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ID PMID Title PublicationDate abstract
35635646 Pain and Fatigue Improvements in Patients Treated with Repository Corticotropin Injection 2022 May 30 Repository corticotropin injection (RCI; Acthar(®) Gel) is approved by the US Food and Drug Administration (FDA) for use in 19 indications, including for the treatment of selected patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), symptomatic sarcoidosis, uveitis, and keratitis. Despite treatment with disease-modifying antirheumatic drugs, many patients with RA, SLE, and other chronic inflammatory rheumatic diseases continue to be affected by severe pain and fatigue, indicating a need for other therapies. To examine the clinical data regarding the impact of RCI treatment on pain and fatigue in selected populations, this review included English-language peer-reviewed publications of clinical trials of any size and cohort studies with more than 10 patients that included pain and/or fatigue based on patient-reported outcomes (PROs) and/or physician-assessed measures in adults following treatment with RCI for RA, SLE, symptomatic sarcoidosis, uveitis, or keratitis. Literature searches identified eight studies that met these criteria. Four studies (reported in five publications) were in patients with RA or SLE, two in patients with sarcoidosis, one in patients with uveitis, and one in patients with noninfectious keratitis. Across the different types of studies assessed (clinical trials, chart reviews, real-world evidence), the results were consistent with respect to the impact of RCI treatment on improving pain and fatigue. As summarized in this review, data from patient- and physician-reported outcome measures in eight studies demonstrate that, in addition to improving more traditional efficacy measures, RCI may also improve pain and fatigue in patients with RA, SLE, symptomatic sarcoidosis, uveitis, and noninfectious keratitis.
35197210 Insights into peptidylarginine deiminase expression and citrullination pathways. 2022 Feb 21 Peptidylarginine deiminases (PADs) are calcium-dependent enzymes that mediate citrullination, an irreversible post-translational modification (PTM). PAD enzymes have received increasing attention in (patho-)physiology since multi-omics analysis accelerated their expression profiling. Here, we provide a comprehensive overview of PAD expression at the RNA and protein levels, and a list of annotated substrates per PAD isozyme. We discuss novel roles of citrullination in cellular growth, epigenetic regulation, tissue remodeling, inflammation, and cancer in mouse models and humans. Additionally, we cluster similar effects of protein deimination to offer a different perspective and improve our understanding of citrullination in health and disease. Citrullination should no longer be considered as a rare PTM, but as an important regulatory mechanism in physiology and pathology.
35274696 Exploring the disparity between inflammation and disability in the 10-year outcomes of peo 2022 Mar 11 OBJECTIVES: To identify groups of people with rheumatoid arthritis (RA) with different disability trajectories over ten years, despite comparable levels of inflammation. METHODS: Data for this analysis came from three European prospective cohort studies of people with RA (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN], Étude et Suivi des Polyarthrites Indifférenciées Récentes [ESPOIR]). Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1/1/2000, <24 months baseline symptom duration, and disability (Health Assessment Questionnaire [HAQ]) and inflammation (two-component disease activity score [DAS28-2C]) recorded at baseline and one other follow-up. People in each cohort also completed patient reported outcome measures at each assessment (pain, fatigue, depressive symptoms). Group-based trajectory models (GBTM) were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up. RESULTS: This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and participants were younger (mean [standard deviation] age: NOAR: 57.1 [14.6], ESPOIR: 47.6 [12.5], ERAN: 56.8 [13.8]; women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesised pattern (comparable DAS28-2C but different HAQ) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories. CONCLUSION: Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function.
