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ID PMID Title PublicationDate abstract
35276806 Vitamin D Concentrations at Birth and the Risk of Rheumatoid Arthritis in Early Adulthood: 2022 Jan 20 BACKGROUND: Low vitamin D in pregnancy may impair the development of the fetal immune system and influence the risk of later development of rheumatoid arthritis (RA) in the offspring. The aim was to examine whether lower 25-hydroxyvitamin D3 (25(OH)D) concentrations at birth were associated with the risk of developing RA in early adulthood. METHODS: This case-cohort study obtained data from Danish registers and biobanks. Cases included all individuals born during 1981-1996 and recorded in the Danish National Patient Register with a diagnosis of RA with age >18 years at first admission. The random comparison consisted of a subset of Danish children. Vitamin D concentrations were measured in newborn dried blood. In total, 805 RA cases and 2416 individuals from the subcohort were included in the final analysis. Weighted Cox regression was used to calculate hazard ratio (HR). RESULTS: The median (interquartile rage (IQR)) 25(OH)D concentrations among cases were 24.9 nmol/L (IQR:15.4;36.9) and 23.9 nmol/L (IQR:13.6;36.4) among the subcohort. There was no indication of a lower risk of RA among individuals in the highest vitamin D quintile compared with the lowest (HRadj.:1.21 (0.90;1.63)). CONCLUSION: The risk of RA in early adulthood was not associated with vitamin D concentrations at birth.
34534283 Effects of biologics on reducing the risks of total knee replacement and total hip replace 2022 May 5 OBJECTIVES: RA damages the joints and increases the risks of total knee replacement (TKR) and total hip replacement (THR). However, the benefits of biologics in preventing TKR or THR remain unclear. METHODS: This retrospective nationwide study used the 2000-2013 claims-based National Health Insurance dataset. Biologics are reimbursed for refractory cases. The risks of TKR and THR in the biologic cohort were compared with those of an age- and sex-matched csDMARD cohort. A multivariate Cox regression model was used to investigate the benefits of bDMARDs for TKR and THR. RESULTS: TKR was performed in 5979 biologic cases and 11 958 matched controls, of which 249 (4.16%) and 871 (7.28%) cases received TKR, respectively. THR was performed in 6245 biologic cases and 12 490 matched controls, of which 159 (2.55%) and 516 (4.13%) cases had THR, respectively. The biologic cohort had significantly lower incidence rates of TKR (11.73 vs 16.33/1000 person-years, P < 0.001) and THR (7.09 vs 9.16/1000 person-years, P < 0.001). After adjustment for confounding factors, the regular bDMARD subgroup (average dose >0.95 defined daily dose/day) had significantly lower risks of TKR (aHR: 0.55, 95% CI: 0.38, 0.81) and THR (aHR: 0.63, 95% CI: 0.40, 0.98). Those without MTX use, with steroid use, with biologic switch, and overlapping antiphospholipid syndrome had significantly higher risks of TKR and THR. CONCLUSIONS: Compared with the csDMARD cohort, the risks of TKR and THR in the bDMARD cohort were the same as those in the low-to-moderate dose subgroups and significantly lower in those with regular bDMARD use.
35213743 Resolution of Th/Tc17-driven inflammation during anti-TNFα treatment of rheumatoid arthri 2022 Jan Rheumatoid arthritis (RA) is a chronic multisystem disease with a complex immunopathology. Its inflammatory state is dominated by pro-inflammatory cytokines such as TNFα and activated Th1/Th17. Only proportion of patients achieve clinical remission despite potent biologics targeting these pathways. This study investigated the resolution of inflammation in RA patients (naïve for biologics) receiving TNFα inhibitors (TNFi) and evaluated the biological mechanisms behind treatment response and assessed them using clinical scoring systems. The majority showed a good clinical response after six months (6M) and a significant drop in DAS28-CRP (P ≤ .002), CDAI (P ≤ .0001) and RheumXpert (P ≤ .0001). Before treatment, the patients demonstrated a chronic innate and adaptive inflammatory state. The improved clinical condition was reflected with a decrease in Th17/Tc17 (P ≤ .05) and an increase in Tregs after 6M (P ≤ .05). Using a logistic regression model on serum data, IL-6, IL-18, IL-21, IL-22, IFNγ and TNFα were identified as the main contributing biomarkers in the chronic inflammatory state of RA. A specific test score (STS) was defined and converted to a single cytokine composite test score (CCTS), which showed the disease outcome on a scale 0-100, providing sensitivity and specificity of ≥90%. Thus, the immunological complexity in RA is driven by a complex interplay of pro-inflammatory cytokines and effector T-cell response dominated by Th17/Tc17. In addition, the resolution of inflammation could be linked to a partially Treg-driven homeostatic innate immune response. Therefore, a more complex therapeutic approach against the above markers might be of value to obtain full clinical remission in the future.
