Treatment of refractory poor aPL-related obstetric outcomes with TNF-alpha blockers: Maternal-fetal outcomes in a series of 18 cases

Abstract

Background: No absolute data on the treatment of antiphospholipid antibodies (aPL) related to refractory obstetric complications exist to date. TNF-α play a major role in this disorder.

Objective: To assess the effectiveness of TNF-α blockers in 18 aPL-positive women with recurrent infertility after therapy with low-molecular-weight heparin (LMWH) plus aspirin (LDA) plus hydroxychloroquine (HCQ).

Methods: Prospective case-series of 12 women fulfilling Sydney criteria for obstetric antiphospholipid syndrome (OAPS) and 6 with incomplete forms (OMAPS). All women tested positive for aPL at least twice. Non-criteria aPL were tested in 15/18. Complement, TNF-α and IL-10 were also evaluated. Women were closely monitored for fetal well-being and possible malformations throughout gestation and the postpartum period.

Results: Sixteen patients were started on adalimumab and 2 on certolizumab. Twelve women completed gestation: 9 at term and 3 pre-term. Differences in laboratory categories and outcomes were observed when OAPS and OMAPS were compared. First trimester miscarriage or implantation failure recurred in 6 cases, all of the OAPS group. Malformations were not seen in the newborns.

Conclusions: Overall, good obstetric results were obtained in 70% of previous LMWH-LDA+HCQ refractory cases. TNF-α blockers were well tolerated without adverse effects. The combination of LMWH plus LDA plus TNF-α blockers appears to be a promising treatment for refractory obstetric complaints related to aPL; nevertheless, outcome differences between OAPS and OMAPS do exist.

Keywords: Antiphospholipid antibody; Antiphospholipid syndrome; Infertility; TNF-α blockers; Treatment.