SIMPONI

Golimumab is a human

IgG1қ monoclonal antibody derived from immunizing genetically engineered mice with human TNFα.

Golimumab binds and inhibits soluble and transmembrane human TNFα.

TNFα is associated with chronic inflammation.

Thus golimumab is indicated for use in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA), (ii) alone or as an adjunct to methotrexate treatment in patients with active psoriatic arthritis (PsA), (iii) as a single agent in patients with active ankylosing spondylitis (AS), and (Intravenous) as a single agent in patients with moderate to severe ulcerative colitis (UC) who require chronic steroids or have experienced intolerance or only a partial response to previous medications.

In the

U.S. and Canada, golimumab is marketed under the brand name Simponi®.

FDA label includes a black box warning of serious infections and malignancy.

Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed.

Used in adults (i) as an adjunct to methotrexate treatment in patients with moderate to severe active rheumatoid arthritis (RA) 3, (ii) in patients 2 years old and above with active psoriatic arthritis (PsA) 3, (iii) as a single agent in patients with active ankylosing spondylitis (AS) or in combination with methotrexate 4, and (Intravenous) in adult and pediatric patients with moderate to severe ulcerative colitis (UC) weighing at least 15 kg.

It is also indicated (v) for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older.

Golimumab inhibits the activity of the cytokine, tumor necrosis factor alpha (TNFα).

In areas such as the joints and blood, increased TNFα is associated with chronic inflammation seen in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

Thus golimumab decreases the inflammation in these conditions.

Concerning ulcerative colitis, the physiological effects of golimumab has yet to be determined.

After subcutaneous administration, golimumab can achieve maximum serum concentrations in 2-6 days and has an approximate bioavailability of 53%.

In healthy volunteers, the maximum average concentration reached was 3.2 ± 1.4 μg/mL.

Intravenous administration, golimumab has a volume of distribution of about 58-126 mL/kg.

The metabolism of golimumab has yet to be determined.

The route of elimination for golimumab has yet to be determined.

Golimumab has a long half-life of about 2 weeks.

After one

Intravenous dose of golimumab, the systemic clearance was about 4.9-6.7 mL/day/kg.

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FDA label includes a black box warning of serious infections and malignancy.

Specifically there have been hospitalizations or death from infections such as bacterial sepsis, tuberculosis (TB), and invasive fungal (histoplasmosis) and other opportunistic infections.

Additionally in children and adolescents taking golimumab, there have been lymphoma and other malignancies observed.

Adult patients with Rheumatoid

Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis: 2 mg/kg intravenous infusion over 30 minutes at weeks and 4, and every 8 weeks thereafter Pediatric patients with polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis: 80 mg/m 2 intravenous infusion over 30 minutes at weeks and 4, and every 8 weeks thereafter Dilution of supplied SIMPONI ARIA solution with 0.9% Sodium Chloride Injection, USP is required prior to administration.

Alternatively, 0.45% Sodium Chloride Injection, USP can also be used 2.1 Dosage in Adults with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis The SIMPONI ARIA dosage regimen is 2 mg per kg given as an intravenous infusion over 30 minutes at weeks and 4, and every 8 weeks thereafter.

Follow the dilution and administration instructions for SIMPONI ARIA.

For patients with rheumatoid arthritis (RA), SIMPONI ARIA should be given in combination with methotrexate.

The efficacy and safety of switching between intravenous and subcutaneous formulations and routes of administration have not been established. 2.2 Dosage in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis The SIMPONI ARIA dosage regimen, based on body surface area (BSA), is 80 mg/m 2 given as an intravenous infusion over 30 minutes at weeks and 4, and every 8 weeks thereafter.

Follow the dilution and administration instructions for SIMPONI ARIA. 2.3 Evaluation for Tuberculosis and Hepatitis B Prior to Dosage Prior to initiating SIMPONI ARIA and periodically during therapy, evaluate patients for active tuberculosis and test for latent infection.

Prior to initiating SIMPONI

ARIA, test patients for hepatitis B viral infection. 2.4 Important Administration Instructions SIMPONI ARIA solution for intravenous infusion should be diluted by a healthcare professional using aseptic technique as follows: Calculate the dosage and the number of SIMPONI ARIA vials needed based on the recommended adult dosage of 2 mg/kg and the patient's weight for RA, PsA and AS.

Calculate the dosage and number of SIMPONI ARIA vials needed based on the recommended pediatric dosage of 80 mg/m and the patient's body surface area (BSA), for pJIA and pediatric patients with PsA.

Each 4 mL vial of SIMPONI ARIA contains 50 mg of golimumab.

Check that the solution in each vial is colorless to light yellow.

The solution may develop a few fine translucent particles, as golimumab is a protein.

Do not use if opaque particles, discoloration, or other foreign particles are present.

Dilute the total volume of the SIMPONI ARIA solution with 0.9% Sodium Chloride Injection, USP to a final volume of 100 mL.

For example, this can be accomplished by withdrawing a volume of the 0.9% Sodium Chloride Injection, USP from the 100-mL infusion bag or bottle equal to the total volume of SIMPONI ARIA.

Slowly add the total volume of SIMPONI ARIA solution to the 100-mL infusion bag or bottle.

Gently mix.

Discard any unused solution remaining in the vials.

Alternatively, SIMPONI ARIA can be diluted using the same method described above with 0.45% Sodium Chloride Injection, USP.

Prior to infusion, visually inspect the diluted SIMPONI ARIA solution for particulate matter or discoloration.

Do not use if these are present.

Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 0.22 micrometer or less).

