COVID-19 vaccination-related delayed adverse events among people with rheumatoid arthritis: results from the international COVAD survey

This study aimed to assess COVID-19 vaccination-related AEs in patients with rheumatoid arthritis (RA), in the COVID-19 Vaccination in Autoimmune Diseases (COVAD)-2 study. An online international cross-sectional survey captured self-reported data on COVID-19 vaccination-related adverse events (AEs) in people with RA, autoimmune diseases (AIDs; rheumatic [r] and non-rheumatic [nr]) and healthy controls (HCs). The survey was circulated by the COVAD study group, comprising 157 collaborators across 106 countries, from February to June 2022. Delayed AEs among RA were compared with other rAIDs, nrAIDs and HCs using multivariable binary regression. A total of 7203 participants were included (1423 [19.7%] RA, 2620 [36.4%] rAIDs, 426 [5.9%] nrAIDs, 2734 [38%] HCs), with 75% female. Compared to HCs, individuals with RA reported higher overall major AEs [OR 1.3 (1.0-1.7)], and an increased number of several minor AEs. Compared to nrAIDs, people with RA had several increased reported minor AEs including myalgia and joint pain. People with active RA had increased major AEs [OR 1.8 (1.1-3.0)] and hospitalisation [OR 4.1 (1.3 - 13.3)] compared to inactive RA. RA patients without autoimmune comorbidities had significantly fewer major and minor AEs than those with other rAIDs. A decreased incidence of hospitalisation was seen in patients taking methotrexate or TNF inhibitors compared to patients not taking these medications. COVID-19 vaccination is associated with minimal to no risks of delayed AEs in patients with RA compared to HCs, and fewer compared to other rAIDs. Active RA and presence of co-existing rAIDs were associated with an increased risk of delayed AEs

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

Disease burden in inflammatory arthritis: an unsupervised machine learning approach of the COVAD-2 e-survey dataset

Objectives: To comprehensively compare the disease burden among patients with RA, PsA and AS using Patient-Reported Outcome Measurement Information System (PROMIS) scores and to identify distinct patient clusters based on comorbidity profiles and PROMIS outcomes. Methods: Data from the global COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 e-survey were analysed. Patients with RA, PsA or AS undergoing treatment with DMARDs were included. PROMIS scores (global physical health, global mental health, fatigue 4a and physical function short form 10a), comorbidities and other variables were compared among the three groups, stratified by disease activity status. Unsupervised hierarchical clustering with eXtreme Gradient Boosting feature importance analysis was performed to identify patient subgroups based on comorbidity profiles and PROMIS outcomes. Results: The study included 2561 patients (1907 RA, 311 PsA, 343 AS). After adjusting for demographic factors, no significant differences in PROMIS scores were observed among the three groups, regardless of disease activity status. Clustering analysis identified four distinct patient groups: low burden, comorbid PsA/AS, low burden with depression and high-burden RA. Feature importance analysis revealed PROMIS global physical health as the strongest determinant of cluster assignment, followed by depression and diagnosis. The comorbid PsA/AS and high-burden RA clusters showed a higher prevalence of comorbidities (56.47% and 69.7%, respectively) and depression (41.18% and 41.67%, respectively), along with poorer PROMIS outcomes. Conclusion: Disease burden in inflammatory arthritis is determined by a complex interplay of factors, with physical health status and depression playing crucial roles. The identification of distinct patient clusters suggests the need for a paradigm shift towards more integrated care approaches that equally emphasize physical and mental health, regardless of the underlying diagnosis

COVID-19 vaccine safety during pregnancy and breastfeeding in women with autoimmune diseases: results from the COVAD study

