TREMFYA

Indications and Usage ( 1.1 , 1.2 ) 09/2025 Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.5 ) 09/2025 Dosage and Administration ( 2.4 ) 09/2025 Warnings and Precautions ( 5.2 , 5.4 ) 09/2025

1 INDICATIONS AND USAGE TREMFYA is an interleukin-23 antagonist indicated for the treatment of: adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with moderate-to-severe plaque psoriasis and who are candidates for systemic therapy or phototherapy. ( 1.1 ) adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with active psoriatic arthritis. ( 1.2 ) adults with moderately to severely active ulcerative colitis. ( 1.3 ) adults with moderately to severely active Crohn's disease. ( 1.4 ) 1.1 Plaque Psoriasis TREMFYA is indicated for the treatment of adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with moderate-to-severe plaque psoriasis and who are candidates for systemic therapy or phototherapy. 1.2 Psoriatic Arthritis TREMFYA is indicated for the treatment of adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with active psoriatic arthritis. 1.3 Ulcerative Colitis TREMFYA is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis. 1.4 Crohn's Disease TREMFYA is indicated for the treatment of adult patients with moderately to severely active Crohn's disease.

2 DOSAGE AND ADMINISTRATION For the treatment of ulcerative colitis or Crohn's disease: Obtain liver enzymes and bilirubin levels prior to initiating treatment with TREMFYA. ( 2.1 , 5.4 ). For the treatment of plaque psoriasis or psoriatic arthritis, if clinically indicated, evaluate liver enzymes and bilirubin at baseline prior to initiating treatment with TREMFYA ( 2.1 , 5.4 ). Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to treatment initiation. ( 2.1 ) Recommended Dosage Plaque Psoriasis Adults 100 mg administered by subcutaneous injection at Week 0, Week 4, and every 8 weeks thereafter. ( 2.2 ) Pediatric Patients 6 Years of Age and Older Who Also Weigh at Least 40 kg 100 mg administered by subcutaneous injection at Week 0, Week 4, and every 8 weeks thereafter. ( 2.2 ) Psoriatic Arthritis Adults 100 mg administered by subcutaneous injection at Week 0, Week 4, and every 8 weeks thereafter. TREMFYA can be used alone or in combination with a conventional DMARD (e.g., methotrexate). ( 2.3 ) Pediatric Patients 6 Years of Age and Older Who Also Weigh at Least 40 kg 100 mg administered by subcutaneous injection at Week 0, Week 4, and every 8 weeks thereafter. TREMFYA may be administered alone or in combination with a conventional disease-modifying antirheumatic drug (e.g., methotrexate). ( 2.3 ) Ulcerative Colitis and Crohn's Disease Induction : 200 mg administered by intravenous infusion over at least one hour at Week 0, Week 4, and Week 8 or 400 mg administered by subcutaneous injection at Week 0, Week 4, and Week 8. ( 2.4 ) Maintenance : 100 mg administered by subcutaneous injection at Week 16, and every 8 weeks thereafter, or 200 mg administered by subcutaneous injection at Week 12, and every 4 weeks thereafter. Use the lowest effective recommended dosage to maintain therapeutic response. ( 2.4 ) 2.1 Recommended Evaluations and Immunizations Prior to Treatment Initiation Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TREMFYA [see Warnings and Precautions (5.3) ] . For the treatment of ulcerative colitis or Crohn's disease, obtain liver enzymes and bilirubin levels prior to initiating treatment with TREMFYA [see Warnings and Precautions (5.4) ] . For the treatment of plaque psoriasis or psoriatic arthritis, if clinically indicated, evaluate liver enzymes and bilirubin prior to initiating treatment with TREMFYA [see Warnings and Precautions (5.4) ]. Complete all age-appropriate vaccinations according to current immunization guidelines [see Warnings and Precautions (5.5) ] . 2.2 Recommended Dosage for Moderate-to-Severe Plaque Psoriasis Administer TREMFYA by subcutaneous injection at Week 0, Week 4, and every 8 weeks thereafter. Adults The recommended dosage is 100 mg. Pediatric Patients 6 Years of Age and Older Who Also Weigh at Least 40 kg The recommended dosage is 100 mg. 2.3 Recommended Dosage for Active Psoriatic Arthritis Administer TREMFYA by subcutaneous injection at Week 0, Week 4, and every 8 weeks thereafter. TREMFYA may be administered alone or in combination with a conventional disease-modifying antirheumatic drug (e.g., methotrexate). Adults The recommended dosage is 100 mg. Pediatric Patients 6 Years of Age and Older Who Also Weigh at Least 40 kg The recommended dosage is 100 mg. 2.4 Recommended Dosage for Moderately to Severely Active Ulcerative Colitis and Crohn's Disease Adults Induction: The recommended induction dosage of TREMFYA is: 200 mg administered by intravenous infusion over at least one hour at Week 0, Week 4, and Week 8 [see Dosage and Administration (2.6) ] or 400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4, and Week 8. Maintenance: The recommended maintenance dosage of TREMFYA is: 100 mg administered by subcutaneous injection at Week 16, and every 8 weeks thereafter, or 200 mg administered by subcutaneous injection at Week 12, and every 4 we …

