OBJECTIVE: Disease activity is a critical indicator for monitoring the progression of ankylosing spondylitis (AS), guiding clinical decision-making, and informing treatment plans. Patient-reported outcome measures (PROMs) have gained prominence in AS clinical management. However, their potential to predict Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) remains unexplored. This study employs machine learning (ML) techniques to develop prediction models utilizing PROMs data to estimate disease activity in patients with AS. METHODS: We utilized data from 389 patients with AS were included sourced from the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from March 2022 to March 2024. This dataset was divided into a training set (80%) and a testing set (20%). A total of 34 variables, including clinician-recorded features and PROMs (e.g., BASDAI, BASFI, BASMI, PGA, VAS, ASAS-HI, FACIT-F, DASS-21), were employed for feature selection and assessment of feature significance using a variety of machine learning methods. Ten models were constructed using Support Vector Machine (SVM) and K-Nearest Neighbour (KNN) classifiers in conjunction with five feature selection methods: Feature Selection with Orthogonal Regression (FSOR), Trace Ratio Criterion (TRC), Robust Feature Selection (RFS), Pearson Correlation Coefficient (PCC), and ReliefF. Model performance was evaluated based on accuracy, specificity, sensitivity, and area under the receiver operating characteristic curve (AUC-ROC). RESULTS: A total of 389 patients with AS were included in the analysis. Key characteristics assessed included Patient Global Assessment (PGA), age, and the impact of disease on daily activities. The results indicated that the FSOR+SVM model achieved the best overall performance, with an AUROC of 0.930 (95%CI: 0.87-0.99) in the validation set. Meanwhile, FSOR+SVM also exhibited the highest sensitivity (83.78%), accuracy (79.35%), and specificity (90.50%). CONCLUSION: The machine learning model developed
OBJECTIVE: Although axial spondyloarthritis (axSpA) is an inflammatory disease primarily affecting the spine, studies investigating cervical spine instability (CSI) are limited, and no research has comprehensively evaluated all forms of CSI. This study aimed to determine the frequency and associated factors of CSI in axSpA patients. METHOD: This retrospective cross-sectional study, conducted in a single tertiary rheumatology unit, included adult axSpA patients with inflammatory back pain duration of > 10 years and receiving biological or targeted synthetic therapy. Patients with any concomitant disease that could affect the spine were excluded. CSI lesions were assessed using lateral neutral, full extension, full flexion, and open-mouth anteroposterior cervical radiographs. Radiographs were evaluated by two blinded rheumatologists. RESULTS: In total, 159 axSpA cases (ankylosing spondylitis: 89.3%; non-radiographic axSpA: 10.7%) were included in the study; 57.9% were male, mean age was 47 years, and mean disease duration was 17 years. A total of 33 CSI lesions was detected in 31 patients (19.5%); the most common was anterior atlantoaxial subluxation (54.5%), followed by subaxial (33.3%) and vertical subluxation (6.1%). In univariate logistic regression analysis; disease duration (p = 0.004), age at first symptom (p = 0.02), uveitis (p = 0.049), and sacroiliitis stage (p = 0.039) were associated with CSI. In multivariate analysis, disease duration was identified as a potential independent predictor of CSI (p = 0.027). CONCLUSION: These results highlight the need for increased clinical awareness of CSI in axSpA, and support consideration of cervical imaging in patients with prolonged disease duration, severe sacroiliitis, or uveitis.
Background Several cases of pyoderma gangrenosum, a rare neutrophilic dermatosis, have been reported in patients initiating biological therapies for rheumatic health conditions. Despite this, systematic analysis across available therapies is lacking. This study investigated pyoderma gangrenosum reporting in association with antirheumatic biologics to the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods Reports from FAERS (2016–second quarter of 2025) were complied, deduplicated, and standardized. Pyoderma gangrenosum cases were classified according to the Medical Dictionary for Regulatory Activities. Proportional reporting ratios (PRRs) and 95% confidence intervals (CIs) were calculated to estimate disproportionality for 20 individual antirheumatic biologics from nine pharmacologic classes. Results During the study period, 13,284,367 adverse events were reported to FAERS, including 1316 pyoderma gangrenosum cases; 868 (65.96%) cases identified an antirheumatic biologic as the primary suspect product. Positive disproportionality signals were detected for 11 study biologics belonging to six pharmacologic classes. All four interleukin (IL)-17 inhibitors exhibited disproportionate pyoderma gangrenosum reporting, with brodalumab (PRR 23.02; 95% CI 8.64–61.36) and bimekizumab (PRR 9.10; 95% CI 4.08–20.29) demonstrating the strongest signals. Positive disproportionality signals were also observed among biologics targeting tumor necrosis factor alpha, IL-6, IL-12/23, IL-23, and CD20. Similar results were obtained in sensitivity analyses. Conclusion Despite its limitations, this hypothesis-generating analysis identified significantly disproportionate pyoderma gangrenosum reporting with several antirheumatic biologics. Clinicians should remain vigilant for these paradoxical reactions in patients undergoing biologic treatment for rheumatic conditions. Key points • Pyoderma gangrenosum has been reported in patients undergoing treatment with biologics for rheumatic indications. • This study analyzed spontaneous postmarketing pyoderma gangrenosum reporting in association with 20 antirheumatic biologics. • Pyoderma gangrenosum disproportionality signals were identified for 11 biologics targeting interleukin (IL)-6, IL-17, IL-12/23, IL-23,
J Rheumatol 2018; doi: 10.3899/jrheum.170487 Recently, the sponsor became aware of data errors related to Bath Ankylosing Spondylitis Metrology Index (BASMI) and the University of California San Francisco (UCSF) Enthesitis Index that occurred during the study. The ensuing tabular and in-text corrections are provided hereinafter.
