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32822057 Dose tapering of biologic agents in patients with rheumatoid arthritis-results from a coho 2021 Mar OBJECTIVE: To assess the association of demographic and clinical factors with the clinical decision of tapering biologic disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) in daily practice. METHODS: All RA patients receiving bDMARDs were documented by 14 rheumatologists when presenting in 9 specialized private practices. Statistical analyses employed multivariable logistic models for dose reduction with the covariates age, gender, disease duration until bDMARD start, smoking status, disease activity, comorbidity, functional capacity, radiographic damage, concomitant methotrexate (MTX) treatment, rheumatoid factor positivity, and glucocorticoid use. In the multivariable model (MVM), missing values were imputed. RESULTS: Data of 586 RA patients on bDMARD treatment were available, 171 of which (29%) received a reduced dose. The highest rates of patients with dose reduction were seen for rituximab (67%) and infliximab (50%). The degree of dose reduction was most prominent for rituximab (57%). In the MVM, 6/11 covariates were significantly associated with dose reduction: age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.05; P = 0.002), time between disease onset and bDMARD start (OR 1.03, 95% CI 1.01-1.06; P = 0.015), DAS 28 < 2.6 (OR 1.55, 95% CI 1.01-2.37; P = 0.045), MTX therapy (OR 1.52, 95% CI 1.03-2.25; P = 0.036), comorbidity (OR 1.20, 95% CI 1.01-1.42; P = 0.036), and glucocorticoid dose (OR 0.82, 95% CI 0.76-0.89; P < 0.001). CONCLUSION: DAS 28 remission, concomitant MTX, and lower glucocorticoid doses were positively associated with dose tapering of bDMARDs in RA patients. While this could be expected, the reason for the association with age, comorbidity, and the time between disease onset and bDMARD start is less clear. Key points • In rheumatology practice, tapering of biologic disease modifying antirheumatic drugs is feasible in nearly 30% of patients with rheumatoid arthritis. • The degree of dose reduction may exceed 50% of the recommended dose. • In a multivariable model, concomitant methotrexate is positively associated with dose tapering of biologic disease modifying antirheumatic drugs.
33058561 Association of Agricultural, Occupational, and Military Inhalants With Autoantibodies and 2021 Mar OBJECTIVE: To determine the association of inhalant exposures with rheumatoid arthritis (RA)-related autoantibodies and severity in US veterans. METHODS: Participants in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were mailed surveys assessing occupational, agricultural, and military inhalant exposures. Demographic characteristics, disease activity, functional status, and extraarticular features were obtained from the VARA registry, while HLA-DRB1 shared epitope (SE) status, anti-cyclic citrullinated peptide (anti-CCP) antibodies, and rheumatoid factor (RF) were measured using banked DNA/serum from enrollment. Associations between inhalant exposures and RA-related factors (autoantibodies, severity, and extraarticular features) were assessed using multivariable linear and logistic regression models adjusted for age, sex, race, and tobacco use and stratified by SE status. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: Questionnaires were returned by 797 of 1,566 participants (50.9%). Survey respondents were older, more often White or male, and less frequently smokers, and had lower disease activity compared to nonrespondents. Anti-CCP positivity was more common among veterans exposed to burn pits (OR 1.66 [95% CI 1.02, 2.69]) and military waste disposal (OR 1.74 [95% CI 1.04, 2.93]) independent of other factors. Among participants who were positive for SE alleles, burn pit exposure (OR 5.69 [95% CI 2.73, 11.87]) and military waste disposal exposure (OR 5.05 [95% CI 2.42, 10.54]) were numerically more strongly associated with anti-CCP positivity. Several inhalant exposures were associated with the presence of chronic lung disease, but not with the presence of RF or the level of disease activity. CONCLUSION: Military burn pit exposure and military waste disposal exposure were independently associated with the presence of anti-CCP antibodies in RA patients. These findings are consistent with emerging evidence that various inhalant exposures influence autoantibody expression and RA risk.
