Management Of Rheumatoid Arthritis Research Articles

Predictors of Drug Retention and Survival Rate of bDMARDs in Rheumatoid Arthritis: A Four-Year Real-Life Tunisian Experience.

This study aims to investigate the efficacy and tolerance of biologic disease-modifying anti-rheumatic drug (bDMARDs) in the current management of rheumatoid arthritis (RA) by identifying the retention time and survival rate of bDMARDs. We conducted a retrospective cohort study including Tunisian patients initiating bDMARD treatment between 2016 and 2018 whose data were collected from the National Health Insurance Fund (NHIF). The NHIF is the national office which organises and centralises patients under bDMARDs from all over the country. Retention and survival rate of bDMARDs at 48 months were analysed using Kaplan-Meier survival curves and compared using the log-rank test. Survival factor analysis was performed using Cox regression. Three hundred seventy-four patients, aged 55.5±12.5years [20-90], (87.2%women), were included. The mean duration of RA was 11.7±6.7 years [2-41]. The mean disease activity score (DAS)28 at initiation of the first bDMARD was 6.01±0.89 [5.37-6.5]. This first bDMARD induced low disease activity (LDA) in 55% of cases. Remission was observed in 28% of patients. The highest LDA and remission rates were observed with Tocilizumab (70.8% and 33.3% of cases, respectively). LDA and remission were achieved within a mean of 45 weeks [26-88] and 72 weeks [31-117] respectively. The 48-month first-line survival rate was 55.9%. Retention time was 41.7 months, 95%CI [39.47-43.91]. Presence of rheumatoid factors, co-prescription of methotrexate, and good initial therapeutic response were factors influencing better survival of bDMARDs (p<0.01). Glucocorticoid use predicted poorer survival (p<10-3). The first bDMARD was interrupted in 39% of cases. Ineffectiveness was the most common cause of treatment cessation (52.7%). This real-life study of the Tunisian population allowed us to establish the factors that can influence the survival and retention rates of bDMARDs.

Ionic liquid-based Ionogel: A novel strategy to improve dermal delivery and in vivo efficacy of etodolac in rheumatoid arthritis management

The systemic delivery of Etodolac (ETO) often triggers side effects e.g., myocardial problems, bleeding, etc. thus impeding its clinical usage. Also, ETO exhibits unfavourable physicochemical properties, compelling the need for chronic dosing which could aggravate the condition. The transdermal route not only avoids the systemic toxicity but also enables site-specific action. Yet, the efficacy of this route is constrained due to skin barriers. In the present work, a choline geranate ionic liquid based transdermal gel (CAGE Ionogel) was prepared to improve permeation of ETO. The solubility of ETO increased by ∼19,600-fold in CAGE IL than water. TEM revealed the colloidal shape of ETO-CAGE IL. Moreover, ETO-CAGE Ionogel displayed sustained release for up to 48 h. The ex vivo permeation study revealed a higher flux (∼1.3-fold) than ETO gel. Cytotoxicity assay showed reduced IC50 (∼2.17) relative to ETO in RAW 264.7 cells. In vivo studies in CIA-induced model revealed a decrease in clinical signs of RA. X-ray imaging displayed reduced bone erosion and swelling. The toxicity study showcased no changes in biomarker level suggesting the safety of formulation. Skin compatibility study showed low TEWL implying suitability for topical delivery. The findings affirm the efficacy of transdermal ETO therapy in alleviating RA manifestations.

