Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
33368709 The effectiveness and safety of Tripterygium wilfordii glycosides combined with disease-mo 2021 Jun OBJECTIVE: This systematic review and meta-analysis were performed to investigate the efficacy and safety of Tripterygium wilfordii glycosides (TG) for rheumatoid arthritis (RA) from the current literature. METHODS: An electronic search was conducted in eight databases (PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese VIP Database, and Wanfang Database) from inception until September 2020. Randomized controlled trials (RCTs) with risk of bias (RoB) score ≥ 4 according to the Cochrane RoB tool were included for the analyses. The primary outcome measures were duration of morning stiffness (DMS), tender joint count (TJC), swollen joint count (SJC), visual analog score (VAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF). The secondary outcome measures were the total clinical effective rate and adverse events. All the analyses were used by the random effects models. The meta-analysis was performed using RevMan 5.3 and STATA 14.0. RESULTS: A total of 40 RCTs with 3092 patients met our inclusion criteria. This meta-analysis showed that TG plus DMARDs for RA could decrease the DMS (p < .001), TJC (p < .001), SJC (p < .001), VAS (p < .001), serum CRP (p < .001), ESR (p < .001), and RF (p < .001) and improve total effective rate (p < .001). In addition, TG was generally safe and well tolerated in RA patients. CONCLUSION: Despite the limitations, the present evidence supports, at least to an extent, that TG can be recommended for routine use for RA patients. More large multicenter and high-quality RCTs are required for further research.
32885317 Cumulative incidence of femoral localized periosteal thickening (beaking) preceding atypic 2021 Feb The incidence of localized periosteal thickening (LPT, also termed beaking) of the lateral cortex that often precedes an atypical femoral fracture (AFF) was not high in patients with rheumatoid arthritis (RA) but incomplete AFFs developed in two patients. Higher-dose prednisolone was a significant risk factor for LPT in patients with RA. INTRODUCTION: Atypical femoral fractures (AFFs) are stress fractures; bisphosphonate (BP) use is a major risk factor for the development of such fractures. Localized periosteal thickening (LPT, also termed beaking) of the lateral cortex often precedes a complete or incomplete AFF. We evaluated the incidence of latent LPT in patients with rheumatoid arthritis (RA), to evaluate LPT progression, and to define LPT risk factors. METHODS: A total of 254 patients with RA were included; all underwent annual X-ray evaluation, dual-energy X-ray absorptiometry, and analyses of serum and bone metabolic markers for 2-3 years. LPT of the lateral cortex was sought in femoral X-rays. RESULTS: The incidence of LPT was 2.4% (6/254). Among patients on both BP and prednisolone (PSL) at enrollment, the incidence was 2.3% (3/131). Two femurs of two patients with LPT developed incomplete AFFs; LPT was extensive and associated with endosteal thickening. One patient had been on BP and PSL and microscopic polyangiitis was comorbidity. The other was on a selective estrogen receptor modulator and PSL. A daily PSL dose >5 mg (OR 11.4; 95%CI 2.15-60.2; p = 0.004) and higher-dose methotrexate (OR 1.22; 95%CI 1.01-1.49; p = 0.043) were significant risk factors for LPT. CONCLUSIONS: The incidence of latent LPT was not high (2.4%) but incomplete AFFs developed in two RA patients. Higher-dose PSL because of a comorbid disease requiring glucocorticoid treatment other than RA or refractory RA were risk factors for LPT; X-ray screening for latent LPT would usefully prevent complete AFFs.
34075162 Clusterin serum levels are elevated in patients with early rheumatoid arthritis and predic 2021 Jun 1 Clusterin (CLU) is a molecular chaperone that participates in a variety of biological processes. Recent studies indicate its possible involvement in the development of bone erosions and autoimmunity. The aim of this study was to investigate its serum concentrations in patients with early rheumatoid arthritis (RA) and to explore their potential relationship with disease activity and treatment response. Serum levels of CLU were measured in 52 patients before and 3 months after the initiation of treatment and in 52 healthy individuals. CLU levels at baseline were significantly increased in patients with early RA compared with healthy subjects (p < 0.0001). After 3 months of treatment, the levels of CLU decreased and reached concentrations comparable to those in controls. Even though there was no relationship between CLU levels and disease activity at baseline, CLU levels positively correlated with disease activity at months 3, 6 and 12 after treatment initiation. Using ROC analysis, lower CLU baseline levels predicted achieving the therapeutic target of low disease activity and remission at months 3, 6 and 12. In summary, we found increased serum concentrations of clusterin in treatment-naïve patients with early rheumatoid arthritis, and we suggest clusterin as a predictive biomarker of disease activity and treatment response.
