Rheumatoid arthritis (RA) is an inflammatory immune-triggered disease that causes synovitis, cartilage degradation, and joint injury. In nanotechnology, conventional liposomes were extensively investigated for RA. However, they frequently undergo rapid clearance, reducing circulation time and therapeutic efficacy. Additionally, their stability in the bloodstream is often compromised, resulting in premature drug release. The current review explores the potential of targeted liposomal-based nanosystems in the treatment of RA. It highlights the pathophysiology of RA, explores selective targeting sites, and elucidates diverse mechanisms of novel liposomal types and their applications. Furthermore, the targeting strategies of pH-sensitive, flexible, surface-modified, PEGylated, acoustic, ROS-mediated, and biofunctionalized liposomes are addressed. Targeted nanoliposomes showed potential in precisely delivering drugs to CD44, SR-A, FR-β, FLS, and toll-like receptors through the high affinity of ligands. In vitro studies interpreted stable release profiles and improved stability. Ex vivo studies on skin demonstrated that ultradeformable and glycerol-conjugated liposomes enhanced drug penetrability. In vivo experiments for liposomal types in the arthritis rat model depicted remarkable efficacy in reducing joint swelling, pro-inflammatory cytokines, and synovial hyperplasia. In conclusion, these targeted liposomes represented a significant leap forward in drug delivery, offering effective therapeutic options for RA. In the future, integrating these advanced liposomes with artificial intelligence, immunotherapy, and precision medicine holds great promise.

Rheumatoid Arthritis (RA) is a persistent autoimmune disease affecting approximately 0.5-1 percent of the world population. RA prevalence is higher in woman aged between 35 and 50 years than in age matched men, though this difference is less evident among elderly patients. The profound immune specific effects of disrupted JAK 3 (Janus kinase 3) signaling highlight the possibility of therapeutic targeting of JAK3 as a highly specific mode of immune system suppression. To address the above problem which is unendurable to patients and in the hope to cater some respite to such suffering we have targeted JAK 3 protein and JAK/STAT signaling pathway with compounds downloaded from FDA database, and performed screening of all available compounds docked against JAK3 protein. The difference between the target protein and other proteins of the same family was studied using cross docking and the compounds having higher binding affinity to JAK3 protein also showed more selectivity towards the particular protein. Density functional theory and molecular dynamics simulation study was done to study the compounds at their atomic level to know more about their drug likeliness. At the end of the study and based on our analysis we have come up with three FDA approved drugs that can be proposed as a treatment option for Rheumatoid Arthritis.

This systematic review aimed to synthesize the content, structure, and delivery characteristics of effective yoga interventions in addition to standard medical treatment for rheumatoid arthritis (RA).

The Joanna Briggs Institute guidelines were followed. Seventeen databases were searched for randomized controlled trials (RCTs) assessing yoga's effectiveness in treating RA outcomes (disease activity score, pain, and function). Meta-analyses and narrative synthesis were conducted.

Nine articles representing five RCTs were included and had low methodological quality scores. Yoga interventions, in addition to standard medical treatment, improved disease activity scores (standardized mean difference [SMD] -0.46, 95% confidence interval [CI] -0.73 to -0.18) and function (SMD -0.42, 95% CI -0.78 to -0.07) but did not effectively reduce pain (SMD -1.06, 95% CI -2.62 to 0.50) compared to standard medical treatment alone. All five RCTs found yoga's beneficial effects on one or more outcomes. All yoga interventions included center-based (supervised, group) sessions, and two included additional home-based (unsupervised, individual) sessions. All interventions incorporated 20 yogic poses (6 standing, 5 supine, 5 prone, and 4 seated), 7 breathing practices, and 4 meditation and relaxation practices. Two interventions offered RA-specific yogic pose modifications. Center-based sessions were delivered at least once weekly for 8 weeks' median duration and around 68 minutes per session. Home-based yoga was recommended thrice weekly for a 10-week mean duration and 40 minutes per session.

Yoga might be useful in addition to standard medical treatment for RA. Given previous studies' methodological limitations, a high-quality RCT should be conducted based on our synthesized key features of effective yoga interventions.

Over the past few decades, there has been a surge in global study on the relationship between gut microbiota and human health. Numerous human illnesses have been linked to dysbiosis. Gram-positive firmicutes and Gram-negative bacteroidetes are the two leading bacterial phyla that make up 90% of the gut microbiome. Many symbionts in the gut environment establish intricate relationships with host defense to stop both local and non-native dangerous bacteria from colonizing and invading. Dysbiosis alters the paracellular route and damages the epithelium, enabling them to penetrate the epithelium and come into contact with the immune cells. Impaired intestinal barrier function, immune regulation mediated by metabolites derived from the gut microbiota, posttranslational modification of host proteins such as increased citrullination, regulation of the gut microbiota's effect on immune cells, intestinal epithelial cell autophagy, interaction between the microbiome and human leukocyte antigen alleles, and interaction with microRNAs are some of the mechanisms involved in rheumatoid arthritis (RA). The gut microbiota, Prevotella copri, and Collinsella spp. were shown to be higher in the early/preclinical phases of RA, while Bacteroidetes, Bifidobacteria, and Eubacterium rectale were found to be lower. Probiotic-based early dietary intervention may reduce inflammation and slow the rate of joint deterioration, and such intervention can also aid in the restoration of gut microbiota equilibrium. This review article describes the gut microbial dysbiosis and role of probiotics in RA.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent inflammation, joint swelling, pain, and progressive joint destruction. Methotrexate (MTX) is the standard first-line treatment for RA, but its clinical application is hindered by poor water solubility and non-specific delivery. In this work, a multifunctional drug-delivery nanoplatform that targets both macrophages and tumor necrosis factor α (TNFα) is developed to enhance the therapeutic efficacy of MTX in RA. The nanoplatform consists of folic acid (FA, for macrophage targeting) and a TNFα-specific Aptamer (TNFα-Apt), facilitating a dual-targeting strategy that significantly improves the accumulation of MTX at the sites of RA lesions (≈3.5-fold). Moreover, the manganese dioxide (MnO₂) and polydopamine (PDA) coatings on the nanoplatform effectively scavenge reactive oxygen species (ROS), generate oxygen, and promote the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2 macrophages. This shift in macrophage polarization restores the expression of key inflammatory cytokines, improving the local inflammatory microenvironment. Ultimately, the nanoplatform significantly ameliorates the inflammation and joint damage in a collagen-induced arthritis (CIA) model, suggesting that this multi-target combination therapy holds considerable potential for the treatment of RA in vivo.

