Rheumatoid Arthritis Disease Research Articles

Tri-signal CdS@SiO2 nanoprobes for accurate and sensitive detection of human immunoglobulin G with enhanced flexibility and internal validation

Accurate and sensitive determination of human immunoglobulin G (HIgG) level is critical for diagnosis and treatment of various diseases, including rheumatoid arthritis, humoral immunodeficiencies, and infectious disease. In this study, versatile tri-signal probes were developed by preparing CdS@SiO2 nanorods that integrate photoluminescence (PL), multi-phonon resonant Raman scattering (MRRS) and infrared absorption (IRA) properties. Through the coating of multiple CdS nanoparticles as cores within SiO2 shells, the PL and MRRS properties of CdS were improved, resulting in a significantly lowered limit of detection (LOD), with the lowest LOD of 12.37 ag mL−1. Integration with the distinctive IRA property of SiO2 shells widened the detection range towards higher concentrations, establishing a final linear range of 50 ag mL−1 to 10 μg mL−1. The remarkable consistency among the three signals highlighted the robust internal verification capability for accurate detection. This approach enhances flexibility in selecting detection methodologies to suit diverse scenarios, facilitating HIgG detection. The tri-signal nanoprobes also exhibited excellent detection selectivity, specificity and repeatability. This study presents a fresh idea for developing high-performance detection strategies.

The Role of Immunohistochemistry in Managing Clinical Hypertension and Other Chronic Inflammatory Processes

Immunohistochemistry (IHC) is a pivotal technique in the visualization of specific proteins within tissue samples, leveraging antigen-antibody interactions to elucidate protein presence, distribution, and abundance. In clinical hypertension, IHC is instrumental in unraveling disease mechanisms, identifying biomarkers, and fostering targeted therapies. This review delves into IHC’s contributions to managing hypertension by examining its role in understanding the pathophysiology and identifying key proteins like those in the renin-angiotensin-aldosterone system. Elevated angiotensin II type 1 receptors in vascular walls, detected via IHC, correlate with hypertension and vascular remodeling. Additionally, IHC identifies inflammatory markers such as interleukin-6 and tumor necrosis factor-alpha, linking chronic inflammation to hypertension. The technique is vital for discovering biomarkers like endothelial nitric oxide synthase and vascular endothelial growth factor, essential for assessing endothelial function. IHC also detects oxidative stress markers, aiding in understanding oxidative mechanisms in hypertension. Evaluating antihypertensive therapies at a molecular level, IHC shows how interventions affect protein expression and vascular health, guiding therapeutic strategies. By revealing proteins differentially expressed in hypertensive tissues, IHC identifies new therapeutic targets, enhancing treatment efficacy. Furthermore, this review explores the application of IHC in other chronic inflammatory conditions, such as rheumatoid arthritis and inflammatory bowel disease, highlighting its broader relevance in disease management. Recent advancements include the development of new drugs targeting specific molecular pathways, such as endothelin 1 receptor antagonists like aprocitentan, approved by the FDA in March 2024 for the treatment of resistant arterial hypertension. Overall, IHC significantly advances both research and clinical practice, promising improved health outcomes through continued methodological advancements.

