The effect of hydroxychloroquine on thrombosis prevention and antiphospholipid antibody levels in primary antiphospholipid syndrome: A pilot open label randomized prospective study

Background: Sporadic studies suggest hydroxychloroquine (HCQ) may be effective for thrombosis prevention in patients with primary antiphospholipid syndrome (PAPS) and may lead to antiphospholipid antibody (aPL) titer reduction but data from randomized studies are lacking.

Methods: We conducted a pilot open-label randomized prospective study aiming to evaluate the safety and efficacy of HCQ for thrombosis prevention in 50 patients with PAPS allocated 1:1 to HCQ plus standard care (systemic anticoagulation and/or antiplatelet therapy) vs. standard care alone, as well as the effect of HCQ on aPL titers of 50 PAPS patients and 15 asymptomatic aPL carriers.

Results: HCQ use plus standard care was associated with lower incidence rate of thrombosis than standard care alone (0.001 vs. 0.007, log-rank p =0.048) over an average 2.6-year follow-up, and a multivariate hazard ratio of 0.09 (95% CI = 0.01-1.26, p = 0.074) after adjusting for the effect of age, sex, traditional cardiovascular risk factors, triple aPL positivity, history of recurrent thrombotic events at baseline, and poor anticoagulation quality (INR levels within therapeutic range for ≤80% of follow-up). No significant difference in safety outcomes was observed between the two groups. Long-term HCQ use was associated with a decrease in aPL titers except for IgM anticardiolipin antibodies, which tended to decrease overtime regardless of treatment allocation.

Conclusions: HCQ may represent an effective adjuvant treatment for thrombosis prevention in patients with PAPS, which may be mediated via a reduction in aPL titers. Larger randomized trials are needed in order to corroborate this finding and investigate the thromboprotective role of HCQ in asymptomatic aPL carriers.