33153343 Foot orthosis treatment improves physical activity but not muscle quantity in patients wit 2021 Sep OBJECTIVES: Foot impairment in rheumatoid arthritis (RA) may exacerbate sarcopenia from physical inactivity because of foot pain while walking. The present study aimed to investigate the prevalence of sarcopenia in patients with RA-associated foot impairment, and whether treatment with a foot orthosis improved physical activity and muscle quantity. METHODS: Thirty-two patients with RA were diagnosed as sarcopenic or nonsarcopenic, and the prevalence of sarcopenia was determined. Eleven patients with sarcopenia were treated with a foot orthosis. The following parameters were compared between baseline and after 6 months of treatment: physical activity (walking, moderate-intensity activity, and vigorous-intensity activity), foot pain while walking, Health Assessment Questionnaire (HAQ) score, and body composition parameters, including muscle quantity. RESULTS: Sarcopenia was present in 25/32 patients (78.1%). The use of a foot orthosis improved walking activity (p = .02), foot pain while walking (p = .02), and HAQ score (p = .02). However, there were no significant changes in moderate- or vigorous-intensity activities or body composition parameters, including muscle quantity. CONCLUSION: Patients with RA-associated foot impairment had a high rate of sarcopenia. Treatment with a foot orthosis increases light-intensity physical activity such as walking, but does not enhance moderate-to-vigorous-intensity activities or increase muscle quantity.
32926219 [Disease-related knowledge acquisition through structured patient information in rheumatoi 2021 May BACKGROUND/OBJECTIVE: The structured patient information for rheumatoid arthritis (StruPi-RA) program was the first standardized outpatient education program in rheumatoid arthritis (RA) in Germany. The main objective of the study was to determine the efficacy of the StruPi-RA program concerning disease-specific knowledge acquisition in patients with early stage RA or after changing the treatment regimen. METHODS: A total of 61 patients were included in a control group design, 32 in the intervention group (IG) and 29 in the control group (CG). Patients of the IG attended 3 modules of 90 min in a structured patient information program (StruPI-RA) including the topics of diagnostics, treatment and living with RA. Patients in the CG only received information material from the German Rheumatism League. The primary target criterion was the disease-related acquisition of knowledge, measured with the patient knowledge questionnaire (PKQ). Data were collected before and after participation in StruPI-RA. RESULTS: The improvement in knowledge in the IG attending the StruPI-RA compared to the CG was significant in time and group comparisons. No influence of disease duration or educational level was observed. The subscale treatment alone showed a significant difference in the group and time comparison. CONCLUSION: Participation in the StruPI-RA program in early RA was associated with a significant increase in disease-specific knowledge compared to the control group of patients. This leads to better decision-making in terms of treatment, a more beneficial doctor-patient communication and better self-management. In the long term an improvement in treatment adherence and quality of life is expected.