Association between dry eye disease subtypes and rheumatoid arthritis

Aim of the workTo evaluate the association of dry eye disease (DED) subtypes (aqueous deficient dry eye, ADDE and evaporative dry eye, EDE) and the presence of rheumatoid arthritis (RA) in patients. Patients and methods260 volunteer DED participants were recruited for an observational cross-sectional study based on the Tear Film Ocular Society Dry Eye Workshop II criteria, which included tear film osmolarity, fluorescence break-up time, and ocular surface damage assessment. Participants were recruited using QR linked to designated mobile forms to obtain symptomatology status, demographics, and RA diagnosis by their medical doctor. Tear meniscus and lipid layer were also evaluated to differentiate between ADDE, EDE, or mixed dry eye in addition to the DED diagnostic criteria. Participants with mixed dry eye were excluded from the analysis to avoid bias. ResultsAfter initial recruitment, 149 eligible participants with an ADDE or EDE diagnosis were included in the final analysis, where 12,1% have an RA diagnosis. The ADDE group had a higher likelihood of having RA (OR = 4.69, 95 %CI = 1.46–15.01) than the EDE group. Additionally, the number of participants with RA in the ADDE group was statistically higher than those in the EDE group (all p = 0.006). Furthermore, a correlation was obtained between RA and a diagnosis of ADDE (p = 0.005). ConclusionThere was a significant association between ADDE and the presence of RA in patients and the association was more likely compared to those with EDE. This finding underscores the need for specific diagnostic and management strategies for RA patients presenting with DED.

Hypertension and insulin resistance in rheumatoid arthritis: unveiling insights with mets-ir index

Aim: Hypertension (HT), together with metabolic dysfunctions and insulin resistance (IR) in its pathophysiology, is a significant risk factor for cardiovascular disease in rheumatoid arthritis (RA) patients. Identifying IR early could enhance HT management, especially in RA patients, where HT prevalence is elevated. The study aimed to assess metabolic indices, particularly the METS-IR, as predictors of HT in RA patients. Material and Methods: This retrospective, cross-sectional study investigated the association between RA, IR, and HT in 80 RA patients and 80 age- and sex-matched controls. Patients with diabetes, pre-diabetes, or other conditions affecting insulin sensitivity were excluded, as were those on glucose-metabolism-affecting medications except low-dose glucocorticoids (

Identification of shared disease marker genes and underlying mechanisms between rheumatoid arthritis and Crohn disease through bioinformatics analysis.

As chronic autoimmune inflammatory diseases, rheumatoid arthritis (RA) and Crohn disease (CD) are closely associated and display a significant positive correlation. However, the underlying mechanisms and disease markers responsible for their cooccurrence remain unknown and have not been systematically studied. Therefore, this study aimed to identify key molecules and pathways commonly involved in both RA and CD through bioinformatic analysis of public sequencing databases. Datasets for RA and CD were downloaded from the GEO database. Overlapping genes were identified using weighted gene co-expression network analysis and differential analysis crossover, and enrichment analysis was conducted for these genes. Protein-protein interaction networks were then constructed using these overlapping genes to identify hub genes. Expression validation and receiver operating characteristic curve validation were performed for these hub genes using different datasets. Additionally, the immune cell correlation, single-cell expression cluster, and the immune cell expression cluster of the core gene were analyzed. Furthermore, upstream shared microRNAs (miRNA) were predicted and a miRNA-gene network was constructed. Finally, drug candidates were analyzed and predicted. These core genes were found to be positively correlated with multiple immune cells that are infiltrated by the disease. Analysis of gene expression clusters revealed that these genes were mostly associated with inflammatory and immune responses. The miRNA-genes network analysis suggested that hsa-miR-31-5p may play an important role in the common mechanism of RA and CD. Finally, tamibarotene, retinoic acid, and benzo[a]pyrene were identified as potential treatment options for patients with both RA and CD. This bioinformatics study has identified ITGB2, LCP2, and PLEK as key diagnostic genes in patients with both RA and CD. The study has further confirmed that inflammation and immune response play a central role in the development of both RA and CD. Interestingly, the study has highlighted hsa-miR-31-5p as a potential key player in the common mechanism of both diseases, representing a new direction in research and a potential therapeutic target. These shared genes, potential mechanisms, and regulatory networks offer new opportunities for further research and may provide hope for future treatment of patients with both RA and CD.

Therapeutic Potential of Plant-Derived Compounds and Plant Extracts in Rheumatoid Arthritis-Comprehensive Review.

