Association of Higher Hydroxychloroquine Blood Levels With Reduced Thrombosis Risk in Systemic Lupus Erythematosus

Abstract

Objective. Hydroxychloroquine (HCQ) has a primary role in the prophylaxis and treatment of systemic lupus erythematosus (SLE) and may be protective against thrombosis in SLE. Optimal weight-based dosing of HCQ is unknown. This study was undertaken to examine the usefulness of HCQ blood monitoring in predicting thrombosis risk in a longitudinal SLE cohort.Methods. HCQ levels were serially quantified from EDTA whole blood by liquid chromatography-tandem mass spectrometry. The mean HCQ blood levels calculated prior to thrombosis or until the last visit were compared using t-tests between patients with and those without thrombosis. Pooled logistic regression was used to analyze the association between rates of thrombosis and HCQ blood level. Rate ratios (RRs) and 95% confidence intervals (95% CIs) were calculated.Results. In 739 patients with SLE, thrombosis occurred in 38 patients (5.1%). The mean ± SD HCQ blood level was lower in patients who developed thrombosis versus those who did not develop thrombosis (720 ± 489 ng/ml versus 935 ± 580 ng/ml; P = 0.025). Thrombosis rates were reduced by 13% for every 200-ng/ml increase in the most recent HCQ blood level (RR 0.87 [95% CI 0.78-0.98], P = 0.025) and by 13% for mean HCQ blood level (RR 0.87 [95% CI 0.76-1.00], P = 0.056). Thrombotic events were reduced by 69% in patients with mean HCQ blood levels ≥1,068 ng/ml versus those with levels <648 ng/ml (RR 0.31 [95% CI 0.11-0.86], P = 0.024). This remained significant after adjustment for confounders (RR 0.34 [95% CI 0.12-0.94], P = 0.037). Conclusion.Low HCQ blood levels are associated with thrombotic events in SLE. Longitudinal measurement of HCQ levels may allow for personalized HCQ dosing strategies. Recommendations for empirical dose reduction may reduce or eliminate the benefits of HCQ in this high-risk population.

Pre-Exposure Prophylaxis with Hydroxychloroquine Does Not Prevent COVID-19 nor Virus Related Venous Thromboembolism

“…The effectiveness of hydroxychloroquine in systemic disease and\or antiphospholipid syndrome has been assessed also regarding the reduction of thrombotic rate. Particularly the reduction was associated to the increase of the dosage of hydroxychloroquine [ 14 , 15 ]. Indeed, the rate of venous thromboembolism in our cohort did not differ between the group that performed pre-exposure with hy-droxychloroquine and the group not receiving HC during the disease.…”

Anti-Rheumatic Drugs May Ameliorate the Clinical Course and Outcome of COVID-19 In Rheumatoid Arthritis Patients

“… 18 This remains to be documented and there are some trials that are trying to support it. 19 – 21 Furthermore, high HCQ blood levels are associated with reduced thrombotic events in SLE patients, 22 which is also a clinical manifestation of SARS-CoV-2 patients. On the other hand, a study by Koning et al found no protection for SARS-CoV-2 infection or the development of the severe form of the disease with the use of HCQ in patients with SLE.…”

Influence of hydroxychloroquine blood levels on adhesion molecules associated with endothelial dysfunction in patients with systemic lupus erythematosus

“…In recent years, HCQ therapy has been associated with positive effect on traditional CV risk factors and a reduction of CV morbidity and mortality in SLE 18 19. Moreover, maintaining an average HCQ whole blood level >1.068 ng/mL significantly reduced the risk of thrombosis in SLE, based on data from 739 patients of the John Hopkins cohort 28. However, it was still unclear if the protective CV effect of HCQ is an indirect result of better control of disease activity or a direct effect of HCQ on the endothelium.…”