34665709 Traditional and disease-related non-computed variables affect algorithms for cardiovascula 2021 Nov OBJECTIVES: Several cardiovascular (CV) risk algorithms are available to predict CV events in the general population. Their performance and validity in rheumatic disease patients is suboptimal as some disease-specific variables which strongly contribute to the pathogenesis of CV disease are not included in these CV algorithms. We aimed to evaluate the performance of two CV algorithms and investigate which variables not included in the score contribute to CV risk score in a cohort of rheumatoid arthritis (RA) and Sjögren's syndrome (SS) patients. METHODS: A consecutive cohort of 77 RA and 68 SS patients without prior CV events was included. Clinical and serological features and traditional CV risk factors were collected. The 10-year CV risk was assessed by Reynold Risk Score (RSS) and "Progetto Cuore" algorithms. RESULTS: Prevalence of traditional CV risk factors and 10-year risk of fatal and non-fatal CV events assessed by RSS and "Progetto Cuore" were similar between the two cohorts. Multiple linear regression model showed that, among variables not included in both algorithms, body mass index (BMI) and disease activity were predictors of "Progetto Cuore" while BMI and bone erosions of RSS in RA. In SS, C-reactive protein was predictor of "Progetto Cuore" while hypertension, ESSDAI and LDL-cholesterol of RSS. CONCLUSIONS: The 10-year risk of fatal and non-fatal CV events is similar in RA and SS. Traditional CV risk factors, as hypertension, strongly contribute to CV risk in these patients. Inflammatory parameters and disease activity are two disease-specific variables which should be included in CV algorithm assessment in rheumatic disease patients.
32657636 Clinical characteristics and social productivity levels of patients with malignant rheumat 2021 May OBJECTIVES: Malignant rheumatoid arthritis (MRA) is defined as rheumatoid arthritis (RA) with systemic vasculitis or other severe extra-articular manifestations. Japan has a nationwide database for MRA. We analyzed the characteristics of Japanese patients with MRA based on data from the Ministry of Health, Labour and Welfare (MHLW). METHODS: We were permitted to use data on 43,108 patients who were registered in the MHLW database from 2003 to 2013. RESULTS: Median age was 65 (interquartile range, 57-72) years. Patients consisted of 71% females. Proportions of patients who had or had experienced interstitial pneumonia and pleuritis were increased, episcleritis was stable, and other MRA manifestations were decreased over time. The number of positive symptoms per patient also decreased over time. The median dose of glucocorticoid, percentage of patients undergoing surgery, and use of non-steroidal anti-inflammatory drugs and apheresis decreased year by year. Steinbrocker stage and class improved over time. Median C-reactive protein levels and erythrocyte sedimentation rate also decreased. Regarding social productivity levels of patients with MRA, the proportion of patients who were working or working from home increased and the proportion of patients recuperating or hospitalized decreased. CONCLUSION: In patients with MRA, disease activity decreased and social productivity improved from 2003 to 2013.
32216091 Most Appropriate Conventional Disease-Modifying Antirheumatic Drug to Combine With Differe 2021 Jun OBJECTIVE: In rheumatoid arthritis, the association between advanced therapies (including biologic disease-modifying antirheumatic drugs [DMARDs] and targeted synthetic DMARDs) and methotrexate (MTX) is recommended by international societies. When MTX cannot be used, other conventional synthetic DMARDs (csDMARDs) may be proposed. We aimed to compare the safety and efficacy of MTX and non-MTX csDMARDs in combination with advanced therapies. METHODS: We systematically searched the literature for studies comparing the effectiveness, retention rate, and safety of MTX versus non-MTX csDMARDs (leflunomide or others) in combination with tumor necrosis factor inhibitors (TNFi), abatacept, rituximab, tocilizumab, and JAK inhibitors. Meta-analysis was performed with RevMan, using an inverse variance approach with fixed or random-effects models. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated. RESULTS: The literature search revealed 3,842 articles; 41 studies were included for the systematic literature review and 21 for the meta-analysis: 13 with TNFi, 3 with abatacept, and 5 with rituximab. For TNFi, the European Alliance of Associations for Rheumatology (EULAR) response at 6 months was lower for patients receiving non-MTX csDMARDs than for those using MTX (RR 0.93 [95% CI 0.87, 1.0], P = 0.04; n = 3,843; I(2) = 28%), with a lower retention rate at 12 months. For abatacept, effectiveness and safety were similar between the 2 groups. For rituximab, a good EULAR response was higher with leflunomide than MTX (RR 1.38 [95% CI 1.13, 1.68], P = 0.001; n = 2,078; I(2) = 0%), with similar adverse event rates. Meta-analysis for tocilizumab or JAK inhibitors could not be performed. CONCLUSION: The different csDMARDs seem safe and efficient to combine with advanced therapies in RA patients. Although MTX seems slightly superior to other csDMARDs in combination with TNFi, leflunomide might be superior to MTX in combination with rituximab.
