ABSTRACT
Background/Purpose: Idiopathic inflammatory myopathies (IIMs) are a group of rare systemic autoimmune rheumatic diseases (AIRDs) with considerable heterogeneity. Little is reported about gender difference in patient-reported outcomes (PROs) of those with IIMs, which have a significant impact on health-related quality of life. We aimed to investigate the gender difference in PROs and treatment regimens of IIM patients utilizing data obtained in the COVID-19 vaccination in autoimmune disease (COVAD) study, a large-scale, international self-reported e-survey assessing the safety of COVID-19 vaccination in patients with various AIRDs including IIMs. Method(s): The COVAD study was launched in April 2021 and continued until December 31, 2021. The survey data regarding demographics, AIRD diagnosis, autoimmune multimorbidity (defined as three or more AIRD diagnoses for each patient), disease activity, current corticosteroid or immunosuppressant use, and PROs including fatigue and pain VAS, PROMIS Short Form -Physical Function 10a (PROMIS PF-10a), general health status, and ability to carry out routine activities were extracted from the COVAD database. Each PRO, disease activity, and treatments were compared between women and men. Patients with inclusion body myositis (IBM) were analyzed separately due to significant difference in treatment regimens and outcomes compared to other IIM subtypes. Factors affecting each PRO were determined by multivariable analysis. Result(s): 1197 complete responses from IIM patients as of August 2021 were analyzed. 845 (70.6%) patients were women. Women were younger (58 [48-68] vs. 69 [58-75] years old, median [interquartile range (IQR)], P0.001), and more likely to suffer from autoimmune multimorbidity compared to men (11.1% vs. 3.1%, P 0.001;Table 1). In patients with non-IBM IIMs, disease activity and corticosteroid use were comparable in both genders, while the distribution of immunosuppressant use was different (P = 0.002), with more hydroxychloroquine use in women (18.3% vs. 6.9%). The median fatigue VAS was significantly higher in women than in men (5 [IQR 3-7] vs. 4 [IQR 2-6], P = 0.004), whereas gender difference in the other PROs was not statistically significant (Table 2). In patients with IBM, on the other hand, no significant gender differences in PROs and treatment regimens were observed. The multivariable analysis in non-IBM IIMs revealed women, living in high-income countries, overlap myositis, and autoimmune multimorbidity as independent factors for higher fatigue VAS. Conclusion(s): Women with IIMs frequently suffer from autoimmune multimorbidity, and also experience more fatigue compared to men, calling for greater attention and further research on targeted treatment approaches. (Table Presented).
ABSTRACT
Background: COVID-19 vaccines have been proven to be safe and effective in the healthy population at large. However, signifcant gaps remain in the evidence of their safety in patients with systemic autoimmune and infammatory disorders (SAIDs). Patients and rheumatologists have expressed concerns regarding vaccination triggered allergic reactions, thrombogenic events, and other adverse events (ADEs) contributing to vaccine hesitancy (1) Objectives: This study aimed to assess and compare short term COVID-19 vaccination associated ADEs in patients with SAIDs and healthy controls (HC) seven days post-vaccination, as well as between patients with SAIDs receiving different vaccines. Methods: We developed an comprehensive, patient self-reporting electronic-survey to collect respondent demographics, SAID details, COVID-19 infection history, COVID-19 vaccination details, 7-day post vaccination adverse events and patient reported outcome measures using the PROMIS tool. After pilot testing, validation, translation into 18 languages on the online platform surveymonkey.com, and vetting by international experts, the survey was circulated in early 2021 by a multicenter study group of >110 collaborators in 94 countries. ADEs were categorized as injection site pain, minor ADEs, major ADEs, and hospitalizations. We analyzed data from the baseline survey for descriptive and intergroup comparative statistics based on data distribution and variable type (data as median, IQR). Results: 10900 respondents [42 (30-55) years, 74% females and 45% Caucasians] were analyzed. 5,867 patients (54%) with SAIDs were compared with 5033 HCs. All respondents included in the fnal analysis had received a single dose of the vaccine and 69% had received 2 primary doses. Pfzer (39.8%) was the most common vaccine received, followed by Oxford/AstraZeneca (13.4%), and Covishield (10.9%). Baseline demographics differed by an older SAID population (mean age 42 vs. 33 years) and a greater female predominance (M:F= 1:4.7 vs. 1:1.8) compared to HCs. 79% had minor and only 3% had major vaccine ADEs requiring urgent medical attention overall. In adjusted analysis, among minor ADEs, abdominal pain [mul-tivariate OR 1. 6 (1.14-2.3)], dizziness [multivariate OR 1. 3 (1.2-1.5)], and headache [multivariate OR 1.67 (1.3-2.2)], were more frequent in SAIDs than HCs. Overall major ADEs [multivariate OR 1. 9 (1.6-2.2)], and throat closure [multivar-iate OR 5.7 (2.9-11.3)] were more frequent in SAIDs though absolute risk was small (0-4%) and rates of hospitalization were similarly small in both groups, with a small absolute risk (0-4%). Specific minor ADEs frequencies were different among different vaccine types, however, major ADEs and hospitalizations overall were rare (0-4%) and comparable across vaccine types in patients with SAIDs (Figure 1). Conclusion: Vaccination against COVID-19 is relatively safe and tolerable in patients with SAIDs. Certain minor vaccine ADEs are more frequent in SAIDs than HCs in this study, though are not severe and do not require urgent medical attention. SAIDs were at a higher risk of major ADEs than HCs, though absolute risk was small, and did not lead to increased hospitalizations. There are small differences in minor ADEs between vaccine types in patients with SAIDs.