35268519 Cardiovascular Magnetic Resonance Detects Inflammatory Cardiomyopathy in Symptomatic Patie 2022 Mar 5 BACKGROUND: Patients with inflammatory joint diseases (IJD) are more likely to develop cardiovascular disease compared with the general population. We hypothesized that cardiovascular magnetic resonance (CMR) could identify cardiac abnormalities in patients with IJD and atypical symptoms unexplained by routine clinical evaluation. PATIENTS-METHODS: A total of 51 consecutive patients with IJD (32 with rheumatoid arthritis, 10 with ankylosing spondylitis, and 9 with psoriatic arthritis) and normal clinical, electrocardiographic and echocardiographic workups, were referred for CMR evaluation due to atypical chest pain, shortness of breath, and/or palpitations. Their CMR findings were compared with those of 40 non-IJD controls who were referred for the same reason. All participants were examined using either a 1.5 T or 3.0 T CMR system. For T1/T2 mapping, comparisons were performed separately for each field strength. RESULTS: Biventricular systolic function was similar between groups. In total, 25 (49%) patients with IJD vs. 0 (0%) controls had replacement-type myocardial fibrosis (p < 0.001). The T2 signal ratio, early/late gadolinium enhancement, and extracellular volume fraction were significantly higher in the IJD group. Native T1 mapping was significantly higher in patients with IJD independent of the MRI field strength (p < 0.001 for both). T2 mapping was significantly higher in patients with IJD compared with controls only in those examined using a 1.5 T MR system-52.0 (50.0, 55.0) vs. 37.0 (33.5, 39.5), p < 0.001. CONCLUSIONS: In patients with IJD and a mismatch between cardiac symptoms and routine non-invasive evaluation, CMR uniquely identified a significant proportion of patients with myocardial inflammation. A CMR examination should be considered in patients with IJD in similar clinical settings.
35331233 Pharmacoeconomic analysis of biologics and methotrexate for rheumatoid arthritis from the 2022 Mar 24 OBJECTIVES: To evaluate the cost-effectiveness of biologics and methotrexate (MTX) for rheumatoid arthritis (RA) using the number needed to treat (NNT) concept and total actual health care cost. METHODS: This study included 121 RA patients with newly prescribed biologics and/or MTX between 2012 and 2017. The NNT was calculated based on the 24 week remission rate of Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI). RESULTS: Remission rates were 76.4% for DAS28-ESR and 45.4% for CDAI in the biologics group and 63.6% and 24.2%, respectively, in the MTX group. The NNT was calculated as 6.4 and 4.2 in the biologics group and 34.2 and 35.2 in the MTX group, respectively. Mean total actual health care costs were 1,044,066 JPY (9835 US$)/24 weeks per treated patient in the biologics group and 75,860 JPY (715 US$)/24 weeks in the MTX group. Although the effectiveness of biologics was superior to MTX from the standpoint of NNT, the mean total health care cost and mean cost per NNT were much higher in the biologics group. CONCLUSIONS: Cost-effectiveness is clearly higher for MTX than biologics from the standpoint of mean total health care cost per adjusted NNT under the Japanese health insurance system.
35296975 Effects of acute aerobic exercise on cytokines, klotho, irisin, and vascular endothelial g 2022 Mar 16 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that causes cartilage and bone damage as well as disability.  AIMS : The aim of this study was to examine the effects of acute aerobic exercise on cytokines such as serum interleukin-6 (IL-6), interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α) and irisin, vascular endothelial growth factor(VEGF) and klotho in RA patients.  METHODS: Forty RA patient and 40 healthy volunteers of the same age participated in this study. All participants walked on the treadmill for 30 minutes at 60-80% of maximal heart rate. Blood samples were taken before and immediately after the exercise. Serum levels of IL-6, IL1β, TNF-α and irisin, VEGF and klotho were measured by enzyme-linked immunosorbent analysis.  RESULTS: Baseline levels of inflammatory cytokines, irisin, VEGF and klotho were found to be higher in RA patients compared to the control group. In both groups, there was an increase in serum klotho levels after exercise compared to baseline (p<0.05), while a decrease in IL1β, TNF-α levels were observed. While serum VEGF level decreased in RA group, it increased in the control group(p<0.05). Irisin levels decreased in both groups. IL-6 level did not change in the control group, while it increased in RA group. A single exercise session had an acute anti-inflammatory effect in RA patients. CONCLUSION: It can be concluded that acute aerobic exercise can be beneficial for patients with RA through cytokine, irisin, klotho and VEGF levels, and also it can be safely implemented to the RA rehabilitation program for additional anti-inflammatory effects. Trial registration ClinicalTrials.gov: NCT04439682.