Rheumatoid arthritis (RA) is the most common chronic autoimmune arthropathy. If the disease is aggressive or left untreated, it becomes debilitating, affects a patient's functionality, and reduces the quality of life. Disease-modifying anti-rheumatic drugs (DMARDs), both conventional, targeted, and biological, decrease the disease progression and are key components of effective treatment. Recently, there has been a continuous debate about the possible carcinogenicity of various DMARDs. Lung cancer is a leading cause of cancer death worldwide. The available data show an increased risk of lung cancer in RA patients, but the link between RA and cancer is poorly understood. Carcinogenesis in RA seems to be related to chronic inflammation, familial predisposition, risky behaviors (e.g., smoking), and iatrogenic complications. The main mechanisms of carcinogenic processes in patients with RA are the up-regulation of interleukin-6 (IL-6) cytokine production and wingless/integrated WNT signaling. Up-regulation of WNT5A is an important mechanism that links chronic inflammatory pathways to carcinogenesis observed in RA patients. Concomitant up-regulation of transcription factor STAT3 promotes cell proliferation and inhibits apoptosis. Conversely, suppressed inflammatory processes by DMARDs may decrease the risk of lung cancer. In this article, we discuss the molecular mechanisms of lung cancer in RA and the role of DMARDs in this process. Furthermore, we analyze the molecular effect of drug-induced cancer, which affects transcription factors and thus modulates carcinogenic processes. Finally, we describe risk factors and present preventive and therapeutic approaches.

Patients with rheumatoid arthritis (RA) or rheumatoid arthritis-associated interstitial lung disease (RA-ILD) are commonly positive for antineutrophil cytoplasmic antibodies (ANCAs). The causal relationship between RA-ILD and ANCAs and the role of ANCAs in RA-ILD remain unclear. The purpose of this study was to estimate the prevalence of ANCAs in RA-ILD patients and to investigate the clinical characteristics and outcomes of ANCA-positive RA-ILD patients.

Data from 104 RA-ILD patients with available ANCA results at our centre from March 2010 to June 2024 were retrospectively reviewed. ANCA positivity was defined as the presence of any one or a combination of perinuclear ANCAs (P-ANCAs), cytoplasmic ANCAs (C-ANCAs), anti-MPO or anti-PR-3. Clinical data from each patient's initial diagnosis were collected and analysed. The clinical characteristics and survival of the ANCA-positive and ANCA-negative RA-ILD groups were compared.

Thirty-three out of the 104 (31.7%) RA-ILD patients were positive for ANCAs. The percentages of patients positive for P-ANCAs, MPO-ANCAs, C-ANCAs, and PR3-ANCAs were 27.9% (29/104), 1.9% (2/104), 1.9% (2/104), and 1.0% (1/104), respectively. Compared with ANCA-negative RA-ILD patients, a greater proportion of ANCA-positive RA-ILD patients had respiratory symptoms, serum autoantibody (ANA) positivity, poorer baseline pulmonary function, and acute exacerbations of ILD (AE-ILD). The usual interstitial pneumonia (UIP) pattern (57.6%) was the most common chest high-resolution computed tomography (HRCT) pattern observed. ANCA-positive RA-ILD patients were more likely to have traction bronchiectasis (P = 0.029), honeycombing (P < 0.001), and oddly shaped cysts (P = 0.020) than were ANCA-negative RA-ILD patients. Univariate Cox analysis revealed that P-ANCA positivity [hazard ratio (HR) = 2.24, 95% confidence interval (CI): 0.91-5.52; P = 0.046] is a trend of survival association in RA-ILD, but this was not confirmed in the multivariate analysis. Multivariate Cox analyses revealed that a history of smoking (HR = 2.53, 95% CI: 1.10-5.83; P = 0.030) and a systolic pulmonary artery pressure (SPAP) ≥ 37 mmHg (HR = 10.24, 95% CI: 4.07-25.77; P < 0.001) were independently associated with shorter survival in RA-ILD patients.

The prevalence of ANCAs in patients with RA-ILD is high, and ANCA testing could be considered in the diagnostic workup for RA-ILD. Oddly shaped cysts with or without a UIP pattern may be a characteristic chest imaging manifestation of ANCA-positive RA-ILD. More attention should be given to RA-ILD patients who have elevated SPAP.

This systematic review aims to identify, summarize, and evaluate the methodological quality of existing clinical prediction models (CPMs) that predict adverse events (AEs) associated with medications prescribed for rheumatic and musculoskeletal diseases (RMDs).

We searched PubMed, Embase, and Medline databases up to March 2024. Studies were included if they developed multivariable CPM predicting AEs in adult patients using RMD medications. Data extraction and quality assessment were conducted using the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) and Prediction model Risk Of Bias Assessment Tool (PROBAST) checklists to ensure consistent reporting and assess the risk of bias (ROB).

Of 2406 studies identified, 1734 titles/abstracts were screened, and 38 were reviewed in full. Twelve studies reporting 17 CPMs met eligibility criteria. Most CPMs (76.4 %) focused on rheumatoid arthritis and disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate (69.2 %) and biologic drugs (15.3 %). Cox proportional hazards or logistic regression models were commonly used. Twelve models (70.5 %) had high overall ROB due to inappropriate variable selection methods and sample size.

This is the first systematic review summarising CPMs for AEs associated with RMD medications. It highlights that existing CPMs are affected by methodological pitfalls, including inappropriate variable selection and lack of clear sample size justification. Future models could consider a broader range of RMDs and medications. Emerging methods such as machine learning with the ability to model complex interactions, and multi-outcome CPMs to predict several AEs to one class of drug may improve predictions.

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints. RA usually results in synovial hyperplasia, expansion of "pannus" and destruction of cartilage. The etiology and pathogenesis of RA are not fully understood, but immunity has been shown to play an important role in the development of autoimmune diseases such as RA. In addition, endogenous retroelements, the remnants of ancient retroviruses in the human genome, are involved in cancer and/or immune disorders. As evidenced by increasing evidences that the aberrant expression of retroelements induces innate immunity, despite the fact that the expression of most retroelements has been epigenetically suppressed over a long period of evolution. With the continuous development of disease-modifying anti-rheumatic drugs (DMARDs), RA disease activity has been alleviated and improved. Unfortunately, some patients have a limited response to DMARDs, and the drugs also have the disadvantages of some side effects and high economic costs. This review summarizes the pathogenic mechanisms of RA and endogenous retroelements in autoimmunity, and concludes with a summary of treatments for RA, along with new therapeutic recommendations.

Rheumatoid arthritis (RA) is a systemic autoimmune disease closely associated with synovial tissue proliferation, pannus formation in small joints such as the hands, wrists, and feet, cartilage destruction, and systemic complications such as pulmonary, cardiovascular, neurological, and skeletal muscle lesions, glucocorticoid-induced osteoporosis and infections. The importance of confirming the diagnosis and determining local activity is given to the study of synovial fluid. A deep understanding of the pathological process in the joint in RA, characterized by changes in autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies, has now been achieved, although much remains to be explored. This article provides an updated overview of the pathogenesis of RA, revealing even more therapeutic targets for the intra-articular pathological process.

