IMPACT Study: IMProve Pregnancy in APS With Certolizumab Therapy

Summary

This treatment trial evaluates the addition of an anti-tumor necrosis factor-alpha drug, certolizumab, to usual treatment (a heparin agent and low-dose aspirin) in pregnant women with antiphospholipid syndrome (APS) and repeatedly positive tests for lupus anticoagulant (LAC) to determine if this regimen will improve pregnancy outcomes. All enrolled patients will receive certolizumab, and pregnancy outcomes will be compared to those of women with APS and repeatedly positive tests for LAC enrolled in a previous study by the investigators.

Timeline

Start

2017-05-17

Primary completion

2027-12

Completion

2027-12

Publications

• Background Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306. doi: 10.1111/j.1538-7836.2006.01753.x.
• Background Committee on Practice Bulletins-Obstetrics, American College of Obstetricians and Gynecologists. Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol. 2012 Dec;120(6):1514-21. doi: 10.1097/01.AOG.0000423816.39542.0f.
• Background Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, Ramire de Jesus G, Erkan D. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care Res (Hoboken). 2013 Nov;65(11):1869-73. doi: 10.1002/acr.22066.
• Background Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet. 2010 Oct 30;376(9751):1498-509. doi: 10.1016/S0140-6736(10)60709-X. Epub 2010 Sep 6.
• Background de Jesus GR, Agmon-Levin N, Andrade CA, Andreoli L, Chighizola CB, Porter TF, Salmon J, Silver RM, Tincani A, Branch DW. 14th International Congress on Antiphospholipid Antibodies Task Force report on obstetric antiphospholipid syndrome. Autoimmun Rev. 2014 Aug;13(8):795-813. doi: 10.1016/j.autrev.2014.02.003. Epub 2014 Mar 17.
• Background Girardi G, Berman J, Redecha P, Spruce L, Thurman JM, Kraus D, Hollmann TJ, Casali P, Caroll MC, Wetsel RA, Lambris JD, Holers VM, Salmon JE. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest. 2003 Dec;112(11):1644-54. doi: 10.1172/JCI18817.
• Background Shamonki JM, Salmon JE, Hyjek E, Baergen RN. Excessive complement activation is associated with placental injury in patients with antiphospholipid antibodies. Am J Obstet Gynecol. 2007 Feb;196(2):167.e1-5. doi: 10.1016/j.ajog.2006.10.879.
• Background Stone S, Pijnenborg R, Vercruysse L, Poston R, Khamashta MA, Hunt BJ, Poston L. The placental bed in pregnancies complicated by primary antiphospholipid syndrome. Placenta. 2006 Apr-May;27(4-5):457-67. doi: 10.1016/j.placenta.2005.04.006. Epub 2005 Jul 6.
• Background Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter TF, Sammaritano L, Stephenson MD, Buyon J, Salmon JE. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum. 2012 Jul;64(7):2311-8. doi: 10.1002/art.34402.
• Background Gilbert WM, Nesbitt TS, Danielsen B. The cost of prematurity: quantification by gestational age and birth weight. Obstet Gynecol. 2003 Sep;102(3):488-92. doi: 10.1016/s0029-7844(03)00617-3.
• Background Gnanendran L, Bajuk B, Oei J, Lui K, Abdel-Latif ME; NICUS Network. Neurodevelopmental outcomes of preterm singletons, twins and higher-order gestations: a population-based cohort study. Arch Dis Child Fetal Neonatal Ed. 2015 Mar;100(2):F106-14. doi: 10.1136/archdischild-2013-305677. Epub 2014 Oct 30.
• Background Pijnenborg R, Vercruysse L, Hanssens M. The uterine spiral arteries in human pregnancy: facts and controversies. Placenta. 2006 Sep-Oct;27(9-10):939-58. doi: 10.1016/j.placenta.2005.12.006. Epub 2006 Feb 20.
• Background Redman CW, Sargent IL. Immunology of pre-eclampsia. Am J Reprod Immunol. 2010 Jun;63(6):534-43. doi: 10.1111/j.1600-0897.2010.00831.x. Epub 2010 Mar 23.
• Background Berman J, Girardi G, Salmon JE. TNF-alpha is a critical effector and a target for therapy in antiphospholipid antibody-induced pregnancy loss. J Immunol. 2005 Jan 1;174(1):485-90. doi: 10.4049/jimmunol.174.1.485.
• Background Redecha P, Tilley R, Tencati M, Salmon JE, Kirchhofer D, Mackman N, Girardi G. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. Blood. 2007 Oct 1;110(7):2423-31. doi: 10.1182/blood-2007-01-070631. Epub 2007 May 29.
• Background Qing X, Redecha PB, Burmeister MA, Tomlinson S, D'Agati VD, Davisson RL, Salmon JE. Targeted inhibition of complement activation prevents features of preeclampsia in mice. Kidney Int. 2011 Feb;79(3):331-9. doi: 10.1038/ki.2010.393. Epub 2010 Oct 13.
• Background Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Epstein FH, Sukhatme VP, Karumanchi SA. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003 Mar;111(5):649-58. doi: 10.1172/JCI17189.
• Background Lubbe WF, Butler WS, Palmer SJ, Liggins GC. Fetal survival after prednisone suppression of maternal lupus-anticoagulant. Lancet. 1983 Jun 18;1(8338):1361-3. doi: 10.1016/s0140-6736(83)92141-4.
• Background Branch DW, Scott JR, Kochenour NK, Hershgold E. Obstetric complications associated with the lupus anticoagulant. N Engl J Med. 1985 Nov 21;313(21):1322-6. doi: 10.1056/NEJM198511213132104.
• Background Cowchock FS, Reece EA, Balaban D, Branch DW, Plouffe L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol. 1992 May;166(5):1318-23. doi: 10.1016/0002-9378(92)91596-3.
• Background Yelnik CM, Laskin CA, Porter TF, Branch DW, Buyon JP, Guerra MM, Lockshin MD, Petri M, Merrill JT, Sammaritano LR, Kim MY, Salmon JE. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results. Lupus Sci Med. 2016 Jan 12;3(1):e000131. doi: 10.1136/lupus-2015-000131. eCollection 2016.
• Background Clark CA, Laskin CA, Spitzer KA. Anticardiolipin antibodies and recurrent early pregnancy loss: a century of equivocal evidence. Hum Reprod Update. 2012 Sep-Oct;18(5):474-84. doi: 10.1093/humupd/dms020. Epub 2012 Jun 13.

Drugs

Indications