Saudi cultural adaptation of the “compliance questionnaire of Rheumatology” for Rheumatoid arthritis patients on disease modifying anti-rheumatic drugs (DMARDs)

Abstract Aim Leflunomide is a disease-modifying antirheumatic drug used in therapy for rheumatoid arthritis (RA). Previous studies indicated that oestrogens and androgens may affect the response to leflunomide in RA patients. The synthesis of androgens is regulated by cytochrome CYB5A. The aim of this study was to examine the association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA. Methods The study included 111 women diagnosed with RA. Leflunomide was administered in monotherapy at a dose of 20 mg/day. All patients underwent a monthly evaluation for 12 months after the initiation of treatment with leflunomide. Results After 12 months of therapy, the changes in individual disease activity parameters, such as: DAS28, ESR, CRP and VAS, were not statistically significantly different between rs1790834 genotypes in the Kruskal–Wallis test. Conclusions The results of our study suggest lack of statistically significant association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA.

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FRI0526 THE INCIDENCE, PREVALENCE AND MEDICATION USE OF RHEUMATOID ARTHRITIS AMONG KOREAN WOMEN IN CHILDBEARING YEARS: A NATIONWIDE POPULATION-BASED STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4249 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 862.2-863

Author(s):

M. K. Chung ◽

J. S. Park ◽

H. S. Lim ◽

C. H. Lee ◽

J. Lee

Keyword(s):

Rheumatoid Arthritis ◽

Lupus Erythematosus ◽

Medication Use ◽

Population Based ◽

Korean Women ◽

Childbearing Age ◽

Disease Modifying Antirheumatic Drugs ◽

Antirheumatic Drugs ◽

Disease Modifying ◽

Incidence Prevalence

Background:Rheumatoid arthritis (RA) predominantly affects women and has a significant impact on childbearing. Several population-based studies identifying incidence, prevalence, and medication use of RA have been reported, yet epidemiological studies focusing on women with RA in childbearing years are missing.Objectives:We aimed to identify the incidence, prevalence and medication use of RA among Korean women in childbearing years.Methods:From National Health Insurance Service (NHIS) data (2009-2016), containing inpatient and outpatient claim information for approximately 97% of the Korean population, we identified 9,217,139 women aged between 20-44 years. Incidence and prevalence of RA in the specific sociodemographic group of women in childbearing age were analyzed, and the prevalence of medication prescription were compared between women with RA and controls without rheumatic diseases such as RA, systemic lupus erythematosus, and ankylosing spondylitis. Individuals with RA were defined by the presence of International Classification of Disease, 10th revision code, M05. The medication use was defined as receiving > 90days prescriptions of NSAIDs, corticosteroids (CSs), and conventional synthetic (cs) disease modifying antirheumatic drugs (DMARDs) or > 1day prescription of biologic (b) DMARDs.Results:Total 24,590 women with RA were identified. The average incidence of RA during 2011-2016 among women in childbearing years was 24.1/100,000 person-years (PYs) (95% CI 20.91-27.31) with a yearly increase from 20.99/100,000 PYs in 2011 to 28.38/100,000 PYs in 2016. The average prevalence of RA during 2009-2016 among women in childbearing years was 105.2/100,000 PYs (95% CI 99.0-111.5) with a minimum of 95.7/100,000 PYs in 2009 and a maximum of 110.5/100,000 PYs in 2016. There were increasing trends in both incidence and prevalence of RA according to age among women in childbearing years peaking in the age group of 40-44 years. The prescriptions of NSAIDs, CSs, csDMARDs and bDMARDs were more frequent in women with RA than controls (NSAIDs; 94.21% vs 21.79%, CSs; 83.65% vs 4.28%, csDMARDs; 91.23% vs 0.41%, bDMARDs; 0.11% vs 0%, p<0.001).Conclusion:The incidence and prevalence of RA are high among Korean women in childbearing years, and medication use was significantly more frequent in this specific population than controls. High disease burden is imposed upon women in childbearing years.References:[1] Won S, Cho SK, Kim D, Han M, Lee J, Jang EJ, Sung YK, Bae SC: Update on the prevalence and incidence of rheumatoid arthritis in Korea and an analysis of medical care and drug utilization. Rheumatol Int 2018, 38(4):649-656.[2] Smeele HTW, Dolhain R: Current perspectives on fertility, pregnancy and childbirth in patients with Rheumatoid Arthritis. Seminars in arthritis and rheumatism 2019, 49(3s):S32-s35.Table 1.Medication use among women with RA and controls in childbearing age between 20-44 years during 2009-2016Control(n=155,486)RA(n=23,756)n(%)n(%)PNSAIDs33,887(21.79)22,380(94.21)<.0001Steroids6,653(4.28)19,871(83.65)<.0001csDMARDs634(0.41)21,673(91.23)<.0001bDMARDs0(0.00)27(0.11)<.0001RA, rheumatoid arthritis; NSAID, non-steroidal anti-inflammatory drug; cs, conventional synthetic; b, biologic; DMARDs, disease modifying antirheumatic drugsDisclosure of Interests:None declared

