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ID PMID Title PublicationDate abstract
32701675 Recent advances in rheumatoid arthritis-associated interstitial lung disease. 2020 Sep PURPOSE OF REVIEW: To provide an overview of recent studies that could be helpful in a better understanding of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to facilitate the clinical management of this severe complication of RA. RECENT FINDINGS: The advances in deciphering the genetic architecture of RA-ILD support the hypothesis of RA-ILD as a complex disease with a complex phenotype encompassing at least the usual interstitial pneumonia (UIP) high-resolution CT pattern and non-UIP. Genetics studies have provided evidence for a shared genetic background in idiopathic pulmonary fibrosis (IPF) and RA-ILD, and more specifically RA-UIP, a disease with high morbidity and mortality. These findings support the rationale for common pathogenic pathways opening new avenues for future intervention in RA-ILD, notably with - drugs that proved active in IPF. In agreement, a recent controlled trial suggests efficacy of nintedanib, an antifibrotic drug, in patients with progressive lung fibrosis, including RA-ILD. However, there is a substantial gap in RA-ILD treatment, notably evaluating the effect of the RA treatments on the ILD course because of no controlled trial yet. SUMMARY: The phenotypical, environmental, and genetic similarities between IPF and RA-ILD have led to a better understanding of the underlying pathogenesis of RA-ILD. Despite the identification of several biomarkers and useful screening tools, several questions remain unanswered regarding the identification of patients with RA at increased risk of ILD and risk of progression. Other substantial gaps are the lack of recommendations for how high-risk patients should be screened and which specific therapeutic strategy should be initiated. International collaborative efforts are needed to address these issues and develop specific recommendations for RA-ILD.
32144210 Group cognitive behavioural courses may reduce fatigue from rheumatoid arthritis. 2020 Mar 6 The studyHewlett S, Almeida C, Ambler N, et al. Reducing arthritis fatigue impact: two-year randomised controlled trial of cognitive behavioural approaches by rheumatology teams (RAFT). Ann Rheum Dis 2019;78:465-72.Hewlett S, Almeida C, Ambler N, et al. Group cognitive behavioural programme to reduce the impact of rheumatoid arthritis fatigue: the RAFT RCT with economic and qualitative evaluations. Health Technol Assess 2019;23:57.This project was funded by the NIHR Health Technology Assessment Programme (project number 11/112/01).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000860/group-cognitive-behavioural-courses-may-reduce-fatigue-from-rheumatoid-arthritis.
33262300 Are Farming and Animal Exposure Risk Factors for the Development of Granulomatosis With Po 2021 Jun OBJECTIVE: To investigate the possible association between animal exposure and risk for granulomatosis with polyangiitis (GPA). METHODS: Patients with GPA at the Department of Rheumatology, Uppsala University Hospital, between January 1, 2011, and December 31, 2018, were consecutively included. All patients filled in a questionnaire on possible environmental exposures: occupation, hobbies, and animal contact. As controls we included 128 patients with rheumatoid arthritis (RA) and 248 population controls collected from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, matched for age, sex, and geographical area of residence. The controls filled out a questionnaire on current and past contact with farming and animals, at the time of the RA patient's diagnosis. RESULTS: A total of 62 patients with GPA, 128 patients with RA, and 248 population controls were included in the study. GPA was significantly associated with horse exposure, with a 2- to 3-fold increased risk compared with RA (OR 3.08, 95% CI 1.34-7.08) and population controls (OR 2.61, 95% CI 1.29-5.29). Borderline increased risks were found for any animal contact, but no association was found when analyzing contact with cats/dogs only. A significant association was found between GPA and farming compared to the population controls (OR 7.60, 95% CI 3.21-17.93). CONCLUSION: This study has identified for the first time, to our knowledge, a significant association between exposure to specific animals, namely horses, and the development of GPA. The results also support previous studies reporting an association between farming and GPA, underscoring the possibility of exogenous factors as initiators in the development of GPA.