Ankylosing spondylitis (AS) is a persistent autoimmune disorder marked by inflammation of the spine and sacroiliac joints, along with atypical bone development. In recent years, DNA methylation, a significant epigenetic modification, has become a pivotal element affecting AS pathogenesis, disease progression, and clinical diagnosis. This review summarizes what we know so far about abnormal DNA methylation patterns in AS-related genes like DKK1, ERAP1, PDCD1, FOXO1/3a, LGR6, and IRF5, as well as how these patterns affect gene expression. It examines the interaction between DNA methylation and essential pathological processes such as inflammatory responses, immune regulation, and bone metabolism. Additionally, the prospective utilization of DNA methylation as a biomarker for the diagnosis and prognosis of AS is analyzed. Finally, we talk about new ways to treat AS that focus on DNA methylation mechanisms. This review seeks to amalgamate recent methylome and transcriptome studies to establish a comprehensive theoretical framework and delineate future research directions aimed at elucidating epigenetic mechanisms in AS and promoting clinical translation.
J Rheumatol 2019; doi: 10.3899/jrheum.180718 Recently, the sponsor became aware of data errors related to Bath Ankylosing Spondylitis Metrology Index (BASMI) and the University of California San Francisco (UCSF) Enthesitis Index. The ensuing tabular and in-text corrections are provided hereinafter.
Heart failure (HF) is an increasingly important cause of morbidity and mortality in patients with autoimmune rheumatic diseases. Despite advances in cardiovascular prevention and treatment, HF incidence continues to rise in this population, driven by chronic systemic inflammation, immune-mediated myocardial injury, microvascular dysfunction, fibrosis, and treatment-related cardiotoxicity. Epidemiological studies consistently demonstrate a markedly increased HF risk across a broad spectrum of rheumatic diseases—including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, ankylosing spondylitis, and primary Sjögren syndrome—often manifesting at younger age and independently of traditional cardiovascular risk factors. Subclinical myocardial involvement is frequent and commonly precedes overt HF, with preserved ejection fraction representing the dominant phenotype, particularly in inflammatory arthritis and systemic sclerosis. Advances in speckle-tracking echocardiography, cardiac magnetic resonance, and circulating biomarkers such as natriuretic peptides and cardiac troponins have enabled earlier detection and refined risk stratification. Although anti-inflammatory therapies, including conventional and biologic disease-modifying antirheumatic drugs, may mitigate HF risk, optimal control of traditional cardiovascular risk factors and cautious use of cardiotoxic agents remain essential.
High-resolution, high-throughput single-cell omics has transformed our understanding of autoimmune disease pathogenesis. We synthesise recent single-cell omics advances across six autoimmune diseases-systemic sclerosis, systemic lupus erythematosus, Sjögren's syndrome, ankylosing spondylitis, IgG4-related disease and rheumatoid arthritis. We further summarise translational progress in targeted therapies. We delineate core pathological networks shared across these conditions, highlight convergent mechanisms, and provide a mechanistic rationale for the clinical activity of agents such as tofacitinib and abatacept across multiple autoimmune settings. These insights support the feasibility of mechanism-informed, cross-disease targeting-deploying shared pathway interventions across distinct clinical entities. Finally, we discuss current technical and interpretative challenges and outline future directions for mechanistic discovery, target prioritisation and precision medicine.
Ankylosing spondylitis (AS) is a chronic inflammatory arthropathy with heritability estimated at approximately 90%, yet the effector genes and regulatory mechanisms beyond the well-established HLA-B*27 association remain incompletely defined. Translating GWAS-identified loci into biological insight requires integration of calibrated association statistics, gene-level prioritization, fine-mapping, molecular prediction, and experimental follow-up. We performed a GWAS meta-analysis of 7,551 AS cases and 1,258,581 controls from the Million Veteran Program, FinnGen, and UK Biobank whole-genome sequencing cohorts. The post-GWAS analysis combined causal transcriptome-wide association study (cTWAS) across four immune-relevant tissues, colocalization, four-method fine-mapping, Geneformer V2 in-silico perturbation, AlphaGenome variant-effect prediction, cross-trait LD-score regression (LDSC), pathway enrichment, structured druggability assessment, and siRNA knockdown in Jurkat T cells. We added LDSC calibration, per-cohort Q-Q plots, heterogeneity summaries, and leave-one-cohort-out sensitivity analyzes for revised quality control. The meta-analysis identified 30 genome-wide significant loci harboring 26,178 significant variants. After LDSC-compatible quality control, the meta-analysis showed lambda_GC = 1.09, LDSC intercept = 1.045 (SE = 0.009), and attenuation ratio = 0.365 (SE = 0.075); per-cohort lambda_GC values were 1.027, 1.080, and 1.018 for MVP, FinnGen, and UKB-WGS, respectively. cTWAS prioritized 64 causal-candidate genes (posterior inclusion probability [PIP] > 0.5), with gene expression explaining 19.5% of AS heritability. Seven genes showed convergent cTWAS and colocalization evidence (TBKBP1, TIMD4, HABP4, XCL1, USP22, ABO, ACTA2). Four-method fine-mapping identified 64 consensus variants, while heterogeneity and leave-one-cohort-out analyzes highlighted cohort-sensitive signals, particularly in the MHC and other high-I2 regions. Cross-trait LDSC showed positive genetic correlations with inflammatory bowel disease and psoriasis, but not rheumatoid arthritis or the available uveitis proxy. siRNA knockdown provided functional support for TBKBP1 and XCL1 in Jurkat T cells, while TIMD4 behaved as a context-specific myeloid/T-cell contrast. This convergent evidence framework prioritizes AS candidate
