Higher Hydroxychloroquine Blood Levels Are Associated with Reduced Thrombosis Risk in Systemic Lupus Erythematosus

2021 ◽  
Author(s):  
Michelle Petri ◽  
Maximilian F. Konig ◽  
Jessica Li ◽  
Daniel W. Goldman
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Blood Levels ◽  
Systemic Lupus ◽  
Thrombosis Risk

scholarly journals Genetic Risk Factors for Thrombosis in Systemic Lupus Erythematosus

2012 ◽  
Vol 39 (8) ◽  
pp. 1603-1610 ◽  
Author(s):  
RACHEL KAISER ◽  
YONGHONG LI ◽  
MONICA CHANG ◽  
JOSEPH CATANESE ◽  
ANN B. BEGOVICH ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Venous Thrombosis ◽  
Lupus Erythematosus ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
Antiphospholipid Antibody ◽  
Systemic Lupus ◽  
Discovery Cohort ◽  
Thrombosis Risk

Objective.Thrombosis is a serious complication of systemic lupus erythematosus (SLE). We investigated whether genetic variants implicated in thrombosis pathways are associated with thrombosis among 2 ethnically diverse SLE cohorts.Methods.Our discovery cohort consisted of 1698 patients with SLE enrolled in the University of California, San Francisco, Lupus Genetics Project and our replication cohort included 1361 patients with SLE enrolled in the PROFILE cohort. Patients fulfilled American College of Rheumatology SLE criteria, and data relevant to thrombosis were available. Thirty-three single nucleotide polymorphisms (SNP) previously shown to be associated with risk of deep venous thrombosis in the general population or implicated in thrombosis pathways were genotyped and tested for association with thrombosis in bivariate allelic analyses. SNP with p < 0.1 in the bivariate analyses were further tested in multivariable logistic regression models adjusted for age, sex, disease duration, antiphospholipid antibody status, smoking, nephritis, and medications.Results.In the discovery cohort, 23% of patients with SLE experienced a thrombotic event. SNP in the following genes demonstrated association with thrombosis risk overall in the discovery or replication cohorts and were assessed using metaanalytic methods: factor V Leiden (FVL) rs6025 (OR 1.85, p = 0.02) and methylenetetrahydrofolate reductase (MTHFR) rs1801133 (OR 0.75, p = 0.04) in whites, and fibrinogen gamma (FGG) rs2066865 (OR 1.91, p = 0.01) in Hispanic Americans. SNP in these genes showed association with venous thrombosis risk in whites: MTHFR rs1801131 (OR 1.51, p = 0.01), MTHFR rs1801133 (OR 0.70, p = 0.04), FVL rs6025 (OR 2.69, p = 0.002), and FGG rs2066865 (OR 1.49, p = 0.02) in whites. A SNP in FGG rs2066865 (OR 2.19, p = 0.003) demonstrated association with arterial thrombosis risk in Hispanics.Conclusion.Our results implicate specific genetic risk factors for thrombosis in patients with SLE and suggest that genetic risk for thrombosis differs across ethnic groups.

scholarly journals Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence

2015 ◽  
Vol 42 (11) ◽  
pp. 2092-2097 ◽  
Author(s):  
Laura Durcan ◽  
William A. Clarke ◽  
Laurence S. Magder ◽  
Michelle Petri
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Renal Failure ◽  
Body Weight ◽  
Disease Activity ◽  
Therapeutic Range ◽  
Lupus Erythematosus ◽  
Ideal Body Weight ◽  
Blood Levels ◽  
Systemic Lupus ◽  
Ideal Body

Objective.Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists recommend weight-based dosing while some other specialists advocate height-based “ideal body weight” dosing.Methods.Patients were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis, the dose was 200 mg after each session, and in renal insufficiency it was 200 mg/day. Levels were measured at each visit with a therapeutic range of 500–2000 ng/ml. Patients were divided according to baseline blood level. To assess the effect of measurement and counseling on adherence, we compared the proportion of patients with a level of 500 ng/ml or higher based on the number of prior assessments.Results.The proportion of patients with HCQ levels in the therapeutic range differed significantly by age, sex, and Vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were therapeutic, and by the third measurement this increased to 80% (p ≤ 0.0001).Conclusion.There was a trend toward higher disease activity with lower HCQ levels. Renal failure dosing led to suboptimum levels. We show that weight-based dosing (max 400 mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling, and repeated testing can increase adherence rates.

scholarly journals Assessment of circulating MCP-1 level and 2518A>G gene polymorphism in systemic lupus erythematosus

2020 ◽  
Vol 36 (5) ◽  
Author(s):  
Phebe Abdel-Messih ◽  
Hussein El-Fishawy ◽  
Hussein S. El-Fishawy ◽  
Abeer Mohamed Ahmed Zahran ◽  
Noha Mahmoud Abdel Baki
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Gene Polymorphism ◽  
Disease Activity ◽  
Blood Level ◽  
Lupus Erythematosus ◽  
Complement C3 ◽  
Blood Levels ◽  
Systemic Lupus ◽  
Significant Difference ◽  
Genotype A

