Can adding hydroxychloroquine to current regimes used in obstetric antiphospholipid syndrome improve pregnancy outcomes? A narrative review.

Emily Smelt

Introduction:

Antiphospholipid syndrome (APS) is an autoimmune disorder characterised by persistent presence of antiphospholipid antibodies, which can present with vascular thrombosis and obstetric complications. In its obstetric form (OAPS), morbidity includes recurrent miscarriage, unexplained fetal death, premature birth, pre-eclampsia and eclampsia. Despite treatment with low-dose aspirin (LDA) and low molecular weight heparin (LMWH), 20-30% of women still experience pregnancy losses and adverse outcomes. This is termed ‘refractory’ OAPS. In this population, additional therapies such as hydroxychloroquine (HCQ), low-dose steroids, intravenous immunoglobulin, statins and biologics have been proposed. A large focus is currently invested in HCQ, due to its antithrombotic and immunomodulatory properties.

Objective:

This narrative review aims to summarise the findings of studies which have investigated whether adding HCQ to a standard regime of LDA and LMWH may improve pregnancy outcomes, including live birth rate, in women with refractory OAPS.

Methods:

A comprehensive search was carried out across PubMed, EMBASE and Cochrane using the keywords “Antiphospholipid”, “Hydroxychloroquine”, “pregnancy”, “outcomes”, “treatment”, “prevention”, “obstetric” and “refractory” with filters for English language and full-text articles applied. Relevant original articles, reviews, meta-analyses and case reports published until April 2025 were included in this review.

Results:

This review confirmed that adding HCQ to conventional treatment shows promise in increasing the live birth rate in women with OAPS. Treatment with HCQ was associated with lower pregnancy morbidity and a higher dose (400mg) with better pregnancy outcomes. To this date, there is no substantial data to define treatment protocols for using HCQ in OAPS. Four randomised-controlled trials (RCTs) are currently underway, hopefully addressing this gap.

Conclusion:

With the ability to improve pregnancy outcomes in women with refractory OAPS, HCQ could be a valuable addition to current conventional treatment. However, results of ongoing RCTs are imperative to corroborate these findings and inform future treatment guidelines.