Infliximab

• Crohn's disease
• Ulcerative colitis
• Rheumatoid arthritis
• Ankylosing spondylitis
• Psoriatic arthritis
• Plaque psoriasis

Infliximab is a chimeric monoclonal antibody that specifically binds and neutralizes tumor necrosis factor-alpha (TNF-α), a key inflammatory cytokine implicated in numerous autoimmune and inflammatory conditions. As one of the first biologic therapies for inflammatory diseases, it has transformed the treatment of conditions ranging from rheumatoid arthritis to inflammatory bowel disease.

Mechanism of Action

Infliximab is a chimeric (mouse-human) monoclonal IgG1 antibody composed of human constant regions and murine variable regions. It binds with high affinity to both soluble and transmembrane forms of TNF-α, preventing TNF-α from binding to its receptors. This neutralization of TNF-α reduces the downstream inflammatory cascade, decreasing the production of pro-inflammatory cytokines, reducing leukocyte migration, and promoting apoptosis of activated T cells in inflamed tissues.

Additionally, infliximab can bind to cells expressing transmembrane TNF-α, potentially inducing antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity, which may contribute to its therapeutic effects in certain conditions.

Available Formulations

Infliximab (Remicade) is available as a lyophilized powder for reconstitution in 100 mg single-dose vials. After reconstitution and dilution, it is administered as an intravenous infusion. Several biosimilar products (Inflectra, Renflexis, Avsola, Ixifi) are also available, providing options for reducing treatment costs while maintaining efficacy. All infliximab products require intravenous administration in a healthcare setting.

FDA-Approved Indications

Infliximab has received FDA approval for a wide range of inflammatory conditions including moderately to severely active Crohn's disease in adults and children 6 years and older, moderately to severely active ulcerative colitis in adults and children 6 years and older, moderately to severely active rheumatoid arthritis (in combination with methotrexate), active ankylosing spondylitis, active psoriatic arthritis, and chronic severe plaque psoriasis. These varied indications reflect the central role of TNF-α in multiple inflammatory pathways.

Dosing Guidelines

Dosing varies by indication. For Crohn's disease and ulcerative colitis, the typical regimen is 5 mg/kg IV at weeks 0, 2, and 6, then every 8 weeks for maintenance. For rheumatoid arthritis, the dose is 3 mg/kg at weeks 0, 2, and 6, then every 8 weeks, used in combination with methotrexate. For ankylosing spondylitis and psoriatic arthritis, the dose is 5 mg/kg at weeks 0, 2, and 6, then every 6 weeks. For plaque psoriasis, 5 mg/kg at weeks 0, 2, and 6, then every 8 weeks is standard. Doses may be adjusted based on response.

Immunogenicity Considerations

As a chimeric antibody, infliximab can induce the formation of anti-drug antibodies (ADAs), which may reduce efficacy and increase infusion reaction risk. Concomitant immunomodulators (methotrexate, azathioprine, 6-mercaptopurine) reduce ADA formation and are recommended, particularly for inflammatory bowel disease. Scheduled maintenance therapy (rather than episodic use) also reduces immunogenicity.

Important Safety Considerations

Infliximab carries boxed warnings for serious infections (including tuberculosis, invasive fungal infections, and opportunistic infections) and malignancy (including lymphoma). All patients should be tested for latent tuberculosis before initiation, and active infections should be controlled before starting therapy. Hepatitis B reactivation can occur in carriers, necessitating screening and monitoring. Heart failure may worsen; avoid use in patients with moderate or severe heart failure.

Infusion Reactions and Monitoring

Infusion reactions ranging from mild (flushing, headache) to severe (hypotension, anaphylaxis) can occur. Premedication with antihistamines, acetaminophen, and/or corticosteroids may reduce reaction risk. Patients should be monitored during and after infusion. Delayed hypersensitivity reactions can occur 3-12 days after infusion. Serum sickness-like reactions have been reported.

Drug Interactions

Live vaccines should not be administered during infliximab therapy due to infection risk. Concurrent use with other biologics (anakinra, abatacept) is not recommended due to increased infection risk. Methotrexate and other immunomodulators are often used concomitantly to reduce immunogenicity. Monitor for additive immunosuppression when used with other immunosuppressants.

Learn more at MedlinePlus