Ankylosing spondylitis (AS) and SAPHO syndrome both involve the spine and sacroiliac joints with bone marrow edema (BME) on MRI, which can lead to spinal structural damage. No previous study has compared BME characteristics between the two diseases. 42 SAPHO and 60 AS patients with spinal or sacroiliac involvement underwent whole-spine and sacroiliac MRI. SPARCC scores for each spinal segment and sacroiliac joints, vertebral unit involvement frequency, and BME range, intensity, depth were compared. Correlation between SPARCC scores of the whole spine and sacroiliac joints and clinical indicators were analyzed in the two groups of patients. SPARCC scores for all spinal segments and sacroiliac joints in AS patients were significantly higher than those in SAPHO syndrome patients (P < 0.01). Defining bone marrow edema as SPARCC score > 0, the positive rate of vertebral units in spinal segments and sacroiliac joints was higher in AS than in SAPHO syndrome (P < 0.05). The incidence of BME in the cervical, thoracic, and sacroiliac joints was higher in AS than in SAPHO syndrome (P<0.001), with no significant difference in the incidence of lumbar spine BME (P > 0.05); the incidence of bilateral sacroiliac joint edema also showed no intergroup difference (P > 0.05). Further analysis of the score composition in SPARCC-positive cases revealed: the extent scores for each spinal segment in AS patients were higher than those in the SAPHO group (P < 0.001), while there were no significant differences in intensity and depth scores between the two groups; in the sacroiliac joints, the extent score was higher in the AS group (P < 0.05), but the intensity score was higher in the SAPHO group (P < 0.05). Correlation analysis in AS and SAPHO patients showed: spinal SPARCC
Rheumatic disease registries systematically collect real-world longitudinal data, improving patient care and research. Despite the high burden of rheumatic diseases, national registries are scarce in the Middle East. Rheumatology Research Center, with support from Iran’s Ministry of Health, launched Rheumatry in 2016 as the country’s first national rheumatic disease registry. To outline the design, governance, and data collection framework of Rheumatry. Rheumatry is a secure, web-based, multicenter registry led by Tehran University’s Rheumatology Research Center. It enrolls patients meeting standardized criteria for major rheumatic diseases (rheumatoid arthritis, Systemic lupus erythematosus, systemic sclerosis, ankylosing spondylitis, Takayasu arteritis, etc.) from over 26 centers nationwide. Comprehensive electronic case report forms (intake and follow-up) capture demographics, disease history, clinical features, laboratory and imaging results, standardized disease activity measures, patient-reported outcomes, and treatment data. As of September 2025, Rheumatry includes ~ 11,900 patients and 26,100 visits. Its multi-disease scope, inclusion of Takayasu arteritis, and alignment with international standards (ACR/EULAR criteria, MedDRA coding) are notable innovations. The registry supports systematic monitoring of disease courses, therapies, and outcomes, addressing a regional gap in real-world evidence. Rheumatry’s national-scale infrastructure provides detailed longitudinal data on diverse rheumatic diseases in Iran. By facilitating research, surveillance, and quality improvement, it bridges a critical information gap in the Middle Eastern context.
Assessing quality of life in patients with axial spondyloarthritis (axSpA) is essential for capturing the full burden of the disease beyond clinical and imaging findings. Quality of life measures support clinicians in identifying unmet patient needs and informing treatment decisions. The aim of this study was to develop and validate the first Bulgarian version of the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. The development of the Bulgarian version of the ASQoL followed a three-stage process: translation, field testing, and psychometric evaluation. Following translation and field testing of the ASQoL, the psychometric evaluation involved administering the ASQoL to a random sample of axSpA patients on two occasions, 10–20 days apart, to assess its reliability and validity. Reliability was examined using internal consistency (Cronbach’s alpha) and test–retest reliability (Spearman’s rank correlation). Convergent validity was evaluated using the Short Form Health Survey Version 2 (SF-36v2) and the Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP). Known-groups validity was assessed based on self-perceived general health and self-perceived disease activity. The Bulgarian version of the ASQoL demonstrated high internal consistency, with Cronbach’s alpha coefficients of 0.884 at time 1 and 0.882 at time 2. Test-retest reliability was excellent (Spearman’s ρ = 0.98, p < 0.001), indicating strong temporal stability. Convergent validity was supported by moderate correlations between ASQoL scores and relevant SF-36 domains, with the strongest associations observed for Physical Functioning, General Health, and Role Limitations. ASQoL scores showed a strong positive correlation with ASDAS-CRP (Spearman’s ρ = 0.70, p < 0.001), indicating close alignment between patient-reported quality of life and clinical disease activity. Known-groups validity was demonstrated by the ASQoL’s ability to distinguish between patient subgroups based on self-perceived general health and
A newsletter aborda o conceito de Gamopatia Monoclonal de Significado Reumatológico (GMSR), enfatizando sua relevância clínica na Crioglobulinemia e no risco de linfoma na Doença de Sjögren. Discute também os resultados de 17 anos do registro REGISPON-3, que revela a instabilidade fenotípica das espondiloartrites e o início tardio de terapias biológicas. Por fim, apresenta avanços no manejo remoto da osteoporose masculina e novos achados imunológicos na dermatomiosite anti-MDA5.