Rheumatoid arthritis (RA) is a persistent autoimmune disorder that is characterized by joint inflammation, discomfort, and impairment. Despite the existence of several therapeutic approaches, their effectiveness is often restricted and may be linked to unfavorable side effects. Consequently, there has been growing interest in investigating naturally derived compounds as plausible therapeutic agents for RA disease. The objective of this review is to summarize the existing preclinical and clinical evidence regarding the efficacy of naturally extracted compounds and plant extracts in the treatment of RA, focusing on their anti-inflammatory, anti-oxidative, and immunomodulatory properties. Some of the problems with using natural chemicals are the uneven quality of commercially available preparations and the poor bioavailability of these compounds. Future investigations should focus on improving the formulations, conducting thorough clinical trials, and exploring different techniques to fully utilize the intrinsic potential of naturally derived chemicals in treating RA.

Risk and predictors of fractures in early rheumatoid arthritis – A long term follow up study of an inception cohort

ObjectivesTo examine the risk of fractures in a cohort of patients with newly diagnosed rheumatoid arthritis (RA), compared to the background population, and predictors of fractures detectable early in RA. MethodsAn inception cohort of patients with RA (N = 233; 164 women/69 men, recruited 1995–2005) was evaluated according to a structured program, including repeated clinical assessments and measures of bone mineral density (BMD), from diagnosis to 10 years later. Matched population controls were identified using the national census register. Fractures through 2019 were identified based on ICD codes. Cox regression models were used to assess the risk of fractures in RA patients compared with controls, and for assessment of potential predictors for fractures in the RA population. ResultsRA patients had an increased risk of fractures (fully adjusted hazard ratio (HR) 1.52, 95 % CI 1.13; 2.06). In the RA cohort, high age, low body mass index, and low BMD were significant baseline predictors of future fractures in multivariate analyses, but baseline RA disease characteristics were not. Worse disability (i.e. higher Health Assessment Questionnaire (HAQ) scores) over time was significantly associated with increased risk of fractures (age-sex-adjusted HR 1.33 per SD, 95 % CI 1.09; 1.63) and there was an inverse association between BMD Z-scores over time and fractures. ConclusionPatients with RA had higher risk of fractures than controls. Fracture risk was related to BMD at baseline and over time in patients with RA. In addition, worse disability (measured by HAQ) over time was associated with higher risk of fractures.

Managing rheumatoid arthritis and cardiovascular disease: the role of physical medicine and rehabilitation.

Cardiovascular disease (CVD) presents a significant challenge in rheumatoid arthritis (RA), a systemic chronic ailment affecting the joints and causing systemic inflammation. Effective RA management, including pharmacological and non-pharmacological interventions, is crucial for mitigating cardiac risk. Pharmacotherapy, though effective, can have adverse effects, leading many patients to seek complementary therapies. This study investigates the impact of physical medicine and rehabilitation on RA management in patients with cardiovascular disease, analyzing clinical data to assess the efficacy of integrated therapeutic approaches. This retrospective monocentric study draws upon data from patient records at the Rheumatology Department of the Regional Clinical Hospital of Shymkent, Kazakhstan, spanning 2019 to 2022. Data collected included demographic information, diagnoses, comorbidities, medical anamneses, lab results, and treatment regimens, including physical medicine and rehabilitation interventions. Data were summarized in Microsoft Excel. Statistical analysis was performed using IBM SPSS Statistics (version 26.0). An analysis of 350 patients with RA identified 143 cases of concomitant CVD, with arterial hypertension being the most common cardiovascular disease. The prevalence of CVD among patients with RA was 40%, with a mean age of 58 years, peaking between 50 and 65 years. The majority of patients were women. A strong association was found between increased RA activity and elevated cardiovascular risk. Despite the widespread use of glucocorticosteroid therapy, rehabilitation coverage remained limited. A significant proportion of patients had elevated cholesterol and C-reactive protein levels, while those who engaged in physical therapy and rehabilitation had lower cholesterol levels. Comparative analysis of yoga integration into rehabilitation programs for patients with RA, alongside other modalities (kinesiotherapy, balneotherapy, and pilates), showed that yoga participants exhibited lower pain levels, reduced morning stiffness duration, and lower mean DAS-28 scores compared to those using alternative rehabilitation methods. Integrating physical medicine and rehabilitation, particularly yoga, with pharmacological treatments appears promising for improving patient outcomes. Yoga has demonstrated benefits in reducing pain, morning stiffness, and disease activity. Continued research is essential to refine these approaches and enhance RA and CVD management in patients.

