SUMMARY

• Please refer to your local labeling for information on STELARA and its effect on fertility.
• The effect of STELARA on human fertility has not been evaluated.¹
• A female fertility toxicity study in mice, and a male fertility study in cynomolgus monkeys are described below.¹
• A real-world study evaluating safety outcomes in patients within the United States (US) Food and Drug Administration Adverse Event Reporting System (FAERS) database who received STELARA for the treatment of psoriasis (PsO) or psoriatic arthritis (PsA) was reported.²
• A prospective study reported the effect of STELARA on sperm deoxyribonucleic acid (DNA) integrity and semen in patients with CD or UC.³
• A retrospective study evaluated neonatal outcomes of pregnancies who had paternal exposure to STELARA within 90 days of conception for the treatment of inflammatory bowel disease (IBD), PsO, PsA, rheumatoid arthritis (RA), or ankylosing spondylitis (AS).⁴
• A data review described pregnancy cases and outcomes in patients within the Janssen Global Medical Safety database who received STELARA for the treatment of PsO, PsA, Crohn’s disease (CD), or ulcerative colitis (UC).⁵
• A retrospective study that observed the effect of STELARA on paternal fertility in male patients with PsO was reported.⁶

COMPANY CORE DATA SHEET

Pregnancy, Breastfeeding, and Fertility

Fertility

The effect of STELARA on human fertility has not been evaluated. No adverse effects on female fertility parameters were identified in a female fertility toxicity study conducted in mice.¹

STELARA Non-Clinical Information

Reproductive Toxicology

Three developmental toxicity studies were conducted in cynomolgus monkeys. No ustekinumab-related maternal toxicity, abortions, still-births, embryotoxicity, developmental delays, malformations or birth defects were observed at doses up to 45 mg/kg following weekly or twice weekly administration of ustekinumab via the intravenous or subcutaneous (SC) routes, respectively. In neonates born from pregnant monkeys treated with ustekinumab no adverse effects on growth or functional development were observed and no deficits were observed in immunotoxicity evaluations. In a male fertility study in cynomolgus monkeys, no ustekinumab related effects on mating behavior, sperm parameters, or serum concentrations of male hormones were observed following twice weekly SC administration of ustekinumab at doses up to 45 mg/kg.¹

A female fertility toxicity study was conducted in mice using an analogous antibody that binds to and inhibits interleukin (IL)-12 and IL-23 activity in mice. Twice weekly SC administration of anti-mouse IL-12/23 antibody was well tolerated at doses up to 50 mg/kg and no adverse effects on female fertility parameters were observed.¹

CLINICAL DATA – PsO and PsA

Real-World Study

Zheng et al (2025)² described safety outcomes in patients within the US FAERS database (through the fourth quarter of 2009 to the third quarter of 2024) who received STELARA for the treatment of PsO and PsA.

• The study focused on 67,765 STELARA-related adverse event (AE) reports, with STELARA identified as a primary suspect.
• Adverse drug event (ADE) reports for STELARA were submitted by consumers (n=9169; 37.16%), physicians (n=5912; 23.96%), and other healthcare professionals (n=5171; 20.96%).
• Overall, 12,263 female patients (49.70%) and 11,461 male patients (46.45%) with PsO and PsA reported ADEs related to STELARA.
• There were 9110 cases (36.92%) marked as unknown where age was not specified. Among the 7753 cases (31.42%) where age was known, the mean age was 55 years (range, 44-64 years).
• STELARA-related ADEs are presented in Table: Signal Strength of STELARA-Related ADEs at SOC Level and PT Level.

CLINICAL DATA - IBD

Prospective Study

Grosen et al (2022)³ conducted a prospective study to assess the effect of STELARA on sperm DNA integrity and semen according to World Health Organization (WHO) criteria in patients with CD or UC at 2 tertiary centers located in the US and Denmark.

