Effect of introducing biologics to patients with rheumatoid arthritis on the risk of venous thromboembolism: a nationwide cohort study

AbstractIn the United States, 100,000–300,000 patients die from venous thromboembolism (VTE) each year, with more than 500,000 people related hospitalizations. While in Europe, 500,000 people die from VTE each year. Patients with rheumatoid arthritis are at increased risk of VTE. The use of biologics in patients with rheumatoid arthritis may be associated with an increased risk of VTE. We identified all patients who had been newly approved for Catastrophic Illness Card of rheumatoid arthritis extracted the claims data from the National Health Insurance research database and Registry for Catastrophic Illness Patient Database from 2003 to 2016. VTE was defined as the presence of inpatient VTE diagnostic codes (including DVT or PE) according to the discharge diagnosis protocol. An analysis of VTE variables indicated that the incidence of VTE in the biologic group (14.33/10,000 person-years) was higher than that in the conventional drug group (12.61/10,000 person-years). As assessed by the Cox proportional hazards model, the relative HR for VTE in the biologic group (HR: 1.11; 95% CI 0.79–1.55) versus that in the conventional drug group did not reach a significant difference. In conclusion, this study found no significant differences in risk were observed between the use of conventional DMARDs and biologics.

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Risk of venous thromboembolism following surgical treatment of superficial venous incompetence

VASA ◽

10.1024/0301-1526/a000656 ◽

2017 ◽

Vol 46 (6) ◽

pp. 484-489 ◽

Cited By ~ 7

Author(s):

Tom Barker ◽

Felicity Evison ◽

Ruth Benson ◽

Alok Tiwari

Keyword(s):

Venous Thromboembolism ◽

Varicose Vein ◽

Lower Incidence ◽

Varicose Veins ◽

Secondary Data ◽

Foam Sclerotherapy ◽

Increased Risk ◽

Significant Difference ◽

Chi Squared ◽

One Year

Abstract. Background: The invasive management of varicose veins has a known risk of post-operative deep venous thrombosis and subsequent pulmonary embolism. The aim of this study was to evaluate absolute and relative risk of venous thromboembolism (VTE) following commonly used varicose vein procedures. Patients and methods: A retrospective analysis of secondary data using Hospital Episode Statistics database was performed for all varicose vein procedures performed between 2003 and 2013 and all readmissions for VTE in the same patients within 30 days, 90 days, and one year. Comparison of the incidence of VTEs between procedures was performed using a Pearson’s Chi-squared test. Results: In total, 261,169 varicose vein procedures were performed during the period studied. There were 686 VTEs recorded at 30 days (0.26 % incidence), 884 at 90 days (0.34 % incidence), and 1,246 at one year (0.48 % incidence). The VTE incidence for different procedures was between 0.15–0.35 % at 30 days, 0.26–0.50 % at 90 days, and 0.46–0.58 % at one year. At 30 days there was a significantly lower incidence of VTEs for foam sclerotherapy compared to other procedures (p = 0.01). There was no difference in VTE incidence between procedures at 90 days (p = 0.13) or one year (p = 0.16). Conclusions: Patients undergoing varicose vein procedures have a small but appreciable increased risk of VTE compared to the general population, with the effect persisting at one year. Foam sclerotherapy had a lower incidence of VTE compared to other procedures at 30 days, but this effect did not persist at 90 days or at one year. There was no other significant difference in the incidence of VTE between open, endovenous, and foam sclerotherapy treatments.

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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

Autoimmunity Highlights ◽

10.1186/s13317-021-00153-5 ◽

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.

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.353 ◽

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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Impact of Weight-Band Dosing of Tinzaparin for Venous Thromboembolism Prophylaxis on Persistent Wound Drainage in Adult Patients Undergoing Hip and Knee Arthroplasty

Annals of Pharmacotherapy ◽

10.1177/10600280211024294 ◽

2021 ◽

pp. 106002802110242

Author(s):

Cassandra Cooper ◽

Ouida Antle ◽

Jennifer Lowerison ◽

Deonne Dersch-Mills ◽

Ashley Kenny

Keyword(s):