32141429 Long non-coding RNA growth arrest-specific transcript 5 regulates rheumatoid arthritis by 2020 Nov OBJECTIVES: It has been proved that fibroblast-like synoviocytes (FSs) play a critical role in the course of rheumatoid arthritis (RA), is a systemic autoimmune disease affecting multiple joints. Until now, no effective treatment has been established. Long non-coding RNA Growth Arrest-Specific Transcript 5 (GAS5) has been identified as a tumour-suppressor lncRNA in various cancers. However, the expression, biological role and clinical significance of GAS5 in RA is completely unknown. In this study, we test the hypothesis that GAS5 might inhibit proliferation and inflammatory response of FSs in RA. METHODS: The expression of GAS5 was examined in synovial tissues from RA patients and normal individuals. RESULTS: The expression of GAS5 was significantly reduced in RA synovial tissues and RA FSs, whereas the expression of homeodomain-interacting protein kinase 2 (HIPK2) was increased, indicating that it plays a critical role in inflammation and autoimmune diseases. We found that overexpression of GAS5 decreased the level of HIPK2, TNF-α and IL-6. CONCLUSIONS: The methylation-specific PCR results suggested that the GAS5 gene promoter was significantly methylated in RA synovial tissues and RA FSs. More importantly, treatment with methylation inhibitor 5-aza-2-deoxycytidine (5-azadC) inhibited hypermethylation of GAS5 promoter and expression of HIPK2. These results indicated that GAS5 regulates RA via potentially targeting HIPK2. Therefore, this study may provide a potential therapeutic target for RA.
32378457 Heart Failure Risk Associated With Rheumatoid Arthritis-Related Chronic Inflammation. 2020 May 18 Background Inflammation may contribute to incident heart failure (HF). Rheumatoid arthritis (RA), a prototypic inflammatory condition, may serve as a model for understanding inflammation-related HF risk. Methods and Results Using the Vanderbilt University Medical Center electronic health record, we retrospectively identified 9889 patients with RA and 9889 control patients without autoimmune disease matched for age, sex, and race. Prevalent HF at entry into the electronic health record or preceding RA diagnosis was excluded. Incident HF was ascertained using International Classification of Diseases, Ninth Revision (ICD-9), codes and medications. Over 177 566 person-years of follow-up, patients with RA were at 21% greater risk of HF (95% CI, 3-42%) independent of traditional cardiovascular risk factors. Among patients with RA, higher CRP (C-reactive protein) was associated with greater HF risk (P<0.001), while the anti-inflammatory drug methotrexate was associated with ≈25% lower HF risk (P=0.021). In a second cohort (n=115) of prospectively enrolled patients with and without RA, we performed proteomics and cardiac magnetic resonance imaging to discover circulating markers of inflammation associated with cardiac structure and function. Artemin levels were higher in patients with RA compared with controls (P=0.009), and higher artemin levels were associated with worse ventricular end-systolic elastance and ventricular-vascular coupling ratio (P=0.044 and P=0.031, respectively). Conclusions RA, a prototypic chronic inflammatory condition, is associated with increased risk of HF. Among patients with RA, higher levels of CRP were associated with greater HF risk, while methotrexate was associated with lower risk.
32427982 A new laboratory surrogate (Monocyte Chemotactic Protein-1) for Disease Activity Score28: 2020 May 19 This prospective one-year follow-up study was conducted from 835 visits in 178 rheumatoid arthritis (RA) patients. Tender-/swollen-joint count, Health Assessment Questionnaire Disability Index (HAQ-DI), Disease Activity Score 28-ESR (DAS28-ESR), DAS28-CRP, Simplified Disease Activity Index (SDAI) and DAS28-monocyte chemotactic protein-1 (DAS28-MCP-1) scores were obtained every 3 months. Radiographs of hands and feet were acquired at baseline and one year. We evaluated the correlation and accuracy of activity scores in predicting remission, HAQ-DI changes and radiographic changes. DAS28-MCP-1 correlated strongly with DAS28-ESR, DAS28-CRP and SDAI scores (0.830, 0.899 and 0.931, respectively, with all P < 0.001). Score changes of DAS28-MCP-1 were comparable to those of DAS28-ESR, DAS28-CRP and SDAI in predicting changes in HAQ-DI and bone erosion. DAS28-MCP-1 (<2.2) was better than DAS28-ESR (<2.6) in indicating modified American Rheumatism Association remission and 2011 American College of Rheumatology/European League Against Rheumatism remission (75.61% vs. 36.99% and 81.71% vs. 49.13%, respectively) with odds ratios of 5.28 and 4.62 (both P < 0.001), respectively. We compared DAS28-MCP-1 with SDAI (≦3.3) in indicating remission with odds ratios of 2.63 (P = 0.002) and 0.98, respectively (and DAS28-MCP-1 with DAS28-CRP < 2.5: 1.33 and 0.92). Therefore, DAS28-MCP-1 is useful as an alternative in assessing RA activity.