35289372 Effectiveness of Tacrolimus Concomitant with Biological Disease-Modifying Anti-Rheumatic D 2022 Mar 15 OBJECTIVES: The study aimed to investigate the effectiveness and tolerance of biological disease-modifying antirheumatic drugs (bDMARDs) therapy administered concomitantly with tacrolimus (TAC) treatment in patients with rheumatoid arthritis. METHODS: 2792 patients who underwent therapy with five bDMARDs (etanercept: ETN, adalimumab: ADA, golimumab: GLM, tocilizumab: TCZ, and abatacept: ABT) were enrolled. Among the study subjects, 1582 were concomitant methotrexate (MTX group), 147 were concomitant TAC (TAC group), and 1063 were non-concomitant MTX and TAC (non-MTX/TAC group). Primary outcome was the incident rate of discontinuation of bDMARDs by adverse events (AEs) or loss of efficacy. RESULTS: Concerning the analysis for each reasons of discontinuation, including AEs and loss of efficacy, the hazards ratio (HR) was significantly lower in TAC group than in non-MTX/TAC group (AEs: HR=0.39, 95 % confidence interval [CI], 0.23-0.68, loss of efficacy: HR=0.49, 95 % CI, 0.30-0.78). The loss of efficacy with the use of ETN and ABT was lower in TAC group than in non-MTX/TAC group. Concomitant TAC did not induce elevated risk for discontinuation of AEs in all bDMARDs analyses. CONCLUSIONS: Concomitant TAC with ABT or ETN showed higher retention rates than bDMARDs therapy without TAC or MTX. AEs did not increase over long-term observation.
35225987 Molecular Dynamics Study of Citrullinated Proteins Associated with the Development of Rheu 2022 Feb 11 Biological activity regulation by protein post-translational modification (PTM) is critical for cell function, development, differentiation, and survival. Dysregulation of PTM proteins is present in various pathological conditions, including rheumatoid arthritis (RA). RA is a systemic autoimmune disease that primarily affects joints, and there are three main types of protein PTMs associated with the development of this disease, namely, glycosylation, citrullination, and carbamylation. Glycosylation is important for the processing and presentation of antigen fragments on the cell surface and can modulate immunoglobulin activity. The citrullination of autoantigens is closely associated with RA, as evidenced by the presence of antibodies specific to citrullinated proteins in the serum of patients. Carbamylation and dysregulation have recently been associated with RA development in humans.In this study, we performed an overview analysis of proteins with post-translational modifications associated with the development of RA adverted in peer-reviewed scientific papers for the past 20 years. As a result of the search, a list of target proteins and corresponding amino acid sequences with PTM in RA was formed. Structural characteristics of the listed modified proteins were extracted from the Protein Data Bank. Then, molecular dynamics experiments of intact protein structures and corresponding structures with PTMs were performed regarding structures in the list announced in the ProtDB service. This study aimed to conduct a molecular dynamics study of intact proteins and proteins, including post-translational modification and protein citrullination, likely associated with RA development. We observed another exhibition of the fundamental physics concept, symmetry, at the submolecular level, unveiled as the autonomous repetitions of outside the protein structural motif performance globule corresponding to those in the whole protein molecule.
35642835 Elucidating a bidirectional association between rheumatoid arthritis and depression: A sys 2022 May 25 BACKGROUND: Rheumatoid arthritis (RA) and depression are conditions which commonly co-exist. Recent longitudinal studies now suggest a bidirectional association between these disorders, with inconsistent results. We conducted a systematic review and meta-analysis to examine this relationship. METHODS: Three electronic databases (PubMed, Embase and PsycINFO) were searched from inception to September 4, 2021 for cohort studies evaluating either the risk of depression in RA patients or the risk of RA in patients with depression, as well as the secondary outcome of all-cause mortality risk in RA patients with depression. A random effects model was used to summarize the included studies. RESULTS: Eleven cohort studies were included, comprising a total of 39,130 RA patients, 550,782 patients with depression and 7,802,230 controls. RA patients had a 47% greater risk of incident depression compared to controls, while patients with depression had a 34% greater risk of developing RA. Subgroup analysis by age was only significant in the ≥60 years old age group. RA patients with depression had an 80% increased risk of all-cause mortality compared to those without depression. LIMITATIONS: The results may have been confounded by factors such as differing methods of depression ascertainment across studies and overlap in presentation between the two conditions. CONCLUSION: There exists a bidirectional association between RA and depression especially in the elderly which increases mortality risk. This invites the need for clinicians to screen and be vigilant for the presence of these conditions.
