data from the EULAR COVAX physician-reported registry

Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND: There is a lack of data on SARS-CoV-2 vaccination safety in children and young people (CYP) with rheumatic and musculoskeletal diseases (RMDs). Current vaccination guidance is based on data from adults with RMDs or CYP without RMDs. OBJECTIVES: To describe the safety of SARS-COV-2 vaccination in adolescents with inflammatory RMDs and adults with juvenile idiopathic arthritis (JIA). METHODS: We described patient characteristics, flares and adverse events (AEs) in adolescent cases under 18 with inflammatory RMDs and adult cases aged 18 or above with JIA submitted to the European Alliance of Associations for Rheumatology COVAX registry. RESULTS: A total of 110 cases were reported to the registry. Thirty-six adolescent cases were reported from four countries, most with JIA (42%). Over half (56%) reported early reactogenic-like AEs. One mild polyarthralgia flare and one serious AE of special interest (malaise) were reported. No CYP reported SARS-CoV-2 infection postvaccination.Seventy-four adult JIA cases were reported from 11 countries. Almost two-thirds (62%) reported early reactogenic-like AEs and two flares were reported (mild polyarthralgia and moderate uveitis). No serious AEs of special interest were reported among adults with JIA. Three female patients aged 20-30 years were diagnosed with SARS-CoV-2 postvaccination; all fully recovered. CONCLUSIONS: This is an important contribution to research on SARS-CoV-2 vaccine safety in adolescents with RMDs and adults with JIA. It is important to note the low frequency of disease flares, serious AEs and SARS-CoV-2 reinfection seen in both populations, although the dataset is limited by its size.publishersversionpublishe

Outcomes of SARS-CoV-2 infection among children and young people with pre-existing rheumatic and musculoskeletal diseases

OBJECTIVES: Some adults with rheumatic and musculoskeletal diseases (RMDs) are at increased risk of COVID-19-related death. Excluding post-COVID-19 multisystem inflammatory syndrome of children, children and young people (CYP) are overall less prone to severe COVID-19 and most experience a mild or asymptomatic course. However, it is unknown if CYP with RMDs are more likely to have more severe COVID-19. This analysis aims to describe outcomes among CYP with underlying RMDs with COVID-19. METHODS: Using the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database, we obtained data on CYP with RMDs who reported SARS-CoV-2 infection (presumptive or confirmed). Patient characteristics and illness severity were described, and factors associated with COVID-19 hospitalisation were investigated. RESULTS: 607 CYP with RMDs <19 years old from 25 different countries with SARS-CoV-2 infection were included, the majority with juvenile idiopathic arthritis (JIA; n=378; 62%). Forty-three (7%) patients were hospitalised; three of these patients died. Compared with JIA, diagnosis of systemic lupus erythematosus, mixed connective tissue disease, vasculitis, or other RMD (OR 4.3; 95% CI 1.7 to 11) or autoinflammatory syndrome (OR 3.0; 95% CI 1.1 to 8.6) was associated with hospitalisation, as was obesity (OR 4.0; 95% CI 1.3 to 12). CONCLUSIONS: This is the most significant investigation to date of COVID-19 in CYP with RMDs. It is important to note that the majority of CYP were not hospitalised, although those with severe systemic RMDs and obesity were more likely to be hospitalised

Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis : Results from the COVID-19 Global Rheumatology Alliance physician registry

