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.

Clinical and prognostic associations of anti-Jo-1 antibody levels in patients with antisynthetase syndrome.

OBJECTIVE: To investigate the association of serum anti-Jo-1 antibody levels with the disease activity and prognosis in anti-Jo-1-positive patients with antisynthetase syndrome (ASS). METHODS: This study included 115 anti-Jo-1-positive patients with ASS who were admitted to China-Japan Friendship Hospital between 2009 and 2019. Anti-Jo-1 antibody serum levels at initial admission and follow-up were determined by enzyme-linked immunosorbent assay (ELISA). Global and organ disease activity was assessed at baseline and follow-up according to the International Myositis Assessment and Clinical Studies guidelines. RESULTS: Among enrolled patients, 70 (60.9%) patients initially presented with interstitial lung disease (ILD), and 46 (40%) patients presented with with muscle weakness at initial admission. At baseline, patients with ILD had lower levels of anti-Jo-1 antibodies than those without ILD (p = 0.012). Baseline anti-Jo-1 antibody levels were higher in patients with muscle weakness, skin involvement, and arthritis (all p < 0.05) compared to those without these manifestations. Baseline anti-Jo-1 antibody levels were positively correlated with skin visual analogue scale (VAS) scores (r = 0.25, p = 0.006), but not with disease activity in other organs. However, changes in anti-Jo-1 antibody levels were significantly positively correlated with the changes in PGA (ß = 0.002, p = 0.001), muscle (ß = 0.003, p < 0.0001), and pulmonary (ß = 0.002, p = 0.013) VAS scores, but not with skin and joint VAS scores. Older age of onset (hazard ratio [HR] 1.069, 95% confidence interval [CI]:1.010-1.133, p = 0.022) and higher C-reactive protein (CRP) levels (HR 1.333, 95% CI: 1.035-1.717, p = 0.026) were risk factors for death. CONCLUSION: Anti-Jo-1 titers appear to correlate more with disease activity changes over time rather than with organ involvement at baseline, which provides better clinical guidance for assessing the disease course using anti-Jo-1 levels.

Prognostic value of elevated lipoprotein (a) in patients with acute coronary syndromes: a systematic review and meta-analysis.

Background: Elevated lipoprotein (a) level was recognized as an independent risk factor for significant adverse cardiovascular events in acute coronary syndrome (ACS) patients. Despite this recognition, the consensus in the literature regarding the prognostic significance of elevated lipoprotein (a) in ACS was also limited. Consequently, we conducted a thorough systematic review and meta-analysis to evaluate the prognostic relevance of elevated lipoprotein (a) level in individuals diagnosed with ACS. Methods and results: A thorough literature review was conducted by systematically searching PubMed, Embase, and Cochrane databases until September 2023. This review specifically examined cohort studies exploring the prognostic implications of elevated lipoprotein (a) level in relation to major adverse cardiovascular events (MACE), including death, stroke, non-fatal myocardial infarction (MI), and coronary revascularization, in patients with ACS. The meta-analysis utilized aggregated multivariable hazard ratios (HR) and their respective 95% confidence intervals (CI) to evaluate prognostic implications between high and low lipoprotein (a) levels [the cut-off of high lipoprotein (a) level varies from 12.5 to 60 mg/dl]. Among 18,168 patients in the identified studies, elevated lipoprotein (a) was independently associated with increased MACE risk (HR 1.26; 95% CI: 1.17-1.35, P < 0.00001) and all-cause mortality (HR 1.36; 95% CI: 1.05-1.76, P = 0.02) in ACS patients. In summary, elevated lipoprotein (a) levels independently forecast MACE and all-cause mortality in ACS patients. Assessing lipoprotein (a) levels appears promising for risk stratification in ACS, offering valuable insights for tailoring secondary prevention strategies. Systematic Review Registration: PROSPERO (CRD42023476543).