32141436 Anxiety impacts rheumatoid arthritis symptoms and health-related quality of life even at l 2020 Nov OBJECTIVES: We explored the burden of symptoms of anxiety and depression on health-related quality of life (HRQL) in patients with rheumatoid arthritis (RA). METHODS: Adults with RA participating in an observational cohort completed PROMIS tests of depression, anxiety, fatigue, physical function (PF), pain interference (PI), sleep disturbance, and participation in social roles and activities at the baseline visit. Clinical measures of disease status were also obtained. We used ANOVA and partial correlation adjusting for the swollen joint count (SJC) to examine associations of anxiety and depression with other aspects of HRQL. Mild and moderate-severe anxiety were defined as T-scores ≥55.4 and ≥ 62.3 and mild and moderate-severe depression was defined as ≥52.5 and ≥58.6 based on previous validated clinical thresholds. Multivariable linear regression (MVR) was used to identify predictors of emotional distress with a subset analysis of those in remission/low disease activity. RESULTS: Of 196 RA participants, 18% had mild anxiety, 9% had moderate-severe anxiety, 18% had mild depression, and 14% had moderate-severe depression symptoms. Anxiety and depression scores were associated with significantly worse mean scores across HRQL domains (p <0.05). In MVR, depression (β=0.75, p<0.001), PF (β=0.14, p=0.024) and fatigue (β=0.15, p=0.015) predicted higher anxiety levels, whereas only anxiety predicted higher depression levels (β=0.70, p=<0.001). In subset analysis, PF no longer predicted higher anxiety levels. CONCLUSIONS: Emotional distress is common in RA, even when disease is well controlled, with considerable impacts on other aspects of HRQL even at mild levels.
32621912 Galantamine in rheumatoid arthritis: A cross talk of parasympathetic and sympathetic syste 2020 Sep 15 The acetylcholinesterase inhibitor, galantamine, has shown therapeutic effect in rat model of rheumatoid arthritis. Hence, the current study aims at determining the mode of action of galantamine by examining different synovium-derived microRNAs (miRs) and their related pathogenic pathways. The study also focuses on how parasympathetic and sympathetic pathways in the synovial tissue could affect the mode of action and anti-arthritic effect of galantamine. Chemical sympathectomy was initiated in 12 adjuvant arthritic rats by exposure to 6-hydroxydopamine (6-OHDA; 2 × 50 mg/kg) on day 9 after adjuvant injection and again (2 × 100 mg/kg) one week later. Six rats were treated with galantamine (2.5 mg/kg/day) to explore the influence of sympathetic impairment on galantamine effect. Another twelve additional adjuvant arthritic rats were exposed to the selective α7 nicotinic acetylcholine receptor blocker methylcaconitine citrate (MLA; 5.6 mg/kg/day), 15 min before galantamine treatment. As control, six adjuvant arthritic rats were treated with galantamine alone. Treatment proceeded for 5 days, from day 14 till day 18 post-adjuvant injection. Different miRs and their related pathogenic pathways were examined. Tyrosine hydroxylase (TH) expression was also measured in joint tissue. Galantamine affected the expression of the different miRs and their related parameters. Both, 6-OHDA and MLA, interrupted the anti-inflammatory/anti-arthritic effect of galantamine to different extent. Additionally, TH expression in the synovium was affected by galantamine, suggesting a novel pathogenic target in the treatment of rheumatoid arthritis.
