The impact of multimorbidity on QoL in inflammatory myopathies: COVAD cluster analysis.

OBJECTIVE: The presence of comorbidities can substantially affect patients' quality of life, but data regarding their impact on idiopathic inflammatory myopathies (IIMs) are limited. METHODS: We examined the prevalence of comorbidities in IIM patients, other autoimmune rheumatic diseases (oAIRDs), and healthy controls (HCs), using data from the self-reported COVAD-2 survey. We defined Basic Multimorbidity (BM) as the presence of ≥ 2 non-rheumatic chronic conditions and Complex Multimorbidity (CM) as the presence of ≥ 3 non-rheumatic chronic conditions affecting ≥3 organ systems. Hierarchical Clustering on Principal Components was performed for grouping. RESULTS: Among the COVAD respondents, 1558 IIMs, 4591 oAIRDs, and 3652 HCs were analysed. IIMs exhibited a high burden of comorbidities (OR: 1.62 vs oAIRDs and 2.95 vs HCs, p< 0.01), BM (OR 1.66 vs oAIRDs and 3.52 vs HCs, p< 0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs, p< 0.01), and mental health disorders (MHDs) (OR 1.33 vs oAIRDs and 2.63 vs HCs, p< 0.01). Among the IIM patients, those with comorbidities or MHDs had lower PROMIS Global Physical (PGP), PROMIS Global Mental (PGM), and PROMIS Physical Function (SF10) scores, and higher fatigue (F4a) scores (all p< 0.001). PGP, PGM, SF10a and F4a were influenced by age, active disease, BM, and MHDs. Four distinct clusters were identified among the IIMs according to comorbidities and PROMIS scores. CONCLUSION: Patients with IIMs have a higher burden of comorbidities that influence physical and mental health, identifiable as clinical clusters for optimized and holistic management approaches.

Myo-regressor Deep Informed Neural NetwOrk (Myo-DINO) for fast MR parameters mapping in neuromuscular disorders.

Magnetic Resonance (MR) parameters mapping in muscle Magnetic Resonance Imaging (mMRI) is predominantly performed using pattern recognition-based algorithms, which are characterised by high computational costs and scalability issues in the context of multi-parametric mapping. Deep Learning (DL) has been demonstrated to be a robust and efficient method for rapid MR parameters mapping. However, its application in mMRI domain to investigate Neuromuscular Disorders (NMDs) has not yet been explored. In addition, data-driven DL models suffered in interpretation and explainability of the learning process. We developed a Physics Informed Neural Network called Myo-Regressor Deep Informed Neural NetwOrk (Myo-DINO) for efficient and explainable Fat Fraction (FF), water-T2 (wT2) and B1 mapping from a cohort of NMDs.A total of 2165 slices (232 subjects) from Multi-Echo Spin Echo (MESE) images were selected as the input dataset for which FF, wT2,B1 ground truth maps were computed using the MyoQMRI toolbox. This toolbox exploits the Extended Phase Graph (EPG) theory with a two-component model (water and fat signal) and slice profile to simulate the signal evolution in the MESE framework. A customized U-Net architecture was implemented as the Myo-DINO architecture. The squared L2 norm loss was complemented by two distinct physics models to define two 'Physics-Informed' loss functions: Cycling Loss 1 embedded a mono-exponential model to describe the relaxation of water protons, while Cycling Loss 2 incorporated the EPG theory with slice profile to model the magnetization dephasing under the effect of gradients and RF pulses. The Myo-DINO was trained with the hyperparameter value of the 'Physics-Informed' component held constant, i.e. λmodel = 1, while different hyperparameter values (λcnn) were applied to the squared L2 norm component in both the cycling loss. In particular, hard (λcnn=10), normal (λcnn=1) and self-supervised (λcnn=0) constraints were applied to gradually decrease the impact of the squared L2 norm component on the 'Physics Informed' term during the Myo-DINO training process. Myo-DINO achieved higher performance with Cycling Loss 2 for FF, wT2 and B1 prediction. In particular, high reconstruction similarity and quality (Structural Similarity Index > 0.92, Peak Signal to Noise ratio > 30.0 db) and small reconstruction error (Normalized Root Mean Squared Error < 0.038) to the reference maps were shown with self-supervised weighting of the Cycling Loss 2. In addition muscle-wise FF, wT2 and B1 predicted values showed good agreement with the reference values. The Myo-DINO has been demonstrated to be a robust and efficient workflow for MR parameters mapping in the context of mMRI. This provides preliminary evidence that it can be an effective alternative to the reference post-processing algorithm. In addition, our results demonstrate that Cycling Loss 2, which incorporates the Extended Phase Graph (EPG) model, provides the most robust and relevant physical constraints for Myo-DINO in this multi-parameter regression task. The use of Cycling Loss 2 with self-supervised constraint improved the explainability of the learning process because the network acquired domain knowledge solely in accordance with the assumptions of the EPG model.