Prevalence, Risk Factors, and Mortality of Invasive Pulmonary Aspergillosis in Patients with Anti-MDA5+ Dermatomyositis: A Retrospective Study in China.

Objective: To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM). Methods: A retrospective analysis was conducted in anti-MDA5+ DM patients diagnosed between January 2016 and March 2023. Patients with lower respiratory tract specimens were categorized into IPA+ and IPA- groups based on the presence of IPA and their clinical characteristics and prognoses then compared. Results: Of the 415 patients diagnosed with anti-MDA5+ DM, 28 cases had IPA (prevalence rate of 6.7%) with Aspergillus fumigatus being the most common species. The patients were categorized into IPA+ (n=28) and IPA- (n=98) groups, with no significant age or gender-related differences (P>0.05). The IPA+ group had a lower lymphocyte count, particularly the CD4+ T-cell count, and reduced serum albumin and higher serum ferritin levels (P all<0.05). An elevated bronchoalveolar lavage fluid (BALF) galactomannan level was found to be the sole independent risk factor for the occurrence of IPA (adjusted OR=2.191, P=0.029) with a cut-off value of 0.585 and area under the curve of 0.779. The mortality rate in the IPA+ group was 25%. Compared to survivors, non-survivors in this group exhibited a higher incidence of rapidly progressive interstitial lung disease, lower lymphocyte counts, and increased co-infection with Pneumocystis jirovecii (P all<0.05). Conclusion: IPA was not rare in patients with anti-MDA5+ DM, with elevated BALF galactomannan levels being an independent risk factor for IPA occurrence. Clinicians must exercise vigilance to identify patients exhibiting the aforementioned risk factors.

Dynamic change in red cell distribution width as a predictor for short-time mortality in dermatomyositis-associated rapid progressive interstitial lung disease.

AIM: We aimed to explore a new and readily available practical marker for rapidly progressive interstitial lung disease (RP-ILD) and poor short-term outcomes in patients with idiopathic inflammatory myopathies (IIM). METHODS: A total of 1822 consecutive patients with IIM between 2009 and 2021 were evaluated retrospectively. All proven cases of naïve ILD with complete medical records were included. Red cell distribution width (RDW) values at the initial stage, 3 months and last follow-up were collected. The clinical characteristics and outcomes of the patients were recorded. RESULTS: We identified 532 patients with IIM with an average follow-up of 4 years. ILD prevalence was higher in patients of elevated RDW (p<0.001). The patients with ILD and elevated RDW had lower levels of PaO2/FiO2, FVC% and DLco% and a higher prevalence of RP-ILD than those with normal RDW (p<0.001). Prognostic analysis revealed that RDW was an independent risk factor for prognosis in patients with IIM-ILD (HR=2.9, p=0.03). Patients with dermatomyositis (DM) with RP-ILD with a change in RDW within 3 months (∆RDW-3) greater than 0 were more likely to die within 3 months. Moreover, the prevalence of ∆RDW-3>0 was higher in patients with RP-ILD and positive for anti-melanoma differentiation-associated gene 5 antibody who died within 3 months (87.5%) compared with those alive at 3 months (24.6%) (p<0.001). CONCLUSION: These findings suggest that repeated RDW assays could assist physicians in identifying patients with DM-ILD who were at a high risk of RP-ILD and death.

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.

Longitudinal study of patients with anti-SAE antibody positive dermatomyositis: a multicenter cohort study in China.

