Elsevier

Autoimmunity Reviews

Volume 14, Issue 6, June 2015, Pages 498-502
Autoimmunity Reviews

Review
The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study

https://doi.org/10.1016/j.autrev.2015.01.012Get rights and content

Abstract

In European multicenter study, we aimed to describe the real-life hydroxychloroquine use in APS patients during pregnancy and determine its benefit in refractory obstetrical APS.

We analyzed the outcome of pregnancies treated by hydroxychloroquine in patients with APS or asymptomatic antiphospholipid (aPL) antibodies carriers.

Thirty patients with APS with 35 pregnancies treated by hydroxychloroquine were analyzed. Comparing the outcome of pregnancies treated by the addition of hydroxychloroquine to previous pregnancies under the conventional treatment, pregnancy losses decreased from 81% to 19% (p < 0.05), without differences in the associated treatments. The univariate analysis showed that the previous intrauterine deaths and higher hydroxychloroquine amount (400 mg per day) were the factors associated with pregnancy outcome. Considering 14 patients with previous refractory obstetrical APS (n = 5 with obstetrical and thrombotic primary APS and n = 9 with purely obstetrical APS), all with previous pregnancy losses under treatment (aspirin with LMWH in 11 cases and LMWH in 3 cases), the addition of hydroxychloroquine resulted in live born babies in 11/14 (78%) cases (p < 0.05).

Our study shows the benefit of hydroxychloroquine addition in patients with refractory obstetrical APS and raises the need of prospective studies to confirm our preliminary 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.

Section snippets

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

  • 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.

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