Clinical Rheumatology最新文献

Objectives: Adult-onset Still's disease (AOSD)-associated macrophage activation syndrome (MAS) is a highly inflammatory condition. Currently, the main treatment method for AOSD-associated MAS is high-dose glucocorticoid shock therapy, but the effect is not satisfactory, and new therapeutic methods or drugs are urgently needed. The aim of this study was to evaluate the efficacy and safety of salvage baricitinib therapy for AOSD-associated MAS following conventional immunosuppressive therapy.

Method: Data from nine patients with MAS treated in the Department of Infection and the Department of Rheumatology, First Affiliated Hospital of Soochow University, from January 2020 to December 2022, were retrospective analysed. Salvage therapy with baricitinib was administered, with an initial dose of 8 mg/day. The patients' clinical symptoms and MAS indices (blood counts and triglyceride, fibrinogen, lactate dehydrogenase, sCD25, and Fer levels) were observed. After a complete response was achieved, the baricitinib dose was gradually reduced to 2-4 mg/day and maintained.

Results: The MAS blood test results of all nine patients improved to varying degrees within 1 week post-treatment. The MAS indices gradually returned to normal approximately 8 weeks after discharge; at the 12-month outpatient follow-up, seven patients did not develop MAS again, but two patients (patients 5 and 9) had MAS recurrence. The follow-up period ended with salvage treatment with emapalumab.

Conclusions: Baricitinib can effectively inhibit the inflammatory response and improve outcomes in the treatment of MAS secondary to rheumatic immunity-related diseases; moreover, this drug treatment is safe. Our study provides a new strategy for MAS salvage therapy. Key Points • Bariticinib may be a palliative treatment option for recurrent/refractory MAS.

Introduction/objective: Janus kinase (JAK) inhibitors have expanded treatment options for rheumatoid arthritis (RA), particularly for patients unresponsive to traditional disease-modifying antirheumatic drugs (DMARDs). However, safety concerns necessitate a thorough post-market evaluation. This study is aimed at comparing the safety profiles of tofacitinib, baricitinib, and upadacitinib using adverse event (AE) reports from the FDA Adverse Event Reporting System (FAERS).

Methods: A retrospective disproportionality analysis was performed using the FAERS data from 2012 to 2022. The AE reports were categorized into cardiovascular, cancer, respiratory, gastrointestinal, musculoskeletal, and arthralgia-related events. Proportional reporting ratio (PRR) and reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated to identify significant safety signals.

Results: Of 273,657 AE reports, tofacitinib had the most (227,144), with increased musculoskeletal-related events (ROR = 1.53, 95% CI 1.49-1.57) and a reduced cancer risk (ROR = 0.44, 95% CI 0.41-0.47). Baricitinib (9305 reports) showed the highest risk of cardiovascular events (ROR = 1.63, 95% CI 1.50-1.78) and cancer (ROR = 2.17, 95% CI 1.83-2.58). Upadacitinib (37,208 reports) had elevated risks for respiratory events (ROR = 2.04, 95% CI 1.88-2.21) and cancer (ROR = 2.24, 95% CI 2.05-2.43).

Conclusion: The distinct safety profiles of these JAK inhibitors suggest that baricitinib poses higher cardiovascular and cancer risks, whereas upadacitinib increases the risk of respiratory and gastrointestinal events. Tofacitinib may be safer for patients with a history of cancer but requires monitoring for musculoskeletal AEs. Personalized risk assessments are critical for safe use of JAK inhibitors. Key Points • This study provides a comprehensive post-market safety assessment of three JAK inhibitors-tofacitinib, baricitinib, and upadacitinib-using the FAERS data from 2012 to 2022. • Distinct safety profiles were identified, with baricitinib showing a higher risk of cardiovascular events and cancer, while upadacitinib posed an increased risk of respiratory and gastrointestinal events. • Tofacitinib demonstrated a lower cancer risk than other JAK inhibitors but was associated with more musculoskeletal-related adverse events. • These findings emphasize the importance of personalized risk assessment and vigilant monitoring when prescribing JAK inhibitors for rheumatoid arthritis.

