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ID PMID Title PublicationDate abstract
32380774 VAV1 Gene Polymorphisms in Patients with Rheumatoid Arthritis. 2020 May 5 INTRODUCTION: Rheumatoid arthritis (RA) is an important public health problem because this disease often causes disability. RA is a chronic, destructive autoimmune disease that leads to joint destruction and the development of extraarticular manifestations. VAV1 is an intracellular signal transduction protein that plays a significant role in signal transduction in T cells and affects T cell development, proliferation and activation. The VAV1 gene contains 27 exons and is located on chromosome 19. In this study, we examined the association between VAV1 rs2546133 and rs2617822 polymorphisms and RA. METHODS: We examined 422 patients with RA and 338 healthy subjects as the control group. RESULTS: Among RA patients, there was a statistically significant increase in the frequency of VAV1 rs2546133 polymorphism in T allele carriers (TT + CT versus CC, odds ratio: 1.69, 95% confidence interval 1.05-2.73, p = 0.035). There was no statistically significant difference in the distribution of the rs2617822 genotypes and alleles between RA patients and the control group. Additionally, patients who carried the VAV1 rs2546133 T and rs2617822 G allele presented an increased frequency of extraarticular manifestations: vasculitis, amyloidosis and Sjogren syndrome. CONCLUSIONS: The results suggest an association between VAV1 gene rs2617822 polymorphism and RA.
32631736 Prolonged presence of SARS-CoV-2 in a COVID-19 case with rheumatoid arthritis taking igura 2020 Oct We report a coronavirus disease 2019 (COVID-19) case with rheumatoid arthritis taking iguratimod. The patient who continued iguratimod therapy without dose reduction was treated with ciclesonide had an uneventful clinical course, but prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed after resolution of symptoms. The effects of disease-modifying antirheumatic drugs (DMARDs) and ciclesonide on clinical course and viral shedding remain unknown and warrant further investigation.
32855529 Deficiency of β-arrestin2 exacerbates inflammatory arthritis by facilitating plasma cell 2021 May β-arrestin2 (β-arr2) is, a key protein that mediates desensitization and internalization of G protein-coupled receptors and participates in inflammatory and immune responses. Deficiency of β-arr2 has been found to exacerbate collagen antibody-induced arthritis (CAIA) through unclear mechanisms. In this study we tried to elucidate the molecular mechanisms underlying β-arr2 depletion-induced exacerbation of CAIA. CAIA was induced in β-arr2(-/-) and wild-type (WT) mice by injection of collagen antibodies and LPS. The mice were sacrificed on d 13 after the injection, spleen, thymus and left ankle joints were collected for analysis. Arthritis index (AI) was evaluated every day or every 2 days. We showed that β-arr2(-/-) mice with CAIA had a further increase in the percentage of plasma cells in spleen as compared with WT mice with CAIA, which was in accordance with elevated serum IgG1 and IgG2A expression and aggravating clinical performances, pathologic changes in joints and spleen, joint effusion, and joint blood flow. Both LPS stimulation of isolated B lymphocytes in vitro and TNP-LPS challenge in vivo led to significantly higher plasma cell formation and antibodies production in β-arr2(-/-) mice as compared with WT mice. LPS treatment induced membrane distribution of toll-like receptor 4 (TLR4) on B lymphocytes, accordingly promoted the nuclear translocation of NF-κB and the transcription of Blimp1. Immunofluorescence analysis confirmed that more TLR4 colocalized with β-arr2 in B lymphocytes in response to LPS stimulation. Depletion of β-arr2 restrained TLR4 on B lymphocyte membrane after LPS treatment and further enhanced downstream NF-κB signaling leading to additional increment in plasma cell formation. In summary, β-arr2 depletion exacerbates CAIA and further increases plasma cell differentiation and antibody production through inhibiting TLR4 endocytosis and aggravating NF-κB signaling.