3 DOSAGE FORMS AND STRENGTHS TREMFYA is a clear and colorless to light yellow solution. Subcutaneous Injection Injection: 100 mg/mL in a single-dose One-Press patient-controlled injector. Injection: 100 mg/mL in a single-dose prefilled pen (TREMFYA PEN). Injection: 200 mg/2 mL in a single-dose prefilled pen (TREMFYA PEN). Injection: 100 mg/mL in a single-dose prefilled syringe. Injection: 200 mg/2 mL (100 mg/mL) in a single-dose prefilled syringe. Intravenous Infusion Injection: 200 mg/20 mL (10 mg/mL) solution in a single-dose vial. Subcutaneous Injection ( 3 ) Injection: 100 mg/mL in a single-dose One-Press patient-controlled injector. Injection: 100 mg/mL in a single-dose prefilled pen (TREMFYA PEN). Injection: 200 mg/2 mL in a single-dose prefilled pen (TREMFYA PEN). Injection: 100 mg/mL in a single-dose prefilled syringe. Injection: 200 mg/2 mL (100 mg/mL) in a single-dose prefilled syringe. Intravenous Infusion ( 3 ) Injection: 200 mg/20 mL (10 mg/mL) solution in a single-dose vial.

4 CONTRAINDICATIONS TREMFYA is contraindicated in patients with a history of serious hypersensitivity reaction to guselkumab or to any of the excipients [see Warnings and Precautions (5.1) ] . History of serious hypersensitivity reactions to guselkumab or to any of the excipients. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of labeling: Hypersensitivity Reactions [see Contraindications (4) and Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Tuberculosis [see Warnings and Precautions (5.3) ] Hepatotoxicity [see Warnings and Precautions (5.4) ] Most common adverse reactions associated with TREMFYA are: Plaque Psoriasis and Psoriatic Arthritis (≥1%): upper respiratory infections, headache, injection site reactions, arthralgia, bronchitis, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections. ( 6.1 ) Ulcerative Colitis (≥3%) : injection site reactions, arthralgia, upper respiratory tract infections, headache, gastroenteritis, fatigue, pyrexia, and rash. ( 6.1 ) Crohn's Disease (≥3%) : respiratory tract infections, abdominal pain, injection site reactions, headache, fatigue, arthralgia, diarrhea, and gastroenteritis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Adults with Plaque Psoriasis In clinical trials, a total of 1823 adult subjects with moderate-to-severe plaque psoriasis received TREMFYA. Of these, 1393 subjects were exposed to TREMFYA for at least 6 months and 728 subjects were exposed for at least 1 year. Data from two placebo- and active-controlled trials (PsO1 and PsO2) in 1441 subjects (mean age 44 years; 70% males; 82% white) were pooled to evaluate the safety of TREMFYA (100 mg administered subcutaneously at Weeks 0 and 4, followed by every 8 weeks). Weeks 0 to 16: In the 16-week placebo-controlled period of the pooled clinical trials (PsO1 and PsO2), adverse events occurred in 49% of subjects in the TREMFYA group compared to 47% of subjects in the placebo group and 49% of subjects in the U.S. licensed adalimumab group. Serious adverse events occurred in 1.9% of subjects in the TREMFYA group (6.3 events per 100 patient-years of follow-up) compared to 1.4% of subjects in the placebo group (4.7 events per 100 patient-years of follow-up), and in 2.6% of subjects in U.S. licensed adalimumab group (9.9 events per 100 patient-years of follow-up). Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the TREMFYA group than in the placebo group during the 16-week placebo-controlled period. Table 1: Adverse Reactions Occurring in ≥1% of Adult Subjects with Moderate-to-Severe Plaque Psoriasis through Week 16 in Trials PsO1 and PsO2 TREMFYA Subjects receiving 100 mg of TREMFYA at Week 0, Week 4, and every 8 weeks thereafter 100 mg N=823 n (%) Adalimumab U.S. licensed adalimumab N=196 n (%) Placebo N=422 n (%) Upper respiratory infections Upper respiratory infections include nasopharyngitis, upper respiratory tract infection (URTI), pharyngitis, and viral URTI. 118 (14.3) 21 (10.7) 54 (12.8) Headache Headache includes headache and tension headache. 38 (4.6) 2 (1.0) 14 (3.3) Injection site reactions Injection site reactions include injection site erythema, bruising, hematoma, hemorrhage, swelling, edema, pruritus, pain, discoloration, induration, inflammation, and urticaria. 37 (4.5) 15 (7.7) 12 (2.8) Arthralgia 22 (2.7) 4 (2.0) 9 (2.1) Diarrhea 13 (1.6) 3 (1.5) 4 (0.9) Gastroenteritis Gastroenteritis includes gastroenteritis and viral gastroenteritis. 11 (1.3) 4 (2.0) 4 (0.9) Tinea infections Tinea infections include tinea pedis, tinea cruris, tinea infection, and tinea manuum infections. 9 (1.1) 0 0 Herpes simplex infections Herpes simplex infections include oral herpes, herpes simplex, genital herpes, genital herpes simplex, and nas …