32653929 Biomarkers for treatment change and radiographic progression in patients with rheumatoid a 2021 Feb 1 OBJECTIVE: To identify biomarkers of treatment change and radiographic progression in patients with RA under remission. PATIENTS AND METHODS: RA patients in remission (DAS28-ESR <2.6) were selected and followed up for 5 years. An MRI of the dominant hand and an US assessment of knees/hands and serum levels of inflammation/angiogenesis biomarkers were performed at baseline and at 12th month. Synovial biopsies were obtained in patients with Power Doppler signal. Conventional radiographies of hands/feet were taken at baseline and after 5 years. Radiographic progression was defined as the change in the modified Sharp van der Heijde Score at 5 years >10.47 (small detectable change). RESULTS: Sixty patients were included, 81.6% were ACPA+ and 45% were taking biological DMARDs. At baseline, 66.6% had Power Doppler signal. After 5 years, 73.3% of patients remained in remission. Change of therapy was performed in 20 patients (33.3%) and was associated with BMI [odds ratio (OR) 1.3, 95% CI: 1, 1.7], lack of biological DMARD therapy (OR 24.7, 95% CI: 2.3, 257.2), first-year progression of MRI erosions (OR 1.2, 95% CI: 1, 1.3) and calprotectin serum levels (OR 2.8, 95% CI: 1, 8.2). Radiographic progression occurred in six (10%) patients. These patients had higher first-year progression of MRI erosions (P =  0.03) and bone oedema (P = 0.04). Among 23 patients undergoing synovial biopsy, mast cell density was independently associated with clinical flares. CONCLUSIONS: One-third of RA patients lost clinical remission and changed therapy throughout the 5 years of follow-up, which was independently associated with BMI, lack of biological DMARDs therapy and first-year progression of MRI erosion score and calprotectin serum levels. Significant radiographic progression was uncommon.
34727834 Analytical and clinical validation of an RNA sequencing-based assay for quantitative, accu 2021 Nov OBJECTIVES: This study reports analytical and clinical validation of a molecular signature response classifier (MSRC) that identifies rheumatoid arthritis (RA) patients who are non-responders to tumor necrosis factor-ɑ inhibitors (TNFi). METHODS: The MSRC integrates patient-specific data from 19 gene expression features, anti-cyclic citrullinated protein serostatus, sex, body mass index, and patient global assessment into a single score. RESULTS: The MSRC results stratified samples (N = 174) according to non-response prediction with a positive predictive value of 87.7% (95% CI: 78-94%), sensitivity of 60.2% (95% CI: 50-69%), and specificity of 77.3% (95% CI: 65-87%). The 25-point scale was subdivided into three thresholds: signal not detected (<10.6), high (≥10.6), and very high (≥18.5). The MSRC relies on sequencing of RNA extracted from blood; this assay displays high gene expression concordance between inter- and intra-assay sample (R(2) > 0.977) and minimal variation in cumulative gene assignment diversity, read mapping location, or gene-body coverage. The MSRC accuracy was 95.8% (46/48) for threshold concordance (no signal, high, very high). Intra- and inter-assay precision studies demonstrated high repeatability (92.6%, 25/27) and reproducibility (100%, 35/35). CONCLUSION: The MSRC is a robust assay that accurately and reproducibly detects an RA patient's molecular signature of non-response to TNFi therapies.