Efferocytosis and Bone Dynamics.

This review summarizes the recently published scientific evidence regarding the role of efferocytosis in bone dynamics and skeletal health. Several types of efferocytes have been identified within the skeleton, with macrophages being the most extensively studied. Efferocytosis is not merely a 'clean-up' process vital for maintaining skeletal homeostasis; it also plays a crucial role in promoting resolution pathways and orchestrating bone dynamics, such as osteoblast-osteoclast coupling during bone remodeling. Impaired efferocytosis has been associated with aging-related bone loss and various skeletal pathologies, including osteoporosis, osteoarthritis, rheumatoid arthritis, and metastatic bone diseases. Accordingly, emerging evidence suggests that targeting efferocytic mechanisms has the potential to alleviate these conditions. While efferocytosis remains underexplored in the skeleton, recent discoveries have shed light on its pivotal role in bone dynamics, with important implications for skeletal health and pathology. However, there are several knowledge gaps and persisting technical limitations that must be addressed to fully unveil the contributions of efferocytosis in bone.

Impact of RA treatment strategies on lipids and vascular inflammation in rheumatoid arthritis: a secondary analysis of the TARGET randomized active comparator trial

BackgroundTreatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this study was to examine lipid and lipoprotein changes associated with two common RA treatment strategies, triple therapy or tumor necrosis factor inhibitor (TNFi), and association with CV risk.MethodsIn this secondary data analysis of the TARGET trial, methotrexate (MTX) inadequate responders with RA were randomized to either add sulfasalazine and hydroxychloroquine (triple therapy), or TNFi for 24-weeks. The primary trial outcome was the change in arterial inflammation measured in the carotid arteries or aorta by FDG-PET/CT at baseline and 24-weeks; this change was described as the target-to-background ratio (TBR) in the most diseased segment (MDS). Routine lipids and advanced lipoproteins were measured at baseline and 24-weeks; subjects on statin therapy at baseline were excluded. Comparisons between baseline and follow-up lipid measurements were performed within and across treatment arms, as well as change in lipids and change in MDS-TBR.ResultsWe studied 122 participants, 61 in each treatment arm, with median age 57 years, 76% female, and 1.5 year median RA disease duration. When comparing treatment arms, triple therapy had on average a larger reduction in triglycerides (15.9 mg/dL, p = 0.01), total cholesterol to HDL-C ratio (0.29, p-value = 0.01), and LDL particle number (111.2, p = 0.02) compared to TNFi. TNFi had on average a larger increase in HDL particle number (1.6umol/L, p = 0.006). We observed no correlation between change in lipid measurements and change in MDS-TBR within and across treatment arms.ConclusionsBoth treatment strategies were associated with improved lipid profiles via changes in different lipids and lipoproteins. These effects had no correlation with change in CV risk as measured by vascular inflammation by FDG-PET/CT.Trial registrationClinicalTrials.gov ID NCT02374021.

Detection of Interstitial Lung Disease in Rheumatoid Arthritis by Thoracic Ultrasound: A Diagnostic Test Accuracy Study.