OBJECTIVES: To describe the longitudinal study and long-term prognosis of multicentre large inception cohort of patients with anti-SAE positive DM. METHODS: We retrospectively recruited patients with anti-SAE+DM in four tertiary referral centers from China between March 2005 and December 2022. Long-term survival analysis was performed in the enrolled patients. The Myositis Damage Index (MDI) and Cutaneous Disease Area and Severity Index (CDASI) were used to evaluate the degree of different organ damage and the extent of skin rashes. Longitudinal computed tomographic (CT) patterns were analyzed. Phenotypes were characterized using unsupervised cluster analysis. RESULTS: All-cause death occurred in 10.5% (4/38) of all patients, in which three patients succumbed to malignancies at 13, 18, and 36 months. Most patients had favorable long-term outcomes, 35.3% of them were in drug-free remission. Skin rashes showed significant improvement evaluated by CDASI with time. However, damage to different systems was observed in 70.6% of the surviving patients using the MDI, which mainly consisted in skin damage, accounting for 47.1%. Nine patients with anti-SAE+DM associated interstitial lung disease (ILD) underwent repeat CT showed marked radiological improvement at 6 months or being stable after 12 months. In further, different characteristics and outcomes were also showed in three clusters identified by unsupervised analysis. CONCLUSIONS: Anti-SAE+DM is characterized with lower mortality rate and the development of malignancies being the primary cause of death. Patients who survived showed notable cutaneous damage, while the ILD tends to stabilize. Clusters identified with unsupervised analysis could assist physicians in identifying higher risk of mortality.

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.

Polymyositis is a rare and favourable outcome subtype of idiopathic inflammatory myopathy in Chinese patients.

OBJECTIVES: To investigate the prevalence and characteristics of typical polymyositis (PM) in Chinese patients with idiopathic inflammatory myopathy (IIM). METHODS: Patients diagnosed with IIM according to the 2017 EULAR/ACR criteria were included. Serological aspects including myositis-specific antibodies (MSA) and pathological data were re-evaluated. The diagnosis of typical PM was strictly done using the pathological criteria, while excluding other IIM subtypes such as dermatomyositis (DM), immune-mediated necrotising myopathies (IMNM), anti-synthetase syndrome (ASS), and sporadic inclusion body myositis (sIBM), based on their respective diagnostic criteria. RESULTS: A total of 544 IIM patients with muscle biopsy were involved, and 129 of them were diagnosed with initial PM according to the 2017 EULAR/ACR criteria. Only 6 (1.1%, 6/544) patients met the strict definition of typical PM after re-evaluation. Patients with typical PM were MSA-negative (100% vs. 35.7%, p=0.003) and had CD8+ T cells surrounding or invading non-necrotic muscle fibres in muscle biopsies (100% vs. 7.8%, p<0.001) compared to the initially diagnosed PM patients. All typical PM patients achieved clinical remission at the second-year follow-up. Typical PM patients had a favourable prognosis compared to MSA-negative IMNM and unspecific myositis patients. CONCLUSIONS: Strictly defined typical PM is a rare clinical subtype in Chinese IIM patients. Typical PM patients with classical pathology were MSA-negative and responded well to treatment and had a favourable prognosis. It is crucial for clinicians to combine clinical, serological, and pathological features to properly distinguish PM from other IIM subtypes.

Novel endotypes of antisynthetase syndrome identified independent of anti-aminoacyl transfer RNA synthetase antibody specificity that improve prognostic stratification.

OBJECTIVES: To systemically analyse the heterogeneity in the clinical manifestations and prognoses of patients with antisynthetase syndrome (ASS) and evaluate the transcriptional signatures related to different clinical phenotypes. METHODS: A total of 701 patients with ASS were retrospectively enrolled. The clinical presentation and prognosis were assessed in association with four anti-aminoacyl transfer RNA synthetase (ARS) antibodies: anti-Jo1, anti-PL7, anti-PL12 and anti-EJ. Unsupervised machine learning was performed for patient clustering independent of anti-ARS antibodies. Transcriptome sequencing was conducted in clustered ASS patients and healthy controls. RESULTS: Patients with four different anti-ARS antibody subtypes demonstrated no significant differences in the incidence of rapidly progressive interstitial lung disease (RP-ILD) or prognoses. Unsupervised machine learning, independent of anti-ARS specificity, identified three endotypes with distinct clinical features and outcomes. Endotype 1 (RP-ILD cluster, 23.7%) was characterised by a high incidence of RP-ILD and a high mortality rate. Endotype 2 (dermatomyositis (DM)-like cluster, 14.5%) corresponded to patients with DM-like skin and muscle symptoms with an intermediate prognosis. Endotype 3 (arthritis cluster, 61.8%) was characterised by arthritis and mechanic's hands, with a good prognosis. Transcriptome sequencing revealed that the different endotypes had distinct gene signatures and biological processes. CONCLUSIONS: Anti-ARS antibodies were not significant in stratifying ASS patients into subgroups with greater homogeneity in RP-ILD and prognoses. Novel ASS endotypes were identified independent of anti-ARS specificity and differed in clinical outcomes and transcriptional signatures, providing new insights into the pathogenesis of ASS.

