central nociceptive processing. The 1990 American College of Rheumatology (ACR) classification criteria, which have been widely used in clinical practice, require the existence of chronic widespread pain (CWP) for >3months, and the presence of at least 11 out of 18 specified tender points upon digital palpation, although this latter criterion has long been criticised. The newer 2010 ACR diagnostic criteria state that FM can be defined as CWP associated with somatic symptoms, and recommend the use of a widespread pain index and a scale to rate symptom severity. A modified version of the 2010 criteria removed the physician assessment of the extent of somatic symptoms and replaced it by a summary score of three self-reported symptoms, thus making it easier to use while maintaining its sensitivity. This review discusses the advantages and limitations of all of these criteria.