To determine the diagnostic accuracy of thoracic ultrasound (TUS) for detecting interstitial lung disease (ILD) in rheumatoid arthritis (RA) with respiratory symptoms. Individuals with RA visiting rheumatologic outpatient clinics in the Region of Southern Denmark were systematically screened for dyspnea, cough, recurrent pneumonia, prior severe pneumonia, or a chest x-ray indicating interstitial abnormalities. Eighty participants with a positive screening were consecutively included. Individuals were not eligible if they had a chest high-resolution computed tomography (HRCT) less than 12 months ago or were already diagnosed with ILD. A blinded TUS expert evaluated TUS, and TUS was registered as positive for ILD if at least 10 B-lines or bilateral thickened and fragmented pleura were present. The primary outcomes were TUS's sensitivity, specificity, and positive predictive value and negative predictive value. An ILD-specialized thoracic radiologist assessed HRCT, followed by a multidisciplinary team discussion, which was the reference standard. The accepted window of HRCT was less than 30 days after TUS was performed. A total of 77 participants received HRCT less than 30 days after TUS, and 23 (30%) were diagnosed with ILD. TUS had a sensitivity of 82.6% (95% confidence interval [CI] 61.2%-95.0%) and a specificity of 51.9% (95% CI 37.8%-65.7%), corresponding to a positive predictive value of 42.2% (95% CI 27.7%-57.8%) and a negative predictive value of 87.5% (95% CI 71.0%-96.5%). To our knowledge, this prospective study is the first to use respiratory symptoms in RA as inclusion criteria. Systematic screening for respiratory symptoms combined with TUS can reduce the diagnostic delay of ILD in RA.

Early predictive factors in routine clinical practice for rituximab therapy response in patients with rheumatoid arthritis.

Identifying early predictive factors of how rheumatoid arthritis (RA) patients respond to rituximab (RTX) treatment is crucial for both individual treatment outcome and the improvement of clinical practice overall. This study aimed to identify early predictive factors available in standard clinical practice for predicting RTX treatment outcomes in RA patients. Data on seventy patients diagnosed with RA treated with RTX (two 1,000 mg doses 2 weeks apart or two 500 mg doses 2 weeks apart) were retrospectively collected. Baseline information collected at the initiation of RTX treatment included patient characteristics such as age, sex, disease duration, disease activity, Health Assessment Questionnaire score, erythrocyte sedimentation rate, C-reactive protein, and serological status regarding rheumatoid factor (RF) and anti-cyclic citrullinated protein antibodies (ACPA). Clinical responses were analyzed 6 months after RTX initiation using the European Alliance of Associations for Rheumatology criteria. Potential predictors associated with positive RTX response at 6 months were identified using a multivariate ordinal logistic regression model. The analysis showed that persistently active RA disease, Disease Activity Score with 28-joint count (DAS28) values at the treatment onset and after 3 months, along with erythrocyte sedimentation rate at treatment initiation, were negatively correlated with the response to RTX therapy (p < 0.05). All these correlations were statistically significant at the 99% confidence interval. The correlation and logistic regression analyses indicate that there are no significant association between RF and ACPA concerning therapy response, despite a higher number of RTX responders in the seropositive groups. Additionally, the study emphasizes the prognostic significance of the DAS28 value at treatment initiation in predicting therapy response at 6 months. The optimal model for predicting RTX response at 6 months involves the interaction of all clinical factors examined in this study, as revealed by the analysis of multiple variables.

Role of Cathepsin G in Rheumatoid Arthritis Diagnosis and Disease Activity Evaluation

Role of Cathepsin G in Rheumatoid Arthritis Diagnosis and Disease Activity Evaluation

Secondary fibromyalgia in children with immune-inflammatory rheumatic diseases

Patients with immune-inflammatory rheumatic diseases (IIRDs) often present with non-inflammatory musculoskeletal pain associated with nociceptive dysfunction, central sensitization, and secondary fibromyalgia (FM). In recent years, an increasing number of publications have appeared dealing with FM in rheumatoid arthritis and systemic connective tissue diseases in adult patients, while this problem is little discussed in pediatric rheumatology, partly due to the differences between the existing diagnostic criteria in children and adults, which complicate the diagnosis of juvenile secondary FM. The consequence of this is often the unfounded prescription or switching of synthetic disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs in patients who do not require intensified antirheumatic therapy, but rather psychotherapy and psychopharmacotherapy, as well as the wider use of physical and rehabilitation medicine methods. In a brief narrative review, we tried to trace the investigation of FM in a rheumatological clinic, including children with IIRD, from a historical perspective, to summarize current literature data on this problem and to point out possible solutions.