Lupus nephritis (LN) is a major contributor to morbidity and mortality in patients with Systemic Lupus Erythematosus (SLE). This study aims to investigate the possible role of a functional polymorphism in the regulatory region of the monocyte chemo-attractant protein-1 (MCP-1) gene and MCP-1 blood level in the diagnosis of LN and in correlating the MCP-1 blood levels with disease activity. The study included 56 SLE patients and 56 controls. All the SLE patients suffered from LN. An analysis of MCP-1 gene polymorphism by polymerase chain reaction was performed followed by restriction fragment length polymorphism (PCR-RFLP) analysis and MCP-1 blood level was determined using the ELISA technique. Calculation of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was performed. Serologic tests included the determination of antinuclear antibody (ANA) and anti-double-stranded (ds) DNA antibodies, Complement C3 and C4 levels. A significant increase in the frequency of genotype A/G and a decrease in the frequency of genotype A/A were found among patients with active LN compared to inactive LN. There was a statistically significant difference in the blood level of MCP-1 between LN patients and controls. Also, MCP-1 blood levels were significantly higher in active LN patients than inactive LN. A significant positive linear correlation was detected between MCP-1 blood level and SLEDAI, creatinine, and 24 hours protein in LN patients. These results suggest that an A/G genotype together with the measurement of the blood level of MCP-1 can be a useful tool for detection and follow up of active LN.  

Decreased blood levels of B lymphocytes and NK cells in patients with systemic lupus erythematosus (SLE) infected with papillomavirus (HPV)

2012 ◽  
Vol 305 (2) ◽  
pp. 117-123 ◽  
Author(s):  
C. Abud-Mendoza ◽  
E. Cuevas-Orta ◽  
E. N. Santillán-Guerrero ◽  
M. U. Martínez-Martínez ◽  
B. Hernández-Castro ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Nk Cells ◽  
B Lymphocytes ◽  
Lupus Erythematosus ◽  
Blood Levels ◽  
Systemic Lupus

Thrombosis risk in systemic lupus erythematosus: the role of thrombophilic risk factors

2007 ◽  
Vol 36 (3) ◽  
pp. 198-205 ◽  
Author(s):  
K. K. Sallai ◽  
E. Nagy ◽  
I. Bodó ◽  
A. Mohl ◽  
P. Gergely
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Thrombosis Risk

scholarly journals Prescription strategy of antimalarials in cutaneous and systemic lupus erythematosus: an international survey

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110025
Author(s):  
Arthur Petitdemange ◽  
Renaud Felten ◽  
Jean Sibilia ◽  
Thierry Martin ◽  
Laurent Arnaud
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Immunosuppressive Agent ◽  
Cross Sectional Study ◽  
Blood Levels ◽  
First Year ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Web Based ◽  
Screening Guidelines

Background: Antimalarial agents (AMs), mainly hydroxychloroquine (HCQ) and chloroquine, are the cornerstone of treatment of cutaneous and systemic lupus erythematosus. However, many aspects of AM prescription remain empirical. The aim of this study was to assess the modalities of AM prescription among physicians treating patients with lupus and to verify the assumption that AM use is heterogeneous and frequently at variance with international guidelines. Methods: We performed an international cross-sectional study among physicians involved in lupus care, using a web-based survey (from September 2019 to July 2020) addressing the main controversial aspects of AM prescription. Results: A total of 298 physicians [median age: 42 (interquartile range: 17) years, mainly internists and rheumatologists] from 35 countries participated to the study. A total of 93% used HCQ as the first-line AM, 69.5% used fixed doses of AMs (mainly 400 mg/day for HCQ) and only 37.9% adjusted the dose in case of renal failure. The main reasons for measuring HCQ blood levels were suspected non-adherence (55.7%) and failure of AM treatment (34.1%). In case of AM failure, 58.0% added an immunosuppressive agent. In case of remission, 49.7% maintained the same dose of AM, whereas 48.3% reduced the dose. One-third of respondents reported not following the American screening guidelines on AM retinal toxicity and 40.9% started retinal screening from the first year of treatment. Conclusion: This study highlights the strong heterogeneity of AM prescription in lupus, as well as several key unmet needs regarding AMs. This may be improved by developing more comprehensive recommendations and favoring dissemination among physicians.

scholarly journals Blood Pressure and Vascular Dysfunction Underlie Elevated Cerebral Blood Flow in Systemic Lupus Erythematosus

2012 ◽  
Vol 39 (4) ◽  
pp. 752-758 ◽  
Author(s):  
CHARLES GASPAROVIC ◽  
CLIFFORD QUALLS ◽  
ERNEST R. GREENE ◽  
WILMER L. SIBBITT ◽  
CARLOS A. ROLDAN
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Lupus Erythematosus ◽  
Control Group ◽  
Blood Levels ◽  
Dynamic Susceptibility ◽  
Systemic Lupus ◽  
Arterial Blood