31969232 Comparable effects of traditional cardiovascular risk factors on subclinical atheroscleros 2020 Sep OBJECTIVES: Patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) have an increased premature prevalence of atherosclerosis. We aimed to determine whether there are differences in the prevalence of classic cardiovascular risk factors between SLE and RA. We also analysed the effect of traditional cardiovascular risk factors on the development of subclinical atherosclerosis in both conditions and if some disease-characteristic features are associated with these traditional cardiovascular risk factors. METHODS: This was a cross-sectional study encompassing 602 individuals, 276 SLE and 326 RA patients. Subclinical atherosclerosis (presence of carotid plaques and carotid intima-media thickness [cIMT]) was determined by carotid ultrasonography. A multivariable regression analysis was performed to evaluate whether classic cardiovascular-related risk factors differentially influence subclinical carotid atherosclerosis in SLE compared to RA patients. RESULTS: Age (interaction factor [if] p=0.000), hypertension (if p=0.034), and diabetes (if p=0.037) had a higher effect on cIMT in RA than in SLE subjects. However, these traditional cardiovascular factors did not yield different effects on the presence of carotid plaques in RA and SLE when the univariate interaction was analysed. In addition, no differences were found in the influence of hypertension, diabetes, dyslipidaemia or current smoking on cIMT or carotid plaque after adjusting for demographics, the presence of other traditional cardiovascular factors, and disease-related data. Moreover, the additive effect of several cardiovascular risk factors on the subclinical carotid atherosclerosis did not differ between the two diseases. CONCLUSIONS: The influence of traditional cardiovascular risk factors on cIMT and carotid plaque is similar in RA and SLE.
32960885 Enhanced treatment strategies and distinct disease outcomes among autoantibody-positive an 2020 Sep BACKGROUND: Based on different genetic and environmental risk factors and histology, it has been proposed that rheumatoid arthritis (RA) consists of 2 types: autoantibody-positive and autoantibody-negative RA. However, until now, this remained hypothetical. To assess this hypothesis, we studied whether the long-term outcomes differed for these 2 groups of RA patients. METHODS AND FINDINGS: In the Leiden Early Arthritis Clinic cohort, 1,285 consecutive RA patients were included between 1993 and 2016 and followed yearly. Treatment protocols in routine care improved over time, irrespective of autoantibody status, and 5 inclusion periods were used as instrumental variables: 1993-1996, delayed mild disease-modifying antirheumatic drug (DMARD) initiation (reference period); 1997-2000, early mild DMARDs; 2001-2005, early methotrexate; 2006-2010, early methotrexate followed by treat-to-target adjustments; 2011-2016, similar to 2006-2010 plus additional efforts for very early referral. Three long-term outcomes were studied: sustained DMARD-free remission (SDFR) (persistent absence of clinical synovitis after DMARD cessation), mortality, and functional disability measured by yearly Health Assessment Questionnaire (HAQ). Treatment response in the short term (disease activity) was measured by Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Linear mixed models and Cox regression were used, stratified for autoantibody positivity, defined as IgG anti-CCP2 and/or IgM rheumatoid factor positivity. In total, 823 patients had autoantibody-positive RA (mean age 55 years, 67% female); 462 patients had autoantibody-negative RA (age 60 years, 64% female). Age, gender, and percentage of autoantibody-positive patients were stable throughout the inclusion periods. Disease activity significantly decreased over time within both groups. SDFR rates increased after introduction of treat-to-target (hazard ratio [HR] 2006-2010 relative to 1993-1996: 3.35 [95% CI 1.46 to 7.72; p = 0.004]; HR 2011-2016: 4.57 [95% CI 1.80 to 11.6; p = 0.001]) in autoantibody-positive RA, but not in autoantibody-negative RA. In autoantibody-positive RA, mortality decreased significantly after the introduction of treat-to-target treatment adjustments (HR 2006-2010: 0.56 [95% CI 0.34 to 0.92; p = 0.023]; HR 2011-2016: 0.33 [95% CI 0.14 to 0.77; p = 0.010]), but not in autoantibody-negative RA (HR 2006-2010: 0.79 [95% CI 0.40 to 1.56; p = 0.50]; HR 2011-2016: 0.36 [95% CI 0.10 to 1.34; p = 0.13]). Similarly, functional disability improved in autoantibody-positive RA for the periods after 2000 relative to 1993-1996 (range -0.16 [95% CI -0.29 to -0.03; p = 0.043] to -0.32 [95% CI -0.44 to -0.20; p < 0.001] units of improvement), but not in autoantibody-negative RA (range 0.10 [95% CI -0.12 to 0.31; p = 0.38] to -0.13 [95% CI -0.34 to 0.07; p = 0.20] units of improvement). Limitations to note were that treatment was not randomized-but it was protocolized and instrumental variable analysis was used to obtain comparable groups-and that a limited spread of ethnicities was included. CONCLUSIONS: Although disease activity has improved in both autoantibody-positive and autoantibody-negative RA in recent decades, the response in long-term outcomes differed. We propose that it is time to subdivide RA into autoantibody-positive RA (type 1) and autoantibody-negative RA (type 2), in the hope that this leads to stratified treatment in RA.