33226212 Recovery of Ggt7 and Ace Expressions in the Colon Alleviates Collagen-Induced Arthritis in 2020 Dec 9 Rheumatoid arthritis (RA) causes swollen joints and irreversible joint damage and may even elevate cancer risks. Several bioactive nonstarch polysaccharides (NSPs) were reported to alleviate RA, but the key colonic genes accountable for this alleviation were elusive. Using collagen-induced arthritis as an RA model, colonic candidate genes related to RA were selected by transcriptome and methylome. The key genes were determined by comparing the transcriptome, methylome, and quantitative reverse transcription polymerase chain reaction profiles in RA rats with and without Lycium barbarum polysaccharides' treatment and further validated using Angelica sinensis polysaccharides and Astragalus propinquus polysaccharides for comparison. Both colonic genes γ-glutamyltransferase 7 (Ggt7) and angiotensin-I-converting enzyme (Ace) were downregulated by RA, and they were upregulated after L. barbarum polysaccharides' and A. sinensis polysaccharides' intervention that reduced the RA-caused hypermethylation status in nucleotide sites in the exon/promoter region of the two genes. However, the A. propinquus polysaccharides' intervention barely reduced the hypermethylation in the corresponding sites, failing to recover the expressions of these two genes and improve RA. Therefore, the colonic Ggt7 and Ace can be considered as key genes accountable for RA alleviation by bioactive NSP intervention. This study provides a more comprehensive insight into diet intervention to improve RA.
31504942 Trends in all-cause and cardiovascular mortality in patients with incident rheumatoid arth 2020 Mar 1 OBJECTIVES: To examine all-cause and cardiovascular disease (CVD) mortality in consecutive cohorts of patients with incident RA, compared with population comparators. METHODS: The Oslo RA register inclusion criteria were diagnosis of RA (1987 ACR criteria) and residency in Oslo. Patients with disease onset 1994-2008 and 10 matched comparators for each case were linked to the Norwegian Cause of Death Registry. Hazard ratios for all-cause and CVD mortality were calculated for 5, 10, 15 and 20 years of observation using stratified cox-regression models. Mortality trends were estimated by multivariate cox-regression. RESULTS: 443, 479 and 469 cases with disease incidence in the periods 94-98, 99-03 and 04-08 were matched to 4430, 4790 and 4690 comparators, respectively. For cases diagnosed between 1994 and 2003, the all-cause mortality of cases diverged significantly from comparators after 10 years of disease duration [hazard ratio (95% CI) 94-98 cohort 1.42 (1.15-1.75): 99-03 cohort 1.37 (1.08-1.73)]. CVD related mortality was significantly increased after 5 years for the 94-98 cohort [hazard ratio (95% CI) 1.86 (1.16-2.98) and after 10 years for the 99-03 cohort 1.80 (1.20-2.70)]. Increased mortality was not observed in the 04-08 cohort where cases had significantly lower 10-year all-cause and CVD mortality compared with earlier cohorts. CONCLUSION: All-cause and CVD mortality were significantly increased in RA patients diagnosed from 1994 to 2003, compared with matched comparators, but not in patients diagnosed after 2004. This may indicate that modern treatment strategies have a positive impact on mortality in patients with RA.
