scholarly journals FRI0452 THE IMPACT OF SINGLE NUCLEOTIDE POLYMORPHISMS IN ADORA2A AND ADORA3 ON THE EARLY RESPONSE TO METHOTREXATE AND PRESENCE OF THERAPY SIDE EFFECTS IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 823.1-823
Author(s):  
J. Roszkiewicz ◽  
D. Michałek ◽  
A. Ryk ◽  
B. Szmyd ◽  
E. Smolewska
Keyword(s):  
Rheumatoid Arthritis ◽  
Juvenile Idiopathic Arthritis ◽  
Side Effects ◽  
Disease Activity ◽  
Global Assessment ◽  
Disease Activity Score ◽  
Clinical Parameters ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Active Arthritis

Background:Juvenile idiopathic arthritis (JIA) is the most frequent rheumatic disease in children, with an estimated prevalence between 16 and 150 per 100 000 [1]. Methotrexate (MTX) administered at the dose 10-15mg/m2is currently recommended as the first-line treatment in most of JIA subtypes [2]. Despite its widespread use in rheumatology, the mechanism of MTX immunomodulatory action remains incompletely understood [3]. Free adenosine is one of the particles possibly associated with the action of MTX, acting via three types of adenosine receptor: ADORA2A, ADORA2B, and ADORA3 [4].Objectives:The aim of our study was to determine the association between single nucleotide polymorphisms inADORA2A(rs2236624, rs2298383) andADORA3(rs3393) receptors genes on the disease activity and presence of MTX therapy side effects in patients with JIA.Methods:One hundred children with JIA of all subtypes treated with MTX were recruited to the study. Demographic and clinical parameters were collected at the baseline of MTX therapy and on a control visit 4-6 months (median 5.09 months) after starting MTX. The clinical parameters included inflammatory markers values, number of joints with active arthritis, number of joints with restricted range of movement, physician’s global assessment of disease activity, parent/patient global assessment of overall well-being, functional ability (measured by the Childhood Health Assessment Questionnaire – CHAQ) and the value of Juvenile Idiopathic Arthritis Disease Activity Score 71 (JADAS 71). Presence of MTX side effects was evaluated on the control visit. SNP genotyping was performed using genomic DNA isolated from peripheral blood samples.Results:Both polymorphic variants ofADORA2A(rs2236624, rs2298383 - CC/CT) were significantly associated with 3.5 times higher odds of gastrointestinal side effects occurrence (OR: 3.52, 95%CI: 1.12-11.03, p=0.03 and OR: 3.49, 95%CI: 0.89-13.66 p=0.07) after adjustment to age, sex, dose and route of MTX administration. In addition, children with theADORA3rs3393 polymorphic variant (CT/CC) after six months of MTX treatment had significantly lower number of joints with active arthritis (0.0 vs 1.0, p=0.04), lower JADAS 71 score (3.0 vs 5.1, p=0.16) and lower value of CRP (0.6 vs 2.4, p=0.02).Conclusion:Although future studies are needed to verify our findings, polymorphisms inADORA2AandADORA3genes may become the determinants of MTX treatment efficacy and gastrointestinal toxicity in children with JIA.References:[1]Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001.J Rheumatol. 2004;31(2):390-392.[2]Ferrara G, Mastrangelo G, Barone P, et al. Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting.PediatrRheumatol Online J. 2018;16(1):46. Published 2018 Jul 11. doi:10.1186/s12969-018-0255-8.[3]Brown, P. M., Pratt, A. G., & Isaacs, J. D. (2016). Mechanism of action of methotrexate in rheumatoid arthritis and the search for biomarkers. Nature Reviews Rheumatology, 12(12), 731–742. doi:10.1038/nrrheum.2016.175.[4]Varani, K. et al. A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release. Arthritis Res. Ther. 13, R197 (2011).Disclosure of Interests:None declared

Association of RETN and TNFRSF1B polymorphisms with TNF-α inhibitor response in rheumatoid arthritis patients