35504203 An update on novel therapeutic intervention in Rheumatoid arthritis. 2022 Apr 30 Rheumatoid arthritis (RA) is an autoimmune disorder that is slow progressive destruction of the joints and is caused by autoantibodies that target a variety of organs thereby leading to auto-destruction. Patients diagnosed with RA develop deformity of joints and show gradual functional impairment if they do not receive treatment within the desired timeline. The availability of biological treatments and the introduction of treat-to-target regimens have dramatically enhanced the outcome for patients treated with RA conditions. Nevertheless, there is still attention required for RA because patients do not respond adequately to currently available treatment regimens. Over the past few decades, newer therapy methods are evolving to better understand the in-depth literature behind the actual cause of RA. Thus, getting an insight into the importance of RA there is a need for a shift in the existing treatment. This article focuses on a comprehensive review of the therapeutic potential of newer targets such as Janus Kinase-signal transducer and activator of transcription pathway, Granulocyte macrophage-colony stimulating factor, Bruton's Tyrosine Kinase Pathway, Phosphoinositide-3-kinase Pathway, Dendritic cells, Neuropathway, Receptor activator of nuclearfactor-kappa-Î’ ligand (RANKL) Inhibitors, Mesenchymal Stem Cells and Synovial Anatomy emphasizing on Synovial fibroblasts Myeloid Cells which have been summarized. In addition, novel therapeutic targets such as proteins, small molecular metabolites, and epigenetics are described in this article. Cytokines, chemokines, and other protein targets are among the protein target. Prostaglandins, leukotrienes, platelet-activating factor, cannabinoids, and specific fatty acid amide hydrolase are all examples of small molecular metabolites. DNA, RNA, and Histone Modification are epigenetic targets. Furthermore, the article provides an in-depth understanding of the exact mechanism in underlying pathophysiology in RA and thereby substantiating their evident therapeutic effect with ongoing clinical trials. Nevertheless, these newer targets would help to bring and paradigm shift in the treatment of this ancient autoimmune disorder.
34997912 Total Hip Replacement in Patients with Rheumatoid Arthritis: Trends in Incidence and Compl 2022 Apr INTRODUCTION: Advances in rheumatoid arthritis (RA) management have made disease remission achievable. We evaluated trends in total hip replacement (THR) and postoperative outcomes in patients with RA in Western Australia (WA) over more than three decades. METHODS: This was a retrospective analysis of routinely collected prospective data from a state-wide registry containing longitudinally linked administrative health data based on International Classification of Diseases (ICD) diagnostic and procedural codes. We included patients with two or more diagnostic codes for RA (between 1980 and 2015) and studied THR incidence rates (THR IR) and complication rates (revision, peri-prosthetic fracture, infection, venous thrombosis, and mechanical loosening). Survival rates were estimated by Kaplan-Meier method and predictors analyzed by Cox regression. RESULTS: We followed 9201 RA patients over 111,625 person-years, during which 1560 patients (16.9%) underwent THR. From 1985 to 2015, THR IR (per 1000 RA patient-years) decreased from 20.8 (95% CI 20.1-21.5) to 7.3 (95% CI 7.2-7.5), and 5-year THR-free survival increased from 84.3 to 95.3% (1980-2015). Ten-year prosthetic survival was 91.2%. Complication rates in the first 5 years post-THR decreased significantly from 13.1 to 3.7% (p < 0.001). Mechanical complications such as loosening and periprosthetic fracture rates decreased significantly (> 35%, P < 0.05), while infection and revision did not change over the observation period (p > 0.05). CONCLUSIONS: Over the last 30 years in RA patients, THR IR and mechanical complication rates decreased significantly, but the medical complication of infection has not changed significantly.