Heterogeneity in nomenclature and abbreviation usage for anti-synthetase syndrome: a scoping review.

Anti-synthetase syndrome constitutes a dynamically evolving subset of Idiopathic Inflammatory Myopathy, however, the nomenclature and abbreviations for this syndrome are plagued by heterogeneity, leading to lack of consistency in literature. The objective of this study is to evaluate existing diversity in disease names and abbreviations, with a future goal to develop consensus on the nomenclature. A scoping review format was used for analysis. A comprehensive PUBMED search was conducted from January 1, 1984 (the initial description of anti-synthetase autoantibodies) to November 30, 2023, encompassing all pertinent articles published within this timeframe. Search terms included, ((antisynthetase syndrome) OR (anti synthetase syndrome)) OR (anti-synthetase syndrome)). The articles were screened for presence of terminology and abbreviations used. The search yielded 936 items with the specified terms. After excluding 303 irrelevant articles and 58 non-English publications, the remaining n = 575 articles underwent detailed review of the abstract and full article. Out of n = 575, 54.7% (n = 314) used 'antisynthetase syndrome' and 43.4% (n = 249) preferred 'anti-synthetase syndrome' with few novel names also. Among these, 394 articles used abbreviations while 181 did not. Most utilized term was ASS; in 64.7% (n = 255), followed AS in 11.9% (n = 47), ASSD in 9.9% (n = 39) and ASyS in 7.6% (n = 30). A discordance in nomenclature is evident, with about half using antisynthetase syndrome and other half using anti-synthetase syndrome. Moreover, significant heterogeneity exists in abbreviation use aswell. There is a pressing need to bridge this disparity and establish a uniform identifier for the disease with an objective to develop greater coherence in future research, educational initiatives, and interdisciplinary collaboration.

COVID-19 severity, breakthrough infections and vaccine safety in young individuals with autoimmune diseases: insights from the COVAD study.

Notwithstanding the wealth of literature on COVID-19, studies focusing on young adults with autoimmune diseases (AD) are lacking. To determine early (within 7 days) and late (after 7 days) anti-SARS-CoV-2 vaccine-related adverse events (AEs), post-vaccine disease flares, COVID-19 severity and breakthrough infections (B-INFs) in young people with rheumatic diseases (RMDs) and non-rheumatic autoimmune diseases (nr-ADs) compared to healthy controls (HC). Data were captured through the international COVID-19 vaccination in autoimmune diseases (COVAD) 1 and 2 questionnaires. Of 20,685 complete responses, we identified 6010 from patients aged 18-35 years (1692 RMD, 400 nrADs, 3918 HC) who received up to 4 vaccine doses. BNT162b2 was the most frequently administered vaccine and prior to vaccination, 7% of people with nrAD were taking immunosuppressants (IS) versus 80% in RMDs. Early mild AEs were more frequent in RMDs (93%) and nr-ADs (92%) compared to HC (85%). The frequency of late mild AEs was < 20% in all groups. Severe AEs were rare. SARS-CoV-2 infection rates were similar across all groups, however, RMD patients reported a single episode of infection more frequently than nrADs and HC, while nrADs reported multiple infections more frequently than RMD. Self-reported disease flares were reported by 10% or RMD and 7% of nrAD patients. Our study reinforces the safety of anti-SARS-CoV-2 vaccine also in young people with ADs, but it also highlights that among young individuals the number and clinical picture of SARS-CoV-2 infections is affected more by the type of AD rather than by coexisting IS therapy.