Body Weight ◽

Venous Thromboembolism ◽

Knee Arthroplasty ◽

Total Joint Arthroplasty ◽

Joint Arthroplasty ◽

Thromboembolism Prophylaxis ◽

Wound Drainage ◽

Increased Risk ◽

Significant Difference ◽

The Impact

Background: Persistent wound drainage and venous thromboembolism (VTE) are potential complications of total joint arthroplasty, and these risks can be challenging to balance in clinical practice. Anecdotal observation has suggested that following joint arthroplasty, persistent wound drainage occurs more frequently with higher body weight and higher doses of tinzaparin when compared with lower body weight and lower doses of tinzaparin. Objective: The overall purpose of this study was to describe the impact of a tinzaparin weight-band dosing table for VTE prophylaxis on wound healing, thrombosis, and bleeding outcomes in patients undergoing total joint arthroplasty. Methods: This retrospective chart review included patients who underwent total hip or knee arthroplasty and received tinzaparin for thromboprophylaxis per their weight-banding category. The primary outcome was the incidence of persistent wound drainage. Secondary outcomes include the occurrence of VTE and clinically important bleeding during hospital admission. Results: A total of 231 patients were included in the analysis. There was no significant difference in persistent wound drainage between the 3 weight categories, and there were no differences in rates of VTE or clinically important bleeding. Concurrent use of low-dose acetylsalicylic acid was associated with a 3-fold increased risk of persistent wound drainage (risk ratio = 3.35; 95% CI = 2.14-5.24; P = 0.00003). Conclusion and Relevance: In joint arthroplasty patients, we observed no significant difference in rates of persistent wound drainage between various weight categories receiving different weight-banded doses of tinzaparin. Our results do not suggest that the current weight-band dosing table for tinzaparin needs to be adjusted to optimize patient outcomes.

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The Latent Tuberculin Test after 1-year Therapy with Anti-TNF in Babylon, Iraq

Journal of University of Babylon for Pure and Applied Sciences ◽

10.29196/jubpas.v26i8.1680 ◽

2018 ◽

Vol 26 (8) ◽

pp. 144-150

Author(s):

Ali Alkazzaz ◽

Murtadha Najah Jawad ◽

Zeyad Tareq Kareem

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Medical History ◽

Demographic Data ◽

Latent Tuberculosis ◽

Tuberculin Test ◽

P Value ◽

Cross Sectional ◽

Increased Risk ◽

Significant Difference

Background: Rheumatoid arthritis (RA) patients receiving receive anti-TNF agents are at increased risk of reactivation of latent tuberculosis infection (LTBI). The tuberculin skin test (TST) is widely used to screen LTBI and providing preventive treatment, in an effort to meet the WHO target of a 90% reduction in TB by 2035. Objectives: To determine the proportion of TST conversion among RA patients after 1 year of anti-TNF treatment and association of positive TST result with patients’ socio-demographic characteristics and medical history. Methods: This community-based cross-sectional study was conducted at the Department of Rheumatology of Marjan Teaching Hospital in Iraq, for a period of 1 year. Patients with RA/and spondyloarthropathy, and who received anti-TNF therapy for >1 year, underwent TST. Their demographic data and medical history were also obtained. All statistical analysis was performed using SPSS (Version 20) and, p < 0.05 was considered as a sign. Data from the baseline and 1 year follow-up was subjected to the Kolmogorov-Smirnov test to determine whether they were normally distributed. Chi-Square test used to test significance of TST among etanrecept and infliximab at the end of the study. Results: A total of 96 patients were enrolled, including 55 (57.3%) males and 41 (42.3%) females with an average age of 41.1, and mostly 68 (70.8%) from Babylon Governorate of Iraq. A total of 40 (41.7%) patients had rheumatoid arthritis alone, and the remaining 56 (58.3%) had a comorbidity of spondyloarthropathy. Majority of the patients 65 (67.7%) received the biological agent infliximab, while 31 (32.3%) patients received Etanercept for RA for a period of 1 year. There was a statistically significant decreasing in the median ESR and disease activity from the baseline to the end of the study (p-value <0.01). There was no significant difference in TST results based on gender or age. Both infliximab and etanercept were significantly associated with a decreasing in ESR and disease activity Conclusion: This study has shown that there was very low TST conversion among RA patients after 1 year of anti-TNF treatment and, age and gender were not associated with TST.

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Abstract P12: Alteplase Reduces Mortality in Patients With Ischemic Stroke and Atrial Fibrillation: Analysis of the IAC Study

Stroke ◽

10.1161/str.52.suppl_1.p12 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Shadi Yaghi ◽

Eva Mistry ◽

Adam H De Havenon ◽

Christopher Leon Guerrero ◽

Amre Nouh ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Infarct Volume ◽

Intravenous Thrombolysis ◽

The United States ◽

Hemorrhagic Transformation ◽

Stroke Patients ◽

Increased Risk ◽

Significant Difference

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p <0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size (< 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.

