Trial of Intravenous Immune Globulin in Dermatomyositis.

BACKGROUND: Intravenous immune globulin (IVIG) for the treatment of dermatomyositis has not been extensively evaluated. METHODS: We conducted a randomized, placebo-controlled trial involving patients with active dermatomyositis. The patients were assigned in a 1:1 ratio to receive IVIG at a dose of 2.0 g per kilogram of body weight or placebo every 4 weeks for 16 weeks. The patients who received placebo and those without confirmed clinical deterioration while receiving IVIG could enter an open-label extension phase for another 24 weeks. The primary end point was a response, defined as a Total Improvement Score (TIS) of at least 20 (indicating at least minimal improvement) at week 16 and no confirmed deterioration up to week 16. The TIS is a weighted composite score reflecting the change in a core set of six measures of myositis activity over time; scores range from 0 to 100, with higher scores indicating greater improvement. Key secondary end points included at least moderate improvement (TIS ≥40) and major improvement (TIS ≥60), and change in score on the Cutaneous Dermatomyositis Disease Area and Severity Index. RESULTS: A total of 95 patients underwent randomization: 47 patients were assigned to the IVIG group, and 48 to the placebo group. At 16 weeks, 79% of the patients in the IVIG group (37 of 47) and 44% of those in the placebo group (21 of 48) had a TIS of at least 20 (difference, 35 percentage points; 95% confidence interval, 17 to 53; P<0.001). The results with respect to the secondary end points, including at least moderate improvement and major improvement, were generally in the same direction as the results of the primary end-point analysis, except for the change in creatine kinase level (an individual core measure of the TIS), which did not differ meaningfully between the two groups. Over 40 weeks, 282 treatment-related adverse events occurred in the IVIG group, including headache (in 42% of patients), pyrexia (in 19%), and nausea (in 16%). A total of 9 serious adverse events that were considered to be related to IVIG occurred, including 6 thromboembolic events. CONCLUSIONS: In this 16-week trial involving adults with dermatomyositis, the percentage of patients with a response of at least minimal improvement based on a composite score of disease activity was significantly greater among those who received IVIG than among those who received placebo. IVIG was associated with adverse events, including thromboembolism. (Funded by Octapharma Pharmazeutika; ProDERM ClinicalTrials.gov number, NCT02728752.).

A review of the evidence for the utility of physical activity monitor use in patients with idiopathic inflammatory myopathies.

Few proven therapies exist for patients with idiopathic inflammatory myopathies (IIMs), partly due to the lack of reliable and valid outcome measures for assessing treatment responses. The current core set measures developed by the International Myositis Assessment and Clinical Studies group were developed to standardize assessments of disease activity and treatment effect. None of the current measures address functional improvement in muscle weakness. Therefore, supplemental measures to more objectively assess physical activity levels and fatiguability in free-living settings are needed to assess disease activity more comprehensively. Validated physical activity monitors (PAMs) have the potential to serve as an objective functional outcome measure in clinical trials and observational studies. This review examines the current evidence for the use of body-worn PAMs in clinical settings with IIM patients. A practical overview of methods for PAM use in clinical patient populations (including measurement details and data processing) that focuses on IIM patients is also presented.

Pain is Common in Myositis and Associated with Disease Activity.

BACKGROUND: Understanding pain in myositis remains challenging. This study aimed to assess patient-reported pain and its correlation with myositis core set measures (CSMs), patient-reported outcomes (PROs), and functional measures. METHODS: Fifty subjects underwent baseline, 3-month, and 6-month assessments, evaluating myositis CSMs, functional measures, and patient-reported outcomes. Pain was measured using three methods: (1) a 10-cm Visual Analogue Scale (VAS), (2) pain score from the HAQ-DI, and (3) SF-36 (Short Form survey) pain questions. Correlations between disease activity measures and pain were examined at baseline, and changes in both were assessed at 6 months, along with longitudinal change of pain. The change in pain was also correlated with the published 2016 ACR/EULAR myositis response criteria, physician/patient's assessment of change. RESULTS: Nearly half of patients (45%) reported moderate to severe pain in all 3 pain scales, with higher severity of pain in PM/NM subset. At baseline, pain severity showed a strong correlation with most CSMs, PROs and functional outcomes in all the 3 pain scales and similar trends were noted for change in pain at the 6 months. On longitudinal analysis, the physical function scores and fatigue showed strong correlation with pain. Pain improved in myositis patients with improvement in disease activity over time. CONCLUSIONS: Pain is common in myositis and is associated with multiple measures of disease activity, PROs, and functional outcomes in myositis. Most importantly pain improves with improvement in disease activity. SF-36 pain questions have good psychometric properties.