Anti-Toxoplasma gondii antibodies as a risk factor for the prevalence and severity of systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the presence of numerous autoantibodies. The interaction of infectious agents (viruses, bacteria and parasites) and a genetically susceptible host may be a key mechanism for SLE. Toxoplasma gondii is a widespread intracellular parasite that has been implicated in the pathogenesis of autoimmune diseases. However, the relationship between T. gondii infection and the increased risk of SLE in Chinese populations remains unclear. METHODS: The seroprevalence of T. gondii infection was assessed in 1771 serum samples collected from Chinese individuals (908 healthy controls and 863 SLE patients) from different regions of China using an enzyme-linked immunosorbent assay. Serum autoantibodies and clinical information were obtained and analysed. RESULTS: Our observations revealed a higher prevalence of anti-T. gondii antibodies (ATxA) immunoglobulin G (IgG) in serum samples from SLE patients (144/863, 16.7%) than in those from the healthy controls (53/917, 5.8%; P < 0.0001), indicating a 2.48-fold increased risk of SLE in the ATxA-IgG+ population, after adjustment for age and sex (95% confidence interval [CI] 1.70-3.62, P < 0.0001). ATxA-IgG+ SLE patients also showed a 1.75-fold higher risk of developing moderate and severe lupus symptoms (95% CI 1.14-2.70, P = 0.011) compared to ATxA-IgG- patients. Relative to ATxA-IgG- patients, ATxA-IgG+ patients were more likely to develop specific clinical symptoms, including discoid rash, oral ulcer, myalgia and alopecia. Seven antibodies, namely anti-ribosomal RNA protein (rRNP), anti-double stranded DNA (dsDNA), anti-cell membrane DNA (cmDNA), anti-scleroderma-70 (Scl-70), anti-cardiolipin (CL), anti-beta2-glycoprotein-I (B2GPI) and rheumatoid factor (RF), occurred more frequently in ATxA-IgG+ patients. When combined with anti-dsDNA and RF/anti-rRNP/anti-cmDNA/ESR, ATxA-IgG significantly increased the risk for severe lupus. CONCLUSIONS: Our results suggest that ATxA-IgG may be a significant risk factor for SLE prevalence and severity in Chinese populations.

Fatty infiltration in the posterior muscles of the lower extremities as an MRI feature in antimitochondrial antibody-associated myopathy.

