Simponi - Drug Monograph

Introduction

Simponi (golimumab) is a biologic medication belonging to the tumor necrosis factor-alpha (TNF-α) inhibitor class. Developed by Janssen Biotech, Inc., it was first approved by the FDA in 2009. Simponi is a human monoclonal antibody that specifically targets and neutralizes TNF-α, a key inflammatory cytokine implicated in various autoimmune disorders. It is available in subcutaneous injection and intravenous formulations for the treatment of several chronic inflammatory conditions.

Mechanism of Action

Golimumab is a human IgG1κ monoclonal antibody that binds with high affinity and specificity to both soluble and transmembrane forms of TNF-α. By binding to TNF-α, golimumab prevents its interaction with the p55 and p75 cell surface TNF receptors. This inhibition disrupts the inflammatory cascade mediated by TNF-α, including:

• Reduction of inflammatory cell migration to sites of inflammation
• Decreased production of other proinflammatory cytokines (IL-1, IL-6)
• Inhibition of metalloproteinases and other enzymes involved in tissue destruction
• Reduction of endothelial activation and angiogenesis

The net effect is a significant reduction in the inflammatory processes that characterize autoimmune diseases.

Indications

Simponi is FDA-approved for the following indications:

• Moderate to severe rheumatoid arthritis (in combination with methotrexate)
• Active psoriatic arthritis (as monotherapy or with methotrexate)
• Active ankylosing spondylitis
• Moderate to severe ulcerative colitis (subcutaneous maintenance therapy following induction)
• Moderate to severe ulcerative colitis (intravenous induction therapy)

Dosage and Administration

• Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis: 50 mg monthly
• Ulcerative colitis: 100 mg initially, then 50 mg or 100 mg every 4 weeks (maintenance)

• 2 mg/kg at weeks 0 and 4

• Subcutaneous injections should be administered in the abdomen, thigh, or upper arm
• Rotate injection sites
• Allow prefilled syringe or autoinjector to reach room temperature (30 minutes) before administration
• Do not administer to areas with skin tenderness, bruising, redness, or hardness

• Hepatic impairment: No dose adjustment recommended
• Renal impairment: No dose adjustment recommended
• Elderly: No dose adjustment recommended
• Pediatric: Safety and effectiveness not established

Pharmacokinetics

Contraindications

• History of serious hypersensitivity reaction to golimumab or any component of the formulation
• Patients with active tuberculosis or other serious infections
• Patients with moderate to severe heart failure (NYHA Class III/IV)

Warnings and Precautions

Drug Interactions

Adverse Effects

• Upper respiratory infections
• Injection site reactions
• Viral infections
• Hypertension
• Elevated liver enzymes

• Serious infections
• Malignancies
• Heart failure
• Hepatic reactions
• Hematologic disorders
• Hypersensitivity reactions
• Neurologic events
• Autoimmunity (lupus-like syndrome)

Monitoring Parameters

• Tuberculosis screening (PPD or interferon-gamma release assay)
• Hepatitis B and C screening
• Complete blood count
• Liver function tests
• Renal function tests
• Pregnancy test if appropriate

• Signs and symptoms of infection (at every visit)
• CBC and LFTs periodically
• Lipid profile (baseline and periodically)
• Clinical response assessment
• Injection site reactions
• Signs of heart failure
• Neurologic symptoms

• Annual TB screening in endemic areas
• Skin examination for melanoma and other skin cancers
• Vaccination status review

Patient Education

• Instruct on proper injection technique and disposal
• Recognize signs of infection (fever, cough, flu-like symptoms)
• Report any new neurological symptoms
• Inform all healthcare providers about Simponi use
• Avoid live vaccines during treatment
• Seek immediate medical attention for signs of allergic reaction
• Understand the increased risk of certain cancers
• Report unusual fatigue, bruising, or bleeding
• Notify provider if planning pregnancy or becoming pregnant
• Store medication properly (refrigerate, do not freeze)
• Do not share medication or injection devices

References

1. Simponi (golimumab) [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2023. 2. Kay J, Matteson EL, Dasgupta B, et al. Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum. 2008;58(4):964-975. 3. Kavanaugh A, McInnes I, Mease P, et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum. 2009;60(4):976-986. 4. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(1):85-95. 5. Keystone EC, Genovese MC, Klareskog L, et al. Golimumab, a human antibody to tumour necrosis factor α given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Ann Rheum Dis. 2009;68(6):789-796. 6. FDA-approved labeling and clinical trial data available at: https://www.accessdata.fda.gov