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ID PMID Title PublicationDate abstract
30709958 Serum Biomarkers for Prediction of Response to Methotrexate Monotherapy in Early Rheumatoi 2019 Jun OBJECTIVE: To investigate baseline levels of 12 serum biomarkers that constitute a multibiomarker disease activity test, as predictors of response to methotrexate (MTX) in patients with early rheumatoid arthritis (eRA). METHODS: In 298 patients from the Swedish Pharmacotherapy (SWEFOT) clinical trial, baseline serum levels of 12 proteins were analyzed for association with disease activity based on the 28-joint count Disease Activity Score (DAS28) after 3 months of MTX monotherapy using uni-/multivariate logistic regression. Primary outcome was low disease activity (LDA; DAS28 ≤ 3.2). RESULTS: Of 298 patients, 104 achieved LDA after 3 months on MTX. Four of the 12 biomarkers [C-reactive protein (CRP), leptin, tumor necrosis factor receptor I (TNF-RI), and vascular cell adhesion molecule 1 (VCAM-1)] significantly predicted LDA based on stepwise logistic regression analysis. Dichotomization of patients using receiver-operating characteristic curve analysis-based cutoffs for these biomarkers showed significantly higher proportions with LDA among patients with lower versus higher levels of CRP or leptin (40% vs 23%, p = 0.004, and 40% vs 25%, p = 0.011, respectively), as well as among those with higher versus lower levels of TNF-RI or VCAM-1 (43% vs 27%, p = 0.004, and 41% vs 25%, p = 0.004, respectively). Combined score based on these biomarkers, adjusted for known predictors of LDA (smoking, sex, and age), associated with decreased chance of LDA (adjusted OR 0.45, 95% CI 0.32-0.62). CONCLUSION: Low baseline levels of CRP and leptin, and high baseline levels of TNF-RI and VCAM-1 were associated with LDA after 3 months of MTX therapy in patients with eRA. Combination of these 4 biomarkers increased accuracy of prediction. [Trial registration number: NCT00764725].
30620289 Rituximab induces a lasting, non-cumulative remodelling of the B-cell compartment. 2019 Jul OBJECTIVES: Reconstitution of B-cells after their therapeutic depletion with rituximab mimics the ontogeny of the B-cell linage in patients with rheumatoid arthritis. However, little is known about the effects of multiple cycles of treatment on the repletion kinetics and their long-lasting effects on the B-cell compartment. We therefore compared the recovery capacity of the B cell subpopulations between patients who experienced their first cycle of rituximab and those who experienced successive cycles. METHODS: The distribution of the different B-cell subsets was characterised by multiparametric flow cytometry in the peripheral blood of 29 patients in the first rituximab course (naïve cycles) and 40 patients in successive cycles. Samples were obtained at baseline and at 3, 6, and 8 months of each cycle. RESULTS: The baseline percentage of B-cell subsets was similar among successive cycles. Therefore, successive cycles were grouped for comparison with naïve cycles. Patients in naïve cycles had higher percentages at baseline of both total and memory B-cells. However, the recovery of the different B-cell subsets was similar between naïve and successive cycles. In naïve patients the percentage of transitional B-cells significantly correlated with disease activity at baseline. CONCLUSIONS: Rituximab induces a long-term reshape of the B-cell compartment while multiple cycles of rituximab do not induce cumulative effects on B-cell subpopulations. Transitional B-cells seem to be associated with higher disease activity, although further studies are needed to determine if they can be used as a biomarker to predict the need for rituximab retreatment.