Despite increasing rheumatic disease prevalence among female individuals in Ontario, Canada, research is limited on whether this has translated to an increased proportion of pregnancies with rheumatic diseases. This study aimed to assess rheumatic disease rates among pregnant individuals in Ontario, Canada. Using healthcare administrative claims databases from ICES, the proportion of pregnancies with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from April 2011 to March 2021 were examined. The Mann-Kendall rank correlation test was used to test for trends in overall and individual rheumatic disease rates across the study period. In total, 1,408,100 pregnancies were recorded from fiscal years 2011-2020 in Ontario. Of these, 4,392 involved patients with rheumatic diseases. The overall rheumatic disease rate among pregnant individuals increased by 24% from 28.3 to 35.2 pregnancies per 10,000 over the study period (p = 0.0157). RA rates increased 22% from 11.1 to 13.5 per 10,000 (p = 0.0056), while PsA rates increased 111% from 0.9 to 1.9 per 10,000 (p = 0.0157). SLE, AS, and multiple rheumatic disease rates did not increase significantly. The proportion of individuals with rheumatic diseases pursuing pregnancy in Ontario has increased, perhaps aided by advancements in disease diagnostics and treatment strategies. Further research is needed to link antirheumatic drug safety to pregnancy outcomes and explore other factors that may influence pregnancy rates among this patient population.
Chronic autoimmune inflammatory rheumatic diseases (AIRD), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis, systemic sclerosis (SSc), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), are characterized by the dysregulation of the immune system and that of the neuroendocrine immune networks, leading to chronic inflammation and tissue damage. Perturbations of T, B, and macrophage cells result in uncontrolled inflammation. Traditional therapeutic approaches have focused on immunosuppressive drugs but more recently the use of biologics targeting specific cytokines or receptors on immune cells, and intracellular JAK pathways has been employed. However, these therapies often have limited efficacy and significant side effects. Moreover, they are not globally accessible due to high drug costs especially in poor as well as low- to middle-income countries. Cell immunotherapy, such as CAR-T and CAR-M cell therapy based on chimeric antigen receptor (CAR) technology, is opening up novel potential avenues for a precision approach to managing AIRD. This area is still experimental and in the research phase. This paper reviews the potential of CAR-M immunotherapy in AIRDs, highlighting its mechanisms of action and therapeutic applications.
CC-99677 (BMS-986371) is a novel, small-molecule covalent inhibitor of mitogen-activated protein kinase-activated protein kinase 2 (MK2). We aimed to evaluate the dose-dependent efficacy and safety of CC-99677 compared with placebo in subjects with ankylosing spondylitis (AS). This was a phase II, multicentre, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of CC-99677 in subjects with AS. Subjects were randomised 1:1:1 to once-daily CC-99677 150 mg, CC-99677 60 mg or placebo. Main inclusion criteria were fulfilment of the modified New York criteria for AS, active symptoms (Bath Ankylosing Spondylitis Disease Activity Index ≥4 and total back pain ≥4) despite ≥2 non-steroidal anti-inflammatory drugs and naïve to biologic disease-modifying anti-inflammatory drugs. The primary end point was Assessment of SpondyloArthritis international Society 20% improvement criteria (ASAS20) response at 12 weeks. 147 subjects were enrolled and 123 (83.7%) subjects completed treatment in the double-blind, placebo-controlled period. The main reason for discontinuation was study termination based on futility at interim analysis. Baseline characteristics were typical of an AS trial population. Treatment with CC-99677 was generally well-tolerated. ASAS20 and ASAS40 at week 12 were 51.2% and 25.6% in the CC-99677 60 mg group, 56.1% and 34.1% in the 150 mg group and 48.8% and 22.0% in the placebo group. No significant treatment group differences were noted for secondary end points. There were trends in active treatment groups for improvement in MRI spine and sacroiliac joint inflammation scores but minimal inhibition of pro-inflammatory cytokines in serum. Inhibition of MK2 by CC-99677 was insufficient to lead to significant clinical benefits in AS. NCT04947579.
To update the existing European Alliance of Associations for Rheumatology (EULAR) points to consider (PtC) for use of antirheumatic drugs in reproduction, pregnancy, and lactation, including additional drugs and adverse outcomes as well as paternal drug safety. According to the EULAR standardised operating procedures, an international task force (TF) defined the questions for a systematic literature review, followed by formulation of the updated statements. A predefined voting process was applied to each overarching principle and statement. Level of evidence and strength of recommendation were assigned, and participants finally provided their level of agreement for each item. The TF proposes 5 overarching principles and 12 recommendations for the use of antirheumatic drugs before and during pregnancy, through lactation, and in male patients. The current evidence indicates that synthetic disease-modifying antirheumatic drugs (DMARDs) compatible with pregnancy include antimalarials, azathioprine, colchicine, cyclosporine, sulfasalazine, and tacrolimus. Regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, a more restrictive approach to their use during pregnancy is recommended. Based on an individualised risk-benefit assessment, all tumour necrosis factor inhibitor (TNFi) biologic DMARDs (bDMARDs) can be used throughout pregnancy, and non-TNFi bDMARDs may be used if needed. In relation to lactation, compatible drugs include antimalarials, azathioprine, colchicine, cyclosporine, glucocorticoids, intravenous immunoglobulin (IVIG), NSAIDs, sulfasalazine, and tacrolimus. All bDMARDs are considered compatible with breastfeeding. Concerning the use of drugs in men, compatible options include antimalarials, azathioprine, colchicine, cyclosporine, IVIG, leflunomide, methotrexate, mycophenolate, NSAIDs, glucocorticoids, sildenafil, sulfasalazine, tacrolimus, and bDMARDs. The updated recommendations provide consensus guidance and will help to improve the quality of care of patients during the phases of reproduction, pregnancy, and lactation.