OBJECTIVE: Idiopathic inflammatory myopathy (IIM) with antimitochondrial M2 antibody (AMA-M2) has been associated with distinct clinical characteristics. In this study, we explore the magnetic resonance imaging (MRI) findings of the muscles of the lower extremities in AMA-M2-positive IIM to gain more insight. METHODS: MRI of 22 lower extremity muscles was retrospectively evaluated in 14 patients with AMA-M2-positive IIM and 37 age- and sex-matched patients with AMA-M2-negative IIM. Muscles with inflammatory edema and fatty infiltration were assessed according to the Stramare and Mercuri criteria. RESULTS: Patients with AMA-M2-positive IIM had significantly higher incidence of MRI involvement with fatty infiltration in five lower extremity muscles, namely the adductor magnus (AM) (13/14 VS 14/37, p < 0.001), semimembranosus (SM) (13/14 VS 17/37, p = 0.002), biceps femoris (BF) (12/14 VS 15/37, p = 0.004), soleus (13/14 VS 23/37, p = 0.041), and the medial head of the gastrocnemius (Gastroc M) (13/14 VS 17/37, p = 0.002) than patients with AMA-M2-negative IIM. Furthermore, the severity scores of fatty infiltrations of the above five muscles in AMA-M2-positive IIM were significantly higher than those in patients with AMA-M2-negative IIM (p < 0.001). CONCLUSIONS: Severe fatty infiltrations of the AM, SM, BF, soleus, and Gastroc M in the posterior muscles of the lower extremities are dominant MRI features in our patients with AMA-M2-positive IIM. This unique muscle MRI character may be a helpful indicator in clinical practice for patients with AMA-M2-positive IIM. Key Points • Striking involvement and prominent fatty infiltrations of five lower extremity muscles (adductor magnus, semimembranosus, biceps femoris, soleus, and the medial head of the gastrocnemius) are interesting MRI performances. • Severe fatty infiltrations in the posterior muscles of the lower extremities are dominant MRI features in AMA-M2-positive IIM. • This unique muscle MRI character may be very helpful for the diagnosis of the AMA-M2-positive IIM.

Spontaneous pneumomediastinum in anti-MDA5-positive dermatomyositis: Prevalence, risk factors, and prognosis.

OBJECTIVE: To depict the clinical panorama of spontaneous pneumomediastinum (SPM) in anti-MDA5 antibody-positive dermatomyositis (anti-MDA5+ DM). METHODS: A total of 1352 patients with idiopathic inflammatory myopathy (IIM), including 384 anti-MDA5+ DM patients were retrospectively enrolled. The clinical profiles of anti-MDA5+ DM-associated SPM were analyzed. RESULTS: We identified that 9.4 % (36/384) of anti-MDA5+ DM patients were complicated with SPM, which was significantly higher than that of non-anti-MDA5+ DM and other IIM subtypes (P all <0.001). SPM developed at a median of 5.5 (3.0, 12.0) months after anti-MDA5+ DM onset. Anti-MDA5+ DM patients complicated with SPM showed a significantly higher frequency of fever, dyspnea, and pulmonary infection including viral and fungal infections compared to those without SPM (P all < 0.05). Cytomegalovirus (CMV) and fungal infections were identified to be independent risk factors for SPM development in the anti-MDA5+ DM. SPM and non-SPM patients in our anti-MDA5+ DM cohort showed comparable short-term and long-term survival (P = 0.236). Furthermore, in the SPM group, we found that the non-survivors had a lower peripheral lymphocyte count, higher LDH level, and higher frequency of intensification of immunosuppressive treatment (IST) than survivors. The elevated LDH level and intensification of IST were independent risk factors for increased mortality in anti-MDA5+ DM-associated SPM patients. CONCLUSIONS: Nearly one-tenth of patients with anti-MDA5+ DM develop SPM. Both CMV and fungal infections are risk factors for SPM occurrence. The development of SPM does not worsen the prognosis of anti-MDA5+ DM patients, and the intensification of IST does harm to the SPM prognosis.

Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical progress.

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis. Although the aetiology and pathology remain unclear, increasing evidence suggests that viral infection is a potential trigger of MDA5-DM. Multiple factors, including T cells, B cells, neutrophils and macrophages, are implicated in the pathophysiology of MDA5-DM. Distinctive skin rashes, rapidly progressive interstitial lung disease, peripheral lymphopenia and elevated serum ferritin levels are the most prominent clinical and laboratory features of MDA5-DM. Concomitant infection is a common complication of MDA5-DM. The proper evaluation of patients with MDA5-DM requires knowledge of the disease heterogeneity and clinical course variability. Several biomarkers, including serum levels of anti-MDA5 antibodies and biomarkers related to macrophage activation, have been identified as useful tools for monitoring disease activity and prognosis. MDA5-DM shows a poor response to conventional glucocorticoid and immunosuppressant therapy and has a poor overall prognosis. Therefore, there is an urgent need to explore the key pathogenic mechanisms of MDA5-DM and develop novel therapeutic options for patients. This Review discusses recent clinical progress and pathogenic findings of MDA5-DM.