Patient reported outcome for physical function in idiopathic inflammatory myopathy.

OBJECTIVES: There is an unmet need to develop patient-reported outcomes (PRO) measures for Idiopathic Inflammatory Myopathies (IIM). To investigate the feasibility, compliance, and psychometric properties of NIH's Patient-Reported Outcomes Measurement Information System (PROMIS) physical function-20 (PF-20) in a large U.S. IIM population. METHODS: "Myositis Patient Centered Tele-Research" (My PACER) is a multicentre prospective observational study of IIM patients, competitively recruited through traditional in-person clinic visits (Center-Based Cohort [CBC]), and remotely using smartphone and web-based technology (Tele-Research Cohort [TRC]). The CBC was further randomly divided (1:1 ratio) into a traditional local sub-cohort, and a remote sub-cohort. Data collected included PRO and other patient self-assessments monthly for 6 months. Clinician-reported outcomes were obtained at baseline and 6 months. RESULTS: 120 IIM patients were enrolled (82 TRC/38 CBC, mean age 55 ± 13.4, 75% females, 81% Caucasians), with similar demographics and mean PROMIS PF-20 score between cohorts. The PROMIS PF-20 score was not associated with age, sex or race. The compliance and completion rates were similar between TRC and CBC as well as sub-cohorts. PROMIS PF-20 showed strong test-retest reliability at 1 month. PROMIS PF-20 was significantly associated with all core set measures except extra-muscular global and CK, as well as with most of symptoms, function and physical activity measures. PROMIS PF-20 illustrated concordant change with myositis response criteria and patient assessment, with a large effect size. CONCLUSIONS: PROMIS PF-20 demonstrates favorable psychometric properties including reliability, validity and responsiveness in a large cohort of myositis patients, with similar adherence in local or remotely enrolled patients.

A patient centered assessment of the 2016 ACR-EULAR Myositis Response Criteria: evaluating the meaningfulness of response.

OBJECTIVES: The ACR-EULAR Myositis Response Criteria (Total Improvement Score [TIS]) is a composite measure calculated using changes in myositis core set measures. It is unclear if achieving improvement per TIS reflects improvement in any symptoms of myositis patients. In this study, we examined the association between achieving TIS improvement and patient-centered outcome measures (PCOMs). METHODS: Adults with myositis were enrolled in a prospective study with baseline and 6-month visits. Six core set measures were collected at each visit along with the following PCOMs: Fatigue (visual analogue scale [VAS] and short form 36 [SF36]), pain (VAS, SF36), health-related quality of life (SF-36), physical function (PROMIS-physical function, SF36, sit-to-stand, timed up-and-go, and six-min walk) and physical activity (actigraphy). Mann-Whitney U was used to compare PCOMs between improvement groups. Spearman correlation and regression models were used for correlation and association between TIS and PCOMs, respectively. RESULTS: Of 50 patients (six polymyositis, 24 dermatomyositis, 9 necrotizing myopathy, 11 anti-synthetase syndrome) enrolled (mean age: 52, 60% female), 21 patients satisfied the TIS improvement criteria at 6-months. PCOMs including fatigue, pain, quality of life, physical activity and physical function demonstrated significantly greater improvement in patients who had minimal TIS improvement compared with those with no improvement. Greater PCOM improvements were seen with moderate-major TIS improvement. TIS correlated moderately-strongly with most PCOMs. CONCLUSION: Achieving improvement criteria was accompanied by significant clinical improvements in fatigue, pain, health-related quality of life, physical function, and physical activity. These results support the use of TIS as a clinically meaningful metric of improvement.

