Immunoprinting: various genes are associated with increased risk to develop rheumatoid arthritis in different groups of adult patients

1995 ◽  
Vol 73 (1) ◽  
pp. 19-29 ◽  
Author(s):  
M. Gomolka ◽  
H. Menninger ◽  
J. E. Saal ◽  
E. -M. Lemmel ◽  
E. D. Albert ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adult Patients ◽  
Increased Risk

scholarly journals Switch from Infliximab to Infliximab-dyyb for Rheumatology Indications

2021 ◽  
pp. 32-36
Author(s):  
Alexi Spoto ◽  
Katie Pitcher ◽  
Rita Hui ◽  
Aeris Lautchang
Keyword(s):  
Rheumatoid Arthritis ◽  
Acute Care ◽  
Emergency Room Visit ◽  
Reference Product ◽  
Adult Patients ◽  
Northern California ◽  
Kaiser Permanente ◽  
Therapeutic Substitution ◽  
Increased Risk ◽  
Risk Of Disease

Introduction Multiple expert panels at Kaiser Permanente approved infliximab-dyyb (Inflectra®), a biosimilar to the reference product infliximab (Remicade®), to be the preferred infliximab agent for therapeutic substitution from infliximab for adult patients with dermatologic, rheumatologic, and/or gastroenterologic diagnoses. The objective of this study was to assess the safety and effectiveness of infliximab-dyyb for Kaiser Permanente Northern California patients with psoriatic and rheumatoid arthritis who switched from infliximab to infliximab-dyyb. Methods This was an observational, data-only, non-inferiority study assessing adult patients with a rheumatologic condition of psoriatic arthritis (PsA) or rheumatoid arthritis (RA) who were switched from infliximab to infliximab-dyyb or used infliximab continuously in the Northern California region of Kaiser Permanente from May 2017 through May 2018. Both groups were followed for 12 months. The primary effectiveness outcome was disease worsening requiring acute care defined as emergency room visit or hospitalization related to the rheumatologic condition or orthopedic surgery intervention. Non-inferiority was set at an upper limit of 4%. Results A total of 70 individuals were identified as continuing infliximab and 727 individuals were switched to infliximab-dyyb. There were 2 patients (2.9%) in the infliximab group and 22 patients (3.0%) in the infliximab-dyyb group who experienced disease worsening requiring acute care (P = 0.03 for non-inferiority). Conclusion There was no increased risk of disease worsening requiring acute care in patients with RA or PsA who switched from infliximab to infliximab-dyyb when compared to patients who remained on infliximab in this population.

Cardiovascular Risk in Rheumatoid Arthritis and Mechanistic Links: From Pathophysiology to Treatment

2020 ◽  
Vol 18 (5) ◽  
pp. 431-446 ◽  
Author(s):  
George E. Fragoulis ◽  
Ismini Panayotidis ◽  
Elena Nikiphorou
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Current Evidence ◽  
Pharmacological Intervention ◽  
Cvd Risk ◽  
The Past ◽  
Increased Risk ◽  
Cv Disease ◽  
Obesity Hypertension ◽  
Inflammatory Burden

Rheumatoid arthritis (RA) is an autoimmune inflammatory arthritis. Inflammation, however, can spread beyond the joints to involve other organs. During the past few years, it has been well recognized that RA associates with increased risk for cardiovascular (CV) disease (CVD) compared with the general population. This seems to be due not only to the increased occurrence in RA of classical CVD risk factors and comorbidities like smoking, obesity, hypertension, diabetes, metabolic syndrome, and others but also to the inflammatory burden that RA itself carries. This is not unexpected given the strong links between inflammation and atherosclerosis and CVD. It has been shown that inflammatory cytokines which are present in abundance in RA play a significant role in every step of plaque formation and rupture. Most of the therapeutic regimes used in RA treatment seem to offer significant benefits to that end. However, more studies are needed to clarify the effect of these drugs on various parameters, including the lipid profile. Of note, although pharmacological intervention significantly helps reduce the inflammatory burden and therefore the CVD risk, control of the so-called classical risk factors is equally important. Herein, we review the current evidence for the underlying pathogenic mechanisms linking inflammation with CVD in the context of RA and reflect on the possible impact of treatments used in RA.

scholarly journals O06 Baseline predictors of methotrexate-related adverse events in methotrexate-naïve patients with RA

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Ahmad A Sherbini ◽  
James M Gwinnutt ◽  
Kimme L Hyrich ◽  
Suzanne M M Verstappen ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Health Assessment ◽  
Prevalence Rates ◽  
Clinical Predictors ◽  
Research Support ◽  
Related Data ◽  
Increased Risk ◽  
One Year