BackgroundPatients with active ankylosing spondylitis (AS) exhibit substantial heterogeneity in their clinical responses to tumor necrosis factor alpha inhibitors (TNFi). Consensus clustering, an unsupervised cluster discovery method, may identify AS subgroups with more homogeneous treatment response patterns to adalimumab (ADA), a widely prescribed TNFi.MethodsWe performed longitudinal consensus clustering based on 8 repeated measurements of 10 core response variables in 438 patients with active AS enrolled in a 24-week phase III randomized controlled trial of ADA or its biosimilar, IBI303. Baseline characteristics and important endpoints—including the Assessment of SpondyloArthritis International Society (ASAS)-based and Ankylosing Spondylitis Disease Activity Score Inactive Disease (ASDAS)-based response criteria—were compared between the identified clusters. Predictive models of cluster membership reconstructed from data beyond week 2 were developed and internally validated to facilitate early, prospective identification of the clusters based on baseline and week-2 data.ResultsTwo longitudinal clusters were characterized: a favorable-response cluster (C1, n = 246, 56.2%) and a less favorable-response cluster (C2, n = 192, 43.8%). Compared with C1, C2 was characterized by older age, longer disease duration, and more frequent prior TNFi exposure, despite comparable baseline C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). For the majority of clinical endpoints except CRP and BASMI, significant divergence emerged as early as week 2 and was sustained through week 24. For instance, C1 achieved significantly higher rates of ASDAS-Inactive Disease (ASDAS-ID) than C2 at week 2 (0.21 [95% CI 0.16, 0.26] vs. 0.01 [95% CI 0.00, 0.02]; Risk Difference [RD]: -0.21 [95% CI -0.26, -0.15], p < 0.001) and week 24 (0.63 [95% CI 0.57, 0.69] vs. 0.14 [95% CI 0.09, 0.18]; RD: -0.49 [95% CI -0.57, -0.42], p < 0.001). A multivariable model incorporating one baseline and
Patients with autoimmune rheumatic diseases (ARDs) face the dual challenge of controlling disease activity while ensuring fetal safety during pregnancy. Biologics are increasingly used to treat ARDs, but evidence regarding their safety during pregnancy remains uncertain. This study aims to systematically evaluate the safety of biologics during pregnancy by performing a systematic review and meta-analysis. A comprehensive search was conducted in major databases to identify studies involving pregnant ARDs patients treated with biologics from inception to 30th September 2024. The outcomes assessed included small for gestational age (SGA), cesarean section, preterm birth (PTB), low birth weight (LBW), gestational diabetes mellitus (GDM), pre-eclampsia, gestational hypertension, severe maternal infection, birth defects (BD), and a composite outcome of fetal miscarriage or death. A total of 40 studies involving 11,712 patients were included. The pooled prevalence of adverse pregnancy outcomes (APOs) in patients exposed to biologics was comparable to those observed in the general ARDs population. Compared to other biologics, tumor necrosis factor inhibitors (TNFis) was associated with a significantly lower prevalence of cesarean section (26.93 % vs. 63.64 %, p = 0.01), early pregnancy loss (10.44 % vs. 18.77 %, p = 0.03), and termination of pregnancy (8.59 % vs. 16.11 %, p < 0.01). Compared to csDMARDs, biologic use during pregnancy did not significantly increase the risk of APOs. Exposure to biologics during pregnancy in ARDs patients does not significantly increase the risk of APOs, with TNFis showing a well-supported safety profile, while non-TNFi biologics may carry higher risks, requiring cautious evaluation.
To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.
Autoimmune rheumatic diseases (ARDs) often affect women during their reproductive years, and early studies of pregnancy in these patients reported high rates of adverse outcomes. Continuation or initiation of safe and effective medications in the preconception period is beneficial for maintaining or achieving disease quiescence throughout pregnancy thereby improving both maternal and pregnancy outcomes. The European Alliance of Associations for Rheumatology, the American College of Rheumatology, and the British Society for Rheumatology have published recommendations and guidelines regarding management of ARDs during pregnancy. The American College of Obstetricians and Gynecologists and the American Gastroenterological Association have also provided guidance statements with relevant recommendations. This review provides an overview of available recommendations for medication use in ARD pregnancy, with discussion of safety considerations for maternal and fetal well-being. Medications considered compatible with pregnancy include hydroxychloroquine, sulfasalazine, azathioprine, cyclosporine, tacrolimus, and TNF inhibitors. Methotrexate, mycophenolate, leflunomide, and cyclophosphamide should be avoided before and during pregnancy. Other medications, most of them newer, are largely discouraged for use in pregnancy due to inadequate data or concerns for neonatal immunosuppression, including non-TNF biologics and small molecule therapies. Further investigation is needed regarding effects of non-TNF biologics, biosimilars, and small molecules in pregnancy. Important efforts for the future will include improved methodologies to gather critical safety data, with consideration of inclusion of pregnant women in clinical trials, a complex and controversial issue. Long-term information on outcomes in offspring of treated women is lacking for many of these medications.