33930048 Predictors of drug survival for biologic and targeted synthetic DMARDs in rheumatoid arthr 2021 In this study we aimed to identify the predictors of drug survival for biologic and targeted synthetic DMARDs (bDMARDs and tsDMARDs) among patients with rheumatoid arthritis (RA) in a real-world setting. Data from RA patients receiving bDMARDs and tsDMARDs between 2007 and 2019 were extracted from the Taiwan Rheumatology Association Clinical Electronic Registry (TRACER). Patients were categorized into tumor necrosis factor-alpha (TNF-α) inhibitors, non-TNF-α inhibitors, and tofacitinib groups. The primary outcome was 3-year drug retention and the causes of bDMARDs and tsDMARDs discontinuation were recorded. Baseline demographic data before the initiation of bDMARDs and tsDMARDs treatment were analyzed to identify the predictors of 3-year drug survival. A total of 1,270 RA patients were recruited (TNF-α inhibitors: 584; non-TNF-α inhibitors: 535; tofacitinib: 151). The independent protective factors for 3-year drug survival were positive rheumatoid factor (RF) (HR: 0.48, 95% CI: 0.27-0.85, p = 0.013) and biologics-naïve RA (HR: 0.61, 95% CI: 0.39-0.94, p = 0.024). In contrast, positive anti-citrullinated protein antibody (ACPA) (HR: 2.24, 95% CI: 1.32-3.79, p = 0.003) and pre-existing latent tuberculosis (HR: 2.90, 95% CI: 2.06-4.09, p<0.001) were associated with drug discontinuation. RA patients treated with TNF-α inhibitors exhibited better drug retention, especially in the biologics-naïve subgroup (p = 0.037). TNF-α inhibitors were associated with lower cumulative incidence of discontinuation due to inefficacy and adverse events (both p<0.001). Baseline RF and ACPA positivity in abatacept-treated patients were associated with a better 3-year drug survival. However, negative ACPA levels predicted superior drug survival of TNF-α inhibitors and tofacitinib. In conclusion, bio-naïve status predicted better drug survival in TNF-α inhibitors-treated RA patients. RF and ACPA positivity predicted better abatacept drug survival. In contrast, ACPA negativity was associated with superior TNF-α inhibitors and tofacitinib survival.
33738687 Prevalence and trajectory of erosions, synovitis, and bone marrow edema in feet of patient 2021 Sep Despite erosions being as prevalent in feet as in hands in patients with rheumatoid arthritis (RA), their development in relation to synovitis and bone marrow edema (BME) have mainly been studied in hands. This study examines the prevalence and longitudinal trajectory of erosions, BME, and synovitis in metatarsophalangeal joints (MTPJs) in patients with early RA over 2 years of treatment. We also describe correlations between erosions, synovitis, and BME at the joint level. Magnetic resonance imaging (MRI) of the most symptomatic forefoot was acquired at baseline, year 1, and ≥ 2 years. Metatarsophalangeal joints 2-5 were scored by a radiologist for erosions, synovitis, and BME according to OMERACT guidelines. Patients were treated per standard of care. Thirty-two patients with early RA were included. Significant reductions in overall synovitis scores, MTPJ2, and MTPJ3 synovitis scores were seen between year 1 and ≥ 2 years. Overall BME scores improved in year 1 and were sustained at ≥ 2 years. BME improved in MTPJ2, MTPJ3, and MTPJ4. Overall erosions did not significantly change. Positive correlations were seen between changes in synovitis and BME in MTPJ2 and MTPJ5. In patients with early RA, standard of care was associated with overall reductions in synovitis by year 2, BME by year 1, and no progression in overall erosion scores on MRI. MTPJ2 and MTPJ3 appeared to be the most active joints. Improvements in synovitis were noted in MTPJ2 and MTPJ3 and reductions in BME in MTPJ2, MTPJ3, and MTPJ4, while other MTPJs did not progress. Key Points • This is one of the few MRI studies that examined longitudinal changes in imaging outcomes in early RA at the joint level in feet. • Erosions, synovitis, and bone marrow edema (BME) visualized on magnetic resonance imaging were most prevalent in metatarsophalangeal joints (MTPJ) 2 and 3 in patients with early rheumatoid arthritis (RA). • Standard of care was associated with improvements in synovitis in MTPJ2 and MTPJ3 and improvements in BME in MTPJ2, MTPJ3, and MTPJ4 over 2 years of treatment.