34655004 Functional capacity vs side effects: treatment attributes to consider when individualising 2022 Mar INTRODUCTION: Individualisation of rheumatoid arthritis (RA) treatment needs to take account of individual patients' preferences to increase patient-centeredness in treatment decisions. The aim of this study was to identify patient-relevant treatment attributes to consider when individualising treatment for patients with RA. METHOD: Patients with RA in Sweden were invited to rank the most important treatment attributes in an online survey (April to May 2020). Semi-structured interviews were conducted (October to November 2020) to further identify and frame potential attributes for shared decision-making. The interviews were audio-recorded, transcribed and analysed using thematic framework analysis. Patient research partners and rheumatologists supported the selection and framing of the treatment attributes across the assessment. RESULTS: The highest ranked attributes (N = 184) were improved functional capacity, reduced inflammation, reduced pain and fatigue and the risk of getting a severe side effect. The framework analysis revealed two overarching themes for further exploration: treatment goals and side effects. 'Treatment goals' emerged from functional capacity, revealing two dimensions: physical functional capacity and psychosocial functional capacity. 'Side effects' revealed that mild and severe side effects were the most important to discuss in shared decision-making. CONCLUSIONS: Functional capacity (physical and psychosocial) and potential side effects (mild and severe) are important treatment attributes to consider when individualising RA treatment. Future research should assess how patients with RA weigh benefits and risks against each other, in order to increase patient-centeredness early on the treatment trajectory.
33931278 Long-term outcomes and duration of outdoor ambulation following primary total knee arthrop 2022 Mar BACKGROUND: The medical treatment of rheumatoid arthritis (RA) has made remarkable progress with the introduction of methotrexate and biological agents. However, there have been few reports of long-term results of total knee arthroplasty (TKA) for RA since the introduction of these drugs. Ambulation is an important form of exercise for maintaining health. We investigated the long-term outcomes and the ability to walk outdoors following TKA in patients with RA. METHODS: We retrospectively reviewed 142 patients with RA (201 knees) who had undergone primary TKA. The mean follow-up was 10.6 years. RESULTS: Markers of RA disease activity all improved significantly postoperatively. Mean Japanese Orthopedic Association scores improved from 49.3 points before surgery to 81.8 at follow-up. The mean maximum flexion angle improved from 107.8° to 112.9°. The causes of TKA revision comprised 2 mechanical loosening, 1 late infection, and 1 fracture of the femoral condyle. The survival rate of TKA was 96.6% at 15 years. Fifty-five patients were not able to walk outdoors. The rate of inability to ambulate outdoors was 38.3 per 1000 person-years. The survival rate of ability to ambulate outdoors were 48.8% at 15 years. Preoperative advanced age, low body weight, steroid use and non-use of biologics were identified as risk factors for inability to ambulate outdoors. CONCLUSIONS: Although the cumulative survival rate of TKA implants was as good as 96.6% in 15 years, the cumulative rate of ability to ambulate outdoors was only 48.8%. The reason for the inability to walk outdoors was thought to be mainly due to deterioration of RA, comorbidity or muscular weakness associated with aging, rather than knee dysfunction.