Stroke is a major cause of mortality and long-term disability worldwide. Patients with autoimmune rheumatic diseases (ARDs) exhibit a significantly increased risk of both ischemic and hemorrhagic strokes, particularly at younger age. Systemic inflammation, immune-mediated vascular injury, antiphospholipid antibodies, accelerated atherosclerosis, and comorbidities contribute to this elevated cerebrovascular burden. This review aims to comprehensively overview stroke epidemiology, pathophysiological mechanisms, clinical characteristics, prevention strategies, and post-stroke rehabilitation in patients with ARDs. Literature searches were conducted using Medline/PubMed, Scopus, Web of Science, and the Directory of Open Access Journals (DOAJ) databases up to February 1, 2026. Studies evaluating stroke incidence, risk factors, mechanistic pathways, prevention approaches, and rehabilitation in rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, ankylosing spondyloarthritis, systemic vasculitides, and Behçet disease were included. Stroke risk is markedly increased across ARDs, with relative risks ranging from 1.3 to 2.5, depending on disease subtype. Systemic lupus erythematosus and systemic vasculitides confer particularly high cerebrovascular risk, often presenting at younger age and associated with worse functional outcomes. Chronic systemic inflammation, endothelial dysfunction, autoantibody-mediated thrombosis, genetic susceptibility, and accelerated atherosclerosis represent central mechanistic pathways. Certain immunomodulatory therapies may mitigate stroke risk through inflammation control, whereas others require careful cardiovascular risk assessment. Post-stroke recovery may be adversely influenced by persistent inflammatory activity and musculoskeletal comorbidities, underscoring the importance of multidisciplinary management. Early risk stratification, tight control of systemic inflammation, individualized immunomodulatory therapy, and structured rehabilitation strategies are essential to improve cerebrovascular outcomes in ARDs. Future research should focus on personalized risk prediction models and targeted preventive interventions in this high-risk population.
The aim of this study was to evaluate the prevalence and severity of spinal structural lesions on radiographs versus opportunistic thoraco-abdomino-pelvic CT (TAP CT) in ankylosing spondylitis (AS). This monocentric retrospective pilot study included AS patients meeting the modified New York criteria for radiographic sacroiliitis who had both spine radiographs and TAP CT within 12 months. On CT, 36 anterior vertebral corners (C7-S1) were graded for erosion/squaring (grade 1), syndesmophytes (grade 2), and bone bridges (grade 3). Posterior facet joint ankylosis was recorded as present or absent, generating anterior, posterior, and total CT-scores (0-216). Radiographic assessment was performed using the Radiographic Ankylosing Spondylitis Spinal Score (RASSS, 0-84). A total of 142 patients were included (median age 54 years [47-62], 70.4% male, 77.6% HLA-B27 positive, median disease duration 14 years [6-26], 43.5% treated with bDMARDs). Structural spinal damage was identified in 62.6% by RASSS and 71.8% by CT. Anterior vertebral lesions were present in 94 patients, and 68 exhibited posterior facet joint ankylosis. Mean RASSS and total CT-scores were 13.1 (±20.0) and 37.2 (±47.2), respectively. Total CT-score correlated with age, disease duration, male sex, HLA-B27 positivity, inflammatory bowel disease, and CRP >5 mg/L (p<0.05). Multivariate analysis confirmed associations with age, disease duration, male sex, and CRP. Intra-reader reliability was excellent for both modalities (ICC >0.90). Opportunistic TAP CT is a reliable, reproducible, and complementary imaging tool to radiography for evaluating anterior and posterior spinal structural damage in AS.
Programmed cell death protein 1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) are immune checkpoints expressed on T cells. Despite recent development of PD-1 agonists in rheumatoid arthritis (RA), little is known about PD-1 and TIGIT coexpression in RA and other immune-mediated inflammatory diseases (IMIDs). This study quantified PD-1 and TIGIT expression in CD4 and CD8 T cells in patients with IMID and examined associations with disease characteristics and anti-tumour necrosis factor (TNF) response. Biologics-naïve patients with RA and spondyloarthritis (AS) were followed prospectively to assess anti-TNF response at 12 months. Sjögren's disease (SjD) patients and healthy volunteers (HV) were also included at baseline. PD-1 and TIGIT expression on CD4 and CD8 T cells was analysed by flow cytometry at baseline and after 3 months of anti-TNF treatment. Plasma cytokines were quantified using the Meso Scale Discovery assay. 67 patients were included. Median CD8+PD-1+TIGIT+ levels were higher in RA (24%) and SjD (23.2%) than in HV (18.8%) and AS (16.2%). CD4+PD-1+TIGIT+ were positively correlated with circulating immunoglobulin G (r=0.698, p<0.001), interferon gamma (r=0.635, p=0.017) and IP-10 (r=0.612 p=0.005) levels in patients with SjD. Baseline CD4+PD-1+TIGIT+ levels were higher in future anti-TNF responders (9.9%) compared with non-responders (6.1%, p=0.003). Both CD4+PD-1+TIGIT+ and CD8+PD-1+TIGIT+ cells increased after 3 months of anti-TNF treatment in RA and AS. CD8+PD-1+TIGIT+ T-cell expression is elevated in SjD and RA compared with HV and AS. CD4+PD-1+TIGIT+ levels are higher in future anti-TNF responders compared with non-responders and rise after treatment in patients with RA and AS. Further studies should clarify the functional role of CD4+PD-1+TIGIT+ cells in IMIDs.
