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ID PMID Title PublicationDate abstract
33010144 Is improvement of fatigue in rheumatoid arthritis a proper effect of biologics? 2021 Mar 1 Background. The objective of our present study is to assess the relation between persistent fatigue and rheumatoid arthritis (RA) disease activity and its functional impact and to determine if the positive effect of biologics on fatigue is due to good disease response or to a different pathway.Methods. A study cohort of patients with established RA was conducted. We included patients who had been prescried a biologic after at least failure of one conventional synthetic Disease Modifying Anti-Rheumatic Drug synthetic (csDMARDs). At baseline, patients had a moderately to highly active disease. Demographic characteristics, disease activity and functional impact were assessed by disease activity score (DAS28CRP) and health assessment questionnaire (HAQ) scores. Fatigue was evaluated by the Functional Assessment of Chronic Illness Therapy-Fatigue scale questionnaire (FACIT-F). Patients were examined before initiating biotherapy, then after three months and six months.Results. Thirty women with RA, with a mean age of 52.5 years, were included. At baseline, 57% received anti-TNFα: Etanercept (n = 9), Adalimumab (n = 6), Infliximab (n = 2) and 43% received Rituximab. Good Eular response was obtained in 80% of patients at the third month and 97% of patients at the sixth month. In the analytic study, a significant amelioration after 3 months of biotherapy was found in both disease response (DAS28CRP) and fatigue (FACIT-F), respectively (p = 0.01, p<0.001 and p<0.001). The disease activity decreased significantly also after sixth month (p = 0.01, p<0.001 and p = 0.012). In the linear multivariate analysis, the regression of visual analogic pain (VAS pain) was the only predictors of the improvement of fatigue.Conclusion. Biologics contribute to improve fatigue in patients with established RA and this effect seems to be independent from the clinical efficacy of this treatment.
33160044 Targets of hydroxychloroquine in the treatment of rheumatoid arthritis. A network pharmaco 2021 Mar OBJECTIVE: This study was performed to investigate the multi-targets mechanism of hydroxychloroquine (HCQ) in the treatment of rheumatoid arthritis (RA). METHODS: The predicted targets of HCQ and the proteins related to RA were returned from databases. Followed by protein-protein interaction (PPI) network, the intersection of the two group of proteins was studied. Furthermore, gene ontology (GO) and KyotoEncyclopediaofGenesandGenomes (KEGG) enrichment was used to analyse these proteins in a macro perspective. Finally, the candidate targets were checked by molecular docking. RESULTS: The results suggested that HCQ in the treatment of RA was mainly associated with 4 targets that are smoothened homolog (SMO), sphingosine kinase (SPHK) 1, SPHK2 and gatty-acid amide hydrolase (FAAH), with their related 3276 proteins' network which regulate ErbB, HIF-1, NF-κB, FoxO, chemokines, MAPK, PI3K/Akt pathways and so forth. Biological process were mainly focused in the regulation of cell activation, myeloid leukocyte activation, regulated exocytosis and so forth. Molecular docking analysis showed that hydrogen bonding and π-π stacking were the main forms of chemical force. CONCLUSIONS: Our research provides protein targets affected by HCQ in the treatment of RA. SMO, SPHK1, SPHK2 and FAAH involving 3276 proteins become the multi-targets mechanism of HCQ in the treatment of RA.