Time-domain diffuse optical imaging technique for monitoring rheumatoid arthritis disease activity: experimental validation in tissue-mimicking finger phantoms

Objective. Effective treatment within 3–5 months of disease onset significantly improves rheumatoid arthritis (RA) prognosis. Nevertheless, 30% of RA patients fail their first treatment, and it takes 3–6 months to identify failure with current monitoring techniques. Time-domain diffuse optical imaging (TD-DOI) may be more sensitive to RA disease activity and could be used to detect treatment failure. In this report, we present the development of a TD-DOI hand imaging system and validate its ability to measure simulated changes in RA disease activity using tissue-mimicking finger phantoms. Approach. A TD-DOI system was built, based on a single-pixel camera architecture, and used to image solid phantoms which mimicked a proximal interphalangeal finger joint. For reference, in silico images of virtual models of the solid phantoms were also generated using Monte Carlo simulations. Spatiotemporal Fourier components were extracted from both simulated and experimental images, and their ability to distinguish between phantoms representing different RA disease activity was quantified. Main results. Many spatiotemporal Fourier components extracted from TD-DOI images could clearly distinguish between phantoms representing different states of RA disease activity. Significance. A TD-DOI system was built and validated using finger-mimicking solid phantoms. The findings suggest that the system could be used to monitor RA disease activity. This single-pixel TD-DOI system could be used to acquire longitudinal measures of RA disease activity to detect early treatment failure.

Time-domain diffuse optical imaging technique for monitoring rheumatoid arthritis disease activity: theoretical development and in silico validation

Objective. Effective early treatment—within 3–5 months of disease onset—significantly improves rheumatoid arthritis (RA) prognosis. Nevertheless, 1 in 3 patients experiences treatment failure which takes 3–6 months to detect with current monitoring techniques. The aim of this work is to develop a method for extracting quantitative features from data obtained with time-domain diffuse optical imaging (TD-DOI), and demonstrate their sensitivity to RA disease activity. Approach. 80 virtual phantoms of the proximal interphalangeal joint—obtained from a realistic tissue distribution derived from magnetic resonance imaging—were created to simulate RA-induced alterations in 5 physiological parameters. TD-DOI images were generated using Monte Carlo simulations, and Poisson noise was added to each image. Subsequently, each image was convolved with an instrument response function (IRF) to mimic experimental measurements. Various spatiotemporal features were extracted from the images (i.e. statistical moments, temporal Fourier components), corrected for IRF effects, and correlated with the disease index (DI) of each phantom. Main results. Spatiotemporal Fourier components of TD-DOI images were highly correlated with DI despite the confounding effects of noise and the IRF. Moreover, lower temporal frequency components ( ⩽ 0.4 GHz) demonstrated greater sensitivity to small changes in disease activity than previously published spatial features extracted from the same images. Significance. Spatiotemporal components of TD-DOI images may be more sensitive to small changes in RA disease activity than previously reported DOI features. TD-DOI may enable earlier detection of RA treatment failure, which would reduce the time needed to identify treatment failure and improve patient prognosis.