33253095 Metabolomic analysis of synovial fluids from rheumatoid arthritis patients using quasi-tar 2021 Nov OBJECTIVES: Synovial fluid (SF) accumulates extensively in joints of individuals with rheumatoid arthritis (RA), which reflects the pathological state of the synovium and disease activity. This study applied quasi-targeted liquid chromatography-mass spectrometry/mass spectrometry, an advanced metabolomics technique, to find characteristic metabolisms in RA. METHODS: SF samples from the patients (n=20) were collected and examined using the metabolomic technique. SF samples from patients with osteoarthritis (OA) (n=20) were used as controls. RESULTS: Four hundred and seventy-nine variable metabolites were detected, and 250 of these metabolites were identified by searching the Human Metabolome Database (HMDB) and a self-constructed information list of possible metabolites. S-plot and volcano plot analysis detected 22 metabolites with differential levels in RA SF compared with those in OA SF. With these 22 candidate metabolites, pathway analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database detected upregulation of pyrimidine metabolism and purine metabolism, and downregulation of fatty acid biosynthesis and unsaturated fatty acid biosynthesis in RA SF. Receiver operating characteristic (ROC) analysis and logistic regression models detected increased levels of guaiacol, naringenin, phenylpropanolamine and vanillylmandelic acid in RA SF. Furthermore, the naringenin level showed positive correlation with rheumatic factor (RF) and anti-cyclic citrillinated peptides (anti-CCP) levels. CONCLUSIONS: Our study suggests disturbed pyrimidine metabolism, purine metabolism, fatty acid biosynthesis and unsaturated fatty acid biosynthesis, as well as increased naringenin level, are characteristic metabolisms in RA.
33229974 Rheumatology in the era of precision medicine: synovial tissue molecular patterns and trea 2021 Jan PURPOSE OF REVIEW: A critical unmet need in rheumatoid arthritis (RA) is the identification of biomarkers that predict which of the available medications will be most effective for an individual in order to lower disease activity sooner than is afforded by the current treat-to-target approach. Here we will discuss recent reports examining the potential for synovial tissue molecular, cellular, and spatial profiling in defining objective measures of treatment response and therein developing personalized medicine for RA. RECENT FINDINGS: Recent high-dimensional molecular profiling of RA synovium has provided unprecedented resolution of the cell types and pathways in tissues affected by rheumatic diseases. Heightened attention to tissue architecture is also emerging as a means to classify individual disease variation that may allow patients to be further stratified by therapeutic response. Although this wealth of data may have already pinpointed promising biomarkers, additional studies, likely including tissue-based functional drug response assays, will be required to demonstrate how the complex tissue environment responds. SUMMARY: Molecular, cellular, and more recently spatial profiling of the RA synovium are uncovering fundamental features of the disease. Current investigations are examining whether this information will provide meaningful biomarkers for individualized medicine in RA.
34462261 Rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome shared 2022 Mar OBJECTIVES: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) share many clinical manifestations and serological features. The aim of this study was to identify the common transcriptional profiling and composition of immune cells in peripheral blood in these autoimmune diseases (ADs). METHODS: We analysed bulk RNA-seq data for enrichment of biological processes, transcription factors (TFs) and deconvolution-based immune cell types from peripheral blood mononuclear cells (PBMCs) in 119 treatment-naive patients (41 RA, 38 pSS, 28 SLE and 12 polyautoimmunity) and 20 healthy controls. The single-cell RNA-seq (scRNA-seq) and flow cytometry had been performed to further define the immune cell subsets on PBMCs. RESULTS: Similar transcriptional profiles and common gene expression signatures associated with nucleosome assembly and haemostasis were identified across RA, SLE, pSS and polyautoimmunity. Distinct TF ensembles and gene regulatory network were mainly enriched in haematopoiesis. The upregulated cell-lineage-specific TFs PBX1, GATA1, TAL1 and GFI1B demonstrated a strong gene expression signature of megakaryocyte (MK) expansion. Gene expression-based cell type enrichment revealed elevated MK composition, specifically, CD41b(+)CD42b(+) and CD41b(+)CD61(+) MKs were expanded, further confirmed by flow cytometry in these ADs. In scRNA-seq data, MKs were defined by TFs PBX1/GATA1/TAL1 and pre-T-cell antigen receptor gene, PTCRA. Cellular heterogeneity and a distinct immune subpopulation with functional enrichment of antigen presentation were observed in MKs. CONCLUSIONS: The identification of MK expansion provided new insights into the peripheral immune cell atlas across RA, SLE, pSS and polyautoimmunity. Aberrant regulation of the MK expansion might contribute to the pathogenesis of these ADs.