ABSTRACT
Background: Idiopathic inflammatory myopathies (IIM) are a rare, multisystem, heterogeneous diseases, and contribute to high psychological burden. The patients' perception of physical health, deteriorating independence and social and environmental relationships may not always be a direct function of disease activity. To face with these aspects, several worldwide specialized organization have recommended the use of patient reported outcome measures (PROMs) both in clinical trials and observational studies to highlight patient's perception of the disease (1). Unfortunately, data on fatigue scores in IIM is limited. Objectives: We compared fatigue VAS scores in patients with IIM, autoimmune diseases (AIDs) and healthy controls (HCs) and triangulated them with PROMIS physical function in a large international cohort made up of answers from the e-survey regarding the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods: Data of 16327 respondents was extracted from the COVAD database on August 31th 2021. VAS fatigue scores were compared between AID, HC and IIM using univariate followed by multivariate analysis after adjusting for baseline differences. We further performed a propensity score matched analysis on 1827 subjects after adjusting for age, gender and ethnicity. The Kruskal-Wallis test was used for continuous variables and chi-square test for categorical variables, and Bonferroni's correction was applied for the post hoc analyses considering IIMs as a reference group. Results: We analyzed answers from 6988 patients, with a mean age of 43.8 years (SD 16.2). The overall percentage of female was 72% and the population ethnicity was mainly composed of White (55.1%), followed by Asian (24.6%), and Hispanic (13.8%). The overall fatigue VAS was 3.6 mm (SD 2.7). IIMs VAS was 4.8 mm (SD 2.6), AIDs 4.5 mm (SD 2.6), and HC 2.8 mm (SD 2.6) (P <0,001). VAS fatigue scores of IIMs were comparable with AIDs (P 0.084), albeit signifcantly higher than the HCs (P <0,001). Notably, fatigue VAS was lower in IIMs than AIDs in two distinct subsets: inactive disease as defned by the patient's perception and the 'excellent' general health condition group, where IIMs had worse scores (P <0,05). Interestingly, fatigue VAS was comparable in active disease defned by physician assessment, patient perception, based on general functional status, or when defned by steroid dose being prescribed. Notably, after propensity matched analysis of patients adjusting for gender, age and ethnicity (1.827 answers, I.e. 609 subjects per group, P =1) the differences disappeared and IIMs and AIDs had comparable fatigue levels across all levels of disease activity, although the fatigue discrepancies with HCs were substantially confrmed. After application of a multivariate linear regression analysis we found that lower fatigue VAS scores were related to HC (P <0,001), male gender (P <0,001), Asian and Hispanic ethnicities (P <0,001 and 0,003). Conclusion: Our study confrms that there is a higher prevalence of fatigue in all the AIDs patients, with comparable VAS scores between IIMs and other AIDs. We can also read our data commenting that females and/or Caucasians patients suffer a higher impact of this manifestation of chronic autoimmune diseases upon their lives. This is why these subjects, to our judgement, should be carefully evaluated during outpatients visits and to whom we should spend some extra time to discuss health related issues and how to improve them.
