ESPE Abstracts

Metreleptin is a leptin analog used to treat metabolic complications of lipodystrophy, a set of rare disorders characterized by generalized (GL) or regional (PL) deficiency of adipose tissue, resulting in insulin resistance, diabetes, dyslipidemia, steatohepatitis, and reproductive dysfunction. Metreleptin increases fertility, particularly in GL; spontaneous pregnancy without metreleptin was reported in only 4 patients with GL. Risks of metreleptin suggested by rodent studies include prolonged gestation and dystocia, and there is theoretical concern that anti-drug antibodies could cross the placenta, causing adverse effects in offspring by binding to endogenous leptin. On the other hand, metabolic disease typically worsens during pregnancy, leading to known pregnancy complications in women with both GL and PL. By controlling metabolic disease, metreleptin might provide benefit during pregnancy. Thus, knowing pregnancy outcomes in patients with metreleptin exposed and unexposed pregnancies is important. To obtain preliminary data on pregnancy outcomes in women with GL and PL who were, vs were not, exposed to metreleptin during pregnancy, we conducted a chart and literature review of pregnancy outcomes in these patients. There were 11 metreleptin treated patients (9 GL; 2 PL), and 50 untreated patients (4 GL; 46 PL). In 9 patients with GL taking metreleptin during pregnancy, live birth occurred in 7 of 13 (54%) pregnancies (5 [71%] term; 2 [29%] preterm), with miscarriage in 6 (46%). 10 pregnancies occurred in 4 patients with GL without metreleptin. Of these, 8 (80%) were live births (7 [88%] term, 1 [12%] preterm; 1 unknown), with 2 (20%) miscarriages. In patients with PL only 2 pregnancies in 2 patients occurred while patients were taking metreleptin, including 1 live term birth (50%) and 1 miscarriage (50%). In patients with PL taking metreleptin during pregnancy, live birth occurred in 71 of 99 (72%) pregnancies, with miscarriage in 27 (27%) and 1 termination. Among the 44 live births in which gestational age was reported, 39 (89%) were term, and 5 (11%) were preterm. These data show higher percentages of miscarriage and preterm delivery in metreleptin-treated women with lipodystrophy. However, conclusions are limited by extremely low numbers of patients with GL with metreleptin unexposed pregnancies (n=4) and PL with metreleptin-exposed pregnancies (n=2). Furthermore, these data may be biased by differences in underlying disease severity in metreleptin treated vs. untreated patients, as well as underreporting of early-term miscarriages. We therefore plan a prospective study to collect pregnancy outcomes in women with metreleptin-treated and untreated pregnancies.