Clinical and experimental rheumatology最新文献

Objectives: We aimed to analyse the characteristics and positive signals of haemorrhage-related adverse event (HrAE) associated with nintedanib in the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: The reports of adverse events (AE) associated with nintedanib as the primary suspect (PS) drug were extracted from the FAERS database from the fourth quarter of 2014 to the third quarter of 2024. HrAE were identified using the Standardized Medical Dictionary for Regulatory Activities Queries (SMQs). The characteristics of AE reports were described and multivariate analysis was used to analyse the factors related to HrAE. Disproportionality analysis was performed to detect AE signals, and a multiplicative and additive model was applied to evaluate the association between drug-drug interaction (DDI) and HrAE. Sensitivity analysis was conducted on serious AE that life-threatening and death, as well as AE reported by physician and pharmacist.

Results: A total of 3,018 patients experienced HrAE associated with nintedanib were included. There was a total of 3,929 AE reports. Compared with non-HrAE, patients age ≥65 years (p≤0.001, OR=1.675, 95% CI 1.376-2.040) and the lower daily dose (p=0.014, OR=1.001, 95% CI 1.000-1.002) were associated with HrAE. The gastrointestinal system was the most frequently affected organ and/or system. Co-administration of antiplatelet agents (ROR=6.02, 95% CI 4.76-7.62), anticoagulants (ROR=4.57, 95% CI 3.85-5.42) or prednisone (ROR=1.63, 95% CI 1.15-2.31) was more common among HrAE patients than among non-HrAE patients. Patients age ≥65 years (p=0.018, OR=1.623, 95%CI 1.088-2.420) and the time-to-onset (TTO) from drug administration to AE onset >90 days (p≤0.001, OR=2.266, 95%CI 1.744-2.944) were associated HrAE when AE reports with life-threatening or fatal were included; male (p=0.004, OR=1.004, 95% CI 1.004-1.007) is associated with HrAE when AE reports by physician or pharmacist were included.

Conclusions: Gastrointestinal bleeding is the most commonly reported HrAE associated with nintedanib. Patients over 65 years were more likely to experience HrAE, especially in life-threatening and death AE reports.

Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with potential vascular complications. Ultrawide-field swept-source optical coherence tomography angiography (SS-OCTA) may serve as a non-invasive tool to assess retinal and choroidal microvasculature. We aimed to evaluate its utility in SLE for early detection and monitoring of SLE vasculopathy.

Methods: 142 eyes of 71 SLE patients (median age 35 years, IQR 23-42) and 194 eyes of 97 healthy controls (median age 33 years, IQR 26-39.25) underwent ultrawide-field SS-OCTA imaging to quantify vascular density (VD) in retinal and choroidal layers. We collected clinical data, including disease activity scores (SLEDAI-2K), organ damage index (SDI), laboratory results, and treatment information (e.g. hydroxychloroquine dose).

Results: Retinal and choroidal VD in SLE patients differed significantly from that of healthy controls (p<0.05). Disease duration and SLEDAI-2K scores correlated with microvasculature parameters, especially in mid-to-large choroidal vessels (MLCV). Longer disease duration (≥5 years) and higher cumulative hydroxychloroquine (HCQ) dose were associated with visual impairment. Deep retinal vessel density distinguished active disease.

Conclusions: Ultrawide-field SS-OCTA reveals distinct retinal and choroidal microvascular remodelling in SLE. MLCV density may serve as a marker for disease progression and HCQ exposure, supporting the potential of SS-OCTA for non-invasive monitoring of SLE-related vascular pathology.

Objectives: This study aimed to develop and validate a risk stratification scale for unfavourable outcomes in adult patients with IgA vasculitis nephritis (IgAVN).

Methods: The derivation cohort in this study was constructed using the existing prognosis data from adult IgAVN cohorts. We extracted the risk factors and their hazard ratios. Only statistically significant risk factors were included in our final risk stratification scale. Then this study validated the risk stratification scale in an external cohort of Chinese patients. The performance of the risk stratification scale was evaluated by the receiver operating characteristic (ROC), calibration, decision, and Kaplan-Meier curves.

Results: Ten cohorts involving 1,814 adult patients with IgAVN were included in this meta-analysis. Serum albumin (ALB), estimated glomerular filtration rate (eGFR), endocapillary hypercellularity (E1), and tubular atrophy/interstitial fibrosis (T1/2) were included in the risk stratification and scored according to their weightings (maximum score: 6.5). An external cohort comprising 133 patients was used to validate the risk stratification scale. The area under the curve (AUC) value of the scoring scale was 0.88 (95%CI: 0.78-0.99), with a sensitivity of 0.79 (95%CI: 0.49-0.95) and specificity of 0.89 (95%CI: 0.82-0.94), at a cut-off value of 3. The calibration, decision, and Kaplan-Meier curves further confirmed the robust performance of the risk stratification scale.

Conclusions: In this study, we established a simple and practical tool to identify adult IgAVN patients at high risk of unfavourable outcomes. Reasonable use of the risk stratification scale can help make early clinical decisions and facilitate the development of precision medicine.

Objectives: Limited data exist on the clinical associations and responsiveness of myositis core set measures (CSMs) and response criteria using health-related quality of life (HRQoL) assessments like the Short Form Health Survey (SF-36). This study evaluates the associations and improvement thresholds of CSMs and Total Improvement Score (TIS) using SF-36 in idiopathic inflammatory myopathies (IIM).