35586514 Comparison of remission criteria in patients with rheumatoid arthritis treated with biolog 2022 BACKGROUND: Biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD) are widely used for treatment of rheumatoid arthritis (RA), enabling patients to better achieve remission. OBJECTIVE: The objective of the study was to investigate and compare remission rates in RA patients treated with different b/tsDMARDs during the period 2013-2019. DESIGN: A longitudinal observational analysis was performed on data from a nationwide RA registry. METHODS: Remission rates in the KOBIO-RA registry were defined by a disease activity score in 28 joints (DAS28), clinical disease activity index (CDAI), simplified disease activity index (SDAI), and Boolean-based assessment. After initiating treatment with b/tsDMARDs, yearly remission rates in response to b/tsDMARDs, either all or as subgroups (tumor necrosis factor-α inhibitors, tocilizumab, abatacept, and Janus kinase inhibitors), were investigated for 5 years. Sustained remission was defined as remission maintained for two consecutive years. RESULTS: Patients (N = 1805) who completed at least one follow-up visit were analyzed (mean age = 55 years; 83.2% female). At month 12, 56.0% of patients achieved remission based on DAS28-C-reactive protein (CRP), 36.2% on DAS28-erythrocyte sedimentation rate (ESR), 10.4% on CDAI, 12.7% on SDAI, and 12.9% on Boolean criteria. Sustained remission rates were 62%, 40%, 13%, 11%, and 8% for the DAS28-CRP, DAS28-ESR, Boolean, SDAI, and CDAI remission criteria, respectively. Remission rates using the DAS28 definition varied most among the b/tsDMARD subgroups. CONCLUSION: Assessment of sustained remission using the CDAI, SDAI, or Boolean criteria is more stringent, yet congruous with the DAS28-based criteria in RA patients treated with b/tsDMARDs.
35368701 Identification of Tissue-Specific Expressed Hub Genes and Potential Drugs in Rheumatoid Ar 2022 Background: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by progressive, destructive polyarthritis. However, the cause and underlying molecular events of RA are not clear. Here, we applied integrated bioinformatics to identify tissue-specific expressed hub genes involved in RA and reveal potential targeted drugs. Methods: Three expression profiles of human microarray datasets involving fibroblast-like synoviocytes (FLS) were downloaded from the Gene Expression Omnibus (GEO) database, the differentially expressed mRNAs (DEGs), miRNAs (DEMs), and lncRNAs (DELs) between normal and RA synovial samples were screened using GEO2R tool. BioGPS was used to identified tissue-specific expressed genes. Functional and pathway enrichment analyses were performed for common DEGs using the DAVID database, and the protein-protein interaction (PPI) network of common DEGs was constructed to recognize hub genes by the STRING database. Based on receiver operating characteristic (ROC) curve, we further investigated the prognostic values of tissue-specific expressed hub genes in RA patients. Connectivity Map (CMap) was run to identify novel anti-RA potential drugs. The DEM-DEG pairs and ceRNA network containing key DEMs were established by Cytoscape. Results: We obtain a total of 418 DEGs, 23 DEMs and 49 DELs. 64 DEGs were verified as tissue-specific expressed genes, most derive from the hematologic/immune system (20/64, 31.25%). GO term and KEGG pathway enrichment analysis showed that DEGs focused primarily on immune-related biological process and NF-κB pathway. 10 hub genes were generated via using MCODE plugin. Among them, SPAG5, CUX2, and THEMIS2 were identified as tissue-specific expressed hub genes, these 3 tissue-specific expressed hub genes have superior diagnostic value in the RA samples compared with osteoarthritis (OA) samples. 5 compounds (troleandomycin, levodopa, trichostatin A, LY-294002, and levamisole) rank among the top five in connectivity score. In addition, 5 miRNAs were identified to be key DEMs, the lncRNA-miRNA-mRNA network with five key DEMs was formed. The networks containing tissue-specific expressed hub genes are as follows: ARAP1-AS2/miR-20b-3p/TRIM3, ARAP1-AS2/miR-30c-3p/FRZB. Conclusion: This study indicates that screening for identify tissue-specific expressed hub genes and ceRNA network in RA using integrated bioinformatics analyses could help us understand the mechanism of development of RA. Besides, SPAG5 and THEMIS2 might be candidate biomarkers for diagnosis of RA. LY-294002, trichostatin A, and troleandomycin may be potential drugs for RA.