Listening to patients, for the patients: The COVAD Study-Vision, organizational structure, and challenges.

BACKGROUND: The pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy. OBJECTIVES: The COVID-19 vaccination in autoimmune diseases (COVAD) study, a series of ongoing, patient self-reported surveys were conceived with the vision of being a unique tool to gather patient perspectives on AIRDs. It involved a multinational, multicenter collaborative effort amidst a global lockdown. METHODS: Leveraging social media as a research tool, COVAD collected data using validated patient-reported outcomes (PROs). The study, comprising a core team, steering committee, and global collaborators, facilitated data collection and analysis. A pilot-tested, validated survey, featuring questions regarding COVID-19 infection, vaccination and outcomes, patient demographics, and PROs was circulated to patients with AIRDs and healthy controls (HCs). DISCUSSION: We present the challenges encountered during this international collaborative project, including coordination, data management, funding constraints, language barriers, and authorship concerns, while highlighting the measures taken to address them. CONCLUSION: Collaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases. The COVAD study demonstrates the potential of online platforms for conducting large-scale, patient-focused research and underscores the importance of integrating patient perspective into clinical care. Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them.

Characteristics of emerging new autoimmune diseases after COVID-19 vaccination: A sub-study by the COVAD group.

BACKGROUND: Despite the overall safety and efficacy of COVID-19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post-vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post-vaccination. METHODS: A cross-sectional study was conducted among participants with self-reported new-onset SAIDs using the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset-a validated, patient-reported e-survey-to analyze the long-term safety of COVID-19 vaccines. Baseline characteristics of patients with new-onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio. RESULTS: Of 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new-onset SAID post-vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new-onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9-9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3-5.3; p = .004). New-onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1-1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3-1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2-4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4-0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs. CONCLUSION: This study reports a low occurrence of new-onset SAIDs following COVID-19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre-existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID-19 vaccination in the general population. However, long-term studies are needed to understand the autoimmune phenomena arising post-vaccination.

Cardiovascular Risk Evaluation in Psoriatic Arthritis by Aortic Stiffness and the Systemic Coronary Risk Evaluation (SCORE): Results of the Prospective PSOCARD Cohort Study.

INTRODUCTION: Psoriatic arthritis (PsA) is associated with increased cardiovascular (CV) risk and mortality. Aortic stiffness measured by carotid-femoral pulse wave velocity (cfPWV) has been shown to predict CV risk in the general population. The present study aimed to examine cfPWV values of patients with PsA compared to healthy controls and to evaluate associations of cfPWV with patient- and disease-associated characteristics, as well as with an established traditional CV prediction score of the European Society of Cardiology (Systemic Coronary Risk Evaluation; SCORE), for the first time. METHODS: cfPWV and SCORE were evaluated in patients with PsA and healthy controls, along with clinical and laboratory disease parameters. Differences in cfPWV measurements between the two groups and associations of cfPWV with patient- and disease-associated characteristics were statistically evaluated. RESULTS: A total of 150 patients with PsA (PSOCARD cohort) and 88 control subjects were recruited. cfPWV was significantly higher in the PsA group compared to controls, even after adjustment for confounders (padj = 0.034). Moreover, cfPWV was independently associated with disease duration (r = 0.304, p = 0.001), age (rho = 0.688, p < 0.001), systolic arterial pressure (rho = 0.351, p < 0.001), glomerular filtration rate (inverse: rho = - 0.264, p = 0.001), and red cell distribution width, a marker of major adverse CV events (MACE) (rho = 0.190, p = 0.02). SCORE revealed an elevated CV risk in 8.73% of the patients, whereas cfPWV showed increased aortic stiffness and end-organ disease in 16.00% of the same cohort. CONCLUSIONS: In the largest cfPWV/PsA cohort examined to date, patients with PsA exhibited increased aortic stiffness compared to healthy controls. PsA duration was the most important independent disease-associated predictor of increased aortic stiffness, next to traditional CV risk factors. cfPWV measurements may help identify subclinical end-organ disease and abnormal aortic stiffness and thus assist CV risk classification in PsA.

