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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.

To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) and at risk of retinal toxicity but with no apparent signs of retinal toxicity and to compare it with that of untreated subjects.Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment5 years or daily HCQ dose5 mg/kg of actual body weight [ABW]) but no alterations on spectral domain-optical coherence tomography, short-wavelength autofluorescence and 10-2 visual field examination were recruited. Healthy subjects matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analysed using the conventional qAF grid by Delori calculating the qAF of eight sectors of the intermediate ring and the mean of those values (qAFThirty-nine patients treated with HCQ (38 females, mean age 52.1 ± 8.6 years) and 39 untreated subjects (38 females, mean age 51.2 ± 8.6 years) were included. In both HCQ patients and untreated subjects, qAFThese results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure.

Despite the considerable research efforts being made to learn more about COVID-19, little is known about the presence of SARS-CoV-2 genetic material in biological fluids other than respiratory droplets, blood, and feces. The aim of this post-mortem study was to assess the presence of SARS-CoV-2 RNA in the knee synovial fluid, synovial tissue, and bone tissue of COVID-19 patients in order to discover whether the joint is a possible route of transmission during orthopaedic surgical procedures, and clarify the possible role of SARS-CoV-2 as a directly arthritogenic virus.Post-mortem synovial fluid, synovial tissue and bone tissue samples were collected from the knees of five patients who died of COVID-19 in our hospital between September and October 2020, and analysed for the presence of SARS-CoV-2 using a commercial real-time polymerase chain reaction (RT-PCR) panel. Quantitative RT-PCR was used to test post-mortem nasopharyngeal swabs of all of the patients.No SARS-CoV-2 RNA was detected in any of the knee samples, despite the positivity of the throat swab.Our findings indicate that SARS-CoV-2 was not detected in knee synovial fluid, synovial membrane or bone. This makes it unlikely that these are potential sources of contagion, and suggests that SARS-CoV-2 is not directly arthritogenic.

While facing potentially high morbidity from COVID-19 without known effective therapies, the off-label use of several non-specific drugs has been advocated, including re-purposed anti- viral (e.g., remdesivir or the lopinavir/ritonavir combination), biologic agents (e.g., tocilizumab), and antimalarial drugs such as chloroquine and hydroxychloroquine, in association with or without azithromycin. Data regarding the effectiveness of these drugs in treating COVID-19 has been shown in some trials and clinical settings, but further randomised controlled trials are still being carried out. One of the main concerns regarding their widespread use, however, is their possible effects on the QT interval and arrhythmogenic potential. Some of these drugs have been associated with QT prolongation and Torsades de Point, a potentially lethal ventricular arrhythmia. The review aims to highlight the magnitude of this problem, to quickly refresh clinically impacting cornerstones of QT interval and TdP pathophysiology, to summarize the available evidence regarding the QT and arrhythmia impact of drugs used in different clinical settings in COVID-19 patients, and to help the physicians dealing with the knowledge needed in the everyday clinical duties in case of doubts regarding QT-induced arrhythmias in this time of emergency.

Medical cannabis (MC) describes the usually inhaled or ingested use of a cannabis plant or cannabis extract for medicinal purposes. The action of whole cannabis plants is extremely complex because their large number of active compounds not only bind to a plethora of different receptors but also interact with each other both synergistically and otherwise. Renewed interest in the medicinal properties of cannabis has led to increasing research into the practical uses of cannabis derivatives, and it has been found that the endocannabinoid system (particularly CB2 receptor activation) is a possible target for the treatment of inflammatory and the autoimmune diseases related to immune cell activation. However, in vivo findings still lack, creating difficulties in applying translational cannabinoid research to human immune functions. In this review, we summarized the main mechanisms of action of medical cannabis plant especially regarding the immune system and the endocannabinoid system, looking at preliminary clinical data in three most important autoimmune diseases of three different specialities: rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease.

Patients with rheumatoid arthritis (RA) or other rheumatic diseases say that pain and stiffness are symptoms affecting their quality of life. Ketoprofen and ibuprofen are the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation and manage mild-to-moderate pain. The aim of this new systematic review of the literature and meta-analysis of randomized controlled trials (RCTs) was to compare the clinical efficacy of ketoprofen and ibuprofen in patients with RA. The MEDLINE and EMBASE scientific databases were systematically searched from their inception to November 2020 to identify RCTs directly comparing the recommended therapeutic doses of oral ketoprofen (50–200 mg/day) with ibuprofen (600–1800 mg/day) for RA pain relief. The meta-analysis was made using the standardized mean differences (SMD) of each of the identified RCTs using a fixed effects model. Four RCTs involving 456 patients met the inclusion criteria. The results of the meta-analysis showed a statistically significant difference in efficacy in favor of ketoprofen (0.33, 95% CI 0.14–0.52, p = 0.0005) at all point-estimates of the mean-weighted size effect. The heterogeneity test for the efficacy outcome (the hypothesis was χ2 = 3.57%, df = 3, p value = 0.31 and the chance of a test effect was 3.49, p = 0.0005) was not significant, and this was confirmed by a Higgins percentage of 16%. The studies included in the meta-analysis did not reveal any significant differences between the two drugs in terms of tolerability or safety. The result of this meta-analysis shows that ketoprofen is more effective than ibuprofen in managing RA pain at therapeutic doses, thus supporting its use in clinical practice.