35237070 Sarcopenia May Be a Risk Factor for Osteoporosis in Chinese Patients with Rheumatoid Arthr 2022 PURPOSE: Osteoporosis (OP) has been classically considered a co-morbidity of rheumatoid arthritis (RA). This investigation determined the clinical significance of sarcopenia in patients with RA combined with OP or whether sarcopenia influences RA when combined with OP. MATERIALS AND METHODS: Data pertaining to the duration of RA, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were collected from 549 RA cases and 158 healthy individuals. Disease activity score at 28 joints (DAS28), the body mass index (BMI), health assessment questionnaire (HAQ), bone mineral density (BMD), and Sharp score were compared between the 2 groups. RESULTS: The prevalence of OP (33.3% vs 12.7%, χ (2)= 69.992, P < 0.0001) and sarcopenia (61.7% vs 9.0%, χ (2)= 135.336, P < 0.01) was greater in patients with RA than in healthy controls. RA patients with sarcopenia had a higher incidence of OP at all measured sites than RA patients without sarcopenia (all P < 0.0001), and the incidence of OP was significantly higher than in patients with mild-to-moderate or severe RA without sarcopenia (P < 0.0001). Differences in age, gender, course of disease, CRP level, ESR, DAS28, BMI, HAQ, BMD, and Sharp score were statistically different between the RA with or without sarcopenia groups (P < 0.01). The incidence of OP and sarcopenia was higher in RA patients treated than not treated with glucocorticoids [GCs] (36.4% vs 29.3%, P < 0.05 and 66.1% vs 56.0%, respectively; P < 0.05). Logistic regression showed that the risk factors for OP in RA individuals were female (OR, 14.671; 95% CI, 6.877-31.300; P < 0.0001), age (OR, 1.100; 95% CI, 1.076-1.124; P < 0.0001), and sarcopenia (OR, 3.561; 95% CI, 2.214-5.726; P < 0.0001). CONCLUSION: OP and sarcopenia are common in RA patients. Sarcopenia may be a risk factor for OP occurrence in Chinese patients with RA.
35277271 Cardiovascular risk assessment with carotid ultrasound in rheumatoid arthritis. 2022 Mar 8 BACKGROUND/OBJECTIVE: To assess the Cardiovascular Risk (CV) in Rheumatoid Arthritis (RA) patients using carotid ultrasound additionally to the traditional CV risk factors. METHODS: A cross-sectional case control study was performed including RA patients and matched controls. This study was performed from July-2019 to January-2020. Population over 75 years old, established CV disease and/or chronic kidney disease (from III Stage) were excluded. Statistical analysis included a multivariate variance analysis (Manova) and a negative binomial regression adjusted by confounding factors. RESULTS: Overall, a total of 200 cases and 111 controls were included in the study. Demographical and clinical variables were comparable between groups. A relationship between age, BMI and high blood pressure was detected in both groups. RA patients showed higher intima-media thickness and higher plaque account compared to controls and it was related to the disease duration and DAS28 score. CONCLUSION: RA leads to a higher intima-media thickness, and this is related to the disease duration and DAS28 score. These findings support that RA acts as an independent cardiovascular risk factor.
35105369 Depression and food insecurity among patients with rheumatoid arthritis in NHANES. 2022 Feb 2 BACKGROUND: Social determinants of health (SDH), including food insecurity, are associated with depression in the general population. This study estimated the prevalence of depression and food insecurity and evaluated the impact of food insecurity and other SDH on depression in adults with rheumatoid arthritis (RA). METHODS: Adults (≥ 18 years) with RA were identified from the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey (NHANES). Depression was defined as a score of ≥ 5 (mild depression: 5-9; moderate-to-severe depression: 10-27) using the Patient Health Questionnaire-9 (PHQ-9). Food insecurity was assessed with the 18-item US Household Food Security Survey Module. Adults with household-level marginal-to-very-low food security were classified as experiencing food insecurity. The prevalence of depression and food insecurity among participants with RA were estimated. Weighted logistic regression was used to evaluate the association between depression and participants' characteristics including SDH. Penalized regression was performed to select variables included in the final multivariable logistic regression. RESULTS: A total of 251 and 276 participants from the 2013-2014 and the 2015-2016 NHANES, respectively, had self-reported RA. The prevalence of depression among these participants was 37.1% in 2013-2014 and 44.1% in 2015-2016. The prevalence of food insecurity was 33.1% in 2013-2014 and 43.0% in 2015-2016. Food insecurity was associated with higher odds of having depression (OR 2.17, 95% CI 1.27, 3.72), and the association varied by depression severity. Compared with participants with full food security, the odds of having depression was particularly pronounced for those with very low food security (OR 2.96, 95% CI 1.48, 5.90) but was not significantly different for those with marginal or low food security. In the multivariable regression, being female, having fair/poor health condition, any physical disability, and ≥ 4 physical limitations were significantly associated with depression. CONCLUSIONS: In adults with self-reported RA, the prevalence of depression and food insecurity remained high from 2013 to 2016. We found that depression was associated with SDH such as food insecurity, although the association was not statistically significant once adjusted for behavioral/lifestyle characteristics. These results warrant further investigation into the relationship between depression and SDH among patients with RA.
