Background: Cardiovascular (CV) morbidity, mortality and metabolic syndrome are associated with rheumatoid arthritis (RA). A recent trial has suggested increased risk of major CV events (MACE) upon the Janus kinase (JAK) inhibitor tofacitinib compared with anti-tumor necrosis factor α (TNF-α) therapy. In our study, we evaluated lipids and other metabolic markers in relation to vascular function and clinical markers in RA patients undergoing one-year tofacitinib therapy. Patients and methods: Thirty RA patients treated with either 5 mg or 10 mg bid tofacitinib were included in a 12-month follow-up study. Various lipids, paraoxonase (PON1), myeloperoxidase (MPO), thrombospondin-1 (TSP-1) and adipokine levels, such as adiponectin, leptin, resistin, adipsin and chemerin were determined. In order to assess flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and arterial pulse-wave velocity (PWV) ultrasonography were performed. Assessments were carried out at baseline, and 6 and 12 months after initiating treatment. Results: One-year tofacitinib therapy significantly increased TC, HDL, LDL, APOA, APOB, leptin, adipsin and TSP-1, while significantly decreasing Lp(a), chemerin, PON1 and MPO levels. TG, lipid indices (TC/HDL and LDL/HDL), adiponectin and resistin showed no significant changes. Numerous associations were found between lipids, adipokines, clinical markers and IMT, FMD and PWV (p < 0.05). Regression analysis suggested, among others, association of BMI with CRP and PWV (p < 0.05). Adipokines variably correlated with age, BMI, CRP, CCP, FMD, IMT and PWV, while MPO, PON1 and TSP-1 variably correlated with age, disease duration, BMI, RF and PWV (p < 0.05). Conclusions: JAK inhibition by tofacitinib exerts balanced effects on lipids and other metabolic markers in RA. Various correlations may exist between metabolic, clinical parameters and vascular pathophysiology during tofacitinib treatment. Complex assessment of lipids, metabolic factors together with clinical parameters and vascular pathophysiology may be utilized in clinical practice to determine and monitor the CV status of patients in relation with clinical response to JAK inhibition.

Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) positive dermatomyositis is a distinct subset of idiopathic inflammatory myopathies (IIMs), often associated with unique cutaneous features and interstitial lung disease (ILD). While East Asian cohorts frequently report high mortality due to rapidly progressive ILD (RP-ILD), data regarding Central and Eastern European populations remain scarce. Methods: We conducted a retrospective multicenter study of anti-MDA5 positive Caucasian patients managed at four Hungarian rheumatology centers between 2020 and 2025. Demographic, clinical, serological, and radiological data were analyzed. Antibody profiling was performed using a standardized 16-antigen immunoblot assay. Results: Anti-MDA5 positivity was confirmed in 24 out of 742 patients (3.23%) treated in the four centers. The median age at diagnosis was 49.5 years (range: 24–81). Classic dermatomyositis was the predominant clinical phenotype (75%), followed by clinically amyopathic dermatomyositis (CADM) (12.5%) and polymyositis (12.5%). ILD was identified in 58.3% of patients, presenting with organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP), and usual interstitial pneumonia (UIP) patterns. At diagnosis, median creatine kinase (CK) (193.5 U/L) and C-reactive protein (CRP) (4.24 mg/L) levels remained low even in the ILD group, whereas lactate dehydrogenase (LDH) was elevated in 91.7% of the cohort. Anti-Ro52 positivity (45.8% overall) emerged as a notable predictor of ILD (odds ratio [OR]: 22.5, 95% confidence interval [CI]: 2.10–240.48; p = 0.0045), being present in 71.4% of affected patients. RP-ILD occurred in two patients (8.3%). Therapeutic management followed an early, aggressive strategy, frequently utilizing cyclophosphamide (45.8%) and methotrexate (37.5%), with Janus kinase (JAK) inhibitors or rituximab employed in refractory cases. Overall disease-specific survival was 100% during the study period (median follow-up: 72.0 months); no mortality was directly attributable to IIM-related complications. Conclusions: Our study demonstrates that anti-MDA5 positive dermatomyositis in a Hungarian cohort is characterized by heterogeneous manifestations and a significant association between anti-Ro52 and ILD. The observed dissociation between low CK/CRP and elevated LDH underscores the necessity for a high index of suspicion, with LDH serving as a superior marker for disease activity. While ILD presents a significant risk, early and intensive multi-modal intervention may yield superior survival outcomes in European patients compared to the historical mortality rates reported in Asian cohorts.