34695882 Trends in hospital visits and healthcare costs of gout and seropositive rheumatoid arthrit 2022 May BACKGROUND/AIMS: We examined temporal trends in the rate of gout and seropositive rheumatoid arthritis (RA) hospital visits and healthcare costs in Korea. METHODS: We conducted a serial cross-sectional analysis of Korean national healthcare claims. We calculated the annual increase in hospital visits (emergency department [ED] visits, outpatient visits, and hospitalizations) and total healthcare costs per visit. RESULTS: From 2010 to 2017, the annual rates of ED visits, outpatient visits, and hospitalizations for gout increased from 6.28 to 21, from 638.38 to 1059.55, and from 12.37 to 15.6 per 100,000 persons, respectively. Before 2013, ED visits for gout were most common in patients over 70 years old, but they were most common in those aged between 30 and 49 years after 2013. The number of patients with ED visits, outpatient visits, and hospitalizations for RA from 2010 to 2017 increased from 1.25 to 1.87, from 219.04 to 307.49 and from 8.44 to 12.32 per 100,000 persons, respectively. However, there was no increase in the prevalence of ED visits for RA in any age group except for those older than 70 years. The cost per ED visit for gout significantly decreased from 496.3 to 273.6 US dollar during the study period. There was no significant change in the cost per ED visit for RA between 2010 and 2017. CONCLUSION: There was a large increase in ED visits for gout during the study period. Further studies are needed to analyze the reason behind increased ED visits for gout and suggest ways on how to improve gout care.
34373899 Has the incidence of total joint arthroplasty in rheumatoid arthritis decreased in the era 2022 May 5 OBJECTIVES: To determine whether the introduction of biological DMARDs (bDMARDs) was associated with reduced incidences of total hip and knee arthroplasty (THA/TKA) among patients with RA compared with OA. METHODS: Using a population-based cohort in British Columbia, Canada, RA and OA patients diagnosed between 1995 and 2007 were divided into semi-annual cohorts according to diagnosis date. For each cohort, we calculated 8-year incidence rates of THA and TKA. We compared levels and trends of THA/TKA incidence in RA/OA patients diagnosed during pre-bDMARDs (1995-2001) and post-bDMARDs (2003-2007) periods using interrupted time-series analysis, adjusting for baseline characteristics. Adjusted 8-year total joint arthroplasty incidence estimated for RA/OA cohorts diagnosed five years after bDMARDs introduction were compared with expected rates assuming no bDMARDs introduction, based on extrapolation of pre-bDMARDs trends. RESULTS: We identified 60 227 RA and 288 260 OA incident cases. For cohorts diagnosed pre-bDMARDs, 8-year THA/TKA incidence rates increased over time in both RA and OA. For cohorts diagnosed post-bDMARDs, these rates decreased over time in RA but continued to increase for OA. For RA, differences between the post- and pre-bDMARDs secular trends in incidence rates were -0.49 (P = 0.002) for THA and -0.36 (P = 0.003) for TKA, compared with +0.40 (P = 0.006) and +0.54 (P < 0.001), respectively, for OA. For RA cohorts diagnosed five years after bDMARDs introduction, 8-year incidences were 26.9% and 12.6% lower for THA and TKA, respectively, than expected rates. In contrast, corresponding rates in OA were higher by 11.7% and 16.6%, respectively. CONCLUSION: Arthritis onset after bDMARDs introduction is associated with a significant reduction in THA/TKA incidence in RA, but not in OA. The reduction reflects a significant improvement in RA treatment during the biological era.
34251303 Comparison of the efficacy and safety of LBAL, a candidate adalimumab biosimilar, and adal 2022 May OBJECTIVES: To evaluate the similarities between LBAL (adalimumab biosimilar candidate) and the adalimumab reference product (ADL) in terms of efficacy and safety, including immunogenicity, in patients with active rheumatoid arthritis despite methotrexate treatment. METHODS: This phase III, multicentre, randomised, double-blind, parallel-group, 56-week study was conducted in Japan and Korea. During the first 24 weeks, patients subcutaneously received 40 mg of LBAL or ADL every two weeks (LBAL and ADL groups). During the subsequent 28 weeks, the LBAL group patients and half of the ADL group patients received LBAL (L-L and A-L arms). The remaining ADL group patients continued to receive ADL (A-A arm). The primary efficacy endpoint was the change from baseline in disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) at Week 24. American College of Rheumatology (ACR) response rates, adverse events (AEs), and anti-drug antibody (ADA) were also assessed. RESULTS: In total, 383 patients were randomised. The least squares (LS) mean changes from baseline in DAS28-ESR at Week 24 were -2.45 and -2.53 in the LBAL (n=191) and ADL (n=190) groups, respectively. The 95% confidence interval (CI; -0.139, 0.304) of the difference (0.08) was within the pre-specified equivalence margin (-0.6, 0.6). Up to Week 52, the decreases in DAS28-ESR were maintained in all three arms. No notable differences in ACR20/50/70 were observed. The AE and ADA incidences were comparable between the arms. CONCLUSIONS: LBAL was equivalent in efficacy and comparable in safety, including immunogenicity, to ADL. Switching from ADL to LBAL did not impact on efficacy and safety.
