Severe hemolytic disease of the fetus and newborn (HDFN) results from red blood cell (RBC) antigen incompatibility when IgG molecules produced by the mother pass through the placenta and destroy fetal RBC cells that express the antigen. Rh-immunoglobulin treatment is routinely given to all Rh-negative mothers around the 28th week of gestation, but early-onset severe HDFN may occur if the Rh-immunoglobin is not given or for alloimmunization against non-RhD antigens. However, early-onset severe HDFN occurs at 24 weeks of gestation or earlier and has a high risk of infant morbidity and mortality, even with standard care, such as intrauterine transfusions and antenatal treatment with intravenous immune globin. A new monoclonal antibody called nipocalimab targets the only known neonatal transplacental IgG Fc receptor (FcRn). Recent open-label, international phase 2 trial results suggest that nipocalimab may be helpful in delaying the onset of severe HDFN. In brief, 13 pregnant women with a high risk of severe HDFN (85% with high titers of anti-D alloantibodies, 15% with high titers of anti-K alloantibodies; and a previous pregnancy with early-onset, severe HDFN) received intravenous nipocalimab (weekly from 14 to 35 weeks of gestation). Seven out of 13 pregnancies (54%) resulted in live births at 32 weeks gestation or later without intrauterine transfusions, which was greater than the clinically meaningful difference from the historical benchmark of 10% (P<0.001). Furthermore, no cases of fetal hydrops occurred, and 10 out of 12 participants delivered at 34 weeks of gestation or later. Treatment with nipocalimab also reduced the number of intrauterine transfusions (6 vs. 11), and delayed the timing of the first intrauterine transfusion (27 weeks and 1 day compared to 20 weeks and 4 days) compared to qualifying pregnancies. While these results are promising for those at risk for severe HDFN, phase 3 clinical trials are needed.
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