ReviewThe efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study☆
Introduction
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by obstetrical complications and thrombotic events associated to antiphospholipid (aPL) antibodies [1], [2], [3]. The pregnancy outcome dramatically improved using the combination of aspirin and low-molecular weighted heparin (LMWH) [4], [5]. Despite this regimen, 10–15% of APS experiences pregnancy losses and constitutes the refractory obstetrical APS [6], [7], [8]. Recently Ruffatti et al. showed that addition of other drugs to conventional APS treatment could ameliorate the APS obstetrical outcome, but the best regimen remains to be determined [9]. In thrombotic APS, one study recently showed that the addition of hydroxychloroquine to oral anticoagulants could prevent the thrombotic recurrences [10]. The studies the addition of hydroxychloroquine reduce the aPL bindings to syncytiotrophoblasts and restore the placental annexin A5 expression [11]. Nevertheless, no clinical data are actually available to demonstrate the interest of hydroxychloroquine to improve obstetrical outcome in APS. In this European multicenter study, we aimed to (1) describe the hydroxychloroquine use in APS patients during pregnancy in real-life practice; and (2) determine the benefit of hydroxychloroquine addition to conventional APS treatment to improve the obstetrical outcome.
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Patients
We retrospectively analyzed the outcome of pregnancies treated by hydroxychloroquine in patients with APS (Sydney criteria) or asymptomatic aPL carriers [1]. All members of European Forum on Antiphospholipid antibodies and Société Nationale Francaise de Médecine Interne (SNFMI) were asked to fulfill a standardized form. The inclusion criteria were: (1) confirmed APS (Sydney criteria) or asymptomatic aPL carriers; and (2) at least one pregnancy under hydroxychloroquine. The exclusion criteria
APS patients' characteristics and pregnancies under hydroxychloroquine
Thirty patients with APS (median age 30 [19–40] years) with 35 pregnancies treated by hydroxychloroquine were analyzed (Table 1). APS was mainly primary (77%) with predominant isolated obstetrical profile (43%) and 20% of asymptomatic carriers. Associated auto-immune disease was present in 23% and consists of rheumatoid arthritis (n = 1), Sjogren's syndrome (n = 1), and undifferentiated connective tissue disease (n = 5).
First, we analyzed the 35 pregnancies treated by hydroxychloroquine of 30 APS
Discussion
In this real-life study of hydroxychloroquine during pregnancy in APS patients, we show an overall value of hydroxychloroquine addition to improve the obstetrical outcome. The most striking results concern the refractory obstetrical APS with 78% live-born babies after addition of hydroxychloroquine.
The conventional APS treatment including aspirin–LMWH combination is highly effective and much more than 80% of pregnancies are improved using this regimen. For resting refractory APS, despite
Take-home message
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Hydroxychloroquine addition to conventionnal APS treatment could ameliorate the obstetrical outcome in refractory obstetrical APS patients.
Acknowledgments
We thank the European Forum on Antiphospholipid Antibodies and Société Nationale Francaise de Médecine Interne (SNFMI).
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Conflicts of interest and funding sources: none.