Biologic therapy significantly improves pregnancy outcomes in women with antiphospholipid syndrome at high risk for serious complications

A landmark clinical trial co-led by Hospital for Special Surgery (HSS) has found that blocking inflammation with the drug certolizumab significantly reduces the risk of serious adverse pregnancy outcomes in women with antiphospholipid syndrome (APS).

The phase 2 IMPACT Trial (IMProve Pregnancy in APS with Certolizumab Therapy) was co-led by Jane E. Salmon, MD, a rheumatologist and the Collette Kean Research Chair at HSS and D. Ware Branch, MD, an obstetrician/gynecologist at University of Utah Health. It is the first clinical trial to evaluate a biologic therapy to prevent serious adverse outcomes in pregnant women with APS and their babies. The study results were published online on April 10, 2025 in Annals of the Rheumatic Diseases.

“The IMPACT study represents a bold and very successful partnership over many years between government, industry, foundations, and academic health research institutions,” said Dr. Salmon, the senior study author. “It is exciting to see our preclinical work in the laboratory, which began more than a decade ago, translate into such promising results for patients. I hope our findings will allow the drug to become widely available so that more pregnant women with APS and high-risk pregnancies can benefit.”

APS is a rare autoimmune disorder affecting up to 0.05% of people. It is frequently associated with lupus, a disease most prevalent in women during their reproductive years. In APS, the body produces autoantibodies that react with blood vessels and circulating cells, causing dangerous blood clots throughout the body, which can lead to strokes, heart attacks, and phlebitis. During pregnancy, APS raises the risk of serious complications arising from issues with the placenta, including fetal death, preeclampsia, and restricted fetal growth.

Previous research led by Dr. Salmon identified lupus anticoagulant (LA), an autoantibody produced by some APS patients, as the strongest predictor of poor pregnancy outcomes in APS patients. Historically, 39% to 86% of pregnant women with APS who are LA positive have faced severe complications, despite treatment with standard-of-care blood thinners like heparin and aspirin. These patients have the greatest need for better treatments.  

Dr. Salmon’s preclinical research in experimental models showed that inflammation in the developing placenta, not blood clots, was the main cause of pregnancy complications in APS. This pivotal discovery led her team to investigate whether TNF-alpha inhibitors, a class of drugs used to treat inflammatory conditions like rheumatoid arthritis, Crohn’s disease and plaque psoriasis, could offer better protection to APS pregnancies than blood thinners alone.

The IMPACT trial enrolled 51 pregnant women ages 18 to 40 with high-risk APS, defined as positive for lupus anticoagulant. All participants were treated with certolizumab, a TNF-alpha inhibitor that does not cross the placenta, in addition to standard-of-care heparin and aspirin, starting at week eight of pregnancy. Medication was stopped at week 28, the point at which the placenta is well-developed. The unique design of the IMPACT study made it possible for pregnant patients from 16 states and one Canadian province to participate.  

The 20% complication rate in patients treated with certolizumab was dramatically lower than their prior pregnancies in which 69% to 79% had severe adverse outcomes, despite standard treatment with heparin and aspirin. The average gestational of age at delivery was 36.5 weeks in certolizumab-treated pregnancies, compared to 24 weeks in patients’ prior pregnancies. Among IMPACT participants, 93% brought home a healthy baby—a remarkable improvement over the 38% survival rate for their previous pregnancies. Notably, none experienced serious infections or lupus flares, a concern when the study began. 

The trial supports the concept derived from basic laboratory studies that targeting inflammation, rather than blood clotting, is effective in preventing pregnancy complications in high-risk pregnant patients with APS. It also shows the power of collaboration between rheumatologists and obstetricians.

“Our study heralds a new era for trials with biologics to prevent adverse pregnancy outcomes. We have shown that it is possible to gain the confidence of regulators and the trust of pregnant women who will enroll in clinical trials,” said Dr. Salmon. “We are grateful to the patients and their care providers, who were committed partners in this trial, and to our funders who watched our trial with anticipation and excitement,” said Dr. Salmon.  

“These results also open a window for studying whether TNF-alpha blockade could help prevent preeclampsia in women without autoimmune disorders,” she added. “Preeclampsia is the most common cause of morbidity and mortality of pregnant women and their babies, and there are currently no effective therapies.” 

The study was supported by funding from the National Institutes of Health, the Lupus Foundation of America, the Morris and Alma Schapiro Fund, the James R. and Jo Scott Research Endowment at the University of Utah and UCB Inc., the maker of certolizumab (Cimzia).