TREMFYA

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 dose is 100 mg. Pediatric Patients 6 Years of Age and Older Who Also Weigh at Least 40 kg The recommended dose 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 dose is 100 mg. Pediatric Patients 6 Years of Age and Older Who Also Weigh at Least 40 kg The recommended dose 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 weeks thereafter. Use the lowest effective recommended dosage to maintain therapeutic response. 2.5 Preparation and Administration Instructions for Subcutaneous Injection TREMFYA is available for subcutaneous use in the following presentations: prefilled pen (TREMFYA PEN), One-Press injector, and prefilled syringes [see Dosage Forms and Strengths (3) and How Supplied/Storage and Handling (16) ] . Each prefilled pen, One-Press injector, or prefilled syringe is for one time use in one patient only. Instruct patients to inject the full amount: 100 mg or 200 mg of TREMFYA (1 mL or 2 mL, respectively). TREMFYA is intended for use under the guidance and supervision of a healthcare professional. After proper training in subcutaneous injection technique: Adults Adults may self-inject with the TREMFYA prefilled syringe, One-Press injector, and prefilled pen. Inject into the front of the thighs, the lower abdomen except for the 2 inches around the navel, or the back of the upper arms (healthcare professional or caregiver only). Pediatric Patients 6 Years of Age and Older Who Also Weigh at Least 40 kg Pediatric self-administration is not recommended. Administration of TREMFYA to pediatric patients with the prefilled syringe, One-Press injector and prefilled pen should be performed by a healthcare provider or by a caregiver who has received training and demonstrated proper subcutaneous injection technique. Inject into the front of the thighs or the lower abdomen except for the 2 inches around the navel. For the prefilled syringe only, injection can also be given in the back of the upper arms. Before injection, remove TREMFYA from the refrigerator and allow to reach room temperature up to 25 °C (77 °F) (30 minutes) without removing the needle cap. Do not inject TREMFYA into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis [see Instructions for Use ]. The TREMFYA Instructions for Use contains more detailed patient instructions on the preparation and administration of TREMFYA [see Instructions for Use ] . If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time. Inspect TREMFYA visually for particulate matter and discoloration prior to administration. TREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles. Do not use if the liquid contains large particles, is discolored or cloudy. TREMFYA does not contain preservatives; therefore, discard any unused product remaining in the prefilled pen, One-Press injector, or prefilled syringe. 2.6 Preparation and Administration Instructions for Intravenous Infusion (Moderately to Severely Active Ulcerative Colitis and Crohn's Disease) Preparation Instructions : Withdraw and then discard 20 mL of the 0.9% Sodium Chloride Injection from the 250 mL infusion bag which is equal to the volume of TREMFYA to be added. Withdraw 20 mL of TREMFYA from the vial and add it to the 250 mL intravenous infusion bag of 0.9% Sodium Chloride Injection for a final concentration of 0.8 mg/mL. Gently mix the diluted solution. Discard the vial with any remaining solution. Visually inspect the diluted solution for particulate matter and discoloration before infusion. Infuse the diluted solution over a period of at least one hour. Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein binding filter (pore size 0.2 micrometer). Do not infuse TREMFYA concomitantly in the same intravenous line with other medicinal products. Dispose any unused medicinal product in accordance with local requirements. Administration Instructions : TREMFYA solution for intravenous infusion must be diluted, prepared, and infused by a healthcare professional using aseptic technique. TREMFYA does not contain preservatives. Each vial is for one time use in one patient only. Inspect TREMFYA visually for particulate matter and discoloration prior to administration. TREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles. Do not use if the liquid contains large particles, is discolored, or is cloudy. Storage of Diluted Solution: The diluted infusion solution may be kept at room temperature up to 25 °C (77 °F) for up to 10 hours. Storage time at room temperature begins once the diluted solution has been prepared. The infusion should be completed within 10 hours after the dilution in the infusion bag. Do not freeze. Discard any unused portion of the infusion solution.