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.

Brepocitinib, a potent and selective TYK2/JAK1 inhibitor: scientific and clinical rationale for dermatomyositis.

Dermatomyositis (DM) is a rare and debilitating, systemic, autoimmune disease. While heterogenous in presentation and severity, DM is primarily characterised by a spectrum of skin and muscle disease, which may include proximal muscle weakness and recalcitrant cutaneous eruptions. DM may also be associated with joint pain and stiffness, inflammatory arthritis, dysphagia, fatigue, and calcinosis. The current standard of care for DM includes glucocorticoids, immunosuppressants, and intravenous immunoglobulin (IVIg). Unfortunately, these medications are not uniformly effective and can lead to adverse events, particularly with chronic use, necessitating discontinuation of therapy. Therefore, a substantial unmet need exists for more tailored and efficacious therapies that target DM pathogenesis. Brepocitinib is an oral, once-daily, novel, and specific TYK2/JAK1 inhibitor. Brepocitinib's potent inhibition of TYK2 and JAK1 reduces the signalling of pro-inflammatory cytokines, including IFN-α/ß, IL-12, IL-23, and IFNγ, that have been implicated in the pathogenesis of DM. Other JAK inhibitors have been used off-label in both case series and open-label clinical trials in patients with DM; and brepocitinib has demonstrated efficacy in phase 2 clinical trials of several other autoimmune diseases, including plaque psoriasis, psoriatic arthritis, Crohn's disease, hidradenitis suppurativa, and ulcerative colitis. Therefore, there is a strong scientific and clinical rationale for the utility and potential effectiveness of brepocitinib in the treatment of DM patients. Currently, the safety, tolerability, and efficacy of brepocitinib is being evaluated in the largest (n=225) double-blind placebo-controlled phase 3 trial in DM patients to date (VALOR - NCT0543726).

Serum cytokine profiles of adults with idiopathic inflammatory myopathies.

OBJECTIVES: There is a paucity of available biomarkers of disease activity in idiopathic inflammatory myopathies (IIM), and serum cytokines/chemokines hold potential as candidate biomarkers. We aimed to determine serum cytokine profiles of IIM patients with active disease as compared to patients in remission and healthy controls. METHODS: The IIM patients with active disease (included patients enrolled in repository corticotropin injection trial), in remission, and healthy controls were enrolled in this cross-sectional observational study. Serum concentrations of 51 cytokines/chemokines were obtained by utilising a bead-based multiplex cytokine assay (Luminex®). The myositis core set measures were obtained for all the patients. Cytokines with the best predictive ability to differentiate these clinical groups were assessed with three methods: 1) Least Absolute Shrinkage and Selection Operator modelling, 2) stepwise approach, and 3) logistic regression model. RESULTS: Twenty-one IIM patients with active disease, 11 IIM patients in remission and 10 healthy controls were enrolled. Myositis patients had elevated levels of chemokines that attract eosinophils (eotaxin) and dendritic cells, NK cells, cytotoxic T-cells and monocytes/macrophages (CXCL-9, IP-10), cytokines that drive T-helper 1 responses (TNF-a, lymphotoxin-a), matrix degrading enzymes (MMP-3 and -9), and IGFBP-2 compared to healthy controls. Myositis patients with active disease had higher levels of lymphotoxin-a, CXCL-9, MIP-1a, MIP-1b and MMP-3 than patients in remission. CONCLUSIONS: This study demonstrated differences in cytokine profiles of IIM patients (active and inactive disease) compared to healthy controls and identified some cytokines that could potentially be used as biomarkers. Larger longitudinal studies are needed to validate our findings.

Performance of the 2017 EULAR/ACR Classification Criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a scoping review.