34510294 Body mass index trend and variability in rheumatoid arthritis. 2022 Feb OBJECTIVE: To characterize and compare trends in body mass index (BMI) and variability in BMI between subjects with rheumatoid arthritis (RA) and matched non-RA subjects and to determine predictors of BMI trends and variability within RA subjects. METHODS: This retrospective population-based cohort study included 1114 Olmsted County, Minnesota residents, 558 with incident RA (age ≥ 18 years, 1987 ACR criteria met in 1995-2009) and 556 non-RA subjects from the same underlying population with similar age, sex, and index calendar year. All subjects were followed until death, migration, or 12/31/2018. Generalized linear models with smoothing splines and random effects to account for multiple measurements per subject were used to examine trends in BMI measurements over time. RESULTS: Mean BMI of patients with incident RA (28.8 kg/m(2)) was not significantly different from that of non-RA subjects (28.9 kg/m(2)). There was no significant difference in BMI trends over time between RA and non-RA cohorts, or between seropositive for rheumatoid factor (RF) and/or citrullinated antibody (CCP-antibody) and seronegative RA patients, or between male and female subjects. RA subjects were noted to have significantly higher BMI variability following diagnosis compared to non-RA subjects [difference in standard deviation between RA and non-RA subjects prior to index (p = 0.12), 0-5 years after index (p = 0.044), and 5-15 years after index (p = 0.013)]. CONCLUSION: The BMI trajectory of the RA population is not significantly different compared to that of the non-RA population, but patients with RA demonstrate higher variability in BMI following diagnosis compared to the non-RA population. Key Points • This study uniquely characterizes longitudinal trajectory in BMI measures and their variability in the RA population versus the non-RA population • This study suggests that RA patients have greater BMI variability compared to the non-RA population, which is highly relevant as BMI variability is increasingly understood as a cardiovascular risk factor.
35000788 The point of no return? Functional disability transitions in patients with and without rhe 2022 Feb OBJECTIVE: To assess transition probability between different levels of functional disability (FD) and time spent with FD in patients with versus without rheumatoid arthritis (RA) after RA incidence/index date. METHODS: This retrospective population-based cohort study included Olmsted County, Minnesota residents (1987 ACR criteria met in 1999-2013) and comparators without RA from the same area with similar age, sex and RA incidence/index date. Activities of Daily Living (ADL) were obtained by self-report questionnaires annually since 1999. FD was defined as having difficulty with ≥1 ADL. Multistate modeling was used to estimate the probability of transitioning between FD states. RESULTS: Five hundred fifty-eight patients with RA and 457 comparators completed ≥2 questionnaires and were included. Patients with RA had increased risk of transitioning from no FD to FD: Hazard Ratio (HR) 2.4; 95%CI:1.9-3.0. Each additional FD at RA onset reduced the probability of returning to no FD by 14%. However, the probability of having ≥1 FD was stable between RA incidence and 10-year follow-up. In the first 15 years of disease, patients with RA spent on average 10.1 years without FD and 3.4 years with ≥1 FD versus 11.6 years and 2.0 years (p<0.001) in comparators. CONCLUSION: Patients with RA remain functionally disadvantaged compared to individuals without RA. The likelihood of returning to no FD in RA decreases with each additional preexisting FD. However, the probability of FD does not increase within 10 years of RA onset, potentially reflective of the benefits of disease-modifying treatments in RA.
33707483 Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level th 2021 Mar 11 Abatacept, an inhibitor of CD28 mediated T-cell activation, has been shown to be effective in controlling inflammation during rheumatoid arthritis (RA). However, its effects on immune regulatory B and T cells (Bregs and Tregs) has not been fully explored. Thirty-one RA patients treated with abatacept for ≥ 6 months along with 31 RA patients treated with other modalities as well as 30 healthy controls were recruited. Of these 62 RA patient, 49 (79%) were females with a mean age of 54 ± 12 years and disease duration of 10 ± 6 years. The blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and Luminex Multiplex assay. Treatment with abatacept significantly enhanced the blood level of IL-35(+) IL-10(+) Bregs (P = 0.0007). Their levels were higher in the blood of remitted patients (DAS28-CRP < 2.6) compared to the unremitted ones (P = 0.0173), 6 months following abatacept treatment initiation. Moreover, abatacept treatment significantly enhanced the blood levels of LAG3(+) conventional and unconventional Tregs of RA patients. This increase in the blood levels of Bregs and Tregs was accompanied with an elevated serum level of IL-35 and IFN-β in abatacept-treated patients. Therefore, Abatacept efficiency to achieve remittance in RA could be attributed, in part, to its ability to enhance immune regulatory cells, especially IL-135(+) IL-10(+) Bregs.