31903118 ASIC1a induces synovial inflammation via the Ca(2+)/NFATc3/ RANTES pathway. 2020 Rationale: Synovial inflammation is one of the main pathological features of rheumatoid arthritis (RA) and is a key factor leading to the progression of RA. Understanding the regulatory mechanism of synovial inflammation is crucial for the treatment of RA. Acid-sensing ion channel 1a (ASIC1a) is an H(+)-gated cation channel that promotes the progression of RA, but the role of ASIC1a in synovial inflammation is unclear. This study aimed to investigate whether ASIC1a is involved in the synovial inflammation and explore the underlying mechanisms in vitro and in vivo. Methods: The expression of ASIC1a and nuclear factor of activated T cells (NFATs) were analyzed by Western blotting, immunofluorescence, and immunohistochemistry both in vitro and in vivo. The Ca(2+) influx mediated by ASIC1a was detected by calcium imaging and flow cytometry. The role of ASIC1a in inflammation was studied in rats with adjuvant-induced arthritis (AA). Inflammatory cytokine profile was analyzed by protein chip in RA synovial fibroblasts (RASF) and verified by a magnetic multi-cytokine assay and ELISA. The NFATc3-regulated RANTES (Regulated upon activation, normal T cell expressed and secreted) gene transcription was investigated by ChIP-qPCR and dual-luciferase reporter assay. Results: The expression of ASIC1a was significantly increased in human RA synovial tissues and primary human RASF as well as in ankle synovium of AA rats. Activated ASIC1a mediated Ca(2+) influx to increase [Ca(2+)]i in RASF. The activation/overexpression of ASIC1a in RASF up-regulated the expression of inflammatory cytokines RANTES, sTNF RI, MIP-1a, IL-8, sTNF RII, and ICAM-1 among which RANTES was increased most remarkably. In vivo, ASIC1a promoted inflammation, synovial hyperplasia, articular cartilage, and bone destruction, leading to the progression of AA. Furthermore, activation of ASIC1a upregulated the nuclear translocation of NFATc3, which bound to RANTES promoter and directly regulated gene transcription to enhance RANTES expression. Conclusion: ASIC1a induces synovial inflammation, which leads to the progression of RA. Our study reveals a novel RA inflammation regulatory mechanism and indicates that ASIC1a might be a potential therapeutic target for RA.
32692720 Mst1 promotes mitochondrial dysfunction and apoptosis in oxidative stress-induced rheumato 2020 Jul 21 In this study, we investigated the role of macrophage stimulating 1 (Mst1) and the AMPK-Sirt1 signaling pathway in the oxidative stress-induced mitochondrial dysfunction and apoptosis seen in rheumatoid arthritis-related fibroblast-like synoviocytes (RA-FLSs). Mst1 mRNA and protein expression was significantly higher in hydrogen peroxide (H(2)O(2))-treated RA-FLSs than untreated controls. H(2)O(2) treatment induced the mitochondrial apoptotic pathway by activating caspase3/9 and Bax in the RA-FLSs. Moreover, H(2)O(2) treatment significantly reduced mitochondrial membrane potential and mitochondrial state-3 and state-4 respiration, but increased reactive oxygen species (ROS). Mst1 silencing significantly reduced oxidative stress-induced mitochondrial dysfunction and apoptosis in RA-FLSs. Sirt1 expression was significantly reduced in the H(2)O(2)-treated RA-FLSs, but was higher in the H(2)O(2)-treated Mst1-silenced RA-FLSs. Pretreatment with selisistat (Sirt1-specific inhibitor) or compound C (AMPK antagonist) significantly reduced the viability and mitochondrial function in H(2)O(2)-treated Mst1-silenced RA-FLSs by inhibiting Sirt1 function or Sirt1 expression, respectively. These findings demonstrate that oxidative stress-related upregulation and activation of Mst1 promotes mitochondrial dysfunction and apoptosis in RA-FLSs by inhibiting the AMPK-Sirt1 signaling pathway. This suggests the Mst1-AMPK-Sirt1 axis is a potential target for RA therapy.