34101073 Penta-acetyl Geniposide Suppresses Migration, Invasion, and Inflammation of TNF-α-Stimula 2021 Dec We previously reported that penta-acetyl geniposide ((Ac)(5)GP, an active derivative of geniposide) showed anti-arthritic effect on adjuvant-induced arthritis (AIA) rats by promoting the apoptosis of AIA fibroblast-like synoviocyte (FLS). This study aimed to demonstrate the effects of (Ac)(5)GP on migration, invasion, and inflammation of TNF-α-stimulated rheumatoid arthritis (RA) FLS (MH7A cell) and to explore the involved mechanisms. MTT assay was used to determine the applied non-cytotoxic doses of (Ac)(5)GP (12.5, 25, 50 μM) in vitro. Results of wound-healing, transwell, and phalloidin staining assays indicated that (Ac)(5)GP reduced the migration, invasion, and F-actin cytoskeletal reorganization of TNF-α-stimulated MH7A. Results of ELISA and western blot assays confirmed that (Ac)(5)GP reduced TNF-α-induced production of pro-inflammatory cytokines (like IL-1β, IL-6, IL-8) and matrix metalloproteinases (MMPs, such as MMP-2 and MMP-9). Moreover, (Ac)(5)GP inhibited TNF-α-induced activation of Wnt/β-catenin pathway, evidenced by reducing the protein levels of Wnt1, p-GSK-3β (Ser9), and β-catenin and preventing β-catenin nuclear translocation. Importantly, the combination of XAV939 (an inhibitor of Wnt/β-catenin) promoted the actions of (Ac)(5)GP on TNF-α-induced migration, invasion, and inflammation, further revealing the involvement of Wnt/β-catenin pathway underlying the therapeutic effects of (Ac)(5)GP on TNF-α-stimulated MH7A. In vivo, (Ac)(5)GP relieved the progression and severity of rat collagen-induced arthritis, related to reducing the levels of IL-1β, IL-6, IL-8, MMP-2, and MMP-9 as well as inhibiting Wnt/β-catenin pathway in synovial tissues. Collectively, (Ac)(5)GP could suppress TNF-α-induced migration, invasion, and inflammation in RA FLS involving Wnt/β-catenin pathway and (Ac)(5)GP might be as a candidate agent for RA treatment.
34330848 Missing data in randomised controlled trials of rheumatoid arthritis drug therapy are subs 2021 Jul OBJECTIVES: To analyse the amount, reporting and handling of missing data, approach to intention-to-treat (ITT) principle application and sensitivity analysis utilisation in randomised clinical trials (RCTs) of rheumatoid arthritis (RA). To assess the trend in such reporting 10 years apart (2006 and 2016). METHODS: Parallel group drug therapy RA RCTs with a clinical primary endpoint. RESULTS: 176 studies enrolling a median of 160 (IQR 62-339) patients were eligible. In terms of actual analysis: 81 (46%) RCTs conducted ITT, 42 (23.9%) conducted modified ITT while 53 (30.1%) conducted non-ITT analysis. Only 58 of 97 (59.8%) RCTs reporting an ITT analysis actually performed it. The median (IQR) numbers of participants completing the trial and included in analysis for primary outcome were 86% (74%-91%) and 100% (97.1%-100%), respectively. 53 (32.7%) and 65 (40.1%) RCTs had >20% and 10%-20% missing primary outcome data, respectively. Missing data handling was unreported by 58 of 171 (33.9%) RCTs. When reported, vast majority used simple imputation methods. No significant trend towards improved reporting was seen between 2006 and 2016. Sensitivity analysis numerically improved from 2006 to 2016 (14.7% vs 21.4%). CONCLUSIONS: There is significant discrepancy in the reported and the actual performed analysis in RA drug therapy RCTs. Nearly one-third of RCTs had >20% missing data. The reporting and methods of missing data handling remain inadequate with high usage of non-preferred simple imputation methods. Sensitivity analysis utilisation was low. No trend towards better missing data reporting and handling was seen.
33655421 Use of conventional synthetic and biologic disease-modifying anti-rheumatic drugs in patie 2021 May To examine whether patients with inflammatory arthritis (IA) treated with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and/or biologic (b) DMARDs, could be affected from SARS-CoV-2 infection and to explore the COVID-19 disease course and outcome in this population. This is a prospective observational study. During the period February-December 2020, 443 patients with IA who were followed-up in the outpatient arthritis clinic were investigated. All patients were receiving cs and/or bDMARDs. During follow-up, the clinical, laboratory findings, comorbidities and drug side effects were all recorded and the treatment was adjusted or changed according to clinical manifestations and patient's needs. There were 251 patients with rheumatoid arthritis (RA), 101 with psoriatic arthritis (PsA) and 91 with ankylosing spondylitis (AS). We identified 32 patients who contracted COVID-19 (17 RA, 8 PsA, 7 AS). All were in remission and all drugs were discontinued. They presented mild COVID-19 symptoms, expressed mainly with systemic manifestations and sore throat, while six presented olfactory dysfunction and gastrointestinal disturbances, and all of them had a favorable disease course. However, three patients were admitted to the hospital, two of them with respiratory symptoms and pneumonia and were treated appropriately with excellent clinical response and outcome. Patients with IA treated with cs and/or bDMARDs have almost the same disease course with the general population when contract COVID-19.
