LAUSR

After reading the review article by Wijnsma et al. [1] with great interest, we would like to comment on the utility of eculizumab dose monitoring in pregnancy. While Wijnsma et al. describe a strategy for dosing eculizumab in atypical hemolytic uremic syndrome (aHUS), it is not emphasized that many patients diagnosed with aHUS are of childbearing age. Dose adjustment of eculizumab is unknown in pregnancy and deserves further investigation given the potential effect of inducing recurrent thrombotic microangiopathy (TMA) with subtherapeutic dose or adverse side effects of opportunistic infection at a supratherapeutic dose [2]. Current knowledge emphasizes individual dose adjustments based on weight, age, and particular disease diagnosis [3–5]. However, weight-based dose modification is still not clearly defined in patients with aHUS who become pregnant [6], despite the anticipated need for dose adjustment due to physiological changes in the volume of distribution [4]. Furthermore, the effect of eculizumab on the fetus and neonate remain largely unknown. We analyzed the levels of eculizumab in a young female using the enzyme-linked immunoassay technique. The patient was diagnosed with aHUS 7 months after her first pregnancy in 2017, at which time she required intubation for generalized seizures and acute hemodialysis due to renal failure. She was subsequently diagnosed with a point mutation of unknown pathologic significance in the coding sequence of the plasminogen gene. In 2019, the patient became pregnant with her second child, at which time she continued to receive eculizumab 1200 mg intravenously every 2 weeks. Plasma eculizumab levels were measured immediately prior to each eculizumab dose (Fig. 1). Subtherapeutic levels were detected during the first, second, and third trimesters (80.0 μg/mL, 60.0 μg/mL, and 54.0 μg/ mL, respectively). One hundred and five days after delivery, standard dosing achieved a therapeutic level of 128 μg/mL. Despite this, no complications were identified with standard dosing throughout pregnancy (Table 1). The patient delivered a healthy 3.6 kg newborn at term, with no postpartum complications. We observed a 58% reduction in drug level during the third trimester compared with the levels measured postpartum (128 μg/mL). In addition to variability in blood levels, we detected eculizumab in the breast milk (Fig. 1). Drug levels were measured in breast milk 48, 96, and 324 h after infusion (0.21, 0.11, and < 0.01 μg/mL, respectively (Fig. 1). In distinction from previous reports regarding patients receiving eculizumab for paroxysmal nocturnal hemoglobinuria, drug levels were detectable in the breast milk. This discrepancy may be explained in part by the higher maintenance dose This comment refers to the article available at https ://doi. org/10.1007/s4026 2-019-00742 -8.