32404570 The clinical impact of absolute lymphocyte count in peripheral blood among patients with m 2020 Jun 20 Regressive lymphoproliferative disorders (R-LPD) after methotrexate (MTX) withdrawal are one of the specific features of methotrexate - associated lymphoproliferative disorders (MTX-LPD). Although the impact of the absolute lymphocyte count (ALC) on the pathogenesis of R-LPD has been recently emphasized, understanding relapse/regrowth events (RRE) and differences among LPD subtypes is necessary. In this study, we confirmed ALC recovery in the regressive group (R-G; R-LPD without RRE) and relapse/regrowth group (R/R-G; R-LPD with RRE). The increase in ALC lasted at least 2 years in R-G, whereas it decreased within 3 years in R/R-G, supporting the better overall survival (OS) in R-G, as previously reported. In addition, our study suggested that an ALC of 1000/µL at the time of development of LPD is a significant predictor for treatment-free survival (TFS). Furthermore, an ALC of 1000/µL at 6 months after MTX withdrawal was found to be a significant indicator of TFS and OS for R-G and R/R-G. The ALC decreased gradually before LPD development in R/R-G, whereas it decreased 6 months before LPD development in R-G, confirming the important role of ALC in the pathogenesis of MTX-LPD such as regressive events and RRE. In addition to ALC, other predictive factors, such as serum C-reactive protein and soluble interleukin-2 receptors, may be helpful in the management of MTX-LPD, including the decision making for an additional chemotherapy for regressive LPD after MTX withdrawal.
31410723 Patient Decision Aid (PDA) for Patients with Rheumatoid Arthritis Reduces Decisional Confl 2020 Feb OBJECTIVES: The aim of this study was to develop and assess the effectiveness of a patient decision aid (PDA) to support treatment decision making in Spanish patients with moderate-to-severe rheumatoid arthritis (RA) who fail to achieve the therapeutic goal with the current disease-modifying antirheumatic treatment strategy. METHODS: The PDA was developed in accordance with the International Patient Decision Aids Standards recommendations. A steering group led the project. Three literature reviews and two focus groups were performed to develop the PDA prototype. To check its comprehensibility, acceptability, and feasibility, alpha-testing was performed using the Decision Support Acceptability Scale (DSAS). Beta-testing was conducted to assess preliminary evidence of PDA efficacy using the Decisional Conflict Scale (DCS) before and after PDA use. Readiness was evaluated using the Preparation for Decision Making Scale (PDMS). RESULTS: The PDA included (1) a brief description of RA, (2) treatment information, and (3) a values clarification section. Alpha-testing revealed that most patients considered that the information was presented in a good or excellent way and it could help clarify their values and facilitate treatment decision making. Most rheumatologists agreed that the PDA was easy to understand, to use, and allowed them to reach a shared decision. Beta-testing showed that PDA significantly reduced overall patients' decisional conflict [33.2 (DE: 21.4) vs 24.6 (23.5); p < 0.001] and prepared the patient for decision making [PDMS: 67.5 (21.0)]. CONCLUSIONS: We developed a PDA for Spanish patients with moderate-to-severe RA that reduces patients' decisional conflict and increases their readiness for decision making. The use of this PDA in routine clinical practice may improve the quality of the decision-making process and the quality of the choices made.