2020 ◽  
Author(s):  
Nga Thi Trinh ◽  
Hyun Jeong Kim ◽  
Woorim Kim ◽  
Sang Oh Kang ◽  
Kyung Hyun Min ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Multivariable Logistic Regression Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Final Model ◽  
Asian Populations ◽  
Tnf Α

Abstract Background: Despite the improvement from the introduction of tumor necrosis factor inhibitors (TNFi) in the rheumatoid arthritis (RA), TNFi therapy fails for more than 30% or results in a partial response. Thus, we aimed to explore treatment marker by examining the association of single nucleotide polymorphisms (SNPs) with response to TNFi therapy.Method: Genes associated with RA or RA treatment were reviewed and fourteen SNPs with minor allele frequency ≥ 20% in the East Asian populations were selected and analyzed. Data were collected from 105 RA patients. Our primary endpoint was the disease activity score using 28-joint count after six months of treatment (DAS28-6month). The secondary outcomes were the subcomponents of DAS28.Results: A total of 88 patients were included in the final analyses. Among the 14 SNPs analyzed, one SNP showed statistical significance in DAS28-6month: patients with the GG allele of RETN rs1862513 had a 4.7 times higher chance of low disease activity at 6-months than GC or CC-carriers (p = 0.033), as indicated by multivariable logistic regression analysis. Rs3397 was marginally significant in univariate analysis (p=0.059), but was significant in the multivariable model (p=0.041). The final model explained 24.5% (Nagelkerke R2) of the variance in DAS28-6month.Conclusion: Our results demonstrated that, among the genes related to RA, SNPs in RETN and TNFRSF1B were associated with the response of TNFi treatment.

The Influence of the Definition of Patient Global Assessment in Assessment of Disease Activity According to the Disease Activity Score (DAS28) in Rheumatoid Arthritis

2011 ◽  
Vol 38 (11) ◽  
pp. 2326-2328 ◽  
Author(s):  
MAXIME DOUGADOS ◽  
MAHAUT RIPERT ◽  
PASCAL HILLIQUIN ◽  
PATRICE FARDELLONE ◽  
OLIVIER BROCQ ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Global Assessment ◽  
Disease Activity Score ◽  
Patient Global Assessment ◽  
Activity Score ◽  
Before And After ◽  
Definition Of ◽  
Very High ◽  
Assessment Of Disease Activity

Objective.Patient global assessment (PGA) is one of the 4 items included in the Disease Activity Score (DAS28) for evaluation of activity of rheumatoid arthritis (RA). We studied the influence of the use of 3 different techniques of PGA on the assessment of disease activity.Methods.We evaluated 3 different DAS28 according to the technique of PGA in 108 patients with active RA before and after 12 weeks of etanercept therapy.Results.The reliability (intraclass coefficient of correlation) between screening and baseline was very high and similar for the 3 DAS28. The percentage of patients in the different states of disease (from remission to higher disease activity) and the sensitivity to change across the 3 DAS28 scales were very similar.Conclusion.The different techniques of collection of PGA to be included in the DAS calculation yield similar results. However, an accepted, unequivocal technique should be encouraged in order to reduce heterogeneity in scoring DAS among patients with RA.

Increasing Treatment in Early Rheumatoid Arthritis Is Not Determined by the Disease Activity Score But by Physician Global Assessment: Results from the CATCH Study

2012 ◽  
Vol 39 (11) ◽  
pp. 2081-2087 ◽  
Author(s):  
LONNIE PYNE ◽  
VIVIAN P. BYKERK ◽  
GILLES BOIRE ◽  
BOULOS HARAOUI ◽  
CAROL HITCHON ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Global Assessment ◽  
Disease Activity Score ◽  
Activity Score ◽  
Joint Involvement ◽  
Tender Joint Count ◽  
Physician Global Assessment ◽  
Treatment Intensification

