Development in the cynomolgus macaque following administration of ustekinumab, a human anti-IL-12/23p40 monoclonal antibody, during pregnancy and lactation.
BACKGROUND
Ustekinumab is a human monoclonal antibody that binds to the p40 subunit of interleukin (IL) 12 and IL-23 and inhibits their pharmacological activity. To evaluate potential effects of ustekinumab treatment during pregnancy, developmental studies were conducted in cynomolgus macaques.


METHODS
Ustekinumab was tested in two embryo/fetal development (EFD) studies and in a combined EFD/pre and postnatal development (PPND) study. In the EFD studies, pregnant macaques (12/group) were dosed with saline or ustekinumab (9 mg/kg IV, 22.5 mg/kg SC, or 45 mg/kg IV or SC during the period of major organogenesis, gestation day [GD] 20-50). Fetuses were harvested on GD100-102 and examined for any effects on development. In the EFD/PPND study, pregnant macaques were injected with saline or ustekinumab (22.5 or 45 mg/kg SC) from GD20 through lactation day 33. Infants were examined from birth through 6 months of age for morphological and functional development. Potential effects on the immune system were evaluated by immunophenotyping of peripheral blood lymphocytes and immunohistopathology of lymphoid tissues in fetuses and infants and by T-dependent antibody response (TDAR) to KLH and TTX and by DTH response in infants. Ustekinumab concentrations were measured in serum from dams, fetus, and infants and in breast milk.


RESULTS
Ustekinumab treatment produced no maternal toxicity and no toxicity in the fetuses or infants, including no effects on the TDAR or DTH responses. Ustekinumab was present in serum from GD100 fetuses and was present in infant serum through day 120 post-birth. Low levels of ustekinumab were present in breast milk.


CONCLUSIONS
Exposure of macaque fetuses and infants to ustekinumab had no adverse effects on pre- and postnatal development.
Centocor Research and Development, Inc., Radnor, Pennsylvania 19087, USA. pmarti27@its.jnj.com
Pauline L
PL
Martin
Clifford
C
Sachs
Noritaka
N
Imai
Hideshi
H
Tsusaki
Satoru
S
Oneda
Qun
Q
Jiao
George
G
Treacy
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000917:Antibody Formation; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007223:Infant; D007774:Lactation / Q000187:drug effects*; D008252:Macaca fascicularis / Q000196:embryology* / Q000276:immunology; D011247:Pregnancy; D000069549:Ustekinumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069549:Ustekinumab