34118460 Circadian clock genes as promising therapeutic targets for autoimmune diseases. 2021 Aug Circadian rhythm is a natural, endogenous process whose physiological functions are controlled by a set of clock genes. Disturbance of the clock genes have detrimental effects on both innate and adaptive immunity, which significantly enhance pro-inflammatory responses and susceptibility to autoimmune diseases via strictly controlling the individual cellular components of the immune system that initiate and perpetuate the inflammation pathways. Autoimmune diseases, especially rheumatoid arthritis (RA), often exhibit substantial circadian oscillations, and circadian rhythm is involved in the onset and progression of autoimmune diseases. Mounting evidence indicate that the synthetic ligands of circadian clock genes have the property of reducing the susceptibility and clinical severity of subjects. This review supplies an overview of the roles of circadian clock genes in the pathology of autoimmune diseases, including BMAL1, CLOCK, PER, CRY, REV-ERBα, and ROR. Furthermore, summarized some circadian clock genes as candidate genes for autoimmune diseases and current advancement on therapy of autoimmune diseases with synthetic ligands of circadian clock genes. The existing body of knowledge demonstrates that circadian clock genes are inextricably linked to autoimmune diseases. Future research should pay attention to improve the quality of life of patients with autoimmune diseases and reduce the effects of drug preparation on the normal circadian rhythms.
32572804 Similar risk of cardiovascular events in idiopathic inflammatory myopathy and rheumatoid a 2021 Jan OBJECTIVES: To estimate the incidence of cardiovascular (CV) events in idiopathic inflammatory myopathy (IIM) compared to patients with rheumatoid arthritis (RA) and the general population. To explore the contribution of traditional CV risk factors to any difference observed. METHODS: A retrospective matched population-based cohort study was conducted using UK Clinical Practice Research Datalink (CPRD) from 1987 to 2013. The incidence of CV events was calculated for each cohort over time and compared using Cox proportional hazards models. Multivariable analyses were used to adjust for traditional CV risk factors. RESULTS: A total of 603 patients with IIM 4047 RA and 4061 healthy controls were included. The rate of CV events in IIM was significantly greater than healthy controls [hazard ratio (HR) 1.47 (95% confidence interval (CI) 1.18-1.83)] and remained significant after adjustment for CV risk factors [HR 1.38 (95% CI 1.11-1.72)]. Risk was similar between IIM and RA [HR 1.01 (95% CI 0.78-1.31)]. The rate of myocardial infarction [HR 1.61 (95% CI 1.27-2.04)] but not stroke [HR 0.92 (95% CI 0.59-1.44)] was significantly greater in IIM compared to healthy controls. After the first 5 years, the rate of CV events for RA remained significantly greater compared to the control group, but appeared to return to that of the healthy controls in the IIM group. CONCLUSION: IIM is associated with an increased risk of CV events in the first 5 years after diagnosis similar to that of RA. Beyond 5 years, the risk appears to return to that of the general population in IIM but not RA. Key Points • The excess risk of cardiovascular events in IIM is similar to that found in RA. • The excess risk of cardiovascular events is greatest in the first 5 years after diagnosis.
33372513 Protective Effect of Tangeretin and 5-Hydroxy-6,7,8,3',4'-Pentamethoxyflavone on Collagen- 2021 Jan 13 Rheumatoid arthritis (RA) is an autoimmune disease characterized by long duration and repeated relapse. This study explored the preventive effect of tangeretin (TAN) and 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone (5-HPMF) on RA, and the underlying molecular mechanism based on a rat model stimulated by bovine type II collagen (BIIC). After the intervention of TAN or 5-HPMF (TAN/5-HPMF) for 5 weeks, the RA lesions and autophagy levels of the synovial tissue were significantly reduced, and the ROS content and HO-1 expression level were down-regulated simultaneously. The relative expression levels of p-AKT and p-mTOR were down-regulated after TAN/5-HPMF feeding. Meanwhile, the relative expression level of p62 increased by more than two-fold for TAN/5-HPMF treated rats at 200 mg/kg BW comparing with those in BIIC group. Results of immunofluorescence staining and Western blotting further confirmed that TAN/5-HPMF treatment reduced BIIC-induced conversion from LC3I to LC3II. Observations under transmission electron microscope also demonstrated that the autophagy level was reduced upon TAN/5-HPMF intervention. Collectively, these results revealed that TAN and 5-HPMF prevented the pathological process of BIIC-stimulated arthritis through inhibiting the autophagy of synovial cells, achieved via the ROS-AKT/mTOR signal axis. Thus, our findings confirmed the protective potential of TAN and 5-HPMF for RA disease.
