scholarly journals A systematic review of CXCL13 as a biomarker of disease and treatment response in rheumatoid arthritis

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Katie Bechman ◽  
Anthony Dalrymple ◽  
Charles Southey-Bassols ◽  
Andrew P. Cope ◽  
James B. Galloway
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Disease Activity ◽  
Treatment Response ◽  
Janus Kinase ◽  
Response To Treatment ◽  
Healthy Controls ◽  
Treatment Prediction ◽  
Randomised Controlled

Abstract Background The B cell chemoattractant CXCL13 is a promising biomarker in rheumatoid arthritis (RA), with a plausible role in supporting diagnosis, monitoring disease activity and as a prognostic value. It is a key chemokine driving the formation of lymphoid follicles within the inflamed synovium. The objective of this systematic review was to evaluate the role of CXCL13 as a viable biomarker in RA. Methods We conducted a systematic literature review of all published cohort and randomised controlled trials evaluating the role of CXCL13 in RA. The primary outcomes were; i) CXCL13 levels in RA patients compared to healthy controls, ii) the correlation between CXCL13 and markers of disease activity, and iii) the association between CXCL13 and treatment response. Results The search produced 278 articles, of which 31 met the inclusion criteria. Of the 12 studies evaluating CXCL13 expression in early or established RA, all reported higher levels than that seen in healthy controls. Twelve of sixteen studies reported a weakly positive correlation between CXCL13 and markers of disease activity including DAS28 and swollen joint count, with rho values between 0.20–0.67. In 2 studies, CXCL13 levels correlated with ultrasonographic evidence of synovitis. Eighteen studies assessed CXCL13 in response to therapeutic intervention. The majority signified a fall in levels in response to treatment including biologics and Janus kinase (JAK) inhibition. In some, this reduction was only seen in treatment responders. High CXCL13 levels predicted failure to achieve disease remission with csDMARDs. The evidence for treatment prediction with biologics was conflicting. Conclusion Despite evidence to suggest a role in diagnosing RA and in detecting synovitis, the heterogeneity of studies included in this review limit our ability to draw robust conclusions. At present there are inadequate results to justify the routine use of CXCL13 as a biomarker in RA routine clinical practice.

scholarly journals POS0677 THE ROLE OF MUSCULOSKELETAL ULTRASOUND IN PREDICTING THE RESPONSE TO JAK INHIBITORS: RESULTS FROM A LARGE MONOCENTRIC COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 583-583
Author(s):  
C. Garufi ◽  
F. Ceccarelli ◽  
F. R. Spinelli ◽  
S. Mancuso ◽  
C. Pirone ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Structural Damage ◽  
Power Doppler ◽  
Response To Treatment ◽  
Jak Inhibitors ◽  
Inflammatory Score ◽  
Inflammatory Status

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos

scholarly journals AB0105 A SYSTEMATIC REVIEW OF THE MULTI-BIOMARKER DISEASE ACTIVITY SCORE FOR THE DIAGNOSIS AND TREATMENT IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1081.1-1081
Author(s):  
D. Abdelhafiz ◽  
M. Bukhari
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Prospective Study ◽  
Disease Activity ◽  
Literature Search ◽  
Clinical Disease ◽  
Diagnosis And Treatment ◽  
Response To Treatment ◽  
Clinical Disease Activity