34919213 Post Hoc Analysis of the Correlation Between Patient-Reported Outcomes and Clinical Respon 2022 Apr PURPOSE: Approximately 6% of patients with rheumatoid arthritis (RA) in the USA have refractory disease that is resistant to standard-of-care therapies. A recent phase IV clinical trial affirmed the safety and efficacy of repository corticotropin injection (RCI; Acthar® Gel) for refractory RA. This post hoc analysis of the clinical trial data assessed whether changes in clinical measures correlated with patient-reported outcome (PRO) improvements. METHODS: Data were assessed from the trial's open-label period when patients received RCI (80 U) twice weekly for 12 weeks. Clinical assessments included hemoglobin A1c, C-reactive protein, erythrocyte sedimentation rate (ESR), total joint count (TJC), swollen joint count (SJC), Disease Activity Score with 28 joint count and ESR (DAS28-ESR), and Clinical Disease Activity Index (CDAI). PROs included pain (Visual Analog Scale), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and activity impairment (Work Productivity and Activity Impairment [WPAI] questionnaire). Patients grouped by minimal clinically important difference (MCID) improvement vs no improvement in PROs were compared with clinical measures at week 12. Correlations were determined by multivariable linear regression analysis and standardized coefficient estimates. RESULTS: RCI responders, defined as patients with DAS28-ESR < 3.2 at week 12, reported significantly greater PRO improvements for pain, disability, fatigue, activity impairment, current work impairment, and overall work impairment than nonresponders. Patients with MCID improvements in all PROs showed significantly greater decreases in mean values for TJC, DAS28-ESR, and CDAI, whereas those with pain, fatigue, and disability improvements had significantly greater SJC and ESR reductions. Multivariable linear regression analysis determined that improvement from baseline in all PROs correlated with significant decreases in TJC, DAS28-ESR, and CDAI. ESR reduction significantly correlated with improvements in pain and disability, but not fatigue or WPAI. CONCLUSIONS: These results confirm that clinical responses to RCI were directly correlated with patient perception of improvement.
35312895 Improvement in disease activity among patients with rheumatoid arthritis who switched from 2022 Mar 21 Infliximab and golimumab are intravenously (IV) administered tumor necrosis factor inhibitors approved to treat moderate-to-severe rheumatoid arthritis (RA) with concomitant methotrexate. Owing to differences in biologic construct, patients with IV-infliximab treatment failure may benefit from switching to IV-golimumab. Utilizing the ACR's Rheumatology Informatics System for Effectiveness (RISE), a large electronic health records registry based in the USA, we assessed RA disease activity in patients switching from IV-infliximab to IV-golimumab. This retrospective, longitudinal, single-arm study included adults (≥ 18 years) with ≥ 1 RA diagnosis code between 2014 and 2018 and ≥ 1 IV-infliximab prescription within 6 months of a new IV-golimumab order (index date). Longitudinal assessments of disease activity using the Clinical Disease Activity Index (CDAI) were calculated in patients continuing IV-golimumab for 6-9- and 9-12-months post-switch. Paired t-tests evaluated significance of mean improvements during the follow-up periods. Most RA patients with disease activity assessments during the 6-month follow-up (N = 100; mean age: 65.3 years; 81% female; 74% white) demonstrated moderate-to-high disease activity (CDAI: 73% [38/52]) at enrollment. On average, patients showed significant improvement in disease activity within 6-9 months of switching; mean CDAI scores improved from 21.3 to 14.1 (p < 0.0001) and were durable through 9-12 months of treatment. Real-world patients with moderate-to-high disease activity who switched from IV-infliximab to IV-golimumab demonstrated significant and sustained improvements post-switch as measured by the CDAI. Key Points • This study used real-world data from the Rheumatology Informatics System for Effectiveness (RISE) registry to evaluate the efficacy of directly switching from intravenous (IV)-infliximab to IV-golimumab to control rheumatoid arthritis (RA) disease activity. • Most IV-infliximab patients had moderate-to-high disease activity at the time of the switch. • On average, IV-golimumab was effective in improving RA disease activity after switching from IV-infliximab as measured by the Clinical Disease Activity Index. • These data suggest that real-world RA patients with persistent symptoms despite treatment with IV-infliximab may realize improved disease control with a switch to IV-golimumab.