35256729 TNF inhibitors increase the risk of nontuberculous mycobacteria in patients with seroposit 2022 Mar 7 The aim of this study is to examine the impact of tumor necrosis factor inhibitors (TNFI) on nontuberculous mycobacterium (NTM) infection in rheumatoid arthritis (RA) patients in a mycobacterium tuberculosis (MTB) endemic area. We selected 1089 TNFI-treated RA patients and 4356 untreated RA patients using propensity-matching analysis according to age, gender, and Charlson comorbidity index using the Korean National Health Insurance Service database from July 2009 to December 2010. Both groups were followed-up until the end of 2016 to measure the incidence of mycobacterial diseases. The incidence rate of NTM in TNFI-treated RA group was similar to those of MTB (328.1 and 340.9 per 100,000 person-years, respectively). The adjusted hazard ratio (aHR) of NTM for TNFI-treated RA compared to untreated RA was 1.751(95% CI 1.105-2.774). The risk of TNFI-associated NTM in RA was 2.108-fold higher among women than men. The age-stratified effects of TNFI on NTM development were significantly high in RA patients aged 50-65 years (aHR 2.018). RA patients without comorbidities had a higher incidence of NTM following TNFI treatment (aHR 1.742). This real-world, observational study highlights the need to increase awareness of NTM in TNFI-treated RA patients in an MTB endemic area.
34107851 A musculoskeletal ultrasound program as an intervention to improve disease modifying anti- 2022 Jan Objectives: To evaluate the effect of a musculoskeletal ultrasound programme (MUSP) applying real-time ultrasonography with reinforcement of findings by a rheumatologist on improving disease-modifying anti-rheumatic drugs (DMARDs) adherence in rheumatoid arthritis (RA).Method: Eligible RA patients with low adherence score (< 6) on the 8-item Morisky Medication Adherence Scale (MMAS-8) were randomized to either an intervention group (receiving MUSP at baseline) or a control group (no MUSP), and followed up for 6 months. Adherence measures (patient-reported and pharmacy dispensing records) and clinical efficacy data were collected. The MUSP's feasibility and acceptability were assessed.Results: Among 132 recruited RA patients, six without baseline visits were excluded; therefore, 126 patients were analysed (62 intervention and 64 control). The primary outcome (proportion of patients with 1 month MMAS-8 score < 6) was significantly smaller (p = 0.019) in the intervention (35.48%) than the control group (56.25%). However, 3 and 6 month adherence and clinical efficacy outcomes were not significantly different between the two groups (all p > 0.05). All 62 patients completed the MUSP (mean time taken, 9.2 min), with the majority reporting moderately/very much improved understanding of their joint condition (71%) and the importance of regularly taking their RA medication(s) (79%). Most patients (90.3%) would recommend the MUSP to another RA patient.Conclusions: The MUSP improved RA patients' DMARDs adherence in the short term and was feasible and well accepted by patients. Future studies could evaluate whether repeated feedback using MUSP could help to sustain the improvement in DMARD adherence in RA patients, and whether this may be clinically impactful and cost-effective.
