The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus

Abstract

Objective. The antimalarial medication hydroxychloroquine has been proposed as a thromboprotective agent in systemic lupus erythematosus (SLE), but studies thus far have been limited by the possibility of confounding by indication. This study was conducted to assess whether exposure to antimalarial drugs is associated with a decrease in thrombovascular events (TEs) in patients with SLE.Methods. The study was designed as a nested case-control study embedded in an inception cohort of patients with SLE, which allowed adjustments for possible confounding by calendar year, duration of disease, duration of observation, and severity of lupus. After controlling for the possible confounding variables in conditional logistic regression models, the use of antimalarial drugs was assessed for its effects on the development of TEs in lupus patients.Results. Fifty-four cases of TE were identified, and these were matched with 108 control subjects (lupus patients without TEs). Univariate analyses identified older age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01-1.07) or being older than age 50 years (OR 3.5, 95% CI 1.4-8.6) and ever having hypertension (OR 2.5, 95% CI 1.0-5.8) as being associated with an increased risk of TEs, whereas use of antimalarial drugs (OR 0.31, 95% CI 0.13-0.71) was associated with a decreased risk of TEs. Separate analyses were done for arterial and venous TEs, which yielded similar results. In multivariate analyses, use of antimalarial drugs (OR 0.32, 95% CI 0.14-0.74) and older age (OR 1.04, 95% CI 1.01-1.07) were the only 2 variables that remained significant.Conclusion. The results from this nested casecontrol study demonstrate that, after accounting for the effects of disease severity, disease duration, and calendar year, antimalarial drugs were found to be thromboprotective, being associated with a 68% reduction in the risk of all TEs, with a range of risk reduction of at least 26% up to as high as 86%.Systemic lupus erythematosus (SLE) is a systemic illness of autoimmune etiology, characterized by either acute or chronic inflammation of multiple organs. The prevalence of SLE in North America is ϳ40 per 100,000 people (1,2), and more than 80% of cases occur in women who develop the illness during their childbearing years. As a consequence, the disease may affect as many as 1 in 1,000 young women. The risk of arterial, venous, or small-vessel thrombovascular events (TEs) in a patient with SLE is significantly higher than that in the

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases

“…Even though HCQ use was initially limited to the more benign manifestations of arthritis and dermatitis in patients with SLE, recent publications have suggested that the use of HCQ improves morbidity and mortality for patients with SLE and this has resulted in increased use of this drug in these patients (Ruiz-Irastorza et al 2010). Other reports have shown that HCQ may have a protective effect on renal damage in patients with lupus nephritis, which is also known to be an important factor influencing mortality in these patients (Sisó et al 2008;Pons-Estel et al 2009) as are thrombovascular events for which there is increasing evidence that they can be prevented by anti-malarials (Jung et al 2010;Ruiz-Irastorza et al 2010;Katz and Russell, 2011).…”

Primary Thrombosis Prophylaxis in Antiphospholipid Antibody–Positive Patients: Where Do We Stand?

“…In a recent prospective cohort study conducted by Tektonidou et al [15], it was shown that HCQ might reduce the thrombosis risk in both aPL-positive (hazard ratio, 0.99; 95% CI, 0.98-1.00) and aPL-negative (hazard ratio, 0.98; 95% CI, 0.95-0.98) patients. In another recent nested, case-control study, Jung et al [67] also demonstrated that HCQ is protective against thrombosis in SLE patients (OR, 0.32; 95% CI, 0.14-0.74). However, this potentially protective effect of HCQ was not confirmed by two other prospective cohort studies in lupus patients [68,69].…”

Top 10 Clinical Research Developments in Antiphospholipid Syndrome

“…In a recent prospective cohort study [14], it was shown that HCQ might reduce the risk of thrombosis in both aPL-positive and aPL-negative SLE patients. In another recent nested, casecontrol study, HCQ was shown to be protective against thrombosis among SLE patients [61]. However, this potentially protective effect of HCQ was not confirmed by two other prospective cohort studies of lupus patients [62,63].…”