Jaume Alijotas-Reig1, Enrique Esteve-Valverde2, Elisa Llurba3, Josep Mª Gris4. 1. Systemic Autoimmune Diseases Unit, Department of Internal Medicine-1, Vall d'Hebron University Hospital, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain; Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: jalijotas@vhebron.net. 2. Department of Internal Medicine, Althaia Network Health, Manresa, Barcelona, Spain. 3. Obstetric and Ginecology Department, Sant Pau University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain. 4. Reproductive Medicine Unit, Obstetric Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
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.
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.
Authors: Hannah Cohen; Maria J Cuadrado; Doruk Erkan; Ali Duarte-Garcia; David A Isenberg; Jason S Knight; Thomas L Ortel; Anisur Rahman; Jane E Salmon; Maria G Tektonidou; David J Williams; Rohan Willis; Scott C Woller; Danieli Andrade Journal: Lupus Date: 2020-10 Impact factor: 2.911