Summary

• The company cannot recommend any practice, procedure, or usage that deviate from the approved labeling.
• Please refer to your local labeling for relevant information regarding STELARA use in nursing mothers.
• Previous animal studies on macaques have shown that there is about 1/1000^th of the serum blood concentration of ustekinumab in breast milk, which is assumed to undergo proteolysis in the stomach and possible degradation, and finally excretion in the gastrointestinal tract through the IgG Fc binding protein.¹
• There are data available from prospective studies and case reports that described the use of STELARA in nursing mothers.^2-6

COMPANY CORE DATA SHEET

Pregnancy, Breast-feeding and Fertility

Breast-feeding

Limited data from published literature suggests that ustekinumab is excreted in human breast milk in very small amounts. While systemic exposure to a breastfed infant is expected to be low because ustekinumab is a large molecule and is degraded in the gastrointestinal tract, it is not known if STELARA is absorbed systemically after ingestion. Because of the potential for adverse reactions in nursing infants from STELARA, a decision should be made whether to discontinue nursing or to discontinue the drug.⁷

PROSPECTIVE STUDIES

Bar-Gil Shitrit et al (2021)² measured ustekinumab levels in the breast milk of nursing mothers with Crohn’s disease (CD) in a single-center, prospective cohort study.

Study Design/Methods

• A total of 6 breastfeeding women were included in this study:
  • A group of 3 breastfeeding mothers with CD who were treated with an intravenous weight-based induction dose of ustekinumab (260 mg to 520 mg) and then 90 mg subcutaneously (SC) every 8 weeks (q8w). Due to a suboptimal response, 1 patient subsequently received 90 mg SC every 4 weeks.
    • Two patients started on ustekinumab before pregnancy and continued treatment throughout and after delivery.
    • The third patient began ustekinumab just after delivering.
  • A negative control group of 3 healthy breastfeeding women without inflammatory bowel diseases (IBD) who were not exposed to immunomodulatory/biologic treatment.
• Post-administration breast milk ustekinumab levels were compared to pre-administration trough serum levels on the day of ustekinumab administration.
  • First breast milk samples were collected 1 hour after the completion of ustekinumab administration.
  • Serum was measured once for each patient at the beginning of the study.
  • All patients provided daily sequential samples of breast milk for up to 2 weeks post-administration of ustekinumab.
  • Serum and breast milk ustekinumab levels were measured by an enzyme-linked immunosorbent assay.
• Infants were followed up for 6 months.

Results

• The serum ustekinumab levels and ustekinumab levels in breast milk samples are summarized in Table: Post-Drug Administration Breast Milk Levels Versus Pre-Drug Administration Trough Serum Levels.

• Ustekinumab levels from additional sequential breast milk samples on the following days post-drug administration are summarized in Table: Ustekinumab Breast Milk Level on the Following Days Post-Drug Administration.

• Ustekinumab was not detected in any of the 3 negative control patient breast milk samples.
• Follow-up of the infants to ages 3-6 months showed normal reaching of developmental milestones.
• No higher rate of infections or hospitalizations was observed.

Matro et al (2018)³ assessed detectability of biologic concentrations (including ustekinumab) in breast milk samples in a multicenter, prospective study of women with IBD and their infants. Pooled analyses on infant infections and developmental delays were also performed.

Study Design/Methods

• This study is part of the Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) registry. Actively breastfeeding women enrolled in the PIANO registry from October 2013 to November 2015 who were taking a biologic medication were asked to provide breast milk samples.
• Breast milk samples (0.5-2.0 mL/sample) were collected 1, 12, 24, and 48 hours after drug administration at various time points after birth. An amendment in December 2014 allowed collection of additional samples at 72, 96, 120, and 168 hours after dosing.
• The primary outcome was the drug concentration and/or detection of the biologic agent in breast milk samples at 1, 12, 24, and 48 hours after dosing and also at 72, 96, 120, and 168 hours from available samples.
• Pooled analyses of all breast milk samples (not specific to ustekinumab samples) were performed to assess the secondary outcomes, which included a range of infant infections and developmental delays defined by Ages and Stages Questionnaire 3 (ASQ3) among all breastfed infants.