The process of apoptosis plays a crucial role in tissue homeostasis, immune system regulation, and organ formation. Apoptotic vesicles (ApoEVs) are involved in efferocytosis, the process by which phagocytes ingest dead cells. ApoEVs also have potential therapeutic applications in cancer treatment, ischemic diseases, and their anti-inflammatory properties make them incredibly versatile for medical applications. These vesicles can induce apoptosis in cancer cells, provide tumor antigens for cancer vaccines, and even serve as effective drug delivery systems. Moreover, they can target hypoxic cells, inhibit inflammatory cell death pathways, and promote tissue regeneration. Also, their potential in addressing inflammatory disorders such as gastrointestinal ailments, osteoarthritis, and diabetes is promising. Additionally, ApoEVs can polarize anti-inflammatory immune cells and suppress inflammatory immune responses which make them a viable option for addressing the unmet need for novel anti-inflammatory medications. Despite a wealth of reviews examining the applications of ApoEVs, very few have thoroughly investigated the mechanisms underlying their anti-inflammatory effects. This distinctive approach positions the current review as timely and immensely relevant, illuminating the intriguing ways these entities function beyond their established advantages.

In the present manuscript, we evaluated the analgesic, anti-inflammatory and anti-arthritic effects of bakuchiol derivative, O-acetyl bakuchiol (BAc), at 5, 10 and 20 mg/kg p.o. doses in adult Sprague-Dawley rats. BAc at 20 mg/kg p.o. exhibited maximum analgesic (47.4%), anti-inflammatory (66.50%) and anti-arthritic effects. Among the different parameters studied for anti-arthritic effects, BAc at 20 mg/kg increased the body weight (2.89%), decreased the paw thickness (72.46%) and decreased the paw inflammation (48.59%) in Freund's complete adjuvant (FCA)-induced arthritic rats. In haematological/serum and biochemical parameters, BAc at 20 mg/kg brought the altered levels of erythrocyte sedimentation rate (ESR), Hb, HCT, RBC, TLC and platelet count, HDL, cholesterol, triglycerides, C-reactive protein (CRP) and rheumatoid arthritis (RA) factor near to the normal. Moreover, the spleen weight was also reduced in BAc-treated rats at 20 mg/kg. Histopathological analysis further revealed that a reduction in paw inflammation was observed in paw ankle joints, and no inflammation was observed in brain, liver, lungs and kidney in BAc-treated rats at 20 mg/kg p.o. Molecular docking studies further revealed that BAc has better binding affinity for tumour necrosis factor alpha (TNF-α) (Protein Data Bank [PDB] ID: 7JRA) -7.19 kcal/mol comparable to standard methotrexate with binding affinity -9.56 kcal/mol. Therefore, the present investigation provided the basis for the development of BAc as a potential candidate for the treatment of arthritis.

Rheumatoid Arthritis (RA) is a globally prevalent chronic disease that presents significant challenges in terms of curability. The etiology and onset of RA are not readily identifiable, and as the disease advances, it is characterized by joint pain, swelling, and damage, potentially resulting in paralysis. The adverse effects associated with existing pharmacological treatments are considerable, and prolonged use may pose significant health risks. Melittin, a naturally occurring anti-rheumatic compound, has garnered increasing scholarly interest. Melittin has demonstrated the potential to significantly augment the therapeutic efficacy of certain first-line pharmacological agents while minimizing adverse effects, thereby rendering it appropriate for prolonged use. Melittin's mechanisms of action in treating RA encompass anti-inflammatory effects, immunomodulatory effects, analgesic effects, reduction of cardiovascular disease risk, and organ-protective effects, targeting multiple aspects of RA to alleviate symptoms. Clarifying the biological functions of melittin and its mechanisms in treating RA can provide valuable insights for the application of melittin in the intervention of RA disease progression. However, melittin can cause allergic reactions, hemolysis, and cytotoxicity in the body, which limit its application. Research has shown that strategies including melittin-based nanomodification, immunoconjugation, and structural regulation can improve the specificity of melittin, decrease cytotoxicity, and mitigate the lytic effects on non-target cells of bee venom. These findings suggest that melittin holds promise for clinical applications. This article provides a comprehensive overview of the disease progression associated with RA, examines the biological properties of Mmelittin, and discusses therapeutic strategies for utilizing melittin in the treatment of rheumatoid arthritis. The objective is to mitigate the toxic side effects of melittin while enhancing its targeted anti-inflammatory effects, thereby investigating its potential clinical value in the prevention of rheumatoid arthritis.

Rheumatoid Arthritis (RA) is a chronic, symmetrical inflammatory autoimmune disorder characterized by painful, swollen synovitis and joint erosions, which can cause damage to bone and cartilage and be associated with progressive disability. Despite expanded treatment options, some patients still experience inadequate response or intolerable adverse effects. Consequently, the treatment options for RA remain quite limited. The enzyme AKT1 is crucial in designing drugs for various human diseases, supporting cellular functions like proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. Therefore, AKT serine/threonine kinase 1 is considered crucial for targeting therapeutic strategies aimed at mitigating RA mechanisms. In this context, directing efforts toward AKT1 represents an innovative approach to developing new anti-arthritis medications. The primary objective of this research is to prioritize AKT1 inhibitors using computational techniques such as molecular modeling and dynamics simulation (MDS) and shape-based virtual screening (SBVS). A combined SBVS approach was employed to predict potent inhibitors against AKT1 by screening a pool of compounds sourced from the ChemDiv and IMPPAT databases. From the SBVS results, only the top three compounds, ChemDiv_7266, ChemDiv_2796, and ChemDiv_9468, were subjected to stability analysis based on their high binding affinity and favorable ADME/Tox properties. The SBVS findings have revealed that critical residues, including Glu17, Gly37, Glu85, and Arg273, significantly contribute to the successful binding of the highest-ranked lead compounds at the active site of AKT1. This insight helps to understand the specific binding mechanism of these leads in inhibiting RA, facilitating the rational design of more effective therapeutic agents.

Rheumatoid arthritis (RA) is one of the most prevalent autoimmune, chronic, inflammatory disease characterized by joint inflammation, synovial swelling, loss of articular structures, swelling, and pain. RA is a major cause of discomfort and disability worldwide, associated with infectious agents, genetic determinants, epigenetic factors, advancing age, obesity, and smoking. Although conventional therapies for RA alleviate the symptoms, but their long-term use is associated with significant side effects. This necessitates the urge to discover complementary and alternative medicine from natural products with minimum side effects.

In this review, natural product's potential mechanism of action against RA has been documented in the setting of in-vivo, in-vitro and pre-clinical trials, which provides new treatment opportunities for RA patients. The bioefficacy of these natural product's bioactive compounds must be further studied to discover novel natural medications for RA with high selectivity, improved effectiveness, and economic replacement with minimum side effects.

