Mechanism of Action and Pathogenesis
To understand how the drug works, it is essential to review the pathogenesis of joint damage in rheumatoid arthritis. Proinflammatory cytokines, primarily TNF-α and IL-1, play a key role. They are secreted by synovial macrophages and trigger a cascade of tissue destruction:
- Stimulate the production of collagenase (an enzyme that degrades joint tissues).
- Enhance bone resorption.
- Inhibit cartilage proteoglycan synthesis.
Chemically, infliximab (Infliximab) is a chimeric (murine-human) IgG1 monoclonal antibody representing targeted biological therapy.
Mechanism of Action: Infliximab binds directly to circulating TNF-α. Unlike etanercept (which acts as a soluble receptor or "decoy protein"), infliximab binds to the cytokine itself, physically preventing its interaction with cellular surface receptors. This interrupts the immune mechanisms of chronic inflammation.
Indications
The drug is prescribed to suppress unwanted immune responses in severe autoimmune conditions. Key clinical indications include:
- Rheumatoid arthritis (critical condition: must be used only in combination with the conventional synthetic DMARD methotrexate).
- Ankylosing spondylitis.
- Psoriasis.
- Crohn's disease.
Adverse Effects and Risks
Blockade of a key proinflammatory cytokine leads to profound suppression of the immune response. This induces iatrogenic immunodeficiency, requiring strict physician monitoring of the patient's condition.
- Infectious Complications: Conditions are created for opportunistic infections to develop. Tuberculosis, severe systemic mycoses, and viral infections pose the greatest danger. Patients require ongoing monitoring.
- Hematologic Abnormalities: Pancytopenia may develop, characterized by a combined reduction in circulating neutrophils, leukocytes, and platelets.
- Local Reactions: Inflammation may occur directly at the injection site.
Formulation and Administration Guidelines
The drug is available as a lyophilized powder in 0.1 g vials.
Unlike other biologics (such as anakinra or etanercept, which are administered subcutaneously), infliximab requires intravenous access.
- Route of Administration: Intravenous infusion.
- Dosage: For the treatment of rheumatoid arthritis, the dose is calculated individually at 3 mg/kg (0.003 g/kg) of body weight.
- Infusion Rate: Administration must be slow, at a rate of approximately 2 mL per minute. The total infusion time is about 2 hours.
- Frequency: Administered once every 2 weeks.