35346353 Effect of resistance exercise on serum leptin levels in a prospective longitudinal study o 2022 Mar 26 BACKGROUND: Exercise has an anti-inflammatory effect and reduces fat mass. Leptin has been known to be proinflammatory adipokines mainly produced by adipocytes. However, few studies have investigated the association between exercise and changes in serum leptin levels of patients with RA. This study evaluated the effect of an individualized resistance exercise on inflammatory markers including leptin as well as muscle strength and exercise capacity in patients with rheumatoid arthritis (RA). METHODS: A total of 42 age- and sex-matched participants were assigned to a resistance exercise program (60 min, once a week for 12 weeks, and self-exercise twice a week) or to a control group. Muscle strength, exercise capacities, and inflammatory markers such as cytokines and adipokines were assessed at baseline and at 12 weeks follow-up. Longitudinal changes in muscle strength, exercise capacity, cytokines, and adipokines between groups were tested with repeated measures analysis of variance or using the generalized estimating equation, with adjustment for baseline disease activity score 28-C response protein as a covariate. RESULTS: A total of 37 of 42 female patients with RA completed this prospective intervention study. Grip strength improved significantly in the exercise group (P < 0.05), while no between-group changes were found. Quadriceps contraction power (P for group-time interaction = 0.035 for the right side and P for group-time interaction = 0.012 for the left side) and 6-minute walking distance (P for group-time interaction = 0.021) were all improved significantly in the exercise group compared with the control group. In addition, serum leptin levels were significantly decreased in the exercise group compared with the control group (P for group-time interaction = 5.22 × 10(-5)), but not the other cytokines or adipokines. The change in serum leptin levels correlated with the changes in fat mass (Rho = 0.491, P= 0.015) and visceral fat area (Rho = 0.501, P= 0.013). CONCLUSION: In addition to muscle strength and exercise capacity, the 12 weeks of individualized resistance exercise reduced serum leptin levels in keeping with body fat mass or visceral fat area, suggesting that serum leptin levels might be a surrogate marker of exercise in RA.
34921986 Impact of photodynamic therapy as an adjunct to non-surgical periodontal treatment on clin 2022 Mar PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) as an adjunct to non-surgical periodontal therapy on the clinical periodontal and biochemical parameters among patients with rheumatoid arthritis (RA) having periodontitis. METHODS: A total of 50 RA patients with periodontitis were included. The subjects were equally divided into two groups: Group A - scaling and root planning (SRP) + PDT; Group B - SRP only, respectively. Plaque score (PS), bleeding on probing (BOP), and pocket depth (PD) were estimated. The biochemical parameters included the assessment of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and rheumatoid factors (RFs). RESULTS: Plaque scores and BOP significantly reduced in both the groups at both 6 and 12 weeks with significant difference between both the groups at 6 weeks follow up (p<0.05). On inter-group comparison, there was a statistically significant reduction seen for BOP in Group A at 12 weeks (p<0.001). PD significantly reduced in both the groups at both time points; however, significant reduction was noted for Group A compared to Group B (p<0.01). IL-6 and TNF-α significantly reduced in both the groups at 6 and 12 weeks follow up. However, the proinflammatory cytokine levels significantly reduced in group A as compared to group B at both 6 and 12 weeks (p<0.05). GCF levels of RF did not show any change in either of the groups at either time point or between the groups (p>0.05). CONCLUSION: PDT significantly reduced the proinflammatory burden in terms of periodontal attachment level and bleeding on probing within the periodontal inflammatory pockets in patients having RA.
35022146 Functional coding haplotypes and machine-learning feature elimination identifies predictor 2022 Jan BACKGROUND: Major challenges in large scale genetic association studies include not only the identification of causative single nucleotide polymorphisms (SNPs), but also accounting for SNP-SNP interactions. This study thus proposes a novel feature engineering approach integrating potentially functional coding haplotypes (pfcHap) with machine-learning (ML) feature selection to identify biologically meaningful, possibly causative genetic factors, that take into consideration potential SNP-SNP interactions within the pfcHap, to best predict for methotrexate (MTX) response in rheumatoid arthritis (RA) patients. METHODS: Exome sequencing from 349 RA patients were analysed, of which they were split into training and unseen test set. Inferred pfcHaps were combined with 30 non-genetic features to undergo ML recursive feature elimination with cross-validation using the training set. Predictive capacity and robustness of the selected features were assessed using six popular machine learning models through a train set cross-validation and evaluated in an unseen test set. FINDINGS: Significantly, 100 features (95 pfcHaps, 5 non-genetic factors) were identified to have good predictive performance (AUC: 0.776-0.828; Sensitivity: 0.656-0.813; Specificity: 0.684-0.868) across all six ML models in an unseen test dataset for the prediction of MTX response in RA patients. INTERPRETATION: Majority of the predictive pfcHap SNPs were predicted to be potentially functional and some of the genes in which the pfcHap resides in were identified to be associated with previously reported MTX/RA pathways. FUNDING: Singapore Ministry of Health's National Medical Research Council (NMRC) [NMRC/CBRG/0095/2015; CG12Aug17; CGAug16M012; NMRC/CG/017/2013]; National Cancer Center Research Fund and block funding Duke-NUS Medical School.; Singapore Ministry of Education Academic Research Fund Tier 2 grant MOE2019-T2-1-138.
