NYU Langone Health researchers have achieved a breakthrough in preventing congenital heart block by successfully using rozanolixizumab, a neonatal Fc receptor (FcRn) inhibitor, in a high-risk pregnancy. This represents the first reported case of using this therapeutic approach to prevent the potentially life-threatening condition, which affects babies born to mothers with anti-SSA/Ro autoantibodies.
The study, published in Annals of the Rheumatic Diseases on October 18, demonstrates how weekly injections of rozanolixizumab administered from weeks 14 to 28 of pregnancy successfully prevented congenital heart block development in a newborn whose mother had systemic lupus erythematosus and high levels of anti-SSA/Ro antibodies.
Mechanism and Treatment Protocol
Rozanolixizumab, a monoclonal antibody drug, works by blocking FcRn receptors on the placenta, preventing maternal antibodies from crossing the placental barrier into fetal circulation. The treatment also reduces autoantibody levels in the mother, with researchers reporting that autoantibody levels dropped by more than half during the treatment period.
The mother in this case study had previously experienced two pregnancies complicated by congenital heart block, with one baby dying before birth and another requiring a pacemaker shortly after birth. Use of rozanolixizumab was granted under federal compassionate drug use protocols given the high-risk nature of the pregnancy.
Clinical Outcomes
The treatment yielded encouraging results. The baby, a girl, was delivered at 37 weeks weighing 6 pounds, 6 ounces (2.89 kilograms) with no heart complications. The mother experienced no serious side effects from the weekly injections. Ultrasound and at-home heart rhythm checks were used throughout the pregnancy to closely monitor the fetal heartbeat.
"This single-patient study suggests the feasibility and safety of using rozanolixizumab to prevent congenital heart block in the offspring of pregnant women who are at high risk of passing along the potentially devastating autoantibodies that associate with fetal disease," said study lead investigator Philip Carlucci, MD, a rheumatology fellow and Colton Center for Autoimmunity – Briedenbach Scholar in the Department of Medicine at the NYU Grossman School of Medicine.
Scientific Significance and Future Research
Study senior investigator Jill Buyon, MD, the Sir Deryck and Lady Va Maughan Professor of Rheumatology at the NYU Grossman School of Medicine and director of the Lupus Center at NYU Langone, emphasized the study's theoretical validation. "Our research offers proof-of-concept data in support of the hypothesis that no autoantibodies equals no congenital heart block," Buyon stated.
The promising results have already catalyzed larger-scale research initiatives. The National Institutes of Health's Office of Autoimmune Disease Research has partnered with the National Institute of Arthritis and Musculoskeletal and Skin Diseases to fund a multicenter trial called AVERT (Atrioventricular Block Elimination with Rozanolixizumab Therapy).
AVERT Multicenter Trial
The AVERT investigation will be led by Buyon and study co-investigators Bettina Cuneo at the University of Arizona in Tucson, and Justin Brandt, MD, director of maternal fetal medicine at NYU Langone and associate professor in the Department of Obstetrics and Gynecology at the NYU Grossman School of Medicine. The trial will enroll pregnant women who have already had a child with congenital heart block and assess whether rozanolixizumab prevents development of the disease.
Drug Background and Regulatory Status
Rozanolixizumab is currently approved by the Food and Drug Administration for treatment of myasthenia gravis, a disease that leads to muscle weakness. The drug is manufactured by UCB (Union Chimique Belge), which provided doses for this study.
Congenital heart block, sometimes referred to as cardiac neonatal lupus, is a rare but potentially life-threatening condition that affects babies born to mothers with anti-SSA/Ro antibodies. These autoantibodies can attack the fetal heart via its electrical conduction system, leading to a slower heart rate. Most surviving infants with congenital heart block eventually require a pacemaker for life.
The study received funding support from a gift from Lauren and Andy Levison, and National Institutes of Health grants R01HD100929, R01AR087521, N01AR42220, and U01AI176244.