30230146 Ten-year retrospective review of the incidence of serious infections in patients on biolog 2019 Apr BACKGROUND: Biologic disease modifying anti-rheumatic drugs (bDMARDs) have significantly improved the prognosis for patients with rheumatoid arthritis (RA). However, due to their immunosuppressive nature, concerns remain about the potential for infection in patients receiving these medications. AIMS: To evaluate the incidence of serious infections (SI) in a Western Australian cohort of patients with RA who are receiving bDMARDs. The role of confounders including age, gender, comorbidities and use of glucocorticoids was also evaluated. The incidence of SI was defined as any infection necessitating admission to the hospital and the use of antibiotics. METHODS: A 10-year retrospective review was conducted of all patients with RA who were receiving bDMARDs at three tertiary hospitals in Western Australia. Discharge summaries and all available clinic letters were reviewed and patient demographics and clinical data were collected. Pearson Chi-squared test and Student's t-test were used for comparing demographic factors and clinical variables between the groups with SI and those without. RESULTS: One hundred and two patients met the inclusion criteria for the period 2006-2016, 25 of whom had been admitted with SI, accounting for a total of 46 admissions. Skin and soft tissue infections were the most common (28%) followed by respiratory infections (26%) and urinary tract infections (20%). The incidence rate of SI was 8.98 per 100 person years. The rate was lowest with adalimumab (5.27 per 100 person years) and highest with infliximab (34.5 per 100 person years). Those with SI were older (68 years vs 60 years; P = 0.02) and had been on bDMARDs for longer period of time (6.05 years vs 4.68 years; P = 0.04). There was no significant increase in length of stay due to co-administration of glucocorticoids. The presence of comorbidities did not play a significant role in increasing the risk of SI. CONCLUSION: Age and duration of bDMARD use were statistically significant factors associated with an increased risk of SI. Comorbidities did not play a significant role in increasing the incidence of SI. Patients who were on both glucocorticoids and bDMARDs did not have a significant increase in length of stay when compared with patients who were just on bDMARDs. More research is needed in this area with larger numbers to draw statistically significant conclusions regarding the role of comorbidities in SI risk and the individual infection risk associated with each bDMARD.
31339385 Celecoxib for the treatment of musculoskeletal arthritis. 2019 Oct Introduction: The cyclooxygenase (COX)-2 inhibitor celecoxib is an approved compound for rheumatoid (RA) and osteoarthritis (OA), combining both anti-inflammatory and analgesic properties with a good gastrointestinal tolerability. Areas covered: This article covers the pharmacological properties and clinical efficacy as well as the latest safety data available for celecoxib with emphasis on the treatment of RA and OA. It is based primarily on a current literature search on PubMed and Web of Science, but also on the professional rheumatological expertise of the authors. Expert opinion: Celecoxib has been shown to be superior to placebo and equivalent to traditional non-steroidal anti-inflammatory drugs (tNSAIDs). Many studies have been published making celecoxib a good and safe treatment option in particular in moderate arthritis and patients without established cardiovascular (CV) disease. Moreover, older patients might gain significant benefits compared to tNSAIDs due to reduced gastrointestinal events even when having a history of ulcer bleedings. Nonetheless, there is still much to learn, especially regarding the prescription of celecoxib in patients with cardiovascular co-morbidities. While low doses seem to be safe according to present data, the knowledge on the more effective, higher doses >400 mg/day is still limited.
31701681 Macrophage migration inhibitory factor promoter polymorphisms are associated with disease 2020 Jan BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine capable of stimulating inflammatory cytokine and matrix metalloproteinase production from macrophages and synovial fibroblasts, which leads to persistent inflammation and bone degradation, two of the major pathological processes in rheumatoid arthritis (RA). The aim of this study was to evaluate the association of MIF promoter polymorphisms (-794CATT(5-8) rs5844572 and -173G > C, rs755622), circulating MIF levels, and mRNA expression with RA susceptibility and disease activity. METHODS: A case-control study was conducted in 200 RA patients and 200 control subjects (CS) from Southern Mexico. Genotyping was performed by conventional PCR and PCR-RFLP methods. MIF mRNA expression was quantified by real-time PCR and MIF serum levels were determined by an ELISA kit. RESULTS: The 7,7 (-794CATT(5-8) ) and -173CC (-173G > C) genotypes were associated with higher disease activity in RA patients. MIF serum levels were increased, and MIF mRNA expression was reduced in RA patients as compared to CS. In addition, RA patients with moderate disease activity had higher MIF levels than those with low disease activity. The -794CATT(5-8) and -173G > C MIF polymorphisms were not associated with RA susceptibility. CONCLUSION: These results suggest an important role of MIF polymorphisms and MIF serum levels with disease activity in RA.