The current review article was designed systematically in chronological order. Plants and their phytochemicals are discussed in an order concerning their mode of action. All the mechanisms of action are depicted in diagrams which are thoroughly generated by the Chembiodraw to maintain the integrity of the work. Moreover, by incorporating the recent data with simple language which is not incorporated previously, we tried to provide a molecular insight to the readers of every level and ethnicity. Moreover, Google Scholar, PubMed, ResearchGate, and Science Direct databases were used to collect the data.

Traditionally, various plant extracts and bioactive compounds are effectively used against RA, but their comprehensive pharmacological mechanistic actions are rarely discussed. Therefore, the objective of this study is to systematically review the efficacy and proposed mechanisms of action of different plants and their bioactive compounds including Tripterygium wilfordii Hook F (celastrol and triptolide), Nigella sativa (thymoquinone), Zingiber officinale (shogaols, zingerone), Boswellia serrata (boswellic acids), Curcuma longa (curcumin), and Syzygium aromaticum (eugenol) against rheumatoid arthritis.

These plants have strong anti-inflammatory, anti-oxidant, and anti-arthritic effects in different study designs of rheumatoid arthritis with negligible side effects. Phytomedicines could revolutionize pharmacology as they act through alternative pathways hence seeming biocompatible.

Rheumatoid arthritis is a chronic autoimmune disease characterised by inflammation and progressive joint damage, necessitating innovative therapeutic strategies. Conventional rheumatoid arthritis treatments, including disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, glucocorticoids, and biologics, often administered through systemic or intra-articular ways. These drugs often have low accumulation and/or retention in articular cartilage, causing dose-limiting toxicities and reduced efficacy. This review summarises recent advances in injectable drug delivery systems, specifically hydrogels, microspheres, and nanoparticles, highlighting their potential to enhance rheumatoid arthritis therapy. The outstanding potential of these systems was demonstrated; however, substantial research remains to be conducted to optimise their performance and safety.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily involves synovial joints. During the past decade, disease-modifying antirheumatic drugs and biologic agents have been introduced for the treatment of RA. However, they have limitations, including incomplete treatment response, adverse effects requiring drug withdrawal, fall off in efficacy over time, high cost of biologic agents, and refractory cases. Consequently, there is a need to establish safe and effective advanced therapeutic modalities for RA to overcome the shortcomings of current treatments.

MSCs after isolation were exposed to 200 nM calcitriol. Rheumatoid arthritis was induced in BALB/c mice using collagen and Freund's complete adjuvant. One week after immunization, the mice were divided into 3 groups including without treatment, groups treated with untreated and treated MSCs. One week after the last injection, mice sacrificed and samples were taken and the desired evaluations were done.

Our results revealed that the respiratory burst capacity, neutrophil phagocytosis, and nitric oxide production in the population of splenocytes were higher in the positive control group compared to the treatment groups. Also, the level of production of IL-4, IL-10 and TGF-β cytokines and INF-γ and IL-17 cytokines showed a significant increase and decrease, respectively, compared to the positive control group.

Treatment of MSCs with calcitriol leads to an improvement in regulatory function and inhibitory effects on inflammatory mediators of innate immune cells, particularly splenocytes, in a rheumatoid arthritis model compared to untreated mesenchymal stem cells.

Polycystic ovarian syndrome (PCOS) is a low-grade and chronic inflammation defined by irregular hormonal status that primarily triggers females in their reproductive age. Multi cysts are a primary manifestation of PCOS; a high level of androgen production characterizes the condition via ovaries. Rheumatoid arthritis (RA) is a chronic, systemic, and symmetrical inflammatory autoimmune disease that affects 1-2 % of adults. Females are more likely to generate RA. During the inflammatory activity, immune cells attack the synovium and the synovial space. This invasion is essential in releasing many cytokines in the synovial and joint spaces, leading to joint damage and pain, stiffens, heat, and tenderness in the joint. To evaluate the strength of the link between PCOS and RA, the cross-sectional study examined hormonal, metabolic, and autoantibodies in PCOS, RA as a positive control and the study groups. Statistical analysis Shapiro-Wilk test, student t-test, one-way ANOVA, and multi-linear regression analysis were used to evaluate the results. The data highlights significant values for the BMI, WHR, and hirsutism of PCOS and RA groups in comparison to the negative control. The ANOVA results of these parameters also showed a significant p < 0.05 among the groups. According to the negative control, the levels of insulin, HOMA-IR, testosterone, LH, estradiol, and CRP showed a substantial increase in the PCOS group. Also, the RA group showed a significant p < 0.05 rise in CRP, RF, and Ani-CCP, and the ANOVA results showed significant value among the groups under investigation. Progesterone D as a model showed a correlation with Anti-CCP B, RF C, Anti-CCP C, CRP D, RF D, and Anti-CCP D with the highest level of f2 between other models. In addition, statistical tests show that progesterone D with R2= 0.565 and RMSE equal to 0.996 have heteroscedasticity, which means that low levels of progesterone are associated inversely with high levels of RF and Anit-CCP. There is a relative association between the progesterone D model and corresponding predictions. Regardless of solid f2, only 56 % of the sample shows an association between the model and predictors; this relation may differ if we consider the study's limitations.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by joint inflammation, synovial hyperplasia, and bone and cartilage destruction, which significantly impairs physical function and quality of life. Disease-modifying antirheumatic drugs, such as sulfasalazine (SSZ), are crucial for altering the course and progression of RA; however, their clinical use is hampered by poor water solubility and lack of specificity for the reactive oxygen species (ROS)-rich environment typical of RA. To overcome these challenges, ROS-sensitive SSZ-loaded ferrocene nanoparticles are developed. The nanoparticles facilitate enhanced solubility and stability of SSZ and particularly enable precision targeting through the distinctive redox properties of ferrocene. Using a 3D synovial hyperplasia model with fibroblast-like synoviocytes derive from RA patients and validate at both the protein and gene levels, these nanoparticles significantly reduce lactate dehydrogenase, ROS, and inflammatory cytokine levels. Further validation using a collagen-induced arthritis model demonstrates therapeutic efficacy and cytokine modulation in vivo. These findings highlight the potential of ferrocene nanoparticles as a novel and effective therapeutic strategy for RA, offering improved drug delivery and reduced systemic toxicity.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the joints and causes pain, swelling, and deformity. Current treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs, often have limited efficacy and adverse side effects. Nanostructured lipid carriers (NLCs) are promising drug delivery agents for treating RA. NLCs are comprised of solid and liquid lipids, forming a nanostructured matrix that enhances drug solubility, stability, and controlled release. They offer advantages over traditional carriers such as improved skin penetration, increased bioavailability, and reduced systemic side effects. Topical NLC formulations show improved stability and skin absorption, targeting drugs specifically to the affected joints, thus reducing the required dose and systemic exposure. Studies on NLCs for delivering anti-inflammatory and antirheumatic drugs, such as methotrexate, indomethacin, and curcumin, in RA animal models indicate the potential for improved therapeutic efficacy and safety. NLCs represent a promising approach for targeted RA drug delivery, offering better efficacy, fewer side effects, and higher patient compliance. However, further research is needed to optimize NLC formulations and evaluate their clinical efficacy and safety in RA patients. The development of NLC-based drug delivery systems for RA treatment may lead to more effective and well-tolerated therapies, thereby improving the quality of life of patients with this debilitating disease.

