scholarly journals Risk of venous thromboembolism in rheumatoid arthritis, and its association with disease activity: a nationwide cohort study from Sweden

2020 ◽  
pp. annrheumdis-2020-218419
Author(s):  
Viktor Molander ◽  
Hannah Bower ◽  
Thomas Frisell ◽  
Johan Askling

ObjectiveTo assess the incidence of venous thromboembolism (VTE) in rheumatoid arthritis (RA) relative to individuals without RA, and to investigate the relationship between aspects of clinical disease activity in RA and the risk of VTE.MethodsWe conducted a nationwide register-based cohort study 2006 through 2018 using the Swedish Rheumatology Quality Register linked to other national patient registers to identify all patients with RA with at least one registered rheumatologist visit during the study period (n=46 316 patients, 322 601 visits). The Disease Activity Score 28 erythrocyte sedimentation rate (ESR) (DAS28 ESR) and its components served as the exposure, and a VTE event within the year following the visit was the main outcome. We also included general population referents (1:5) matched on age, sex and residential area.ResultsBased on 2241 incident VTE events within 1 year of each included visit, and 5301 VTE events in the general population cohort, the risk ratio for VTE in RA was 1.88 (95% CI 1.65 to 2.15). Among patients with RA, the risk (and risk ratio) increased with increasing RA disease activity, from 0.52% following visits in remission to 1.08% following visits with DAS28 ESR high disease activity, RR compared with remission=2.03, 95% CI 1.73 to 2.38. Compared with the general population, also patients with RA in DAS28 ESR remission were at elevated VTE risk.ConclusionsThis study demonstrates a strong association between clinical RA disease activity measured by DAS28 ESR and the risk of VTE. RA disease activity can be used as an additional tool for VTE risk stratification in patients with RA.

2017 ◽  
Vol 39 (39) ◽  
pp. 3608-3614 ◽  
Author(s):  
Alexis Ogdie ◽  
Neilia Kay McGill ◽  
Daniel B Shin ◽  
Junko Takeshita ◽  
Thorvardur Jon Love ◽  
...  

Rheumatology ◽  
2021 ◽  
Author(s):  
Rugina I Neuman ◽  
Hieronymus T W Smeele ◽  
A H Jan Danser ◽  
Radboud J E M Dolhain ◽  
Willy Visser

Abstract Objectives An elevated sFlt-1/PlGF-ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with rheumatoid arthritis (RA). We explored whether the sFlt-1/PlGF-ratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since sulfasalazine has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether sulfasalazine could affect sFlt-1 or PlGF levels. Methods Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21–42 years, were included, with a median gestational age of 30 + 3 weeks. Results No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (p= 0.07 and p= 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r=-0.01 and r=-0.05, respectively). Four (2%) women with a sFlt-1/PlGF-ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio > 38, corresponding to a negative predictive value of 98.1%. Sulfasalazine users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-sulfasalazine users (n = 164, p= 0.91 and p= 0.11). Conclusion Our study shows that in pregnant women with RA, the sFlt-1/PlGF-ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, sulfasalazine use did not affect sFlt-1 or PlGF levels in this population.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 23.2-24
Author(s):  
V. Molander ◽  
H. Bower ◽  
J. Askling

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


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 561.2-562
Author(s):  
X. Liu ◽  
Z. Sun ◽  
W. Guo ◽  
F. Wang ◽  
L. Song ◽  
...  