Background: Osteoarthritis knee poses a substantial and pervasive global health challenge.

Methods: The data was extracted from the Global Burden of Disease 2021 Study database. First, numbers and age-standardized rates (ASRs) of incidence, prevalence, and disability-adjusted life years (DALYs) of osteoarthritis knee were assessed globally and by sub-types in 2021. Subsequently, we employed a linear regression model to analyze the temporal trends from 1990 to 2021. To predict the future burden, we utilized the age-period-cohort model and the Bayesian age-period-cohort model. Furthermore, we conducted a sensitivity analysis using the Autoregressive Integrated Moving Average model and the Exponential Smoothing model.

Results: In 2021, osteoarthritis knee accounted for 30.85 million incidence cases, 374.74 million prevalence cases, and 12.02 million DALYs cases globally, with ASRs of 353.67, 4294.27, and 137.59, respectively. Females and individuals over 50 years old were identified as high-risk populations, while higher socio-demographic index regions emerged as high-risk areas. From 1990 to 2021, incidence cases rose from 14.13 million to 30.85 million, prevalence cases from 159.80 million to 374.74 million, and DALYs cases from 5.15 million to 12.02 million, accompanied by increases in their respective ASRs. Projections using the APC model predict a continued increase in incidence, prevalence, and DALYs cases for both genders until 2046. Specifically, male incidence cases are projected to increase to 18.45 million and female incidence to 25.60 million. Similarly, male prevalence cases are projected to rise to 235.41 million and female prevalence to 365.97 million. Male DALYs cases are expected to increase to 7.52 million and female DALYs to 11.55 million. The BAPC models also indicate an upward trend in number of cases.

Conclusion: In conclusion, osteoarthritis knee represents a formidable threat to global public health, necessitating the development of proactive and tailored strategic interventions that account for global-specific contexts. Key Points • Females and individuals over 50 years old were identified as high-risk populations. • Higher socio-demographic index regions were identified as high-risk areas. • The disease burden attributable to osteoarthritis knee increased from 1990 to 2019. • The number of deaths and DALYs cases would still increase in the next 25 years.

Objectives: Familial Mediterranean fever (FMF) is a multifaceted autoimmune disease and requires a diligent strategical approach considering disease periods and mutation subtypes. We aimed to investigate serum levels of autoimmunity-related cell-free miRNAs and inflammatory and apoptotic markers in FMF patients.

Methods: Sixty FMF patients, of which 30 were in attack (FMF-A) and 30 were in remission (FMF-R) periods, and 25 age-, sex-, and BMI-matched healthy controls were included in our study. The expression levels of miR-26a-5p, miR-146a-5p, miR-155-2-5p, and miR-451a were analyzed with reverse-transcriptase quantitative polymerase chain reaction, and protein levels of interleukin-18 (IL18) and soluble Fas cell surface death receptor (sFAS) were measured with enzyme-linked immunosorbent assay. Serum CRP levels were analyzed by nephelometry, ferritin levels by chemiluminescence, and routine biochemical parameters by spectrophotometry. Correlation analyses were performed to seek potential associations of miRNAs with serum markers and biochemical parameters. Potential biomarkers were tested with receiver operating characteristic analysis.

Results: We observed elevated serum IL18 levels but not sFAS, in FMF patients, particularly during attack period. IL18 demonstrated diagnostic value and was significantly correlated with acute-phase markers namely CRP, fibrinogen, and ferritin. Altered levels of IL18 and miR-451a could distinguish FMF patients in the attack period from the ones in remission. miR-26a-5p, miR-146a-5p, and miR-155-2-5p were downregulated in FMF patients carrying M694V mutations.

Conclusions: These findings suggest that IL18 and specific miRNAs can serve as potential biomarkers for FMF pathogenesis. Discovering promising targets for FMF-related miRNAs using mechanistic strategies will enhance our understanding of FMF disease management and therapy. Key Points • miR-451a and IL18 can serve as an indicator in distinguishing familial Mediterranean fever patients in attack and remission periods. • miR-26a-5p, miR-146a-5p, and miR-155-2-5p were dysregulated in FMF patients carrying M694V mutation.

