Actemra (Tocilizumab) Usage and Dosage
Rheumatoid Arthritis
For adult patients with rheumatoid arthritis, tocilizumab is administered intravenously at 4 mg/kg every 4 weeks as the starting dose, with escalation to 8 mg/kg every 4 weeks based on clinical response, or subcutaneously at 162 mg every other week (for patients <100 kg) or weekly (for patients ≥100 kg), with dose escalation based on clinical response. 1
Intravenous Dosing
- Starting dose: 4 mg/kg every 4 weeks 1
- Escalation: Increase to 8 mg/kg every 4 weeks based on clinical response 1
- Maximum dose: Do not exceed 800 mg per infusion 1
- Administration: Dilute to 100 mL in 0.9% or 0.45% Sodium Chloride and infuse over 1 hour 1
- Combination therapy: May be used alone or in combination with methotrexate or other non-biologic DMARDs 1
Subcutaneous Dosing
- Patients <100 kg: 162 mg every other week, with escalation to weekly dosing based on clinical response 1
- Patients ≥100 kg: 162 mg weekly 1
Clinical Evidence
- The 8 mg/kg IV dose every 4 weeks is more effective than placebo, methotrexate, or other DMARDs in reducing disease activity and improving quality of life 2
- The 4 mg/kg dose in combination with methotrexate was not statistically different from 8 mg/kg, supporting its use as the recommended starting dose in the United States 2
- Both doses inhibit structural joint damage in patients with inadequate response to methotrexate 2
Systemic Juvenile Idiopathic Arthritis (sJIA)
For children with systemic JIA, tocilizumab is strongly recommended as initial biologic therapy following inadequate response to NSAIDs and/or glucocorticoids, with intravenous dosing of 12 mg/kg (for patients <30 kg) or 8 mg/kg (for patients ≥30 kg) every 2 weeks, or subcutaneous dosing of 162 mg every 2 weeks (for patients <30 kg) or weekly (for patients ≥30 kg). 3, 1
Intravenous Dosing
- Patients <30 kg: 12 mg/kg every 2 weeks 1
- Patients ≥30 kg: 8 mg/kg every 2 weeks 1
- Dilution: For patients <30 kg, dilute to 50 mL in 0.9% or 0.45% Sodium Chloride; for patients ≥30 kg, dilute to 100 mL 1
- Administration: Infuse over 1 hour 1
Subcutaneous Dosing
Treatment Algorithm for sJIA
- Initial therapy: IL-1 and IL-6 inhibitors (including tocilizumab) are strongly recommended over conventional synthetic DMARDs for inadequate response to NSAIDs and/or glucocorticoids 3
- Positioning: Tocilizumab is recommended for active joint count >0 following treatment with anakinra (level B evidence) or methotrexate/leflunomide (level B evidence) 3
- Conventional synthetic DMARDs are strongly recommended against as initial monotherapy 3
Clinical Efficacy
- In a randomized trial, 85% of patients receiving tocilizumab achieved the primary endpoint (absence of fever and ≥30% improvement in ACR core set) compared to 24% with placebo at week 12 4
- At week 52,80% of patients had ≥70% improvement with no fever, 48% had no joints with active arthritis, and 52% discontinued oral glucocorticoids 4
- Subcutaneous tocilizumab provides exposure and risk/benefit profiles similar to intravenous administration, with 53% of sJIA patients achieving clinical remission on treatment by week 52 5
Polyarticular Juvenile Idiopathic Arthritis (pJIA)
For children with polyarticular JIA, tocilizumab is conditionally recommended in combination with a DMARD for inadequate response to methotrexate, with intravenous dosing of 10 mg/kg (for patients <30 kg) or 8 mg/kg (for patients ≥30 kg) every 4 weeks, or subcutaneous dosing of 162 mg every 3 weeks (for patients <30 kg) or every 2 weeks (for patients ≥30 kg). 3, 6, 1
Intravenous Dosing
- Patients <30 kg: 10 mg/kg every 4 weeks 1
- Patients ≥30 kg: 8 mg/kg every 4 weeks 1
- Dilution: For patients <30 kg, dilute to 50 mL; for patients ≥30 kg, dilute to 100 mL in 0.9% or 0.45% Sodium Chloride 1
- Administration: Infuse over 1 hour 1
Subcutaneous Dosing
Treatment Algorithm for pJIA
- Initial therapy: DMARD (preferably methotrexate) is strongly recommended over NSAID monotherapy 3
- Escalation: For moderate/high disease activity with inadequate response to DMARD monotherapy, adding a biologic (including tocilizumab) is conditionally recommended 3, 6
- Combination therapy: Tocilizumab in combination with a DMARD is conditionally recommended over biologic monotherapy (low quality evidence) 3
- After TNF inhibitor failure: Switching to a non-TNF biologic (tocilizumab or abatacept) is conditionally recommended over switching to a second TNF inhibitor 6
Clinical Evidence
- Subcutaneous tocilizumab achieved steady-state minimum concentration >5th percentile of IV tocilizumab in 100% of pJIA patients 5
- By week 52,31% of pJIA patients achieved clinical remission on treatment with subcutaneous tocilizumab 5
Laboratory Monitoring and Safety Considerations
Pre-Treatment Requirements
- Do not initiate in patients with absolute neutrophil count <2000/mm³, platelet count <100,000/mm³, or ALT/AST >1.5 times upper limit of normal for RA, pJIA, and sJIA 1
- Tuberculosis screening is required before initiating tocilizumab 3
Common Adverse Events
- Infections: Reported in 78.4% of sJIA patients and 69.2% of pJIA patients in clinical trials 5
- Injection site reactions: Occur in 41.2% of sJIA patients and 28.8% of pJIA patients receiving subcutaneous administration 5
- Neutropenia: Grade 3 or 4 neutropenia developed in 17% of patients in clinical trials 4
- Elevated aminotransferases: Occurred in patients with levels >2.5 times upper limit of normal 4
Critical Safety Warnings
- Serious infections: Do not administer during active infection; interrupt treatment until infection is controlled 1
- Gastrointestinal perforation: Use with caution in patients at increased risk 1
- Hypersensitivity reactions: Including anaphylaxis and DRESS syndrome have been reported; discontinue immediately and treat promptly 1
- Live vaccines: Avoid use with tocilizumab 1