There are several disease-modifying antirheumatic drugs currently available to treat rheumatoid arthritis (RA). However, the optimal combination therapy with methotrexate for treating RA remains unclear. We aimed to identify combination therapies with high-efficacy and safety by employing the Bayesian method in a network meta-analysis. We systematically searched PubMed, Embase, CENTRAL, Ichushi web, and PMDA review reports and application materials through October 2020, and found 86 randomized controlled trials. The primary efficacy outcome was the 50% improvement rate according to the American College of Rheumatology criteria (ACR50), and the primary safety outcome was the incidence of serious adverse events. We calculated odds ratios (ORs) and its 95% credible intervals (CrIs) between each treatment, and the surface under the cumulative ranking curve (SUCRA) score for each treatment to rank disease-modifying antirheumatic drug combinations. Individually, most disease-modifying antirheumatic drugs combined with methotrexate are more likely to achieve ACR50 than methotrexate monotherapy, with significant differences (p < 0.05), whereas the incidence of serious adverse events was not significantly different compared with methotrexate monotherapy (p > 0.05). Infliximab combined with methotrexate had the highest efficacy ranking (OR = 10.53, 95% CrI: [3.20, 42.87], SUCRA score: 0.884), and etanercept combined with methotrexate had the highest safety ranking (OR = 0.29, 95% CrI: [0.03, 2.04], SUCRA score: 0.893). Comprehensive cluster analysis revealed that the combination of etanercept, an Fc-fusion protein targeting tumor necrosis factor α, with methotrexate demonstrated higher efficacy and safety. These findings could support the selection of combination therapies for the treatment of RA.

Syringin (SRG) is well-known for its anti-inflammatory effects. However, its pharmacological mechanisms against rheumatoid arthritis (RA) are not fully understood.

We assessed the anti-RA effects of SRG using a collagen-induced arthritis (CIA) rat model. And, we employed single-cell RNA sequencing (scRNA-seq) to analyze the changes in cell types and gene expression in the synovial tissues. Building on these observations, we investigated the effects of SRG on M1 macrophage polarization and RA-fibroblast-like synoviocytes (FLS) proliferation.

Our findings highlighted the anti-RA effects of SRG on CIA rat. scRNA-seq of rat synovial tissues revealed significant changes in M1 and RA-FLS. Specifically, SRG decreased the levels of inflammatory factors in the supernatants of LPS and IFN-γ induced THP-1 cells and downregulated M1-polarized markers in these cells. Further analysis indicated that SRG's regulation of phosphodiesterase 4 (PDE4) and its associated factors was crucial for its anti-M1 polarization effects. Besides, we found that SRG inhibited the activation of FLS in vivo but showed no direct effects on RA-FLS in vitro. However, in RA-FLS, co-cultured with supernatant from SRG-treated M1-polarized THP-1 cells exhibited lower ability of cell proliferation and activation as compared to co-cultured with supernatant from M1-polarized THP-1 cells.

By integrating scRNA-seq analysis with in vivo and in vitro validations, our study revealed that SRG achieved its anti-RA effects by blocking the interaction between macrophages and RA-FLS, with PDE4 playing a central role. This study may provide a novel research paradigm in studying the multi-cell regulatory mechanisms of natural compounds.

Rheumatoid arthritis (RA) is an autoimmune disorder that impacts around 1% of the global population. Up to 20% of people become disabled within a year, which has a severely negative impact on their health and quality of life. RA has a complicated pathogenic mechanism, which initially affects small joints and progresses to larger ones over time. It can damage the skin, eyes, heart, kidney, and lung. Oral medications, intra-articular injections, and other treatments are being used; nevertheless, they have drawbacks, including low bioavailability, numerous adverse effects, and poor patient compliance. Dissolving microneedles (DMNs) are a safe and painless method for transdermal drug delivery, achieved through their ability to physically penetrate the epidermal barrier. They enable targeted drug delivery, significantly enhancing the bioavailability of medications and improving patient compliance. DMNs are particularly effective in delivering both lipophilic and high molecular weight biomolecules. The superior bioavailability of DMNs is demonstrated by the fact that low-dose DMN administration can achieve up to 25.8 times higher bioavailability compared to oral administration. This paper provides a comprehensive review of recent advancements in the use of DMNs for RA treatment, encompassing various materials (such as hyaluronic acid, chitosan, etc.), fabrication techniques (such as the two-step casting method, photopolymerization), and performance evaluations (including morphology, mechanical properties, skin penetration capability, solubility, and pharmacodynamics). Additionally, a thorough safety assessment has been conducted, revealing that DMNs cause minimal skin irritation and exhibit low cytotoxicity, ensuring their safety for clinical application. DMNs provide a highly effective and promising alternative to oral and injectable drug delivery systems, offering a novel therapeutic approach for RA patients that significantly improves treatment outcomes and enhances their quality of life.

Introduction: Rheumatoid arthritis (RA) is a systemic inflammatory and autoimmune disease characterized by joint swelling, pain, damage to the cartilage, and disability. In the present study, we aimed to evaluate the anti-oxidant, anti-inflammatory, and immune-modulatory properties of Quantum Health Accelerator® as water enriched with vital bio-quantum information/energy (EW) following complete Freund's adjuvant (CFA)-induced RA in rats. Methods: Forty adult male Wistar rats (180-220 g) were divided into five groups. Arthritis was induced on day one using a single subcutaneous injection of CFA into the left hind footpad of the rat. Rats were assigned to receive methotrexate (MTX, 2 mg/kg/week, intraperitoneally), EW (orally, instead of normal water ad libitum), or their combination for 29 days. The anti-RA activities were determined by paw edema, joint diameter, arthritis score, and several nociceptive behavioral tests (thermal hyperalgesia, cold allodynia, and tactile allodynia). The levels of inflammatory (TNF-α, CRP, RF, and anti-CCP), anti-inflammatory (IL-10), and oxidative stress (NO, MDA, and GSH) markers were measured in serum. In addition, the levels of IFN-γ, IL-4, IL-17, and TGF-β were assessed in the spleen-isolated lymphocytes. Results: We found that treatment with MTX, EW, and their combination remarkably ameliorated thermal hyperalgesia, cold allodynia, and tactile allodynia results following CFA-induced RA in rats. In addition, EW also notably attenuated arthritis score, joint diameter, inflammatory cytokines, and oxidative markers while propagating anti-inflammatory and anti-oxidative mediators. Conclusions: We reveal that EW possesses anti-arthritic effects, possibly through anti-oxidative, anti-inflammatory, and immunomodulatory properties. Collectively, EW may be a promising therapeutic agent for treating RA.