Objectives: We investigated COVID-19 vaccine safety in pregnant and breastfeeding women with autoimmune diseases (AID) in the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods: Delayed-onset (>7 days) vaccine-related adverse events (AE), disease flares (DF), and AID-related treatment modifications were analyzed upon diagnosis of AID versus healthy controls (HC) and the pregnancy/breastfeeding status at the time of at least one dose of vaccine. Results: Among the 9201 participants to the self-administered online survey, 6787 (73.8%) were women. Forty pregnant and 52 breastfeeding patients with AID were identified, of whom the majority had received at least one dose of COVID-19 vaccine (100% and 96.2%, respectively). AE were reported significantly more frequently in pregnant than in non-pregnant patients (overall AE 45% vs 26%, p= 0.01; minor AE 40% vs 25.9%, p= 0.03; major AE 17.5% vs 4.6%, p< 0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC with respect to AE. Post-vaccination DF were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18.3% of age- and disease-matched non-pregnant and non-breastfeeding patients (n = 262). All pregnant/breastfeeding patients who experienced a DF were managed with glucocorticoids; 28.6% and 20% of them required initiation or change in immunosuppressants, respectively. Conclusion: This study provides reassuring insights into the safety of COVID-19 vaccines administered to women with AID during the gestational and post-partum periods, helping overcome hesitant attitudes, as the benefits for the mother and the fetus by passive immunization appear to outweigh potential risks

Characteristics of and risk factors for COVID-19 breakthrough infections in idiopathic inflammatory myopathies: results from the COVAD study

Objectives: The objective of this study was to explore the prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIMs) 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 two vaccine doses. We compared BI characteristics and severity among patients with IIMs, patients with other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HCs). Multivariable Cox regression models were used to assess the risk factors for BI, severe BI, and hospitalizations among patients with IIMs. Results: Among the 9449 included responses, BIs occurred in 1447 respondents (15.3%). The median age was 44 years [interquartile range (IQR) 21], 77.4% were female, and 182 BIs (12.9%) occurred among the 1406 patients with IIMs. Multivariable Cox regression among the data for patients with IIMs showed increasing age to be a protective factor for BIs [hazard ratio (HR) = 0.98, 95% CI = 0.97-0.99], and HCQ and SSZ 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 a 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 hospitalization. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIMs = 6.0% vs AIRDs = 1.8%, nrAIDs = 2.2% and HCs = 0.9%), intensive care unit admission (IIMs = 2.2% vs AIRDs = 0.6%, nrAIDs and HCs = 0%), advanced treatment with antiviral or monoclonal antibodies (IIMs = 34.1% vs AIRDs = 25.8%, nrAIDs = 14.6% and HCs = 12.8%) and had more hospitalization (IIMs = 7.7% vs AIRDs = 4.6%, nrAIDs = 1.1% and HCs = 1.5%). Conclusion: Patients with IIMs are susceptible to severe COVID-19 BIs. Age and immunosuppressive treatments were related to the risk of BIs

Determinants of physical function, as measured using PROMIS PF-10a, in patients with rheumatoid arthritis: results from the international COVID-19 Vaccination in Autoimmune Diseases (COVAD) study

Objectives: Physical function in RA is largely influenced by multiple clinical factors, however, there is a growing body of evidence that psychological state and other comorbidities also play an essential role. Using data obtained in the COVID-19 Vaccination in Autoimmune Diseases study, an international self-reported e-survey, we aimed to explore the predictive ability of sociodemographic and clinical variables on Patient-Reported Outcomes Measurement Information System Physical Function Short Form 10a (PROMIS PF-10a) in RA and to investigate variation in disease activity and functional outcomes based on country-level socio-economic parameters. Methods: Patient demographics, disease characteristics including current symptom status, functional status and treatment variables, as well as income level of the country of residence, were extracted from survey responses. PROMIS PF-10a scores were compared across country income levels. The influence of extracted variables on reversed PROMIS PF-10a scores were investigated using negative binomial univariable- and multivariable regression. Results: A total of 1342 RA patients were included in this analysis. In the optimised parsimonious predictive model for reversed PROMIS PF-10a, older age, female gender, disease duration, fatigue and pain levels were independently associated with worse physical function, whereas Asian ethnicity, higher overall physical health ratings, ability to carry out everyday activities and residing in a country with an upper-middle or high-income level were independently associated with better physical function. Conclusion: Our study highlights that clinical factors remain strong predictors of physical function in RA, irrespective of individual and country-level socio-economic differences. Interestingly, high country-level income was associated with better physical function, irrespective of individual sociodemographic and clinical factors