Nintedanib could potentially lead to improvements in anti-melanoma differentiation-associated 5 dermatomyositis-associated interstitial lung disease.

OBJECTIVES: To determine the efficacy and safety of nintedanib in patients with anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5+ DM-ILD). METHODS: The study was a retrospective cohort design that evaluated patients with anti-MDA5+ DM who either received or did not receive nintedanib. Clinical symptoms, laboratory tests, and survival were compared in the two groups using a propensity score-matched analysis. The primary endpoint was mortality, while adverse events were recorded descriptively. RESULTS: After propensity score matching, 14 patients who received nintedanib (nintedanib+ group) and matched 56 patients who did not receive nintedanib (nintedanib- group) were enrolled. Compared with the nintedanib- group, the nintedanib+ group had a lower incidence of heliotrope and arthritis, higher lymphocyte counts, lower serum ferritin levels, and greater 12-month survival (all p<0.005). Although lung function, HRCT score, and lung VAS were not statistically different between the two groups, the longitudinal study showed significant improvement in HRCT scores (p=0.028) and pulmonary VAS (p=0.019) in the nintedanib+ group. Adverse events occurred in 28.6% of patients, with the most common adverse event with nintedanib being diarrhoea. CONCLUSIONS: Nintedanib may be effective for improving clinical symptoms, laboratory parameters, lung lesions, and survival in anti-MDA5+ DM. Diarrhoea was the most common adverse event associated with nintedanib, although the drug was well tolerated by most patients.

Expansion of exhausted CD8+ T cells associates with increased pulmonary fungal infection risk in anti-melanoma differentiation associated gene 5 dermatomyositis.

OBJECTIVES: Anti-MDA5+ dermatomyositis was associated with poor prognosis due to the high incidence of rapid progressive interstitial lung disease, pulmonary infection. The aim of this study is to investigate the abundance and clinical relevance of exhaustion markers on peripheral CD8 T cells from patients with idiopathic inflammatory myopathy (IIM). METHODS: Twenty-nine healthy controls (HCs) and 71 patients with IIM were enrolled, including 42 with anti-MDA5+ and 18 with anti-MDA5- dermatomyositis (DM) and 11 with anti-synthetase syndrome (ASS). Flow cytometry was applied to detect PD-1, TIM-3 and LAG-3 in CD8 T cells. The clinical associations of the CD8 T cell exhaustion phenotype in patients with anti-MDA5+ DM were analysed. RESULTS: CD8 T cells from patients with anti-MDA5+ DM showed significantly increased LAG-3, TIM-3 and PD-1 compared to those from patients with anti-MDA5- IIM (18 with anti-MDA5- DM and 11 with ASS) or HCs (adjusted p all < 0.05). CD8 T cells with distinct exhaustion levels were all significantly increased in anti-MDA5+ DM patients compared with HCs (p all < 0.05). Patients with high level of PD-1+ TIM-3+LAG-3+ CD8+ T cells had a significant higher incidence of pulmonary fungal infections but lower counts of CD4+ and CD8+ T cells. ROC analysis revealed that the frequency of PD-1+TIM-3+LAG-3+CD8+ T cell significantly predicted pulmonary fungal infections (area under the curve: 0.828). CONCLUSIONS: CD8 T cells from patients with anti-MDA5+ DM show significant exhausted phenotype, and increased exhausted CD8 T cells were associated with high risk of pulmonary fungal infection.

Telitacicept in patients with active systemic lupus erythematosus: results of a phase 2b, randomised, double-blind, placebo-controlled trial.