35265215 Ultrasound imaging tracking of mesenchymal stem cells intracellularly labeled with biosynt 2022 Rationale: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and damage to articular tissues that can lead to irreversible joint damage and progressive disability. The multipotent mesenchymal stem cells (MSCs) play an important role in immune disorders and tissue regeneration. However, their immunosuppressive effects and the underlying mechanisms are largely unclear due to the lack of tools for real-time imaging of MSCs in vivo. Gas vesicles (GVs) are biosynthetic nanobubbles that are ejected from aquatic microbes, such as bacteria and archaea, and have an excellent ultrasound imaging capacity. Methods: We harvested MSCs from the bone marrow of Sprague Dawley (SD) rats. Then, GVs were synthesized and incubated with MSCs to obtain intracellularly labeled MSCs. We firstly tested the ultrasound imaging of GV@MSCs in vitro and in vivo and then explored the therapeutic effect of GV@MSCs combined with methotrexate (MTX) in RA rats. Results: These GV@MSCs showed significant contrast-enhanced ultrasound signals without a loss of viability and differentiation capacity. In addition, the GV@MSCs could be imaged in real-time for 5 days using ultrasound both in vitro and in vivo, making it possible to visually track their migration and homing to the joint cavity from the subcutaneous layer of lateral malleolus joints in the injected RA rats. Furthermore, GV@MSCs significantly enhanced the curative effect of methotrexate (MTX) against RA, resulting in decreased paw thickness, lower arthritis index score, reduced bone erosion and cartilage destruction, compared to the PBS, free MTX, and GV@MSCs groups. Conclusion: We developed a novel therapeutic strategy against RA using GVs-loaded MSCs that can be tracked in vivo in real-time.
34906696 Impact of multimorbidity on disease modifying antirheumatic drug therapy in early rheumato 2022 May OBJECTIVE: Multimorbidity is frequent in rheumatoid arthritis (RA) and could interfere with the therapeutic response. The aim of this study was to evaluate multimorbidity in the French cohort of early arthritis, the ESPOIR cohort, and its possible impact on the therapeutic response. METHODS: We included patients fulfilling 2010 ACR/EULAR criteria for RA. An adapted MultiMorbidity Index (aMMI) was developed. Each patient was assigned scores of binary aMMI (0=no comorbidity, 1=at least 1 comorbidity) and counted and weighted aMMI. The primary endpoint was achievement of Clinical Disease Activity Index (CDAI) low disease activity after initiation of a first disease-modifying antirheumatic drug (DMARD) according to the aMMI. We collected data from the visit preceding the first DMARD initiation and the visit after at least 3 months of treatment. The impact of aMMI on therapeutic maintenance at 1, 3, 5 and 10 years was evaluated. RESULTS: Analyses involved 472 patients: 302 (64%) had at least 1 comorbidity. Overall, 45.3% and 44.7% with binary aMMI=0 or 1, respectively (non-significant), achieved CDAI low disease activity. Similar results were found with counted and weighted aMMI. Therapeutic maintenance was significantly better with binary aMMI=1 than binary aMMI=0 (OR at 10 years=14.0 [CI 95% 3.3-59.4]). Increased counted aMMI was associated with increased probability of still being on the first initiated DMARD at each time point. CONCLUSION: In the ESPOIR cohort, therapeutic response to a first DMARD was not affected by multimorbidity but therapeutic maintenance was better in multimorbid patients.