Molecular and cellular contributors of Rheumatoid Arthritis

Review Molecular and Cellular Contributors of Rheumatoid Arthritis Qingxin Bang 1, Weihua Song 2, and Xiaomeng Wang 1,3,4,* 1 Centre for Vision Research, Duke NUS Medical School, 8 College Road, Singapore 169857, Singapore2 Innoland Biosciences, 400 East Building, 6 West Beijing Road, Taicang 215414, China3 Singapore Eye Research Institute (SERI) The Academia, 20 College Road, Level 6 Discovery Tower, Singapore 169856, Singapore4 Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Proteos, 61 Biopolis Dr, Singapore 138673, Singapore * Correspondence: xiaomeng.wang@duke-nus.edu.sg Received: 7 March 2024; Revised: 17 May 2024; Accepted: 18 May 2024; Published: 29 August 2024 Abstract: Rheumatoid arthritis (RA) is a chronic immune-mediated condition affecting about 1% of the world population. Persistent synovial inflammation (synovitis) triggers the hyperplastic transformation of the synovium which eventually destroys juxta-articular bones and articular cartilage. As the disease progresses, RA patients may present systemic and extra-articular manifestations. Particularly, RA patients are at an increased risk of developing cardiovascular events and mortality as compared to individuals without RA. Recent advances in understanding the molecular and cellular mechanisms of RA led to the development of disease-modifying drugs and reliable assessment tools that have significantly improved the management of RA. This review focuses on the current understanding of RA pathogenesis and treatment strategies.

Attitudes, practices and perceived barriers toward implementing non-pharmacological management for rheumatoid arthritis among rheumatologists: an online cross-sectional survey.

Our study aimed to evaluate the integration level of non-pharmacological management (NPM) for rheumatoid arthritis (RA), analyze attitudes, practices, and perceived barriers towards NPM implementation, and identify factors contributing to the underutilization of non-pharmacological treatment in RA. A descriptive and analytical cross-sectional study was conducted among rheumatologists in Morocco. Rheumatologists received an online questionnaire gathering sociodemographic data, NPM integration level for RA, exploring their attitudes, practices and perceived barriers regarding the integration of NPM for RA, using a Likert scale ranging from 1 to 5. Univariate analyses were conducted to identify risk factors for under-integration of NPM for RA. Out of 440 questionnaires sent, 132 rheumatologists responded to the survey (mean age of 44 ±12 years, 112 (84.8%) females, median professional experience of 15 years [4.7; 26.3]) with a response rate of 30%. All rheumatologists agreed on the importance of NPM integration into their practice with 130 (98.5%) supporting the necessity of tailored recommendations of NPM of RA for the Moroccan context. Sixty-nine (52.3%) reported a lack of NPM integration for RA. Only 36 (27.3%) consistently provided personalized NPM from RA diagnosis and 47 (35.6%) involved patients in decision-making. Comment perceived barriers included difficulties in organizing multidisciplinary care (122; 92.4%), difficulties with time management in consultation (119; 90.2%), and lack of multidisciplinary team members (116; 87.9%). In univariate analysis, lack of suitable training and lack of knowledge on NPM of RA were risk factors of under-integration of NPM of RA with respectively an odds ratio (OR) of 0.09, 95% CI: 0.01-0.86 and OR of 0.34, 95% CI: 0.15-0.76. Our study revealed significant insufficiencies in the integration of NPM of RA among Moroccan rheumatologists. Perceived barriers, including insufficient training, lack of knowledge, and infrastructural limitations, hinder effective implementation. Addressing these through tailored education and multidisciplinary collaboration is essential for improving RA management.

Challenges in implementing treat-to-target in rheumatoid arthritis: a perspective from Brazilian rheumatologists

BackgroundPatient management in rheumatoid arthritis (RA) has evolved to a “treat-to-target” (T2T) approach, which entails intensive treatment and regular follow-up with the goal of achieving low levels of disease activity or clinical remission. Even though a T2T approach is endorsed by professional organizations and yields superior outcomes, its implementation remains incomplete. EVEREST (EleVatE care in RhEumatoid arthritiS with Treat-to-target) is a quality-improvement initiative designed to improve the widespread implementation of a personalized T2T strategy and enable patients with RA to reach their full potential for remission. We describe the Brazilian results from the Global T2T Survey, first part of the EVEREST program.MethodsBetween June and September 2022, we conducted an online survey targeting rheumatologists in Brazil. Our objective was to evaluate the barriers and knowledge gaps hindering the effective implementation of T2T strategies. To achieve this, we employed a set of multiple-choice questions specifically crafted to elicit responses categorized in a structured order.Results166 rheumatologists participated in the survey, 51% of them with more than 21 years of experience in rheumatology. Regarding the perceived challenges in the management of RA in clinical practice, the highest percentage of agreement/strong agreement among the participants was related to the contradictory results of disease activity measures (60%). In terms of the main barriers to assess the disease activity in clinical practice, the lack of adherence to treatment and contradictory assessments between patient-reported outcomes and composite measures were indicated by 75% and 59% of the participants, respectively, as a moderate/serious barrier. The most frequently knowledge and skill gaps related to the management of RA pointed out by the participants were on the difficulty to assess patients’ health literacy (54% stated to have no more than intermediate knowledge on standardized methods to assess it and 43% no more than intermediate skills on determining the level of health literacy of the patients). In general, the use of tools to support the management of RA patients in clinical practice was indicated to be unusual by the participants. Self-reflection questionnaires, patient education materials and treatment consideration checklists were pointed out as the least frequently used tools (85%, 64% and 62% of the participants stated to use them never, rarely, or only sometimes, respectively).ConclusionsOur findings indicate a greater need for design, selection, and uptake of practical strategies to further improve communication between healthcare providers and patients with RA, as well as for promoting well-informed, collaborative decision-making in their care.