Background/Objectives: Connective tissue disease-associated interstitial lung disease (CTD-ILD) is linked to substantial morbidity and mortality. While nintedanib (NTB) slows lung function decline in progressive pulmonary fibrosis (PPF), real-world data—particularly regarding radiographic outcomes—remain limited. We aimed to evaluate the real-world effectiveness and tolerability of antifibrotic therapy—predominantly NTB—on radiographic and functional outcomes in a Hungarian CTD-ILD cohort. Methods: We conducted a retrospective observational cohort study including 72 patients with progressive CTD-ILD who initiated antifibrotic therapy at two Hungarian tertiary centers between January 2021 and June 2025. The primary endpoint was the proportion of patients without significant radiographic progression at 6–12 months, based on blinded assessment of paired high-resolution computed tomography (HRCT) scans by two thoracic radiologists. Secondary endpoints included changes in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) at 6 and 12 months, safety and tolerability, and correlations between lung function and disease-related factors. Results: The cohort comprised systemic sclerosis–ILD (n = 25), rheumatoid arthritis–ILD (n = 23), and other CTD-ILD (n = 24). Radiographic stability was observed in 65.8–78.9% of patients, with improvement most commonly seen in ground-glass opacities, while traction bronchiectasis remained largely unchanged. Radiographic disease extent showed the strongest inverse correlation with baseline FVC and DLCO (p < 0.05). Significant improvements in FVC and DLCO were observed at 6 and 12 months (p < 0.001). Antifibrotic therapy was well tolerated, including in combination with immunosuppressive treatment. Conclusions: These real-world data support the effectiveness and safety of NTB in PPF–CTD-ILD and highlight radiologic disease burden as a key determinant of functional impairment.

Spondyloarthritis associated with inflammatory bowel diseases (IBD-SpA), also known as enteropathic arthritis, is an independent entity belonging to the spondyloarthritis (SpA) group. In recent years, a great amount of new data has been published regarding the pathogenesis and treatment of the disease. In this narrative review we present the main pathogenetic pathways along the gut–joint axis, the genetics of IBD and SpA, the role of environmental factors and that of the microbiome, as well as the main immunopathological processes including immune cells and inflammatory mediators. We cover the clinical picture, the specifics of axial and peripheral SpA-IBD, and briefly discuss the diagnostics. There are common options in the pharmacotherapy of SpA and IBD; however, some drugs that control arthritis (e.g., NSAIDs, IL-17 inhibitors) might not be suitable for the treatment of IBD. Based on the pathogenetic role of the microbiome, it is suggested that pharmacotherapy can be supplemented with non-pharmacological remedies, such as diet including the administration of short-chain fatty acids (SCFAs). Finally, we briefly look at the future that might include rational, even personalized treatment.

Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies are critical biomarkers in myositis, associated with distinct clinical features and prognosis. This study aimed to evaluate the proportion of anti-MDA5 positivity and compare the diagnostic performance of local immunoblotting (IB) with gold-standard immunoprecipitation (IP). We performed a retrospective analysis of 3272 physician-requested anti-MDA5 IB determinations over a five-year period (2019–2023). A subsequent exploratory pilot study of ten Hungarian patients with myositis was conducted to compare IB results with radiolabeled protein IP. Confirmatory in-house enzyme-linked immunosorbent assay (ELISA) was used to distinguish between 140 kDa bands (anti-MDA5 vs. anti-NXP2). Indirect immunofluorescence (IIF) on HEp-2 cells was also evaluated. In the retrospective cohort, 3.7% (n = 121) of samples were non-negative. Among 64 borderline patients, only one (1.6%) had a definitive diagnosis of dermatomyositis (DM). Conversely, the proportion of confirmed myositis cases was notably higher among patients with strong positive IB results. In our exploratory cross-sectional pilot study, complete concordance between the two assays was observed for negative and strong positive results. Discrepancies were noted in borderline and weak positivity ranges, where anti-MDA5 was not detected by IP; instead, alternative autoantibodies were identified. The three IP-confirmed MDA5 positive samples were all validated by ELISA. The characteristic IIF cytoplasmic staining was identifiable in 2 out of 10 cases (20%). In our cohort, borderline IB cases were frequently potential false positives, highlighting the need for careful clinical evaluation. Borderline and weak results require clinical correlation or confirmatory testing to avoid misdiagnosis.

Systemic sclerosis (SSc) is a severe autoimmune rheumatic disease with high mortality. Epigenetic factors, particularly micro-RNAs (miRNAs), may contribute to its pathogenesis by regulating gene expression. In this cross-sectional study, we assessed altered miRNA–mRNA regulatory networks in SSc and associated them with disease-related biological processes. We analyzed the miRNA profiles and differentially expressed genes (DEGs) of peripheral blood mononuclear cells (PBMCs) from 52 SSc patients (42 women and 10 men; mean age: 59.1 years) and 24 age- and gender-matched healthy controls. Total RNA was isolated and subjected to high-throughput next-generation sequencing for both miRNA and mRNA profiling. We identified 58 differentially expressed miRNAs (DEMs), 33 upregulated and 25 downregulated in SSc. In parallel, 6610 DEGs were detected (Mann–Whitney U-test, p < 0.05); 31 remained upregulated and nine downregulated after false discovery rate (FDR) correction. Integration of miRNA and mRNA data revealed 180 validated inverse miRNA–mRNA interactions. Notably, 22 of 31 upregulated DEGs corresponded to targets of downregulated miRNAs, indicating coordinated derepression. Functional enrichment analyses highlighted pathways related to extracellular matrix (ECM) remodeling, immune responses, fibrosis, and transcriptional regulation. Our findings suggest that altered miRNA expression contributes to widespread transcriptional dysregulation in SSc, promoting pro-fibrotic and immune-activated molecular pathways through coordinated miRNA–mRNA interactions.