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).
About HSS:
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the 15th consecutive year), No. 3 in rheumatology by U.S. News & World Report (2024-2025), and the best pediatric orthopedic hospital in NY, NJ and CT by U.S. News & World Report “Best Children’s Hospitals” list (2024-2025). In a survey of medical professionals in more than 20 countries by Newsweek, HSS is ranked world #1 in orthopedics for a fifth consecutive year (2025). Founded in 1863, the Hospital has the lowest readmission rates in the nation for orthopedics, and among the lowest infection and complication rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center five consecutive times. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State, as well as in Florida. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. In addition, more than 200 HSS clinical investigators are working to improve patient outcomes through better ways to prevent, diagnose, and treat orthopedic, rheumatic and musculoskeletal diseases. The HSS Innovation Institute works to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is a trusted leader in advancing musculoskeletal knowledge and research for physicians, nurses, allied health professionals, academic trainees, and consumers in more than 165 countries.