ABSTRACT
Background: Signifcant gaps are present in the evidence of the spectrum and severity of COVID-19 infection in idiopathic infammatory myopathies (IIM). IIM patients typically require immunosuppressive therapy, may have multiple disease sequelae, and frequent comorbidities, and thus may be more susceptible to severe COVID-19 infection and complications (1). The possibility of attenuated immunogenicity and reduced efficacy of COVID-19 vaccines due to concomitant immunosuppressive medication is a major concern in these patients, and there is little data available on COVID-19 vaccine breakthrough infections (BI) in IIM (2). Objectives: This study aimed to compare disease spectrum and severity and COVID-19 BI in patients with IIM, other systemic autoimmune and infammatory diseases (SAIDs) and healthy controls (HCs). Methods: We developed an extensive self-reporting electronic-survey (COVAD survey) featuring 36 questions to collect respondent demographics, SAID details, COVID-19 infection history, COVID-19 vaccination details, 7-day post vaccination adverse events and patient reported outcome measures using the PROMIS tool. After pilot testing, validation, translation into 18 languages on the online platform surveymonkey.com, and vetting by international experts, the COVAD survey was circulated in early 2021 by a multicenter study group of >110 collaborators in 94 countries. BI was defned as COVID-19 infection occurring more than 2 weeks after receiving 1st or 2nd dose of a COVID-19 vaccine. We analyzed data from the baseline survey for descriptive and intergroup comparative statistics based on data distribution and variable type. Results: 10900 respondents [mean age 42 (30-55) years, 74% females and 45% Caucasians] were analyzed. 1,227 (11.2%) had IIM, 4,640 (42.6%) had other SAIDs, and 5,033 (46.2%) were HC. All respondents included in the fnal analysis had received a single dose of the vaccine and 69% had received 2 primary doses. Pfzer (39.8%) was the most common vaccine received, followed by Oxford/AstraZeneca (13.4%), and Covishield (10.9%). IIM patients were older, had a higher Caucasian representation and higher Pfzer uptake than other SAIDs, and HC. A higher proportion of IIM patients received immu-nosuppressants than other SAIDs. IIMs were at a lower risk of symptomatic pre-vaccination COVID-19 infection compared to SAIDs [multivariate OR 0.6 (0.4-0.8)] and HCs [multivariate OR 0.39 (0.28-0.54)], yet at a higher risk of hospitalization due to COVID-19 compared to SAIDs [univariate OR 2.3 (1.2-3.5)] and HCs [multivariate OR 2.5 (1.1-5.8)]. BIs were very uncommon in IIM patients, with only 17 (1.4%) reporting BI. IIM patients were at a higher risk of contracting COVID-19 prior to vaccination than ≤2 weeks of vaccination [univariate OR 8 (4.1-15)] or BI [univariate OR 4.6 (2.7-8.0)]. BIs were equally severe compared to when they occurred prior to vaccination in IIMs, and were comparable between IIM, SAIDs, and HC (Figure 1), though BI disease duration was shorter in IIMs than SAIDs (7 vs 11 days, p 0.027). 13/17 IIM patients with BI were on immunosuppressants. Conclusion: IIM patients experienced COVID-19 infection less frequently prior to vaccination but were at a higher risk of hospitalization and requirement for oxygen therapy compared with patients with HC. Breakthrough COVID-19 infections were rare (1.4%) in vaccinated IIM patients, and were similar to HC and SAIDs, except for shorter disease duration in IIM.