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Assessment of the Ovarian Reserve by Serum Anti-Müllerian Hormone in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis

International Archives of Allergy and Immunology ◽

10.1159/000520133 ◽

2021 ◽

pp. 1-8

Author(s):

Xian-hui Zhang ◽

Ying-an Zhang ◽

Xin Chen ◽

Peng-yan Qiao ◽

Li-yun Zhang

Keyword(s):

Rheumatoid Arthritis ◽

Ovarian Reserve ◽

Meta Analysis ◽

Cochrane Library ◽

Dmard Treatment ◽

Standard Mean Difference ◽

Increased Risk ◽

Significant Difference ◽

Newcastle Ottawa Scale ◽

The Cochrane Library

Background: The ovarian reserve has been reported to be diminished in patients with rheumatoid arthritis. However, these results are still controversial. Anti-Müllerian hormone (AMH) is considered a reliable biomarker for the ovarian reserve. We thus performed a meta-analysis to evaluate the AMH levels and the effect of DMARDs on the ovarian reserve in rheumatoid arthritis patients. Methods: PubMed, EMBASE, the Cochrane Library, and 2 Chinese databases (CNKI and Wanfang database), up to September 2021, were searched for relevant studies. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the included studies. Pooled standard mean difference (SMD) with 95% confidence intervals (CIs) were determined with the random-effects model. The heterogeneity was described by I2 statistic and p value from the Cochrane Q test. Results: Eight eligible studies (679 patients and 1,460 controls) were included in the meta-analysis. Compared with healthy control, the AMH levels in RA patients were significantly lower with the pooled SMD of −0.40 (95% CI: −0.66 to −0.14). However, in comparison of AMH with and without DMARD treatment, there was no significant difference with the pooled SMD of −0.1 (95% CI: −0.39 to 0.19). Conclusion: The results indicated that there was an increased risk of ovarian failure in RA patients and which is not related to DMARD treatment.

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Association of APOL1 Genotypes With Measures of Microvascular and Endothelial Function, and Blood Pressure in MESA

Journal of the American Heart Association ◽

10.1161/jaha.120.017039 ◽

2020 ◽

Vol 9 (17) ◽

Author(s):

Teresa K. Chen ◽

Ronit Katz ◽

Michelle M. Estrella ◽

Wendy S. Post ◽

Holly Kramer ◽

...

Keyword(s):

Blood Pressure ◽

High Risk ◽

Kidney Disease ◽

Endothelial Function ◽

Aortic Distensibility ◽

The United States ◽

Flow Mediated Dilation ◽

Arterial Elasticity ◽

Increased Risk ◽

Significant Difference

Background APOL1 high‐risk genotypes are associated with increased risk for hypertension‐attributed kidney disease among Black adults in the United States. Biopsy studies show differences in kidney vasculature by APOL1 status; less is known about the variants' associations with systemic vascular and endothelial function. Whether APOL1 risk variants are associated with blood pressure (BP) is also uncertain. Methods and Results Using linear regression, we examined cross‐sectional associations of APOL1 risk genotypes (high=2 risk alleles, low=0 or 1 risk allele) with subclinical measures of vascular function (small arterial elasticity, n=1586; large arterial elasticity, n=1586; ascending aortic distensibility, n=985) and endothelial function (flow‐mediated dilation, n=777). Using linear mixed‐effects models, we studied longitudinal associations of APOL1 risk genotypes with BP (n=1619), adjusting for age, sex, and African ancestry. Among 1619 (12% APOL1 high‐risk) Black participants in MESA (Multi‐Ethnic Study of Atherosclerosis), mean age was 62 years old, 58% had hypertension, and mean systolic BP was 131 mm Hg at baseline. At examination 1 (2000–2002), there was no significant difference in small arterial elasticity, large arterial elasticity, ascending aortic distensibility, or flow‐mediated dilation in participants with APOL1 high‐ versus low‐risk genotypes ( P >0.05 for all). Over a mean follow‐up of 7.8 years, relative annual changes in systolic and diastolic BP and pulse pressure did not differ significantly by APOL1 risk status (between‐group differences of −0.20, −0.14, and −0.25, respectively; P >0.05 for all). Conclusions Among Black participants in MESA, APOL1 high‐risk genotypes were not associated with subclinical vascular and endothelial function or BP trajectories. The relationship of APOL1 with kidney disease may be intrinsic to the kidney rather than through peripheral effects on systemic vasculature or BP.