Abstract Background/Aims  Methotrexate (MTX) is the most common treatment for rheumatoid arthritis (RA). The prevalence of adverse events (AEs) associated with MTX treatment for RA have been studied extensively, but there are limited data on the predictors of these AEs. This study aims to summarise the prevalence rates of MTX AEs, including gastrointestinal (GI), neurological, mucocutaneous, and elevated alanine transaminase (ALT) enzyme, and to identify baseline demographic and clinical predictors of these AEs. Methods  The Rheumatoid Arthritis Medication Study (RAMS) is a UK multi-centre prospective cohort study of patients with RA starting MTX for the first time. Relevant demographic, medication, clinical and disease related data were collected at baseline. AEs were reported at six and twelve months follow-ups. The prevalence rates of AEs were calculated based on the proportions of patients who reported having had an AE within one year of follow-up. The associations between candidate baseline predictors and AEs were assessed using multivariable logistic regression. Results  A total of 2,089 patients were included with a mean age of 58.4 (standard deviation: 13.5) years, 1390 (66.5%) were women. 1,814 and 1,579 patients completed the 6 and 12 months follow-up visits, respectively. The prevalence rates of the AEs within one year of follow-up were: GI = 777 (40.6%), mucocutaneous = 441 (23.1%), neurological = 487 (25.5%), elevated ALT (> upper limit of normal [ULN]) = 286 (15.5%). Younger age and being a woman were associated with increased risk of GI AEs, (age: OR 0.97 per year increase in age, 95% CI 0.98, 1.00; male sex: OR 0.58 vs female, 95% CI 0.46, 0.74) (Table 1). Higher baseline Health Assessment Questionnaire (HAQ) score was an independent predictor of GI, mucocutaneous, and neurological AEs. Furthermore, having ALT >1xULN at baseline or history of diabetes was associated with increased risk of subsequent ALT elevation during the study follow-up. Conclusion  In patients with RA starting MTX, GI AEs were the most commonly reported AEs during the first year of follow-up. The identified predictors of AEs may facilitate discussions between clinicians and patients prior to commencing MTX, and may lead to increased adherence and consequently improved effectiveness. Disclosure  A.A. Sherbini: None. J.M. Gwinnutt: Grants/research support; BMS. K.L. Hyrich: Member of speakers’ bureau; Abbvie. Grants/research support; Pfizer, UCB, BMS. S.M.M. Verstappen: Consultancies; Celltrion. Member of speakers’ bureau; Pfizer. Grants/research support; BMS.

scholarly journals OP0098 POLYPHARMACY IS ASSOCIATED WITH A POORER TREATMENT RESPONSE AND INCREASED RISK OF ADVERSE EVENTS IN EARLY RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 54.1-54
Author(s):  
S. Benamar ◽  
C. Lukas ◽  
C. Daien ◽  
C. Gaujoux-Viala ◽  
L. Gossec ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Treatment Response ◽  
Univariate Analysis ◽  
Group Versus ◽  
Biological Database ◽  
Lower Probability ◽  
Research Support ◽  
Early Ra ◽  
Increased Risk