30420245 Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoi 2019 Jun OBJECTIVES: To evaluate the incidence of anti-drug antibody (ADA) occurrences and ADA-related risk factors under adalimumab and infliximab treatment in rheumatoid arthritis (RA) patients. METHODS: The study combined retrospective cohorts from the ABIRISK project totaling 366 RA patients treated with adalimumab (n = 240) or infliximab (n = 126), 92.4% of them anti-TNF naive (n = 328/355) and 96.6% of them co-treated with methotrexate (n = 341/353) with up to 18 months follow-up. ADA positivity was measured by enzyme-linked immunosorbent assay. The cumulative incidence of ADA was estimated, and potential bio-clinical factors were investigated using a Cox regression model on interval-censored data. RESULTS: ADAs were detected within 18 months in 19.2% (n = 46) of the adalimumab-treated patients and 29.4% (n = 37) of the infliximab-treated patients. The cumulative incidence of ADA increased over time. In the adalimumab and infliximab groups, respectively, the incidence was 15.4% (5.2-20.2) and 0% (0-5.9) at 3 months, 17.6% (11.4-26.4) and 0% (0-25.9) at 6 months, 17.7% (12.6-37.5) and 34.1% (11.4-46.3) at 12 months, 50.0% (25.9-87.5) and 37.5% (25.9-77.4) at 15 months and 50.0% (25.9-87.5) and 66.7% (37.7-100) at 18 months. Factors associated with a higher risk of ADA development were: longer disease duration (1-3 vs. < 1 year; adalimumab: HR 3.0, 95% CI 1.0-8.7; infliximab: HR 2.7, 95% CI 1.1-6.8), moderate disease activity (DAS28 3.2-5.1 vs. < 3.2; adalimumab: HR 6.6, 95% CI 1.3-33.7) and lifetime smoking (infliximab: HR 2.7, 95% CI 1.2-6.3). CONCLUSIONS: The current study focusing on patients co-treated with methotrexate for more than 95% of them found a late occurrence of ADAs not previously observed, whereby the risk continued to increase over 18 months. Disease duration, DAS28 and lifetime smoking are clinical predictors of ADA development.
30457056 Anti-Arthritic Effect of Garcinol Enriched Fraction Against Adjuvant Induced Arthritis. 2019 BACKGROUND: Garcinia indica also known as kokum is used in traditional system of medicine for relieving inflammation and rheumatic pain. Garcinol, a benzophenone obtained from its fruit rind is reported to have anti-inflammatory effect via modulating arachidonic acid metabolism, suppressing iNOS expression, NF-κB activation and COX-2 expression. It has also been studied for antioxidant and anticancer activity. Apart from these, few patents claim that garcinol also has anti-obesity and hepatoprotective effect and has a potential to be used for the treatment of renal disorders, endometriosis and cardiac dysfunction. OBJECTIVE: Garcinol Enriched Fraction (GEF) from the fruit rind of Garcinia indica should be effective in the treatment of arthritis, one of the chronic inflammatory disorder owing to its anti-inflammatory property as indicated by earlier experiments. METHODS: GEF was prepared from the fruit rind of Garcinia indica and quantified using LC-MS/MS. It was found to contain 89.4% w/w of garcinol. GEF was evaluated at the dose of 10mg/kg for its efficacy against Complete Freund's Adjuvant (CFA) induced arthritis in Wistar albino rats. Paw volumes of both sides were measured by Plethysmometer and body weight was recorded on 0, 1, 5, 12 and 21st day. The hyperalgesic response was also measured by motility test and stair climbing test. RESULTS: GEF showed a significant reduction in paw swelling (p < 0.0001) and arthritis index (p < 0.0001) exhibiting anti-inflammatory potential. It also improves the motility and stair climbing ability of experimental animals (p < 0.05), thus reducing hyperalgesia. CONCLUSION: Garcinol enriched fraction shows anti-arthritic activity in experimental animals.
31559770 Use of Disease Activity Score (DAS28) and Routine Assessment of Patient Index Data 3 (RAPI 2019 Jul INTRODUCTION: Patient outcomes in rheumatoid arthritis (RA) have significantly improved with the advent of disease modifying anti rheumatic drugs and the newer biological agents. Various scoring systems available for monitoring disease activity in RA have not yet been put into full use in patient management in India. We aim to study the disease activity score 28 (DAS28) and Routine assessment of patient index 3 (RAPID3), their correlation and patient outcomes in RA. MATERIALS AND METHODS: The study was conducted between March 2011-May 2011. A total of 81 patients were included. Patient's history was noted. Clinical examination for tender and swollen joint counts was performed. DAS28 was calculated. MDHAQ was administered to each patient in a language they understood and responses noted. Correlation between DAS28 and RAPID3 was studied using Pearson's correlation coefficient. RESULTS: RAPID3 and DAS28 showed Pearson's correlation coefficient of 0.8699 (p<0.001). Of the 53 patients who met with DAS28 severity criteria of >5.1, 82.7% showed similar results with RAPID3 suggesting severe disease activity. (X2 = 33.512 and p<0.001). A greater proportion of those whose DMARD initiation was 2 years after disease onset, had higher disease activity as compared to those with earlier initiation.