Objective This study aimed to investigate the effects of yoga-based exercises, combined with aerobic exercises, on spinal mobility, disease activity and functional capacity in Ankylosing spondylitis (AS). Methods A total of 51 patients with AS (27 males, 24 females; mean age: 40.7 ± 9.1 years; range 24-57 years) completed in this prospective, randomized, controlled study. Group 1 (n = 25) received only aerobic exercise therapy, while group 2 (n = 26) received yoga therapy in combination with aerobic exercises. The intensity of the aerobic exercise program were determined using Cardiopulmonary Exercise Testing (CPET). The aerobic program was administered for 30 min over 12 sessions, under physician supervision with monitoring using a lower extremity ergometer. In group 2, in addition to the aerobic program, a yoga-based exercise consisting of spinal flexibility, relaxation, breathing and meditation exercises was administered for 30 min over 12 sessions. Spinal mobility (chest expansion(CE) and BASMI), peripheral muscle strength and laboratory measures (ESR and CRP), were recorded pre- and post-treatment. SpA-specific clinical measures included the ASDAS-CRP, BASFI, ASQoL scale, fibromyalgia scores. Functional capacity was evaluated using the 6-Minute Walk Test (6-MWT). Respiratory parameters and aerobic capacity levels, recorded using Pulmonary Function Tests (PFT) and CPET. Results In the analysis comparing pre- and post-treatment delta gain values between the two groups, statistically significant differences favoring group 2 were found in CE (p = 0.002), BASMI (p = 0.025), right and left handgrip strength (p = 0.023, 0.044), BASFI (p = 0.03), 6-MWT (p = 0.005) and resting systolic blood pressure (p = 0.012). In the Holm-Bonferroni-adjusted sensitivity analysis of between-group delta comparisons, chest expansion, BASMI, and 6-MWT remained statistically significant among clinical and functional secondary outcomes, whereas handgrip strength and BASFI no longer remained statistically significant Conclusion This study showed that a physician-supervised combined aerobic and yoga-based exercise program may
Rheumatic diseases (RDs) are chronic immune-mediated disorders associated with disproportionately increased cardiovascular morbidity and mortality. Accelerated atherogenesis in these diseases is driven by persistent systemic inflammation, autoantibody-mediated endothelial injury, oxidative stress, and dysregulated lipid metabolism, resulting in premature vascular remodeling manifested by increased carotid intima-media thickness, arterial stiffness, impaired flow-mediated dilation, and coronary artery calcification. This review synthesizes evidence regarding subclinical atherosclerosis and cardiometabolic risk across common RDs. In rheumatoid arthritis and systemic lupus erythematosus, vascular alterations correlate with inflammatory burden, disease duration, autoantibody profiles, renal involvement, and glucocorticoid exposure. Emerging biomarkers-including apolipoprotein B48, FIB-4 index, asymmetric dimethylarginine, and adhesion molecules-provide incremental prognostic value beyond traditional lipid parameters. Advanced imaging modalities, such as ^18F-sodium fluoride PET/CT and vascular elastography, enhance early detection of arterial calcification and stiffness. Growing evidence in primary Sjögren syndrome, Behçet disease, systemic sclerosis, and ankylosing spondylitis similarly confirms increased subclinical atherosclerosis and endothelial dysfunction. Importantly, tight disease control and targeted immunomodulatory therapies-including methotrexate, biologic agents, antimalarials, and cytokine-directed treatments-are associated with improved vascular and metabolic profiles and attenuation of disease progression. Subclinical atherosclerosis represents a critical interface between autoimmunity and cardiovascular disease in RDs. Early vascular assessment integrated with disease-specific and metabolic risk stratification is essential to implement precision-based cardiovascular prevention in this high-risk population.
Spondyloarthritis (SpA) comprises a heterogeneous group of chronic inflammatory rheumatic diseases affecting the axial skeleton, peripheral joints, and entheses. It is uniquely characterized by the coexistence of inflammation and pathological new bone formation, ultimately leading to ankylosis. Although the precise pathogenic sequence remains incompletely defined, experimental animal models have provided essential mechanistic insights by reproducing key immunological and structural features of the disease. This narrative review synthesizes current knowledge on SpA pathophysiology derived from these models. Rodent models have demonstrated the central role of the IL-23/IL-17 axis. The HLA-B27 transgenic rat and the SKG mouse illustrate how dysregulated type 3 immunity, often amplified by intestinal dysbiosis, drives sustained entheseal inflammation. Non-HLA-B27 inflammatory models, such as proteoglycan-induced arthritis and spontaneous arthritis in DBA/1 mice, have clarified the contribution of osteogenic pathways, particularly Wnt and BMP/TGF-β signaling, in the transition from inflammation to pathological bone formation. Other models highlight the continuum between inflammatory, destructive, and anabolic processes. In transmembrane TNF transgenic mice, severe ossification occurs independently of major erosions. The TNF^ΔARE (TNFTg197) model has been instrumental in establishing a mechanistic link between impaired Wnt inhibition and ankylosis, as pharmacological blockade of Dkk-1 shifts the phenotype from erosive sacroiliitis to complete joint fusion. Together, these models have elucidated the interplay between immune activation, the microbiota, and osteogenic pathways in SpA. They remain indispensable for mechanistic research and therapeutic development and are increasingly integrated with OMICS-based approaches.