Rheumatoid arthritis (RA) is an enduring autoimmune illness characterized by persistent inflammation and joint damage. Recent advancements in B cell depletion therapies (BCDTs) have provided new avenues for managing RA. This review article delves into the pathophysiology of RA, highlighting the pivotal role of B cells in disease progression. We explore the mechanisms underlying B cell depletion, focusing on monoclonal antibodies such as rituximab as well as innovative approaches like chimeric antigen receptor (CAR) T cell therapies. An in-depth analysis of clinical studies reveals the efficacy and limitations of these therapies, including success rates, side effects, and cost implications for patients. Despite promising outcomes, the incomplete depletion of B cells and associated risks underscore the need for further research. This review aims to provide a comprehensive understanding of BCDTs in RA, shed light on their potential and challenges, and guide future therapeutic strategies.

Mesenchymal stem cells (MSCs), one of the most significant categories of stem cells, have garnered considerable attention for their potential in disease treatment due to their unique regenerative properties. MSCs can modulate immune responses through various mechanisms, including the secretion of anti-inflammatory cytokines like IL-10, TGF-β, and extracellular vesicles such as exosomes. The immunomodulatory properties of exosomes have led to their use in treating multiple autoimmune diseases, including rheumatoid arthritis (RA), a common inflammatory joint disease worldwide. Patients with RA experience chronic joint pain, movement disorders, joint and cartilage deformities, and significant treatment costs. The primary treatments for RA consist of pharmacological, non-pharmacological, and surgical methods, which mainly focus on alleviating symptoms and relieving pain rather than offering a complete cure for the disease. Recent clinical trials suggest that cell therapy along with exosome therapy, may be a promising and effective treatment option. Exosomes possess unique features that enable them to transport a variety of medicinal and biological compounds, as well as secrete anti-inflammatory substances and growth factors. Thus, exosomes can help reduce inflammation and pain in patients with rheumatoid arthritis while promoting joint repair and regeneration. In this review, we discuss the remarkable therapeutic effects of MSC-derived exosomes in reducing inflammation, facilitating joint repair, and providing pain relief in RA patients. We also detail the characteristics of MSC-derived exosomes, their isolation techniques, and the pathways of their secretion.

Rheumatoid arthritis (RA) is a prevalent autoimmune disorder marked by chronic inflammatory arthritis and systemic effects. The etiology of RA is complex, involving genetic factors like HLA-DR4 and HLA-DR1, as well as environmental influences, particularly smoking, which heightens disease risk. Affecting approximately 1% of the global population, RA is associated with considerable morbidity and mortality, with its prevalence expected to increase due to demographic shifts, especially in certain regions. RA symptoms commonly manifest between ages 35 and 60 but can also affect children under 16 in cases of juvenile RA. Symptoms include prolonged joint stiffness, pain, fatigue, and, in advanced cases, joint deformities. Current treatment approaches involve disease-modifying antirheumatic drugs, biologics, and glucocorticoids to manage symptoms and slow disease progression, though these treatments often present limitations due to adverse effects and varied patient response. The identification of genetic markers, such as HLA-DRB1 and PTPN22, supports the growing emphasis on personalized treatment strategies that account for genetic and lifestyle factors. Non-pharmacological approaches - diet adjustments, physical activity, and stress management - are increasingly valued for their complementary role in RA management. Lifestyle interventions, including whole-food, plant-based diets and physical therapy, show promise in reducing inflammation and improving joint function. Technological advancements, like telemedicine, mobile health applications, and artificial intelligence, are enhancing RA diagnosis and treatment, making care more precise and accessible. Despite these advancements, RA remains incurable, necessitating continued research into novel therapeutic targets and approaches. A comprehensive, patient-centered approach that integrates lifestyle modifications, preventive strategies, and innovative treatments is essential for improving RA management and patient outcomes.

The Janus kinase (JAK) inhibitors are treatment options for autoimmune diseases. Numerous safety concerns have been raised. The European Medicines Agency updated the product information of tofacitinib to include the risk of fractures-but not for other JAK inhibitors. We conducted a global pharmacovigilance analysis of previously investigated JAK inhibitors to investigate a potential class effect.

Individual case safety reports (ICSRs) for all licensed JAK inhibitors were identified from the global WHO pharmacovigilance database. The primary outcome of interest was a bone fracture. Disproportionality analyses using reporting odds ratios (RORs) were conducted.

We identified 122,037 ICSRs for tofacitinib, 27,786 ICSRs for upadacitinib, 14,616 ICSRs for baricitinib, 830 for filgotinib, and 350 for abrocitinib. Among the ICSRs, we identified 2198 (1.8%), 634 (2.3%), and 144 (1.0%) reports, where a bone fracture was reported for tofacitinib, upadacitinib, and baricitinib, respectively. Few reports were available for the newest drugs filgotinib (10) and abrocitinib (1). JAK inhibitors were associated with increased reporting for fracture: tofacitinib (ROR 3.34, 95% confidence interval [CI] 3.20-3.48), upadacitinib (ROR 4.23, 95% CI 3.80-4.48), baricitinib (ROR 1.80, 95% CI 1.52-2.11) and filgotinib (ROR 2.24, 95% CI 1.11-3.94). Patients with bone fractures were more often female, older and had a higher number of co-reported medications. They were more likely to use glucocorticoids, opioids, and bisphosphonates.

The results from this pharmacovigilance analysis, based on a spontaneous reporting database associated with inherent limitations, suggest a potential risk of fractures with JAK inhibitors, indicating that a class effect cannot be ruled out.

Rheumatoid Arthritis (RA) is among the most prevalent chronic inflammatory diseases affecting millions of people with a significant expenditure of resources by National Healthcare Systems. This study aimed to analyze all available treatments exclusively for RA to highlight the costs of each treatment type and raise awareness of the use of biosimilar drugs.

In an Italian healthcare authority, all prescriptions made for the diagnosis of RA were extracted to verify consumption expressed in Defined Daily Dose (DDD) and the expenditure incurred expressed in euros. Consequently, a grouping into three major drug categories has been performed: anti - tumor necrosis factor alpha agents (TNFα), other injectable formulations, and novel oral formulations.

Prescriptions for the second half-year 2022 and 2023 have been analyzed, with a total cost of almost 7 million euros in the sample considered. All pharmaceutical categories showed an increase in consumption, but only anti- TNFα recorded a decrease in costs from 25% in 2022 to 22% in 2023, thanks to the lower cost of the biosimilar drug.

The costs of RA may represent a significant spending commitment for central governments. As a result, actions are needed to encourage the preferential use of biosimilar drugs.