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) ] . Serious hypersensitivity reactions to guselkumab or to any of the excipients. ( 4 )

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions : Serious hypersensitivity reactions, including anaphylaxis, may occur. ( 5.1 ) Infections : TREMFYA may increase the risk of infections. Do not initiate treatment with TREMFYA in patients with clinically important active infection until the infection resolves or is adequately treated. If such an infection develops, discontinue TREMFYA until the infection resolves. ( 5.2 ) Tuberculosis (TB) : Evaluate for TB prior to initiating treatment with TREMFYA. Monitor patients for signs and symptoms of active TB during and after treatment with TREMFYA. ( 5.3 ) Hepatotoxicity : Drug-induced liver injury has been reported. For the treatment of ulcerative colitis or Crohn’s disease, evaluate liver enzymes and bilirubin levels at baseline, for at least 16 weeks of treatment, and periodically thereafter according to routine patient management. For the treatment of plaque psoriasis or psoriatic arthritis, if clinically indicated, evaluate liver enzymes and bilirubin at baseline, and periodically thereafter according to routine patient management. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. ( 5.4 ) Immunizations : Avoid use of live vaccines. ( 5.5 ) 5.1 Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis, have been reported with post market use of TREMFYA. Some cases required hospitalization. If a serious hypersensitivity reaction occurs, discontinue TREMFYA and initiate appropriate therapy. 5.2 Infections TREMFYA may increase the risk of infection [see Adverse Reactions (6.1) ] . In placebo-controlled clinical trials of up to 48 weeks in subjects with ulcerative colitis and Crohn’s disease, serious infections occurred in ≤ 2% of subjects who received TREMFYA. In the 16-week placebo-controlled trials in subjects with plaque psoriasis, the rate of serious infections for the TREMFYA group and the placebo group was ≤ 0.2%. A similar rate of serious infections was seen in placebo-controlled trials in subjects with psoriatic arthritis. The overall rates of infections were similar between subjects in the TREMFYA groups and subjects in the placebo groups in clinical trials for all indicated populations [see Adverse Reactions (6.1) ] . Treatment with TREMFYA should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated. In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing TREMFYA. Instruct patients to seek medical help if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, monitor the patient closely and discontinue TREMFYA until the infection resolves. 5.3 Tuberculosis Evaluate patients for tuberculosis (TB) infection prior to initiating TREMFYA treatment. Do not administer TREMFYA to patients with active TB infection. Initiate treatment of latent TB prior to administering TREMFYA. Consider anti-TB therapy prior to initiating TREMFYA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor all patients for signs and symptoms of active TB during and after TREMFYA treatment. In clinical trials, 105 subjects with plaque psoriasis, 71 subjects with psoriatic arthritis, 43 subjects with ulcerative colitis, and 36 subjects with Crohn's disease with latent TB who were concurrently treated with TREMFYA, and appropriate TB prophylaxis did not develop active TB. In clinical trials of TREMFYA in subjects with Crohn's disease, active TB was reported in 2 subjects during treatment with TREMFYA [see Adverse Reactions (6.1) ] . 5.4 Hepatotoxicity A serious adverse reaction of drug-induced liver injury was reported in a clinical trial subject with Crohn's disease following three doses of a higher than the recommended induction regimen. This subject had peak alanine aminotransferase (ALT) of 18x the upper limit of normal (ULN), aspartate aminotransferase (AST) of 11x ULN, and total bilirubin of 2.4x ULN. TREMFYA was subsequently discontinued, and the liver test abnormalities resolved following administration of corticosteroids [see Adverse Reactions (6.1) ] . In patients with ulcerative colitis or Crohn's disease, evaluate liver enzymes and bilirubin at baseline, for at least 16 weeks of treatment, and periodically thereafter according to routine patient management. In patients with plaque psoriasis or psoriatic arthritis, if clinically indicated, evaluate liver enzymes and bilirubin at baseline, and periodically thereafter according to routine patient management. Consider other treatment options in patients with evidence of acute liver disease or cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction. 5.5 Immunizations Avoid use of live vaccines in patients treated with TREMFYA. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines. Prior to initiating therapy with TREMFYA, complete all age-appropriate vaccinations according to current immunization guidelines. No data are available on the response to live or inactive vaccines.

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) ] .