Funding Information: Competing interests JAS is supported by the National Institute of Arthritis and Funding Information: Musculoskeletal and Skin Diseases (grant numbers K23 AR069688, R03 AR075886, L30 AR066953, P30 AR070253 and P30 AR072577), the Rheumatology Research Foundation (K Supplement Award and R Bridge Award), the Brigham Research Institute, and the R Bruce and Joan M Mickey Research Scholar Fund. JAS has received research support from Amgen and Bristol-Myers Squibb and performed consultancy for Bristol-Myers Squibb, Gilead, Inova, Janssen and Optum, unrelated to this work. ZSW reports grant support from Bristol-Myers Squibb and Principia/ Sanofi and performed consultancy for Viela Bio and MedPace, outside the submitted work. His work is supported by grants from the National Institutes of Health. MG is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K01 AR070585 and K24 AR074534; JY). KLH reports she has received speaker’s fees from AbbVie and grant income from BMS, UCB and Pfizer, all unrelated to this study. KLH is also supported by the NIHR Manchester Biomedical Research Centre. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories such as, among other institutions, AbbVie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal and UCB Pharma. LG reports research grants from Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz and Sanofi; consulting fees from AbbVie, Amgen, BMS, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi Aventis and UCB, all unrelated to this study. EFM reports that LPCDR received support for specific activities: grants from AbbVie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal, MSD, Celgene, Medac, Pharma Kern and GAfPA; grants and non-financial support from Pfizer; and non-financial support from Grünenthal, outside the submitted work. AS reports grants from a consortium of 13 companies (among them AbbVie, BMS, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi Aventis and UCB) supporting the German RABBIT register, and personal fees from lectures for AbbVie, MSD, Roche, BMS and Pfizer, outside the submitted work. AD-G has no disclosures relevant to this study. His work is supported by grants from the Centers for Disease Control and Prevention and the Rheumatology Research Foundation. KMD is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258) and the Rheumatology Research Foundation. NJP is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258). PD has received research support from Bristol-Myers Squibb, Chugai and Pfizer, and performed consultancy for Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Sanofi, Pfizer, Chugai, Roche and Janssen, unrelated to this work. NS is supported by the RRF Investigator Award and the American Heart Association. MFU-G reports grant support from Janssen and Pfizer. SB reports no competing interests related to this work. He reports non-branded consulting fees for AbbVie, Horizon, Novartis and Pfizer (all <$10 000). RG reports no competing interests related to this work. Outside of this work she reports personal and/or speaking fees from AbbVie, Janssen, Novartis, Pfizer and Cornerstones, and travel assistance from Pfizer (all <$10 000). JH reports no competing interests related to this work. He is supported by grants from the Rheumatology Research Foundation and the Childhood Arthritis and Rheumatology Research Alliance. He has performed consulting for Novartis, Sobi and Biogen, all unrelated to this work (<$10 000). JL has received research funding from Pfizer, outside the submitted work. ES is a Board Member of the Canadian Arthritis Patient Alliance, a patient-run, volunteer-based organisation whose activities are largely supported by independent grants from pharmaceutical companies. PS reports no competing interests related to this work. He reports honorarium for doing social media for American College of Rheumatology journals (<$10 000). PMM has received consulting/speaker’s fees from AbbVie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all <$10 000). PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). PCR reports no competing interests related to this work. Outside of this work he reports personal consulting and/or speaking fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and UCB, and travel assistance from Roche (all <$10 000). JY reports no competing interests related to this work. Her work is supported by grants from the National Institutes of Health, Centers for Disease Control, and the Agency for Healthcare Research and Quality. She has performed consulting for Eli Lilly and AstraZeneca, unrelated to this project. Publisher Copyright: © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.Objective To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). Methods We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. Results Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. Conclusions People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.publishersversionPeer reviewe

Outcomes of SARS-CoV-2 infection among children and young people with pre-existing rheumatic and musculoskeletal diseases.