31580792 Chemokines: A Potential Therapeutic Target to Suppress Autoimmune Arthritis. 2019 BACKGROUND: Chemokines are a family of low molecular weight proteins that induce chemotaxis of inflammatory cells, which mainly depends on the recognition of a chemo-attractant gradient and interaction with the substratum. In Rheumatoid Arthritis (RA), abundant chemokines are expressed in synovial tissue, cause inflammatory cells migration into the inflamed joint that necessitates the formation of new blood vessels i.e. angiogenesis. Over the decades, studies showed that continuous inflammation may lead to the loss of tissue architecture and function, causing severe disability and cartilage destruction. In spite of the advancement of modern drug therapy, thousands of arthritic patients suffer mortality and morbidity globally. Thus, there is an urgent need for the development of novel therapeutic agents for the treatment of RA. METHODS: This review is carried out throughout a non-systematic search of the accessible literature, will provide an overview of the current information of chemokine in RA and also exploring the future perspective of the vital role of targeting chemokine in RA treatment. RESULTS: Since, chemokines are associated with inflammatory cells/leucocyte migration at the site of inflammation in chronic inflammatory diseases and hence, blockade or interference with chemokines activity showing a potential approach for the development of new anti-inflammatory agents. Currently, results obtained from both preclinical and clinical studies showed significant improvement in arthritis. CONCLUSION: This review summarizes the role of chemokines and their receptors in the pathogenesis of RA and also indicates possible interactions of chemokines/receptors with various synthetic and natural compounds that may be used as a potential therapeutic target in the future for the treatment of RA.
30837252 Delays between the onset of symptoms and first rheumatology consultation in patients with 2019 Mar 4 OBJECTIVE: To investigate delays from symptom onset to rheumatology assessment for patients with a new onset of rheumatoid arthritis (RA) or unclassified arthritis. METHODS: Newly presenting adults with either RA or unclassified arthritis were recruited from rheumatology clinics. Data on the length of time between symptom onset and first seeing a GP (patient delay), between first seeing a general practitioner (GP) and being referred to a rheumatologist (general practitioner delay) and being seen by a rheumatologist following referral (hospital delay) were captured. RESULTS: 822 patients participated (563 female, mean age 55 years). The median time between symptom onset and seeing a rheumatologist was 27.2 weeks (IQR 14.1-66 weeks); only 20% of patients were seen within the first 3 months following symptom onset. The median patient delay was 5.4 weeks (IQR 1.4-26.3 weeks). Patients who purchased over-the-counter medications or used ice/heat packs took longer to seek help than those who did not. In addition, those with a palindromic or an insidious symptom onset delayed for longer than those with a non-palindromic or acute onset. The median general practitioner delay was 6.9 weeks (IQR 2.3-20.3 weeks). Patients made a mean of 4 GP visits before being referred. The median hospital delay was 4.7 weeks (IQR 2.9-7.5 weeks). CONCLUSION: This study identified delays at all levels in the pathway towards assessment by a rheumatologist. However, delays in primary care were particularly long. Patient delay was driven by the nature of symptom onset. Complex multi-faceted interventions to promote rapid help seeking and to facilitate prompt onward referral from primary care should be developed.