34689406 Lactiplantibacillus plantarum HG20 attenuates II type collagen-induced rheumatoid arthriti 2022 Mar AIMS: This study aimed to explore the therapeutic effects of Lactiplantibacillus plantarum HG20 (HG20) on collagen-induced arthritis (CIA) rats and its mechanism. METHODS AND RESULTS: CIA rats were established by injecting bovine type II collagen for 7 days, and treated by intragastric administration HG20 for 21 days. The foot palm temperature and arthritis score were measured once a week. The pathological changes in the knee joint were observed by hematoxylin and eosin staining. The levels of cytokines were detected by enzyme linked immunosorbent assay, and the effects of HG20 on inflammatory and apoptosis pathway of spleen cells were detected by western blot analysis. The results indicated that HG20 reduced the joint swelling degree and foot palm temperature, inhibited the development of joint histopathology, decreased the levels of pro-inflammatory cytokines, down-regulate the expression of pro-inflammatory cytokines by nuclear factor kappa-B pathway, and inhibited the apoptosis of spleen cells by inhibiting phosphatidylinositol 3-kinase/protein kinase B pathway and regulating apoptosis pathways. CONCLUSIONS: HG20 had an adjuvant therapeutic effect on arthritis in CIA rats, and its mechanism might be related to the inflammatory and apoptosis pathway. SIGNIFICANCE AND IMPACT OF STUDY: These results revealed that HG20 could be used as a functional probiotic in the field of food and medical, and which played a potential role in the prevention and treatment of arthritis.
35172859 Prediction of flare following remission and treatment withdrawal in early rheumatoid arthr 2022 Feb 16 BACKGROUND: Drug-free remission is a desirable goal in rheumatoid arthritis (RA) for both patients and clinicians. The aim of this post hoc analysis was to investigate whether clinical and magnetic resonance imaging (MRI) variables in patients with early RA who achieved remission with methotrexate and/or abatacept at 12 months could predict disease flare following treatment withdrawal. METHODS: In the AVERT study of abatacept in early RA, patients with low disease activity at month 12 entered a 12-month period with all treatment discontinued (withdrawal, WD). This post hoc analysis assessed predictors of disease flare at WD+6months (mo) and WD+12mo of patients with Disease Activity Score in 28 joints (DAS28)-defined remission (DAS28[C-reactive protein (CRP)] <2.6) at withdrawal using univariate and multivariable regression models. Predictors investigated included the Health Assessment Questionnaire-Disability Index (HAQ-DI), pain, Patient Global Assessment; MRI synovitis, erosion, bone edema, and combined (synovitis + bone edema) inflammation scores. RESULTS: Remission was achieved by 172 patients; 100 (58%) and 113 (66%) patients had experienced a flare at WD+6mo and WD+12mo, respectively. In univariate analyses, higher HAQ-DI and MRI synovitis, erosion, bone edema, and combined inflammation scores at WD were identified as potential predictors of flare (P ≤ 0.01). In multivariable analysis, high scores at WD for HAQ-DI and MRI erosion were confirmed as independent predictors of flare at WD+6mo and WD+12mo (P < 0.01). CONCLUSION: In patients with early RA achieving clinical remission, patient function (HAQ-DI), and MRI measures of bone damage (erosion) predicted disease flare 6 and 12 months after treatment withdrawal. These variables may help identify patients with early RA in clinical remission as candidates for successful treatment withdrawal. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01142726 (date of registration: June 11, 2010).
35334603 Association between Hematological Indicesand Disease Activity in Patients with Rheumatoid 2022 Mar 15 Background and Objective: Hematological indices have been considered reliable markers for assessment of disease activity in rheumatoid arthritis (RA). This study assessed whether hematological indices reflect changes in disease activity in patients with RA treated with Janus kinase (JAK) inhibitors. Materials and Methods: This study recruited 123 patients with RA who completed a regimen of JAK inhibitors, including baricitinib or tofacitinib, for 24 weeks, and 80 age- and sex-matched healthy control subjects. Hematological indices were systemic immune-inflammation index (SII), neutrophil-to-hemoglobin and lymphocyte (NHL) score, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). Disease Activity Score 28 joints using erythrocyte sedimentation rate (DAS28-ESR) was evaluated as a measure of RA disease activity. Results: At baseline, patients with RA had a significantly higher SII, NHL score, NLR, and PLR than controls (p < 0.001 for all). SII, NHL score, NLR, and PLR at baseline were associated with DAS28-ESR (p < 0.05 for all). Changes in SII, NHL score, NLR, and PLR were associated with those in DAS28-ESR during treatment with JAK inhibitors. Such treatment markedly decreased SII, NHL score, and NLR values compared to those at baseline (p < 0.001 for all) but did not decrease PLR (p = 0.056). There were no differences in changes in SII, NHL score, NLR, and PLR between baricitinib and tofacitinib treatments. No hematological index showed predictive potential with respect to non-response to JAK inhibitor treatment. Conclusions: This study showed that hematological indices might be useful in monitoring changes in disease activity in patients with RA treated with JAK inhibitors.