35609788 Alamandine, a new member of the renin-angiotensin system (RAS), attenuates collagen-induce 2022 May 21 Alamandine is a novel component of the renin-angiotensin system (RAS) as well as an important biologically active peptide. It has predominantly been studied in cardiovascular context. However, its role in rheumatoid arthritis (RA) remains unknown. Here we illustrated its effects on inflammatory cytokines production by synovial fibroblasts from RA and pathological changes in collagen-induced arthritis (CIA) mice. Alamandine (0.1, 1 and 10 µg/ml) did not affect the survival of the synovial fibroblasts, but decreased the migration and proinflammatory cytokines expression in TNF-α (10 ng/ml) stimulated cells in vitro. Additionally, alamandine selectively decreased phosphorylated-JNK expression induced by TNF-a stimulation in RA FLS. DBA/1 J mice were induced arthritis by a primary injection with an emulsion of bovine type II collagen (CII) and complete Freund's adjuvant (day 0) and a booster injection of CII in incomplete Freund's adjuvant (day 21). Mice were then given alamandine intraperitoneally in saline (50 μg/kg/day) from days 21-42. Histology and multiplex immunobead assay showed that alamandine treatment inhibited the development of arthritis and reduced the joint damage. This effect was accompanied by the reduced inflammatory cytokines (IL-6, IL-23, IFN-γ) mRNA expression in local joints, the decreased TNF-α, IL-6, IL-17 and the increased IL-10 levels in the serum from alamandine administrated CIA mice. In conclusion, alamandine attenuates the development of arthritis by suppressing inflammatory cytokines expression in RA synovial fibroblasts via MAPK signaling pathway, suggesting a potential therapeutic role for RA.
35585779 Lessons from 20 years with COX-2 inhibitors: importance of dose-response considerations an 2022 May 18 Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the enzyme cyclooxygenase (COX), which forms prostaglandins involved in pain and inflammation. COX inhibitors have analgesic and anti-inflammatory effects, but also increase risks for gastrointestinal ulcers, bleeding, and renal and cardiovascular adverse events. Identification of two isoforms of COX, COX-1 and COX-2, led to the development of selective COX-2 inhibitors, which were launched as having fewer gastrointestinal side effects since gastroprotective prostaglandins produced via COX-1 are spared. The balance between COX-1 mediated prothrombotic thromboxane and COX-2 mediated antithrombotic prostacyclin is important for thrombotic risk. An increased risk of suffering myocardial infarction and death with COX-2 inhibitor treatment is well established from clinical trials and observational research. Rofecoxib (Vioxx) was withdrawn from the market for this reason, but the equally COX-2 selective etoricoxib has replaced it in Europe but not in the United States. The "traditional" NSAID diclofenac is as COX-2 selective as celecoxib and increases cardiovascular risk dose dependently. COX inhibitor dosages should be lower in osteoarthritis than in rheumatoid arthritis. Randomized trials comparing COX-2 inhibitors with NSAIDs have exaggerated their gastrointestinal benefits by using maximal NSAID doses regardless of indication, and/or hidden the cardiovascular risk by comparing with COX-2 selective diclofenac instead of low-dose ibuprofen or naproxen. Observational studies show increased cardiovascular risks within weeks of treatment with COX-2 inhibitors and high doses of NSAIDs other than naproxen, which is the safest alternative. COX inhibitors are symptomatic drugs that should be used intermittently at the lowest effective dosage, especially among individuals with an increased cardiovascular risk.