34464884 Assessment of genetic polymorphisms within nuclear factor-κB signaling pathway genes in r 2021 Nov OBJECTIVE: This study was performed to replicate the associations of genetic polymorphisms within nuclear factor-κB (NF-κB) signaling pathway genes with rheumatoid arthritis (RA), and to further examine genetic interactions in a Chinese population. METHODS: A total of eleven single-nucleotide polymorphisms (SNPs) were genotyped in 594 RA patients and 604 healthy controls. RESULTS: Genetic association analysis revealed that NFKBIE rs2233434, TNIP1 rs10036748 and BLK rs13277113 were significantly associated with RA, cyclic citrullinated peptide (CCP)-positive RA and rheumatoid factor (RF)-positive RA, and TNFAIP3 rs2230926 was significantly associated with CCP-positive RA. Significant additive interaction was observed between NFKB1 rs28362491 and IKBKE rs12142086 (RERI = 0.76, 95% CI 0.13-1.38; AP = 0.57, 95% CI 0.11-1.03), NFKBIE rs2233434 and BLK rs13277113 (RERI = 1.41, 95% CI 0.88-1.94; AP = 0.85, 95% CI 0.50-1.20), NFKBIL rs2071592 and TNIP1 rs10036748 (RERI = 0.59, 95% CI 0.17-1.02; AP = 0.46, 95% CI 0.05-0.87), UBE2L3 rs5754217 and TNFSF4 rs2205960 (RERI = 0.50, 95% CI 0.16-0.84; AP = 0.57, 95% CI 0.09-1.05). Significant multiplicative interaction was detected between BLK rs13277113 and UBE2L3 rs5754217 (p = 0.02), BLK rs13277113 and TNFSF4 rs2205960 (p = 0.03). CONCLUSIONS: Our results lent further support to the role of NF-κB signaling pathway in the pathogenesis of RA from a genetic perspective.
32004421 Outcomes Reported in Prospective Long-Term Observational Studies and Registries of Patient 2021 May OBJECTIVE: Prospective long-term observational studies (LOS) in rheumatoid arthritis (RA) lack a core set of universally collected outcome measures, particularly patient-centered outcomes, precluding accurate comparisons across studies. Our aim was to identify long-term outcome measures collected and reported in these studies. METHODS: We conducted a systematic review of registries and LOS of patients with RA, searching in ClinicalTrials.gov, the Agency for Healthcare Research and Quality Registry of Patient Registries, and Google Scholar. The names and acronyms of registries and LOS were further searched in the Medline and Embase databases to retrieve published articles. Two independent reviewers undertook data collection, quality appraisal, and data extraction. RESULTS: We identified 88 registries/LOS that met our eligibility criteria. These were divided into 2 groups: disease-based (52 [59%]) and therapy-based (36 [41%]). Methodologic and reporting standards varied across the eligible studies. For clinical outcomes, disease activity was recorded in 88 (100%) of all LOS/registries. The most commonly reported measure (86 [98%]) was the composite outcome Disease Activity Score using 28 joints. Of the patient-centered outcomes collected, physical functioning was most frequently reported (75 [85%]) with the Health Assessment Questionnaire (75 [85%]) as the most commonly used instrument within this domain. Other domains of patient-centered outcomes were comparatively infrequently recorded: mental (29 [33%]), social (20 [23%]), and health-related quality of life (37 [42%]). CONCLUSION: Most registries/LOS collect measures of disease activity and physical function. However, there is substantial heterogeneity in the collection of relevant patient-centered outcomes that measure symptom burden and mental and social ramifications of RA.
34161226 Mental health and well-being during the COVID-19 pandemic: stress vulnerability, resilienc 2021 May OBJECTIVES: The COVID-19 pandemic severely increased the stress levels in the population. The aim of present study was to investigate the impact of the lockdown measures on emotional well-being and disease activity in patients with fibromyalgia (FM) and rheumatoid arthritis (RA) through a telemedicine approach. METHODS: An on-line survey, including demographic characteristics, disease-activity and psychometric scales (Stress-related Vulnerability Scale, Resiliency scale), Zung Anxiety and Depression Self-assessment Scale), was anonymously administered to FM, RA and healthy controls (HC). Disease activities were compared to the pre-lockdown cohort referring to our centre. RESULTS: Levels of anxiety and depression worthy of psychiatric attention were documented in 36.7% of FM, 14.6% of RA, 12.5% of HC and in 50% of FM, 17.1% of RA, 15% of HC, respectively. HC featured the highest stress scores, followed FM and then RA. RA showed higher resiliency than FM. Both anxiety and depression scores were significantly higher in FM than RA and HC. Disease severity was higher in RA patients and lower in FM patients when compared to the respective historical cohorts. CONCLUSIONS: Lockdown significantly affected emotional well-being and disease activity of patients suffering from rheumatic diseases. While HC showed a higher vulnerability to stress, RA patients showed a greater resilience compared to both HC and to FM patients, especially. Emotional disturbances are greater in patients with RDs and in particular with FM. The use of a telemedicine approach to screen for severe symptoms represents a useful addition to the overall management of rheumatic patients.