34975909 Diversity of Vascular Niches in Bones and Joints During Homeostasis, Ageing, and Diseases. 2021 The bones and joints in the skeletal system are composed of diverse cell types, including vascular niches, bone cells, connective tissue cells and mineral deposits and regulate whole-body homeostasis. The capacity of maintaining strength and generation of blood lineages lies within the skeletal system. Bone harbours blood and immune cells and their progenitors, and vascular cells provide several immune cell type niches. Blood vessels in bone are phenotypically and functionally diverse, with distinct capillary subtypes exhibiting striking changes with age. The bone vasculature has a special impact on osteogenesis and haematopoiesis, and dysregulation of the vasculature is associated with diverse blood and bone diseases. Ageing is associated with perturbed haematopoiesis, loss of osteogenesis, increased adipogenesis and diminished immune response and immune cell production. Endothelial and perivascular cells impact immune cell production and play a crucial role during inflammation. Here, we discuss normal and maladapted vascular niches in bone during development, homeostasis, ageing and bone diseases such as rheumatoid arthritis and osteoarthritis. Further, we discuss the role of vascular niches during bone malignancy.
35017341 Severe acute respiratory syndrome coronavirus 2 and risk of inhospital mortality among end 2021 Mar According to the elevated infection mortality risks, the incidence of coronavirus disease 2019 (COVID-19) could be raised in rheumatoid arthritis patients with end-stage renal disease (ESRD). Our objectives are to describe the impact of COVID-19 infection on rheumatoid arthritis patients with end-stage renal disease and to identify the risk of in-hospital mortality, comorbid conditions. and the proper way to deal with this category. It was a retrospective analysis of COVID-19 patients in Saudi Arabia from March 1, 2020 to April 27, 2020 and from May 27, 2020 to August 20, 2020. Of 10,482 patients with COVID-19, 419 had ESRD. We assessed main (in-hospital death) outcomes and secondary (mechanical breathing and residence) outcomes. Patients with ESRD were aged and more comorbid disorders. Rheumatoid arthritis patients with ESRD were aged. ESRD rheumatoid arthritis patients have a higher hospital mortality risk relative to rheumatoid arthritis patients not getting complicated with ESRD (31.7% vs. 25.4%, chances 1.38, and 95% trust range 1.12-1.70). After population and comorbid conditions had changed, the rate of rise stayed the same (changed chances: 1.37, 1.09-1.73). In both the crude and modified study (1.62, 1.26-2.07; vs. 1.57, 1.22-2.02), chances for the period of stay of seven or more days have been higher inside a group than in the non-ESRD group. Old age, respiratory support, lymphopenia, and elevated blood urea nitrogen and low serum ferritin were the independent contributing factors for the in-hospital mortality of ESRD rheumatoid arthritis patients infected with severe acute respiratory syndrome coronavirus 2.
33307512 Iguratimod inhibits osteoclastogenesis by modulating the RANKL and TNF-α signaling pathwa 2021 Jan BACKGROUND: Iguratimod, a small molecular drug, has been proven to have effective bone protection for treatment of patients with bone loss-related diseases, such as rheumatoid arthritis (RA). However, the exact bone protective mechanism of iguratimod remains to be determined. The purpose of this study was to better explore the underlying mechanism of bone protection of iguratimod. METHODS: Bone marrow monocytes from C57/BL6 mice were stimulated with either RANKL or TNF-α plus M-CSF. The effects of iguratimod on morphology and function of osteoclasts were confirmed by TRAP staining and bone resorption assay, respectively. The expression of osteoclast related genes was detected by RT-PCR and the activation of signal pathway was detected by Western blotting. We used rodent models of osteoporosis (ovariectomy) and of arthritis (modified TNF-α-induced osteoclastogenesis) to evaluate the osteoprotective effect of iguratimod in vivo. RESULTS: Iguratimod potently inhibited osteoclast formation in a dose-dependent manner at the early stage of RANKL-induced osteoclastogenesis, whereas iguratimod had no effect on M-CSF-induced proliferation and RANK expression in bone marrow monocytes. Bone resorption was significantly reduced by both early and late addition of iguratimod. Administration of iguratimod prevented bone loss in ovariectomized mice. The blockage of osteoclastogenesis elicited by iguratimod results from abrogation of the p38、ERK and NF-κB pathways induced by RANKL. Importantly, Iguratimod also dampened TNF-α-induced osteoclastogenesis in vitro and attenuated osteoclasts generation in vivo through disrupting NF-κB late nuclear translocation without interfering with IκBα degradation. CONCLUSIONS: Iguratimod not only suppresses osteoclastogenesis by interfering with RANKL and TNF-α signals, but also inhibits the bone resorption of mature osteoclasts. These results provided promising evidence for the therapeutic application of iguratimod as a unique treatment option against RA and especially in prevention of bone loss.