Objective.In previous studies cerebral blood flow (CBF) was found to be altered in patients with systemic lupus erythematosus (SLE) compared to controls. We investigated the relationships between CBF and clinical data from subjects with SLE with the aim of determining the pathologic factors underlying altered CBF in SLE.Methods.A total of 42 SLE subjects and 19 age- and sex-matched healthy control subjects were studied. Dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) was used to measure CBF. Patients and controls underwent complete clinical and laboratory evaluations in close proximity with their MRI studies.Results.A higher CBF was present in the SLE group and was independently associated in statistical models with higher systolic blood pressure (SBP; p < 0.01). The intensity of the relationships (slope of curve) between CBF and mean arterial blood pressure, diastolic blood pressure, or blood levels of tissue plasminogen activator in the SLE group was significantly blunted relative to the control group.Conclusion.These findings are consistent with an underlying cerebral hyperperfusion in SLE induced by elevated but nonhypertensive levels of SBP. The factors underlying this relationship may be functional and/or structural (atherosclerotic, thrombotic, thromboembolic, or vasculitic) cerebrovascular disease.

scholarly journals OP0160 HYDROXYCHLOROQUINE BLOOD LEVELS AND RISK OF THROMBOTIC EVENTS IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 100.1-101
Author(s):  
M. A. Petri ◽  
M. Konig ◽  
J. LI ◽  
D. Goldman
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Venous Thrombosis ◽  
Blood Level ◽  
Lupus Erythematosus ◽  
Arterial Thrombosis ◽  
Blood Levels ◽  
Prospective Analysis ◽  
Type I ◽  
Primary Role ◽  
Systemic Lupus

Background:Hydroxychloroquine (HCQ) has a primary role in the treatment of systemic lupus erythematous (SLE). Beyond its pleiotropic immunomodulatory effects on Toll-like receptor and type I interferon signaling, HCQ use has been found to be protective for thrombosis in SLE (1). Optimal dosing of HCQ in SLE is unknown. The longitudinal measurement of HCQ blood levels may provide an opportunity to individualize weight-based dosing strategies and reduce risk of toxicity.Objectives:Examine the association of HCQ blood levels with thrombotic events in a longitudinal SLE cohort.Methods:812 SLE patients with HCQ blood level measured prior to the thrombosis were included: 93% female, 43% African-American, 46% Caucasian. HCQ blood levels were quantified by liquid chromatography-tandem mass spectrometry. Mean HCQ blood levels (± standard deviation) over all cohort visits prior to occurrence of thrombosis were calculated for each patient. Thromboses were defined as venous (DVT/PE or other venous) or arterial thrombosis (stroke, myocardial infarction, digital gangrene or other arterial).Results:Thrombosis had occurred during prospective follow up in 43 patients (5.5%), venous in 3.0% and arterial in 2.9%. Lupus anticoagulant was strongly associated with a history of any thrombosis (OR 3.25, p<0.0001), venous thrombosis (OR 3.53, p<0.0001), and arterial thrombosis (OR 3.08, p<0.0001). A prospective analysis shows that for any thrombosis and for venous thrombosis, the HCQ blood level was significantly lower (Table 1). Higher prescribed doses of HCQ (as opposed to HCQ blood levels) were also associated with decreased odds of any thrombosis and venous thrombosis in a separate cross-sectional analysis (OR 0.88, p=0.04 and OR 0.83, p=0.009, respectively for each 1 mg/kg increase in prescribed HCQ).Table 1.Thrombotic Events are Associated with Lower Mean HCQ Blood LevelMean HCQ Blood Level (± Std. Dev.)Thrombotic EventNo EventP-valueAny thrombosis695 ±464887 ± 5620.029Any venous thrombosis682 ± 374881 ± 5600.10DVT/PE only615 ± 384881 ± 5590.055Any arterial thrombosis708 ± 539882 ± 5580.13Stroke720 ± 643880 ± 5570.27Conclusion:HCQ blood levels are inversely associated with risk of any thrombosis and of venous thrombosis in patients with SLE in a prospective analysis. Reduction of HCQ dosing, as suggested by the American Academy of Ophthalmologists (2), could reduce or eliminate the benefit of hydroxychloroquine to prevent thrombosis.References:[1]Petri M. Use of hydroxychloroquine to prevent thrombosis in systemic lupus erythematosus and in antiphospholipid antibody–positive patients. Curr Rheumatol Rep 2011;13:77–80.[2]Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 2016;123:1386–1394.Acknowledgments:The Hopkins Lupus Cohort is supported by NIH Grant RO1 AR069572Disclosure of Interests:Michelle A Petri Grant/research support from: GSK, Eli Lilly and Company, Consultant of: Eli Lilly and Company, Maximilian Konig: None declared, Jessica Li: None declared, Daniel Goldman: None declared

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