Objective.To determine the factors most strongly associated with an increase in therapy of early rheumatoid arthritis (ERA).Methods.Data from the Canadian Early Arthritis Cohort (CATCH) were included if the patient had ≥ 2 visits and baseline and 6 months data. A regression analysis was done to determine factors associated with treatment intensification.Results.Of 1145 patients with ERA, 790 met inclusion criteria; mean age was 53.4 years (SD 14.7), mean disease duration 6.1 months (SD 2.8), 75% were female, baseline Disease Activity Score-28 (DAS28) was 4.7 (SD 1.8) and 2.9 (SD 1.8) at 6 months for included patients. Univariate factors for intensifying treatment were physician global assessment (MDGA; OR 7.8 and OR 7.4 at 3 and 6 months, respectively, p < 0.0005), swollen joint count (SJC; OR 4.7 and OR 7.3 at 3 and 6 months, p < 0.0005), and DAS28 (OR 3.0 and OR 4.6 at 3 and 6 months, p < 0.0005). In the regression model only MDGA was strongly associated with treatment intensification (OR 1.5 and OR 1.2 at 3 and 6 months, p < 0.0005); DAS28 was not consistently predictive (OR 1.0, p = 0.987, and OR 1.2, p = 0.023, at 3 and 6 months). DAS28 was the reason for treatment intensification 2.3% of the time, compared to 51.7% for SJC, 49.9% for tender joint count, and 23.8% for MDGA. For the same SJC, larger joint involvement was more likely to influence treatment than small joints at 3 months (OR 1.4, p = 0.027).Conclusion.MDGA was strongly associated with an increase in treatment at 3 and 6 months in ERA, whereas DAS28 was not. Physicians rarely stated that DAS28 was the reason for increasing treatment.

scholarly journals SAT0096 DISCORDANCE BETWEEN SUBJECTIVE AND OBJECTIVE INDEX OF THE DISEASE ACTIVITY SCORE MAY REDUCE THE CORRELATION BETWEEN CLINICAL AND ULTRASOUND ASSESSMENT IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 981.2-982
Author(s):  
A. Xie ◽  
L. Ji ◽  
Z. Zhang
Keyword(s):  
Disease Activity ◽  
Global Assessment ◽  
Disease Activity Score ◽  
Power Doppler ◽  
Activity Score ◽  
Clinical Parameters ◽  
Sum Score ◽  
Ultrasound Findings ◽  
Ultrasound Assessment ◽  
Ultrasound Parameters

Background:There was discordance between subjective and objective index of the disease activity score, or between clinical parameters and ultrasound findings in some RA patients. Therefore, we set out to determine whether the discordance between subjective and objective index of the composite score could reduce the correlation between clinical and ultrasound parameters in RA.Objectives:To investigate whether the discordance between tender and swollen joint count (TJC and SJC) as well as patient’s and evaluator’s global assessment (PGA and EGA) influences the correlation between clinical and US parameters in RA.Methods:RA patients with available ultrasonography of 28 joints from Jan 2014 to Jan 2018 were enrolled in the study. Gray-scale (GS) synovial hypertrophy and Power Doppler (PD) synovitis were measured and semi-quantitatively graded. The total GS/PD score was the sum score of 28 joints. SJC and TJC based on 28 joints, PGA and EGA of all the patients were evaluated by one rheumatologist. The numeric difference between TJC and SJC (ΔTSJ) and that between PGA and EGA (ΔPEG) were calculated. The correlation between clinical and ultrasound parameters in different ΔTSJ and ΔPEG subgroups was explored.Results:Totally 163 patients were enrolled in the study. Clinical composite disease activity scores and all the components were significantly correlated with the total GS and PD scores (p<0.01 for all). But the relevance between the clinical disease parameters and total PD score became weak, with the increase of ΔTSJ. For the patients with ΔTSJ > 5, the total PD score was only correlated with CRP, EGA and PGA, while the total GS score was only correlated with CRP. Similarly, no correlation between total PD score and clinical parameters, except for SJC, was observed in patients with ΔPEG < 0 (p < 0.05).Conclusion:Total PD/GS score was correlated well with the clinical parameters of disease activity, including both the subjective and objective indexes. But for patients with ΔTSJ > 5,there was no correlation between total GS/PD scores and clinical composite disease activity scores, except that only the objective index (CRP, SJC and EGA) were more likely to correlate with total GS/PD scores.Disclosure of Interests:None declared

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