31346885 The expression of GAS5, THRIL, and RMRP lncRNAs is increased in T cells of patients with r 2019 Nov OBJECTIVE: Long non-coding RNAs (lncRNAs) comprise a large and diverse group of non-coding RNAs (ncRNAs) with important regulatory roles in various biological processes, including the immune system regulation. Rheumatoid arthritis (RA) as an autoimmune disease initiates inflammation in the synovial joints. T cells infiltrating into the synovial membrane have an important role in the pathogenesis of RA. The aim of the current investigation was to analyze the expression of four lncRNAs in the T cells from RA patients and healthy controls. METHODS: In the current study, we investigated the expression of GAS5, RMRP, IFNϒ-AS1, and THRIL lncRNAs in circulating T cells from 20 patients with RA and 18 healthy matched controls by quantitative real-time PCR. T cell isolation was accomplished using the MAC method. We also analyzed the correlation between lncRNA expression and clinical parameters. Also, the mRNA expression levels of IL-17 and TNF-α and the association between lncRNAs and these cytokines were examined. RESULTS: The results indicate that T cells of RA patients display increased levels of GAS5 (3.31-fold, p = 0.007), RMRP (2.43-fold, p = 0.02), and THRIL (2.14-fold, p = 0.03) lncRNAs compared with those of controls. Furthermore, a positive correlation was found between RMRP expression and disease duration in RA. Receiver operating characteristic (ROC) curve of GAS5, RMRP, and THRIL has a discriminative value in comparing RA patients and controls. CONCLUSION: The results suggest lncRNAs may be involved in T cell dysfunction in RA. Further studies are required to see whether these lncRNAs have an effect on dysregulation of immune responses in RA disease. Key Points • 70% of non-coding sequences in the human genome are transcribed to RNA. • A growing body of evidence shows the importance of lncRNAs in innate and adaptive immune cell differentiation and functions. • Important recent works suggest a key role of immune cell lncRNAs in autoimmune processes and diseases including RA.
31507104 [THE EMERGENCE OF RHEUMATOID ARTHRITIS AT THE AGE OF OVER 60 - A COMPARISON OF CLINICAL MA 2019 Sep INTRODUCTION: The aging process of rheumatoid arthritis (RA) requires re-assessment of diagnostic and treatment approaches in patients who developed RA at 60-69 years (EORA-Elderly-Onset RA), 70 years and older (LORA-Late Onset RA) compared with CORA patients - Common Onset RA (35 - 50 years). METHODS: Comparing data of CORA, EORA and LORA patients: gender, nationality; swollen and tender joints (out of 28 joints), Disease Activity Score (DAS28), inflammatory markers, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA); treatment with corticosteroids and disease modifying anti rheumatic drugs (DMARDs). RESULTS: Patients' files were examined: CORA (39, 33.5%), EORA (37, 30.8%) and LORA (44, 36.7%). No differences were observed between swollen and tender joints, inflammatory markers, DAS28, RF, and ACPA. Methotrexate was introduced in 94.9% of CORA patients versus EORA (77.3%) and LORA (78.4%); 88.6% LORA-patients received corticosteroids versus 69.2% CORA; 43.2% of LORA patients and 92.3% CORA received synthetic disease-modifying antirheumatic drugs (DMARDs); 43.6% CORA versus 16.2% EORA and 9.3% LORA patients received biologics. CONCLUSIONS: No clinical and laboratory differences were found between CORA, EORA, and LORA groups. EORA and LORA patients received less synthetic and biological DMARDs. It is necessary to change the attitude to EORA and LORA and to promote advanced optimal treatments. Prospective studies on the efficacy and safety of novel drugs in EORA and LORA patients are needed.
31004003 A Constitutional Activating MET Mutation Makes the Genetic Link between Malignancies and C 2019 Jul 15 PURPOSE: The genesis of all cancers results from an accumulation of mutations, constitutional and/or acquired when induced by external mutagenic factors. High-speed technologies for genome sequencing have completely changed the study of disease genetics, but with limited knowledge of the functional value of most genetic changes. EXPERIMENTAL DESIGN: Here, we proposed an innovative individual approach by studying tissue samples from a young woman with an unusual association of breast cancer, polycythemia vera, and rheumatoid arthritis. We performed genomic analyses for copy number variations and point mutations on laser-microdissected tumor cells from the breast cancer, and on CD34(+) cells sorted from bone marrow aspiration, to identify gene abnormalities common to these two types of cell populations. RESULTS: Using ONCOSCAN technology, we identified a constitutional pR988C, c2962C>T mutation of MET. Using CRISPR-Cas9 technology, we established pR988C MET-mutated transgenic mice, which reproduced the autoimmune diseases and myeloproliferation found in our index-case; one of the transgenic mice spontaneously developed a skin squamous cell carcinoma. We also showed that additional mutagenic factors were required to induce cancers, including skin squamous cell carcinoma and thyroid cancer. Using an anti-MET drug, cabozantinib, we demonstrated for the first time the functional role of this mutation in the maintenance of myeloproliferation and rheumatoid arthritis, and in cancer genesis. CONCLUSIONS: Our study opens a considerable field of application in the domain of constitutional genetics, to establish genetic links between cancers and other very different severe diseases.