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Behcet’s disease and pregnancy: obstetrical and neonatal outcomes in a population-based cohort of 12 million births

Journal of Perinatal Medicine ◽

10.1515/jpm-2018-0161 ◽

2019 ◽

Vol 47 (4) ◽

pp. 381-387 ◽

Cited By ~ 4

Author(s):

Seohyuk Lee ◽

Nicholas Czuzoj-Shulman ◽

Haim Arie Abenhaim

Keyword(s):

Venous Thromboembolism ◽

Behçet’S Disease ◽

Behcet’S Disease ◽

Behçet's Disease ◽

The United States ◽

Population Based ◽

Fetal Outcomes ◽

Behcet's Disease ◽

Increased Risk ◽

In Pregnancy

AbstractBackgroundBehcet’s disease (BD) is a rare, multi-systemic inflammatory disorder for which only limited and contradictory data exists in the context of pregnancy. Our objective was to estimate the prevalence of BD in pregnancy and to evaluate maternal and fetal outcomes associated with pregnant women living with BD.MethodsUsing the 1999–2013 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from the United States, we performed a population-based retrospective cohort study consisting of pregnancies that occurred during this time period. ICD-9 codes were used to identify delivery admissions to women with or without BD. Multivariate logistic regression was used to estimate the adjusted effects of BD on maternal and fetal outcomes.ResultsAmong the 12,592,676 pregnancies in our cohort, 144 were to women with BD, for an overall prevalence of 1.14 cases/100,000 births between 1999 and 2013. Over the study period, the prevalence of BD rose from 0.5 to 2.4/100,000 births. Women with BD demonstrated a two-fold greater frequency of non-delivery hospital admissions during pregnancy, and were more likely to be Caucasian, have private medical insurance, be of the upper income quartiles, and deliver at an urban teaching hospital. Women with BD were at greater risk for preterm labor and postpartum venous thromboembolism, while their newborns were more likely to be born premature.ConclusionBD-associated pregnancies are increasing in prevalence and are associated with a greater risk for adverse maternal and fetal outcomes in pregnancy. Appropriate thromboprophylaxis during pregnancy should be considered given the increased risk for venous thromboembolism.

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Effect of Early Intravenous Immunoglobulin Therapy in Kawasaki Disease: A Systematic Review and Meta-Analysis

Frontiers in Pediatrics ◽

10.3389/fped.2020.593435 ◽

2020 ◽

Vol 8 ◽

Author(s):

Fan Yan ◽

Huayong Zhang ◽

Ruihua Xiong ◽

Xingfeng Cheng ◽

Yang Chen ◽

...

Keyword(s):

Systematic Review ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Meta Analysis ◽

The United States ◽

Cochrane Library ◽

Ivig Treatment ◽

Intravenous Immunoglobulin Therapy ◽

Increased Risk ◽

Significant Difference

Background: In the latest 2017 American Heart Association guidelines for Kawasaki disease (KD), there are no recommendations regarding the early administration of intravenous immunoglobulin (IVIG). Therefore, the purpose of this systematic review and meta-analysis was to investigate the effects of early IVIG therapy on KD.Methods: We searched databases including the PubMed, Medline, the Cochrane Library, and the Clinicaltrials.gov website until July 2019.Results: Fourteen studies involving a total of 70,396 patients were included. Early treatment with IVIG can lead to an increased risk of IVIG unresponsiveness [OR 2.24; 95% CI (1.76, 2.84); P = 0.000]. In contrast to the studies performed in Japan [OR 1.27; 95% CI (0.98, 1.64); P = 0.074] that found no significant difference in coronary artery lesions (CAL) development, studies conducted in China [OR 0.73; 95% CI (0.66, 0.80); P = 0.000] and the United States [OR 0.50; 95% CI (0.38, 0.66); P = 0.000] showed a reduced risk in the occurrence of CAL with early IVIG treatment.Conclusions: At present, the evidence does not support the treatment with IVIG in the early stage of the onset of KD. But, early IVIG treatment could be a protective factor against the development of CAL, which needs to be further clarified.

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