OBJECTIVES: Some adults with rheumatic and musculoskeletal diseases (RMDs) are at increased risk of COVID-19-related death. Excluding post-COVID-19 multisystem inflammatory syndrome of children, children and young people (CYP) are overall less prone to severe COVID-19 and most experience a mild or asymptomatic course. However, it is unknown if CYP with RMDs are more likely to have more severe COVID-19. This analysis aims to describe outcomes among CYP with underlying RMDs with COVID-19. METHODS: Using the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database, we obtained data on CYP with RMDs who reported SARS-CoV-2 infection (presumptive or confirmed). Patient characteristics and illness severity were described, and factors associated with COVID-19 hospitalisation were investigated. RESULTS: 607 CYP with RMDs <19 years old from 25 different countries with SARS-CoV-2 infection were included, the majority with juvenile idiopathic arthritis (JIA; n=378; 62%). Forty-three (7%) patients were hospitalised; three of these patients died. Compared with JIA, diagnosis of systemic lupus erythematosus, mixed connective tissue disease, vasculitis, or other RMD (OR 4.3; 95% CI 1.7 to 11) or autoinflammatory syndrome (OR 3.0; 95% CI 1.1 to 8.6) was associated with hospitalisation, as was obesity (OR 4.0; 95% CI 1.3 to 12). CONCLUSIONS: This is the most significant investigation to date of COVID-19 in CYP with RMDs. It is important to note that the majority of CYP were not hospitalised, although those with severe systemic RMDs and obesity were more likely to be hospitalised

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments

Dynamic Automated Synovial Imaging (DASI) for differentiating between rheumatoid and psoriatic arthritis: automated versus manual interpretation in contrast-enhanced ultrasound