Candidacy 2.0 (CC) – an enhanced theory of access to healthcare for chronic conditions: lessons from a critical interpretive synthesis on access to rheumatoid arthritis care

BackgroundThe Dixon-Woods et al. Candidacy Framework, a valuable tool since its 2006 introduction, has been widely utilized to analyze access to various services in diverse contexts, including healthcare. This social constructionist approach examines micro, meso, and macro influences on access, offering concrete explanations for access challenges rooted in socially patterned influences. This study employed the Candidacy Framework to explore the experiences of individuals living with rheumatoid arthritis (RA) and their formal care providers. The investigation extended to assessing supports and innovations in RA diagnosis and management, particularly in primary care.MethodsThis systematic review is a Critical Interpretive Synthesis (CIS) of qualitative and mixed methods literature. The CIS aimed to generate theory from identified constructs across the reviewed literature. The study found alignment between the seven dimensions of the Candidacy Framework and key themes emerging from the data. Notably absent from the framework was an eighth dimension, identified as the “embodied relational self.” This dimension, central to the model, prompted the proposal of a revised framework specific to healthcare for chronic conditions.ResultsThe CIS revealed that the eight dimensions, including the embodied relational self, provided a comprehensive understanding of the experiences and perspectives of individuals with RA and their care providers. The proposed Candidacy 2.0 (Chronic Condition (CC)) model demonstrated how integrating approaches like Intersectionality, concordance, and recursivity enhanced the framework when the embodied self was central.ConclusionsThe study concludes that while the original Candidacy Framework serves as a robust foundation, a revised version, Candidacy 2.0 (CC), is warranted for chronic conditions. The addition of the embodied relational self dimension enriches the model, accommodating the complexities of accessing healthcare for chronic conditions.Trial RegistrationThis study did not involve a health care intervention on human participants, and as such, trial registration is not applicable. However, our review is registered with the Open Science Framework at https://doi.org/10.17605/OSF.IO/ASX5C.

Exploring the Role of Homeopathy in Rheumatoid Arthritis: A Comprehensive Review

Background: Rheumatoid arthritis (RA) is a prevalent and debilitating chronic condition, affecting approximately 1–2% of the population. It is characterized by systemic inflammation and primarily targets the flexible, synovial joints, leading to symptoms such as joint swelling, stiffness, pain, and reduced functionality. Aim/Objective: This review aims to explore the role of homeopathic interventions in the management of RA, focusing on the potential benefits of homeopathic consultations in improving patient outcomes and well-being. Specifically, the objective is to investigate how homeopathy, as a holistic approach to healthcare, addresses the multifaceted nature of RA and its impact on patients' lives. Methodology : A comprehensive search of electronic databases including PubMed, SCOPUS, and Google Scholar was conducted to identify relevant literature on homeopathic treatments for RA. Keywords such as 'Rheumatoid arthritis,' 'Homeopathy,' and related terms were utilized. Result: The initial database search yielded a substantial number of records, from which relevant studies were selected based on predefined inclusion criteria. After screening for duplicates and applying exclusion criteria, a total of 13 studies were included in the review. These studies encompassed RCT, Observational studies, randomized open-label interventional Study, In Vitro studies and clinical trials, providing insights into the potential benefits of homeopathy in RA management. Conclusion: Homeopathy shows promise as an adjunctive therapy for RA, considering the holistic nature of the disease.