34380068 Circulating Mir-140 and leptin improve the accuracy of the differential diagnosis between 2022 Jan The differential diagnosis of psoriatic arthritis (PsA) and rheumatoid arthritis (RA) is difficult because of the lack of diagnostic clinical signs and reliable biomarkers. This study investigated microRNAs (miRNA) and adipokines as potential additional markers to discriminate PsA from RA. The expression profile of miRNA (miR-21, miR-140, miR-146a, miR-155, miR-181b, miR-223, miR-let-7e) and inflammatory cytokines (IL-1β, IL-6, IL-17a, IL-23a, TNF-α) from peripheral blood mononuclear cells of PsA and RA patients compared to healthy controls (HC) were evaluated by real-time PCR, and serum adipokines (adiponectin, chemerin, leptin, resistin, visfatin) and cytokines by ELISA assay. Univariable binary logistic regression was used to find the association between PsA and potential predictors. The gene expression of miRNA and cytokines and the serum levels of adipokines were found significantly different in PsA and RA patients compared to HC, as well as in PsA versus RA. MiR-140 gene expression resulted up-regulated in PsA patients and reduced in RA in comparison to HC, and, for the first time, significantly higher in PsA compared with RA. Serum levels of IL-23a and leptin were significantly increased in PsA and RA populations than in HC, as well as in PsA versus RA. Furthermore, circulating TNF-α was up-regulated in PsA and RA in comparison to controls, while resulted higher in RA than in PsA. Univariable binary logistic regression analysis found the above-mentioned markers associated to PsA versus RA. Our results first demonstrated an increased expression of circulating miR-140 and serum leptin in PsA patients compared to RA, which were identified as potential additional biomarkers to discriminate PsA from RA. Since the differential diagnosis of PsA and RA poses challenges in clinical practice, our data may help to enhance the diagnostic performance of PsA in daily practice.
33579481 PAMAM dendrimers functionalised with an anti-TNF α antibody and chondroitin sulphate for 2021 Feb Rheumatoid arthritis is a chronic autoimmune disease characterised by joint synovial inflammation, along with cartilage and bone tissue destruction. Dendrimers can offer new opportunities as drug delivery systems of molecules of interest. Herein we aimed to develop poly(amidoamine) dendrimers (PAMAM), functionalised with chondroitin sulphate (CS), lined with anti-TNF α antibodies (Abs) to provide anti-inflammatory properties. Physicochemical characterisation demonstrated that anti-TNFα Abs-CS/PAMAM dendrimer NPs were successfully produced. The in vitro studies revealed that CS/PAMAM dendrimer NPs did not affect the ATDC5 and THP-1 cell lines' metabolic activity and proliferation, presenting good cytocompatibility and hemocompatibility. Moreover, anti-TNFα Abs-CS/PAMAM dendrimer NPs showed suitable TNF α capture capacity, making them appealing for new immunotherapies in RA patients.