Introduction: Rheumatoid (RA) and psoriatic arthritis (PsA) are common diseases affecting about 1% of population and are characterized by chronic joint inflammation. Although both have peculiar features such as the presence of specific autoantibodies, in the case of RA, or involvement of skin and nails, in the case of PsA, they show many similarities. Joint distribution, clinical and radiological manifestations may be so identical -especially early in the beginning of disease- that differentiation gets impossible except for hard to gain biopsy specimens showing distinct vascularization patterns for both diseases. Among all forms of arthritides, RA has the worst outcome. Early identification and treatment is considered imperative. Synovitis in RA is consistent with inflammation, synovial hyperplasia and neovascularization, that correlates with disease activity, aggressiveness and joint destruction. Synovitis is in RA the primary event, in PsA secondary to inflammation of entheses, capsules and other perisynovial structures. In RA inflammatory vessels are homogenously distributed in synovia and show linear and branching architecture. In PsA vessel distribution is more inhomogeneous in synovial and perisynovial regions and are more tortuous and bushy. Contrast enhanced ultrasonography (CEUS) has been proven to be a very sensitive method in assessing inflammatory neovascularization equivalent to magnetic resonance imaging. The possibility to discriminate RA from PsA with the help of vascularization patterns detected non-invasively by CEUS has not yet been tested. Material and methods: 107 outclinic patients presenting arthritis of finger joints were recruited, 56 with defined RA and 51 with defined PsA. The most active joint was chosen for CEUS exams. The hands were water-immersed and steady probe was used to increase image quality. While contrast bolus injection, contrast tune imaging with low mechanical index was used for image acquisition. CEUS images were validated manually by radiologists for both CEUS grade and presumptive diagnosis of RA or PsA considering histopathological differences. RA was assumed to present with a more homogenous and synovial enhancement and faster time of contrast appearance due to linear and branching vessel architecture, whereas PsA with inhomogeneous enhancement both in synovial and perisynovial region representing entheses and capsules, and later contrast appearance due to tortuous, bushy vessels. Further contrast kinetics were analyzed by ad hoc automated analysis software including a new developed pixel-based and a region-based procedure similar to available commercialized systems. Contrast kinetics of each image pixel was described by a gamma curve f(t)=A(t-t0)a×e(t-t0)/b, and 98 flow parameters in synovial and perisynovial tissue were derived and analyzed. 37 of these parameters proved to be significantly different (p<0.05) between RA and PsA populations. A linear discriminant classifier was trained to identify the transformation optimizing the linear separability of the two groups, and each patient was assigned to RA or PsA with a Bayesian classification algorithm providing the a posteriori probability to belong to the RA or PsA group. The diagnostic power of the identified vascularization pattern was tested by means of leave-one-out analysis. Correlations between flow parameters and clinical data were calculated. Results: Accuracy of automated pixel-based CEUS analysis to discriminate RA from PsA was 0.93 in training and 0.83 in test conditions, by adding data about rheumatoid factor and anti-cyclic citrullinated peptides accuracy was enhanced to 0.99 and 0.93 respectively. Accuracies of manual (0.69) and region-based automated analysis (0.61) were definitively lower. The best flow parameters for the construction of vascularization pattern discriminating between RA and PsA were mean synovial raise time (faster in RA), mean synovial raise constant (lower in RA), time to synovial peak (faster in RA), mean synovial peak value (higher in RA), synovial active regions (more numerous in RA), mean dimension of synovial active regions (greater in RA), synovial and perisynovial blood volume (both greater in RA), synovia/perisynovia blood volume and flow (all higher in RA). No correlations were identified between flow parameter and clinical data. Conclusion: Dynamic automated synovial imaging (DASI) is consistent with a new tool to study directly vascularization patterns in synovitis, which was possible only by histologic specimens up to now. DASI is highly effective to differentiate RA from PsA by identifying distinct vascularization patterns.Riassunto Introduzione: L’artrite reumatoide (AR) e l’artrite psoriasica (APs) sono delle affezioni comuni, che colpiscono l'1% della popolazione generale, e sono caratterizzate dalla infiammazione articolare cronica. Anche se presentano delle peculiarità distintive, quali la presenza di autoanticorpi, nel caso dell’AR, e il coinvolgimento della pelle e delle unghie, nel caso dell’APs, entrambe le forme di artrite presentano molti elementi in comune. La distribuzione articolare e le manifestazioni cliniche e radiologiche possono essere identiche, soprattutto nelle fasi inziali della malattia, cosicché la distinzione diventa impossibile, se non attraverso lo studio istologico della membrana sinoviale, che presenta un tipo di vascolarizzazione specifica per le due artriti, ma però non è facilmente reperibile. Tra le varie artriti l’AR ha la prognosi più sfavorevole e pertanto una diagnosi e terapia precoci sono imperative. La sinovite reumatoide consiste di infiammazione, iperplasia sinoviale e neovascolarizzazione, che correla con l’attività di malattia, aggressività e