Uncovering the mechanisms of Zhubi decoction against rheumatoid arthritis through an integrated study of network pharmacology, metabolomics, and intestinal flora

Ethnopharmacological relevanceZhubi Decoction (ZBD) is a modified formulation derived from the classic traditional Chinese medicine prescription “Er-Xian Decoction” documented in the esteemed “Clinical Manual of Chinese Medical Prescription”. While the utilization of ZBD has exhibited promising clinical outcomes in treating rheumatoid arthritis (RA), the precise bioactive chemical constituents and the underlying mechanisms involved in its therapeutic efficacy remain to be comprehensively determined. Aim of the studyThis study aims to systematically examine ZBD's pharmacological effects and molecular mechanisms for RA alleviation. Materials and methodsUtilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of ZBD in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. The UPLC-MS/MS technique was utilized to analyze the compounds of ZBD. The potential therapeutic targets and signaling pathways of ZBD in the management of RA were predicted using network pharmacology. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. Key targets and predicted pathways were further validated using immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16 S rDNA sequencing and investigated the effects of ZBD on the microbiota of CIA rats through bioinformatics and statistical methods. ResultsZBD exhibited remarkable efficacy in alleviating RA symptoms in CIA rats without notable side effects. This included reduced paw redness and swelling, minimized joint damage, improved the histopathology of cartilage and synovium, mitigated the inflammatory state, and lowered serum concentrations of cytokines TNF-α, IL-1β and IL-6. Notably, the effectiveness of ZBD was comparable to MTX. Network pharmacology analysis revealed inflammation and immunity-related signaling pathways, such as PI3K/AKT, MAPK, IL-17, and TNF signaling pathways, as vital mediators in the effectual mechanisms of ZBD. Immunofluorescence analysis validated ZBD's ability to inhibit PI3K/AKT pathway proteins. Serum metabolomics studies revealed that ZBD modulates 170 differential metabolites, partially restored disrupted metabolic profiles in CIA rats. With a notable impact on amino acids and their metabolites, and lipids and lipid-like molecules. Integrated analysis of metabolomics and network pharmacology identified 6 pivotal metabolite pathways and 3 crucial targets: PTGS2, GSTP1, and ALDH2. Additionally, 16 S rDNA sequencing illuminated that ZBD mitigated gut microbiota dysbiosis in the CIA group, highlighting key genera such as Ligilactobacillus, Prevotella_9, unclassified_Bacilli, and unclassified_rumen_bacterium_JW32. Correlation analysis disclosed a significant link between 47 distinct metabolites and specific bacterial species. ConclusionZBD is a safe and efficacious TCM formulation, demonstrates efficacy in treating RA through its multi-component, multi-target, and multi-pathway mechanisms. The regulation of inflammation and immunity-related signaling pathways constitutes a crucial mechanism of ZBD's efficacy. Furthermore, ZBD modulates host metabolism and intestinal flora. The integrated analysis presents experimental evidence of ZBD for the management of RA.

Gelsolin alleviates rheumatoid arthritis by negatively regulating NLRP3 inflammasome activation.

Despite numerous biomarkers being proposed for rheumatoid arthritis (RA), a gap remains in our understanding of their mechanisms of action. In this study, we discovered a novel role for gelsolin (GSN), an actin-binding protein whose levels are notably reduced in the plasma of RA patients. We elucidated that GSN is a key regulator of NLRP3 inflammasome activation in macrophages, providing a plausible explanation for the decreased secretion of GSN in RA patients. We found that GSN interacts with NLRP3 in LPS-primed macrophages, hence modulating the formation of the NLRP3 inflammasome complex. Reducing GSN expression significantly enhanced NLRP3 inflammasome activation. GSN impeded NLRP3 translocation to the mitochondria; it contributed to the maintenance of intracellular calcium equilibrium and mitochondrial stability. This maintenance is crucial for controlling the inflammatory response associated with RA. Furthermore, the exacerbation of arthritic symptoms in GSN-deficient mice indicates the potential of GSN as both a diagnostic biomarker and a therapeutic target. Moreover, not limited to RA models, GSN has demonstrated a protective function in diverse disease models associated with the NLRP3 inflammasome. Myeloid cell-specific GSN-knockout mice exhibited aggravated inflammatory responses in models of MSU-induced peritonitis, folic acid-induced acute tubular necrosis, and LPS-induced sepsis. These findings suggest novel therapeutic approaches that modulate GSN activity, offering promise for more effective management of RA and a broader spectrum of inflammatory conditions.