Understanding the basis of osteoarthritis (OA) has seen some interesting advancements in recent years. It has been observed that cartilage degeneration is preceded by subchondral bone lesions, suggesting a key role of this mechanism within the pathogenesis and progression of OA, including the formation of ectopic bone and osteophytes. Moreover, low-grade, chronic inflammation of the synovial lining has gained a central role in the definition of OA pathophysiology, and central immunological mechanisms, innate but also adaptive, are now considered crucial in driving inflammation and tissue destruction. In addition, the role of neuroinflammation and central sensitization mechanisms has been characterized as underlying causes of pain chronicity. This has led to a renewed definition of OA, which is now intended as a complex multifactorial joint pathology caused by inflammatory and metabolic factors underlying joint damage. Since this evidence can directly affect the definition of the correct therapeutic approach to OA, an improved understanding of these pathophysiological mechanisms is fundamental. This review provides an overview of the most updated evidence on OA pathogenesis; it presents the most recent insight on the pathophysiology of OA, describing the interplay between immunological and biochemical mechanisms proposed to drive inflammation and tissue destruction, as well as central sensitization mechanisms. Moreover, although the therapeutic implications consequent to the renewed definition of OA are beyond this review scope, some suggestions for intervention have been addressed.

Understanding of the basis of osteoarthritis (OA) has seen some interesting advancements in recent years. It has been observed that cartilage degeneration is preceded by subchondral bone lesions, suggesting a key role of this mechanism within the pathogenesis and progression of OA, as well as the formation of ectopic bone and osteophytes. Moreover, low-grade, chronic inflammation of the synovial lining has gained a central role in the definition of OA physiopathology, and central immunological mechanisms, innate but also adaptive, are now considered crucial in driving inflammation and tissue destruction. In addition, the role of neuroinflammation and central sensitization mechanisms as underlying causes of pain chronicity has been characterized. This has led to a renewed definition of OA, which is now intended as a complex multifactorial joint pathology caused by inflammatory and metabolic factors underlying joint damage. Since this evidence can directly affect the definition of the correct therapeutic approach to OA, an improved understanding of these pathophysiological mechanisms is fundamental. To this aim, this review provides an overview of the most updated evidence on OA pathogenesis; it presents the most recent insights on the pathophysiology of OA, describing the interplay between immunological and biochemical mechanisms proposed to drive inflammation and tissue destruction, as well as central sensitization mechanisms. Moreover, although the therapeutic implications consequent to the renewed definition of OA are beyond this review scope, some suggestions for intervention have been addressed.

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

The goal of this study was to explore additional evidence of convergent and discriminant validity of the Central Sensitization Inventory (CSI) in a large sample of subjects with fibromyalgia (FM).Patients were consecutively enrolled for a cross-sectional assessment comprehensive of three FM-specific measures (the revised Fibromyalgia Impact Questionnaire [FIQR], the modified Fibromyalgia Assessment Status [modFAS], and the Polysymptomatic Distress Scale [PDS]) and of CSI. To test the convergent validity, the Spearman's rho was used to measure the degree of correlation between the variables CSI and the FM-specific measures. To assess discriminant validity, CSI scores were grouped according to FIQR disease severity states, and differences between these groups studied with the Kruskal-Wallis test. Interpretative cutoffs were established with the interquartile reconciliation approach.The study included 562 FM patients, 199 (35.4%) were classified as having central sensitization syndrome (CSI ≥40). CSI was largely correlated with modFAS (ρ = 0.580; p 0.0001), FIQR (ρ = 0.542; p 0.0001), and PDS (ρ = 0.518; p 0.0001). The differences between the CSI scores in accordance with the FIQR were significant (p 0.000001). CSI cutoffs proposed for FM: 21 between remission and mild severity, 30 between mild and moderate severity, 37 between moderate and severe disease, and 51 between severe and very severe disease.The current study successfully showed additional evidence of the convergent and discriminant validity of the CSI in FM patients.

Since January 2020, the whole world has been facing the worst epidemic for a century. SARS-CoV- 2 infection has so far caused more than one million deaths, with the only measures capable of containing the spread of the virus being social distancing, frequent hand washing, and the wearing of masks. Vaccine development was urgently needed and there are now more than 90 candidate vaccines being developed using different technologies. The European Medicines Agency has recently approved a second mRNA-based vaccine, but the introduction of vaccines has raised some doubts about patients with rheumatic disease, who are at high risk of infection because of disease activity and the therapies used to treat it. The aim of this study was to investigate how vaccines may interact with the immune system and treatment of such patients, and how to monitor the post-vaccine antibody titres and T cell responses in order to assess their efficacy and safety.