32958509 Circulating microbial small RNAs are altered in patients with rheumatoid arthritis. 2020 Dec OBJECTIVES: To determine if plasma microbial small RNAs (sRNAs) are altered in patients with rheumatoid arthritis (RA) compared with control subjects, associated with RA disease-related features, and altered by disease-modifying antirheumatic drugs (DMARDs). METHODS: sRNA sequencing was performed on plasma from 165 patients with RA and 90 matched controls and a separate cohort of 70 patients with RA before and after starting a DMARD. Genome alignments for RA-associated bacteria, representative bacterial and fungal human microbiome genomes and environmental bacteria were performed. Microbial genome counts and individual sRNAs were compared across groups and correlated with disease features. False discovery rate was set at 0.05. RESULTS: Genome counts of Lactobacillus salivarius, Anaerobaculum hydrogeniformans, Staphylococcus epidermidis, Staphylococcus aureus, Paenisporosarcina spp, Facklamia hominis, Sphingobacterium spiritivorum, Lentibacillus amyloliquefaciens, Geobacillus spp, and Pseudomonas fluorescens were significantly decreased in the plasma of RA compared with control subjects. Three microbial transfer RNA-derived sRNAs were increased in RA versus controls and inversely associated with disease activity. Higher total microbial sRNA reads were associated with lower disease activity in RA. Baseline total microbial sRNAs were threefold higher among patients who improved with DMARD versus those who did not but did not change significantly after 6 months of treatment. CONCLUSION: Plasma microbial sRNA composition is altered in RA versus control subjects and associated with some measures of RA disease activity. DMARD treatment does not alter microbial sRNA abundance or composition, but increased abundance of microbial sRNAs at baseline was associated with disease activity improvement at 6 months.
32247619 Effects of adjuvant-induced arthritis on the ventral prostate of rats treated with angiote 2020 Jul 1 AIMS: To analyze the prostatic compartments, extracellular matrix, microvascularization, transforming growth factor-beta (TGF-β) and angiotensin II receptors type 1 (AT(1)) levels, and histopathology of the ventral prostate in a rat model for rheumatoid arthritis, and to evaluate the effect of angiotensin II AT(1) receptor blocker (ARB) in the disease. MAIN METHODS: Fifteen male rats (90 days old) were divided into three groups (n = 5/group): control, adjuvant-induced arthritis without (AIA) or with AT(1) receptor blocker (AIA + ARB). Animals were euthanized 60 days after immunization. The ventral prostate was collected, weighed, and processed for histological and immunohistochemical analysis. KEY FINDINGS: Our results show that AIA increases production of the prostatic epithelium and extracellular matrix, accompanied by a reduction in the number of tissue capillaries. ARB treatment promotes decreased production of extracellular matrix and increased TGF-β and AT(1) receptor immunostaining. SIGNIFICANCE: AIA may activate specific mechanisms that modify the prostatic environment; the use of ARB attenuates some altered prostate parameters in a rat model for arthritis.
32791688 Switching from originator infliximab to biosimilar infliximab in Japanese patients with rh 2020 Jul 24 BACKGROUND: The introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) into clinical practice has dramatically improve the clinical outcomes of individuals with rheumatoid arthritis (RA). However, bDMARDs are associated with high costs, which has resulted in restricted treatment access and a burden on medical insurance finances. Although biosimilars offer cost-saving, their effectiveness and safety must be established in Post-Marketing Surveillance (PMS). Infliximab (IFX), a chimeric monoclonal antibody to TNF-alpha, is the first bDMARD; its biosimilar, CT-P13, is the first biosimilar DMARD approved for RA treatment in Japan. We will evaluate whether switching from originator IFX to CT-P13 is not inferior for maintaining non-clinical relapse to continued treatment with originator IFX in RA patients achieving clinical remission. METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm against historical control and noninferiority clinical trial with a 24-week follow-up. Eighty RA patients who are treated by originator IFX for ≥24 weeks and are achieving clinical remission will be included. Patients will be switched to CT-P13 with the unchanged dosing regimen. We will evaluate disease activity by measuring clinical disease activity indices and by using musculoskeletal ultrasound (MSUS). The primary endpoint is the ratio of patients who experience a nonclinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of many biomarkers such as cytokines and chemokines. DISCUSSION: The study results are expected to show the noninferiority of switching to CT-P13 over the continuation of originator IFX. The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices but also MSUS to accurately and objectively evaluate disease activity at the joint level among patients drawn from multiple centers with a standardized evaluation by MSUS. We will explore whether parameters at baseline can predict a nonclinical relapse after switching from originator IFX to CT-P13 by integrating multilateral assessments, i.e., clinical disease activity indices, MSUS findings, and serum biomarkers. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on October 11, 2019 as jRCTs071190030.
