Tocilizumab

TOCILIZUMAB

Mechanism of Action

Tocilizumab, a newer biologic humanized antibody, binds to sol-uble and membrane-bound IL-6 receptors, and inhibit the IL-6-mediated signaling via these receptors. IL-6 is a proinflammatory cytokine produced by different cell types including T cells, B cells, monocytes, fibroblasts, and synovial and endothelial cells. IL-6 is involved in a variety of physiologic processes such as T-cell activation, hepatic acute-phase protein synthesis, and stimulation of the inflammatory processes involved in diseases such as rheu-matoid arthritis.

Pharmacokinetics

The half-life of tocilizumab is dose-dependent, approximately 11 days for the 4 mg/kg dose and 13 days for the 8 mg/kg dose. IL-6 can suppress several CYP450 isoenzymes; thus, inhibiting IL-6 may restore CYP450 activities to higher levels. This may be clinically relevant for drugs that are CYP450 substrates and have a narrow therapeutic window (eg, cyclosporine or warfarin), and dosage adjustment of these medications may be needed.

Tocilizumab can be used in combination with nonbiologic DMARDs or as monotherapy. The recommended starting dose is 4 mg/kg intravenously every 4 weeks followed by an increase to 8 mg/kg dependent on clinical response. Additionally, dosage modifications are recommended on the basis of certain laboratory changes, elevated liver enzymes, neutropenia, and thrombocytopenia.

Indications

Tocilizumab is indicated for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonists.

Adverse Effects

Serious infections including tuberculosis, fungal, viral, and other opportunistic infections have occurred. Screening for tuberculosis should be done prior to beginning tocilizumab. The most com-mon adverse reactions were upper respiratory tract infections, headache, hypertension, and elevated liver enzymes.

Neutropenia and reduction in platelet counts occur occasionally, and lipids (eg, cholesterol, triglycerides, LDL, and HDL) should be monitored. GI perforation has been reported when using tocilizumab in patients with diverticulitis or who are using corticosteroids.