31701537 Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects With Rheumatoid Arthriti 2020 Apr Upadacitinib (ABT-494) is a selective Janus kinase (JAK)1 inhibitor being developed for treatment of several inflammatory disorders. A population pharmacokinetic model was developed for upadacitinib using 11,658 plasma concentrations from 1145 subjects from 4 phase 1 and 5 phase 2 studies in healthy subjects and subjects with rheumatoid arthritis, Crohn's disease, ulcerative colitis, or atopic dermatitis. A 2-compartment model with first-order absorption and lag time for the immediate-release formulation and mixed zero- and first-order absorption with lag time for the extended-release formulation, and linear elimination adequately described upadacitinib plasma concentration-time profiles. The oral bioavailability of upadacitinib extended-release formulation was estimated to be approximately 80% relative to the immediate-release formulation. Covariates included in the final model were creatinine clearance, subject population (healthy subjects vs subjects with atopic dermatitis, ulcerative colitis, or Crohn's disease vs subjects with rheumatoid arthritis) and sex on apparent oral clearance and sex and body weight on apparent volume of distribution of the central compartment. Female subjects had 21% higher upadacitinib steady-state area under the plasma concentration-time curve (AUC) compared to male subjects. Compared to healthy subjects, subjects with atopic dermatitis, ulcerative colitis, or Crohn's disease had 21% higher upadacitinib steady-state AUC, while subjects with rheumatoid arthritis had 35% higher steady-state AUC. Subjects with mild or moderate renal impairment were estimated to have 10% or 22% higher AUC, respectively, compared to subjects with normal renal function. Based on final model parameter estimates, effects of the tested covariates are not expected to result in clinically relevant changes in upadacitinib steady-state exposures.
30894208 Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate re 2019 Mar 20 BACKGROUND: Sarilumab is a human immunoglobulin G1 anti-interleukin-6 (IL-6) receptor monoclonal antibody that blocks IL-6 from binding to membrane-bound and soluble IL-6 receptor α. This bridging study assessed the efficacy and safety of sarilumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA) and inadequate response to MTX (MTX-IR). METHODS: In this phase III study, 243 patients were randomized 2:2:1:1 to receive subcutaneous sarilumab 150 mg every 2 weeks (q2w), sarilumab 200 mg q2w, placebo switching to sarilumab 150 mg q2w + MTX at 24 weeks, or placebo switching to sarilumab 200 mg q2w at 24 weeks, all in combination with MTX, for a total of 52 weeks (double-blind, placebo-controlled 24-week period followed by a single-blind 28-week extension). The primary endpoint was the proportion of patients achieving American College of Rheumatology 20% improvement criteria (ACR20) responses at week 24. RESULTS: ACR20 response rates at week 24 were 67.9%, 57.5%, and 14.8% for sarilumab 150 mg, sarilumab 200 mg, and placebo, respectively. Serious treatment-emergent adverse events were reported by 9.9%, 6.3%, 0%, and 13.3% of patients in the sarilumab 150 mg, sarilumab 200 mg, placebo to sarilumab 150 mg, and placebo to sarilumab 200 mg groups, respectively. No deaths occurred. The incidence of infections ranged from 52.5 to 67.9%, with five serious infections for the sarilumab 150 mg group and one for the group switched from placebo to 200 mg sarilumab. Absolute neutrophil count < 1.0 Giga/l occurred in 13.6% and 7.5% of patients in the sarilumab 150 and 200 mg groups, respectively, and was not associated with infection. CONCLUSIONS: In Japanese MTX-IR RA patients treated with sarilumab (150 and 200 mg q2w) in combination with MTX, sustained clinical efficacy was shown by significant improvement in signs, symptoms, and physical function; bridging between this and a previous global study was achieved. At week 52, the safety profiles of both doses of sarilumab were generally similar, as previously observed and as expected based on IL-6 class. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02293902 . Registered on 19 November 2014.