32955222 Coping strategies observed in women with rheumatoid arthritis. 2020 Sep 11 When faced with a chronic disease such as rheumatoid arthritis, the patient attempts to cope with the stressful situation by applying coping strategies. The main aim of rheumatoid treatment is not only improving health but also increasing the quality of life. The research objective was to determine the relationship among socio demographic factors, duration of the disease and its associated ailments, attitude to the disease, self-assessment of one's knowledge of RA, and the application of coping strategies in stressful situations by women with rheumatoid arthritis. The study involved 193 patients of the Clinic of Rheumatology and Systemic Connective Tissue Diseases, and the Rheumatology Unit of the Specialist Outpatient Clinic of the Independent Public Teaching Hospital No. 4 in Lublin, from November 2016 - June 2017. The Coping Orientations to Problems Experienced Inventory (COPE) Questionnaire and an author's Original Questionnaire were used in the study. Analysis of variance (ANOVA) and Tukey's range test were applied for statistical analysis. A p-value<0.05 defined the statistical differences. Analysis was performed using the commercial SPSS Statistics 19 software (IBM Corp., Armonk, NY, USA). The respondents usually use instrumental social support (11.5±1.7), focus on and vent emotions (11.4±1.9), use emotional social support (11.4±1.8), employ active coping (11.4±2.1) and positive reinterpretation and growth (11.2±1.8), and least often rely on their sense of humour (5.5±1.4) or use alcohol or drugs (5±1.1). The factors which determine the types of strategy used are age, education, the duration of the disease, ailments experienced, and attitude towards the disease. Those respondents who declared a greater knowledge of RA more often applied positive reinterpretation and growth, and more rarely used alcohol or drugs. In the treatment and rehabilitation processes it is important to reinforce in the patient positive expectations for the treatment, seek advantages and benefits in one's present health status, and educate patients about the disease, its therapy and appropriate coping strategies.
32448869 Analysis of association of ADORA(2)A and ADORA(3) polymorphisms genotypes/haplotypes with 2020 Dec Adenosine receptors ADORA(2)A and ADORA(3) are part of the adenosine-mediated antiinflammatory pathway and are overexpressed in patients with Rheumatoid arthritis (RA). Methotrexate (MTX) antiinflammatory effects are partially mediated via increased release of adenosine into extracellular space. Polymorphisms in ADORA(2)A and ADORA(3) genes may have an impact on the efficacy and toxicity of MTX in RA patients. The study included 127 RA patients. Treatment efficacy was estimated using the changes in Disease activity score (DAS28) after 6 months of MTX monotherapy, according to EULAR response criteria. Patients with good and moderate response were classified as "responders", and with a poor response as "nonresponders". Adverse effects were collected during the follow-up period. Genotyping for polymorphisms within ADORA(2)A gene (rs2298383, rs2236624, rs5751876, rs17004921) and ADORA(3) gene (rs2298191, rs1544223, rs3393) was performed using the KASPar assays. Among patients 112 (88.19%) were responders (18.8% good, 81.2% moderate). We observed no association between analyzed genotypes or alleles and MTX response by EULAR criteria but carriers of ADORA(2)A rs17004921 T allele (CT + TT) had a higher DAS28 decrease after 6 months of treatment than patients with CC genotype (p = 0.013). Adverse effects were reported in 31 patients (24.41%). Bone erosions were present in 82 (64.6%) patients. Haplotype block was observed among all 3 analyzed polymorphisms within ADORA(3) gene and TAA haplotype was associated with bone erosions (29% vs 15.6%, p = 0.023) and hepatotoxicity (51.3% vs 21.6%, p = 0.013). According to our study, ADORA(3) TAA haplotype may be associated with bone erosions and hepatotoxicity in RA patients treated with MTX.