Background:Biomarkers are important tools that can be used in the diagnosis and monitoring of rheumatoid arthritis (RA). The multi-biomarker disease activity (MBDA) score has shown a clinical value in the overall management of patients with RA.Objectives:To systematically explore the role of MBDA score for diagnosis and treatment of RA.Methods:A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Key words used included: ‘Rheumatoid Arthritis’, ‘Biomarkers’, ‘Diagnosis’, ‘Treatment’, ‘Outcome’, ‘Response to treatment’, ‘Disease Activity’, and ‘MBDA’. The literature search included papers published in 2020 and in the English language.Results:This literature search has yielded 5 studies that investigated the impact of MBDA score on the diagnosis, treatment or disease progression of RA and have reported clear and clinically validated diagnostic or therapeutic effects. The first study prospectively investigated 130 patients with RA, and has shown that the MBDA score moderately correlated with disease activity at baseline (r = 0.36 for adjusted MBDA score, r = 0.44 for unadjusted MBDA score) and at 16 weeks follow up (r = 0.20 for adjusted MBDA, r = 0.30 unadjusted MBDA) but did not predict treatment response to methotrexate. There was also moderate correlation between MBDA scores and erythrocyte sedimentation rate (ESR) at baseline (r = 0.54 and 0.59) and week 16 (r = 0.42 and 0.51). The second was a cross-sectional study, which included 104 patients (50% female) and demonstrated that adjusted and unadjusted MBDA score correlated similarly with clinical disease activity. Adjustment for leptin reduced the influence of adiposity, particularly among women but significantly estimated higher disease activity in thin men and women. However, MBDA score predicted disease activity and response to tofacitinib treatment, measured by musculoskeletal ultrasound score (MSUS), in RA patients as demonstrated by the third prospective study that included 25 patients (all p< 0.05). Correlation was found between baseline MSUS and MBDA score, and with 12-week changes in clinical disease activity (r = 0.45–0.62, p < 0.05). Regression analysis showed associations between baseline MBDA score and 6-week (all p< 0.05) and 12-week change in change in clinical disease activity (p= 0.03). The fourth prospective study which included 92 patients with RA, showed that MBDA could predict response to treatment of methotrexate with or without prednisolone. The improvement was faster in the first month of treatment followed by gradual improvement over the following 6 months. Changes from baseline to 12 months for disease activity and MBDA score showed a significant correlation for methotrexate and prednisolone (r= 0.57, p= 0.002), methotrexate and placebo (r= 0.57, p= 0.001) and for all groups (r= 0.56, p< 0.001). The final prospective study which included 148 patients, showed that MBDA predicted remission in RA and could differentiate between small differences in disease activity (low disease activity vs remission states). Baseline MBDA score discriminated baseline remission, area under the curve (AUC) 0.68-0.75, and intermittent/sustained remission (AUC 0.65-0.74). MBDA also predicted long term remission after one year.Conclusion:MBDA appears to be a useful tool in day-to-day clinical practice that can be used in the diagnosis, monitoring of treatment and prediction of outcomes of patients with RA. MBDA correlated well with disease activity and response to treatment. It is also a good predictor of long-term disease remission.Disclosure of Interests:None declared

scholarly journals Predictors of response to TNF inhibitors in rheumatoid arthritis: an individual patient data pooled analysis of randomised controlled trials

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e001882
Author(s):  
Johan Law-Wan ◽  
Marc-Antoine Sparfel ◽  
Sophie Derolez ◽  
Nicolas Azzopardi ◽  
Philippe Goupille ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Group ◽  
Disease Activity ◽  
Randomised Controlled Trials ◽  
Disease Duration ◽  
Individual Patient Data ◽  
Patient Data ◽  
Response To Treatment ◽  
Controlled Trials ◽  
Randomised Controlled

ObjectiveTo identify patient characteristics associated with responsiveness to tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA).Materials and methodsIndividual patient data from 29 randomised controlled trials (RCTs) evaluating the efficacy of a TNFi versus placebo or conventional therapy were obtained. Response to treatment was assessed in subgroups according to the following baseline characteristics: smoking status, physical activity, sex, age, body mass index, autoantibody profile, disease duration, high initial disease activity defined by Disease Activity Score on 28 joints (DAS28)(C reactive protein (CRP)) >5.1. The primary outcome was the between-treatment group difference in DAS28(CRP) change from baseline to 6 months. The secondary endpoints were the between-treatment group difference in final DAS28(CRP) measured until 6 months and EULAR response criteria until 6 months. Data from each RCT were then pooled by the Mantel-Haenszel method using a random effects model. A linear metaregression was also carried out on two data-sharing platforms separately to support the results.ResultsIndividual data of 11 617 patients from 29 RCTs were analysed. Until 6 months, a significantly higher EULAR non-response rate was observed in obese patients (OR 0.52 vs 0.36 for non-obese, p=0.01). A multivariable regression model performed on 7457 patients indicated that patients treated by TNFi had a final DAS28(CRP) decreased by 0.02 for each year of disease duration (p<0.001), and a 0.21 decreased for patients with a baseline DAS28(CRP) >5.1 (p<0.001).ConclusionsIn RA, patients who are more responsive to TNFi are those who are non-obese, have a long disease duration and have a high initial disease activity.

