Embryo/fetal development in cynomolgus monkeys exposed to natalizumab, an α4 integrin inhibitor

Abstract

Natalizumab had no abortifacient or teratogenic effects, but was associated with changes in fetal hematopoiesis and leukocyte trafficking.

Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study

“…Studies of natalizumab in MS have shown reduced relapse rates and disability progression, but less is known about its effects on pregnancy outcomes [10, 11]. Natalizumab is classified as a pregnancy category C drug, as potential fetal effects have been reported in animal studies [12–14] and there is a paucity of well-controlled human studies [6]. Although some animal studies have shown that natalizumab can cross the placental barrier and produce hematologic effects on fetal guinea pigs and primates [6, 12, 14, 15], others have not shown fetal interaction [16].…”

“…Natalizumab is classified as a pregnancy category C drug, as potential fetal effects have been reported in animal studies [12–14] and there is a paucity of well-controlled human studies [6]. Although some animal studies have shown that natalizumab can cross the placental barrier and produce hematologic effects on fetal guinea pigs and primates [6, 12, 14, 15], others have not shown fetal interaction [16]. Human studies and case reports have not shown increases in spontaneous abortions or birth defects; however, results are limited by small sample sizes [17–20].…”

Development in the cynomolgus macaque following administration of ustekinumab, a human anti‐il‐12/23p40 monoclonal antibody, during pregnancy and lactation

“…In order to evaluate any potential effects of ustekinumab treatment during pregnancy, it was necessary to conduct developmental studies in cynomolgus macaques. The cynomolgus macaque is a species frequently used for the non-clinical safety evaluation of human therapeutic monoclonal antibodies (Chellman et al, 2009;Martin, 2008;Martin et al, 2007Martin et al, , 2009Wehner et al, 2009). The cynomolgus macaque is physiologically and endocrinologically similar to humans (Chellman et al, 2009;Weinbauer et al, 2008a,b).…”

Update on reproductive safety of current and emerging disease-modifying therapies for multiple sclerosis

“…However, in preclinical studies, no cardiac abnormalities were reported in monkeys treated with doses up to 30 mg/kg. 14 Information on pregnancy outcomes is limited. In the natalizumab MS and Crohn's disease clinical trial program, 41 pregnancies were reported.…”