33556758 Ultra-microangiography in evaluating the disease activity of rheumatoid arthritis and enha 2021 Apr OBJECTIVE: Ultra-microangiography (UMA) is a novel Doppler technique that has high sensitivity for low-velocity blood flows. In this study, a distinctive imaging feature, penetrating blood vessels on the surface of eroded bones within the inflamed joints, was observed on UMA. We aimed to investigate the feasibility of UMA in assessing disease activity and identify the clinical value of the UMA feature for evaluating rheumatoid arthritis (RA). METHODS AND MATERIALS: Power-Doppler ultrasound (PDUS) and UMA were performed on small joints of RA patients. The semiquantitative scores of PDUS and UMA of the joints were assessed and compared. The UMA imaging feature of penetrating vessels on the surface of eroded bones was evaluated, and the patients were divided into three groups based on imaging features. (Group 1: no inflammatory signs; Group 2: inflammatory US features but no UMA features; and Group 3: detected UMA features). The correlations between the groups and clinical parameters were assessed. RESULTS: A total of 52 patients with RA were recruited, with 364 joints (MCP, PIP, MTP and wrist) scanned. Synovial blood vessel signals were detected for 68 by PDUS and for 93 by UMA (display rate of blood vessel signals: 18.68 % VS 25.55 %). UMA presented better display capability of blood vessels within the inflamed regions than that of PDUS in overall. Significant differences were detected in clinical scores (P < 0.0001 for DAS28 [ESR], DAS28 [CRP], SDAI, CDAI, CRP P = 0.0303, SJC P = 0.0059, and TJC P = 0.0423) between Group 2 and 3. Significant correlations between the groups and clinical parameters were also observed (DAS28 [ESR] ρ=0.750; DAS28 [CRP] ρ=0.762; SDAI ρ=0.778; CDAI ρ=0.773; CRP ρ= 0.524; SJC ρ=0.742; TJC ρ=0.693, P < 0.0001), indicating that the UMA feature was related to high disease activity. CONCLUSIONS: UMA can help enhance the detection rate of micro-vascularization. The UMA feature of the penetrating vessels on the surface of eroded bones is likely to be associated with severe disease activity.
34276648 IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption. 2021 OBJECTIVE: Autoantibodies are detected in most patients with rheumatoid arthritis (RA) and can be of the IgM, IgG or IgA subclass. Correlations between IgA autoantibodies and more severe disease activity have been previously reported, but the functional role of IgA autoantibodies in the pathogenesis of RA is ill understood. In this study, we explored the effect of IgA immune complexes on osteoclast mediated bone resorption. METHODS: Anti-citrullinated peptide antibody (ACPA) and anti-carbamylated protein (anti-CarP) antibody levels of the IgA and IgG isotype and rheumatoid factor (RF) IgA were determined in synovial fluid (SF) of RA patients. Monocytes, neutrophils, and osteoclasts were stimulated with precipitated immune complexes from SF of RA patients or IgA- and IgG-coated beads. Activation was determined by neutrophil extracellular trap (NET) release, cytokine secretion, and bone resorption. RESULTS: NET formation by neutrophils was enhanced by SF immune complexes compared to immune complexes from healthy or RA serum. Monocytes stimulated with isolated SF immune complexes released IL-6 and IL-8, which correlated with the levels of ACPA IgA levels in SF. Osteoclasts cultured in the presence of supernatant of IgA-activated monocytes resorbed significantly more bone compared to osteoclasts that were cultured in supernatant of IgG-activated monocytes (p=0.0233). Osteoclasts expressed the Fc receptor for IgA (FcαRI; CD89) and Fc gamma receptors. IgA-activated osteoclasts however produced significantly increased levels of IL-6 (p<0.0001) and IL-8 (p=0.0007) compared to IgG-activated osteoclasts. Both IL-6 (p=0.03) and IL-8 (p=0.0054) significantly enhanced bone resorption by osteoclasts. CONCLUSION: IgA autoantibodies induce release of IL-6 and IL-8 by immune cells as well as osteoclasts, which enhances bone resorption by osteoclasts. We anticipate that this will result in more severe disease activity in RA patients. Targeting IgA-FcαRI interactions therefore represents a promising novel therapeutic strategy for RA patients with IgA autoantibodies.