Collating the voice of people with autoimmune diseases: Methodology for the Third Phase of the COVAD Studies.

INTRODUCTION: The growing recognition of holistic patient care highlights the various factors shaping the quality of life of individuals with autoimmune and rheumatic diseases (AIRDs). Beyond the traditional disease measures, there is an emerging acknowledgment of the less-explored aspects, including subjective well-being, social determinants of health, comorbidities, mental health, and medication adherence. Moreover, digital health services have empowered patients to engage actively in decision-making alongside clinicians. To explore these domains within the context of AIRDs, the "Collating the Voice of People with Autoimmune Diseases" COVAD survey was conceived, a successor of the previous two COVAD surveys. In this document, we present the study protocol in comprehensive detail. METHODS: The COVAD-3 survey is a cross-sectional patient self-reported e-survey incorporating multiple widely accepted scales/scores to assess various aspects of patients' lifestyles objectively. To ensure the survey's accuracy and usability across diverse regions, it will be translated into multiple languages and subjected to rigorous vetting and pilot testing. It will be distributed by collaborators via online platforms and data will be collected from patients with AIRDs, and healthy individuals over eight months. Data analysis will focus on outcome measures related to various social, demographic, economic, and psychological factors. CONCLUSION: With the increasing awareness to adopt a holistic treatment approach encompassing all avenues of life, the COVAD-3 survey aims to gain valuable insights into the impact of social, demographic, economic, and psychological determinants of health on the subjective well-being in patients with AIRDs, which will contribute to a better understanding of their overall health and well-being.

A critical view on autoantibodies in lupus nephritis: Concrete knowledge based on evidence.

Deposition of autoantibodies in glomeruli is a key factor in the development of lupus nephritis (LN). For a long time, anti-dsDNA and anti-C1q antibodies were thought to be the main cause of the kidney damage. However, recent studies have shown that the list of autoantibidies that have renal tropism and deposit in the kidney in LN is increasing and the link between anti-dsDNA and renal pathology is weak due to potential confounders. Aspecific bindings of dsDNA with cationic antibodies and of anti-dsDNA with several renal antigens such as actinin, laminin, entactin, and annexinA2 raised doubts about the specific target of these antibodies in the kidney. Moreover, the isotype of anti-dsDNA in SLE and LN has never received adequate interest until the recent observation that IgG2 are preponderant over IgG1, IgG3 and IgG4. Based on the above background, recent studies investigated the involvement of anti-dsDNA IgG2 and of other antibodies in LN. It was concluded that circulating anti-dsDNA IgG2 levels do not distinguish between LN versus non-renal SLE, and, in patients with LN, their levels do not change over time. Circulating levels of other antibodies such as anti-ENO1 and anti-H2 IgG2 were, instead, higher in LN vs non-renal SLE at the time of diagnosis and decreased following therapies. Finally, new classes of renal antibodies that potentially modify the anti-inflammatory response in the kidney are emerging as new co-actors in the pathogenetic scenario. They have been defined as 'second wave antibodies' for the link with detoxifying mechanisms limiting the oxidative stress in glomeruli that are classically stimulated in a second phase of inflammation. These findings have important clinical implications that may modify the laboratory approach to LN. Serum levels of anti-ENO1 and anti-H2 IgG2 should be measured in the follow up of patients for designing the length of therapies and identify those patients who respond to treatments. Anti-SOD2 could help to monitor and potentiate the anti-inflammatory response in the kidney.

Idiopathic inflammatory myopathies: one year in review 2023.

Idiopathic inflammatory myopathies are a group of rare, autoimmune, diseases typically involving striate muscle and also variously affecting several other systems or organs, such as joints, skin, lungs, heart and gastrointestinal tract. IIM are mainly characterised by subacute onset and chronic course and are burdened by significant morbidity and mortality. Despite the rarity of these conditions, several efforts have been undertaken in the last years to better understand their pathogenesis, as well as to achieve a more precise classification and to define the optimal therapeutic approach. The aim of this review is to provide an up-to-date digest of the most relevant studies published on this topic over the last year.

