Women with atypical hemolytic uremic syndrome (aHUS) treated with eculizumab have similar pregnancy outcomes to women who were not treated with eculizumab, according to a review of post-marketing safety data presented at the 2019 Congress of the International Society on Thrombosis and Haemostasis.
"Pregnancy outcomes in [this patient population] are not well reported," said Marie Scully, MD, lead author and professor of hematology at University College London Hospitals. aHUS is a rare, genetic, chronic disease caused by genetic abnormalities that result in chronic uncontrolled complement activation leading to complement-mediated thrombotic microangiopathy. Eculizumab, an inhibitor of the terminal complement pathway, was approved for the treatment of aHUS in October 2011.
This report analyzed patient data from women who became pregnant while enrolled in the Global aHUS Registry, which was initiated in April 2012. As of December 2018, 39 pregnancies were recorded in 36 patients. Evaluable pregnancy data were not available in three women, and two pregnancies were ongoing at the time of data presentation, leaving data for 34 pregnancies in this analysis. Of these, 24 pregnancies occurred in women were treated with eculizumab and 10 were not exposed to the drug.
In most of the eculizumab-exposed pregnancies (n=17), patients were dosed according to recommendations in the prescribing information, Dr. Scully noted.
The researchers observed a higher proportion of live births in non-exposed compared with eculizumab-exposed patients (80% vs. 58%), as well as more elective terminations (33% vs. 10%), though p values for these comparisons were not reported. Pregnancy outcomes are presented in the TABLE.
"Real-world data from the Global aHUS Registry showed no increase in poor outcomes in pregnant patients exposed to eculizumab."
â€”Marie Scully, MD
A total of three patients (9%) experienced a relapse of aHUS – one eculizumab-exposed patient and two non-exposed patients.
Five patients received dialysis during pregnancy, all of whom were exposed to eculizumab, including one patient who had an aHUS relapse.
Notably, in the entire study population, no malformations or anomalies were reported within three months of birth, though there was a higher proportion of complement mutations in eculizumab-exposed patients (63% vs. 33%; p value not reported).
"Real-world data from the Global aHUS Registry showed no increase in poor outcomes in pregnant patients exposed to eculizumab," the authors concluded, "with the proportion of miscarriages consistent with the general population (up to 20% of pregnancies)." The findings of this analysis are limited by the small population, and the investigators noted that further evaluation of this aHUS subpopulation is ongoing.
The authors report relationships with Alexion Pharmaceuticals, the manufacturers of eculizumab.