Background:Experts emphasize early diagnosis and treatment in RA, but the widely used diagnostic criterias fail to meet the accurate judgment of early rheumatoid arthritis. In 2012, Professor Zhanguo Li took the lead in establishing ERA “Chinese standard”, and its sensitivity and accuracy have been recognized by peers. However, the optimal first-line treatment of patients (pts) with undifferentiated arthritis (UA), early rheumatoid arthritis (ERA), and rheumatoid arthritis (RA) are yet to be established.Objectives:To evaluate the efficacy and safety of Iguratimod-based (IGU-based) Strategy in the above three types of pts, and to explore the characteristics of the effects of IGU monotherapy and combined treatment.Methods:This prospective cohort study (ClinicalTrials.gov Identifier NCT01548001) was conducted in China. In this phase 4 study pts with RA (ACR 1987 criteria[1]), ERA (not match ACR 1987 criteria[1] but match ACR/EULAR 2010 criteria[2] or 2014 ERA criteria[3]), UA (not match classification criteria for ERA and RA but imaging suggests synovitis) were recruited. We applied different treatments according to the patient’s disease activity at baseline, including IGU monotherapy and combination therapies with methotrexate, hydroxychloroquine, and prednisone. Specifically, pts with LDA and fewer poor prognostic factors were entered the IGU monotherapy group (25 mg bid), and pts with high disease activity were assigned to combination groups. A Chi-square test was applied for comparison. The primary outcomes were the proportion of pts in remission (REM)or low disease activity (LDA) that is DAS28-ESR<2.6 or 3.2 at 24 weeks, as well as the proportion of pts, achieved ACR20, Boolean remission, and good or moderate EULAR response (G+M).Results:A total of 313 pts (26 pts with UA, 59 pts with ERA, and 228 pts with RA) were included in this study. Of these, 227/313 (72.5%) pts completed the 24-week follow-up. The results showed that 115/227 (50.7%), 174/227 (76.7%), 77/227 (33.9%), 179/227 (78.9%) pts achieved DAS28-ESR defined REM and LDA, ACR20, Boolean remission, G+M response, respectively. All parameters continued to decrease in all pts after treatment (Fig 1).Compared with baseline, the three highest decline indexes of disease activity at week 24 were SW28, CDAI, and T28, with an average decline rate of 73.8%, 61.4%, 58.7%, respectively. Results were similar in three cohorts.We performed a stratified analysis of which IGU treatment should be used in different cohorts. The study found that the proportion of pts with UA and ERA who used IGU monotherapy were significantly higher than those in the RA cohort. While the proportion of triple and quadruple combined use of IGU in RA pts was significantly higher than that of ERA and UA at baseline and whole-course (Fig 2).A total of 81/313 (25.8%) pts in this study had adverse events (AE) with no serious adverse events. The main adverse events were infection(25/313, 7.99%), gastrointestinal disorders(13/313, 4.15%), liver dysfunction(12/313, 3.83%) which were lower than 259/2666 (9.71%) in the previous Japanese phase IV study[4].The most common reasons of lost follow-up were: 1) discontinued after remission 25/86 (29.1%); 2) lost 22/86 (25.6%); 3) drug ineffective 19/86 (22.1%).Conclusion:Both IGU-based monotherapy and combined therapies are tolerant and effective for treating UA, ERA, and RA, while the decline in joint symptoms was most significant. Overall, IGU combination treatments were most used in RA pts, while monotherapy was predominant in ERA and UA pts.References:[1]Levin RW, et al. Scand J Rheumatol 1996, 25(5):277-281.[2]Kay J, et al. Rheumatology 2012, 51(Suppl 6):vi5-9.[3]Zhao J, et al. Clin Exp Rheumatol 2014, 32(5):667-673.[4]Mimori T, et al. Mod Rheumatol 2019, 29(2):314-323.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1450.2-1450
Author(s):  
H. Bjørngaard ◽  
H. Koksvik ◽  
B. Jakobsen ◽  
M. Wallenius

Background:Treat to target is a goal, also in pregnant women with Rheumatoid arthritis (1). There is increasing evidence on safe use with TNF inhibitors during pregnancy. Adjusted use of TNF inhibitors preconception and throughout pregnancy may stabilize disease activity and prevent flares (2). Low disease activity is also beneficial for the fetus.Objectives:To study the use of TNF-inhibitors among women with Rheumatic arthritis during and after pregnancy.Methods:RevNatus is a Norwegian, nationwide quality register that monitors treatment of inflammatory rheumatic diseases before, during and after pregnancy. Data from RevNatus in the period October 2017 to October 2019 was used to map the use of all types of TNF inhibitors among 208 women with rheumatoid arthritis, diagnosed by the ACR/EULAR criteria. The use of medication was reported at the time of visit in outpatient clinic. The frequency of use of TNF inhibitors registered at seven timepoints from pre-pregnancy to twelve months after delivery.Results:The use of medication was reported at each visit for all the women with rheumatoid arthritis. Most of the women were not using TNF inhibitors before and beyond conception. Most of the women continuing TNF inhibitors beyond conception used certolizumab or etanercept. Adalimumab and infliximab were used in pregnancy (tabell 1).Tabell 1.certoliz-umabetane-rceptadalim-umabgolim-umabinflixi-mabNo TNF-inhibitorBefore pregnancyn=10521% (22)9% (10)3% (3)1% (1)66% (69)1.trimestern=8119% (15)10% (8)71% (58)2.trimestern=8810% (9)10% (9)80% (70)3.trimestern=9111% (10)5% (5)83% (76)6 weeks post partum n=9622% (21)13% (13)1% (1)1% (1)63% (60)6 months post partum n=8824% (21)18% (16)4% (4)1% (1)53% (46)12 months post partum n=8421% (18)17% (15)7% (6)2% (2)53% (43)Conclusion:Most of the women with rheumatic arthritis were not treated with TNF inhibitors before or in pregnancy. Women with rheumatic arthritis that continuing treatment with TNF inhibitors through pregnancy were using certilozumab and etanercept.References:[1]Gotestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. 2016;75(5):795-810.[2]van den Brandt S, Zbinden A, Baeten D, Villiger PM, Ostensen M, Forger F. Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arthritis and axial spondyloarthritis patients. Arthritis Res Ther. 2017;19(1):64.Disclosure of Interests:None declared


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