The 2017 EULAR/ACR classification criteria for adult/juvenile idiopathic inflammatory myopathies (IIM) were established using a data-driven approach by an international group of myositis experts to allow classification of IIM and its major subtypes. Since their publication, the performance of the criteria has been tested in multiple cohorts worldwide and significant limitations have been identified. Moreover, the understanding and classification of IIM have evolved since 2017. This scoping review was undertaken as part of a large international project to revise the EULAR/ACR criteria and aims to i) summarise the evidence from the current literature on the performance characteristics of the 2017 EULAR/ACR classification criteria in various cohorts and IIM subtypes, and ii) delineate the factors that need to be considered in the revision of the classification criteria. A systematic search of Medline (via PubMed), Cumulative Index to Nursing and Allied Health Literature, and conference abstract archives was conducted independently by three investigators for studies on the EULAR/ACR criteria published between October 2017 and January 2023. This scoping review of 19 articles and 13 abstracts revealed overall good performance characteristics of the EULAR/ACR criteria for IIM, yet deficiencies in lack of inclusion of certain IIM subtypes, such as immune mediated necrotising myopathy, amyopathic dermatomyositis, antisynthetase syndrome and overlap myositis. Published modifications that may improve the performance characteristics of the criteria for classification of IIM subtypes were also summarised. The results of this review suggest that a revision of the EULAR/ACR criteria is warranted.

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.

COVID-19 breakthrough infections in type 1 diabetes mellitus: a cross-sectional study by the COVID-19 Vaccination in Autoimmune Diseases (COVAD) Group.

To investigate the frequency, profile, and severity of COVID-19 breakthrough infections (BI) in patients with type I diabetes mellitus (T1DM) compared to healthy controls (HC) after vaccination. The second COVID-19 Vaccination in Autoimmune Diseases (COVAD-2) survey is a multinational cross-sectional electronic survey which has collected data on patients suffering from various autoimmune diseases including T1DM. We performed a subgroup analysis on this cohort to investigate COVID-19 BI characteristics in patients with T1DM. Logistic regression with propensity score matching analysis was performed. A total of 9595 individuals were included in the analysis, with 100 patients having T1DM. Among the fully vaccinated cohort, 16 (16%) T1DM patients had one BI and 2 (2%) had two BIs. No morbidities or deaths were reported, except for one patient who required hospitalization with oxygen without admission to intensive care. The frequency, clinical features, and severity of BIs were not significantly different between T1DM patients and HCs after adjustment for confounding factors. Our study did not show any statistically significant differences in the frequency, symptoms, duration, or critical care requirements between T1DM and HCs after COVID-19 vaccination. Further research is needed to identify factors associated with inadequate vaccine response in patients with BIs, especially in patients with autoimmune diseases.

Breakthrough SARS-CoV-2 infection and disease flares in patients with rheumatoid arthritis: result from COVAD e-survey study.

COVID-19 has been suggested as a possible trigger of disease flares in patients with rheumatoid arthritis (RA). However, factors associated with disease flares remain unknown. This study aimed to identify factors associated with breakthrough infection (BIs) and disease flares in patients with RA following COVID-19. We analysed data from RA patients who participated in the COVID-19 vaccination in autoimmune diseases (COVAD) study. Demographic data, patient-reported outcomes, comorbidities, pharmacologic treatment and details regarding disease flares were extracted from the COVAD database. Factors associated with disease flare-ups were determined by multivariate logistic regression analysis. The analysis comprised 1928 patients with RA who participated in the COVAD study. Younger age, Caucasian ethnicity, comorbidities with obstructive chronic pulmonary disease and asthma were associated with COVID-19 breakthrough infection. Moreover, younger age (odds ratio (OR): 0.98, 95% CI 0.96-0.99, p < 0.001), ethnicity other than Asian, past history of tuberculosis (OR: 3.80, 95% CI 1.12-12.94, p = 0.033), treatment with methotrexate (OR: 2.55, 95% CI: 1.56-4.17, p < 0.001), poor global physical health (OR: 1.07, 95% CI 1.00-1.15, p = 0.044) and mental health (OR: 0.91, 95% CI 0.87-0.95, p < 0.001) were independent factors associated disease flares in patients with RA. Our study highlights the impact of socio-demographic factors, clinical characteristics and mental health on disease flares in patients with RA. These insights may help determine relevant strategies to proactively manage RA patients at risk of flares.

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.

Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies.