Do not infuse SIMPONI

ARIA concomitantly in the same intravenous line with other agents.

No physical biochemical compatibility studies have been conducted to evaluate the use of SIMPONI ARIA with other intravenous agents in the same intravenous line.

Infuse the diluted solution over 30 minutes.

Once diluted, the infusion solution can be stored for up to 4 hours at room temperature.

® (golimumab) Injection is a colorless to light yellow solution available in packs of 1 vial NDC 57894-350-01.

Each single-dose vial contains 50 mg of SIMPONI ARIA per 4 mL of solution.

ARIA at 36 ⁰F to 46 ⁰F (2 ⁰C to 8 ⁰C) and protect from light.

Keep the product in the original carton to protect from light until the time of use.

Do not freeze.

Do not shake.

If needed, SIMPONI ARIA may be stored at room temperature up to 77 ºF (25 ºC) for a maximum single period of 30 days in the original carton to protect from light.

ARIA has been stored at room temperature, do not return the product to the refrigerator.

If not used within 30 days at room temperature, discard SIMPONI ARIA.

ARIA at 36 ⁰F to 46 ⁰F (2 ⁰C to 8 ⁰C) and protect from light.

Keep the product in the original carton to protect from light until the time of use.

Do not freeze.

Do not shake.

If needed, SIMPONI ARIA may be stored at room temperature up to 77 ºF (25 ºC) for a maximum single period of 30 days in the original carton to protect from light.

ARIA has been stored at room temperature, do not return the product to the refrigerator.

If not used within 30 days at room temperature, discard SIMPONI ARIA.

Available data from postmarketing case reports with golimumab use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

An observational study of northern

European births observed similar unadjusted rates of major birth defects in infants exposed in utero to golimumab compared to no treatment or non-biologic systemic therapy.

However, this study had important limitations.

Monoclonal antibodies, such as golimumab, are transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant.

There are clinical considerations for the use of SIMPONI ARIA in pregnant women.

In an animal reproductive study, golimumab administered by the subcutaneous route to pregnant monkeys, during the period of organogenesis, at doses that produced exposures approximately 200 times the maximum recommended human dose (MRHD) had no adverse fetal effects.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.

In the

U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and of miscarriage is 15–20%, respectively.

Fetal/Neonatal Adverse Reactions Golimumab crosses the placenta during pregnancy.

TNF-blocking monoclonal antibody administered during pregnancy was detected for up to 6 months in the serum of infants.

Consequently, these infants may be at increased risk of infection.

Administration of live vaccines to infants exposed to SIMPONI ARIA in utero is not recommended for 6 months following the mother's last SIMPONI ARIA infusion during pregnancy.

An observational, exposure-based, cohort study based on data from the Swedish, Danish, and Finnish Medical Birth Registers conducted between 2006–2020 (Sweden and Denmark) and 2006–2019 (Finland) compared the risk of major birth defects in 134 live-born infants exposed to golimumab (116 from women treated for rheumatic conditions, 18 from women treated for ulcerative colitis) to no treatment or nonbiologic systemic therapy.

The unadjusted rate of major birth defects in infants exposed in utero was similar across all groups.

However, this study had important limitations such as a small number of pregnant women exposed to golimumab, a wide exposure ascertainment window, and incomplete risk adjustment for potential confounders.

In an embryofetal developmental toxicology study in which pregnant cynomolgus monkeys were treated with golimumab during the period of organogenesis from gestation days (GD) 20 to 51, exposures up to 200 times greater than the exposure at the MRHD (on an area under the curve (AUC) basis with maternal subcutaneous doses up to 50 mg/kg twice weekly) produced no evidence of fetal malformations or embryotoxicity.

There was no evidence of maternal toxicity.

Umbilical cord blood samples collected at the end of the second trimester showed that fetuses were exposed to golimumab during gestation.

In a pre.

• and postnatal developmental study in which pregnant cynomolgus monkeys were treated with golimumab from gestation day to postpartum day 33, maximal drug concentrations up to 33 times greater than that found with the MRHD (on a maximum blood concentration (C max ) basis at steady-state with maternal subcutaneous doses up to 50 mg/kg twice weekly) were not associated with any evidence of developmental defects in infants.

Golimumab was present in fetal serum at the end of the second trimester and in neonatal serum from the time of birth and for up to 6 months postpartum.

Safety and effectiveness of SIMPONI

ARIA for active polyarticular juvenile idiopathic arthritis and PsA have been established in pediatric patients 2 years and older.

ARIA in these age groups is supported by evidence from adequate and well-controlled studies of SIMPONI ARIA in adults with RA and PsA, pharmacokinetic data from adult patients with RA and PsA and pediatric patients with JIA with active polyarthritis, and safety data from a clinical study in 127 pediatric patients to < 18 years of age with JIA with active polyarthritis.

The observed pre-dose (trough) concentrations are generally comparable between adults with RA and PsA and pediatric patients with JIA with active polyarthritis, and the PK exposure is expected to be comparable between adult PsA and pediatric patients with PsA.

Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with golimumab and other TNF-blocking agents.

The safety and effectiveness in pediatric patients below the age of 2 years have not been established in pJIA or in PsA.

The safety and effectiveness of SIMPONI

ARIA in pediatric patients with conditions other than pJIA and PsA have not been established.

RA, the number of patients ages 65 or older was too small to make comparisons with younger SIMPONI ARIA-treated patients.

Because there is a higher incidence of infections in the geriatric population in general, caution should be used in treating geriatric patients with SIMPONI ARIA.