32159414 Clinical aspects in patients with rheumatoid arthritis complicated with lymphoproliferativ 2021 Jan OBJECTIVES: To identify predictive factors for lymphoproliferative disorders (LPDs) that persist after methotrexate (MTX) withdrawal (Persistent-LPD) and the optimal treatment for rheumatoid arthritis (RA) after LPD regression. METHODS: Among 3666 patients with RA treated with MTX in our department from 2006 to 2017, 26 cases of LPD that regressed after MTX withdrawal (Regressive-LPD) and 25 cases of Persistent-LPD were compared. Multivariate logistic analysis was performed to identify predictive factors for Persistent-LPD. Retention rates of biological disease-modifying antirheumatic drugs (bDMARDs) were calculated using the Kaplan-Meier Method. RESULTS: In Persistent-LPD, the incidence of diffuse large B-cell lymphoma was higher (76%). The overall 2-year survival rate was 83.9%: 95.8% for Regressive-LPD and 71.0% for Persistent-LPD. The International Prognostic Index (IPI) risk classification was useful for predicting Persistent-LPD. bDMARDs were introduced in 38 RA patients after LPD regression. Unadjusted retention rate of bDMARDs in the 51 LPD patients was significantly lower than that in the 1668 non-LPD RA patients in our bDMARD cohort (controls) (p = 0.029). The 1-year retention rates for bDMARDs were 69% and 64% for tocilizumab and abatacept, respectively vs. 46% for TNF-inhibitor (TNFi). CONCLUSION: Risk assessment using IPI predicted Persistent-LPD. After LPD regression, non-TNFi tended to have higher retention rates.
33337995 Rheumatoid factor and anti-citrullinated peptide antibodies in the general population: hep 2021 Jan OBJECTIVES: The study aimed to determine the prevalence of rheumatoid factor (RF) and anti-citrullinated peptides (ACPA), to estimate the association with hepatitis B (HBV) or C (HCV) virus infections and the 15-year risk of developing RA in a large cohort from a Northern Italian region. METHODS: In 1998, 15,907 subjects between the ages of 18 and 75 were randomly selected 1:4 for HBV and HCV testing; more recently, we tested a subgroup of sera for RF (n=2196) and ACPA (n=2525). Administrative databases were searched after 15 years for incident RA diagnoses occurring between 1998 and 2013. RESULTS: RF was positive in 8.1% of cases with 10% of RF-positive subjects having HBsAg (p=0.004) and 9% anti-HCV. ACPA were detected in 4.8% of subjects with 5% of the ACPA-positive subjects having HBsAg and 5.9% anti-HCV. Older subjects had higher positivity rates for both RF and ACPA. HBsAg and anti-HCV were detected in 5.5% and 4.3% of sera, respectively. Over 15 years, 10 RA cases were recorded (9 women, median age at diagnosis 52 years) with RF previously positive in 2/10 and ACPA in 5/10 cases. RF and ACPA were associated with relative risks for developing RA of 5.7 (adjusted for HBsAg status; 95% CI 1.2-26.3) and 13.2 (95% CI 3.8-46.3), respectively. CONCLUSIONS: Our data in a large cohort from an unselected general population confirm a higher risk of RA development associated with ACPA compared to RF. HBV exposure correlates with RF but not with ACPA positivity.