distruzione articolare. Nell’AR la sinovite è l’evento primitivo, invece nella APs è secondaria all’infiammazione delle entesi, capsule e altre strutture peri-articolari. Nell’AR i vasi infiammatori di morfologia retta e arborescente sono omogeneamente disposti nella sinovia. Nell’APs invece sono tortuosi e “a cespuglio” e la loro distribuzione è disomogenea nella sinovia e peri-sinovia. L’ecografia con mezzo di contrasto (contrast-enhanced ultrasound, CEUS) è una metodica per lo studio vascolare, soprattutto della neovascolarizzazione infiammatoria, molto sensibile raggiungendo il livello della risonanza magnetica. La possibilità di discriminare con la CEUS l’AR dalla APs attraverso l’analisi non-invasiva degli specifici tipi di vascolarizzazione non è ancora stato studiata Materiali and metodi: 107 pazienti afferenti alla nostra unità di Reumatologia ed affetti da artrite delle mani sono stati reclutati. 56 erano stati diagnosticati come AR e 51 come APs. L’articolazione più attiva riferita dal paziente è stata scelta per l’esame CEUS. Le mani sono state immersi in acqua usando una sonda fissa per migliorare la qualità di immagine. Durante l’iniezione di contrasto le immagini sono state acquisite tramite la modalità per contrasto, che hanno in utilizzo indici meccanici bassi. Le immagini CEUS sono state validate manualmente dai radiologici sia per il grado CEUS che per la presunta diagnosi di artrite tendendo conto delle differenze istologiche note. Si assumeva che l’AR presentasse un rinforzo contrastografico sinoviale più omogeno e un tempo di arrivo del contrasto più breve dato la morfologia retta e arborescente dei vasi, mentre l’APs con un rinforzo disomogeneo sia nella zona sinoviale che in quella peri-sinoviale comprendenti le entesi e capsule, e un arrivo del contrasto tardivo per i vasi tortuosi e “a cespuglio”. Inoltre le cinetiche del contrasto sono state analizzate da un sistema analitico automatizzato programmato ad hoc per questo studio. Le analisi hanno compreso una procedura a base di singoli pixel, sviluppata ex novo, e a base di intere regioni, analoga a sistemi attualmente commercializzati. La cinetica dei singoli pixel è stata descritta tramite una curva f(t)=A(t-t0)a×e(t-t0)/b, e 98 parametri di flusso diversi sono stati identificati ed analizzati nella zona sinoviale e peri-sinoviale. 37 di questi parametri presentavano differenze significative tra pazienti con AR e APs (p<0.05). Un classificatore lineare discriminatore è stato allenato per identificare le trasformazioni necessarie per ottimizzare la separabilità lineare dei due gruppi. Ciascun paziente è stato assegnato al gruppo AR o APs attraverso un algoritmo di classificazione bayesiana per determinare la probabilità a posteriori di appartenere ad un gruppo invece che all’altro. La potenza diagnostica del prototipo di vascolarizzazione così creato è stata verificata tramite un’analisi “leave-one-out”. Infine correlazioni tra parametri di flusso CEUS e dati clinici sono stati ricercati. Risultati: L’accuratezza nel discriminare pazienti con AR da quelli con APs è 0.93 per l’analisi CEUS automatizzata a base di pixel nella fase di allenamento e 0.83 nella fase di verifica. Aggiungendo i dati su fattore reumatoide ed anticorpi contro peptidi citrullinati ciclici l’accuratezza aumentava al 0.99 e 0.93 relativamente nella fase di allenamento e verifica. L’accuratezza dell’analisi CEUS manuale (0.69) e dell’analisi automatizzata a base di regioni (0.61) erano definitivamente più basse. I parametri di flusso contrastografico più importanti nella creazione del prototipo di vascolarizzazione discriminante tra AR e APs erano la velocità media di incremento sinoviale (più veloce in AR), la costante di incremento sinoviale (più basso in AR), il tempo al picco sinoviale (più veloce in AR), il valore medio del picco (più alto in AR), il numero delle regioni sinoviali attive (più numerose in AR), la dimensione media della regioni sinoviali attive (più grande in AR), il volume sanguigno sinoviale e peri-sinoviale (più ampio in AR), il volume e flusso sanguigno sinovia/peri-sinovia. Non vi erano correlazioni tra parametri di flusso CEUS e dati clinici. Conclusione: Lo studio di immagini dinamico e automatizzato della sinovia (dynamic automated synovial imaging, DASI) costituisce un nuovo strumento per lo studio diretto della vascolarizzazione in corso di artrite, che finora era solo possibile tramite la biopsia invasiva. DASI è altamente efficace nel discriminare l’AR dall’APs attraverso l’identificazione di un prototipo di vascolarizzazione distinto

Semi Automatic Detection of Synovial Boundaries in Water-Immersion Ultrasound Examination

Rheumatoid arthritis (RA) is a chronic multisystemic autoimmune disease. Its early diagnosis and activity assessment are essential to adjust the proper therapy. Ultrasonography (US) allows direct visualization of early inflammatory joint changes, while being rapidly performed and easily accepted by patients. We propose an algorithm to semi automatically detect synovial boundaries on US images, making minimal use of a priori information on the morphological shape or on the appearance of the joint and of the synovia. After an image denoising step, three joint landmarks are manually identified. In order to identify the synovia-bone and the synovia-soft tissues interfaces, and to tackle the morphological variability of diseased joints, a cascade of two different active contours is developed, whose composition identifies the whole synovial boundary. By comparison with a manual segmentation performed by two radiologists, we obtained an overall mean sensitivity of 86.4% \ub1 11.6%, and a mean value of 76.8% \ub1 7.8% for Dice's similarity index