34713769 Kruppel like factor 10 up-regulates PDZ and LIM domain containing protein 2 via nuclear fa 2022 Jan Rheumatoid arthritis (RA) is an autoimmune disease caused by synovitis. Two genes, KLF10 (Kruppel like factor 10) and PDZ and LIM domain containing protein 2 (PDLIM2), play key roles in cell inflammation and proliferation. However, the specific roles of the two on inflammation and proliferation of RA-fibroblastoid synovial cell (RA-FLS) have not been reported so far. RT-qPCR and Western blot detected the expressions of PDLIM2 and KLF10 in Human Rheumatoid arthritis FLSs (HFLSs-RA). Cell transfection techniques overexpressed PDLIM2 and KLF10 or inhibited the expression of KLF10. JAPAR database predicted the binding sites of PDLIM2 and KLF10, and the binding between the two was detected and verified using luciferase reporter genes and ChIP. Subsequently, CCK-8 technology, TUNEL staining, Western blot, wound healing and ELISA detected proliferation-related indicators, migration-related indications and inflammation-related indicators. Finally, western blot was used to detect the expression of NF-κB pathway-related proteins to further explore the mechanism.The expression of PDLIM2 was decreased in HFLSs-RA. Overexpression of PDLIM2 inhibited proliferation, migration and inflammation in HFLSs-RA. KLF10 can transcriptionally activate PDLIM2. Interfering with KLF10 reversed the inhibition effects of PDLIM2 overexpression on the proliferation, migration and inflammation, which was possibly through the NF-κB pathway. Overall, KLF10 can up-regulate PDLIM2 by regulating the NF-κB pathway to inhibit inflammation and proliferation of HFLSs-RA.
34319508 Prevalence and Factors Associated with Concomitant Chinese Medicine Use by Rheumatoid Arth 2022 Mar OBJECTIVE: To determine the prevalence, factors associated with and patterns of concomitant Chinese medicine (CM) with Western treatment use among patients with rheumatoid arthritis (RA) in a tertiary referral centre (Singapore General Hospital) in Singapore. METHODS: We conducted a cross-sectional interviewer-administered survey of a consecutive sample of patients with RA in Singapore General Hospital centre regarding their CM use including data on patient demographics, disease characteristics, concomitant use of CM and reasons, concerns and disclosure patterns from March to August 2015. Univariate and multivariate logistic regression analyses were performed to determine the associations of CM use. RESULTS: Prevalence of CM use among the 258 patients surveyed (male: female 42: 216; Chinese: Malay: Indian 191: 29: 34; mean age: 61 years; mean duration of RA: 10 years) was 46.1% (119/258). On multivariate analysis, Chinese ethnicity (OR, 95% CI: 4.11, 1.49-11.36), Chinese speakers (OR, 95% CI: 2.35, 1.03-5.54), middle-income group (OR, 95% CI: 2.53, 1.01-6.31) and greater learned helplessness (OR, 95% CI: 1.13, 1.04-1.22) were significantly associated with CM use. More CM users disclosed their CM use to CM physicians (87.3%, 96/110), sought advice from them on treatment interactions (59.4%, 57/96) and how best to combine treatments (49.0%, 47/96) than did so with rheumatologists (42.0%, 50/119; 40.0%, 20/50; and 42.0%, 21/50, respectively). Forty-two percentage (29/69) of patients who concealed CM use from rheumatologists because their rheumatologists did not specifically enquire about CM use. CONCLUSIONS: Concomitant CM use among patients with RA treated in a tertiary referral centre in Singapore is high but voluntary disclosure is low. The associations identified can help doctors identify and enquire about CM use, minimizing potential adverse interactions.