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 )
1.1Plaque 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.
1.2Psoriatic 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.
1.3Ulcerative Colitis
TREMFYA is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.
1.4Crohn's Disease
TREMFYA is indicated for the treatment of adult patients with moderately to severely active Crohn's disease.
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 )
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 )
5.1Hypersensitivity 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.
5.2Infections
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.
5.3Tuberculosis
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, 143 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) ] .
5.4Hepatotoxicity
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 18× the upper limit of normal (ULN), aspartate aminotransferase (AST) of 11× ULN, and total bilirubin of 2.4× 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.
5.5Immunizations
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 inactivated vaccines.
Interactions
7.1CYP450 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) ] .
Pregnancy and breastfeeding
8.1Pregnancy 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.
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 .
6.1Clinical 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 (PsA1 and PsA2) 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 (q8w) thereafter and 373 subjects received TREMFYA 100 mg every 4 weeks (q4w). 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 with 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 with 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. TREMFYA was additionally studied in a placebo-controlled trial (PsA3) in 1054 subjects with psoriatic arthritis (668 subjects on TREMFYA and 386 subjects on placebo). Of the 668 subjects who received TREMFYA, 388 subjects received TREMFYA 100 mg at Week 0, Week 4, and q8w thereafter and 280 subjects received TREMFYA 100 mg q4w.
The overall safety profile observed in subjects with psoriatic arthritis treated with TREMFYA in trial PsA3 is consistent with the safety profile observed in trials PsA1 and PsA2. Specific Adverse Reactions Elevated Liver Enzymes In the 24-week placebo-controlled period in trials PsA1, PsA2, and PsA3, elevated liver enzymes were reported more frequently in the TREMFYA q4w (6.1%)
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
GUSELKUMAB 100MG/ML
Official product information
Drugs@FDA lists the approved labels, letters and reviews for application BLA761061.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