Coined in 1975 by Resnick et al., diffuse idiopathic skeletal hyperostosis describes a systemic condition that is mainly characterized by flowing ossification of the spine and, less frequently, peripheral entheses. Its overall incidence is 6-12%, but it is more frequently observed in males than in females and subjects aged >50 years, and its increased prevalence in people aged >70 years suggests that the course of the disease begins between the third and fifth decade of life but its clinical manifestations do not appear until later. Its pathogenesis and etiology remain unknown, but it has been reported to be associated with a number of genetic, metabolic, and constitutional factors. The aim of this review is to describe the main features of the disease and stimulate research into its pathogenesis, prevention, and treatment.

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 increased risk of cardiovascular disease (CVD) among patients with autoimmune rheumatic diseases such as rheumatoid arthritis, spondyloarthritis and systemic lupus erythematosus has been extensively documented. Sub-clinical atherosclerosis can be assessed using various non-invasive imaging techniques. However, the mechanisms underlying the higher risk of atherosclerotic CVD in patients with autoimmune rheumatic diseases are not fully known, although they seem to include chronic low-grade systemic inflammation leading to prolonged endothelial activation, accompanied by a pro-thrombotic/pro-coagulant and autoantibody state. Furthermore, sub-clinical atherosclerosis is also influenced by other traditional risk factors for CVD. Including the individual components of the metabolic syndrome (MetS: obesity, impaired glucose metabolism, dyslipidemia and high blood pressure), the degree of which is higher in these patients than in controls. The aim of this narrative review is to discuss the CV manifestations and risk factors involved in the increased risk of CVD among patients with autoimmune rheumatic diseases.

The first-line treatment of axial spondyloarthritis (SpA) is with non-steroidal anti-inflammatory drugs (NSAIDs) and is followed by tumor necrosis factor (TNF) inhibitors (the main treatment for patients not responding to NSAIDs) or drugs targetting the IL-23/IL-17 pathway. The efficacy of disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate and sulfasalazine (SSZ) has not been demonstrated, although SSZ can be considered in patients with concomitant peripheral arthritis.This review describes the beneficial and toxicological effects of the drugs used to treat axial SpA.Growing concerns about the safety of anti-TNF drugs underline the need to ensure that all clinicians are capable of taking appropriate preventive action and adequately treating affected patients.

COVID-19 is an emerging infection caused by a novel coronavirus that is moving so rapidly that on 30 January 2020 the World Health Organization declared the outbreak a Public Health Emergency of International Concern and on 11 March 2020 as a pandemic. An early diagnosis of COVID-19 is crucial for disease treatment and control of the disease spread. Real-time reverse-transcription polymerase chain reaction (RT-PCR) demonstrated a low sensibility; therefore chest computed tomography (CT) plays a pivotal role not only in the early detection and diagnosis, especially for false negative RT-PCR tests, but also in monitoring the clinical course and in evaluating the disease severity. This paper reports the CT findings with some hints on the temporal changes over the course of the disease: the CT hallmarks of COVID-19 are bilateral distribution of ground glass opacities with or without consolidation in the posterior and peripheral lung, but the predominant findings in later phases include consolidations, linear opacities, "crazy-paving" pattern, "reversed halo" sign and vascular enlargement. The CT findings of COVID-19 overlap with the CT findings of other diseases, in particular the viral pneumonia including influenza viruses, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, etc. There are differences as well as similarities in the CT features of COVID-19 compared with those of the severe acute respiratory syndrome. The aim of this article is to review the typical and atypical CT findings in COVID-19 patients in order to help radiologists and clinicians to become more familiar with the disease.

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.

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.

Spondyloarthritis are chronic inflammatory diseases affecting spine, peripheral joints and enthesis, as well as extra-articular sites (bowel, eyes, skin). Diagnosis of spondyloarthritis often is slow and requires a multidisciplinary approach. The “Early SpA Clinic” project aimed at improving the patient care and journeys, by solving some organizational issues existing in Rheumatology Clinics. The “Early SpA Clinic” involved 19 Italian Rheumatology Centers using in-depth organizational analyses to identify areas for improvement. From the results of the analyses, some organizational solutions were suggested, and their impact measured at the end of the project through specific KPI. With the implementation of the suggested organizational solutions, Centers achieved relevant results, positively impacting on all the phases of the patient journey: decrease in waiting lists (−23%) and in the time length to transit the Center (−22%), increase in the percentage of new diagnoses (+20%), in the saturation of outpatient clinic capacity (+16%), and in the patient satisfaction (+4%). Centers involved in the “Early SpA Clinic” implemented several organizational actions based on an overall assessment of their activities and on solutions that required no additional resources. Overall, the Centers achieved the “Early SpA Clinic” objectives in terms of better management of resources, personnel, spaces, equipment, in relation to the volumes of patients.

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

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.

ObjectivesTocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database.MethodsPatients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months.ResultsNinety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference −1.0, 95% CI −3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (−6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles.ConclusionAlthough this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.