33677724 Patient-controlled outpatient follow-up on demand for patients with rheumatoid arthritis: 2021 Sep INTRODUCTION: Scheduled routine visits in patients with rheumatoid arthritis (RA) may be in a stable period without active disease. Consequently, there is a demand for developing outpatient control procedures which cater to the needs of the individual patient. OBJECTIVE: This study aims to compare a patient-controlled outpatient follow-up system, Open Outpatient Clinic Programme (OOCP), with traditional scheduled routine follow-up (TSRF) regarding patient satisfaction and disease activity markers in RA patients. METHOD: In a 2-year randomized controlled trial, RA patients were allocated to OOCP or TSRF. OOCP patients had no scheduled appointments but were allowed acute appointments with their rheumatologist and had access to nurse-led consultations and a telephone helpline. Appointments for the TSRF group were scheduled according to routine procedures (clinical parameters: DAS-28, C-reactive protein, VAS pain, tender and swollen joint count, HAQ-DI and radiographs; psychological parameters: VAS patient satisfaction and EQ-5D). RESULTS: Of 282 patients, 239 completed the study (OOCP/TSRF characteristics: age 61.4 ± 10.5/60.9 ± 12.2 years, females 77/74%, ACPA positive 66/65%). At years 1 and 2, OCCP had fewer visits (year 2: 2.6 ± 1.6 vs. 3.5 ± 2; p < 0.0005) but more phone calls (year 2: 0.7 ± 1.4 vs. 0.1 ± 0.3; p < 0.0005) compared to TSRF. OOCP was comparable to TSRF regarding clinical and psychological outcome measures, and no radiographic progression was observed. CONCLUSIONS: OOCP was associated with significantly fewer visits but with more phone calls to the nurse and was comparable with TSGentofte University HospitalRF regarding clinical, psychological and radiographic outcomes. Thus, the organization of outpatient care according to OOCP may be applied to strengthen patient-centred care in patients with RA. ClinicalTrials.gov Identifier (July 20, 2020): NCT04476875 Key points • In a patient-controlled outpatient follow-up system, RA patients had significantly fewer visits compared to traditional follow-up. • The patient-controlled follow-up system was comparable with traditional follow-up regarding clinical, psychological and radiographic outcomes. • Organization of outpatient care according to a patient-controlled follow-up system may be applied to strengthen patient-centred care in patients with RA.
34941954 Staying moving, staying strong: Protocol for developing culturally appropriate information 2021 INTRODUCTION: Addressing disparities in arthritis care is an important yet unmet health need for Aboriginal and Torres Strait Islander people in Australia (respectfully Aboriginal people herewith). Despite the significant prevalence and burden of arthritis within Aboriginal communities, access to care for arthritis is low. One means to reduce existing disparities in health care is to address current challenges relating to the appropriateness and acceptability of health care information resources for Aboriginal people. Health information sources can help to empower patients and their families to have greater involvement in their care and to engage in self-management of their condition. Despite an extensive range of arthritis information resources being available, currently no resources have been culturally adapted and developed in collaboration with Aboriginal consumers with arthritis. This paper outlines the processes that will be undertaken within the Staying Moving, Staying Strong project. This project aims to develop culturally secure arthritis information for Aboriginal people with osteoarthritis, rheumatoid arthritis, lupus and gout. METHODS AND ANALYSIS: The overarching principle guiding this project is cultural security, referring to the incorporation of processes such that the research will not compromise the cultural rights, values and expectations of Aboriginal people. This project will prioritise partnerships, community engagement, community benefit, sustainability, transferability, and capacity building and therefore uphold the cultural rights and values of Aboriginal people. In this six-phase project we will; 1) Establish a community reference group and advisory committee; 2) Explore the health information needs and preferences of Aboriginal people with arthritis; 3) Synthesise the existing key recommendations in high quality clinical practice guidelines on arthritis care; 4) Culturally adapt key clinical recommendations; 5) Develop culturally appropriate arthritis resources and; 6) Qualitatively evaluate the developed resources.