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POS0287 USE OF BIOLOGIC DISEASE MODIFYING ANTI-RHEUMATIC DRUGS IN RELATION TO THE RISK OF LYMPHOMA: A COHORT STUDY OF US VETERANS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3395 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 369.1-369

Author(s):

N. Singh ◽

A. Peterson ◽

A. Baraff ◽

A. Korpak ◽

M. Vaughan-Sarrazin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Native American ◽

Diagnostic Code ◽

Health Administration ◽

Inception Cohort ◽

Regular User ◽

Psoriatic Arthropathy ◽

Disease Modifying ◽

Us Veterans ◽

Lymphoma Risk

Background:Epidemiologic studies suggest that disease duration and degree of inflammatory activity of rheumatoid arthritis (RA) contribute to lymphoma development. However, the association of the use of biologic disease modifying anti-rheumatic drugs (bDMARDs) in patients with RA on lymphoma risk needs further evaluation.Objectives:Examine the effect of administration of bDMARDS on the incidence of lymphoma in an inception cohort of RA.Methods:We identified patients diagnosed with RA in any US Veterans Affairs (VA) facility from 1/1/2002 and 12/31/2018 using the Veteran’s Health Administration (VHA) databases. To be included, each patient was required to meet the following criteria: 1) 2+ RA diagnostic codes at least 7 days apart but no more than 365 days apart 2) a prescription for a conventional synthetic DMARD (csDMARD) within 90 days of the first RA diagnosis 3) One inpatient or outpatient visit 30 days to 2 years preceding first RA diagnosis (indicating they are a regular user of the VHA). We excluded patients for any of the following if they preceded the first RA diagnosis: 1) a prior single RA diagnostic code 2) a prescription for any DMARD medication 3) a concomitant diagnosis of another inflammatory arthritis (e.g. psoriatic arthropathy) 4) a diagnosis of lymphoma. Index date for the study is the date of the first qualifying RA diagnosis. Lymphoma diagnoses were identified through VHA records using the International Classification of Diseases-Oncology codes.Results:We identified 27,536 veterans with RA in the study period meeting the inclusion and exclusion criteria. Of these, 53% (n=14,705) were in the age range 60 to 80 years. The cohort was 89% male, 75.5% White, 13.7% African American. Over the study period, 1.2% (n=332) of the study population developed a lymphoma.Conclusion:Using the nationwide VHA we have identified a large inception cohort of patients with RA of whom 1.2% developed lymphoma over study follow-up. This data will be used in future analyses to produce estimates of the effect of biologic medications on lymphoma risk, adjusting for confounding by indication and other variables.Table 1.Baseline characteristics of the cohort based on bDMARD exposure statusCharacteristicbDMARD-naive (n= 19,095)bDMARD-exposed (n=8,441)Overall Lymphomas Age (years)171161 18-4046 40-606378 60-8010074 >8043 Males17,206 (90%)7,270 (86%)Race White14,150 (74%)6,627 (76%) Black2,674 (14%)1,090 (13%) Asian96 (0.5%)46 (0.5%) Native American or Pacific Islander371 (2%)187 (2.2%) Missing1,804 (9%)491 (6%)Acknowledgements:The work in this abstract is supported by Investigator Award from the Rheumatology Research Foundation to Dr Singh.Disclosure of Interests:None declared

