TREMFYA

Guselkumab is a human immunoglobulin

G1 lambda (IgG1λ) monoclonal antibody that selectively blocks interleukin-23.

IL-23 is an inflammatory cytokine that activates the CD4+ T-helper (Th17) cell pathway to mediate the inflammatory cascade that induces psoriatic plaque formation 2.

In clinical trials, guselkumab demonstrated improved skin clearance and symptomatic improvements in dermatological manifestations of psoriasis.

Developed by

Janssen, the subcutenous injection form of guselkumab was approved in July 2017 under the market name Tremfya for the treatment of adult patients with moderate-to-severe plaque psoriasis.

Guselkumab 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. 5 the treatment of adults and pediatric patients 6 years of age and older who also weigh at least 40 kg with active psoriatic arthritis. 5 the treatment of adults with moderately to severely active ulcerative colitis. 5 the treatment of adults with moderately to severely active Crohn's disease.

Guselkumab is shown to reduce serum levels of IL-17A, IL-17F and IL-22 5.

Following a 100 mg subcutaneous administration, the peak plasma concentration (Cmax) of guselkumab is 8.09 ± 3.68 mcg/mL which is reached after approximately 5.5 days 5.

The apparent volume of distribution is 13.5 L 5.

Like other human

IgG monoclonal antibodies, guselkumab is expected to be degraded into small peptides and amino acids via catabolic pathways 5.

Like other human

IgG monoclonal antibodies, guselkumab is expected to be both renally and fecally excreted as smaller peptide units.

Mean half-life of guselkumab is approximately 15-18 days in subjects with plaque psoriasis 5.

Apparent clearance in subjects with plaque psoriasis is 0.516 L/day 5.

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Animal studies to assess the effect of guselkumab on carcinogenesis, mutagenesis and impairment on fertility have not been conducted.

Subcutaneous injected into guinea pigs, the doses of guselkumab up to 100 mg/kg twice-weekly demonstrated no effects on fertility parameters 5.

is contraindicated in patients with a history of serious hypersensitivity reaction to guselkumab or to any of the excipients.

Serious hypersensitivity reactions to guselkumab or to any of the excipients.

For the treatment of ulcerative colitis or Crohn’s disease: Obtain liver enzymes and bilirubin levels prior to initiating treatment with TREMFYA.

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.

Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to treatment initiation.

Adults 100 mg administered by subcutaneous injection at Week 0, Week 4, and every 8 weeks thereafter.

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 can be used alone or in combination with a conventional DMARD (e.g., methotrexate).

TREMFYA may be administered alone or in combination with a conventional disease-modifying antirheumatic drug (e.g., methotrexate).

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.

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. 2.1 Recommended Evaluations and Immunizations Prior to Treatment Initiation Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TREMFYA.

For the treatment of ulcerative colitis or Crohn’s disease, obtain liver enzymes and bilirubin levels prior to initiating treatment with TREMFYA.

For the treatment of plaque psoriasis or psoriatic arthritis, if clinically indicated, evaluate liver enzymes and bilirubin prior to initiating treatment with TREMFYA.

Complete all age-appropriate vaccinations according to current immunization guidelines. 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.

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.

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 or 400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4, and Week 8.

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.

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).

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.

The TREMFYA Instructions for

Use contains more detailed patient instructions on the preparation and administration of TREMFYA.

If a dose is missed, administer the dose as soon as possible.

Thereafter, resume dosing at the regular scheduled time.

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.

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.

Do not use if the liquid contains large particles, is discolored, or is cloudy.

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.

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 °C to 8 °C (36 °F to 46 °F).

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.

TREMFYA is sterile and preservative-free.

Discard any unused portion.

Store in a refrigerator between 2 °C to 8 °C (36 °F to 46 °F).

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.

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 by calling 1-877-311-8972, or emailing MotherToBaby@health.ucsd.edu.

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.

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 to 18 times the exposure (AUC) in humans administered 200 mg intravenously and to 16 times the exposure (AUC) to the 400 mg dose given subcutaneously.

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.

• 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.

Plaque Psoriasis The safety and effectiveness of TREMFYA for the treatment of moderate-to-severe plaque psoriasis have been established in pediatric patients 6 years of age and older who are candidates for systemic therapy or phototherapy.

The safety and effectiveness of

TREMFYA have not been established in pediatric patients with plaque psoriasis who are younger than 6 years of age.

Psoriatic Arthritis The safety and effectiveness of TREMFYA have been established for treatment of active psoriatic arthritis in pediatric patients 6 years of age and older.

Use of

TREMFYA in this is supported by evidence from adequate and well controlled trials of TREMFYA in adults with plaque psoriasis and psoriatic arthritis, pharmacokinetic data from adult subjects with plaque psoriasis and psoriatic arthritis and pediatric subjects with plaque psoriasis, and safety data from a clinical trial in 120 subjects to 17 years of age with plaque psoriasis.

The observed pre-dose (trough) concentrations are generally comparable between adult subjects with plaque psoriasis, adult subjects with psoriatic arthritis and pediatric subjects with plaque psoriasis, and the systemic exposure is expected to be comparable between adult and pediatric patients with psoriatic arthritis.

TREMFYA have not been established in pediatric patients with psoriatic arthritis who are younger than 6 years of age.

Ulcerative Colitis The safety and effectiveness of TREMFYA have not been established in pediatric patients with ulcerative colitis.

Crohn's Disease The safety and effectiveness of TREMFYA have not been established in pediatric patients with Crohn’s disease.

Of the 5723 subjects with plaque psoriasis, psoriatic arthritis, ulcerative colitis, or Crohn's disease exposed to TREMFYA, a total of 313 subjects were 65 years or older, and 32 subjects were 75 years or older.

Clinical studies of

TREMFYA, within each indication, did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

No clinically meaningful differences in the pharmacokinetics of guselkumab were observed based on age.