Rheumatoid arthritis (RA) is an autoimmune condition that predominantly affects synovial joints, manifesting with joint swelling, pain, and stiffness. In advanced stages, unchecked inflammation can inflict damage on bone and cartilage, resulting in disabilities and deformities of the joints. Additionally, systemic and extra-articular complications may arise due to the consequences of uncontrolled inflammation. Helicobacter pylori (H. pylori) is one of the most prevalent chronic bacterial infections in humans. This microorganism is a spiral-shaped, flagellated, microaerophilic gram-negative bacterium. Prolonged exposure leads to the activation of the immune system, with infected gastric mucosa epithelial cells continuously producing cytokines. This production, in turn, triggers the generation of antibodies as well as T Helper 1 and T Helper 2 effector T cells. The persistent antigenic stimulation resulting from H. pylori infection could lead to the progression of autoimmune diseases. Numerous clinical and pharmacological trials have illustrated the efficacy of traditional Chinese medicine against H. pylori. This review aims to delve into the connection between H. pylori and rheumatoid arthritis so as understand the pathogenesis. The concluding section of this review explores the interplay of Chinese medicine and Helicobacter pylori concerning rheumatoid arthritis.

While modern treatments can prevent progressive bone destruction in patients with rheumatoid arthritis (RA) achieving clinical remission, it is unclear whether residual clinical activity may cause or be associated with progressive joint damage. This post hoc analysis evaluated the association between clinical disease activity and structural progression in patients with RA treated with filgotinib (FIL) in FINCH 1 (NCT02889796).

Patients with RA and inadequate response to methotrexate (MTX) use were randomized 3:3:2:3 to FIL 200 mg (FIL200) or FIL 100 mg (FIL100) once daily, adalimumab 40 mg biweekly, or placebo, all with background MTX. We evaluated the change from baseline (CFB) in modified total Sharp score (mTSS), erosion score, and joint space narrowing score among patients achieving Clinical Disease Activity Index (CDAI) remission (CDAI ≤ 2.8), low disease activity (LDA; 2.8 < CDAI ≤ 10), medium disease activity (MDA; 10 < CDAI ≤ 22), and high disease activity (HDA; CDAI > 22) at 24 weeks.

At week 24, the least squares (LS) mean CFB in mTSS was similarly low across treatments among patients who achieved CDAI remission (range 0.00-0.11) or LDA (n = 285 and 575, respectively). In patients with MDA and HDA (n = 471 and 157, respectively), smaller LS mean CFB in mTSS was seen in the FIL200 group vs. the placebo group (P < 0.05 for both).

RA clinical remission and LDA achievement were associated with suppressed progression of joint destruction over 24 weeks in all treatment groups. Only FIL200 significantly inhibited joint damage compared with placebo in patients with MDA or HDA, indicating an uncoupling of clinical disease activity and structural progression in patients receiving FIL200.

NCT02889796.

MicroRNAs (miRNAs) have emerged as intricate players in rheumatoid arthritis (RA), holding promise as discerning biomarkers for diagnostic and prognostic purposes. The lack of sensitivity and specificity in current diagnostic techniques, such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), causes diagnosis delays in RA. The miR-146a and miR-155 act in inflammatory cascades and reduce joint deterioration, and miR-223 is paradoxical, acting differently in different illness scenarios. The microenvironment of RA is shaped by the complex modulation of gene expression and cytokine dynamics by miR-126 and miR-24. miRNAs serve as a promising candidate for precision medicine in the management of RA. There are obstacles encountered in validation, delivery optimization, and off-target effect mitigation before miRNA-based biomarkers may be applied in clinical settings. Machine learning (ML) and artificial intelligence (AI) have been used to integrate miRNA expression patterns with clinical data to greatly advance the treatment of RA. Because of the disease's inherent complexity and variability, these state-of-the-art models provide accurate predictions regarding the onset, development, and response to treatment of RA. By using clinical information and miRNA expression data, ML algorithms are revolutionizing the treatment of RA by predicting the onset and course of the disease with remarkably high accuracy. The development of therapeutic modalities and miRNA profiling has great potential to transform the diagnosis, prognosis, and treatment of RA, providing fresh hope for better patient outcomes.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by joint inflammation and destruction. Recent studies emphasize the importance of vitamins D, B12, C, and K in managing RA and enhancing patient health. Vitamin D deficiency is common in RA patients and correlates with increased disease severity, indicating its potential to modulate immune responses and reduce inflammation. Supplementation has shown promise in improving disease activity scores and lowering inflammatory markers. Vitamin B12 is vital for energy and neurological function; its deficiency can worsen fatigue in RA sufferers. Vitamin C, with its antioxidant properties, aids collagen synthesis and may reduce joint inflammation. Vitamin K, particularly through Matrix Gla-Protein (MGP), is essential for bone health and may help prevent joint calcification and osteoporosis. Collectively, these vitamins play critical roles in immune modulation, inflammation reduction, and bone health in RA management, warranting further research on optimal dosages and combinations for effective treatment strategies.

To assess the efficacy/safety of ivarmacitinib, a selective Janus kinase (JAK) 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

Patients were randomised (1:1:1) to receive either placebo (n=188), ivarmacitinib 4 mg (n=189) or ivarmacitinib 8 mg (n=189) once daily, with background csDMARDs allowed. After 24 weeks, patients on placebo switched to ivarmacitinib 4 mg for an additional 28 weeks, while those on ivarmacitinib continued their initial dosage. The primary endpoint was the proportion of patients achieving a 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24.

At week 24, ACR20 response rates were significantly higher in the ivarmacitinib 4 mg (70.4%) and 8 mg (75.1%) groups compared with the placebo group (40.4%; both p<0.0001). Both ivarmacitinib doses achieved numerically higher Disease Activity Score 28-joint count C reactive protein of <2.6/≤3.2 response rates compared with placebo. Improvements in efficacy and patient-reported outcomes were sustained through 52 weeks and were noted in patients who switched from placebo after week 24. During the placebo-controlled period, treatment-emergent adverse events (TEAEs) occurred in 81.5% and 90.5% of patients in the ivarmacitinib 4 mg and 8 mg groups, versus 79.3% in the placebo group. Infection-related TEAEs were slightly higher in the ivarmacitinib groups.

Ivarmacitinib may offer a potential therapeutic option for patients with RA who have an inadequate response to csDMARDs, with a safety profile that was generally manageable over 1 year of treatment and similar to other JAK inhibitors.

NCT04333771.

Rheumatoid arthritis (RA) is a chronic inflammatory disease presenting with articular and extra-articular manifestations that could be related to genetic and environmental factors. Seropositive RA is marked by the presence of autoantibodies, which are associated with worse prognoses and increased risk of extra-articular manifestations, including cardiovascular diseases, lung disorders, and malignancies. Untreated RA can lead to substantial morbidity, reduced life expectancy, and poor quality of life. The development of disease-modifying antirheumatic drugs has paved the way for improving disease outcomes and reducing morbidity and complications related to disease. However, adherence to therapy remains a challenge, often influenced by drug intolerance, misconceptions, and negative beliefs regarding potential side effects and drug toxicity. Here, we report three cases presenting with devastating complications due to long-standing untreated or inadequately treated seropositive RA. This emphasizes the huge disease burden and poor quality of life as part of the natural course and progression of untreated RA. Comprehensive patient education on the disease course, treatment benefits, and potential side effects is essential to enhance adherence and facilitate shared decision-making.

