Infliximab
Introduction to Infliximab
Infliximab (brand names include Remicade, Inflectra, Renflexis) is a chimeric monoclonal antibody targeting tumor necrosis factor-alpha (TNF-α). It belongs to the class of biological disease-modifying antirheumatic drugs (bDMARDs) and is used to treat various inflammatory conditions in both adults and children. Infliximab was first approved by the FDA in 1998 for Crohn's disease and has since gained approval for numerous other indications.
In pediatrics, infliximab has been a game-changer in the treatment of inflammatory bowel diseases and certain rheumatological conditions, offering improved outcomes for children with severe disease unresponsive to conventional therapies.
Mechanism of Action
Infliximab works by binding with high affinity to both soluble and transmembrane forms of TNF-α. Its mechanism of action includes:
- Neutralization of TNF-α: Prevents TNF-α from binding to its receptors
- Induction of apoptosis: Causes programmed cell death in activated T lymphocytes
- Complement-dependent cytotoxicity: Leads to lysis of cells expressing transmembrane TNF-α
- Antibody-dependent cell-mediated cytotoxicity: Triggers immune cell-mediated destruction of TNF-α expressing cells
- Reverse signaling: Induces apoptosis in TNF-α producing cells
This multi-faceted mechanism effectively suppresses inflammation and modulates immune responses in various autoimmune and inflammatory disorders.
Indications in Pediatrics
- Crohn's Disease:
- Approved for patients 6 years of age and older
- Used for moderately to severely active Crohn's disease
- Indicated for patients who have had an inadequate response to conventional therapy
- Ulcerative Colitis:
- Approved for patients 6 years of age and older
- Used for moderately to severely active ulcerative colitis
- Indicated for patients who have had an inadequate response to conventional therapy
- Juvenile Idiopathic Arthritis (off-label use):
- Used in polyarticular JIA and systemic JIA
- Considered when other TNF inhibitors have failed
- Pediatric Psoriasis (off-label use):
- Used in severe cases unresponsive to other therapies
Pharmacokinetics
- Distribution:
- Volume of distribution: 3-4.5 L
- Primarily found in the vascular compartment
- Metabolism:
- Not extensively metabolized
- Eliminated through proteolytic degradation
- Elimination:
- Half-life: approximately 7.7-9.5 days
- Clearance: 11-15 mL/hour
- Pediatric considerations:
- Clearance increases with body weight
- Higher doses may be needed in children compared to adults
Dosage and Administration
Infliximab is administered as an intravenous infusion. Dosing varies based on the indication:
- Pediatric Crohn's Disease and Ulcerative Colitis:
- Induction: 5 mg/kg at weeks 0, 2, and 6
- Maintenance: 5 mg/kg every 8 weeks
- Juvenile Idiopathic Arthritis (off-label):
- Typically 3-6 mg/kg every 4-8 weeks
Administration notes:
- Infuse over a period of not less than 2 hours
- Use an in-line, sterile, non-pyrogenic, low-protein-binding filter (pore size ≤1.2 μm)
- Do not administer with other medications in the same IV line
Side Effects
Common side effects:
- Infusion-related reactions (e.g., fever, chills, urticaria)
- Upper respiratory tract infections
- Headache
- Nausea
- Abdominal pain
Serious side effects:
- Increased risk of serious infections:
- Tuberculosis (including reactivation of latent TB)
- Invasive fungal infections
- Opportunistic infections
- Malignancies (including lymphoma)
- Hepatotoxicity
- Demyelinating disorders
- Heart failure (new onset or worsening)
- Lupus-like syndrome
- Cytopenias
Monitoring
- Before treatment:
- Screen for tuberculosis
- Test for hepatitis B virus
- Baseline complete blood count and liver function tests
- During treatment:
- Monitor for signs and symptoms of infection
- Periodic complete blood count and liver function tests
- Monitor for signs of heart failure
- Assess for neurological symptoms
Drug Interactions
- Live vaccines: Avoid concurrent use
- Other biological therapies: Increased risk of infections
- Anakinra and abatacept: Increased risk of serious infections
- Methotrexate: May reduce immunogenicity of infliximab
- CYP450 substrates: May require dose adjustment
Special Populations
- Pregnancy: Limited data available; use if clearly needed
- Lactation: Limited data; probably compatible with breastfeeding
- Renal impairment: No dose adjustment necessary
- Hepatic impairment: Use with caution
