背景:在胎儿和新生儿的早发性严重溶血病(HDFN)中,母体抗红细胞IgG同种抗体经胎盘转移导致胎儿贫血,导致使用高危宫内输血以避免胎儿水肿和胎儿死亡.Nipocalimab,抗新生儿Fc受体阻滞剂,抑制胎盘IgG转移并降低母体IgG水平。
方法:在国际上,开放标签,单组,第二阶段研究,我们评估了在妊娠14~35周期间静脉注射尼波卡利单抗(每周30mg/kg体重或45mg/kg体重)治疗复发性早发性重度HDFN高危妊娠的参与者.主要终点为妊娠32周或更晚不进行宫内输血的活产,对照历史基准(0%;有临床意义的差异,10%)。
结果:在妊娠32周或之后没有宫内输血的活产发生在13例妊娠中有7例(54%;95%置信区间,25到81)在研究中。无一例胎儿水肿发生,6名参与者(46%)未接受任何产前或新生儿输血.6例胎儿接受了宫内输血:5例胎儿在妊娠24周或更晚,1例胎儿在妊娠22周和5天胎儿丢失之前。活产发生在12次怀孕中。分娩时的中位胎龄为36周和4天。在12个活产婴儿中,1例接受了一次交换输血和一次简单输血,5例仅接受了简单输血。在母体样品和脐带血中观察到同种抗体滴度和IgG水平的治疗相关降低。未观察到异常的母体或儿科感染。严重不良事件与HDFN一致,怀孕,或早产。
结论:Nipocalimab治疗延迟或预防了胎儿贫血或宫内输血,与历史基准相比,早发重度HDFN风险较高的孕妇。(由JanssenResearchandDevelopment资助;UNITYClinicalTrials.gov编号,NCT03842189。).
BACKGROUND: In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti-neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels.
METHODS: In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks\' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks\' gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%).
RESULTS: Live birth at 32 weeks\' gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks\' gestation or later and one fetus before fetal loss at 22 weeks and 5 days\' gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity.
CONCLUSIONS: Nipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.).