OBJECTIVES: In dermatomyositis (DM), autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with an increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies. METHODS: Phage ImmunoPrecipitation Sequencing using sera from 43 patients with DM suggested that transcription factor Sp4 is a novel autoantigen; this was confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein. Sera from 371 Johns Hopkins patients with myositis (255 with DM, 28 with antisynthetase syndrome, 40 with immune-mediated necrotising myopathy, 29 with inclusion body myositis and 19 with polymyositis), 80 rheumatological disease controls (25 with Sjogren's syndrome, 25 with systemic lupus erythematosus and 30 with rheumatoid arthritis (RA)) and 200 healthy comparators were screened for anti-SP4 autoantibodies by ELISA. A validation cohort of 46 anti-TIF1γ-positive patient sera from the University of Pittsburgh was also screened for anti-Sp4 autoantibodies. RESULTS: Anti-Sp4 autoantibodies were present in 27 (10.5%) patients with DM and 1 (3.3%) patient with RA but not in other clinical groups. In patients with DM, 96.3% of anti-Sp4 autoantibodies were detected in those with anti-TIF1γ autoantibodies. Among 26 TIF1γ-positive patients with anti-Sp4 autoantibodies, none (0%) had cancer. In contrast, among 35 TIF1γ-positive patients without anti-Sp4 autoantibodies, 5 (14%, p=0.04) had cancer. In the validation cohort, among 15 TIF1γ-positive patients with anti-Sp4 autoantibodies, 2 (13.3%) had cancer. By comparison, among 31 TIF1γ-positive patients without anti-Sp4 autoantibodies, 21 (67.7%, p<0.001) had cancer. CONCLUSIONS: Anti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk.

Discordance between patient- and physician-reported disease activity in adult idiopathic inflammatory myopathy.

OBJECTIVES: Patient-reported global disease activity (patient-global) is a myositis core set measure. Understanding the drivers of patient-global is important in patient assessment, and disagreements between physician and patient perception of disease activity may negatively impact shared decision making. We examined the determinants of patient-global and discordance between patient-global and physician-reported global disease activity (physician-global) in idiopathic inflammatory myopathies (IIMs). METHODS: Adults with IIM were enrolled in a prospective observational cross-sectional study. The following myositis outcome measures were collected: patient-global, physician-global, extramuscular and muscle disease activity, manual muscle testing, HAQ, creatine kinase, fatigue, pain, Patient-Reported Outcomes Measurement Information System physical function, 36-item Short Form, sit to stand, timed up and go, 6-minute walk and Actigraph steps/min/day count. A linear regression model was used to determine the contribution of each measure to patient-global. Discordance was defined as ≥3 points difference between patient-global and physician-global. RESULTS: Fifty patients [60% females; mean age 51.6 years (s.d. 14.9)] with probable/definite IIM (EULAR/ACR classification criteria for IIM) were enrolled. Physical function and fatigue measures contributed to patient-global the most, followed by measures of pain, physical activity, quality of life and muscle disease, while physician-global was primarily driven by muscle disease activity. Patient-global was discordant with physician-global in 30% of the patients, of which patient-global was higher than physician-global in 66%. Pain, fatigue and physical activity contributed more to patient-global than physician-global. CONCLUSION: Fatigue, pain and physical activity are important driving factors of the differences observed in the patient vs physician assessment of myositis disease activity. Understanding the gap between patient and physician perspectives may help provide better patient-centred care.

Correlation between B cell epitope profile and clinical features of anti-MDA5 antibody-positive dermatomyositis.