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CO0005 C-C CHEMOKINE RECEPTOR TYPE 5 AND ITS LIGANDS CCL4, 8 AND 11 CAN LINK COVID-19, RHEUMATOID ARTHRITIS AND HYDROXYCHLOROQUINE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6801 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 213.3-214

Author(s):

M. Y. Hachim ◽

S. Hannawi

Keyword(s):

Rheumatoid Arthritis ◽

Mechanism Of Action ◽

Immune Cells ◽

Health Concern ◽

Healthy Controls ◽

Global Public Health ◽

Ccr5 Expression ◽

Disease Modifying Drugs ◽

Link Type ◽

Disease Modifying

Background:Coronavirus disease (COVID-19) caused by SARS-COV2 represents an unprecedented global public health concern with a particular burden on patients with chronic diseases and those on immune-modulating drugs. It is especially worrisome to patients with rheumatoid arthritis (RA) who are on immune suppression regimens[1]. On the other side, many reports showed and recommended the use of some Disease-Modifying Drugs commonly used to treat rheumatic diseases like hydroxychloroquine. However, the general understanding of COVID-19 characteristics in this population and the mechanism of action of these drugs in COVID-19 is still unknown[2].Objectives:Explore publicly available transcriptomic dataset of patients infected with SARS-COV2 compared to uninfected to identify differentially expressed genes (DEGs) related to the immune system that might be pathogenic in RA synovium. Then explore the effect of Disease-Modifying Drugs on their local expression that might give hints about their possible mechanism of action.Methods:RNAseq dataset (GSE147507) were retrieved using the Gene Expression Omnibus (GEO) and used to identify DEGs between infected and uninfected lung samples using BioJupies tools [3]. The DEGs were explored for common pathways using Metascape online tool (http://metascape.org) [10], as shown in figure (1). The chemokines genes were filtered out, and their common receptor (CR) was identified. The immune cells that express a higher level of the identified receptor were explored using DICE project tool (https://dice-database.org/). The expression of CR was searched in a microarray dataset (GSE77298) of synovial biopsies of RA and healthy controls. RNAseq dataset (GSE97165) of synovial biopsies taken from 19 early RA patients at baseline and after six months of Triple Disease-Modifying Anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine, and hydroxychloroquine) treatment.Results:84 DEGs were identified between uninfected and COVID-19 infected lung samples. These DEGs were enriched in pathways specific to (response to the virus, response to interferon, leukocyte activation, and chemotaxis). Interestingly, SARS-COV-2 infected lungs express more CCL4, CCL8, and CCL11; the three ligands shared the same receptor, which is CCR5. Top immune cells that express CCR5 were CD4 T memory T reg cells, Th17, Th1, and monocytes. CCR5 was significantly upregulated in RA compared to healthy controls synovium (p=0.04) and was dramatically downregulated after six months of tDMARD treatment (p=0.004), as shown in figure (2).Conclusion:Using publicly available transcriptomic datasets properly highlighted the possible beneficiary effect of DMARDs in patients with COVID-19, which can block CCR5 rich immune cells recruitment.References:[1]Favalli, E.G., et al.,COVID-19 infection and rheumatoid arthritis: Faraway, so close!Autoimmun Rev, 2020. 19(5): p. 102523.[2]Gianfrancesco, M.A., et al.,Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries.The Lancet Rheumatology, 2020. 2(5): p. e250-e253.[3]Torre, D., A. Lachmann, and A. Ma’ayan,BioJupies: Automated Generation of Interactive Notebooks for RNA-Seq Data Analysis in the Cloud.Cell Systems, 2018. 7(5): p. 556-561.e3.Figure 1.Flowchart of transcriptomic analysisFigure 2.(A) Top immune cells that express CCR5 (B) CCR5 expression in synovial biopsies of RA and control (C) CCR5 expression at baseline and after 6 months of tDMARD treatment.Disclosure of Interests:None declared