33331309 [Clinical characteristics and related factors of rheumatoid arthritis complicated with tub 2020 Dec 18 OBJECTIVE: To investigate the clinical characteristics and high risk factors of Rheumatoid arthritis (RA) complicated with tuberculosis infection. METHODS: Patients with rheumatoid arthritis diagnosed in the hospital of Sichuan Provincial People's Hospital from January 2007 to January 2017 was retrospectively collected, who were enrolled in the study group. A control group was randomly selected from the RA patients hospitalized in the same period without co-infection at a ratio of 1 :2. The general data, clinical data, laboratory test data, treatment plan, etc. of the two groups were collected in detail for single factor statistical analysis. Then multivariate Logistic regression was used to analyze the independent risk factors of RA complicated with tuberculosis infection with statistical significance in univariate analysis. RESULTS: The clinical manifestations of fever (83.3%) were most common, followed by cough (69%) and body mass loss (45.2%). In the infected group, pulmonary tuberculosis accounted for 73.3%. In the infected group the chest CT showed two or more cases, accounting for 59%. There were 9 cases (33.3%) occurring in the typical tuberculosis occurrence site. Compared with the control group, the erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) levels, and the daily average dose of glucocorticoid in 1 year in the infected group were higher than those in the control group. And those differences were statistically significant(P < 0.05). There were no significant differences in gender, age, disease duration, disease activity score, white blood cell (WBC), platelet (PLT), hemoglobin (Hb), immunoglobulin G (IgG), complement (C), Anti cyclic citrullinated peptide antibody (anti-CCP), CD4(+)T cell count, and immunosuppressant use (P > 0.05). Multivariate Logistic regression analysis showed that CRP levels(OR=1.016, 95%CI:1.002-1.031) and the daily average dose of glucocorticoid in 1 year(OR=1.229, 95%CI:1.066-1.418)were the independent risk factors of RA complica-ted with tuberculosis infection. CONCLUSION: RA patients with tuberculosis infection are mainly phthisis. The clinical manifestations of RA combined with tuberculosis infection are lack of specificity, and the chest imaging features of pulmonary tuberculosis are diverse, which are easy to be misdiagnosed. CRP levels and the daily average dose level of glucocorticoid in 1 year were risk factors for RA and tuberculosis infection.
32476277 A comparative study of PF-06438179/GP1111 (an infliximab biosimilar) and reference inflixi 2020 Jul AIM: PF-06438179/GP1111 (PF-SZ-IFX) is a biosimilar of reference infliximab (Remicade(®) ). This analysis compared the efficacy of PF-SZ-IFX and reference infliximab sourced from the European Union (IFX-EU) in patient subgroups from a randomized, comparative study of PF-SZ-IFX versus IFX-EU. METHODS: Patients with rheumatoid arthritis were randomized 1:1 to PF-SZ-IFX (n = 324) or IFX-EU (n = 326); study drug (3 mg/kg) was administered intravenously at weeks 0, 2, and 6, then every 8 weeks thereafter. Subgroup analyses of efficacy endpoints such as American College of Rheumatology criteria for ≥20% clinical improvement (ACR20), change in high-sensitivity C-reactive protein (hs-CRP), and change in Disease Activity Score in 28 joints, four components based on hs-CRP (DAS28-CRP) at weeks 14 and 30 were performed by age, gender, race, region, immunogenicity status, and treatment history. RESULTS: Overall, ACR20 response rates as well as changes in DAS28-CRP and hs-CRP at week 14 were similar between PF-SZ-IFX and IFX-EU within the subgroups of age, gender, race, region, treatment history, and immunogenicity status. Results to week 30 support overall similarity in efficacy between the two treatment arms in all subgroups. CONCLUSION: Overall, PF-SZ-IFX and IFX-EU were similar in efficacy within the analyzed subgroups of age, gender, race, region, treatment history, and immunogenicity status. The efficacy results from these subgroup analyses were aligned with the previously described results for the overall population up to week 30.
32828309 The anti-inflammatory effect of the gut lactic acid bacteria-generated metabolite 10-oxo-c 2020 Sep 10 We evaluated the effect of gut bacterial metabolites of polyunsaturated fatty acids on inflammation and found that 10-oxo-cis-6,trans-11-octadecadienoic acid (γKetoC) strikingly suppressed LPS-induced IL-6 release from bone marrow-derived macrophages (BMMs), which was accompanied by reduced mRNA expression of Il6, TNF, and Il1b. γKetoC decreased the cAMP concentration in BMMs, suggesting that γKetoC stimulated G protein-coupled receptors. A Gq agonist significantly suppressed LPS-induced IL-6 expression in BMMs, whereas a Gi inhibitor partially abrogated γKetoC-mediated IL-6 suppression. Cytosolic Ca(2+) was markedly increased by γKetoC, which was partly but not fully abrogated by an ion channel inhibitor. Taken together, these data suggest that γKetoC suppresses inflammatory cytokine expression in macrophages primarily through Gq and partially through Gi. γKetoC suppressed osteoclast development and IL-6 expression in synovial fibroblasts from rheumatoid arthritis (RA) patients, suggesting the beneficial effect of γKetoC on the prevention or treatment of RA.
