Tocilizumab

• Rheumatoid Arthritis
• Giant Cell Arteritis
• Juvenile Idiopathic Arthritis
• Cytokine Release Syndrome

Tocilizumab is a humanized monoclonal antibody that inhibits interleukin-6 (IL-6) receptor signaling. It is used to treat rheumatoid arthritis, giant cell arteritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, cytokine release syndrome, and systemic sclerosis-associated interstitial lung disease.

Mechanism of Action

Tocilizumab blocks IL-6 signaling:

• IL-6 receptor antagonism: Binds to both soluble and membrane-bound IL-6 receptors
• Blocks IL-6 signal transduction: Prevents IL-6 from exerting its pro-inflammatory effects
• Reduces acute phase reactants: Decreases CRP, ESR, serum amyloid A
• Modulates immune response: Affects T cell and B cell function, hepatic protein synthesis

IL-6 is a pleiotropic cytokine involved in inflammatory and immune responses.

Available Formulations

• IV solution: 80 mg/4 mL, 200 mg/10 mL, 400 mg/20 mL
• SC prefilled syringe: 162 mg/0.9 mL
• SC autoinjector (ACTPen): 162 mg/0.9 mL

Medical Uses

FDA-Approved Indications:

• Rheumatoid arthritis (moderate to severe)
• Giant cell arteritis
• Polyarticular juvenile idiopathic arthritis (PJIA) in patients ≥2 years
• Systemic juvenile idiopathic arthritis (SJIA) in patients ≥2 years
• Cytokine release syndrome (CRS) - severe or life-threatening
• Systemic sclerosis-associated interstitial lung disease (SSc-ILD)
• COVID-19 in hospitalized patients requiring supplemental oxygen (emergency use)

Dosing Guidelines

Rheumatoid Arthritis:

• IV: 4 mg/kg every 4 weeks; may increase to 8 mg/kg (max 800 mg)
• SC: 162 mg every other week; may increase to weekly if inadequate response

Giant Cell Arteritis:

• SC: 162 mg weekly (with tapering glucocorticoids)

Cytokine Release Syndrome:

• IV: 8 mg/kg (max 800 mg) for patients ≥30 kg; 12 mg/kg for patients <30 kg
• May repeat doses if no clinical improvement

SJIA/PJIA:

• Weight-based IV dosing every 2-4 weeks

Important Safety Information

Boxed Warning:

• Serious infections: Patients are at increased risk for serious infections

Contraindications:

• Known hypersensitivity to tocilizumab

Warnings and Precautions:

• Serious infections: TB, invasive fungal, bacterial, viral, opportunistic; do not initiate during active infection
• GI perforation: Risk increased in patients with diverticulitis
• Hepatotoxicity: Monitor liver enzymes
• Neutropenia, thrombocytopenia: Monitor CBC
• Lipid abnormalities: Monitor lipids 4-8 weeks after starting
• Immunizations: Avoid live vaccines

Drug Interactions

• CYP450 substrates: IL-6 inhibition may affect CYP expression; monitor narrow therapeutic index drugs (warfarin, theophylline, cyclosporine)
• Live vaccines: Avoid
• Other biologics: Not recommended in combination with TNF inhibitors or other biologics

Special Populations

• Hepatic Impairment: Not recommended if ALT/AST >1.5x ULN
• Renal Impairment: No adjustment for mild to moderate
• Pregnancy: May affect infant immune response; use only if benefit outweighs risk
• Lactation: Unknown if excreted in milk
• Elderly: Higher infection risk
• Pediatric: Approved for SJIA and PJIA ≥2 years