• Male patients with CD or UC were included in this study if they were between the ages of 18-45 years and received STELARA maintenance therapy for more than 3 months.
• A healthy control group was used for comparison, which consisted of first-time contacts to a sperm bank.
• Semen volume, sperm concentration, morphology, and motility were recorded.
  • Morphology was analyzed by Kruger’s strict criteria.
  • Motility was recorded as total motility and progressive motility and expressed as percentages.
  • Sperm fragmentation was expressed using the DNA fragmentation index (DFI) and a DFI above 20% was associated with reduced fertility.
• Sperm DNA fragmentation was analyzed using flowcytometric technique sperm chromatin structure assay (SCSA) in a single, certified fertility lab.
• Seminal plasma and serum samples were assessed for ustekinumab concentrations. Additionally, blanks seminal plasma samples were used as negative controls.
• There were 12 patients and 40 healthy controls included in this study. Eleven of the 12 patients had CD and 3 patients were receiving concomitant adalimumab treatment.
• All 12 patients received STELARA 90 mg every 6-12 weeks and with a median duration of therapy of 7.5 (range, 3.7-15.7) months before providing the sample.
• Semen samples were provided a median of 15 (range, 0-56) days after the most recent injection of STELARA.
• One couple conceived while the patient was receiving STELARA; another patient started STELARA while his partner was in the second trimester (gestational week 14) of pregnancy. Both pregnancies were uncomplicated and resulted in 2 healthy children.
• For differences in semen parameters between patients treated with STELARA and healthy controls, please see Table: Semen Parameters in Patients Treated With STELARA vs Healthy Controls.

• One of the 3 patients receiving concomitant therapy with adalimumab had impaired sperm motility (progressive motility 7.7%; lower WHO reference limit ≥32%). All other parameters were above lower WHO reference limits and the median DFI was 15 (range, 14-17).
• STELARA was not detected in seminal plasma samples of 10 patients assessed with available samples.

CLINICAL DATA - PsO, PsA, IBD, RA, or AS

Retrospective Study

Barber et al (2022)⁴ conducted a retrospective cohort study that evaluated 958,804 pregnancies of which 13,535 pregnancies involved a paternal immune-mediated diagnosis including IBD, PsO, PsA, RA, or AS.

• A total of 80 pregnancies had paternal exposure to IBD medications, including STELARA (defined as having an insurance claim for the medication within 90 days of conception).
• The neonatal outcomes of these paternal exposures are summarized in Table: Paternal Exposure to STELARA and Neonatal Outcomes.

CLINICAL DATA - PsO, PsA, or IBD,

Global Medical Safety Database

Mahadevan et al (2022)⁵ described pregnancy cases and outcomes in patients within the Janssen Global Medical Safety database (through August 2020) who received STELARA for the treatment of PsO, PsA, CD, or UC.

Study Design/Methods

• Paternal exposure was approximated in the pregnancies where the father was exposed to STELARA periconceptionally.
• Paternal exposure to ustekinumab was defined as exposure in the period from 15 weeks (5 half-lives) prior to and including conception date.

Results

• There were 133 pregnancies with paternal exposure to STELARA of which 10 pregnancy cases reported paternal exposure prior to conception and 123 cases reported exposure around conception/T1 (first trimester).
• The exact date of conception was not reported and was extrapolated from the last menstrual period (36 pregnancies [27.1%]) or pregnancy due date (85 pregnancies [63.9%]).
• Adverse pregnancy outcomes with paternal exposure to STELARA for prospectively and all (prospectively and retrospectively) pregnancies were reported in 9.2% (8/87) pregnancies and 13.3% (15/113) pregnancies, respectively.
• In the prospective analysis, there was 1 pregnancy (1.2%) reported major congenital anomalies among the live birth, which was a polydactyly ulnar aspect left hand.
• For a summary of medically confirmed known paternal pregnancy outcomes in patients treated with STELARA, please see Table: Confirmed Paternal Pregnancy Outcomes of Patients Treated With STELARA for PsO, PsA, CD, or UC.

CLINICAL DATA - PsO

Retrospective Study

Filippi et al (2020)⁶ conducted a retrospective study evaluating the effects of biologic therapy on paternal exposure in 500 male patients with moderate to severe PsO in Italy from 2009 to 2019.

• Paternal exposure to biologics was defined as the time after at least one administration prior to conception. There were 32 male patients who fathered 38 children while receiving biologic therapy. Of these patients, 6 patients were receiving STELARA.
• The mean age at conception and mean disease duration were 37±5.3 years and 17.3±7.5 years, respectively.
• No male patients in this study required fertility assistance and there were no congenital defects or cognitive disorders observed at birth and at the time of this analysis (maximum follow-up period: 10 years).
• Patient characteristics of those that fathered children while receiving STELARA can be found in Table: Characteristics of Male Patients With Psoriasis who Fathered Children While Receiving STELARA.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 25 March 2025.