Correlation of DAS 28 Score and Treatment Compliance with Depression and Anxiety in Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by synovial inflammation, joint destruction, and significant disability. Psychological factors, particularly depression and anxiety, are prevalent among RA patients and can impact disease management and treatment adherence. Understanding the relationship between disease activity, treatment compliance, and mental health is essential for comprehensive RA management. Objective: To investigate the correlation between Disease Activity Score 28 (DAS28) and treatment compliance with levels of depression and anxiety in patients with rheumatoid arthritis. Methods: This cross-sectional study was conducted at the Department of Rheumatology and Immunology, Sheikh Zayed Hospital, Lahore, over six months. A total of 130 RA patients were enrolled using non-probability convenience sampling. Inclusion criteria were adults aged 18 years and above, diagnosed with RA based on ACR/EULAR criteria, and compliant with medication for at least three months prior to the study. Exclusion criteria included other autoimmune diseases, significant concurrent medical conditions, history of substance abuse, and recent initiation of biologic treatments. Data collection involved demographic details, RA onset and duration, and assessments of depression and anxiety using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales, respectively. RA disease activity was measured using DAS28, and systemic inflammation markers (ESR and CRP) were recorded. Data analysis was performed using SPSS version 25.0, employing descriptive statistics, correlation analysis, and regression analysis to determine the relationships between variables. Results: The study included 59 males (45.4%) and 71 females (54.6%), with a mean age of 49.69 years (SD = 18.82). The mean duration of RA diagnosis was 14.07 years (SD = 8.69). Higher PHQ-9 scores were associated with lower treatment adherence (B = -1.264, p &lt; 0.001), and higher GAD-7 scores also negatively impacted adherence (B = 0.870, p &lt; 0.01). The regression model explained 40.3% of the variance in treatment adherence (R² = 0.403, F(7, 122) = 11.779, p &lt; 0.001). Weak negative correlations were observed between DAS28 ESR and treatment adherence (r = -0.150), indicating that higher disease activity slightly reduced adherence. Conclusion: The study highlighted the significant role of mental health in the management of RA. Depression and anxiety were found to be major barriers to treatment adherence, underscoring the need for integrating psychological care into RA management. Addressing mental health issues could enhance treatment adherence and improve overall disease outcomes. Keywords: Rheumatoid Arthritis, DAS28, Treatment Adherence, Depression, Anxiety, Psychological Factors, Systemic Inflammation, PHQ-9, GAD-7, Chronic Disease Management, SPSS 25.0, Cross-Sectional Study, ACR/EULAR Criteria

Prevalence and Characteristics of Adults with Difficult-to-Treat Rheumatoid Arthritis in a Large Patient Registry.

An estimated 5-20% of patients with rheumatoid arthritis (RA) fail multiple treatments and are considered "difficult-to-treat" (D2T), posing a substantial clinical challenge for rheumatologists. A European Alliance of Associations for Rheumatology (EULAR) task force proposed a definition of D2T-RA in 2021. We applied EULAR's D2T definition in a cohort of patients with established RA to assess prevalence and we compared clinical characteristics of participants with D2T-RA with matched comparisons. Data from the longitudinal Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry was used. Participants were classified as D2T if they met EULAR's definition. A comparison group of non-D2T RA patients were matched 2:1 to every D2T patient, and differences in characteristics were evaluated in descriptive analyses. Prevalence rates of D2T were estimated using Poisson regression. We estimated the prevalence of D2T-RA to be 14.4 (95% CI: 12.8-16.3 per 100 persons) among 1,581 participants with RA, and 22.3 (95% CI: 19.9-25.0 per 100 persons) among 1,021 who were biologic/targeted synthetic DMARD experienced. We observed several differences in demographics, comorbidities, and RA disease activity between D2T-RA and non-D2T RA comparisons. Varying EULAR sub-criteria among all participants in BRASS resulted in a range of D2T-RA prevalence rates, from 0.6-17.5 per 100 persons. EULAR's proposed definition of D2T-RA identifies patients with RA who have not achieved treatment targets. Future research should explore heterogeneity in these patients and evaluate outcomes to inform the design of future studies aimed at developing more effective RA management protocols.

Antifibrotics in the Management of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Prospective Real-World Experience From an Interstitial Lung Disease Clinic in India.