Glucocorticoid sparing effect of Janus Kinase inhibitors compared to biological Disease Modifying Anti-Rheumatic Drugs in rheumatoid arthritis, a single-center retrospective analysis.

Glucocorticoid sparing in rheumatoid arthritis (RA) treatment is crucial to minimizing adverse effects associated with long-term use. Janus kinase inhibitors (JAKi) could potentially offer a more potent glucocorticoid-sparing effect than biological Disease-Modifying Antirheumatic Drugs (bDMARDs). This is a single-center retrospective analysis of RA patients treated with JAKi or bDMARDs. Glucocorticoid tapering, rescue therapy and discontinuation were analyzed through mixed-effects models, Poisson regression, and multivariable logistic regression, respectively, adjusting for baseline disease activity, demographic factors, and treatment line. A total of 716 RA patients treated with JAKi (n = 156) or bDMARDs (n = 560) were evaluated. JAKi treatment was associated with a more rapid reduction in glucocorticoid dose within the first 6 months and 60% higher odds of discontinuation compared with bDMARDs (adjusted odds ratio 1.63, 95% CI 1.02-2.60, p 0.039). Despite a higher baseline glucocorticoid dose, over 50% of JAKi-treated patients discontinued glucocorticoids after 12 months, vs ∼40% for bDMARDs. The need for glucocorticoid rescue therapy was significantly higher in the bDMARD group (rate ratio 2.66 (95% CI, 1.88-3.74)). Our findings indicate that JAK inhibitors facilitate more rapid glucocorticoid tapering compared with bDMARDs in RA patients. These results underscore the potential of JAK inhibitors to reduce long-term glucocorticoid exposure, highlighting their value in RA management strategies, including minimizing glucocorticoid-related adverse effects.

Rheumatoid Arthritis Treatment: Harnessing Novel Molecular Targets and Therapeutics for Improved Patient Outcomes

Rheumatoid arthritis (RA) is a chronic autoimmune disease that has significant unmet needs for improved treatment outcomes. This review provides an overview of emerging molecular targets and potential new therapies for managing RA. The discussed targets, such as CD40-CD40 ligand, programmed death protein 1 (PD-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 receptor-associated kinases (IRAKs), tyrosine kinase 2 (TYK2), bradykinin receptor 1 (B1R), and OX40-OX40 ligand, have shown promising results in preclinical studies and clinical trials. These findings stimulate continued efforts to develop more effective and safer therapeutic options, encouraging stakeholders to contribute to improving RA management.

Emerging Landscape of In Vitro Models for Assessing Rheumatoid Arthritis Management.

Rheumatoid arthritis (RA) is a complex condition that is influenced by various causes, including immunological, genetic, and environmental factors. Several studies using animal models have documented immune system dysfunction and described the clinical characteristics of the disease. These studies have provided valuable insights into the pathogenesis of inflammatory arthritis and the identification of new targets for treatment. Nevertheless, none of these animal models successfully replicated all the characteristics of RA. Additionally, numerous experimental medications, which were developed based on our enhanced comprehension of the immune system's function in RA, have shown potential in animal research but ultimately proved ineffective during different stages of clinical trials. There have been several novel therapy alternatives, which do not achieve a consistently outstanding therapeutic outcome in all patients. This underscores the importance of employing the progress in in vitro models, particularly 3D models like tissue explants, and diverse multicomponent approaches such as coculture strategies, synovial membrane, articular cartilage, and subchondral bone models that accurately replicate the structural characteristics of RA pathophysiology. These methods are crucial for the advancement of potential therapeutic strategies. This review discusses the latest advancements in in vitro models and their potential to greatly impact research on managing RA.