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 nasal herpes simplex. 9 (1.1) 0 2 (0.5) Adverse reactions that occurred in < 1% but > 0.1% of subjects in the TREMFYA group and at a higher rate than in the placebo group through Week 16 in trials PsO1 and PsO2 were migraine, candida infections, and urticaria. Specific Adverse Reactions Infections Infections occurred in 23% of subjects in the TREMFYA group compared to 21% of subjects in the placebo group through 16 weeks of treatment. The most common (≥ 1%) infections that occurred more frequently in the TREMFYA group than in the placebo group were upper respiratory infections, gastroenteritis, tinea infections, and herpes simplex infections; all cases were mild to moderate in severity and did not lead to discontinuation of TREMFYA. The rate of serious infections for the TREMFYA group and the placebo group was ≤ 0.2%. Elevated Liver Enzymes Elevated liver enzymes were reported more frequently in the TREMFYA group (2.6%) than in the placebo group (1.9%). Of the 21 subjects who were reported to have elevated liver enzymes in the TREMFYA group, all events except one were mild to moderate in severity and none of the events led to discontinuation of TREMFYA. Safety through Week 48 Through Week 48, no new adverse reactions were identified with TREMFYA use and the frequency of the adverse reactions was similar to the safety profile observed during the first 16 weeks of treatment. Adverse Reactions in Pediatric Subjects with Plaque Psoriasis The safety of TREMFYA was studied in one placebo- and active-controlled clinical trial (PsO5) that included 120 pediatric subjects 6 years of age and older with moderate-to-severe plaque psoriasis [see Clinical Studies (14.1) ] . The safety profile observed in pediatric subjects 6 years of age and older treated with TREMFYA up to 52 weeks was consistent with the safety profile observed in adult subjects with moderate-to-severe plaque psoriasis. Adverse Reactions in Adults with Psoriatic Arthritis TREMFYA was studied in two placebo-controlled trials in adult subjects with psoriatic arthritis (748 subjects on TREMFYA and 372 subjects on placebo). Of the 748 subjects who received TREMFYA, 375 subjects received TREMFYA 100 mg at Week 0, Week 4, and every 8 weeks thereafter and 373 subjects received TREMFYA 100 mg every 4 weeks. The overall safety profile observed in adult subjects with psoriatic arthritis treated with TREMFYA is generally consistent with the safety profile in adult subjects with plaque psoriasis with the addition of bronchitis and neutrophil count decreased. In the 24-week placebo-controlled period, combined across the two studies, bronchitis occurred in 1.6% of subjects in the TREMFYA q8w group and 2.9% of subjects in the TREMFYA q4w group compared to 1.1% of subjects in the placebo group. Neutrophil count decreased occurred in 0.3% of subjects in the TREMFYA q8w and 1.6% of subjects in the TREMFYA q4w group compared to 0% of subjects in the placebo group. The majority of events of neutrophil count decreased were mild, transient, not associated with infection and did not lead to discontinuation. A similar risk of infection and serious infections was seen in placebo-controlled trials in subjects with psoriatic arthritis as in subjects with plaque psoriasis. Adverse Reactions in Adults with Ulcerative Colitis TREMFYA was studied up to 12 weeks in adult subjects with moderately to severely active ulcerative colitis in a randomized, double-blind, placebo-controlled induction trial (UC1) and a randomized, double-blind, placebo-controlled, induction dose-finding trial (UC3; NCT04033445). Long-term safety up to 44 weeks was evaluated in subjects who responded to induction therapy in trials UC1 or UC3 in a randomized, double-blind, placebo-controlled maintenance trial (UC2). In a randomized, double-blind, placebo-controlled trial (UC4), subjects received subcutaneous TREMFYA at Weeks 0, 4, and 8 followed by one of two recommended subcutaneous TREMFYA dosing regimens for a total duration of up to 24 weeks [see Clinical Studies (14.3) ] . Trials UC1, UC2 and UC3 In the induction trials (UC1 and UC3), 522 subjects received at least one dose of the TREMFYA intravenous induction regimen (i.e., 200 mg at Week 0, Week 4, and Week 8). Clinical response was defined as a decrease in modified Mayo score (mMS) of ≥30% and ≥2 points from baseline with either a ≥1 decrease from baseline in rectal bleeding subscore (RBS) or RBS of 0 or 1. In the maintenance trial (UC2), subjects who achieved clinical response after 12 weeks of TREMFYA intravenous induction treatment were randomized and received either TREMFYA 100 mg every 8 weeks (with the first dose given at Week 4 of trial UC2) or TREMFYA 200 mg every 4 weeks (with the first dose given at Week 0 of trial UC2), by subcutaneous (SC) injection for up to an additional 44 weeks. Respiratory tract infections occurred in ≥2% of subjects treated with TREMFYA and at a higher rate than placebo (8.8% TREMFYA-treated subjects vs. 7.3% placebo-treated subjects) through Week 12 in the induction trials (UC1 and UC3). Respiratory tract infections included COVID-19, influenza, nasopharyngitis, respiratory tract infection, upper respiratory tract infection, and viral respiratory tract infection. Adverse reactions that occurred in ≥3% of subjects treated with TREMFYA and at a higher rate than placebo through Week 44 in the maintenance trial (UC2) are shown in Table 2. Table 2: Adverse Reactions Occurring in ≥3% of Adult Subjects with Moderately to Severely Active Ulcerative Colitis through Week 44 in Trial UC2 TREMFYA Subjects receiving TREMFYA 100 mg at Week 16 and every 8 weeks thereafter or TREMFYA 200 mg at Week 12 and every 4 weeks thereafter. 100 mg Subcutaneous Injection N=186 n (%) TREMFYA 200 mg Subcutaneous Injection N=190 n (%) Placebo N=192 n (%) Injection site reactions Injection site reactions include administration site pain, injection site hematoma, injection site hemorrhage, injection site hypersensitivity, injection site erythema, injection site pain, injection site pruritus, injection site rash, injection site reaction, and injection site urticaria. 2 (1.1) 17 (8.9) TREMFYA 200 mg was administered as two 100 mg injections. 2 (1) Arthralgia 8 (4.3) 15 (7.9) 13 (6.8) Upper respiratory tract infection 6 (3.2) 13 (6.8) 8 (4.2) Trial UC4 In trial UC4, 418 subjects were enrolled, of whom 279 subjects were randomized to receive TREMFYA. Randomization was 1:1:1 to subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 100 mg every 8 weeks (with the first dose given at Week 16) for up to an additional 8 weeks (from Week 16 through Week 24); subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 200 mg every 4 weeks (with the first dose given at Week 12 for up to an additional 12 weeks (from Week 12 through Week 24); or placebo. Adverse reactions reported in trial UC4 through Week 24 in ≥3% of subjects treated with either subcutaneous TREMFYA dosing regimen and at a higher rate than placebo are shown in Table 3. Table 3: Adverse Reactions Occurring in ≥3% of Adult Subjects with Moderately to Severely Active Ulcerative Colitis through Week 24 in Trial UC4 TREMFYA 400 mg/100 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 100 mg as a subcutaneous injection at Week 16 and every 8 weeks thereafter. N=139 n (%) TREMFYA 400 mg/200 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 200 mg as a subcutaneous injection at Week 12 and every 4 weeks thereafter. N=140 n (%) Placebo N=139 n (%) Arthralgia 11 (7.9) 7 (5.0) 3 (2.2) Upper respiratory tract infections Upper respiratory tract infections include upper respiratory tract infection and viral upper respiratory tract infection. 11 (7.9) 5 (3.6) 9 (6.5) Injection site reactions Injection site reactions include injection site erythema, injection site swelling, injection site pain, injection site paresthesia, injection site edema, injection site bruising, injection site induration, injection site pruritus, application site edema, application site erythema, and application site pain. 7 (5.0) 9 (6.4) 4 (2.9) Headache Headache includes headache, migraine, and sinus headache. 8 (5.8) 7 (5.0) 3 (2.2) Gastroenteritis 4 (2.9) 3 (2.1) 0 Fatigue 2 (1.4) 4 (2.9) 1 (0.7) Pyrexia 1 (0.7) 4 (2.9) 2 (1.4) Rash Rash includes rash and rash pruritic. 4 (2.9) 1 (0.7) 1 (0.7) Specific Adverse Reactions Infections In the 44-week trial (UC2), serious infections occurred in 0.8% of subjects treated with TREMFYA versus 0% of subjects in the placebo group. In the 24-week trial (UC4), serious infections occurred in 1.8% of subjects treated with TREMFYA versus 0.7% of subjects in the placebo group. Adverse Reactions in Adults with Crohn's Disease TREMFYA was studied in four clinical trials in adult subjects with moderately to severely active Crohn's disease [see Clinical Studies (14.4) ] . In two randomized, double-blind, placebo-controlled trials (CD1, CD2) and one randomized, double-blind, dose-ranging trial (CD4, NCT03466411); subjects received intravenous TREMFYA at Weeks 0, 4, and 8 followed by one of two recommended subcutaneous TREMFYA dosing regimens for a total duration of up to 48 weeks. In a randomized, double-blind, placebo-controlled trial (CD3); subjects received subcutaneous TREMFYA at Weeks 0, 4, and 8 followed by one of two recommended subcutaneous TREMFYA dosing regimens for a total duration of up to 48 weeks. Trials CD1, CD2, and CD4 In trials CD1, CD2, and CD4; 1349 subjects were enrolled, of whom 649 