Characteristics and risk factors of COVID-19 breakthrough infections in Idiopathic Inflammatory Myopathies: Results from the COVAD study.

OBJECTIVES: To explore prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIM) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after 2 vaccine doses. We compared BIs characteristics and severity among IIMs, other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HC). Multivariable Cox regression models assessed the risk factors for BI, severe BI and hospitalisations among IIMs. RESULTS: Among 9449 included response, BIs occurred in 1447 (15.3%) respondents, median age 44 years (IQR 21), 77.4% female, and 182 BIs (12.9%) occurred among 1406 IIMs. Multivariable Cox regression among IIMs showed age as a protective factor for BIs [Hazard Ratio (HR)=0.98, 95%CI = 0.97-0.99], hydroxychloroquine and sulfasalazine use were risk factors (HR = 1.81, 95%CI = 1.24-2.64, and HR = 3.79, 95%CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for severe BI (HR = 3.61, 95%CI = 1.09-11.8). Non-White ethnicity (HR = 2.61, 95%CI = 1.03-6.59) was a risk factor for hospitalisation. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIM = 6.0% vs AIRD = 1.8%, nrAID = 2.2%, and HC = 0.9%), intensive care unit admission (IIM = 2.2% vs AIRD = 0.6%, nrAID, and HC = 0%), advanced treatment with antiviral or monoclonal antibodies (IIM = 34.1% vs AIRD = 25.8%, nrAID = 14.6%, and HC = 12.8%), and had more hospitalisation (IIM = 7.7% vs AIRD = 4.6%, nrAID = 1.1%, and HC = 1.5%). CONCLUSION: Patients with IIMs are susceptible to severe COVID-19 BI. Age and immunosuppressive treatments were related to the risk of BIs.

Impaired health-related quality of life in idiopathic inflammatory myopathies: a cross-sectional analysis from the COVAD-2 e-survey.

Objectives: To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods: Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results: We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10-15] IIMs vs 13 [11-15] non-IIM AIRDs vs 15 [13-17] nrAIDs vs 17 [15-18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10-15) IIMs vs 15 (13-17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion: Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs.

Association between ischemia-modified albumin (IMA) and peripheral endothelial dysfunction in rheumatoid arthritis patients.

The identification of circulating biomarkers of endothelial dysfunction (ED), a precursor to atherosclerosis, in rheumatoid arthritis (RA) would facilitate early risk stratification and prevention strategies. Ischemia-modified albumin (IMA) has emerged as a potential biomarker of oxidative stress, ischemia, and ED. However, studies examining the relationship between IMA and ED in RA patients are lacking. We measured serum IMA concentrations by using an albumin cobalt binding test and peripheral vasodilatory capacity by EndoPAT in 113 RA patients without previous cardiovascular events enrolled in the EDRA study (ClinicalTrials.gov: NCT02341066). The mean peripheral vasodilatory capacity, expressed by the log of reactive hyperemia index (logRHI), was 0.82, corresponding to 27% RA patients having ED. The mean plasma concentrations of IMA were 0.478 absorbance units. We observed a significant and inverse association between peripheral vasodilatory capacity and serum IMA concentrations (rho = - 0.22, p = 0.02). In univariate logistic regression, ED was significantly associated with serum IMA concentrations [OR 1173 (95% CI 1.3568 to 101,364), p = 0.040) and higher disease activity. In multivariate logistic regression, the independent association between ED and IMA remained significant after correction for disease activity and other RA-confounders [OR 2252 (95% CI 1.0596 to 4,787,505), p = 0.048 in Model 1; OR 7221 (95% CI 4.1539 to 12,552,859), p = 0.02 in Model 2]. Conclusions: This study suggests that IMA is a promising biomarker of ED in RA. Further research is needed to confirm our findings and determine the clinical utility of IMA in detecting and managing early atherosclerosis in RA patients.

Correlates of breakthrough COVID-19 in vaccinated patients with systemic sclerosis: survival analysis from a multicentre international patient-reported survey.