31620132 Long Non-coding RNA HIX003209 Promotes Inflammation by Sponging miR-6089 via TLR4/NF-κB S 2019 Accumulating studies have suggested that long non-coding RNAs (lncRNAs) have drawn more and more attention in rheumatoid arthritis (RA), which can function as competitive endogenous RNAs (ceRNAs) in inflammation and immune disorders. Previously, we have found that lncRNA HIX003209 is differentially expressed in RA. However, the precise mechanism of lncRNA HIX003209 in RA is still vague. We aim to elucidate the role and its targeted microRNA of lncRNA HIX003209 in RA as ceRNA. Significantly increased expression of lncRNA HIX003209 was observed in the peripheral blood mononuclear cells (PBMCs) from RA cases. It was positively associated with TLR2 and TLR4 in RA. Besides, peptidoglycan (PGN) and lipopolysaccharide (LPS) could enhance the expression of lncRNA HIX003209, which reversely promoted the proliferation and activation of macrophages through IκBα/NF-κB signaling pathway. Moreover, HIX003209 was involved in TLR4-mediated inflammation via targeting miR-6089 in macrophages. LncRNA HIX003209 functions as a ceRNA and exaggerates inflammation by sponging miR-6089 through TLR4/NF-κB pathway in macrophages, which offers promising therapeutic strategies for RA.
31713730 Diagnostic test accuracy of magnetic resonance imaging and ultrasound for detecting bone e 2020 Apr OBJECTIVE: To evaluate and compare the diagnostic test accuracy of magnetic resonance imaging (MRI) and ultrasound (US) for bone erosion in rheumatoid arthritis (RA) patients for a specific and efficient diagnostic recommendation. METHOD: To evaluate the diagnostic accuracy, the sensitivity, specificity, area under the summary receiver operating characteristic curve, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of MRI and US for detecting bone erosion were calculated. Subgroup analyses were conducted to evaluate the performance of these values with different standard references when compared with types of machines and scanning positions. RESULTS: Data from 26 articles were extracted for calculation. The comprehensive values of sensitivity and specificity were 0.77 (95% CI 0.63, 0.87)/0.89 (95% CI 0.80, 0.95) and 0.61 (95% CI 0.43, 0.77)/0.95 (95% CI 0.88, 0.98) for MRI and US, respectively. The 1.5-T Signa MRI system, General Electric© (sensitivity 0.66; specificity 0.90), and different models of LOGIQ US units and General Electric© (sensitivity 0.66; specificity 0.91) had better diagnostic capability to detect bone erosion, while the 2nd metacarpophalangeal joint (sensitivity 0.70; specificity 0.98) showed the best diagnostic performance among the hand joints with US. CONCLUSIONS: Neither MRI nor US showed satisfactory diagnostic test accuracy in detecting bone erosion. However, the 1.5-T Signa MRI system, General Electric©, and different models of LOGIQ US units and General Electric© showed similarly good performance in detecting bone erosion in RA patients, while the 2nd metacarpophalangeal joint is the best recommended scanning position during US. KEY POINTS: • In this study, we evaluated the diagnostic accuracy of US and MRI for bone erosion in RA patients, neither MRI nor US showed perfect diagnostic test accuracy.• 1.5-T Signa system and the LOGIQ units both from General Electric© are the machine types of MRI and US with the greatest performance, respectively.• The 2nd MCP joint is the scanning position recommended during US test.• Different reference standards will greatly influence the judgment of the results.
32172753 The effects of total glucosides of paeony (TGP) and paeoniflorin (Pae) on inflammatory-imm 2019 Jan Rheumatoid arthritis (RA) is a chronic inflammatory and systemic autoimmune disease with an unknown aetiology. Accumulative studies suggest that the pathogenesis of RA involves the excessive activation of synoviocytes and immune cells, increasing the secretion of inflammatory mediators and cytokines in synoviocytes, causing dysfunctional E-prostanoid (EP)-G-protein-cyclic adenosine monophosphate (cAMP) and mitogen-associated-protein kinase (MAPK) signalling in synoviocytes. Total glucosides of paeony (TGP) extracted from the roots of Paeonia lactiflora Pall, was approved by the China Food and Drug Administration as an anti-inflammatory and immuno-modulator drug in 1998. Paeoniflorin (Pae), a water-soluble monoterpene glucoside,is the main effective component of TGP. TGP and Pae produce anti-inflammatory and immuno-regulatory effects by suppressing immune cells and synoviocytes activation, decreasing inflammatory substance production and restoring abnormal signalling in synoviocytes. In this review, the regulation of the inflammatory-immune responses and the therapeutic mechanism between RA and TGP and Pae are discussed in detail. The aim of this review was to provide novel insights into the treatment of RA.