scholarly journals AB0111 THE COMPARISON OF SYNDECAN-4 LEVEL IN SERA, SYNOVIAL FLUID AND SYNOVIUM OF RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1356.1-1356
Author(s):  
J. Zhao ◽  
X. Ye ◽  
Z. Zhang
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Migration ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Heparan Sulphate ◽  
Healthy Controls ◽  
Baseline Serum

Background:Syndecan-4, one of the members of heparan sulphate proteoglycans (HSPGs), has been shown to be involved in regulating inflammatory responses, angiogenesis, and cell migration. Its role has been proved in animal arthritis models, however not clearly elucidated in rheumatoid arthritis (RA) patientsObjectives:To investigate the role of Syndecan-4 in the pathogenesis of RA, by detecting Syndecan-4 expression in the serum, synovial fluid and synovium of RA patients and comparing with osteoarthritis (OA) patientsMethods:The concentrations of syndecan-4 in sera and synovial fluid of RA and osteoarthritis (OA) patients were detected by ELISA. The expression of syndecan-4 in synovium of RA and OA patients was detected by immunohistochemistry. In another cohort of 60 RA patients, the association analysis was performed. All the RA patients were with disease duration more than 6 months and with DAS28-CRP>3.2 although after csDMARDs (including MTX and/or leflunomide) treatment for more than 3 months. The RA patients were treated with tumour necrosis factor α (TNFα) inhibitor (TNFi) and MTX 10mg per week for 12 weeks. The correlations between sera Syndecan-4 and disease activity of RA as well as therapeutic response to TNFi were analyzed.Results:The serum Syndedcan-4 level of RA patients [637.1 (483.6-1069.6) pg/mL] was significantly higher than that of OA patients [345.0 (287.9-421.1) pg/mL] and healthy controls [195.6 (165.0-225.2) pg/mL](P<0.001, P<0.001, respectively). The serum concentration of Syndecan-4 is also higher in OA patients than that in healthy controls (P<0.001). It was also higher in RF-positive RA patients than in RF-negative ones [603.0 (100.0-8879.1) pg/mL vs 460.3 (178.7-2468.9) pg/mL, (p=0.026)]. The Syndedcan-4 level in synovial fluid and synovia were comparable between RA and OA patients. No correlation was found between serum Syndedcan-4 and disease activity of RA. TNFi treatment did not change the serum Syndecan-4 level significantly. The baseline serum Syndecan-4 did not show predictive value for TNFi response.Conclusion:Syndecan-4 can be expressed in the synovia of RA and OA patients. The serum Syndecan-4 is higher in RA patients than in OA patients and healthy controls, and significantly higher in sero-positive RA patients than in sero-negative ones. Syndecan-4 may participate in the pathogenesis of RA.References:[1]Leonova EI, Galzitskaya OV. Role of Syndecans in Lipid Metabolism and Human Diseases. Adv Exp Med Biol, 2015, 855: 241-58.[2]Xie J, Wang J, Li R, Dai Q, Yong Y, Zong B, et al. Syndecan-4 over-expression preserves cardiac function in a rat model of myocardial infarction. J Mol Cell Cardiol 2012; 53: 250-8.[3]Strand ME, Aronsen JM, Braathen B, Sjaastad I, Kvaløy H, Tønnessen T, et al. Shedding of syndecan-4 promotes immune cell recruitment and mitigates cardiac dysfunction after lipopolysaccharide challenge in mice. J Mol Cell Cardiol. 2015;88:133-44.[4]Endo T, Ito K, Morimoto J, Kanayama M, Ota D, Ikesue M, et al. Syndecan 4 Regulation of the Development of Autoimmune Arthritis in Mice by Modulating B Cell Migration and Germinal Center Formation. Arthritis Rheumatol. 2015; 67:2512-22.Disclosure of Interests:None declared

scholarly journals The role of extracellular vesicles in rheumatoid arthritis: a systematic review

2021 ◽  
Author(s):  
Tommaso Schioppo ◽  
Tania Ubiali ◽  
Francesca Ingegnoli ◽  
Valentina Bollati ◽  
Roberto Caporali
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Chronic Inflammatory Disease ◽  
Healthy Controls ◽  
Economic Costs ◽  
Permanent Disability ◽  
Meta Analyses