Background:Polypharmacy is steadily increasing in patients with rheumatoid arthritis (RA). They may interfere with treatment response and the occurrence of serious adverse events. Medications taken by a patient may reflect active comorbidities, whereas comorbidity indices usually used include past or current diseases.Objectives:To evaluate whether polypharmarcy is associated with treatment response and adverse events in an early RA cohort and to establish whether polypharmacy could represent a substitute of comorbidities.Methods:We used data from the French cohort ESPOIR, including 813 patients with early onset arthritis. Patients included the current study had to start their first disease modifying anti-rheumatic drug (DMARD) within 24 months of inclusion in the cohort. Disease activity data were collected at one, five and ten years from the initiation of the first DMARD. For each patient, treatments were collected at baseline and at five years. Medications count included all specialties other than background RA therapy, analgesics/NSAIDs and topicals. Polypharmacy was defined as a categorical variable based on the median and tertiles of distribution in the cohort. Treatment response was assessed by achieving DAS28 ESR remission (REM) at 1 year, 5 years and 10 years from the initiation of the first DMARD. The occurrence of severe adverse events (SAE) was measured by the occurrence of severe infection, hospitalization, or death during the 10-year follow-up. The association between patient’s characteristics and achievement of REM and occurrence of SAE were tested in univariate analysis. A logistic regression model was used to evaluate associations between polypharmacy and REM at 1 year, 5 years and 10 years (we used baseline polypharmacy for the 1-year analysis and five years polypharmacy for the 5- and 10-years analyses). Multivariate adjustment was made for age, sex, BMI, duration of disease, initial DAS28 ESR, initial HAQ, smoking status, rheumatic disease comorbidity index (RDCI).Results:The proportion of patients who achieved REM one year after the initiation of the first DMARD was 32.1% in the polypharmacy according to the median group (patients taken ≥2 medication) versus 67.9% in the non-polypharmacy group (p=0.07). At 5 years after the first DMARD, the proportion of patients with REM was 45.0% in the polypharmacy group versus 56.3% in the non-polypharmacy group (p=0.03). At 10 years the proportion of patients with REM was 32.5% in the polypharmacy group versus 67.5% (p=0.06). Patients who take greater or equal to 2 medications had a 40% lower probability of achieving REM (OR = 0.60 [0.38-0.94] p = 0.03) at 5 years from the first DMARD (if RDCI index was not included in the model). At 10 years, patients receiving multiple medications had a 43% lower probability of achieving REM (OR = 0.57 [0.34-0.94] p = 0.02). SAE incidence was 61 per 1000 patient-years. For patients who developed SAE all causes 71.4% where in the polypharmacy group versus 57.8% were in the non-polypharmacy group (p = 0.03; univariate analysis). These results are no longer significant after adjustment for comorbidities indices.Conclusion:In this early RA cohort, polypharmacy is associated with a poorer treatment response and increased risk of adverse events. Polypharmacy may represent a good substitute of comorbidities for epidemiological studies.Acknowledgements:We are grateful to Nathalie Rincheval (Montpellier) who did expert monitoring and data management and all theinvestigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine; MC. Boissier, Paris-Bobigny; A. Cantagrel, Toulouse; B. Combe, Montpellier; M. Dougados, Paris-Cochin; P. Fardellone and P. Boumier, Amiens; B. Fautrel, Paris-La Pitié; RM. Flipo, Lille; Ph. Goupille, Tours; F. Liote, Paris- Lariboisière; O. Vittecoq, Rouen; X. Mariette, Paris-Bicêtre; P. Dieude, Paris Bichat; A. Saraux, Brest; T. Schaeverbeke, Bordeaux; and J. Sibilia, Strasbourg).The work reported on in the manuscript did not benefit from any financial support. The ESPOIR cohort is sponsored by the French Society for Rheumatology. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. Pfizer, Abbvie, Lilly and more recently Fresenius and Biogen also supported the ESPOIR cohort.Disclosure of Interests:Soraya Benamar: None declared, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Claire Daien Speakers bureau: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Consultant of: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Cécile Gaujoux-Viala Speakers bureau: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Consultant of: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Grant/research support from: Pfizer, Laure Gossec Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Anne-Christine Rat Speakers bureau: Pfizer, Lilly, Consultant of: Pfizer, Lilly, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Novartis, Pfizer, and Roche-Chugai., Jacques Morel Speakers bureau: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Consultant of: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Grant/research support from: BMS, Pfizer

scholarly journals Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies

2021 ◽  
Vol 14 ◽  
pp. 117954412110287
Author(s):  
Mir Sohail Fazeli ◽  
Vadim Khaychuk ◽  
Keith Wittstock ◽  
Boris Breznen ◽  
Grace Crocket ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Literature Review ◽  
Rheumatoid Factor ◽  
Qualitative Evidence Synthesis ◽  
Cvd Risk ◽  
Rheumatoid Arthritis Risk ◽  
Published Evidence ◽  
Increased Risk

Objective: To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents. Methods: Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out. Results: A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients. Conclusion: Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.

scholarly journals FRI0072 DISCONTINUATION OF DMARD USE IN RHEUMATOID ARTHRITIS PATIENTS WITH LUNG DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 612.1-613
Author(s):  
S. Pedro ◽  
T. Mikuls ◽  
J. Zhuo ◽  
K. Michaud
Keyword(s):  
Rheumatoid Arthritis ◽  
Lung Disease ◽  
Pulmonary Disease ◽  
Treatment Patterns ◽  
Dmard Treatment ◽  
Increased Risk ◽  
Pulmonary Manifestations ◽  
Clinical Models ◽  
Comorbidity Index ◽  
Time Varying Covariates