34534689 All-cause and cause-specific mortality of patients with rheumatoid arthritis in Korea: A n 2022 Jan OBJECTIVE: To compare all-cause and cause-specific mortality between rheumatoid arthritis (RA) patients versus the general population of Korea. METHODS: A nationally representative RA population aged≥40 years was identified from Korea National Health Insurance Service (KNHIS) database. We estimated age- and sex-adjusted all-cause and cause-specific standardized mortality ratios (SMRs) with 95% confidence intervals (CIs), comparing RA patients to the general population. Subgroup analyses were done by sex, age group, calendar year, and biologics use. RESULTS: We identified 79,352 RA patients with 6404 deaths during 2011-2016. The all-cause SMR [95% CI] of RA patients compared to the general population was 1.53 [1.49-1.56]. The top five causes of death were cancer (19.5%), respiratory disease (19.1%), cardiovascular disease (18.8%), systemic rheumatic diseases (9.5%, 9.1% due to RA), and infection (6.1%). Cause-specific SMRs [95% CI] were 0.95 [0.90-1.01] for cancer, 3.34 [3.15-3.52] for respiratory disease, 1.26 [1.18-1.33] for cardiovascular disease, 3.41 [3.08-3.75] for infection, and 4.88 [3.10-6.65] for non-RA systemic rheumatic disease. The SMR of RA population was slightly higher among men than women, and highest in their 60s and 70s. The yearly SMR increased from 1.10 [1.01-1.18] in 2011 to 1.85 [1.75-1.95] in 2016 due to population aging and comorbidity accumulation. Users of biologics showed a higher SMR than non-users (1.82 [1.69-1.96] vs. 1.50 [1.46-1.54]), due to higher RA activity, and more comorbidities despite a younger mean age. CONCLUSION: RA patients in Korea experienced 1.5-fold increase in all-cause mortality compared to the general population. Except for cancer, the top five causes of death were associated with excess mortality among RA patients. RA-associated mortality was largely determined by age, RA activity, and comorbidity status.
34353032 Comparative efficacy and safety of four classical prescriptions for clearing damp-heat rec 2021 Jul BACKGROUND: In China, along with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), some herbal formulae for clearing damp-heat are widely applied in treating rheumatoid arthritis (RA). We aimed to summarize and compare the clinical effects of 4 guideline-recommended formulae, including Baihuguizhi decoction, Dangguiniantong decoction, Simiao pill, and Xuanbi decoction. METHODS: PubMed, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technique Journals (CQVIP), WanFang, and SinoMed (CBM) databases were searched for randomized controlled trials from inception to July 2020 evaluating the efficacy and safety of these recommended herbal formulae combined with 1 csDMARD versus csDMARD alone in RA patients. A pairwise meta-analysis was conducted in RevMan 5.3 software, and a Bayesian network meta-analysis (NMA) was performed with Stata 14.0, R 4.0.2, GeMTC 0.14.3, and JAGS 4.3.0 software. Cochrane Handbook 5.1.0 was used to assess the risk of bias. Publication bias was evaluated using Egger's test, the trim-fill adjustment, and funnel plots. Trial sequential analysis (TSA) was performed to validate the overall results. The rank probability of interventions was calculated and clustered by the surface under the cumulative ranking curve (SUCRA). Pharmacologic actions of formulae were explored through the network pharmacology approach. RESULTS: A total of 15 studies, including 1,079 individuals, were identified. Simiao pill + csDMARD [SMPPD, odds ratio (OR) =6.62, 95% confidence interval (CI): 2.88 to 16.84] was superior to csDMARDs alone in clinical efficiency, and was more able to reduce C-reactive protein and erythrocyte sedimentation rate levels [mean difference (MD) =-7.91, 95% CI: -17.41 to -1.25; MD =-9.31, 95% CI: -14.48 to -5.56 respectively]. Although publication bias was observed (P=0.033), the trim-fill method indicated that the pooled values kept stable. Fewer adverse events (AEs) were shown with SMPPD (6.45%). TSA confirmed the results of efficacy rate at SMPPD. Network pharmacology included 5 common components and 66 common targets among 4 formulae in treating RA, involving regulating immunity and relieving inflammation. DISCUSSION: SMPPD might be a preferable complementary therapy for RA. However, considering the limitations of this study, recommendations for clinical practice should be validated by the results of further well-designed studies.
33704557 [Safety aspects of the treatment with glucocorticoids for rheumatoid arthritis]. 2021 May Glucocorticoids (GC) are still the recommended initial treatment for rheumatoid arthritis, although the treatment should be temporary and confined to the administration of low doses. The complex mechanism of action is accompanied by side effects that particularly occur in long-term treatment exceeding 5 mg prednisolone per day. In this dosage range they promote osteoporosis, diabetes and hyperglycemia as well as cardiovascular events and infections, thereby contributing to an excess mortality. The risks of GC treatment are dependent on patient-related parameters, such as age, comorbidity and additional medication. A negative influence of very low steroid doses on overall survival is possibly due to high cumulative steroid doses; however, the data in this respect are contradictory. Recently, a validated index was developed to monitor GC-related toxicity. In the future, this index should help to describe the advantages of steroid-sparing treatment strategies. In the future, more selectively acting substances could achieve an uncoupling of desired and adverse effects.