33504345 Better clinical outcome of total knee arthroplasty for rheumatoid arthritis with periopera 2021 Jan 27 BACKGROUND: Previous evidence suggested that perioperative anti-rheumatic therapy for patients receiving total knee arthroplasty (TKA) helped improve postoperative rehabilitation for rheumatoid arthritis (RA), yet long-term effects and outcomes of perioperative drug therapy in TKA presently remain unclear. This study investigated whether perioperative treatment with glucocorticoids (GC) and disease-modifying anti-rheumatic drugs (DMARDs) can improve clinical outcomes for patients with RA undergoing TKA. METHODS: Patients between January 2000 and December 2011 were allocated into three groups based on perioperative drug therapy: A, control group (no GC or DMARDs), B, DMARD group (DMARDs given without GC), and C, co-therapy group (DMARDs plus GC). The patients were followed up for average 11.4 years. Baseline characteristics, pre- and post-operative Hospital for Special Surgery score (HSS), laboratory parameters, and complications were recorded by follow-up. RESULTS: Fifty-six RA patients undergoing 91 TKAs were included in this study. Patients who received perioperative GC with DMARDs (group C) achieved larger/increased range of motion (ROM) (C:122.17 vs A:108.31 vs B:108.07, p = 0.001, partial eta squared (η(2) p) = 0.18) at 1 year, better HSS score (C, 83.01 vs A, 79.23 vs B, 77.35, p = 0.049, η(2) p = 0.067), pain relief (C, 1.09 vs A, 1.17 vs B, 1.75, p = 0.02, η(2) p = 0.094), and ROM (C, 130.81 vs A, 112.82 vs B, 113.58, p = 0.001, η(2) p = 0.142) at latest follow-up comparing with the other treatment groups. No differences were noted in laboratory tests, blood loss, volume of transfusion, or complications among groups. CONCLUSIONS: Compared with the other perioperative anti-rheumatic treatments, the combination of GC and DMARDs results in improved HSS score, better function, larger range of motion, and reduced postoperative pain for TKA patients with RA in the long term. Further investigation is warranted to look for a better understanding of more specific medication effects and strike a good balance between the benefits and complications for long-term pharmacotherapy.
33582243 Serum levels of the soluble urokinase plasminogen activator receptor (suPAR) correlates wi 2021 Jun Soluble urokinase plasminogen activator receptor (suPAR) is intensively studied as a biomarker of inflammation and disease outcome in various diseases. In rheumatoid arthritis (RA), suPAR have shown an association with inflammation and swollen joints, but data on suPAR in relation to early disease course and disease progression are lacking. This study investigates the potential of suPAR to predict or reflect disease outcome in early RA. Serum suPAR was measured by enzyme-linked immunosorbent assay at disease onset and after 3 and 36 months in 252 patients from a Swedish prospective observational early RA cohort. Levels and changes of suPAR were analyzed in relation to the 28-joint disease activity score (DAS28) and joint damage according to the Larsen score at inclusion and during follow-up. 100 healthy blood donors served as controls. Circulating levels of suPAR were higher in RA patients at all time points as compared to healthy controls. Baseline suPAR was significantly associated with baseline disease activity whereas suPAR levels at 36 months were associated with joint damage at 36 months. No predictive value of suPAR levels or changes in suPAR levels over time were found. In conclusion, suPAR levels associate with disease activity in early untreated RA and reflects joint damage at later stages. Increased suPAR in established RA could indicate patients in need of frequent monitoring of joint status, irrespective of disease activity. In the view of suPAR as a rapidly emerging biomarker, it is important to be aware of its ability to reflect both inflammation and subsequent damage.