32588274 A theory-based intervention to promote medication adherence in patients with rheumatoid ar 2021 Jan INTRODUCTION/OBJECTIVES: Adherence to prescribed medication regimens is fundamental to the improvement and maintenance of the health of patients with rheumatoid arthritis. It is therefore important that interventions are developed to address this important health behavior issue. The aim of the present study was to design and evaluate a theory-based intervention to improve the medication adherence (primary outcome) among rheumatoid arthritis patients. METHODS: The study adopted a pre-registered randomized controlled trial design. Rheumatoid arthritis patients were recruited from two University teaching hospitals in Qazvin, Iran from June 2018 to May 2019 and randomly assigned to either an intervention group (n = 100) or a treatment-as-usual group (n = 100). The intervention group received a theory-based intervention designed based on the theoretical underpinnings of the health action process approach (HAPA). More specifically, action planning (making detailed plans to follow medication regimen), coping planning (constructing plans to overcome potential obstacles that may arise in medication adherence), and self-monitoring (using a calendar to record medication adherence) of the HAPA has been used for the treatment. The treatment-as-usual group received standard care. RESULTS: Data analysis was conducted based on the principle of intention to treat. Using a linear mixed-effects model (adjusted for age, sex, medication prescribed, and body mass index), the results showed improved medication adherence scores in the intervention group (loss to follow-up = 16) compared to the treatment-as-usual group (loss to follow-up = 12) at the 3-month (coefficient = 3.9; SE = 0.8) and 6-month (coefficient = 4.5; SE = 0.8) follow-up. Intervention effects on medication adherence scores were found to be mediated by some of the theory-based HAPA variables that guided the study. CONCLUSION: The results of the present study support the use of a theory-based intervention for improving medication adherence among rheumatoid arthritis patients, a group at-risk of not adhering to medication regimens. TRIAL REGISTRATION (IN IRANIAN REGISTRY OF CLINICAL TRIALS): irct.ir, IRCT20180108038271N1 Key Points • Theoretical underpinnings of the health action process approach are useful to improve medication adherence for RA patients.
32778364 [Adherence to biological therapies in patients with rheumatoid arthritis, psoriatic arthri 2021 Mar BACKGROUND: To quantify adherence to biological disease-modifying anti-rheumatic drugs (DMARD) and to determine the factors that can predict adherence in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis in daily clinical practice. METHODS: An observational, descriptive, cross-sectional and single-center study was carried out. Patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis who were in treatment with subcutaneous biological DMARD were included. Variables related to socioeconomic status, disease, biological therapy and safety were recorded. Adherence was calculated by using medication possession ratio, Compliance Questionnaire on Rheumatology and Morisky Medication Adherence Scale Questionnaire. RESULTS: One hundred twelve patients and 6 different biological DMARDs were included. Mean age was 56.8±13.2 years and 52.7% were women. The percentage of adherent patients was 59.3% in rheumatoid arthritis, 62.5% in psoriatic arthritis and 76.2% in ankylosing spondylitis. Lesser adherence was associated with the administration of the drug by a family member and/or caregiver (odds ratio: 9.6; 95% confidence interval: 1.5-61.8 (p <.05)). There were no differences between adherent and non-adherent patients in terms of the biological DMARD used. CONCLUSIONS: There are no differences in adherence to biological therapies among patients with chronic inflammatory arthropathies. Adherence correlates negatively with administration of biological DMARD by a family member and / or caregiver.
34653764 Different protective efficacies of a novel antigen-specific DNA vaccine encoding chicken t 2021 Dec Tolerizing DNA vaccines encoding key autoantigens are one of emerging strategies for the treatment of rheumatoid arthritis (RA). Among these vaccines, the most representative is pcDNA-CCOL2A1, an antigen-specific DNA vaccine encoding chicken type Ⅱ collagen (CCⅡ) with significant therapeutic and prophylactic efficacy in collagen-induced arthritis (CIA) rat models. We compared the in situ expression levels of CCOL2A1-mRNA and CCⅡ protein and the protective efficacies against CIA after a single dose (300 μg/kg) of this vaccine via intramuscular (IM), subcutaneous (SC) and intravenous (IV) vaccinations. The IM vaccination routes resulted in good protective efficacies in terms of decreasing CIA incidence and severity and significantly improved radiographic and histopathologic findings and scores of joints. Furthermore, IM, SC, and IV vaccinations markedly decreased serum levels of anti-type Ⅱ collagen (CⅡ) IgG antibodies, but only IM vaccination significantly reduced serum levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody. The vaccine exhibited a continuous CCOL2A1-mRNA expression in the tail and abdominal subcutaneous tissue injection sites, but no CCOL2A1-mRNA signal was observed in muscle. Strikingly, CCⅡ protein expression levels at the three injection sites were comparable with minimal variation. IM administration may be considered the preferred route for RA treatment in clinical practice.
