Remicade - Drug Monograph

Introduction

Remicade (infliximab) is a chimeric monoclonal antibody biologic medication that targets tumor necrosis factor-alpha (TNF-α), a key inflammatory cytokine. Developed by Janssen Biotech, it was first approved by the FDA in 1998 and has since become a cornerstone therapy for several immune-mediated inflammatory conditions. As a biologic DMARD (disease-modifying antirheumatic drug), Remicade represents a significant advancement in the treatment of autoimmune disorders.

Mechanism of Action

Remicade exerts its therapeutic effects by specifically binding to both soluble and transmembrane forms of TNF-α with high affinity. TNF-α is a proinflammatory cytokine that plays a central role in the pathogenesis of various inflammatory conditions. By neutralizing TNF-α, infliximab inhibits its binding to TNF receptors, thereby preventing TNF-mediated cellular responses including:

• Inhibition of cytokine production (IL-1, IL-6)
• Reduction of adhesion molecule expression
• Decreased neutrophil and eosinophil chemotaxis
• Attenuation of acute phase reactants
• Reduction of tissue degradation enzymes

This comprehensive anti-inflammatory action results in decreased inflammation and tissue damage in affected organs.

Indications

FDA-approved indications for Remicade include:

• Rheumatoid arthritis (moderate to severe, in combination with methotrexate)
• Crohn's disease (moderate to severe, fistulizing)
• Ulcerative colitis (moderate to severe)
• Ankylosing spondylitis
• Psoriatic arthritis
• Plaque psoriasis (chronic severe)

Off-label uses (with varying evidence levels) include:

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

Dosage and Administration

• Rheumatoid arthritis: 3 mg/kg at 0, 2, and 6 weeks, then every 8 weeks (may increase to 10 mg/kg or reduce interval to 4 weeks)
• Crohn's disease/Ulcerative colitis: 5 mg/kg at 0, 2, and 6 weeks, then every 8 weeks
• Ankylosing spondylitis/Psoriatic arthritis: 5 mg/kg at 0, 2, and 6 weeks, then every 6-8 weeks
• Plaque psoriasis: 5 mg/kg at 0, 2, and 6 weeks, then every 8 weeks

• Route: Intravenous infusion only
• Duration: Typically 2-3 hours for initial infusion; may reduce to 1-2 hours for subsequent infusions if tolerated
• Premedication: Consider pre-treatment with antihistamines, acetaminophen, or corticosteroids to prevent infusion reactions

• Hepatic impairment: No specific dosage recommendations
• Renal impairment: No dosage adjustment required
• Elderly: Use with caution due to increased infection risk
• Pediatric: Approved for pediatric Crohn's disease (6-17 years) at 5 mg/kg

Pharmacokinetics

Factors affecting pharmacokinetics:

• Formation of antibodies to infliximab (ATI) increases clearance
• Concomitant immunosuppressants (methotrexate) reduce ATI formation
• Body weight influences volume of distribution and clearance

Contraindications

• Hypersensitivity to infliximab, other murine proteins, or any component of the formulation
• Moderate to severe heart failure (NYHA Class III/IV)
• Active tuberculosis or other serious infections
• History of severe hypersensitivity reaction to previous infliximab administration

Warnings and Precautions

1. Serious infections: Increased risk of serious and sometimes fatal infections including tuberculosis, invasive fungal infections, and bacterial/viral infections 2. Malignancy: Increased risk of lymphoma and other malignancies, particularly in children and adolescents 3. Hepatosplenic T-cell lymphoma: Rare but fatal lymphoma reported in adolescents and young adults with Crohn's disease

• Hepatotoxicity: Severe hepatic reactions including acute liver failure
• Hematologic effects: Pancytopenia, aplastic anemia, leukopenia, thrombocytopenia
• Neurologic events: Demyelinating disorders, seizure, optic neuritis
• Heart failure: New onset or worsening of existing heart failure
• Autoimmunity: Lupus-like syndrome, autoantibody formation

Drug Interactions

• Anakinra: Increased risk of serious infections (avoid combination)
• Abatacept: Increased risk of serious infections (avoid combination)
• Live vaccines: Avoid concurrent administration
• Other TNF blockers: Increased risk of adverse effects (contraindicated)
• CYP450 substrates: May affect metabolism of drugs metabolized by CYP450 enzymes

• Methotrexate: Co-administration reduces immunogenicity and improves efficacy
• Corticosteroids: May be used concomitantly for disease management
• Immunosuppressants: May increase infection risk requiring careful monitoring

Adverse Effects

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

• Serious infections (pneumonia, sepsis, cellulitis)
• Hepatitis
• Heart failure
• Hematologic disorders
• Demyelinating disorders
• Lupus-like syndrome

• Tuberculosis reactivation
• Invasive fungal infections
• Hepatosplenic T-cell lymphoma
• Severe hepatic reactions
• Aplastic anemia

Monitoring Parameters

• Tuberculosis screening (PPD or interferon-gamma release assay)
• Hepatitis B and C serology
• Complete blood count with differential
• Comprehensive metabolic panel
• Pregnancy test if appropriate
• Cardiac assessment in patients with heart failure risk factors

• Signs and symptoms of infection at every visit
• CBC and LFTs every 3-6 months
• Regular skin examinations for malignancy screening
• Monitoring for signs of heart failure
• Neurologic assessment
• Disease-specific activity measures

• Infliximab levels and antibody testing for loss of response
• CRP and ESR for inflammatory activity assessment

Patient Education

• Report any signs of infection immediately (fever, cough, fatigue, skin lesions)
• Avoid live vaccines during therapy
• Inform all healthcare providers about Remicade therapy
• Be aware of increased malignancy risk and report unusual symptoms
• Understand the importance of regular monitoring and follow-up appointments
• Recognize infusion reaction symptoms and report them promptly
• Discuss pregnancy plans with healthcare provider before conception
• Be aware of potential delayed effects (symptoms may occur days after infusion)

• Practice good hygiene to reduce infection risk
• Avoid individuals with contagious illnesses
• Maintain regular health screenings
• Report any new or worsening symptoms promptly

References

1. Hanauer SB, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541-1549. 2. Maini R, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Lancet. 1999;354(9194):1932-1939. 3. Rutgeerts P, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462-2476. 4. Remicade® (infliximab) prescribing information. Janssen Biotech, Inc. 2023. 5. Lichtenstein GR, et al. Serious infection and mortality in patients with Crohn's disease: more than 5 years of follow-up in the TREAT™ registry. Am J Gastroenterol. 2012;107(9):1409-1422. 6. Singh JA, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26. 7. Torres J, et al. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis. 2020;14(1):4-22.