[Use of hydroxychloroquine in recurrent immune-mediated obstetric diseases (excluding systemic lupus): Scientific basis and evidence]

Abstract

Hydroxychloroquine (HCQ), a synthetic antimalarial, is recognized for its immunomodulatory, anti-inflammatory and vascular-protective effects. In 20-30% of cases of primary obstetrical antiphospholipid syndrome (APS), the combination of antiplatelet aggregation and prophylactic anticoagulation fails to prevent obstetrical complications, a situation referred to as refractory obstetrical APS. This is partly due to the pro-inflammatory effects of antiphospholipid antibodies (aPL) binding to decidual and trophoblastic cells, which compromise embryonic implantation and placentation. Experimental studies in vitro and in mouse models have shown that HCQ can inhibit the detrimental effect of aPLs on trophoblastic invasion, findings corroborated by retrospective observational clinical studies. However, no randomized controlled trial has evaluated the addition of HCQ to conventional therapy for refractory obstetric APS. The hypothesis of allo-immune and/or autoimmune mechanisms involved in cases of recurrent pregnancy loss (RPL) with no identified cause and in chronic intervillositis of unknown etiology (CIUE) has led to the empirical use of HCQ in these indications. However, current evidence does not support its use in unexplained RPL. A few clinical studies of low scientific evidence suggest a benefit of HCQ in CIUE, but further data are needed. Finally, pre-eclampsia (PE) is another pregnancy-related condition at risk of recurrence, and its pathogenesis also seems to involve an imbalance in immune responses. HCQ's antioxidant properties could have a positive effect on endothelial dysfunction, a key component of PE.

Keywords: Antiphospholipid antibody syndrome; Avortement spontané; Complications de la grossesse; Hydroxychloroquine; Maladies du placenta; Placenta diseases; Pregnancy complications; Spontaneous abortion; Syndrome des anticorps antiphospholipides.