OBJECTIVES: Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) dermatomyositis patients exhibit a variety of clinical features. We therefore investigated whether patterns of B cell epitope recognition are linked to the clinical course of MDA5+ dermatomyositis. METHODS: Our cross-sectional study used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 24 MDA5+ myositis patients. Correlations between clinical features and standardized anti-MDA5 subfragment antibody titers were assessed via Spearman's rank correlation coefficients. RESULTS: Twenty-four MDA5+ patients submitted serum samples within a median of 0 (interquartile range, 0-74) days from the initial clinic visit. In addition to typical dermatomyositis rashes, these patients exhibited muscle symptoms (n = 11), vascular dysfunction (n = 9), and interstitial lung disease (ILD) (n = 16). Female patients exhibited higher titers of antibodies recognizing fragment H (aa 905-1026) compared to male patients. Muscle involvement was associated with higher levels of anti-fragment F (aa 646-801) antibody. Conversely, patients with vascular abnormalities had higher anti-fragment B (aa 130-284) and E (aa 517-671) antibody titers than those without vascular dysfunction. Four patients died due to ILD progression and showed higher anti-fragment A (aa 1-155) antibody titers than the other 20 patients. Differences in the ratio of anti-fragment to anti-full length MDA5 antibody titers were found for sex (H: anti-MDA5) and vascular dysfunction (anti-fragment B, E: anti-MDA5). CONCLUSIONS: Various clinical features of MDA5+ dermatomyositis correlated with levels of antibodies targeting selected subfragments of this autoantigen, providing a link between fragment-specific immune responses and disease course.

COVID-19 vaccination in autoimmune diseases (COVAD) study: vaccine safety and tolerance in rheumatoid arthritis.

OBJECTIVES: The COVID-19 vaccination in autoimmune diseases (COVAD) study aimed to assess short-term COVID-19 vaccination-related adverse events (AEs) in RA patients. METHODS: An online self-reported questionnaire (March-December 2021) was used to capture data related to COVID-19 vaccination-related AEs in RA, other autoimmune rheumatic diseases (AIRDs) (excluding RA and inflammatory myositis), non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs). Descriptive and multivariable regression analyses were performed. RESULTS: Of the 9462 complete respondents, 14.2% (n = 1347) had been diagnosed with RA; they had a mean (s.d.) age of 50.7 (13.7) years, 74.2% were women and 49.3% were Caucasian. In total, 76.9% and 4.2% of patients with RA reported minor and major AEs, respectively. Patients with active and inactive RA had similar AE and hospitalization frequencies. Overall, AEs were reported more frequently by BNT162b2 and mRNA-1273 recipients and less frequently by BBV152 recipients compared with the rest. Major AE and hospitalization frequencies were similar across recipients of different vaccines. Patients receiving methotrexate and hydroxychloroquine reported fewer minor AEs than those patients not on them. Compared with HCs and patients with other AIRDs, patients with RA reported similar total AEs, overall minor AEs, and hospitalizations. Compared with nrAIDs, patients with RA reported lower frequencies of overall AEs, minor AEs (both odds ratio [OR] = 0.7; 95% CI: 0.5, 0.9), and injection site pain (OR = 0.6; 95% CI: 0.5, 0.8) with similar major AE and hospitalization frequencies. CONCLUSION: Despite the differences in AE frequency across different COVID-19 vaccines, all were well tolerated in patients with RA and were comparable to HCs, providing reassurance as to the safety of COVID-19 vaccination.

Performance of the 2016 ACR-EULAR myositis response criteria in juvenile dermatomyositis therapeutic trials and consensus profiles.

OBJECTIVES: The 2016 ACR-EULAR Response Criteria for JDM was developed as a composite measure with differential weights of six core set measures (CSMs) to calculate a Total Improvement Score (TIS). We assessed the contribution of each CSM, representation of muscle-related and patient-reported CSMs towards improvement, and frequency of CSM worsening across myositis response criteria (MRC) categories in validation of MRC. METHODS: Data from JDM patients in the Rituximab in Myositis trial (n = 48), PRINTO JDM trial (n = 139), and consensus patient profiles (n = 273) were included. Observed vs expected CSM contributions were compared using Sign test. Characteristics of MRC categories were compared by Wilcoxon tests with Bonferroni adjustment. Spearman correlation of changes in TIS and individual CSMs were examined. Agreement between physician-assessed change and MRC categories was evaluated by weighted Cohen's kappa. RESULTS: Of 457 JDM patients with IMACS CSMs and 380 with PRINTO CSMs, 9-13% had minimal, 19-23% had moderate and 41-50% had major improvement. The number of improved and absolute percentage change of CSMs increased by MRC improvement level. Patients with minimal improvement by MRC had a median of 0-1 CSM worsened, and those with moderate/major improvement had a median of zero worsening CSMs. Of patients improved by MRC, 94-95% had improvement in muscle strength and 93-95% had improvement in ≥1 patient-reported CSM. IMACS and PRINTO CSMs performed similarly. Physician-rated change and MRC improvement categories had moderate-to-substantial agreement (Kappa 0.5-0.7). CONCLUSION: The ACR-EULAR MRC perform consistently across multiple studies, supporting its further use as an efficacy end point in JDM trials.