were randomized to intravenous TREMFYA 200 mg at Weeks 0, 4, and 8 followed by either subcutaneous TREMFYA 100 mg every 8 weeks (with the first dose given at Week 16) for up to an additional 32 weeks (from Week 16 through Week 48) or subcutaneous TREMFYA 200 mg every 4 weeks (with the first dose given at Week 12) for up to an additional 36 weeks (from Week 12 through Week 48); and 211 subjects were randomized to receive placebo. Through Week 12 in trials CD1, CD2, and CD4; headache (including headache, migraine, and sinus headache) was reported in ≥3% of subjects treated with intravenous TREMFYA and at a greater rate than placebo (3.4% TREMFYA-treated subjects vs. 1.9% placebo-treated subjects). In TREMFYA-treated subjects in trial CD2, one case of active extrapulmonary TB was reported between Weeks 12–48 and one case of active pulmonary TB was reported after Week 48. Both subjects had negative baseline screenings and resided in TB-endemic regions [see Warnings and Precautions (5.3) ] . In general, the safety profile in subjects treated with subcutaneous TREMFYA from Week 12 up to Week 48 in these trials was generally similar to that reported with intravenous TREMFYA through Week 12. Trial CD3 In trial CD3, 347 subjects were enrolled, of whom 230 subjects were randomized to receive TREMFYA. Randomization was 1:1:1 to subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 100 mg every 8 weeks (with the first dose given at Week 16) for up to an additional 32 weeks (from Week 16 through Week 48); subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 200 mg every 4 weeks (with the first dose given at Week 12) for up to an additional 36 weeks (from Week 12 through Week 48); or placebo. Adverse reactions reported in trial CD3 through Week 48 in ≥3% of subjects treated with either subcutaneous TREMFYA dosing regimen and at a higher rate than placebo are shown in Table 4. Table 4: Adverse Reactions Occurring in ≥3% of Adult Subjects with Moderately to Severely Active Crohn's Disease Treated with Either Recommended Subcutaneous TREMFYA Regimen through Week 48 in Trial CD3 TREMFYA 400 mg/100 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 100 mg as a subcutaneous injection at Week 16 and every 8 weeks thereafter. TREMFYA 400 mg/200 mg Subcutaneous Injection TREMFYA 400 mg as a subcutaneous injection at Weeks 0, 4, and 8, followed by TREMFYA 200 mg as a subcutaneous injection at Week 12 and every 4 weeks thereafter. Placebo N=115 n (%) N=115 n (%) N=117 n (%) Respiratory tract infections Respiratory tract infections include bronchitis, COVID-19, H1N1 influenza, influenza, influenza like illness, nasopharyngitis, pneumonia, respiratory tract infection, tonsillitis, upper respiratory tract infection, and viral upper respiratory tract infection. 44 (38.3) 35 (30.4) 30 (25.6) Abdominal pain Abdominal pain includes abdominal pain, abdominal pain lower, and abdominal pain upper. 14 (12.2) 16 (13.9) 8 (6.8) Injection site reactions Injection site reactions includes application site hypersensitivity, application site pruritus, injection site edema, injection site erythema, injection site hemorrhage, injection site mass, injection site rash, injection site reaction, and injection site swelling. 5 (4.3) 4 (3.5) 0 Fatigue 3 (2.6) 4 (3.5) 0 Headache Headache includes headache and tension headache. 7 (6.1) 9 (7.8) 5 (4.3) Arthralgia 6 (5.2) 5 (4.3) 4 (3.4) Diarrhea 6 (5.2) 4 (3.5) 3 (2.6) Gastroenteritis 4 (3.5) 2 (1.7) 1 (0.9) Specific Adverse Reactions Infections In the 48-week clinical trial in subjects with Crohn’s disease (CD3), serious infections occurred in 1.5% of subjects treated with TREMFYA versus 0% of subjects in the placebo group. Elevated Liver Enzymes Through Week 12 in CD1, CD2, and CD4; ALT ≥5× ULN was reported in 2/645 (0.3%) subjects treated with intravenous TREMFYA 200 mg at Weeks 0, 4, and 8 and 0/211 subjects treated with placebo. These elevations occurred without concomitant elevations in total bilirubin. Through Week 48 in CD3, ALT ≥5× ULN was reported in 0/115 subjects treated with subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 100 mg every 8 weeks; 2/115 (1.7%) subjects treated with subcutaneous TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 200 mg every 4 weeks; and 0/117 subjects treated with placebo. These elevations occurred without concomitant elevations in total bilirubin. 6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval of TREMFYA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to TREMFYA exposure. Immune system disorders: Hypersensitivity, including anaphylaxis [see Warnings and Precautions (5.1) ] Skin and subcutaneous tissue disorders: Rash [see Warnings and Precautions (5.1) ]

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.