Background: Tripterygium wilfordii Hook F (TwHF) is a prominent Chinese herbal formula. It exhibits significant clinical efficacy in treating systemic lupus erythematosus (SLE), though its mechanisms remain unclear. Our study employs network pharmacology and molecular docking to explore active compounds of TwHF and their associated targets for SLE treatment.

Methods: Primary active compounds of TwHF and their targets were sourced from the TCMSP, SwissTargetPrediction, and UniProt databases. SLE-relevant target proteins were identified from the OMIM and GeneCards databases. Enrichment analyses were conducted to reveal results of common TwHF-SLE targets. STRING and Cytoscape software were used to systematically analyze and construct protein-protein interaction (PPI) networks, compound-target-pathway, and target-organ networks. Molecular docking was utilized to confirm the binding of key targets to the top active compounds.

Results: A total of 14 active compounds and 300 overlapping targets between TwHF and SLE were identified. PPI network analysis revealed 29 core targets. Several pathways were found to contribute to the potential therapeutic effects of TwHF in SLE, including PI3K-Akt signaling pathway, Th17 cell differentiation, chemokine signaling, and T cell receptor signaling. Disease Ontology (DO) analysis highlighted the involvement of TwHF in genes associated with myocardial infarction (MI), atherosclerosis (AS), breast carcinoma, and ischemia. Molecular docking results demonstrated strong binding affinities, with 37 signal molecule-receptor interactions in SLE and 97 interactions in SLE-related MI and AS showing binding energies lower than -7 kJ/mol.

Conclusions: This research effectively anticipates the potent constituents, probable targets, and pathways implicated in treating SLE with TwHF, specifically addressing complications such as MI and AS. Comprehending the precise molecular mechanism targeting SLE of TwHF and its efficacious bioactive components furnishes a theoretical groundwork for enhancing its clinical utilization. Key Points •SLE is characterized by aberrant immune activation and persistent inflammation. •TwHF exerts immunomodulatory and anti-inflammatory effects. •TwHF exhibits prospects in the treatment of SLE with unknown molecular mechanisms. •Network pharmacology and molecular docking reveal promise in the mechanism of TwHF.

Objectives: ADAMTS-2 is a procollagen N-proteinase that plays an important role in inflammation regulation. The objective of our research is to explore the expression of ADAMTS-2 in Systemic Lupus Erythematosus (SLE), and analyze its relationship with clinical features of SLE, and evaluate the potential value of ADAMTS-2 as a diagnostic biomarker in SLE.

Methods: ADAMTS-2 expression in PBMCs was detected by RT-qPCR in SLE patients, RA patients, and healthy controls (HC). The diagnostic value of ADAMTS-2 for SLE was evaluated by ROC curve, and the correlation between ADAMTS-2 and the clinical characteristics of SLE was analyzed by Spearman's rank correlation coefficient. The expression profiles of GSE8650 and GSE82221 were downloaded from the GEO database. We performed GSEA to further understand the functions of ADAMTS-2 in SLE. CIBERSORT was utilized for immune cell infiltration analysis.

Results: RT-qPCR results validated that the expression of ADAMTS-2 in PBMCs was significantly increased in SLE patients than RA patients and HC. ROC anaylsis suggested that ADAMTS-2 has significant value in distinguishing new-onset SLE patients from RA patients and HC (AUC = 0.805, p < 0.0001). The expression of ADAMTS-2 was negatively correlated with C3, WBC, PLT, neutrophil, and monocyte level. PBMCs samples with high ADAMTS-2 expression were enriched in TNFA_SIGNALING_VIA_NFKB pathway. We found that ADAMTS-2 was positively correlated with neutrophils, M0 macrophages and M2 macrophages.