Management of Rheumatoid Arthritis By Development of Nanocarriers and their Significance Over Conventional Dosage Forms

Background: Rheumatoid Arthritis is one of the most common auto-immune diseases that cause inflammation. It is characterized by pain, stiffness, tenderness, and swelling in joints, which may even lead to heart, lungs, or brain-related problems where age is the major factor involved, as around 55% older adults have been affected by it. Treatments including non-steroidal anti- inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs) etc., that are modified and formulated as nanocarriers for enhanced bioavailability, majorly aim at enhancing the rate and extent of drug reaching the bloodstream such as solid-lipid nanoparticles, liposomes, polymeric- micelles, polymeric nanoparticles etc. are used in the management of rheumatoid arthritis. Methods: The following tools (Pubmed, Scopus, Google search engine, Google Scholar, Medline Search Engine, Elsevier) were used in the literature search. Results: Through the literature review, the development of nanocarrier shows a promising approach in the management of rheumatoid arthritis as compared to the conventional drug treatment such as biologic agents and non-steroidal anti-inflammatory drugs etc. Conclusion: Rheumatoid Arthritis is a condition that occurs when the immune system, which normally helps to protect the body from infection and disease, attacks its own tissues. The disease causes pain, swelling as well as loss of function in joints. Therefore, life-long management is required by reducing the dose frequency and dosage regimen, which can be effectively approached by the development of a nano-carrier for significant drug uptake and low toxicity.

Helicobacter pylori upregulates PAD4 expression via stabilising HIF-1α to exacerbate rheumatoid arthritis

ObjectiveHelicobacter pylori infection has been reported to aggravate rheumatoid arthritis (RA), but the relevant mechanism remains unclear. This study aimed to investigate the underlying pathogenic mechanism of H. pylori infection...

Targeting next-generation PDE4 inhibitors in search of potential management of rheumatoid arthritis and psoriasis

Immune-mediated inflammatory diseases (IMIDs) comprise a broad spectrum of conditions characterized by systemic inflammation affecting various organs and tissues, for which there is no known cure. The isoform-specific inhibition of phosphodiesterase-4B (PDE4B) over PDE4D constitutes an effective therapeutic strategy for the treatment of IMIDs that minimizes the adverse effects associated with non-selective PDE4 inhibitors. Thus, we report a new class of isoquinolone derivatives as next-generation PDE4 inhibitors for effective management of rheumatoid arthritis (RA) and psoriasis. Among the series, 8 compounds i.e. 1e, 1l, 1m, 1n, 1o, 2m, 2o and 3o showed promising PDE4B inhibition (>80 %) in vitro with IC50 ∼ 1.4–6.2 µM. The compound 1l was identified as an initial hit and was pursued for further studies. According to structure–activity relationship (SAR), an allyl group at C-4 position improved PDE4B inhibition. The correlation between in vitro activity data and binding affinities obtained via molecular docking suggested that the high-affinity binding to PDE4B is a prerequisite for the effective inhibition of PDE4B. Notably, the hit 1l showed selectivity towards PDE4B over PDE4D in vitro. Furthermore, 1l treatment (30 mg/kg) in the adjuvant-induced arthritis (AIA) rat model induced by complete Freund’s adjuvant (CFA) demonstrated anti-arthritic potential via ameliorating paw swelling and body weight, narrowing joint space, reducing excessive immune cells infiltration and pannus formation in addition to reducing mRNA expression of pro-inflammatory cytokines such as TNF-α and IL-6 in synovial tissues of experimental rats. Additionally, 1l reduced the hyper-proliferative state and colony forming potential of IMQ-induced psoriatic keratinocytes. The treatment of these cells with 1l markedly reduced the protein levels of Ki67 and mRNA levels of pro-inflammatory cytokines e.g. IL-17A and TNF-α suggesting its potent anti-psoriatic potential. Furthermore, 1l did not show any significant adverse effects when evaluated in a systematic toxicity (e.g. teratogenicity, hepatotoxicity and cardiotoxicity) studies in zebrafish at the tested concentrations (1–100 µM) and the NOAEL (no-observed-adverse-effect level) was found to be 100 µM. Thus, with promising anti-inflammatory effects both in vitro and in vivo along with PDE4B selectivity with an acceptable safety margin, 1l emerged as a new and promising inhibitor for further studies.