Performance of the 2016 ACR-EULAR Myositis Response Criteria in adult dermatomyositis/polymyositis therapeutic trials and consensus profiles.

OBJECTIVE: The ACR-EULAR Myositis Response Criteria (MRC) were developed as a composite measure using absolute percentage change in six core set measures (CSMs). We aimed to further validate the MRC by assessing the contribution of each CSM, frequency of strength vs extramuscular activity improvement, representation of patient-reported outcome measures (PROM), and frequency of CSM worsening. METHODS: Data from adult dermatomyositis/polymyositis patients in the rituximab (n = 147), etanercept (n = 14), and abatacept (n = 19) trials, and consensus patient profiles (n = 232) were evaluated. The Total Improvement Score (TIS), number of improving vs worsening CSMs, frequency of improvement with and without muscle-related CSMs, and contribution of PROM were evaluated by MRC category. Regression analysis was performed to assess contribution of each CSM to the MRC. RESULTS: Of 412 adults with dermatomyositis/polymyositis, there were 37%, 24%, 25%, and 14% with no, minimal, moderate, and major MRC improvement, respectively. The number of improving CSMs and absolute percentage change in all CSMs increased by improvement category. In minimal-moderate improvement, only physician-reported disease activity contributed significantly more than expected by MRC. Of patients with at least minimal improvement, 95% had improvement in muscle-related measures and a majority (84%) had improvement in PROM. Patients with minimal improvement had worsening in a median of 1 CSM, and most patients with moderate-major improvement had no worsening CSMs. Physician assessment of change generally agreed with MRC improvement categories. CONCLUSION: The ACR-EULAR MRC performs consistently across multiple studies, further supporting its use as an efficacy end point in future myositis therapeutic trials.

Safety and tolerance of vaccines against SARS-CoV-2 infection in systemic lupus erythematosus: results from the COVAD study.

OBJECTIVE: To determine COVID-19 vaccine-related adverse events (AEs) in the seven-day post-vaccination period in patients with SLE vs autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HC). METHODS: Data were captured through the COVID-19 Vaccination in Autoimmune Diseases (COVAD) questionnaire (March-December 2021). Multivariable regression models accounted for age, gender, ethnicity, vaccine type and background treatment. RESULTS: Among 9462 complete respondents, 583 (6.2%) were SLE patients (mean age: 40.1 years; 94.5% females; 40.5% Asian; 42.9% Pfizer-recipients). Minor AEs were reported by 83.0% of SLE patients, major by 2.6%, hospitalization by 0.2%. AE and hospitalization frequencies were similar between patients with active and inactive SLE. Rashes were more frequent in SLE patients vs HC (OR; 95% CI: 1.2; 1.0, 1.5), chills less frequent in SLE vs AIRDs (0.6; 0.4, 0.8) and nrAIDs (0.5; 0.3, 0.8), and fatigue less frequent in SLE vs nrAIDs (0.6; 0.4, 0.9). Pfizer-recipients reported higher overall AE (2.2; 1.1, 4.2) and injection site pain (2.9; 1.6, 5.0) frequencies than recipients of other vaccines, Oxford/AstraZeneca-recipients more body ache, fever, chills (OR: 2.5, 3.0), Moderna-recipients more body ache, fever, chills, rashes (OR: 2.6, 4.3). Hospitalization frequencies were similar across vaccine types. AE frequencies were similar across treatment groups, although chills were less frequent in antimalarial users vs non-users (0.5; 0.3, 0.9). CONCLUSION: While COVID-19 vaccination-related AEs were reported by four-fifths of SLE patients, those were mostly minor and comparable to AEs reported by healthy individuals, providing reassurance regarding COVID-19 vaccination safety in SLE.