What are the indications and dosing guidelines for Tocilizumab (Actemra)?

From the Guidelines

Tocilizumab (Actemra) is indicated for several inflammatory conditions, including rheumatoid arthritis (RA), giant cell arteritis (GCA), polyarticular juvenile idiopathic arthritis (pJIA), systemic juvenile idiopathic arthritis (sJIA), cytokine release syndrome (CRS), and severe COVID-19 with respiratory failure, with dosing guidelines varying by condition and age. The most recent and highest quality study, 1, provides recommendations for the use of IL-6 pathway inhibitors, including tocilizumab, in patients with COVID-19. Key points to consider when using tocilizumab include:

• For adult RA, the typical dosing is 4-8 mg/kg intravenously every 4 weeks or 162 mg subcutaneously weekly or every other week.
• For GCA, the recommended dose is 162 mg subcutaneously weekly or every other week, often combined with a tapering course of glucocorticoids.
• In pJIA (age ≥2 years), dosing is weight-based: 10 mg/kg for patients <30 kg and 8 mg/kg for those ≥30 kg, given intravenously every 4 weeks, or 162 mg subcutaneously every 2-3 weeks depending on weight.
• For sJIA (age ≥2 years), the IV dose is 12 mg/kg for patients <30 kg and 8 mg/kg for those ≥30 kg every 2 weeks, or 162 mg subcutaneously weekly or every other week based on weight.
• For CRS, weight-based IV dosing ranges from 8-12 mg/kg, with a maximum single dose of 800 mg.
• For COVID-19, a single IV dose of 8 mg/kg (maximum 800 mg) is typically used, as recommended by guidelines such as those from the NIH, which suggest its use in hospitalized patients with rapidly increasing supplemental oxygen needs or oxygen saturation <90% on room air 1. Before initiating treatment, patients should be screened for latent tuberculosis, hepatitis, and assessed for absolute neutrophil count, platelet count, and liver enzymes, as tocilizumab can cause serious infections, neutropenia, thrombocytopenia, and elevated liver enzymes, as noted in studies such as 1, 1, and 1. Tocilizumab works by blocking interleukin-6 receptors, thereby reducing inflammation and modifying immune responses in these conditions. It is essential to consider the potential risks and benefits of tocilizumab, including the increased risk of infectious respiratory adverse events, as highlighted in a systematic review and meta-analysis of RCTs conducted in patients with rheumatoid arthritis 1. Overall, the use of tocilizumab should be guided by the most recent and highest quality evidence, with careful consideration of the individual patient's condition, age, and potential risks and benefits.

From the FDA Drug Label

2.11 Dosage Modifications due to Serious Infections or Laboratory Abnormalities 3 DOSAGE FORMS AND STRENGTHS Intravenous Infusion Injection: 80 mg/4 mL, 200 mg/10 mL, 400 mg/20 mL as a clear, colorless to pale yellow solution in 20 mg/mL single-dose vials for further dilution prior to intravenous infusion. Subcutaneous Injection Injection: 162 mg/0.9 mL clear, colorless to slightly yellowish solution in a single-dose prefilled syringe or single-dose prefilled ACTPen® autoinjector.

The indications for Tocilizumab (Actemra) are not explicitly stated in the provided text, but the dosing guidelines are as follows:

• Intravenous Infusion: 80 mg/4 mL, 200 mg/10 mL, 400 mg/20 mL
• Subcutaneous Injection: 162 mg/0.9 mL Dosage modifications are recommended due to serious infections or laboratory abnormalities, such as:
• Holding ACTEMRA treatment if a patient develops a serious infection
• Dose reduction or holding for liver enzyme abnormalities, low neutrophil counts, and low platelet counts 2

From the Research

Indications for Tocilizumab

• Tocilizumab, also known as Actemra, is an interleukin-6 receptor antagonist that has been used to treat various conditions, including rheumatoid arthritis and COVID-19-associated cytokine storm syndrome 3, 4, 5, 6, 7.
• In the context of COVID-19, tocilizumab has been used to treat patients with severe respiratory distress, thought to be mediated by cytokine release 3, 4, 5, 6.
• The use of tocilizumab in COVID-19 patients has been associated with improved clinical outcomes, including reduced risk of invasive mechanical ventilation or death 6.

Dosing Guidelines for Tocilizumab

• The dosing guidelines for tocilizumab vary depending on the specific condition being treated and the patient's weight.
• In the study by 3, patients received tocilizumab at a mean dose of 724 mg (7.4 mg/kg).
• In the study by 5, patients received 4-8 mg/kg of tocilizumab, with Chinese treatment guidelines.
• In the study by 6, tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total).

Administration and Monitoring

• Tocilizumab can be administered intravenously or subcutaneously, depending on the specific formulation and treatment guidelines 6.
• Patients receiving tocilizumab should be monitored for clinical improvement, including changes in oxygenation status, inflammatory markers, and other relevant parameters 3, 4, 5, 6.
• The use of tocilizumab has been associated with potential side effects, including new infections and transient abnormal liver or renal function indicators 5, 6.