31578102 Axillary lymph-node metabolic activity assessment on (18)F-FDG-PET/CT in rheumatoid arthri 2020 Mar Objective: Recent studies have provided new insights into the role of lymph nodes (LNs) in rheumatoid arthritis (RA). The aim of this study was to evaluate the metabolic activity of the axillary LNs in relation to that of the upper limb joints and the clinical assessment of disease activity in RA patients treated with biologic therapies.Method: (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography ((18)F-FDG-PET/CT) scans were acquired for 64 patients with RA at baseline and after 6 months of biologic therapy, and the patients' clinical status was evaluated. The maximum standardized uptake value (SUV(max)), metabolic active volume, and total lesion glycolysis (TLG) were used to assess glucose metabolism in the LNs and 12 joints. Clinical evaluations included serum markers and the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate (DAS28-ESR).Results: Changes in the SUV(max) and TLG for the axillary LNs correlated significantly with those of the ipsilateral wrist joints. There was a positive correlation between the changes in the three metabolic parameters of the axillary LNs and the changes in disease activity after treatment. After 6 months of biologic therapy, all metabolic parameters for the axillary LNs in patients with a DAS28-ESR < 3.2 were significantly lower than those of patients with a DAS28-ESR ≥ 3.2.Conclusion: A relationship between the glucose metabolism of the axillary LNs and the ipsilateral wrist joints was demonstrated by the (18)F-FDG-PET/CT parameters. The metabolic activity and active volume of axillary LNs may reflect the therapeutic response to the biologic treatment of RA.
32700001 JAK Inhibitors: What Is New? 2020 Jul 22 PURPOSE OF THE REVIEW: Three Janus kinase (JAK) inhibitors are approved for rheumatoid arthritis (RA) with a fourth awaiting approval. Multiple clinical trial results with these molecules have recently been reported. These were the first small molecule oral targeted synthetic DMARDs (tsDMARDs) to be approved for RA. RECENT FINDINGS: Preclinical studies have suggested differential affinity for JAK isoform inhibition but it is not presently clear that there is any difference in efficacy in the clinic with these therapies. Preliminary data has suggested that filgotinib may have a modestly different safety profile but lacking direct comparisons, this will be difficult to confirm. Long-term safety studies have suggested similar safety signals to biologics although a possible signal for VTE/PE risk has been noted with tofacitinib and baricitinib. Having an oral small molecule such as the JAK inhibitors with similar or better efficacy than biologics has been a major advance in RA treatment.
31646431 Should ultrasound be used routinely in the diagnosis of rheumatoid arthritis? 2020 May INTRODUCTION: A growing body of evidence indicates the benefits of early diagnosis of rheumatoid arthritis (RA) and prompt treatment with disease-modifying anti-rheumatic drugs (DMARDS) in terms of relieving symptoms, improving prognosis, and reducing long-term complications. There is however some controversy over the most beneficial method of imaging in providing accurate early diagnosis. Though current practice favours clinical and radiological assessment, this is increasingly supplemented by ultrasound techniques (and, to a lesser extent, CT and MRI scanning). While EULAR and ESSR favour the use of ultrasonography (US) as the first-line investigation in cases of suspected RA, a recent NICE review upholds the traditional place of plain film radiographs of hands and feet to detect erosions as early signs of synovitis. This review considers the evidence for US in the early diagnosis of RA and the case for it becoming the primary assessment modality in rheumatology clinics. AIMS: This paper aims to assess the current literature on the efficacy of ultrasonography in diagnosing early RA, by comparing US with alternative imaging modalities. The goal is to propose the most appropriate method of diagnosis to improve early initiation of DMARD treatment for optimum disease outcomes. METHODS: Searches for related studies and review articles were carried out using electronic databases and hand searches. Additional references were gleaned from the bibliographies of included papers. Related articles and pop-outs from PubMed were also used. The search was refined in PubMed, by only using reviews which were written in English and published in past 10 years and had full free text available. RESULTS: This review confirms that US has a high level of sensitivity in diagnosing RA (and hence a low risk of missing cases of RA which might benefit from early treatment with DMARDs). It also has a high level of specificity (and hence a low risk of falsely diagnosing somebody with RA who may suffer adverse effects of DMARD therapy). US is already widely available and well accepted by clinicians and patients. It does not involve exposure to radiation and can be readily delivered by appropriately trained staff. CONCLUSION: This review of relevant studies indicates that US should become accepted as the investigation with the most favourable balance of benefits to risks in the early diagnosis of RA. Given the continuing controversy surrounding studies of different imaging techniques in RA, further research into the diagnostic role of US in RA is indicated.