ABSTRACT
Background: Evaluation of physical function is fundamental in the management of idiopathic infammatory myopathies (IIMs). Patient-Reported Outcome Measurement Information System (PROMIS) is a National Institute of Health initiative established in 2004 to develop patient-reported outcome measures (PROMs) with improved validity and efficacy. PROMIS Physical Function (PF) short forms have been validated for use in IIMs [1]. Objectives: To investigate the physical function status of IIM patients compared to those with non-IIM autoimmune diseases (AIDs) and healthy controls (HCs) utilizing PROMIS PF data obtained in the coronavirus disease-2019 (COVID-19) Vaccination in Autoimmune Diseases (COVAD) study, a large-scale, international self-reported e-survey assessing the safety of COVID-19 vaccines in AID patients [2]. Methods: The survey data regarding demographics, IIM and AID diagnosis, disease activity, and PROMIS PF short form-10a scores were extracted from the COVAD study database. The disease activity (active vs inactive) of each patient was assessed in 3 different ways: (1) physician's assessment (active if there was an increased immunosuppression), (2) patient's assessment (active vs inactive as per patient), and (3) current steroid use. These 3 defnitions of disease activity were applied independently to each patient. PROMIS PF-10a scores were compared between each disease category (IIMs vs non-IIM AIDs vs HCs), stratifed by disease activity based on the 3 defnitions stated above, employing negative binominal regression model. Multivariable regression analysis adjusted for age, gender, and ethnicity was performed clustering countries, and the predicted PROMIS PF-10a score was calculated based on the regression result. Factors affecting PROMIS PF-10a scores other than disease activity were identifed by another multivariable regression analysis in the patients with inactive disease (IIMs or non-IIM AIDs). Results: 1057 IIM patients, 3635 non-IIM AID patients, and 3981 HCs responded to the COVAD survey until August 2021. The median age of the respondents was 43 [IQR 30-56] years old, and 74.8% were female. Among IIM patients, dermatomyositis was the most prevalent diagnosis (34.8%), followed by inclusion body myositis (IBM) (23.6%), polymyositis (PM) (16.2%), anti-syn-thetase syndrome (11.8%), overlap myositis (7.9%), and immune-mediated necrotizing myopathy (IMNM) (4.6%). The predicted mean of PROMIS PF-10a scores was signifcantly lower in IIMs compared to non-IIM AIDs or HCs (36.3 [95% (CI) 35.5-37.1] vs 41.3 [95% CI 40.2-42.5] vs 46.2 [95% CI 45.8-46.6], P < 0.001), irrespective of disease activity or the defnitions of disease activity used (physician's assessment, patient's assessment, or steroid use) (Figure 1). The largest difference between active IIMs and non-IIM AIDs was observed when the disease activity was defned by patient's assessment (35.0 [95% CI 34.1-35.9] vs 40.1 [95% CI 38.7-41.5]). Considering the subgroups of IIMs, the scores were signifcantly lower in IBM in comparison with non-IBM IIMs (P < 0.001). The independent factors associated with low PROMIS PF-10a scores in the patients with inactive disease were older age, female gender, and the disease category being IBM, PM, or IMNM. Conclusion: Physical function is signifcantly impaired in IIMs compared to non-IIM AIDs or HCs, even in patients with inactive disease. The elderly, women, and IBM groups are the worst affected, suggesting that developing targeted strategies to minimize functional disability in certain groups may improve patient reported physical function and disease outcomes.
ABSTRACT
Background: Several reports have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may trigger a vigorous immune response that could lead to the appearance of various autoantibodies such as antinuclear antibodies, antiphospholipid antibodies or anti-neutrophil cytoplasmic antibodies, among others. Moreover, the pulmonary involvement in SARSCoV-2 may resemble that of patients with anti-MDA5 positive syndrome or acute form of antisynthetase syndrome. Objectives: Our aim was to analyse the presence of anti-MDA5 and other myositis-specific autoantibodies such as the antisynthetase antibodies in patients diagnosed with severe acute respiratory syndrome caused by SARS-CoV-2. Methods: Retrospective observational study performed in a tertiary care center. We included 28 patients admitted to the intensive care unit with severe acute respiratory syndrome, 14 at the onset of the disease (group A) and 14 after 30 days of being treated in an intensive care unit (group B). Chest CT was performed at the admission. We analyzed the presence of anti-MDA5 and antisynthetase antibodies by immunoblot (Euroimmune®) and in those who were positive we performed a confirmatory test by immunoprecipitation. Results: All chest CT showed bilateral ground glass pattern. Three out of 14 patients of group A (12 males, 86%, mean ± SD age 67.1 ± 12.2) were positive for antisynthetase antibodies (2 anti-PL7, 1 anti-Jo1), and 6 out of 14 patients of the group B (6 males, 48%, mean ± SD age 68.7 ± 8.1) were positive to antisynthetase antibodies (2 anti-PL7, 2 anti-PL-12, 1 anti-EJ, 1 anti-OJ+PL7). Immunoblots also show positivity for other myositis-specific or associated antibodies, such as anti-TIF1g, anti-PM75, anti-SAE and anti-SRP. All of these results found by immunoblotting were negative by immunoprecipitation. None of the 28 patients were positive for anti-MDA5 antibodies. Conclusion: Severe SARS-CoV-2 pneumonia is characterized by ground glass pattern in chest CT, as it is found in anti-MDA5 or antisynthetase syndrome. The positivity of several myositis related autoantibodies showed in immunoblot appears to be more related to the vigorous immune response producing polyclonal immunoglobulins than triggering a real myositis-associated interstitial lung disease. Clinicians must be aware about these false positive results in patients with severe COVID-19 acute respiratory syndrome.