This study aimed to assess the incidence, predictors, and outcomes of breakthrough infection (BI) following coronavirus disease (COVID-19) vaccination in patients with systemic sclerosis (SSc), a risk group associated with an immune-suppressed state and high cardiopulmonary disease burden. Cross-sectional data from fully vaccinated respondents with SSc, non-SSc autoimmune rheumatic diseases (AIRDs), and healthy controls (HCs) were extracted from the COVAD database, an international self-reported online survey. BI was defined according to the Centre for Disease Control definition. Infection-free survival was compared between the groups using Kaplan-Meier curves with log-rank tests. Cox proportional regression was used to assess the association between BI and age, sex, ethnicity, and immunosuppressive drugs at the time of vaccination. The severity of BI in terms of hospitalization and requirement for oxygen supplementation was compared between groups. Of 10,900 respondents, 6836 fulfilled the following inclusion criteria: 427 SSc, 2934 other AIRDs, and 3475 HCs. BI were reported in 6.3% of SSc, 6.9% of non-SSc AIRD, and 16.1% of HCs during a median follow-up of 100 (IQR: 60-137) days. SSc had a lower risk for BI than HC [hazard ratio (HR): 0.56 (95% CI 0.46-0.74)]. BIs were associated with age [HR: 0.98 (0.97-0.98)] but not ethnicity or immunosuppressive drugs at the time of vaccination. Patients with SSc were more likely to have asymptomatic COVID-19, but symptomatic patients reported more breathlessness. Hospitalization [SSc: 4 (14.8%), HCs: 37 (6.6%), non-SSc AIRDs: 32(15.8%)] and the need for oxygenation [SSc: 1 (25%); HC: 17 (45.9%); non-SSc AIRD: 13 (40.6%)] were similar between the groups. The incidence of BI in SSc was lower than that in HCs but comparable to that in non-SSc AIRDs. The severity of BI did not differ between the groups. Advancing age, but not ethnicity or immunosuppressive medication use, was associated with BIs.

Global disparities in the treatment of idiopathic inflammatory myopathies: results from an international online survey study.

OBJECTIVES: We aimed to explore current practice and interregional differences in the treatment of idiopathic inflammatory myopathies (IIMs). We triangulated these observations considering countries' gross national income (GNI), disease subtypes, and symptoms using patient-reported information. METHODS: A cross-sectional ancillary analysis of the 'COVID-19 vaccination in auto-immune disease' (COVAD) e-survey containing demographic characteristics, IIM subtypes (DM, PM, IBM, anti-synthetase syndrome [ASSD], immune-mediated necrotizing myopathy [IMNM], overlap myopathies [OM]), current symptoms (surrogate for organ involvement) and treatments (corticosteroids [CS], immunomodulators [IM], i.e. antimalarials, immunosuppressants [IS], IVIG, biologic treatments and targeted-synthetic small molecules). Treatments were presented descriptively according to continents, GNI, IIM and organ involvement, and associated factors were analysed using multivariable binary logistic regressions. RESULTS: Of 18 851 respondents from 94 countries, 1418 with IIM were analysed (age 61 years, 62.5% females). DM (32.4%), IBM (24.5%) and OM (15.8%) were the most common subtypes. Treatment categories included IS (49.4%), CS (38.5%), IM (13.8%) and IVIG (9.4%). Notably, treatments varied across regions, GNI categories (IS mostly used in higher-middle income, IM in lower-middle income, IVIG and biologics largely limited to high-income countries), IIM subtypes (IS and CS associated with ASSD, IM with OM and DM, IVIG with IMNM, and biologic treatments with OM and ASSD) and disease manifestations (IS and CS with dyspnoea). Most inter-regional treatment disparities persisted after multivariable analysis. CONCLUSION: We identified marked regional treatment disparities in a global cohort of IIM. These observations highlight the need for international consensus-driven management guidelines considering patient-centred care and available resources.

Flares in IIMs and the timeline following COVID-19 vaccination: a combined analysis of the COVAD-1 and -2 surveys.

OBJECTIVES: Disease flares in the post-coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). METHODS: The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. RESULTS: Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7-235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) were associated with disparity between self-reported and IS-denoted flares. CONCLUSION: A diagnosis of IIMs confers an equal risk of flares in the post-COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.