Infliximab - Drug Monograph

Introduction

Infliximab is a chimeric monoclonal antibody that specifically targets tumor necrosis factor-alpha (TNF-α), a key inflammatory cytokine. As a biologic response modifier, it represents a cornerstone in the treatment of several immune-mediated inflammatory disorders. First approved by the FDA in 1998, infliximab has revolutionized the management of conditions that were previously difficult to control with conventional therapies.

Mechanism of Action

Infliximab binds with high affinity to both soluble and transmembrane forms of TNF-α, preventing TNF-α from binding to its receptors. This neutralization inhibits TNF-α-mediated cellular responses, including:

• Reduction of inflammatory cytokine production (IL-1, IL-6)
• Decreased expression of adhesion molecules
• Inhibition of neutrophil activation and migration
• Attenuation of matrix metalloproteinase production
• Reduction of tissue degradation and inflammation

The drug does not neutralize TNF-β (lymphotoxin-α), demonstrating specificity for TNF-α pathways.

Indications

FDA-approved indications include:

• Moderately to severely active Crohn's disease in adults and pediatric patients (≥6 years) who have inadequate response to conventional therapy
• Fistulizing Crohn's disease
• Moderately to severely active ulcerative colitis in adults and pediatric patients (≥6 years) who have inadequate response to conventional therapy
• Rheumatoid arthritis (in combination with methotrexate)
• Ankylosing spondylitis
• Psoriatic arthritis
• Plaque psoriasis

Off-label uses may include:

• Behçet's disease
• Sarcoidosis
• Non-infectious uveitis
• Pyoderma gangrenosum

Dosage and Administration

• Crohn's disease: 5 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks
• Ulcerative colitis: 5 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks
• Rheumatoid arthritis: 3 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks (may increase to 10 mg/kg or adjust frequency)
• Ankylosing spondylitis: 5 mg/kg IV at 0, 2, and 6 weeks, then every 6-8 weeks
• Psoriatic arthritis: 5 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks
• Plaque psoriasis: 5 mg/kg IV at 0, 2, and 6 weeks, then every 8 weeks

• Administer as IV infusion over at least 2 hours
• Premedication with antihistamines, acetaminophen, and/or corticosteroids may be considered to prevent infusion reactions
• Must be administered under supervision of healthcare professionals experienced in biologic therapy

• Hepatic impairment: No dosage adjustment recommended
• Renal impairment: No dosage adjustment recommended
• Elderly: Use with caution due to increased infection risk
• Pediatrics: Approved for Crohn's disease and ulcerative colitis in children ≥6 years

Pharmacokinetics

Contraindications

• Hypersensitivity to infliximab or any component of formulation
• Severe hypersensitivity reactions to other murine proteins
• Moderate to severe heart failure (NYHA Class III/IV)
• Active tuberculosis or other serious infections
• Sepsis

Warnings and Precautions

Drug Interactions

• Live vaccines: Avoid concurrent administration
• Anakinra: Increased risk of serious infections (not recommended)
• Abatacept: Increased risk of serious infections (not recommended)
• Other TNF blockers: Increased risk of adverse effects (contraindicated)
• Methotrexate: Concomitant use may decrease immunogenicity and increase infliximab concentrations

Adverse Effects

• Upper respiratory infections
• Headache
• Abdominal pain
• Infusion reactions (fever, chills, pruritus, urticaria)
• Cough
• Fatigue

• Serious infections (pneumonia, sepsis, opportunistic infections)
• Tuberculosis reactivation
• Hepatotoxicity
• Heart failure exacerbation
• Hematologic disorders
• Malignancies
• Severe hypersensitivity reactions
• Neurologic events
• 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
• Pregnancy test if appropriate
• Cardiac assessment in patients with heart failure risk factors

• Signs and symptoms of infection
• Infusion reactions
• CBC and LFTs periodically
• Clinical response assessment
• Antibody formation assessment if loss of response occurs
• Periodic skin examination for melanoma risk

• Annual tuberculosis screening in endemic areas
• Regular assessment for signs of malignancy
• Monitoring for neurologic symptoms

Patient Education

• Report any signs of infection (fever, cough, flu-like symptoms) immediately
• Inform all healthcare providers about infliximab therapy
• Avoid live vaccines during treatment
• Seek immediate medical attention for signs of allergic reaction
• Understand the increased malignancy risk, particularly in pediatric patients
• Report any new neurological symptoms
• Notify provider if pregnant or planning pregnancy
• Understand the importance of keeping all scheduled infusions
• Report any chest pain, shortness of breath, or swelling

References

1. Hanauer SB, et al. Gastroenterology. 2002;122(6):1592-1608. 2. Rutgeerts P, et al. N Engl J Med. 2005;353(23):2462-2476. 3. Maini RN, et al. Lancet. 1999;354(9194):1932-1939. 4. FDA Prescribing Information: Remicade (infliximab). 2023. 5. Lichtenstein GR, et al. Am J Gastroenterol. 2018;113(4):481-517. 6. Singh JA, et al. Arthritis Care Res (Hoboken). 2019;71(6):717-734. 7. Papp KA, et al. J Am Acad Dermatol. 2015;73(2):242-247. 8. Colombel JF, et al. Clin Gastroenterol Hepatol. 2016;14(8):1123-1136.