Clinical practice guidelines support evidence-based care and aim to reduce unwarranted variation in healthcare. Despite evidence that guideline-adherent physiotherapy is associated with reduced healthcare utilisation, adherence among physiotherapists remains inconsistent. This scoping review aimed to synthesise evidence on determinants of guideline adherence and implementation strategies in physiotherapy and to identify research gaps relevant to guideline implementation. Scoping review. MEDLINE (PubMed), EMBASE, the Cochrane Library, PEDro and CINAHL were searched from database inception to July 2023 and updated in July 2025. Grey literature sources, including Grey Literature Report, OpenGrey and Web of Science Conference Proceedings, were also searched. Reference lists of included studies were screened. Studies were eligible if they examined determinants of guideline adherence and/or implementation strategies in physiotherapy. Studies involving physiotherapists across all clinical fields and settings were included. Only studies published in English or German were considered. Determinants were analysed using qualitative content analysis and mapped to the Consolidated Framework for Implementation Research (CFIR). Implementation strategies were summarised using Proctor's reporting recommendations. Fifty-eight studies were included: 29 examined determinants, 25 implementation strategies and four both. Determinants were identified across all CFIR domains, with most relating to the Inner Setting and Characteristics of Individuals. Implementation strategies primarily targeted individual-level change, such as education, reminders and feedback, whereas few addressed system-level factors, including organisational leadership or reimbursement structures. Guideline implementation in physiotherapy is shaped by determinants across individual, organisational and system levels, yet current strategies predominantly focus on individual clinicians. This individual-level focus may contribute to the responsibilisation of clinicians for care quality, while organisational and system-level strategies that have shown promise in other fields remain underutilised in physiotherapy. Future implementation initiatives should adopt broader, system-oriented approaches to enhance long-term
Inadequate response to tumor necrosis factor inhibitors (TNFi) in ankylosing spondylitis (AS) remains common. As the immunoregulatory and immunometabolic alterations across TNFi inadequate responder (TNFi-IR) subsets remain unexplored, we characterized molecular profiles across distinct immune subsets in TNFi-IRs and identified signatures linked to TNFi-IR. We compared subset-specific expression in 16 TNFi-IRs and 13 TNFi responders (TNFi-Rs). Gene expression demonstrated fair-good discriminative power (area under the curve: 0.70-0.87). TNFi-IRs displayed distinct transcriptomic profiles and aberrant transcription factor activity amplifying inflammatory responses across immune subsets. Pathway analysis revealed synergistic association between immune subsets and inadequate response, with recurrent alterations in mitochondrial respiration accompanied by metabolic reprogramming exacerbating immune activation. Altered cell-cell communication hinted at impaired IL-10 and IL-19 regulatory signaling. We identified candidates with repurposing potential for TNFi-IRs. These findings reveal crucial therapeutic targets spanning genes, transcription factors, pathways, metabolites, and cell-cell communication signaling for bench-to-bedside investigation.
Targeted therapies (TTs), including biologic and targeted synthetic DMARDs, have transformed the management of inflammatory arthritis (IA). However, their use in patients with a history of cancer raises concerns due to the role of immunity in tumor surveillance and the lack of randomized controlled trial data in this population. Recent observational studies and systematic reviews, including over 15,000 patient-years of follow-up, show no increased risk of new or recurrent malignancy with TNF inhibitors compared with csDMARDs. Rituximab appears safe in patients with prior lymphoma, while caution remains warranted for JAK inhibitors and abatacept given potential safety signals observed in other contexts. Importantly, TNF inhibitors initiated within five years of a cancer diagnosis were not associated with higher recurrence risk. The 2024 EULAR Points to Consider provide updated guidance, recommending individualized therapeutic strategies based on cancer type, remission status, and comorbidities, with close collaboration between rheumatologists and oncologists. While current evidence is reassuring for TNF inhibitors, data on other TTs remain limited. Future research should focus on long-term safety, inclusion of broader IA subtypes, and development of personalized cancer risk stratification tools.
Background: The optimal perioperative management of biologic disease-modifying antirheumatic drugs (bDMARDs) in inflammatory rheumatic disease (IRD) patients undergoing total joint arthroplasty (TJA) remains debated, with current guidelines based on low-to-moderate quality evidence.Methods: Using the Taiwan National Health Insurance Research Database (NHIRD, 2004–2020), we identified IRD patients undergoing primary TJA and propensity score-matched them with non-IRD controls. Within the IRD cohort, patients were categorized by perioperative bDMARD strategy: continuation (n=623) versus withholding (n=631). Primary outcomes included surgical site infection (SSI), delayed wound healing, and disease flares within 30 days.Results: Among 1,254 propensity-matched IRD patients, SSI rates were comparable between continuation and withholding groups, consistent with prior studies [12,17], (2.91% vs 2.51%; OR 1.31, p=0.39), as was delayed wound healing (2.21% vs 1.09%; OR 2.02, p=0.43). Disease flares were significantly lower with continuation (6.12% vs 22.33%; OR 0.13, p=0.03). Healthcare costs were lower in the continuation group.Conclusions: Perioperative bDMARD continuation did not increase SSI or wound complications but substantially reduced disease flares. Blanket bDMARD discontinuation may not be warranted, supporting individualized perioperative management.