33735663 Has the excess risk of acute myocardial infarction in rheumatoid arthritis relative to the 2021 Apr OBJECTIVE: To evaluate secular trend in ten-year risk of incident acute myocardial infarction (AMI) in incident rheumatoid arthritis (RA) relative to the general population. METHODS: We conducted a retrospective study of population-based incident RA cohorts with RA incidence from 1997 to 2004 in British Columbia, Canada, with matched general population comparators, using administrative health data. RA and their matched cohorts were divided according to the year of RA incidence, defined according to the first RA visit of the case definition. Incident AMI was defined as the first event occurring within 10 years from RA incidence. Secular trend was assessed using delayed-entry Cox models with an interaction term between the year of RA onset and indicator of RA vs. general population. Linear, quadratic and spline functions of year of RA onset were compared to assess possibility of nonlinear trends. The model with the lowest AIC was selected to interpret the results. Sensitivity analyses were conducted to account for potential effect of unmeasured (e.g. smoking) or partially measured (e.g. obesity) confounders in administrative data, on the interaction term. RESULTS: Overall, 23,237 RA and 46,474 general population controls experienced 1,133 and 1,606 incident AMIs, respectively. A linear Cox model was selected as the model best fitting the AMI events. Overall, RA patients were found to have a 21% higher risk of AMI than the matched general population controls [1.21 (1.10, 1.32); p < 0.001]. A significant linear decline in risk of AMI was observed in RA patients [0.94 (95% CI 0.91, 0.97) p = <0.0001], and in the general population [0.93 (0.91, 0.95); p = <0.0001]. The change in AMI risk over time did not differ in RA compared to the general population [p-value of interaction term=0.49]. Our results remained similar after adjusting for the potential effect of confounders on the interaction term, and no difference in the change in risk of AMI over time was observed between RA and the general population. CONCLUSION: Our findings suggest a decline in 10-year risk of AMI in RA, and in the general population. The decline in the risk of AMI over time did not differ between RA and the general population, such that the excess risk of AMI in RA relative to the general population, has remained the same.
34397890 Biologic therapy for amyloid A amyloidosis secondary to rheumatoid arthritis treated with 2021 Aug 13 INTRODUCTION: Secondary amyloidosis is a rare complication of rheumatoid arthritis (RA) that is histologically characterized by the deposition of amyloid fibrils in target organs, such as the kidneys and gastrointestinal tract. Controlling the inflammatory response is essential to prevent organ dysfunction in amyloid A (AA) amyloidosis secondary to RA, and no clear treatment strategy exists. PATIENT CONCERNS AND DIAGNOSIS: A 66-year-old woman with RA, who had been treated with disease-modifying anti-rheumatic drugs for 1 year, presented with recurrent abdominal pain and prolonged diarrhea. Endoscopy showed chronic inflammation, and colon tissue histology confirmed AA amyloidosis. INTERVENTIONS AND OUTCOMES: After tocilizumab therapy was begun, her diarrhea and abdominal pain subsided, and articular symptoms improved. Biologic drugs for RA have been used in patients with secondary AA amyloidosis, including tumor necrosis factor and Janus kinase inhibitors, interleukin 6 blockers, and a T cell modulator. Here, we systematically review existing case reports and compare the outcomes of RA-related AA amyloidosis after treatment with various drugs. CONCLUSION: The data indicate that biologic drugs like tocilizumab might be treatments of choice for AA amyloidosis secondary to RA.