Interstitial lung disease (ILD) in rheumatoid arthritis (RA) is a serious complication with varied prevalence ranging from 4% to as high as 68%, with varied presentation. Immunosuppressants and antifibrotics are used in the management of RA ILD. The clinicodemographic profile and presentation in our country need to be further explored. We assessed the efficacy and safety profile of antifibrotic drugs in combination with immunosuppressants among RA ILD patients. A prospective observational study was conducted in the Interstitial Lung Disease (ILD) Clinic in the Department of Pulmonary Medicine, All India Institute of Medical Sciences Raipur, India, between January 2022 to January 2023. RA patients with dyspnea and chronic cough were referred to us for evaluation of ILD. Patients underwent clinical examination, complete lung function study including spirometry, single breath diffusion capacity for carbon monoxide (DLCO), six-minute walk test, and high-resolution computed tomography of the thorax. Quality of life was assessed using the King's Brief Interstitial Lung Disease (KBILD) questionnaire. Two hundred eighteen RA patients were evaluated and out of these, 43 (20.8%) had features of ILD on high-resolution computed tomogram (HRCT) thorax. Twenty-six (2.18%) met the inclusion criteria for starting antifibrotics. The mean ± SD. age of the patients was 52.96 ± 14.04 and the majority (77%) were females. Fourteen (53.38%) patients had usual interstitial pneumonia (UIP)/probable UIP pattern and 12 (46.22%) had nonspecific interstitial pneumonia (NSIP) patterns on HRCT. Out of 26 patients, 24 (92.3%) were started on antifibrotics. Fourteen (53.8%) patients were on nintedanib and 10 (38.4%) were on pirfenidone. The mean ± SD forced vital capacity (FVC)% predictedwas 62.5 ± 20.04.The mean ± SD. The DLCO percentage predicted was 54.4 ± 22.8. Twenty-two (84.6%) patients did not experience any side effects. The mean ± SD. KBILD score was 59.9 ± 11.17 and was similar in both sexes. In our study, the prevalence of RA ILD was nearly 20.8% and more common in females. Twenty-four (2%) patients were included for antifibrotic treatment. There was an improvement in lung function at the end of six months, but the change was not significant. All patients tolerated antifibrotics well without any serious adverse events.

CD40 ligand antagonist dazodalibep in Sjögren’s disease: a randomized, double-blinded, placebo-controlled, phase 2 trial

Sjögren’s disease (SjD) is a chronic, systemic autoimmune disease with no approved disease-modifying therapies. Dazodalibep (DAZ), a novel nonantibody fusion protein, is a CD40 ligand antagonist that blocks costimulatory signals between T and B cells and antigen-presenting cells, and therefore may suppress the wide spectrum of cellular and humoral responses that drive autoimmunity in SjD. This study was a phase 2, randomized, double-blinded, placebo (PBO)-controlled trial of DAZ with a crossover stage in two distinct populations of participants with SjD. Population 1 had moderate-to-severe systemic disease activity and population 2 had an unacceptable symptom burden and limited systemic organ involvement. All participants had a diagnosis of SjD, with 21.6% and 10.1% having an associated connective tissue disease (rheumatoid arthritis or systemic lupus erythematosus) in populations 1 and 2, respectively. The remaining participants would be considered as having primary Sjögren’s syndrome. The primary endpoint for population 1 (n = 74) was the change from baseline in the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index at day 169. The primary endpoint for population 2 (n = 109) was the change from baseline in the European League Against Rheumatism Sjögren’s Syndrome Patient Reported Index at day 169. The primary endpoints (least squares mean ± standard error) were achieved with statistical significance for both population 1 (DAZ, −6.3 ± 0.6; PBO, −4.1 ± 0.6; P = 0.0167) and population 2 (DAZ, −1.8 ± 0.2; PBO, −0.5 ± 0.2; P = 0.0002). DAZ was generally safe and well tolerated. Among the most frequently reported adverse events were COVID-19, diarrhea, headache, nasopharyngitis, upper respiratory tract infection, arthralgia, constipation and urinary tract infection. In summary, DAZ appears to be a potential new therapy for SjD and its efficacy implies an important role for the CD40/CD40 ligand pathway in its pathogenesis. ClinicalTrials.gov identifier: NCT04129164.