A novel biologic therapy has demonstrated remarkable success in protecting high-risk pregnancies in women with antiphospholipid syndrome (APS), according to groundbreaking clinical trial results. The IMProve Pregnancy in APS with Certolizumab Therapy (IMPACT) trial found that certolizumab pegol, an anti-inflammatory biologic, dramatically improved outcomes when added to standard treatment protocols.
The study, co-led by experts from the Hospital for Special Surgery and the University of Utah Health, represents the first clinical trial to examine a biologic treatment specifically targeting adverse pregnancy outcomes in women with APS. Results recently published in the Annals of the Rheumatic Diseases show significant improvements in pregnancy success rates.
Dramatic Improvement in Pregnancy Outcomes
The IMPACT trial enrolled 51 pregnant women aged 18 to 40 with APS who tested positive for lupus anticoagulant, a marker associated with particularly high-risk pregnancies. Participants received certolizumab alongside traditional treatments of heparin and aspirin, beginning at week 8 of pregnancy and continuing through week 28.
The results were striking: only 20% of women experienced adverse pregnancy outcomes—a dramatic reduction compared to the 69-79% complication rate these same women had experienced in previous pregnancies despite receiving standard care.
"We previously showed that pregnancy in lupus patients whose disease is quiescent is likely to be uncomplicated," explained Dr. Jane Salmon, lead investigator of the IMPACT study. "Now with IMPACT, we show the potential to prevent preeclampsia and other serious pregnancy complications in high-risk pregnancies."
Perhaps most remarkable was the improvement in live birth rates. An impressive 93% of participants successfully brought home a healthy baby, compared to just 38% in their previous pregnancies. Additionally, the average gestational age at delivery increased significantly from 24 weeks to 36.5 weeks—a critical improvement for newborn health and development.
Targeting Inflammation: A Paradigm Shift
The success of certolizumab represents a significant shift in understanding how to manage APS in pregnancy. While traditional treatments focus primarily on preventing blood clots with anticoagulants, the IMPACT trial suggests that inflammation plays a crucial role in pregnancy complications.
Dr. Salmon's previous research identified inflammation in the placenta—rather than blood clotting alone—as a primary driver of pregnancy complications in APS. This insight led to investigating TNF-alpha inhibitors like certolizumab, which specifically target inflammatory pathways.
"This study shows that focusing on inflammation, rather than thrombosis or blood clots, may help prevent pregnancy complications in high-risk women with lupus and APS," noted the Lupus Foundation of America, which supported the trial through a three-year grant.
Understanding Antiphospholipid Syndrome
APS is an autoimmune disorder characterized by the presence of autoantibodies that can trigger dangerous blood clots, resulting in potentially life-threatening complications including strokes and pregnancy losses. The condition is particularly challenging during pregnancy, when it can lead to poor placental development, inadequate fetal growth, preeclampsia, and preterm birth.
Previous studies have shown that women with APS who test positive for lupus anticoagulant face significantly higher risks of severe pregnancy complications, with rates ranging from 39% to 86% despite standard treatments.
Safety Profile and Future Directions
An important finding from the trial was the safety profile of certolizumab during pregnancy. None of the participants experienced serious infections or lupus flares—a concern when the study began. This safety data adds to the growing evidence supporting certolizumab's use during pregnancy.
The IMPACT trial's success opens new avenues for research into biologic therapies for pregnancy complications. Researchers are now considering whether similar approaches could prevent conditions like preeclampsia in women without autoimmune disorders—a leading cause of maternal and fetal complications worldwide.
The study highlights the importance of collaboration between rheumatologists and obstetricians in addressing complex health challenges at the intersection of autoimmunity and reproductive health.
"Our study opens the door for trials with biologics to prevent adverse pregnancy outcomes," Dr. Salmon stated. "We are grateful to the patients and their care providers who were our brave and committed partners in this trial."
For the thousands of women with APS who wish to have children, the IMPACT trial results offer new hope for successful pregnancies and healthy babies—a significant advancement in reproductive health for those affected by this challenging condition.