Results

• Among the 824 women who completed the breastfeeding status questionnaire, submitted samples from 72 women receiving biologic therapy were analyzed for drug concentrations (infliximab, adalimumab, certolizumab pegol, golimumab, ustekinumab and natalizumab).
• Of the 72 women who submitted samples, 4 of 6 ustekinumab-treated patients had detectable ustekinumab concentrations in breast milk samples, with peak concentrations observed 12 to 72 hours after injection (peak range: 0.72 to 1.57 µg/mL).  
• All of the women with detectable concentrations provided samples out to 7 days and 3 of these women had ustekinumab concentrations in their breast milk detected beyond 48 hours.

Case reports

Saito et al (2022)⁴ described a case report of a 36-year-old female patient with ulcerative colitis (UC) who was treated with STELARA during pregnancy and lactation.

• The patient was diagnosed with UC at age 24. STELARA 90 mg subcutanous every 2-3 months was initiated 2 weeks before pregnancy confirmation and continued until week 29 of gestation (administered at 5, 17, and 29 weeks of gestation). Oral 5-aminosalicyclic acid (4800 mg/day) was also administered during pregnancy and lactation.
• During pregnancy, her UC symptoms remained in remission.
• Her baby was delivered via cesarean section at 38 weeks and 3 days of gestation. The infant’s Apgar score at 1 minute and 5 minutes were 8 and 9, respectively. Normal developmental progress and no congenital malformations were reported. The infant received routine vaccinations with no reported adverse events. Live vaccines, including the rotavirus and Bacillus Calmette-Guerin vaccines, were not administered until 6 months of life.
• STELARA therapy was resumed at week 7 postpartum.
• Ustekinumab was detected in infant serum (229.0 ng/mL) collected 71 days after the last maternal dose (5 days postpartum).
• Ustekinumab concentration in breast milk reached a peak at approximately 9 days after the fifth treatment (48 days postpartum) and decreased gradually thereafter.
• Maximum ustekinumab concentration in breastmilk was 13.6 ng/mL approximately 9 days after the last maternal dose (57 days postpartum). Detected ustekinumab concentrations are summarized in Table: Ustekinumab Concentrations in Maternal Serum, Cord Blood, Infant Serum, and Breast Milk.

Klenske et al (2019)⁵ described a case report of a 24-year-old female patient with CD who was treated with STELARA during pregnancy and breastfeeding.

• The patient had a 7-year history of refractory ileocolic CD. Prior treatments included azathioprine, adalimumab, infliximab, and vedolizumab. Patient also underwent an ileocecal resection.
• STELARA therapy was started with an induction dose of 390 mg and then 90 mg q8w. Clinical remission was achieved after 8 weeks and the patient became pregnant 14 weeks after initiation of STELARA.
• Treatment was continued due to her therapy-refractory disease course and STELARA was continued through week 30 of her pregnancy. Her baby was born healthy at week 38 of her pregnancy.
• STELARA was re-initiated with 390 mg 7 weeks after her delivery. Patient was receiving STELARA during breastfeeding. At month 12 of follow-up, complete normal physical and mental development of her baby were reported.
• Ustekinumab trough serum levels were reported throughout pregnancy and immediately after birth, in addition to the ustekinumab cord blood level at delivery. After ustekinumab re-initiation, ustekinumab levels in the breast milk were evaluated at different intervals, in addition to the serum trough level 16 weeks after re-initiation. Results are summarized in Table: Ustekinumab Drug Levels in the Serum Blood, Cord Blood, and Breast Milk.

Mugheddu et al (2019)⁶ described a case report of a 38-year-old female patient with severe psoriasis and the use of STELARA during pregnancy and breastfeeding.

• The patient had a history of biologic exposure within some of the duration of her 3 pregnancies (adalimumab, 1st pregnancy; ustekinumab, 2nd and 3rd pregnancy). A preterm delivery occurred in all 3 pregnancies and all babies were born healthy.
• During the first two pregnancies, biologic treatment was reintroduced immediately after breastfeeding. After her 3rd pregnancy, her psoriasis was completely unmanageable after delivery and she received ustekinumab during breastfeeding with no noted complication for her baby and a normal growth curve.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 19 December 2024.