Pathogenetic Rationale for Use
In rheumatoid arthritis, synovial macrophages play a key role in joint destruction. They excessively secrete pro-inflammatory cytokines—interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α). These substances trigger an aggressive cascade of reactions in tissues:
- Dramatically stimulate the synthesis of the enzyme collagenase, which directly cleaves and destroys joint structures.
- Significantly increase bone resorption, weakening the bone.
- Inhibit the synthesis of cartilage proteoglycans, depriving it of the ability to repair.
Genetically engineered biologic agents are designed to interrupt this pathological process. They act in a targeted manner: either by binding the cytokines themselves or by blocking their cellular receptors.
Interleukin-1 (IL-1) Blockers
In medical literature, the term "receptor antagonist" is most commonly associated with anakinra. This is a recombinant biologic agent representing a recombinant cytokine receptor antagonist.
- Mechanism of action: Anakinra competitively binds to IL-1 receptors. By taking the place of interleukin on the cell surface, the drug reliably blocks its action, thereby suppressing inflammation and halting cartilage destruction.
- Indications and regimen: The drug is prescribed for severe forms of rheumatoid arthritis, including cases where other conventional disease-modifying antirheumatic drugs (DMARDs) have proven ineffective. It is administered subcutaneously once daily.
- Adverse effects: Therapy is associated with the risk of neutropenia. Furthermore, due to deep interference with the immune response, there is a high risk of opportunistic infections and tuberculosis, requiring constant medical monitoring.
Tumor Necrosis Factor (TNF-α) Blockers
This group is represented by drugs that neutralize TNF-α through different mechanisms.
- Etanercept is a recombinant human soluble TNF receptor fusion protein. It acts as a "decoy protein": circulating in the blood, it binds free TNF-α and physically blocks its interaction with actual cellular receptors. The drug is indicated for moderate-to-severe forms of rheumatoid arthritis. It is administered subcutaneously twice a week. It can be used either as monotherapy or in combination with methotrexate. It features relatively low toxicity, with injection site reactions being the most common adverse effect.
- Infliximab is a chimeric (murine-human) monoclonal antibody of the IgG class against TNF-α. Unlike etanercept, infliximab binds directly to the cytokine itself, preventing it from binding to the receptor. In rheumatoid arthritis, it is prescribed exclusively in combination with methotrexate. The drug is also used for psoriasis, ankylosing spondylitis, and Crohn's disease. It is administered as an intravenous infusion (lasting about two hours) every two weeks. Local reactions (infusion site reactions) and severe hematologic complications, such as pancytopenia (decreased neutrophils, leukocytes, and platelets), are possible.
Risks of Immunosuppressive Therapy
Biologic therapy for rheumatoid arthritis belongs to the class of immunosuppressive interventions. The main complication of such therapy is profound suppression of the immune response, leading to iatrogenic (medically induced) immunodeficiency.
This condition creates ideal conditions for the development of severe opportunistic infections. While receiving cytokine antagonists, patients become extremely vulnerable to tuberculosis reactivation, severe systemic mycoses, and various viral infections. For this reason, the prescription of biologic agents requires careful preliminary screening and continuous monitoring of blood counts throughout the entire course of treatment.