Rheumatoid arthritis (RA) is a long-term systemic autoimmune disorder that causes joint inflammation, swelling, pain, bone erosion, and deformities. Recent findings emphasize the anti-inflammatory and antioxidant properties of bioactive natural compounds, such as polyphenols extracted from plants and fruits, and their possible synergistic effect when used in combination with current therapies to improve the prognosis and symptoms of inflammatory rheumatic diseases. Here, we report that Sicilian extra virgin olive oil polyphenol-enriched extracts (PE-EVOOs) reduce intracellular reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), in peripheral mononuclear cells (PBMCs) obtained from both RA patients and healthy subjects (HSs) treated with lipopolysaccharides (LPS) as a control. HPLC-ESI-MS analysis highlighted that PE-EVOOs are rich in different polyphenolic compounds responsible for many of the observed biological effects. At molecular levels, Western blotting analyses revealed that PE-EVOO treatment is associated with the downregulation of the phosphorylated and active form of the inflammatory transcription factor NF-κB and the pro-inflammatory enzyme cyclooxygenase 2 (COX2). In addition, PE-EVOOs upregulated the transcription factor Nrf2 and its target antioxidant enzyme catalase and manganese superoxide dismutase (MnSOD). Collectively, these results suggest a possible use of PE-EVOOs as potential adjuvants for the treatment of RA.

DARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.

Eligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol. Patients received filgotinib 200 mg/day, except 15 men who received filgotinib 100 mg/day. The primary endpoints were safety and tolerability, which were assessed by the incidence of treatment-emergent adverse events (TEAEs). Safety and efficacy analyses included all enrolled patients who received ≥1 dose of filgotinib in DARWIN 3.

739 patients entered the LTE. The total patient-years of exposure (PYE) to filgotinib was 3706.3 years; the mean exposure duration was 259.8 weeks. 497 patients (67.3%) discontinued prematurely (including 266 TEAEs and 172 withdrawals due to the patient's decision or 'sponsor request'). Overall exposure-adjusted incidence rate (EAIR) was 67 (95% CI 62 to 72.2)/100 PYE for TEAEs and 3.8 (95% CI 3.2 to 4.5)/100 PYE for serious TEAEs. EAIR of infections was 23.3 (95% CI 21.2 to 25.6)/100 PYE, 1.3 (95% CI 0.9 to 1.7)/100 PYE for serious infections and 1.3 (95% CI 0.9 to 1.7)/100 PYE for herpes zoster. EAIRs of major adverse cardiovascular events (0.19 (95% CI 0.8 to 0.39)/100 PYE) and malignancies (0.6 (95% CI 0.4 to 0.9)/100 PYE) were low. Disease response assessed using non-responder imputation plateaued at LTE week 12 before slowly declining over time, with overall American College of Rheumatology (ACR)20/50/70 response rates of 26.9%/20.2%/14.7% at week 396.

Filgotinib was well tolerated in patients with RA for up to 8 years. Safety and efficacy profiles were maintained in patients previously receiving either filgotinib plus methotrexate or filgotinib monotherapy.

The Sharp-van der Heijde score (SvH) is crucial for assessing joint damage in rheumatoid arthritis (RA) through radiographic images. However, manual scoring is time-consuming and subject to variability. This study proposes a multistage deep learning model to predict the Overall Sharp Score (OSS) from hand X-ray images. The framework involves four stages: image preprocessing, hand segmentation with UNet, joint identification via YOLOv7, and OSS prediction utilizing a custom Vision Transformer (ViT). Evaluation metrics included Intersection over Union (IoU), Mean Absolute Error (MAE), Root Mean Squared Error (RMSE), Huber loss, and Intraclass Correlation Coefficient (ICC). The model was trained using stratified group 3-fold cross-validation on a dataset of 679 patients and tested externally on 291 subjects. The joint identification model achieved 99% accuracy. The ViT model achieved the best OSS prediction for patients with Sharp scores < 50. It achieved a Huber loss of 4.9, an RMSE of 9.73, and an MAE of 5.35, demonstrating a strong correlation with expert scores (ICC = 0.702, P < 0.001). This study is the first to apply a ViT for OSS prediction in RA. It presents an efficient and automated alternative for overall damage assessment. This approach may reduce reliance on manual scoring.

T cells mediate pathogenesis of several autoimmune disorders by recognizing self-epitopes presented on Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) complex. The majority of autoantigens presented to T cells in various autoimmune disorders are not known, which has impeded autoantigen identification. Recent advances in immunopeptidomics have started to unravel the repertoire of antigenic epitopes presented on MHC. In several autoimmune diseases, immunopeptidomics has led to the identification of novel autoantigens and has enhanced our understanding of the mechanisms behind autoimmunity. Especially, immunopeptidomics has provided key evidence to explain the genetic risk posed by HLA alleles. In this review, we shed light on how immunopeptidomics can be leveraged to discover potential autoantigens. We highlight the application of immunopeptidomics in Type 1 Diabetes (T1D), Systemic Lupus Erythematosus (SLE), and Rheumatoid Arthritis (RA). Finally, we highlight the practical considerations of implementing immunopeptidomics successfully and the technical challenges that need to be addressed. Overall, this review will provide an important context for using immunopeptidomics for understanding autoimmunity.

Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology that causes progressive and destructive inflammation in the joints. Superb microvascular imaging (SMI) is a new ultrasound technique that allows visualization of slow blood flow in synovitis. This study aimed to report on the clinical value and utility of the SMI technique and its grading for monitoring RA by determining the correlation with clinical disease activity scores (DAS 28) and power Doppler ultrasound (PDUS).All RA patients with clinically apparent synovitis were assessed using DAS 28. Synovitis was investigated with PDUS and SMI and each joint was graded semi-quantitatively. All assessments were carried out at baseline and repeated at least at the 4-month follow-up. Correlations between scores were investigated using Spearman's correlation.60 RA patients with 552 affected joints were recruited. Clinical and sonographic scores were significantly improved at follow-up (p<0.001). SMI showed significantly more joint count and flow signal scores than clinical examination and PDUS. Moderate correlations were found between the SMI score and clinical scores (p<0.001, 0.586 for SMI score vs. DAS 28-CRP, p=0.001, 0.432 for SMI vs. DAS 28-ESR). There were also stronger correlations between the SMI score and PDUS score at both baseline and follow-up (p<0.001, r = 0.817, 0.842 respectively).SMI provides greater utility and ability to detect synovial vascularity and to monitor disease activity than PDUS. A new activity scoring system based on SMI and clinical objective findings is required to improve reliability and validity.