32124964 Expression and clinical significance of circular RNAs hsa_circ_0000175 and hsa_circ_000841 2020 Apr Circular RNAs (circRNAs) are a novel class of RNAs that may be used as biomarkers in clinical blood samples. However, the role of circRNAs in rheumatoid arthritis (RA) has not been extensively investigated. In the present study, six circRNAs, including hsa_circ_0082689, hsa_circ_0087798, hsa_circ_0000175, hsa_circ_0008410, hsa_circ_0049356 and hsa_circ_0032959 levels were determined in peripheral blood mononuclear cells (PBMCs) collected from 24 patients with RA and 24 healthy controls (HC) by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis. Hsa_circ_0000175 and hsa_circ_0008410 were selected for further evaluation in an independent cohort consisting of 63 patients with RA, 50 with systemic lupus erythematosus (SLE), 24 with ankylosing spondylitis (AS) and 21 HC. Spearman's rank correlation coefficient was used to analyze the correlation between these two circRNAs and the clinical characteristics of RA, and receiver operating characteristic (ROC) curves were constructed to evaluate their value in RA diagnosis. Multivariate analysis (logistic regression) was used to analyze the risk factors. Of the six selected circRNAs, the expression of hsa_circ_0000175 was found to be significantly reduced and the expression of hsa_circ_0008410 was significantly elevated in PBMCs from patients with RA compared with their levels in HC. The expression of hsa_circ_0000175 in patients with RA was correlated with anti‑citrullinated protein antibodies, white blood cell count, lymphocyte count, lymphocyte percentage, neutrophil count, neutrophil percentage and neutrophil‑to‑lymphocyte ratio. Furthermore, the expression of hsa_circ_0008410 was correlated with tender joint count, disease duration, platelet count and plateletcrit, indicating the activity and severity of RA. ROC curve analysis suggested that hsa_circ_0000175, hsa_circ_0008410, and the combination of hsa_circ_0000175 and hsa_circ_0008410 have significant value in the diagnosis of RA. Hsa_circ_0000175 and hsa_circ_0008410 also differed significantly between patients with RA, and those with SLE and AS. Moreover, logistic regression analysis revealed that the expression of PBMC hsa_circ_0000175 and hsa_circ_0008410 were risk factors for RA. Therefore, PBMC hsa_circ_0000175, hsa_circ_0008410, and the combination of PBMC hsa_circ_0000175 and hsa_circ_0008410 may improve the diagnostic accuracy for RA. In addition, the expression levels of PBMC hsa_circ_0000175 and hsa_circ_0008410 were associated with disease activity and severity of RA.
32963049 Infectious complications of rheumatoid arthritis and psoriatic arthritis during targeted a 2020 Dec Biological therapies have improved the outcomes of several major inflammatory, autoimmune and also neoplastic disorders. Those directed towards cytokines or other soluble mediators, cell-surface molecules or receptors or various components of intracellular signalling pathways may be associated with the occurrence of infections whose diversity depends on the particular immune target. In this context and following a keynote lecture given by one of us at the European League Against Rheumatism meeting on June 2018, a multidisciplinary group of experts deeply involved in the use of targeted and biological therapies in rheumatoid and psoriatic arthritis decided to summarise their recent vision of the immunological basis and epidemiology of infections occurring during targeted and biological therapies, and provide useful indications for their management and prevention.
31957303 Factors associated with successful discontinuation of certolizumab pegol in early rheumato 2020 Mar AIM: The Certolizumab-Optimal Prevention of joint damage for Early Rheumatoid Arthritis (C-OPERA) study demonstrated that in methotrexate (MTX)-naïve early RA patients with poor prognostic factors, 1-year certolizumab pegol (CZP) therapy added to the first year of 2-year optimized MTX therapy brings radiographic and clinical benefits through 2 years even after stopping CZP. This exploratory analysis aimed to identify factors at baseline and at CZP discontinuation associated with successful CZP discontinuation. METHODS: MTX-naïve early RA patients with poor prognostic factors entered C-OPERA (NCT01451203), a multicenter, randomized controlled trial. Patients were randomized to CZP + MTX (n = 159) or PBO + MTX (n = 157); those who completed the 1-year, double-blind period received MTX alone in Year 2 (CZP + MTX→MTX, n = 108; PBO + MTX→MTX, n = 71). Association between factors at baseline or at discontinuation of CZP and clinical/radiographic outcomes were evaluated by multiple logistic regression analysis. Predictive value cut-offs were calculated using receiver operating characteristic analysis. RESULTS: Sex (male) and low baseline Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR) were associated with simple disease activity index (SDAI) remission (≤3.3), whereas high baseline DAS28-ESR and modified total Sharp score (mTSS) were associated with clinically relevant radiographic progression (yearly progression mTSS > 3) at Week 104 (across both treatment arms). Low DAS28-ESR (<2.1) and rheumatoid factor (RF; <74 IU/mL) at discontinuation of CZP were associated with SDAI remission at Week 104. At Week 104, SDAI remission was achieved by 75.0% (42/56) of patients with low DAS28-ESR and RF at discontinuation, compared to 15.4% (2/13) of patients with high DAS28-ESR and RF. CONCLUSION: Patients with low RF and low disease activity after treatment with CZP + MTX may be able to discontinue CZP without risk of loss of response.