7 DRUG INTERACTIONS 7.1 CYP450 Substrates The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, interferon) during chronic inflammation. Results from an exploratory drug-drug interaction trial in subjects with moderate-to-severe plaque psoriasis suggested a low potential for clinically relevant drug interactions for drugs metabolized by CYP3A4, CYP2C9, CYP2C19 and CYP1A2 but the interaction potential cannot be ruled out for drugs metabolized by CYP2D6. However, the results were highly variable because of the limited number of subjects in the trial. Upon initiation of TREMFYA in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment as needed [see Clinical Pharmacology (12.3) ] .

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy registry that monitors pregnancy outcomes in women exposed to TREMFYA during pregnancy. Patients should be encouraged to enroll in the registry by visiting www.mothertobaby.org/ongoing-study/tremfya-guselkumab, by calling 1-877-311-8972, or emailing MotherToBaby@health.ucsd.edu. Risk Summary Available data from literature, post-marketing reports, and ongoing pregnancy registry with TREMFYA use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Monoclonal antibodies are actively transported across the placenta (see Clinical Considerations ). In a combined embryofetal development and pre- and post-natal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of guselkumab during organogenesis through parturition at doses up to 18 times the exposure (AUC) in humans administered 200 mg intravenously and 16 times the exposure (AUC) to the 400 mg dose given subcutaneously. Neonatal deaths in monkeys were observed at 4 to 18 times the exposure (AUC) in humans administered 200 mg intravenously and 4 to 16 times the exposure (AUC) to the 400 mg dose given subcutaneously (see Data ) . The clinical significance of these nonclinical findings is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated Maternal and Embryo/Fetal Risk Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. Fetal/Neonatal Adverse Reactions Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses and peaks during the third trimester. Therefore, TREMFYA may be present in infants exposed in utero . The potential clinical impact of guselkumab exposure in infants exposed in utero should be considered. Data Animal Data In a combined embryofetal development and pre- and post-natal development study, pregnant cynomolgus monkeys were administered weekly subcutaneous doses of guselkumab from the beginning of organogenesis to parturition at a dose (50 mg/kg) resulting in exposures (AUC) 18 times the exposure in humans administered 200 mg intravenously and 16 times the human exposure at 400 mg given subcutaneously. Neonatal deaths occurred in the offspring of one control monkey, three monkeys administered guselkumab at 10 mg/kg/week (4 times the exposure (AUC) in humans administered 200 mg intravenously or 400 mg given subcutaneously) and three monkeys administered guselkumab at 50 mg/kg/week (18 times the exposure (AUC) in humans administered 200 mg intravenously and 16 times the exposure (AUC) following a 400 mg subcutaneous dose). The clinical significance of these findings is unknown. No guselkumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age. 8.2 Lactation Risk Summary There are no data on the presence of guselkumab in human milk, the effects on the breastfed infant, or the effects on milk production. Guselkumab was not detected in the milk of lactating cynomolgus monkeys. Endogenous maternal IgG and monoclonal antibodies are transferred into human milk. The effects of local gastrointestinal exposure and the extent of systemic exposure in the breastfed infant to g …