33624882 Role of natural products in alleviation of rheumatoid arthritis-A review. 2021 Apr Rheumatoid arthritis (RHA) is one of the most prevalent complex, chronic, inflammatory diseases, manifested by elevated oxidative stress and inflammatory biomarkers. Prolonged administration of NSAIDs, steroids, and DMARDs, used in the treatment of RHA, is associated with deleterious side effects. This necessitates the urge of new and safe approaches for RHA management, based on the complementary and alternative system of medicine. Documented evidences have suggested that supplementation with nutritional, dietary, and herbal components; can play a crucial role as an adjuvant, in the alleviation of the RHA symptoms, through their influence on the pathological inflammatory processes. Dietary phenolic compounds, flavonoids, carotenoids, and alkaloids with their ability to modulate prooxidant and pro-inflammatory pathways, have been effective in delaying the arthritic disease progression. Moreover, in scientific explorations, herbs containing phenolic compounds, alkaloids, carotenoids flavonoids, spices such as ginger, turmeric, Ayurvedic formulations, different diets such as Mediterranean diet, vegan diet, beverages, and oils such as sesame oil, rice bran oil, vitamins, and probiotics are proven to modulate the action of inflammatory molecules, involved in RHA pathology. Subsequently, the purpose of this review article is to summarize various in vitro, in vivo, and clinical studies in RHA, which have documented remarkable insights into the anti-inflammatory, antioxidant, analgesic, and immunomodulatory, bone erosion preventing properties of dietary, nutritional, and herbal components with the focus on their molecular level mechanisms involved in RHA. Even though major findings were derived from in vitro studies, several in vivo and clinical studies have established the use of diet, herbal, and nutritional management in RHA treatment. PRACTICAL APPLICATIONS: Thickening of the synovial membrane, bone erosion, and cartilage destruction is known to trigger rheumatoid arthritis causing inflammation and pain in bone joints. Continuous intake of NSAIDs, steroids, and DMARD therapy are associated with detrimental side effects. These side effects can be overcome by the use of dietary, nutritional, and herbal interventions based on the complementary and alternative therapy. This concept portrays the food components and other natural components having the potential to promote health, improve general well-being, and reduce the risk of RHA.
34721413 Elevated Peripheral T Helper Cells Are Associated With Atrial Fibrillation in Patients Wit 2021 Patients with rheumatoid arthritis (RA) have a significantly high risk of atrial fibrillation (AF). This study aimed to compare the absolute and relative changes in peripheral T cells in patients with RA who were also affected with and without AF. To help make an early diagnosis and prevent the initiation and progression of AF, the changes in the lymphocyte subsets were assessed in RA patients with and without AF. A propensity score matching (PSM) system (1:3) was used to perform a matched case-control study with 40 RA-AF cases and 120 RA controls. Changes in the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-citrullinated peptide antibody (ACPA), and rheumatoid factor (RF) were examined. The percentage and absolute number of T, B, natural killer (NK), T helper (Th)1, Th2, Th17, and T-regulatory (Treg) cells in the peripheral blood of patients with and without RA-AF were determined using flow cytometry. Univariate and multivariate analyses were performed to determine the association between peripheral lymphocytes and RA-AF. Demographic data, ESR, CRP, ACPA, and the percentage, as well as the absolute value of B, NK, Th2, and Treg cells, showed no significant differences between the propensity score-matched groups of RA and RA-AF. Meanwhile, the absolute number and percentage of Th1 cells, the absolute number of Th17 cells, the ratio of Th1/Treg, Th17/Treg, and RF were significantly higher in patients with RA-AF than those in the control groups (P < 0.05). Univariate and multivariate logistic regression analyses also revealed that the percentage of Th1 cells, the absolute number of Th17 cells, and the ratio of Th1/Treg were associated with a significantly higher risk of AF. This PSM study demonstrated that the incidence of AF was higher in RA patients with Th cell immunological derangements.
33848528 Intra-Articular Dual Drug Delivery for Synergistic Rheumatoid Arthritis Treatment. 2021 Jul Systemic rheumatoid arthritis (RA) regimens fail to attain effective drug level at the affected joints and are associated with serious side effects. Herein, an attempt made to improve therapeutic outcomes of both leflunomide (LEF) which is a disease modifying antirheumatic and dexamethasone (Dex) through local delivery of combination therapy by intra-articular route. LEF and Dex were encapsulated in nanostructured lipid carriers (NLCs) and PLGA nanoparticles (NPs), respectively. Both nanocarriers were loaded into chitosan/β glycerophosphate (CS/βGP) thermo-sensitive hydrogels and injected intra-articularly in adjuvant induced RA rat model. Particle size of LEF NLCs and selected Dex NPs formulations were 200 and 119 nm, respectively. Dex NPs and LEF NLCs showed a sustained release profile for up to 58 and 17 days, respectively. After 14 days of treatment remarkable joint healing was observed for groups treated with Dex NPs in combination with either free LEF or LEF NLCs in CS/βGP hydrogel. Joint diameter measurements, TNF α levels and histopathological examination of dissected joints showed comparable values to the negative control group. This might be attributed to the synergistic effect of drug combination besides the ability of nanocarriers loaded hydrogel to prolong joint residence time and enhance joint healing potential.