Background:Pulmonary manifestations such as interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) are frequent extra-articular features that carry a poor prognosis in Rheumatoid Arthritis (RA). Little data is available on how RA patients (pts) with pulmonary disease are managed in real-world settings.Objectives:To assess treatment patterns and DMARD discontinuation in RA patients with comorbid lung disease in comparison with other RA patients.Methods:The study included RA Patients enrolled in the Forward Databank with ≥1 year observation after 2000 initiating a DMARD. Forward is a large longitudinal rheumatic disease registry in the US. RA patients’ diagnoses were rheumatologist-confirmed, and every 6 months participants completed comprehensive questionnaires regarding symptoms, disease outcomes, medications, and clinical events. Lung disease (LD+) was defined as at least one of the following: emphysema, asthma, bronchitis, COPD, pleural effusion, fibrosis of the lung, “RA lung”, or ILD, the later classified by ICD9 codes (England 2019). DMARDs were categorized hierarchically into four groups: csDMARDs, TNFi and NTNFi (bDMARDs), and tsDMARDs. Percentage of patients who initiated different DMARDs were reported for pts with LD+/LD-. Discontinuation was analyzed by Kaplan Meier (KM) curves, log-ranks tests, and Cox regression models using time-varying covariates. Best models were created using backward selection models (10% probability of removal) and pre-defined clinical models.Results:Of the 21,525 eligible RA patients, 13.8% had LD+ at the time they initiated a DMARD (follow-up: 69,597 pt-yrs (median 1.9 yrs/pt)). LD+ patients tended to have more severe RA outcomes and comorbidities. MTX-monotherapy (48% vs 44%, p<0.001) and NTNFi were initiated more frequently in LD+ pts with lower use of TNFi (Figure). DMARD discontinuation rates were higher among LD+ patients for all DMARD groups, but KM curves were only significantly different for csDMARDs and TNFi. Different HRs for LD+ were found depending on the model used ranging from 1.18 to 1.28, and all models revealed an increased risk of discontinuation for LD+ patients. Compared to csDMARDs, TNFi were more often discontinued (Table). Other variables associated with an increased risk of discontinuation included: HAQ, Rheumatoid Disease (RD) comorbidity index, pain, prior bDMARDs, and csDMARDs.Conclusion:Different DMARD treatment patterns were found for LD+ patients, who tended to initiate more csDMARD and NTNFi and less likely to initiate a TNFi. LD+ patients were at a higher risk of discontinuation irrespectively of the DMARD treatment, but with greater risk for TNF users.References:[1]England BR, et al. Arth Care Res. doi:10.1002/acr.24043.Figure.DMARD treatment initiators by disease groupTable .Cox models for DMARD discontinuation by stepwise (removal probability 10%) and clinical models including DMARD treatment.Model of DMARD persistence*Model 1- Stepwise-Without drugsModel 2 – StepwiseModel 3 - ClinicalLD+ vs LD–1.181.281.20(1.08 - 1.29)(1.13 - 1.45)(1.08 - 1.34)TNF vs csDmard1.321.22(1.08 - 1.63)(1.04 - 1.44)NTNF vs csDmard1.131.13(0.83 - 1.52)(0.90 - 1.41)tsDmard vs csDmard1.301.02(0.65 - 2.60)(0.64 - 1.62)*Best models searched/Clinical adjusted for LD+/LD-, DMARDs, age, sex, education, HAQ disability, RD comorbidity index, smoking, pain, glucocorticoids, year of entry, prior bDMARDs and csDMARDs counts and MRC breath scale.Disclosure of Interests:Sofia Pedro: None declared, Ted Mikuls Grant/research support from: Horizon Therapeutics, BMS, Consultant of: Pfizer, Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Kaleb Michaud: None declared

scholarly journals Effect of janus kinase inhibitors and methotrexate combination on malignancy in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vinod Solipuram ◽  
Akhila Mohan ◽  
Roshniben Patel ◽  
Ruoning Ni
Keyword(s):  
Rheumatoid Arthritis ◽  
Combination Therapy ◽  
Randomized Controlled Trials ◽  
Random Effect ◽  
Janus Kinase ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Significant Difference ◽  
Risk Of Malignancy

Abstract Background Rheumatoid arthritis (RA) is a systemic autoimmune disease. The combination therapy of methotrexate (MTX) and Janus kinase inhibitor (JAKi) is commonly used. Patients with RA are at increased risk of malignancy, however, it remains unclear whether the combination therapy is associated with a higher risk. Objective To assess the malignancy risk among patients with RA receiving combination therapy of JAKi and MTX compared to MTX alone. Methods PubMed, Cochrane and Embase were thoroughly searched for randomized controlled trials (RCTs) in patients with RA receiving JAKi and MTX, from inception to July 2020. Primary endpoints were malignancy events, Non melanomatous skin cancer (NMSC) and malignancy excluding NMSC and secondary endpoints were serious adverse events (SAE), deaths. Risk ratio (RR) and 95% CI were calculated using the Mantel–Haenszel random-effect method. Results 659 publications were screened and 13 RCTs with a total of 6911 patients were included in the analysis. There was no statistically significant difference in malignancy [RR = 1.42; 95% CI (0.59, 3.41)], neither NMSC [RR = 1.44 (0.36, 5.76)] nor malignancies excluding NMSC [RR = 1.12 (0.40, 3.13)]. No statistically significant difference between the two groups for SAE [RR = 1.15 (0.90, 1.47)] and deaths [RR = 1.99 (0.75, 5.27)] was found. Conclusion The adjunction of JAKi to MTX is not associated with an increased risk of malignancy when compared to MTX alone. There is no increased risk of SAE and deaths when compared to MTX alone in patients with RA.