Barriers to, Facilitators of, and Interventions to Support Treat-to-Target Implementation in Rheumatoid Arthritis: A Systematic Review.

Treat-to-target (T2T) is recommended in the management of rheumatoid arthritis (RA) but its implementation is suboptimal. We aimed to identify interventional strategies targeted at improving T2T implementation in RA by systematically reviewing published evidence on barriers to, facilitators of, and interventions to support T2T implementation. Systematic and scoping literature searches in PubMed/MEDLINE®, BIOSIS Previews®, Derwent Drug File, Embase®, EMCare®, International Pharmaceutical Abstracts, and SciSearch® were conducted to identify barriers/facilitators and interventions relating to T2T implementation in RA. The quality of included studies was assessed using Critical Appraisal Skills Programme (CASP) checklists. Data related to barriers/facilitators and interventions were extracted, grouped, and summarized descriptively, and a narrative synthesis was generated. In total, 146 articles were analyzed, of which 123 (84%) included ≥50% of the items assessed by CASP checklists. Of the 146 studies, 76 evaluated T2T barriers and facilitators, from which 329 relevant statements were identified and regrouped into 18 target areas, including: healthcare professionals' (HCPs') or patients' knowledge or perceptions; patient-HCP communication or alignment; and time or resources. Overall, 56 interventions were identified from 70 studies across the 18 target areas; 54% addressed disease activity or patient-reported outcome assessments. Of the 56 interventions identified, 36 improved T2T implementation and/or patient outcomes in RA. Despite long-established T2T recommendations, there remain many barriers to its implementation. Interventions to improve T2T should be developed further and assessed, with a particular focus on tailoring them to individual countries, regions, and healthcare settings.

Application of foot massage therapy to reduce pain scale of elderly with rheumatoid arthritis

Rheumatoid Arthritis (RA) is a chronic autoimmune disorder characterized by systemic inflammation, joint damage, and persistent pain, particularly in older adults. The debilitating nature of RA significantly impairs individuals' quality of life, leading to diminished independence and increased reliance on pharmacological interventions. While pharmaceutical treatments play a crucial role in managing RA symptoms, complementary and alternative therapies, such as massage, have garnered attention for their potential to alleviate pain and improve overall well-being. This study adopts a descriptive approach to examine the efficacy of foot massage as an intervention for RA-related pain in older adults. Two participants diagnosed with RA were selected for the case study. Family nursing care principles were integrated into the intervention to provide holistic support. Pain scale assessments were conducted before and after each foot massage session to measure changes in pain intensity. Analysis of the data revealed a significant reduction in pain intensity among participants following the foot massage sessions. Pain levels decreased from moderate to mild, indicating the efficacy of foot massage in alleviating RA-associated pain in older adults.The findings of this study support the notion that foot massage can serve as a viable intervention for managing RA-related pain in older adults. The mechanisms underlying the efficacy of foot massage, including its ability to stimulate vasodilation and enhance endorphin production, highlight its potential therapeutic benefits for individuals grappling with RA. Foot massage emerges as a promising adjunctive therapy for alleviating pain and improving the well-being of older adults living with Rheumatoid Arthritis. Integrating foot massage into holistic care approaches can enhance pain management strategies and contribute to the overall quality of life for individuals affected by this debilitating condition. Further research is warranted to explore the long-term effects and optimal frequency of foot massage in RA management.