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OP0033 REGULATORY T CELL CD39 EXPRESSION AS A PREDICTOR OF EARLY REMISSION-INDUCTION WITH METHOTREXATE IN NEW-ONSET RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2030 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 18.2-18

Author(s):

P. Brown ◽

A. Anderson ◽

B. Hargreaves ◽

A. Morgan ◽

J. D. Isaacs ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

Cd4 T Cells ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Disease Modifying Therapy ◽

Blood Mononuclear Cells ◽

Treatment Naïve ◽

Disease Modifying ◽

Pre Treatment

Background:The long term outcomes for patients with rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate remains the key first line disease modifying therapy for the majority of patients, with 40% achieving an ACR50 on monotherapy(1). There are at present no effective biomarkers to predict treatment response, preventing effective personalisation of therapy. A putative mechanism of action of methotrexate, the potentiation of anti-inflammatory adenosine signalling, may inform biomarker discovery. By antagonism of the ATIC enzyme in the purine synthesis pathway, methotrexate has been proposed to increase the release of adenosine moieties from cells, which exert an anti-inflammatory effect through interaction with ADORA2 receptors(2). Lower expression of CD39 (a cell surface 5-’ectonucleotidase required for the first step in the conversion of ATP to adenosine) on circulating regulatory T-Lymphocytes (Tregs) was previously identified in patients already established on methotrexate who were not responding (DAS28 >4.0 vs <3.0)(3). We therefore hypothesised that pre-treatment CD39 expression on these cells may have clinical utility as a predictor of early methotrexate efficacy.Objectives:To characterise CD39 expression in peripheral blood mononuclear cells in RA patients naïve to disease modifying therapy commencing methotrexate, and relate this expression to 4 variable DAS28CRP remission (<2.6) at 6 months.Methods:68 treatment naïve early RA patients starting methotrexate were recruited from the Newcastle Early Arthritis Clinic and followed up for 6 months. Serial blood samples were taken before and during methotrexate therapy with peripheral blood mononuclear cells isolated by density centrifugation. Expression of CD39 by major immune subsets (CD4+ and CD8+ T-cells, B-lymphocytes, natural killer cells and monocytes) was determined by flow cytometry. The statistical analysis used was binomial logistic regression with baseline DAS28CRP used as a covariate due to the significant association of baseline disease activity with treatment response.Results:Higher pre-treatment CD39 expression was observed in circulating CD4+ T-cells of patients who subsequently achieved clinical remission at 6 months versus those who did not (median fluorescence 4854.0 vs 3324.2; p = 0.0108; Figure 1-A). This CD39 expression pattern was primarily accounted for by the CD4+CD25 high sub-population (median fluorescence 9804.7 vs 6455.5; p = 0.0065; Figure 1-B). These CD25 high cells were observed to have higher FoxP3 and lower CD127 expression than their CD39 negative counterparts, indicating a Treg phenotype. No significant associations were observed with any other circulating subset. A ROC curve demonstrates the discriminative utility of differential CD39 expression in the CD4+CD25 high population for the prediction of DAS28CRP remission in this cohort, showing greater specificity than sensitivity for remission prediction(AUC: 0.725; 95% CI: 0.53 - 0.92; Figure 1-C). Longitudinally, no significant induction or suppression of the CD39 marker was observed amongst patients who did or did not achieve remission over the 6 months follow-up period.Figure 1.Six month DAS28CRP remission versus pre-treatment median fluorescence of CD39 expression on CD4+ T-cells (A); CD25 High expressing CD4+ T-cells (B); and ROC curve of predictive utility of pre-treatment CD39 expression on CD25 High CD4+ T-cells (C).Conclusion:These findings support the potential role of CD39 in the mechanism of methotrexate response. Expression of CD39 on circulating Tregs in treatment-naïve RA patients may have particular value in identifying early RA patients likely to respond to methotrexate, and hence add value to evolving multi-parameter discriminatory algorithms.References:[1]Hazlewood GS, et al. BMJ. 2016 21;353:i1777[2]Brown PM, et al. Nat Rev Rheumatol. 2016;12(12):731-742[3]Peres RS, et al. Proc Natl Acad Sci U S A. 2015;112(8):2509-2514Disclosure of Interests:None declared

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