Introduction
Tocilizumab is a recombinant humanized monoclonal antibody IL-6 receptor inhibitor used to treat inflammatory and autoimmune conditions. It was first described in the literature in 2003 when Chugai, a subsidiary of Roche began developing IL-6 inhibiting monoclonal antibodies. It is currently being investigated to treat severely ill patients with COVID-19.
Uses
Tocilizumab is an interleukin-6 (IL-6) receptor antagonist used to treat Cytokine Release Syndrome (CRS), Systemic Juvenile Idiopathic Arthritis (sJIA), Giant Cell Arteritis (GCA), and Rheumatoid Arthritis (RA).
Tocilizumab is indicated to treat moderate to severe rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome.
Associated Conditions
Pharmacodynamics
Tocilizumab is an IL-6 inhibiting monoclonal antibody used to treat autoimmune and inflammatory conditions. Tocilizumab has a long duration of action as it is generally given every 4 weeks and has a wide therapeutic index. Patients should be counselled regarding the risk of infections, GI perforation, and hepatotoxicity.
Mechanism of Action
Interleukin 6 (IL-6) is a pro-inflammatory cytokine produced by cells including T-cells, B-cells, lymphocytes, monocytes, fibroblasts. IL-6 rapidly induces C-reactive protein, serum amyloid A, fibrinogen, haptoglobin, and α-1-antichymotrypsin while inhibiting production of fibronectin, albumin, and transferrin. IL-6 also induces antibody production, induces cytotoxic T-cell differentiation, and inhibits regulatory T-cell differentiation. Tocilizumab binds soluble and membrane bound IL-6 receptors, preventing IL-6 mediated inflammation.
Absorption
A 162mg subcutaneous dose given weekly has a Cmax of 51.3±23.2µg/mL and an AUC of 8254±3833µg*h/mL. A 162mg subcutaneous dose given every 2 weeks has a Cmax of 13±8.3µg/mL and an AUC of 3460±2530µg*h/mL. A 162mg subcutaneous dose given every 4 weeks has a Cmax of 154±42µg/mL and an AUC of 39216±14304µg*h/mL.
Volume of Distribution
In rheumatoid arthritis patients, the central volume of distribution is 3.5L, the peripheral volume of distribution is 2.9L, and the volume of distribution at steady state is 6.4L. In giant cell arteritis patients, the central volume of distribution is 4.09L, the peripheral volume of distribution if 3.37L, and the volume of distribution at steady state is 7.46L. In pediatric patients with polyarticular juvenile arthritis, the central volume of distribution is 1.98L, the peripheral volume of distribution is 2.1L, and the volume of distribution at steady state is 4.08L. In pediatric patients with systemic juvenile idiopathic arthritis, the central volume of distribution is 1.87L, the peripheral volume of distribution is 2.14L, and the volume of distribution at steady state is 4.01L.
Protein Binding
Data regarding the serum protein binding of tocilizumab is not readily available.
Route of Elimination
Data regarding the exact route of elimination of monoclonal antibodies is not readily available.
Half Life
The half life of tocilizumab is concentration dependent. The terminal half life in rheumatoid arthritis patients is 21.5 days. The absorption half life in rheumatoid arthritis and giant cell arteritis patients was 4 days, and in polyarticular juvenile idiopathic arthritis patients and systemic juvenile idiopathic arthritis patients was 2 days.
Clearance
The linear clearance in rheumatoid arthritis patients is 12.5mL/h, in giant cell arteritis patients is 6.7mL/h, in polyarticular juvenile idiopathic arthritis patients is 5.8mL/h, and in systemic juvenile idiopathic arthritis is 5.7mL/h. Clearance is dose dependent and changes from non linear at low doses to linear at higher doses.
Toxicity
Data regarding overdoses of tocilizumab are not readily available. Patients experiencing an overdose may develop neutropenia. In case of overdose, monitor patients for signs of adverse reactions and provide symptomatic and supportive treatment.
Food Interactions
No interactions found.
Dosage
Rheumatoid Arthritis: Tocilizumab may be used as monotherapy or concomitantly with methotrexate or other non-biologic DMARDs as an intravenous infusion.
Recommended Intravenous Dosage Regimen:
- The recommended dosage of Tocilizumab for adult patients given as a 60-minute single intravenous drip infusion is 4 mg per kg of body weight every 4 weeks followed by an increase to 8 mg per kg of body weight every 4 weeks based on clinical response.
- Reduction of dose from 8 mg per kg of body weight to 4 mg per kg of body weight is recommended for management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia
- Doses exceeding 800 mg per infusion are not recommended in RA patients
subcutaneous injection alone or in combination with methotrexate. Do not change dose based solely on a single body weight measurement, as weight may fluctuate.
Recommended Intravenous Dosage Regimen: The recommended dosage of Tocilizumab for PJIA patients given once every 4 weeks as a 60-minute single intravenous drip infusion is:
- Patients less than 30 kg weight: 10 mg per kg of body weight
- Patients at or above 30 kg weight: 8 mg per kg of body weight
Recommended Intravenous Dosage Regimen: The recommended dose of Tocilizumab for SJIA patients given
once every 2 weeks as a 60-minute single intravenous drip infusion is:
- Patients less than 30 kg weight: 12 mg per kg of body weight
- Patients at or above 30 kg weight: 8 mg per kg of body weight
intravenous infusion as follows:
- Patients less than 30 kg weight: 12 mg per kg of body weight
- Patients at or above 30 kg weight: 8 mg per kg of body weight
Cytokine Release Syndrome: Use only the intravenous route for treatment of CRS. The recommended dose of Tocilizumab for treatment of CRS given as a 60-minute intravenous infusion is:
Recommended Intravenous CRS Dosage
- Patients less than 30 kg weight: 12 mg per kg of body weight Alone or in combination with corticosteroids.
- Patients at or above 30 kg weight: 8 mg per kg of body weight Alone or in combination with corticosteroids.
Giant Cell Arteritis:
- The recommended dosage of Tocilizumab for adult patients given as a 60-minute single intravenous drip infusion is 6 mg per kg of body weight every 4 weeks in combination with a tapering course of glucocorticoids.
- Tocilizumab can be used alone following discontinuation of glucocorticoids
- Doses exceeding 600 mg per infusion are not recommended in GCA patients
- The recommended dose of Tocilizumab for adult patients with SSc-ILD is 162 mg given once every week as a subcutaneous injection.
- Intravenous administration is not approved for SSc-ILD
- For adults with RA, GCA, CRS, PJIA and SJIA patients at or above 30 kg, dilute to 100 mL in 0.9% or 0.45% Sodium Chloride Injection, USP for intravenous infusion using aseptic technique
- For PJIA, SJIA and CRS patients less than 30 kg, dilute to 50 mL in 0.9% or 0.45% Sodium Chloride Injection, USP for intravenous infusion using aseptic technique
- Administer as a single intravenous drip infusion over 1 hour; do not administer as bolus or push.