Last updated: October 29, 2014
Trade Names: Actemra
Drug Class: Biologic DMARD, IL-6 receptor antagonist
Preparations: IV: 80 mg/4 mL, 200 mg/10 mL, 400 mg/20mL
Subcutaneous injection: 162 mg/0.9 mL prefilled syringe
Dose: Adults IV: initially 4 mg/kg every 4 weeks, dose may be increased to 8 mg/kg depending on response, maximum dose is 800 mg.
Subcutaneous injection: less than 100 kg – 162 mg every other week, may increase to every week depending on response; 100 kg or heavier – 162 mg every week. Adjust dose according to monitoring of LFTs, platelets and absolute neutrophil count (ANC).
If AST/ALT increased >1 up to 3x normal: Check other drugs; for persistent increases reduce to low dose (i.e., 4 mg/kg (IV) or reduce frequency of subcutaneous injection to every 2 weeks) or interrupt therapy till AST/ALT normalized.
If AST/ALT increased 3-5x normal: Confirm with a repeat test and interrupt therapy till below 3x normal and then restart at low dose (as above). If enzymes do not fall below 3x normal discontinue tocilizumab.
If AST/ALT increased more than 5x normal: Discontinue tocilizumab.
If platelet count 50,000-100,000/mm3 or ANC 500-1000/mm3: Interrupt therapy till platelets more than 100,000/mm3 or ANC more than 1,000/mm3 and then restart at low dose.
If platelet count less than 50,000/mm3 or ANC less than 500/mm3: Discontinue tocilizumab.
Mechanism of Action: Binds to IL-6 receptors and blocks the effects of the cytokine
Contraindications: Hypersensitivity, active infection, do not initiate if ANC less than 2000/mm3, or platelets less than 100,000/mm3, or AST or ALT more than 1.5x upper limit of normal. Do not use with TNF-antagonists, biologics, tofacitinib, abatacept. Do not use if hepatic impairment. Avoid live virus vaccines and BCG.
Precautions: Increased risk of serious infections including TB and fungal. Exclude latent or active TB with a skin test or TB blood test (interferon-gamma release assays or IGRA). Caution in debilitated or high risk of infection. Exclude active hepatitis B infection or carriage. Rare CNS demyelination and gastrointestinal perforation – caution if preexisting risk. IV infusion should be performed in a center able to deal with anaphylaxis.
Monitoring: Check CBC with diff, LFTs, cholesterol at baseline and exclude TB. Check CBC , platelets, ANC, AST, ALT every 4-8 weeks for 6 months after initiation and then every 2-3 months. Lipid panel after 4-8 weeks and then every 6 months. After therapy started, additional TB testing may be indicated for individuals likely to have exposure to TB.
Pregnancy Risk: C
Common: Increased cholesterol, increased liver enzymes, infusion reactions (IV), injection site reactions (subcutaneous), hypertension, headache, upper respiratory tract infections
Less common: Allergy, rash, serious infection (bacterial, viral (e.g., zoster) and also atypical and opportunistic infections), decrease in neutrophil or and platelet count
Rare: Neutropenia, thrombocytopenia, anaphylaxis, gastrointestinal perforation, demyelinating CNS disease, hepatitis, vasculitis
Live virus vaccines and BCG: Avoid
Other biologics and potent immunosuppressants: Avoid, increased risk of infection
Patient Instructions: Avoid live virus vaccines. Avoid pregnancy. Stop injections if have an infection
Comments: The 8 mg/kg IV dose was generally more effective than the 4 mg/kg dose in clinical trials. Doses lower than 4 mg/kg IV are not recommended because of increased immunogenicity and decreased efficacy. Tocilizumab is effective for RA as monotherapy but generally responses have been greater when combined with methotrexate. In a monotherapy trial tocilizumab 8 mg/kg IV every 4 weeks was more effective than adalimumab 40 mg subQ every 2 weeks. IL6 drives CRP production, therefore CRP decreases dramatically. The clinical significance of the increase in cholesterol as regards cardiovascular risk is not known; treat increased cholesterol according to current guidelines. Limited information on long-term risks (e.g. malignancy). Limited information in other conditions – case series or case reports suggest possible efficacy in giant cell arteritis, polymyalgia rheumatica, Takayasu’s arteritis, adult onset Still’s disease, Castleman’s disease and other conditions.
Clinical Pharmacology: Half-life is 6-13 days. Biologic agents are not metabolized and have few drug interactions.
Smolen JS, Schoels MM, Nishimoto N, et al. Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions. Ann Rheum Dis 2013;72:482-92. PMID: 23172750.
Gabay C, Emery P, van Vollenhoven R, et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. 2013;381:1541-50. PMID: 23515142.
Nam JL, Ramiro S, Gaujoux-Viala C, et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2014 ;73(3):516-28. PMID:24399231