12.1 Mechanism of Action Guselkumab is a human monoclonal IgG1λ antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Guselkumab inhibits the release of proinflammatory cytokines and chemokines.

11 DESCRIPTION Guselkumab, an interleukin-23 antagonist, is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. Guselkumab is produced in a mammalian cell line using recombinant DNA technology and has an approximate molecular weight of approximately 147 kDa. TREMFYA ® (guselkumab) injection is a sterile, preservative free, clear, and colorless to light yellow solution. TREMFYA for Subcutaneous Injection Available as a 100 mg/mL solution in a 1 mL or 2 mL glass prefilled syringe, in a 1 mL or 2 mL prefilled pen (TREMFYA PEN), or in a 1 mL One-Press patient-controlled injector for subcutaneous use. Each TREMFYA 1 mL prefilled syringe, prefilled pen (TREMFYA PEN), or One-Press patient-controlled injector delivers 100 mg guselkumab, L-histidine (0.6 mg), L-histidine monohydrochloride monohydrate (1.5 mg), polysorbate 80 (0.5 mg), sucrose (79 mg) and water for injection at pH 5.8. Each TREMFYA 2 mL prefilled syringe or prefilled pen (TREMFYA PEN) delivers 200 mg guselkumab, L-histidine (1.2 mg), L-histidine monohydrochloride monohydrate (3 mg), polysorbate 80 (1 mg), sucrose (158 mg) and water for injection at pH 5.8. TREMFYA for Intravenous Infusion Available as 10 mg/mL solution in a 20 mL single-dose vial for intravenous use. Each TREMFYA 20 mL vial delivers 200 mg guselkumab, EDTA disodium dihydrate (0.4 mg), L-histidine (11.3 mg), L-histidine monohydrochloride monohydrate (26.6 mg), L-methionine (8 mg), polysorbate 80 (10 mg), sucrose (1700 mg) and water for injection at pH 5.8.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied TREMFYA ® (guselkumab) injection is a clear and colorless to light yellow solution supplied as follows: Subcutaneous Injection Carton of one 100 mg/mL single-dose One-Press patient‐controlled injector (NDC: 57894-640-11) Carton of one 100 mg/mL single-dose prefilled pen (TREMFYA PEN) (NDC: 57894-640-06) Carton of one 200 mg/2 mL single-dose prefilled pen (TREMFYA PEN) (NDC: 57894-651-02) Induction Pack for Ulcerative Colitis or Crohn's Disease: Carton containing two 200 mg/2 mL single-dose prefilled pens (400 mg/4 mL total) (TREMFYA PEN) (NDC: 57894-651-04) Carton of one 100 mg/mL single-dose prefilled syringe with a 27G, half inch fixed needle assembled in a passive needle guard delivery system (NDC: 57894-640-01) Carton of one 200 mg/2 mL (100 mg/mL) single-dose prefilled syringe with a 27G, half inch fixed needle assembled in a passive needle guard delivery system (NDC: 57894-651-22) Intravenous Infusion Carton of one 200 mg/20 mL (10 mg/mL) single-dose vial (NDC: 57894-650-02) Storage and Handling TREMFYA is sterile and preservative-free. Discard any unused portion. Store in a refrigerator between 2 oC to 8 oC (36 oF to 46 oF). Store in original carton until time of use. Protect from light until use. Do not freeze. Do not shake. Not made with natural rubber latex.