scholarly journals OP0034 DOES THE RISK OF VENOUS THROMBOEMBOLISM VARY WITH DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 23.2-24
Author(s):  
V. Molander ◽  
H. Bower ◽  
J. Askling
Keyword(s):  
Rheumatoid Arthritis ◽  
Logistic Regression ◽  
Venous Thromboembolism ◽  
Disease Activity ◽  
Das28 Score ◽  
Logistic Regression Models ◽  
Highly Active ◽  
Increased Risk ◽  
Das28 Remission ◽  
One Year

Background:Patients with rheumatoid arthritis (RA) are at increased risk for venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) (1). Several established risk factors of VTE, such as age, immobilization and comorbid conditions, occur more often patients with RA (2). In addition, inflammation may in itself also increase VTE risk by upregulating procoagolatory factors and causing endothelial damage (3). Recent reports indicate an increased risk of VTE in RA patients treated with JAK-inhibitors (4), pointing to the need to better understand how inflammation measured as clinical RA disease activity influences VTE risk.Objectives:To investigate the relationship between clinical RA disease activity and incidence of VTE.Methods:Patients with RA were identified from the Swedish Rheumatology Quality Register (SRQ) between July 1st2006 and December 31st2017. Clinical rheumatology data for these patients were obtained from the visits recorded in SRQ, and linked to national registers capturing data on VTE events and comorbid conditions. For each such rheumatologist visit, we defined a one-year period after the visit and determined whether a VTE event had occurred within this period or not. A visit followed by a VTE event was categorized as a case, all other visits were used as controls. Each patient could contribute to several visits. The DAS28 score registered at the visit was stratified into remission (0-2.5) vs. low (2.6-3.1), moderate (3.2-5.1) and high (>5.1) disease activity. Logistic regression with robust cluster standard errors was used to estimate the association between the DAS28 score and VTE.Results:We identified 46,311 patients with RA who contributed data from 320,094 visits. Among these, 2,257 visits (0.7% of all visits) in 1345 unique individuals were followed by a VTE within the one-year window. Of these, 1391 were DVT events and 866 were PE events. Figure 1 displays the absolute probabilities of a VTE in this one-year window, and odds ratios for VTE by each DAS28 category, using DAS28 remission as reference. The one-year risk of a VTE increased from 0.5% in patients in DAS28 remission, to 1.1% in patients with DAS28 high disease activity (DAS28 above 5.1). The age- and sex-adjusted odds ratio for a VTE event in highly active RA compared to RA in remission was 2.12 (95% CI 1.80-2.47). A different analysis, in which each patient could only contribute to one visit, yielded similar results.Figure 1.Odds ratios (OR) comparing the odds of VTE for DAS28 activity categories versus remission. Grey estimates are from unadjusted logistic regression models, black estimates are from logistic regression models adjusted for age and sex. Absolute one-year risk of VTE are estimated from unadjusted models.Conclusion:This study demonstrates a strong association between clinical RA inflammatory activity as measured through DAS28 and risk of VTE. Among patients with high disease activity one in a hundred will develop a VTE within the coming year. These findings highlight the need for proper VTE risk assessment in patients with active RA, and confirm that patients with highly active RA, such as those recruited to trials for treatment with new drugs, are already at particularly elevated risk of VTE.References:[1]Holmqvist et al. Risk of venous thromboembolism in patients with rheumatoid arthritis and association with disease duration and hospitalization. JAMA. 2012;308(13):1350-6.[2]Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007;44(2):62-9.[3]Xu J et al. Inflammation, innate immunity and blood coagulation. Hamostaseologie. 2010;30(1):5-6, 8-9.[4]FDA. Safety trial finds risk of blood clots in the lungs and death with higher dose of tofacitinib (Xeljanz, Xeljanz XR) in rheumatoid arthritis patients; FDA to investigate. 2019.Acknowledgments:Many thanks to all patients and rheumatologists persistently filling out the SRQ.Disclosure of Interests:Viktor Molander: None declared, Hannah Bower: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma

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