OBJECTIVES: This phase 2b, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of telitacicept, a novel fusion protein that neutralises signals of B lymphocyte stimulator and a proliferation-inducing ligand, in active systemic lupus erythematosus (SLE). METHODS: Adult patients with active SLE (n=249) were recruited from 29 hospitals in China and randomised 1:1:1:1 to receive subcutaneous telitacicept at 80 mg (n=62), 160 mg (n=63), 240 mg (n=62) or placebo (n=62) once weekly in addition to standard therapy. The primary endpoint was the proportion of patients achieving an SLE Responder Index 4 (SRI-4) response at week 48. Missing data were imputed using the last observation carried forward method. RESULTS: At week 48, the proportion of patients achieving an SRI-4 response was 75.8% in the 240 mg telitacicept group, 68.3% in the 160 mg group, 71.0% in the 80 mg group and 33.9% in the placebo group (all p<0.001). Significant treatment responses were observed in secondary endpoints, including a ≥4-point reduction on the Systemic Lupus Erythematosus Disease Activity Index, a lack of Physician's Global Assessment score worsening and a glucocorticoid dose reduction in the 240 mg group. Telitacicept was well tolerated, and the incidence of adverse events and serious adverse events was similar between the telitacicept and placebo groups. CONCLUSIONS: This phase 2b clinical trial met the primary endpoint. All telitacicept groups showed a significantly higher proportion of patients achieving an SRI-4 response than the placebo group at week 48, and all doses were well tolerated. These results support further investigations of telitacicept in clinical trials involving more diverse populations and larger sample sizes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02885610).

Comparison of clinical features between patients with anti-synthetase syndrome and dermatomyositis: Results from the MYONET registry.

OBJECTIVES: To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations, and malignancy, between adults with anti-synthetase syndrome (ASyS) and dermatomyositis (DM). METHODS: Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1É£/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V sign, erythroderma, and/or periorbital rash). RESULTS: In total 1,054 patients were included (DM, n = 405; ASyS, n = 649). In ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease, and cardiac involvement differentiated ASyS-DMskin from DM (all p< 0.001), whereas higher frequency of any of four DM-type rashes: heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%) differentiated DM from ASyS-DMskin (all p< 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both p< 0.001). CONCLUSION: DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.

Efficacy and Safety of Tofacitinib in Anti-Melanoma Differentiation-Associated 5 Gene Antibody-Positive Dermatomyositis.

OBJECTIVES: This study aimed to evaluate the efficacy and safety of tofacitinib for the treatment of anti-melanoma differentiation-associated 5 gene (anti-MDA5) antibody-positive dermatomyositis (DM). METHODS: This study included 52 patients with anti-MDA5 antibody-positive DM (MDA5 + DM) who were treated with tofacitinib and followed up. Clinical and laboratory data of these patients were recorded between January 2019 and June 2022. SPSS was used for all statistical analyses. RESULTS: The mean age of patients with MDA5 + DM was 45 ± 12.4 years, and the median disease duration was 6.5 months (range, 3-13 months). The mean dosage of glucocorticoids was 34.7 ± 20.9 mg/d at the initiation of tofacitinib therapy. Overall, 47 patients were followed up for a mean duration of 7.8 ± 6.2 months. We found that the clinical symptoms of 28 patients (59.6%) were improved, but 1 patient (2.1%) died because of severe infection. Moreover, complications occurred in 25 patients (53.2%), among whom 19 patients had infections. Older age and C-reactive protein levels close to the upper value in reference range at the initial treatment were found to be the potential risk factors of infection. Furthermore, patients with cutaneous ulcers were found to have a lower risk of infection. CONCLUSION: Tofacitinib can be used as a potential therapeutic option for MDA5 + DM. The occurrence of infection requires special attention during treatment, particularly in patients with older age and C-reactive protein levels close to the upper value in reference range.