32929463 Predictors of joint damage progression and stringent remission in patients with establishe 2021 Jan 5 OBJECTIVES: To study if clinical, radiographic and MRI markers can predict MRI and radiographic damage progression and achievement of stringent remission in patients with established RA in clinical remission followed by a targeted treatment strategy. METHODS: RA patients (DAS28-CRP <3.2, no swollen joints) receiving conventional synthetic DMARDs were randomized to conventional or MRI-targeted treat-to-target strategies with predefined algorithmic treatment escalations. Potentially predictive baseline variables were tested in multivariate logistic regression analyses. RESULTS: In the 171 patients included, baseline MRI osteitis independently predicted progression in MRI erosion [odds ratio (OR) 1.13 (95% CI 1.06, 1.22)], joint space narrowing [OR 1.15 (95% CI 1.07, 1.24)] and combined damage [OR 1.23 (95% CI 1.13, 1.37)], while tenosynovitis independently predicted MRI erosion progression [OR 1.13 (95% CI 1.03, 1.25)]. A predictor of radiographic erosion progression was age, while gender predicted progression in joint space narrowing. Following an MRI treat-to-target strategy predicted stringent remission across all remission definitions: Clinical Disease Activity Index remission OR 2.94 (95% CI 1.25, 7.52), Simplified Disease Activity Index remission OR 2.50 (95% CI 1.01, 6.66), ACR/EULAR Boolean remission OR 5.47 (95% CI 2.33, 14.13). Similarly, low tender joint count and low patient visual analogue scale pain and global independently predicted achievement of more stringent remission. CONCLUSION: Baseline MRI osteitis and tenosynovitis were independent predictors of 2 year MRI damage progression in RA patients in clinical remission, while independent predictors of radiographic damage progression were age and gender. Following an MRI treat-to-target strategy, low scores of patient-reported outcomes and low tender joint count predicted achievement of stringent remission. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov), NCT01656278.
33605862 Contribution of Ultrasonography of Hands and Wrists in Early Rheumatoid Arthritis. 2021 OBJECTIVES: Early diagnosis and management of rheumatoid arthritis (RA) have improved the outcome of patients. In the last decade, musculoskeletal Ultrasonography (MSUS) had demonstrated its superiority over clinical examination in detecting synovitis in RA. We conducted this present study in order to assess the added value of MSUS in diagnosing early RA. METHODS: A cross-sectional study was conducted, including one hundred patients diagnosed RA based on the physician's opinion and presenting with inflammatory arthralgia or swollen joints for more than 6 weeks and less than 2 years. Patients underwent clinical, laboratory, and radiographic examination. MSUS was performed by a radiologist blinded to clinical findings assessing 22 joints of hands. A US ACR/EULAR 2010 score was calculated by replacing the swollen joints of hands with those expressing synovitis in Greyscale US. Agreement between clinical and US ACR/EULAR score was assessed. RESULTS: Among the 2200 joints scanned by the US, synovitis was detected in 81% of patients, an intra-articular effusion in 36% patients, and PD signals in 51% of patients. Flexor tenosynovitis was present in 55% of patients and extensor tenosynovitis in 59% of patients. Synovitis and PD signals were more often detected in wrists. PD mode was found to be correlated with CRP results (r=0,302, p=0,023). The MSUS assessment has demonstrated synovitis on 71% (N=22) patients who were free of swollen joints on clinical examination. Through 13 patients expressing monoarthritis at clinical examination, 69% (N=9) patients were reclassified with oligo or polyarthritis. By adding US data, a further 13 patients accomplished the ACR/EULAR score. A good level of agreement was found between clinical and US ACR/EULAR criteria (k=0,684, p=0,001). CONCLUSION: MSUS is an inexpensive and accessible examination tool, which should be considered in patients in the onset of an inflammatory rheumatic disease in order to benefit of the window of opportunity and reach remission.