33124566 Interleukin-33 promotes proliferation and inhibits apoptosis of fibroblast-like synoviocyt 2021 Jul OBJECTIVES: The aim of our study was to determine the effect of interleukin (IL)-33 on the proliferation, apoptosis, and secretion of inflammatory cytokines by fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) and to investigate the underlying mechanisms. METHODS: Cultured RA FLSs and osteoarthritis (OA) FLSs were cocultured with different concentrations of IL-33. TUNEL assay and flow cytometry were used to detect apoptosis. Western blotting and Real-time (RT)-PCR were used to detect the expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), while the Cell Counting Kit-8 was used to determine cell proliferation in each cocultured group. Enzyme-linked immunosorbent assay was used to detect the expression levels of tumour necrosis factor (TNF)-α and IL-6 in the supernatant from each cell culture. Western blot analysis was used to determine the phosphorylated expression levels of the nuclear factor-kappa light chain enhancer of the activated B cells (NF-κB) pathway in each group. RESULTS: IL-33 inhibited RA FLS apoptosis, promoted FLS proliferation, increased Bcl-2 protein expression levels, and decreased Bax protein expression levels. It also increased the expression levels of inflammatory cytokines TNF-α and IL-6 and increased the expression levels of P-NF-κ B in FLSs. CONCLUSIONS: IL-33 inhibited apoptosis and promoted proliferation of FLSs; in addition, IL-33 increased the serum levels of inflammatory cytokines. The effect of IL-33 on RA FLSs was likely mediated via the NF-κB pathway.
32710102 Pre-operative withholding of infliximab and the risk of infections after major surgery in 2020 Dec 1 OBJECTIVES: Withholding TNF inhibitors (TNFI) before surgery has been recommended due to concern for post-operative infection. We examined the risks of post-operative infections and mortality in patients with RA in relation to the pre-operative timing of infliximab infusion. METHODS: In this population-based retrospective cohort study, we used US Medicare claims data from 2007 to 2015 to identify patients with RA who underwent coronary artery bypass grafting (CABG), aortic or vascular surgery, or bowel resection, and who were treated with infliximab in the 90 days prior to surgery. We examined associations between the timing of infusion and infections and mortality in the 30 days after surgery. We adjusted for the predicted probability of post-operative infection or death, demographic characteristics, use of MTX, post-operative blood transfusion and hospital volume. RESULTS: We studied 712 patients with CABG, 244 patients with vascular surgery and 862 patients with bowel resections. Post-operative pneumonia occurred in 7.4-11.9%, urinary tract infection in 9.0-15.2%, surgical site infection in 3.2-18.9%, sepsis in 4.2-9.6% and death in 3.5-7.0% among surgery cohorts. There was no association between the time from last infliximab dose to surgery and the risk of post-operative infection or mortality in any surgical cohort. No subgroups were identified that had an increased risk of infection with more proximate use of infliximab. CONCLUSION: Among elderly patients with RA, risks of infection and mortality after major surgery were not related to the pre-operative timing of infliximab infusion.