Methods: Adults with IIM enrolled in two clinical trials and one observational study were assessed. Demographics and myositis CSMs including patient-global assessment (PtGA), physician-global assessment (PhGA), extra global disease activity score (EXGLB), manual muscle testing (MMT-8), Health Assessment Questionnaire (HAQ), creatine kinase (CK), and SF-36 were collected longitudinally. TIS was calculated at 6 months. Spearman's correlation assessed associations between SF-36 domains and summary scores for physical health (PCS) and mental health (MCS) with all CSMs and TIS. A mixed linear model examined longitudinal association. Minimal clinically important difference (MCID) was determined using the anchor method.

Results: The study included 105 IIM patients. Most SF-36 domains showed moderate to strong correlations with all CSMs at baseline as well as 6-month changes (delta change), except CK levels at baseline. TIS exhibited significant correlations with delta changes in most SF-36 domains. Longitudinally, significant associations were observed between SF-36 and most CSMs (except MMT-8). Higher thresholds in CSMs and TIS aligned with incremental improvements in PCS. MCIDs for PhGA, PtGA, EXGLB, HAQ, MMT-8 and TIS were 1.1, 1.84, 0.85, 0.65, 3.7, 23.7, respectively.

Conclusions: Most CSMs and TIS in IIM significantly correlated with SF-36 domains, reflecting concurrent HRQoL improvements.

Objectives: Idiopathic inflammatory myopathies (IIM) can affect multiple organs, including the heart, potentially leading to arrhythmia, heart failure, and thereby a poor prognosis. We hypothesised that cardiac and skeletal muscle involvement in patients with IIM share pathological mechanisms, and that severe skeletal muscle involvement may be associated with cardiac involvement. The aim of this study was to identify disease-related parameters that indicate cardiac involvement in newly diagnosed patients with IIM.

Methods: In this prospective study, 34 newly diagnosed patients with IIM and 9 age- and gender-matched healthy controls underwent cardiac magnetic resonance imaging, blood analyses for skeletal muscle markers, and assessments of IIM-specific disease features.

Results: Cardiac involvement was detected by cardiac magnetic resonance imaging in 47% of patients with newly diagnosed IIM, presenting as ongoing myocarditis/perimyocarditis (44%), ongoing pericarditis (25%) or previous myocarditis (31%). IIM patients with cardiac involvement had significantly more prevalent myositis (p=0.018) and higher levels of serum markers of muscle inflammation (myoglobin, p=0.039; alanine aminotransferase, p=0.045 and aspartate aminotransferase p=0.005) compared to IIM without cardiac involvement. IIM with ongoing myocarditis/peri-myocarditis displayed significantly elevated cardiac troponin I (cTnI) levels than IIM with ongoing pericarditis (p=0.015) or previous myocarditis (p=0.015). Additionally, cTnI levels were strongly correlated to myositis (as clinical manifestation, p=0.011), creatin kinase (p=0.001), myoglobin (p=0.001), lactate dehydrogenase (p=0.008) and aspartate aminotransferase (p=0.0.001).

Conclusions: Cardiac involvement as detected by cardiac magnetic resonance imaging is common at time of diagnosis in patients with IIM and is closely linked to the severity of skeletal muscle involvement.

Muscle dysfunction presenting with weakness and elevated muscle enzymes poses a significant diagnostic challenge for rheumatologists, particularly in differentiating idiopathic inflammatory myopathies (IIM) from other mimicking conditions. This review systematically categorises non-inflammatory muscle diseases, including drug-induced myopathies, endocrine myopathies, genetic muscular dystrophies, metabolic and mitochondrial myopathies, and neuromuscular junction disorders, that can clinically and histologically resemble myositis. We emphasise the importance of a detailed clinical evaluation, including history, pattern of muscle involvement, extramuscular features, and comprehensive laboratory and biopsy investigations, to avoid misdiagnosis. Awareness of these mimickers is crucial for guiding appropriate diagnostic workup and management, given the distinct therapeutic approaches required for each condition. This framework aims to assist rheumatologists in improving diagnostic accuracy, optimising patient management, and enhancing referral decisions in patients presenting with muscle weakness.

Objectives: To explore the heterogeneity and the corresponding clinical significance of lymphocyte subsets in dermatomyositis patients with anti-melanoma differentiation-associated gene 5 positive autoantibody (anti-MDA5+ DM).

Methods: 268 anti-MDA5+ DM patients and 536 gender-age matched healthy controls (HCs) were retrospectively enrolled. Patients' clinical data, serological parameters, peripheral blood lymphocyte subsets, imagological examinations, treatment regimens and follow-up were collected. Cluster analysis based on peripheral blood lymphocyte subsets was conducted in anti-MDA5+ DM patients.

Results: The absolute number of CD3+ T lymphocytes, CD3+CD4+ T cells, CD3+CD8+ T cells, CD3-CD19+ B cells and CD16+CD56+ NK cells were significantly reduced in anti-MDA5+ DM patients compared with HCs. The absolute counts of the above cell subsets were remarkably reduced in non-survivors compared to the survivors of anti-MDA5+ DM. Cluster analysis based on lymphocyte subsets divided anti-MDA5+ DM patients into cluster 1(n=125) and cluster 2 (n=143). Patients in cluster 1 presented with lower counts of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, CD3-CD19+ B cells and NK cells compared with cluster 2. Notably, RP-ILD rate, three-month and six-month death rate in cluster 1 were dramatically higher than in cluster 2, p<0.001, respectively.

Conclusions: Lymphocytes and their subsets were significantly altered in anti-MDA5+ DM patients. There was remarkable heterogeneity of lymphocyte subsets in anti-MDA5+ DM patients between survivors and non-survivors. Anti-MDA5+ DM patients were divided into two groups with distinct symptoms and survival rate by cluster analysis based on lymphocyte subsets.