Infliximab

Approved Indications:

• Rheumatoid Arthritis (RA): In combination with methotrexate to reduce signs and symptoms, inhibit structural damage, and improve physical function in adults with moderate to severe active disease.
• Crohn’s Disease:
• Adults: For moderate to severe active Crohn’s disease with inadequate response to conventional therapy.
• Adults and children (≥6 years): For moderate to severe Crohn’s disease refractory to corticosteroids or immunomodulators.
• Fistulizing Crohn’s disease: To reduce the number of draining enterocutaneous fistulas.
• Ulcerative Colitis (UC):
• Adults: For moderate to severe active UC with inadequate response to conventional therapy.
• Pediatrics (≥6 years): For moderate to severe active UC.
• Ankylosing Spondylitis (AS): To reduce signs and symptoms in adults with active disease.
• Psoriatic Arthritis (PsA): To reduce signs and symptoms and inhibit progression of structural damage in adults with active disease.
• Plaque Psoriasis: Adults with chronic severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Important Off-Label / Clinically Accepted Uses:

• Sarcoidosis (refractory cases).
• Behçet’s disease with ocular involvement.
• Autoimmune uveitis.
• Pyoderma gangrenosum.
• Kawasaki disease (resistant to IVIG).
• Refractory vasculitides (e.g., Takayasu arteritis, granulomatosis with polyangiitis).

Administration Route: Intravenous infusion only.

Adults:

• RA: 3 mg/kg IV at weeks 0, 2, 6, then every 8 weeks; given with methotrexate.
• Crohn’s Disease / UC: 5 mg/kg IV at weeks 0, 2, 6, then every 8 weeks; may increase to 10 mg/kg for loss of response.
• AS, PsA, Plaque Psoriasis: 5 mg/kg IV at weeks 0, 2, 6, then every 6–8 weeks.

Pediatrics:

• Crohn’s Disease / UC (≥6 years): 5 mg/kg IV at weeks 0, 2, 6, then every 8 weeks.

Elderly:

• No specific adjustment; use with caution due to increased infection risk.

Special Populations:

• Renal or hepatic impairment: No specific dose adjustment; use with caution and monitor closely due to limited data.

Infusion Guidelines:

• Administer over at least 2 hours.
• Premedication with antihistamines, acetaminophen, and/or corticosteroids may be considered to reduce infusion reactions.
• Observe for infusion-related or delayed hypersensitivity reactions.

Infliximab is a chimeric monoclonal IgG1 antibody composed of human constant and murine variable regions. It specifically binds to both soluble and transmembrane forms of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine involved in immune-mediated inflammation. By neutralizing TNF-α, infliximab prevents its interaction with TNF receptors (p55 and p75) on cell surfaces, leading to reduced expression of inflammatory mediators, decreased leukocyte migration, and suppression of inflammatory tissue destruction. This blockade results in clinical improvement in autoimmune and inflammatory diseases.

• Absorption: Not applicable (IV administration gives 100% bioavailability).
• Distribution: Volume of distribution ~3–6 L; primarily distributed in vascular and interstitial compartments.
• Metabolism: Catabolized into peptides and amino acids via nonspecific proteolytic pathways.
• Half-life: ~8–10 days (range 7–12 days); detectable for up to 12 weeks post-dose.
• Excretion: Clearance via reticuloendothelial system; not renally excreted.
• Onset: Clinical improvement may be seen within 2 weeks for inflammatory bowel disease and within weeks for arthritis and psoriasis.

• Pregnancy: Former FDA Category B. Available data do not suggest increased teratogenic risk; however, due to placental transfer (especially in 2nd and 3rd trimesters), the neonate may have detectable drug levels for months, increasing infection risk.
• Lactation: Low levels in breast milk; large protein structure suggests minimal oral absorption by infant. Use with caution; consider timing doses to reduce exposure.
• Recommendation: Avoid live vaccines in infants exposed in utero until at least 6 months of age.

• Primary Class: Biologic Disease-Modifying Antirheumatic Drug (bDMARD)
• Subclass: Anti–TNF-α monoclonal antibody

• Known hypersensitivity to infliximab, murine proteins, or any excipients.
• Moderate to severe heart failure (NYHA class III/IV) at doses >5 mg/kg.
• Active severe infections, including tuberculosis, sepsis, or opportunistic infections.

• Infections: Increased risk of serious bacterial, fungal, viral, and opportunistic infections; test for latent TB before initiation.
• Malignancy: Increased risk of lymphoma and other malignancies, especially in pediatric and adolescent patients.
• Hepatotoxicity: Severe hepatic reactions including acute liver failure.
• Heart failure: Avoid in moderate to severe cases.
• Demyelinating disorders: May exacerbate or induce (e.g., multiple sclerosis, optic neuritis).
• Hematologic reactions: Rare aplastic anemia, pancytopenia.
• Infusion Reactions: May occur during or up to 24 hours post-infusion; delayed hypersensitivity can occur 3–12 days post-dose.
• Monitoring: CBC, liver function tests, infection screening, and regular malignancy surveillance in long-term use.

Common:

• Infusion-related: Fever, chills, pruritus, headache.
• GI: Abdominal pain, nausea.
• Respiratory: Sinusitis, pharyngitis, cough.
• Musculoskeletal: Arthralgia, back pain.

Serious:

• Severe infections (TB, sepsis, invasive fungal).
• Heart failure exacerbation.
• Hepatic injury (jaundice, hepatitis).
• Demyelinating disease onset.
• Hematologic disorders.

Rare:

• Lupus-like syndrome.
• Psoriasis-like skin lesions.
• Stevens–Johnson syndrome/toxic epidermal necrolysis.

• Other biologics (e.g., anakinra, abatacept, other TNF inhibitors): ↑ risk of serious infections; avoid combination.
• Live vaccines: Avoid during therapy and for several months after.
• Immunosuppressants (e.g., azathioprine, methotrexate): May increase infection and malignancy risk but also may reduce immunogenicity.
• Warfarin / CYP-metabolized drugs: No major CYP interaction, but infection/inflammation resolution may alter drug metabolism indirectly.

• EMA and FDA updated safety communications emphasizing no live vaccines in infants exposed in utero for at least 6 months.
• ECCO and ACR guidelines reaffirm infliximab as first-line biologic in severe inflammatory bowel disease when rapid induction is needed.
• New recommendations for therapeutic drug monitoring (trough levels, anti-drug antibodies) to optimize efficacy and minimize immunogenicity.

• Store vials at 2°C–8°C (36°F–46°F); do not freeze.
• Protect from light; keep in original carton until use.
• Reconstituted solution: Stable for 3 hours at room temperature; use immediately if possible.
• Do not shake vials; gently swirl during reconstitution.