32735474 Differentiating Rheumatoid and Psoriatic Arthritis of the Hand: Multimodality Imaging Char 2020 Sep Accurate diagnosis and therapeutic intervention at an early stage is paramount for the management of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), which are the two major types of inflammatory arthritis that involve the hand joints. As more disease-specific medications are developed, medication selection according to the correct diagnosis becomes more important. A delay in diagnosis and inappropriate medication selection may result in poor functional prognosis. However, clinical differentiation between RA and PsA can be challenging and may become largely dependent on imaging interpretation results. Although there is substantial overlap in the imaging findings of RA and PsA, there are differences in the affected primary target sites, reflected by the various patterns of joint involvement, and different microanatomic localization of abnormalities within a single joint in each disease. Therefore, appropriate use of various imaging modalities and accurate image interpretation add significant value to the diagnosis and treatment process. The synovio-entheseal complex is an important concept for understanding the imaging features of PsA. The authors review the different features of RA and PsA of the hands seen with various imaging modalities, including radiography, US, MRI, and dual-energy CT, with updates on the contemporary role of imaging in diagnosis and treatment. The radiologist should have sufficient knowledge to interpret imaging findings and understand the strengths and weaknesses of each modality to recommend the appropriate imaging method and differentiate both diseases accurately. (©)RSNA, 2020.
30482075 Clinical predictors of inadequate response to conventional synthetic disease-modifying ant 2020 Jan Objectives: To investigate predictors of inadequate response to first conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) including methotrexate (MTX) in untreated rheumatoid arthritis (RA) patients in daily clinical practice.Methods: Inadequate response to MTX or other csDMARDs was defined as being not low disease activity at 12 months in more than 3 of 4 composite measures, and discontinuation or start of biologic DMARDs. The association between baseline factors and csDMARDs-IR was assessed by univariate and multivariate logistic regression analyses.Results: Four hundred and eleven and 146 patients were started on MTX and other csDMARDs, respectively; 218 patients were responsive to MTX, with a response rate of 47.0%. Tender joint count (TJC, ≥6 in 28joints, odds ratio [OR] = 1.67, 95% confidence interval [CI] 1.06-2.64) and CRP (≥1.0 mg/dL, OR = 1.72, 95%CI: 1.10-2.70) at baseline were identified as predictors on multivariate logistic regression analysis. TJC (OR = 3.60, 95%CI: 1.29-10.00) was the factor identified as a predictor of the development of other csDMARDs-IR.Conclusion: In this observational study, patients with untreated RA at risk of inadequate response to MTX included those with a higher TJC and higher CRP, while a higher TJC was the only independent predictor of an inadequate response to csDMARDs other than MTX.
33044725 Accessibility to biologics and its impact on disease activity and quality of life in patie 2021 May OBJECTIVE: Biologics are indicated in rheumatoid arthritis (RA) in case of persistent high disease activity despite conventional disease-modifying anti-rheumatic drugs (cDMARDs) or patients with contraindications to cDMARDs or poor prognostic factors. The purpose of this study was to compare the prescription rates of biologics in Kuwaiti and non-Kuwaiti patients and to assess whether this had an impact on disease activity and quality of life in RA patients. METHODS: Data were extracted from the Kuwait Registry for Rheumatic Diseases. Adult patients who satisfied the ACR classification criteria for RA from four major hospitals in Kuwait were evaluated from February 2013 through May 2018. The treatment agents, disease activity, and quality of life of Kuwaiti patients were compared with non-Kuwaiti patients. RESULTS: A total of 1651 RA patients were included; 806 (48.8%) were Kuwaiti patients. Among Kuwaiti patients, 62.5% were on biologic drugs in comparison with 14% of non-Kuwaiti patients. In comparison with non-Kuwaiti patients, Kuwaiti patients had significantly lower numbers of swollen joints (p < 0.001) and disease activity score-28 scores (p = 0.02) and less steroid use (p < 0.001) yet a significantly higher health assessment questionnaire-disability index (p < 0.001). Regression analysis showed that DAS-28 scores were significantly associated with the treatment type (p < 0.001) and that nationality was significantly predictive of the treatment type (p < 0.001). CONCLUSION: In the setting of easy accessibility to treatment for Kuwaiti patients, biologics were prescribed by rheumatologists at a higher rate than for non-Kuwaitis. This may explain the lower disease activity and the lower rate of steroid use in Kuwaiti patients than non-Kuwaitis. KEY POINTS: • Significant discrepancies in the rates of prescribing biologic therapies between KP and NKP in Kuwait were observed. • Several treatment outcomes were significantly better in the KP group than in the NKP group even after adjustment of confounding factors. • The poor access to biologic therapies was suggested to limit the effectiveness of RA treatments in the NKP group.