Conclusion: ADAMTS-2 may be a potential biomarker of SLE patients and closely related to the occurrence and development of SLE. ADAMTS-2 is expected to be a new target for SLE treatment. Key Points • ADAMTS-2 is a potential biomarker of disease activity in SLE patients that develop a flare. • Samples with high ADAMTS-2 expression are enriched in TNFA_SIGNALING_VIA_NFKB pathway in SLE. • ADAMTS-2 expression is positively correlated with neutrophils, M0 macrophages and M2 macrophages.

Introduction / objectives: While presence of concomitant SLE and frailty has been associated with greater emergency department (ED) use than SLE alone in young/mid-aged adults, whether frailty increases ED use in older adults with SLE remains unknown. In a nationally representative United States administrative claims dataset, we investigated the association of frailty duration with use of ED services in the SLE population compared with individuals without systemic rheumatic disease (SRD).

Method: We identified Medicare beneficiaries ≥ 65 years with SLE and matched them (1:4) by age and gender with non-SRD comparators with osteoarthritis. Frailty was determined using a claims-based index and examined each study year (1/2006-9/2015). We used mixed-effect Poisson regression to ascertain the effect of frailty duration exposure on the risk of ED visits in those with SLE and in non-SRD participants, adjusting for covariates.

Results: At baseline (2006), frailty prevalence was similar in participants with SLE (N = 1338; 43.7%) and no SRD (N = 5352; 42.4%) (p = 0.37). Frailty prevalence significantly increased and diverged over time between participants with SLE versus no SRD (67.6% versus 63.7% in 2010 and 83.5% versus 78.1% in 2014) (p < 0.05). As frailty duration increased, risk of ED visits increased in both groups, including after covariate adjustment (SLE: incidence rate ratio [IRR] 1.10, 95% confidence interval [CI] 1.09-1.12; non-SRD: IRR 1.09, 95% CI 1.08-1.10).

Conclusions: In this cohort of older adults, duration of frailty conferred similar increased risk of ED visits among those with and without SLE. This underscores the importance of measuring frailty in older populations with SLE. Key Points • Frailty prevalence was similar at baseline, and increased over time, in participants with SLE and those with no systemic rheumatic disease; however, frailty prevalence increased to a greater extent in those with SLE. • Frailty duration conferred similar increased risk of ED visits among older adults with and without SLE. • This underscores the importance of identifying, preventing, and/or reversing frailty in older populations with SLE and not assuming that SLE alone adequately explains health risks.

Objectives: To estimate the prevalence of late-onset axial spondyloarthritis (lo-axSpA) and to identify clinical, laboratory, and imaging features associated with this phenotype.

Methods: This single-center, observational study included patients diagnosed with axSpA from the "Reuma-check" SpA program. Patients with a symptom onset ≥ 45 years were classified as lo-axSpA, as opposed to early-onset axSpA (eo-axSpA, onset < 45 years). The prevalence of lo-axSpA was calculated, and lo-axSpA and eo-axSpA were compared in terms of clinical, laboratory and imaging characteristics. Factors associated with lo-axSpA were analyzed with univariable followed by multivariable logistic regression.

Results: A total of 126 patients were included, 35 (28%) were lo-axSpA. Comparing lo-axSpA vs. eo-axSpA, significant differences were observed: higher female prevalence in lo-axSpA vs. eo-axSpA (51% vs. 29%), lower NSAID response (52% vs. 73%), increased skin psoriasis prevalence (42% vs. 17%,), and shorter diagnosis delay (40 vs. 93 months). In the multivariable analysis, male sex and diagnosis delay were independently and inversely associated with lo-axSpA (OR 0.2, 95% CI 0.06-0.8 and OR 0.9, 95% CI 0.96-0.99, respectively), while psoriasis was associated with a higher odds for lo-axSpA (OR 4.8, 95% CI 1.1-29).

Conclusion: lo-axSpA was present in more than a quarter of the patients. Although recall bias in the symptom duration cannot be excluded, the presentation with lo-axSpA seems to be associated with distinct features, being more frequent in females and more associated with psoriasis and with a shorter diagnostic delay. Key Points • Late-onset axSpA (≥ 45Y) is observed in 28% in our cohort, a higher frequency than previously reported. • Female sex and psoriasis are associated with a higher likelihood for late-onset axSpA.