NYC Gazette

A clinical trial co-led by the Hospital for Special Surgery (HSS) has demonstrated that the inflammation-blocking drug certolizumab can significantly reduce the risk of serious pregnancy complications in women suffering from antiphospholipid syndrome (APS). The phase 2 IMPACT trial marks the first clinical evaluation of a biologic therapy aimed at preventing adverse pregnancy outcomes in women with APS and their unborn children. The complete results have been published in the Annals of the Rheumatic Diseases.

Dr. Jane E. Salmon, a rheumatologist at HSS, and Dr. D. Ware Branch, an obstetrician/gynecologist at University of Utah Health, co-led the trial. "The IMPACT study represents a bold and very successful partnership over many years between government, industry, foundations, and academic health research institutions," noted Dr. Salmon.

APS, a rare autoimmune disorder often associated with lupus, wreaks havoc through autoantibodies that interact with blood vessels and cause clots leading to strokes and heart attacks. During pregnancy, APS can cause fetal death, preeclampsia, and restricted fetal growth due to placental issues. Previous studies by Dr. Salmon identified lupus anticoagulant (LA) as a predictor of pregnancy complications in APS patients—39% to 86% of LA-positive pregnancies face serious issues despite treatment with blood thinners.

Dr. Salmon's preclinical research revealed that inflammation, rather than blood clots, causes complications in APS pregnancies. This resulted in testing the effectiveness of TNF-alpha inhibitors like certolizumab, commonly used for inflammatory conditions, in reducing these complications.

The IMPACT trial involved 51 high-risk APS patients, aged 18 to 40, who received certolizumab in combination with heparin and aspirin. Treatment began at the eighth week of pregnancy and was stopped at the 28th week. Patients experienced a significant drop in complications from a prior rate of 69% to 79% to just 20% with certolizumab treatment. The study reported that 93% of participants delivered healthy babies, compared to a previous survival rate of only 38%.

Dr. Salmon emphasizes that this trial's success demonstrates the potential of targeting inflammation instead of clotting in preventing complications. "Our study heralds a new era for trials with biologics to prevent adverse pregnancy outcomes," she said. "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."

Additionally, the study opens possibilities for using TNF-alpha inhibitors to prevent preeclampsia in non-autoimmune patients. "Preeclampsia is the most common cause of morbidity and mortality of pregnant women and their babies, and there are currently no effective therapies," Dr. Salmon remarked.

The trial received 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 manufacturer of certolizumab (Cimzia).