SUMMARY

• The company cannot recommend any practices, procedures or usage that deviate from the approved labeling.
• Please refer to the local labeling for additional information on TREMFYA and pregnancy.
• In moderate to severe plaque psoriasis (PsO), data from 24 pregnant women exposed to TREMFYA in the clinical development program are summarized below.¹
• Pregnancy outcomes of women with moderate to severe plaque PsO enrolled in the PSOLAR registry study are summarized below.^2,3
• The Organization of Teratology Information Specialists (OTIS) is a non-profit professional scientific organization comprised of experts in the field of assessing and evaluating risks to pregnancy and breastfeeding outcomes from medications and other exposures. OTIS and its information service, MotherToBaby, provide evidence-based information to parents, health professionals, and the general public. Currently, MotherToBaby is enrolling pregnant women in a registry-based study examining the use of TREMFYA to treat psoriasis or psoriatic arthritis during pregnancy. North American (United States and Canada) patients should be encouraged to enroll by visiting https://mothertobaby.org/ongoing-study/tremfya-guselkumab or by calling 1-877-311-8972.^4,5

BACKGROUND

• In TREMFYA clinical studies, pregnant females and females who intend to become pregnant were excluded from participation.¹
• Patients who enrolled in TREMFYA clinical studies were instructed to use highly effective methods of contraception during the study period.¹
• If patients became pregnant, TREMFYA was discontinued.¹

Clinical Data in moderate to severe plaque psoriasis

TREMFYA Clinical Development Program

Kimball et al (2020)¹ reported the pregnancy outcomes of women exposed to TREMFYA in the clinical development program.

Study Design/Methods

• Pregnancy cases reported from female participants (maternal pregnancy) across all indications in the clinical development program for TREMFYA with suspected exposure during any time of pregnancy or within 3 months prior to conceptions were reviewed.
• The dataset included unblinded medically confirmed individual patient cases within the Global Medical Safety global safety database through 12 July 2019.

Results

• A total of 24 maternal pregnancies were reported (Table: Characteristics of Cases Reporting Maternal Pregnancy for TREMFYA-treated Patients in the Clinical Development Program).
  • Suspected exposure to TREMFYA occurred during the first trimester in all pregnancies.

• A summary of pregnancy outcomes is noted in Table: Pregnancy Outcomes for TREMFYA-treated Patients Across All Indications in the Clinical Trials and Real World Development Program.

• The mean age of the female participants with the 7 live birth cases was 32.3 years. The mean±SD gestational age was 40.1±0.8 weeks (n=7), the mean±SD 5-minute APGAR was 9.7±0.6 (n=3), and the mean±SD birth weight was 7.8±1.0 pounds (n=5). No congenital anomalies were reported in the 7 live birth cases.
• Among the 2 spontaneous abortion cases, 1 case involved a 38-year-old female who had a history of 2 elective/induced abortions, and no risk factors were reported in the other case (26-year-old female). Both women participated in a clinical study of TREMFYA as healthy patients.
• The ages of the female participants with elective/induced abortion were 26 and 38 years old.
• One case reporting abortion missed, (unspecified) concerned a 31-year-old female with a medical history of 1 other spontaneous abortion. No other risk factors were reported.

PSOLAR Registry Study

Kimball et al (2020)² and Kimball et al (2021)³ reported pregnancy outcomes of women with moderate to severe PsO enrolled in the Psoriasis Longitudinal Assessment Registry (PSOLAR) registry study.

Study Design/Methods

• PSOLAR is a multicenter, disease-based, observational study evaluating long-term safety and clinical outcomes of patients receiving (or eligible to receive) treatment for PsO with biologics and/or conventional systemic agents.
• All pregnancy data for this registry study were considered based on exposure to ustekinumab, infliximab (not including biosimilars) or golimumab/golimumab IV, other sponsor biologic (eg, predominantly etanercept and adalimumab but could also include TREMFYA, secukinumab, risankizumab, alefacept, efalizumab, tildrakizumab, brodalumab, and ixekizumab) within, or outside of, the prenatal period.
  • Within the prenatal period: exposure to agent within 1 year prior to birth or within 6 months prior to spontaneous abortion
  • Outside the prenatal period: exposure to agent at any other time outside the above parameters

Results

• As of August 2019, 5456 of 12,090 (45.1%) patients enrolled in PSOLAR were female.³
• A total of 2224 women (12,929 patient-years of follow-up) were of childbearing age (18-45 years).
• In PSOLAR, the general fertility rate was 18.9/1000 annually in women 18-45 years of age.
• Available data for 298 pregnancies in 220 patients (median duration of enrollment, 7.2 [range, 3.3-8.0] years per patient) were summarized: 159 patients with 1 pregnancy, 48 patients with 2 pregnancies, 10 patients with 3 pregnancies, and 3 patients with 4 or 5 pregnancies.
• Clinical characteristics of the pregnancy cohort and the females of childbearing age cohort are noted in Table: Demographic and Clinical Characteristics in the Pregnancy Cohort and in All Women of Childbearing Age in PSOLAR.

Demographic and Clinical Characteristics in the Pregnancy Cohort and in All Women of Childbearing Age in PSOLAR^3a

• Of 298 pregnancies, there were 244 births (81.9%; including 1 stillbirth), 41 (13.8%) spontaneous abortions, and 13 (4.4%) elective terminations.³
  • No elective terminations were known to derive from a congenital anomaly or other medical issue.
• Most live births (90.9%; 221/243) were full term and 9.1% (22/243) were premature.
• Among the live births, 2 congenital anomalies were reported; both occurred in women who had received ustekinumab during the prenatal period.
  • One premature newborn (gestational age of 36 weeks) with a posterior cleft palate required hospitalization for 16 days. The infant also had a left coronal craniosynostosis. The mother of the infant received her last dose of ustekinumab
    26 days before birth.
  • A full-term newborn was born with nonketotic hyperglycinemia requiring tube feeding, ventilation, and hospitalization for 3 weeks. The mother of the infant realized she was pregnant approximately 10 months after starting ustekinumab therapy; treatment was discontinued at that time and gave birth more than 7 months later.
• A total of 10 infants had neonatal adverse events (3 respiratory issues [2 related to prematurity and 1 to aspiration pneumonia], 2 preterm deliveries related to pre-eclampsia, and 1 each of the following: ABO blood type mismatch, low birth weight due to early delivery [1 of 2 infants in a twin birth], opioid withdrawal, hyperemesis, and hypoglycemia).
• A total of 252 pregnancies occurred in women who were exposed to biologic therapy before or during pregnancy, 168 of which had exposure during the prenatal period.
• A total of 46 pregnancies occurred in women who were never exposed to biologic therapy but may have received another systemic therapy or phototherapy before or during pregnancy
• The pregnancy outcomes are detailed in Table: Pregnancy Outcomes by Age Group and Table: Pregnancy Outcomes by Time of Exposure (Biologics and Non-biologics) as of August 2018 and Table: Pregnancy Outcomes by Time of Exposure to Biologic and Nonbiologic Therapies as of August 2019.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 12 March 2024.