32662403 Painless and painful synovitis have similar ultrasound and clinical outcomes: one-year coh 2021 May OBJECTIVES: We aimed to compare the painless synovitis evolution with painful synovitis, based on bone erosion by ultrasonography over a year in women with longstanding rheumatoid arthritis. Ultrasound inflammatory measurements and radiographic, functional and clinical findings were also compared between groups at the end of the same follow-up. METHODS: A prospective cohort study was rolled out, involving 60 women with RA, divided into two groups: painless and painful, with 30 patients in each group. The wrist and MCPs joints were assessed by ultrasound and plain x-ray, initially and after 12 months (T0 and T12). There was also a clinical assessment (activity scores, functional tests, disease and treatment progression variables) at 6 and 12 months. RESULTS: Patients' average age was 58.0±12.8 and average length of disease 16.4±9.8 years. Initially, the demographic characteristics were similar between groups, however, the painful group had worse clinical and functional scores. There were no statistically significant differences in the majority of US bone erosions and US inflammatory measurements, nor in radiographic progression variables between the groups. Over one year, pinch strength test and DAS 28 remained worse in the painful group (p<0.05). Clinical worsening variables and change of treatment evolved similarly between the groups, on T6 and T12. CONCLUSIONS: According to the study, the painless group progressed similarly to the painful one over a year, as regards bone erosion, ultrasound inflammatory measurements, radiographic findings, clinical worsening and change of treatment in female longstanding RA patients.
34432202 Inokosterone Is A Potential Drug Target of Estrogen Receptor 1 in Rheumatoid Arthritis Pat 2021 Oct OBJECTIVE: To elucidate the active compounds and the molecular mechanism of Cyathula Officinalis as a drug treatment for rheumatoid arthritis (RA). METHODS: The target genes of active ingredients from Cyathula Officinalis were obtained from bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine. The protein-protein interaction between the target genes were analyzed using STRING and Genemania. The transcriptome of RA patients compared to healthy people (GSE121894) were analyzed using R program package Limma. The relative expression of the target genes was obtained from the RNA-seq datasets. The molecular docking analyses were processed based on the molecular model of estrogen receptor 1 (ESR1) binding with estradiol (PDB ID:1A52). The binding details were analyzed by SYBYL. RESULTS: Inokosterone, ecdysterone, and cyaterone were the 3 active ingredients from Cyathula Officinalis that bind to target genes. Of all the significantly changed genes from RA patients, ESR1, ADORA1, and ANXA1 were significantly increased in mRNA samples of RA patients. CONCLUSION: ESR1, the transcription factor that binds inokosterone in the molecular binding analysis, is the target protein of Cyathula Officinalis.
34994138 [Mechanism of Huangqi Guizhi Wuwu Decoction in treatment of rheumatoid arthritis based on 2021 Dec In this study, ultra-high performance liquid chromatography-linear ion trap/electrostatic field orbit trap combined-type mass spectrometry(UPLC-LTQ-Orbitrap-MS) was used to analyze the main active components of Huangqi Guizhi Wuwu Decoction(HQGZ). A total of 50 active components were identified from HQGZ and 108 potential targets of the components related to the treatment of rheumatoid arthritis were retrieved based on network pharmacology, including 87 key targets, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. The result indicated that HQGZ may exert therapeutic effects mainly through the sphingolipid signaling pathway, tumor necrosis factor(TNF) signaling pathway, as well as the positive regulation of ribonucleic acid(RNA) polymerase Ⅱ promoter transcription, inflammatory response and other biological processes. At the same time, cell experiment was performed to verify the key proteins in the TNF signaling pathway. The results demonstrated that HQGZ significantly reduced the expression of caspase-3(CASP3), TNF, relaxed(RELA) protein, and IkappaB kinase beta(IKBKB) in fibroblast-like synoviocytes induced by TNF-α. The results of UPLC-LTQ-Orbitrap-MS, network pharmacology and cell experiment showed that the active components in HQGZ may inhibit inflammatory response and regulate immune function and cell apoptosis by modulating key proteins in TNF signaling pathway to treat rheumatoid arthritis.