Lupus (2013) 0,
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LETTER TO THE EDITOR Are there additional options for the treatment of refractory obstetric antiphospholipid syndrome? Sir, Recently, Alijotas-Reig1 reported a comprehensive review focused on the management of refractory cases of antiphospholipid syndrome (APS) presenting during the obstetric period. The author addressed some potential alternatives for the treatment of refractory obstetric APS, including double anti-aggregant therapy, intravenous immunoglobulins, and biologic therapies, especially anti-tumor necrosis factor (TNF)-a agents.1 We would like to comment on two additional treatment options. Alijotas-Reig especially emphasized the potential utility of anti-TNF-a agents, including infliximab (INF), etanercept (ETC), and adalimumab (ADA); however, no mention of certolizumab (CZP) was made. Additionally, the author does not comment on the potential role of plasma exchange (PE) therapy during pregnancy, including catastrophic APS (CAPS) events.2,3 CZP is a PEGylated Fab’ fragment of humanized anti-TNF-a monoclonal antibody, rather than a whole human immunoglobulin G1 (IgG1) antibody, such as INF or ADA.4 Whole IgG antibodies cross the placenta via specific neonatal receptors (FcRns).5 Most information about the use of anti-TNF-a therapies during pregnancy comes from inflammatory bowel disease studies5,6 and from national registries.7 Although anti-TNF-a drugs do not seem to increase the risk of complications during pregnancy and seem to be safe for the newborn, an increased rate of spontaneous abortions was observed in women exposed to anti-TNF-a therapies at conception.7 Despite the fact that anti-TNF-a could be relatively safe for the baby, those therapies are not free of adverse events for the mother. Those adverse effects include infusion or injection site reactions, increased risk of serious infections, including bacterial infections, tuberculosis, and opportunistic
Correspondence to: Jose A Go´mez-Puerta, Division of Rheumatology, Immunology and Allergy, Section of Clinical Sciences, Brigham and Women’s Hospital, 221 Longwood Ave., Boston, MA 02115 USA. Email:
[email protected] Received 8 February 2013; accepted 20 April 2013
infections, among others. So, clinicians must be aware of those events and balance the benefits and risks of using them during pregnancy. If the decision to continue INF or ADA throughout pregnancy is made, it should be avoided during the third trimester when transplacental transfer is at its greatest. The placental transfer is not the same for all anti-TNF-a therapies. Recently, Mahadevan et al.5 reported a study that included 31 pregnant women with Crohn’s disease who were exposed to three different anti-TNF therapies. Eleven pregnant patients were exposed to INF, 10 patients to CZP, and 10 patients to ADA. When comparing placental transfer measured by cord blood levels at birth, CZP had minimal placental transfer. Conversely, INF and ADA levels were considerably higher. IFX and ADA could be detected in the infants for as long as six months, thus raising some concerns regarding the risk of infection and response to vaccines during the neonatal period. Finally, we would like to stress the utility of PE sessions in pregnant patients with APS and, especially, with CAPS. The basic principle of PE is the removal of large molecular-weight substances, including autoantibodies and immune complexes.8 PE has been used in pregnant patients with primary APS with previous thrombotic events2 and is crucial in CAPS.9 El-Haeig et al.10 evaluated the efficacy of PE plus low doses of prednisone in 18 pregnant APS patients, most of them with previous history of fetal losses and/or severe preeclampsia. The authors achieved very satisfactory results, with a live birth rate of 100%, no neonatal deaths, and no cases of severe preeclampsia. Therefore, CZP and PE sessions must be included in the therapeutic arsenal for refractory obstetric APS.
Funding This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors.
Conflict of interest None declared.
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10.1177/0961203313490433
Lupus Letter to the Editor
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References 1 Alijotas-Reig J. Treatment of refractory obstetric antiphospholipid syndrome: The state of the art and new trends in the therapeutic management. Lupus 2013; 22: 6–17. 2 Bontadi A, Ruffatti A, Marson P, et al. Plasma exchange and immunoadsorption effectively remove antiphospholipid antibodies in pregnant patients with antiphospholipid syndrome. J Clin Apher 2012; 27: 200–204. 3 Go´mez-Puerta JA, Cervera R, Espinosa G, et al. Catastrophic antiphospholipid syndrome during pregnancy and puerperium: Maternal and fetal characteristics of 15 cases. Ann Rheum Dis 2007; 66: 740–746. 4 Deeks ED. Certolizumab pegol: A review of its use in the management of rheumatoid arthritis. Drugs 2013; 73: 75–97. 5 Mahadevan U, Wolf DC, Dubinsky M, et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2013; 11: 286–292. 6 Schnitzler F, Fidder H, Ferrante M, et al. Outcome of pregnancy in women with inflammatory bowel disease treated with antitumor necrosis factor therapy. Inflamm Bowel Dis 2011; 17: 1846–1854.
7 Verstappen SM, King Y, Watson KD, Symmons DP, Hyrich KL. Anti-TNF therapies and pregnancy: Outcome of 130 pregnancies in the British Society for Rheumatology Biologics Register. Ann Rheum Dis 2011; 70: 823–826. 8 Pons-Estel GJ, Salerni GE, Serrano RM, et al. Therapeutic plasma exchange for the management of refractory systemic autoimmune diseases: Report of 31 cases and review of the literature. Autoimmun Rev 2011; 10: 679–684. 9 Go´mez-Puerta J, Espinosa G, Cervera R. Catastrophic antiphospholipid syndrome: Diagnosis and management in pregnancy. Clin Lab Med, Epub ahead of print 22 April 2013. 10 El-Haieg DO, Zanati MF, El-Foual FM. Plasmapheresis and pregnancy outcome in patients with antiphospholipid syndrome. Int J Gynaecol Obstet 2007; 99: 236–241.
JA Go´mez-Puerta1 and R Cervera2 1
Division of Rheumatology, Immunology and Allergy, Section of Clinical Sciences, Brigham and Women’s Hospital, Boston, MA, USA; and 2Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Catalonia, Spain
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