Effect of Additional Treatments Combined with Conventional Therapies in Pregnant Patients with High-Risk Antiphospholipid Syndrome: A Multicentre Study

Abstract

The effect of additional treatments combined with conventional therapy on pregnancy outcomes was examined in high-risk primary antiphospholipid syndrome (PAPS) patients to identify the most effective treatment strategy. The study's inclusion criteria were (1) positivity to lupus anticoagulant alone or associated with anticardiolipin and/or anti-β2 glycoprotein I antibodies; (2) a history of severe maternal-foetal complications (Group I) or a history of one or more pregnancies refractory to conventional therapy leading to unexplained foetal deaths not associated with severe maternal-foetal complications (Group II). Two different additional treatments were considered: oral-low-dose steroids (10-20 mg prednisone daily) and/or 200 to 400 mg daily doses of hydroxychloroquine and parenteral-intravenous immunoglobulins at 2 g/kg per month and/or plasma exchange. The study's primary outcomes were live birth rates and pregnancy complications. A total of 194 pregnant PAPS patients attending 20 tertiary centres were retrospectively enrolled. Hydroxychloroquine was found to be linked to a significantly higher live birth rate with respect to the other oral treatments in the Group II patients. The high (400 mg) versus low (200 mg) doses of hydroxychloroquine ( = 0.036) and its administration before versus during pregnancy ( = 0.021) were associated with a significantly higher live birth rate. Hydroxychloroquine therapy appeared particularly efficacious in the PAPS patients without previous thrombosis. Parenteral treatments were associated with a significantly higher live birth rate with respect to the oral ones ( = 0.037), particularly in the Group I patients. In conclusion, some additional treatments were found to be safe and efficacious in high-risk PAPS pregnant women.

Obstetric antiphospholipid syndrome

“…In severe cases with recurrent late pregnancy morbidities, despite treatment with LDA and LMWH, low-dose steroids (10 mg prednisolone) and hydroxychloroquine may be added. 86 In severe treatment-resistant cases, intravenous gamma globulin or repeated plasma exchange/apheresis could, based on small case series with favourable outcomes, be considered. 87 …”

Hydroxychloroquine and the Prevention of Pregnancy Losses

“…This study did not separate women who had APS only from those with APS and SLE, and therefore the prevalence of SLE was not uniform across the two groups. However a study isolating subjects with APS (without SLE) and a history of previous pregnancy complications resulted in similar findings of a higher live birth rate and fewer severe pregnancy complications in those treated with HCQ [36]. In a third retrospective study, Mekinian et al showed that women with obstetric APS and refractory obstetric APS treated with HCQ had better pregnancy outcomes, i.e., fewer miscarriages, compared to those without HCQ [37].…”

Anti-Phosphatidylserine/Prothrombin Antibodies in Healthy Women with Unexplained Recurrent Pregnancy Loss

“…The addition of HCQ, a drug possibly capable of restoring some of the damage exerted by aPL on trophoblasts in mice models [ 40 , 41 ], has been regarded as the next step in obstetrical APS treatment [ 42 ]. This drug has been reported to be safe in pregnancy and in women with obstetric APS pregnancies, with no [ 43 , 44 ] or minor side-effects [ 45 ], probably due to a limited duration of treatment [ 46 ]. However, we decided to be cautious and only prescribe HCQ to patients with a previously unsuccessful treatment regimen with LMWH and ASA.…”