AbstractRheumatoid arthritis (RA) is a chronic inflammatory disease that carries high social and economic costs and can lead to permanent disability. RA pathogenesis has not been completely elucidated yet. Extracellular vesicles (EVs) are membrane-contained vesicles released by cells playing a role in cell-to-cell communication and they could be involved in different diseases. Evidence on the involvement of EVs in RA is currently inconclusive. Therefore, a systematic review on the role of EVs in RA was performed in order to explore this relationship. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research was conducted on PubMed, Scopus, and Embase up to March 5, 2020: 41 studies were analyzed out of 674 screened. The total plasmatic and synovial fluid (SF) EV number seems increased in RA as compared with healthy controls. Both RA plasma and SF contained EVs subpopulations of heterogenous origin, especially derived from platelets and immune system cells. No univocal evidence emerged on miRNA expression and EV content profile within RA patients. EVs showed to enhance pro-inflammatory pathways, such as cytokines and chemokine release and TNF blockade seemed to revert this effect. Our work highlights the requirement to standardize study methodologies in order to make results comparable and draw conclusions that remain, at present, unclear.

scholarly journals TREATMENT RESPONSE PREDICTION IN PATIENTS WITH RHEUMATOID ARTHRITIS. Review

2020 ◽  
Vol 16 (1) ◽  
pp. 67-76
Author(s):  
D.L. Fedkov ◽  
M.O. Komkina
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Treatment Response ◽  
Adhesion Molecule ◽  
Tumor Necrosis ◽  
Response To Treatment ◽  
Predictors Of Response ◽  
Tnf Α ◽  
Necrosis Factor

Relevance. A variety of targeted therapies for rheumatoid arthritis (RA) treatment exist. Therefore, reliable predictors are needed that could be used to accurately predict the efficacy or inefficacy of these therapies in individual patients. This could allow clinicians to improve diagnosis and prognosis, to make the treatment personalized and to reduce healthcare expenses. Objectives: to analyze and systemize the predictors of response to treatment in patients with RA. Materials and Methods. We analyzed the recently discovered predictors of treatment response in RA patients using papers cited on PubMed, Lilacs, and EMBASE databases from Jan 2005 until Jan 2020.  Predictive factors were grouped into four categories: methotrexate (MTX)-treated RA, tumor necrosis factor (TNF)-α inhibitors-treated RA, interleukin (IL)-6 inhibitors-treated RA, and rituximab (RTX)-treated RA. Results. Based on the results of several studies, predictors of response to methotrexate were high Disease Activity Score (DAS), concentration of myeloid-related proteins 8/14, high P-glycoprotein levels, low serum calprotectin and leptin levels, baseline serum concentration of tumor necrosis factor (TNF)-α, TNF receptor I, interleukin (IL)-1β, soluble CD163, numbers of CD14+highCD16, vascular cell adhesion molecule, lower expression of hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p. A positive response to biological therapy was determined by male gender, younger age, lower health assessment questionnaire, erythrocyte sedimentation rate or C-reactive protein, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, tender joint count (or swollen joint count) scores, absence of comorbidities, baseline albumin, IL-34, IL-1β, D-dimer, fibrinogen, matrix metalloproteinase 3, DAS 28 and Simplified Disease Activity Index (SDAI). The plasma interferon (IFN) activity and the IFN beta/alpha ratio, IL-1Ra level were predictive in TNF antagonist-treated patients. Predictors of response to IL-6 inhibitors were anti–citrullinated protein antibody (ACPA)+, baseline Sharp/van der Heijde score, myeloid soluble intercellular adhesion molecule 1, serum levels of sIL-6R, IL-8, calprotectin, and lymphoid activation and bone remodeling markers. The prediction of the best response for rituximab was determined to be a combination of IL-33, rheumatoid factor or ACPA, IgG, and also lower number of previous biological therapies. Genetic factors, such as single-nucleotide polymorphisms at gene locus rs10919563, rs11541076, rs12083537, rs11265618, and rs1801274, and rs396991 can also be used to predict a response to treatment. Conclusions. One of the leading problems in the development of predictors remains the collection of high-quality and complete information from a large number of patients. For this, it is necessary to develop an digital program for collecting specific data (depending on the specific disease) and developing new algorithms for predicting the response to treatment.

Role of 14-3-3η (Eta) Protein as Immunological Marker for Disease Activity in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 11 (2) ◽  
pp. 2234
Author(s):  
Muhannad Mohammed Ali AL-Salami ◽  
Abeer Thaher Naji AL-Hasnawi ◽  
Mohammed Abd AbdulHussein Abusabe
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Immunological Marker
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