31333004 The Importance of Log Ferritin and Transferrin /Log Ferritin in Differentiating Iron Defic 2019 Jan The most common types of anemia in rheumatoid arthritis (RA) are iron deficiency anemia (IDA) and anemia of chronic disease (ACD).The differentiation between both is important and challenging. Our objective is to select the most accurate method that differentiates IDA from ACD in RA patients. This case control study was carried out on 80 RA patients. 40 RA patients with anemia and 40 RA patients without anemia, complete blood count, assessment of disease activity using DAS 28 score, serum iron, transferrin level, transferrin saturation (TSAT), serum ferritin, log ferritin and transferrin /log ferritin were tested, anemic patients were divided into 2 subgroups according to TSAT: group Ia (with low TSAT) and group Ib (with normal TSAT). There was a statistically significant difference between anemic and non-anemic RA patients as regard serum iron level and transferrin saturation. Among the anemic group 67.5% had low TSAT (IDA) and 32.5% had normal TSAT (ACD). In these 2 subgroups there was no significant differences as regard DAS28 score, blood indices, serum ferritin and transferrin /log ferritin) and there was a positive correlation between TSAT and ferritin and log ferritin and a significant negative correlation between TSAT and transferrin/log ferritin. In conclusions, Iron deficiency anemia is prevalent in RA patients. A combination of serum ferritin and TSAT is simple and accurate parameter to differentiate both. Log ferritin and transferrin /log ferritin may be promising new parameters in diagnosis of IDA in general population but their use in inflammatory diseases like RA still has a limitation.
31476270 Smoking cessation intervention for reducing disease activity in chronic autoimmune inflamm 2019 Sep 2 BACKGROUND: Chronic inflammatory joint diseases (IJDs) affect 1% to 2% of the population in developed countries. IJDs include rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and other forms of spondyloarthritis (SpA). Tobacco smoking is considered a significant environmental risk factor for developing IJDs. There are indications that smoking exacerbates the symptoms and worsens disease outcomes. OBJECTIVES: The objective of this review was to investigate the evidence for effects of smoking cessation interventions on smoking cessation and disease activity in smokers with IJD. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library; PubMed/MEDLINE; Embase; PsycINFO; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); and three trials registers to October 2018. SELECTION CRITERIA: We included randomised controlled trials testing any form of smoking cessation intervention for adult daily smokers with a diagnosis of IJD, and measuring smoking cessation at least six months after baseline. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included two studies with 57 smokers with a diagnosis of rheumatoid arthritis (RA). We identified no studies including other IJDs. One pilot study compared a smoking cessation intervention specifically for people with RA with a less intensive, generic smoking cessation intervention. People included in the study had a mean age of 56.5 years and a disease duration of 7.7 years (mean). The second study tested effects of an eight-week cognitive-behavioural patient education intervention on cardiovascular disease (CVD) risk for people with RA and compared this with information on CVD risk only. The intervention encouraged participants to address multiple behaviours impacting CVD risk, including smoking cessation, but did not target smoking cessation alone. People included in the study had a mean age of 62.2 years (intervention group) and 60.8 years (control group), and disease duration of 11.6 years (intervention group) and 14.1 years (control group). It was not appropriate to perform a meta-analysis of abstinence data from the two studies due to clinical heterogeneity between interventions. Neither of the studies individually provided evidence to show benefit of the interventions tested. Only one study reported on adverse effects. These effects were non-serious, and numbers were comparable between trial arms. Neither of the studies assessed or reported disease activity or any of the predefined secondary outcomes. We assessed the overall certainty of evidence as very low due to indirectness, imprecision, and high risk of detection bias based on GRADE. AUTHORS' CONCLUSIONS: We found very little research investigating the efficacy of smoking cessation intervention specifically in people with IJD. Included studies are limited by imprecision, risk of bias, and indirectness. Neither of the included studies investigated whether smoking cessation intervention reduced disease activity among people with IJD. High-quality, adequately powered studies are warranted. In particular, researchers should ensure that they measure disease markers and quality of life, in addition to long-term smoking cessation.