31826682 Predictors of new bone erosion in rheumatoid arthritis patients receiving conventional syn 2021 Jan OBJECTIVE: To investigate new bone erosion and cartilage destruction predictors in rheumatoid arthritis (RA) patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODS: Placebo-treated patient data from two 12-month, randomized, double-blind, phase 2 (DRIVE) and 3 (DESIRABLE) trials that evaluated denosumab efficacy in csDMARD-treated RA patients were used. Change from baseline in erosion score (ES) of ≥1.0 at 12 months was considered new bone erosion; predictors were identified using a multivariate model. RESULTS: Among 306 patients, mean ± standard deviation disease activity score 28-C-reactive protein (CRP) at baseline was 3.58 ± 1.03. New bone erosion was observed in 90 patients (29.4%). Univariate analysis identified female sex, anti-cyclic citrullinated peptide (CCP) antibody positivity, rheumatoid factor (RF) positivity, tender joint count ≥6, CRP ≥0.3 mg/dL, erythrocyte sedimentation rate (ESR) ≥28 mm/h, and baseline ES ≥3 as significant predictors for new bone erosion. In multivariate analysis, predictors were anti-CCP antibody positivity, CRP ≥0.3 mg/dL, and baseline ES ≥3; RF and ESR were excluded as they strongly correlated with anti-CCP antibody and CRP, respectively. CONCLUSION: In RA patients treated with csDMARDs, new bone erosion predictors were seropositivity, elevated inflammatory markers, and baseline ES ≥3. TRIAL REGISTRATION NUMBER: DRIVE, JapicCTI-101263; DESIRABLE, NCT01973569.
33076964 TREAT Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid arthritis 2020 Oct 16 BACKGROUND: We present a study protocol for a randomized, double-blind, placebo-controlled trial that investigates the hypothesis if intervention in the symptomatic phase preceding clinical arthritis (clinically suspect arthralgia (CSA)) is effective in preventing progression from subclinical inflammation to clinically apparent persistent arthritis. Currently, rheumatoid arthritis (RA) can be recognized and diagnosed when arthritis (joint swelling) has become detectable at physical examination. Importantly, at this time, the immune processes have already matured, chronicity is established, and patients require long-standing treatment with disease-modifying anti-rheumatic drugs. The TREAT EARLIER trial studies the hypothesis that intervention in the symptomatic phase preceding clinical arthritis is more often successful in permanent disease modification because of less matured underlying disease processes. METHODS: A two-level definition to identify patients that are prone to develop RA is used. First, patients should have CSA and recent-onset arthralgia (< 1 year) that is suspect to progress to RA according to the expertise of the treating rheumatologist. Second, patients need to have subclinical inflammation of the hand or foot joints at 1.5 T MRI. The trial aims to recruit 230 participants from secondary care hospital settings across the south-west region of The Netherlands. Intervention will be randomly assigned and includes a single-dose of intramuscular 120 mg methylprednisolon followed by methotrexate (increasing dose to 25 mg/week orally) or placebo (both; injection and tablets) over the course of 1 year. Thereafter, participants are followed for another year. The primary endpoint is the development of clinically detectable arthritis, either fulfilling the 2010 criteria for RA or unclassified clinical arthritis of ≥ 2 joints, which persists for at least 2 weeks. DMARD-free status is a co-primary endpoint. The patient-reported outcomes functioning, along with workability and symptoms, are key secondary endpoints. Participants, caregivers (including those assessing the endpoints), and scientific staff are all blinded to the group assignment. DISCUSSION: This proof-of-concept study is the logical consequence of pre-work on the identification of patients with CSA with MRI-detected subclinical joint inflammation. It will test the hypothesis whether intervention in patients in this early phase with the cornerstone treatment of classified RA (methotrexate) hampers the development of persistent RA and reduce the disease burden of RA. TRIAL REGISTRATION: Dutch Trial Register NL4599 (NTR4853). Registered on 20 October 2014.