AYURVEDIC MANAGEMENT OF RHEUMATOID ARTHRITIS WSR TO AMAVATA- A CASE REPORT

Introduction: The Ayurveda described Mandagni as the root cause of all the diseases. The Acharyas mentioned Amavata as one of the common disorders caused by the impairment of Agni, formation of Ama and vitiation of Vata Dosha. The Ama is carried by the vitiated Vata and deposited in Shleshmasthanas producing symptoms like Angmarda, Aruchi, Alasya, Sandhiruk and Sandhishoth. On the basis of sign and symptoms Amavata can be equated to Rheumatoid Arthritis in modern era. Rheumatoid arthritis is a systemic autoimmune disease characterised by inflammatory arthritis and extra articular involvement. The onset of disease, beginning with prodrome of fatigue, weakness, joint stiffness, vague arthralgias followed by pain and swelling of joints. Aim: To evaluate the efficacy of Oral Ayurvedic drugs in management of Amavata. Method: In the present case, a female patient aged 36 years presented in OPD Of Asthi-SandhirogaVibhaga of RGGPG Ayurvedic College Paprola Distt. Kangra (H.P.) with the complaints of pain in multiple joints since 2 years. She also complained of generalised weakness and morning stiffness. The investigations were advised and oral Ayurvedic formulations like Vishtindukvati, Amavatari Ras and TrikatuChurna were prescribed to the patient. Result: The Ayurvedic management showed desired results in relieving the symptoms of patient. Discussion: The Ayurvedic drugs are effective in treating Amavata equated to RA and better alternative to NSAIDS, DMARDS and steroids in Rheumatoid arthritis management in todays world.

Therapeutic Potential of Nanocarriers in the Management of Rheumatoid Arthritis.

RA is characterized by chronic inflammation, joint damage, and systemic complications. Despite available treatments, many patients experience inadequate responses or adverse effects. Novel therapeutic strategies are needed to address these challenges. Nanoparticulate technologies offer promising opportunities to enhance drug delivery and targeting in RA treatment. The main objective is to explore recent advancements in nanoparticulate technologies for RA treatment, focusing on their potential to improve drug delivery and efficacy while minimizing adverse effects. This review examines recent studies on nanoparticulate technologies for treating rheumatoid arthritis (RA), focusing on the use of nanocarriers for targeted drug delivery. Studies investigating the effectiveness of nanocarriers in delivering drugs specifically for RA treatment were included in the analysis. Nanoparticulate technologies have shown promise in improving the delivery and efficacy of RA treatments. Various nanocarriers, such as liposomes, polymeric nanoparticles, and micelles, have been developed to enhance drug delivery to inflamed joints. These nanocarriers loaded with curcumin, Aceclofenac, Boswellic acid, methotrexate, resveratrol, etc. can improve drug stability, prolong circulation time, and enhance targetability to inflamed tissues. By overcoming the limitations of traditional therapies, these technologies have the potential to improve patient outcomes and quality of life. Future research should focus on optimizing nanocarrier design, evaluating long-term safety, and conducting clinical trials to validate their efficacy in RA management.

Autoantibodies to joint-related peptides as predictive markers in early rheumatoid arthritis.

For better management of rheumatoid arthritis (RA), new biomarkers are needed to predict the development of different disease courses. This study aims to identify autoantibodies against epitopes on proteins in the joints and to predict disease outcome in patients with new onset RA. Sera from new onset RA patients from the Swedish BARFOT and TIRA-2 cohorts (n = 1986) were screened for autoantibodies to selected peptides (JointIDs) in a bead-based multiplex flow immunoassay. Disease outcomes included Boolean remission 1.0, swollen joint count and radiographic destruction. Multivariate logistic regression and zero-inflated negative binomial models that accounted for clinical factors were used to identify JointIDs with the strongest potential to predict prognosis. Boolean remission was predicted with 42% sensitivity and 75% specificity in male patients positive for antibodies to a non-modified collagen type II (COL2) peptide at 12 months. When antibodies to a specific citrullinated cartilage oligomeric protein (COMP) peptide were absent and the patient was in Boolean remission at 6 months, the sensitivity was 13% and the specificity 99%. Positivity for the non-modified COL2 peptide also reduced the frequency of swollen joints by 41% and 33% at 6 and 12 months, respectively. Antibodies to cyclic citrullinated peptides (aCCP) predicted joint destruction with low specificity (58%). Positivity for a COL2 and a glucose-6-phosphate dehydrogenase peptide in citrullinated forms increased specificity (86%) at the expense of sensitivity (39%). Autoantibodies against joint-related proteins at RA diagnosis predict remission with high specificity and, in combination with clinical factors, may guide future treatment decisions.