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Test Catalog

Test ID: TCZ    
Tocilizumab Quantitation, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Quantitation of tocilizumab

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Tocilizumab is a recombinant humanized IgG1 kappa monoclonal antibody that targets the interleukin-6 (IL-6) receptor. By binding soluble and membrane-bound IL-6 receptors, it blocks the pro-inflammatory effects of IL-6 mediated signaling. IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. Although a critical component of the immune response against infection, IL-6 is an important mediator in many autoimmune diseases. For example, IL-6 is produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis (RA). Studies in a variety of autoimmune diseases demonstrated that blocking IL-6 led to improved clinical outcomes. Tocilizumab is currently FDA-approved for the treatment of RA (moderate to severe), giant cell arteritis, systemic juvenile idiopathic arthritis (JIA), and polyarticular JIA.

 

IL-6 is also a critical component of the cytokine release syndrome (CRS). CRS results from an overactive immune response and leads to significantly enhanced expression of multiple inflammatory cytokines. CRS can occur in a variety of situations, including autoimmune disease, infection, and immune therapies. Chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of large B-cell non-Hodgkin lymphomas and acute lymphoblastic leukemia. In this therapy, the patient’s T cells are isolated and genetically engineered to express chimeric antigen receptors, which target the tumor cells. Some patients experience CRS after the engineered T cells are re-administered; in some cases the magnitude of the CRS can be life-threatening with manifestations including hypotension, tachycardia, and multi-organ failure. Tocilizumab is approved for treatment of CRS associated with CAR T-cell therapy. It is also being investigated for treatment of CRS in other clinical situations.

 

Pharmacokinetics of tocilizumab is characterized by nonlinear elimination, which is a combination of linear clearance and Michaelis-Menten elimination. The nonlinear part of tocilizumab elimination leads to an increase in exposure that is more than dose-proportional. The pharmacokinetic parameters of tocilizumab do not change with time. Due to the dependence of total clearance on tocilizumab serum concentrations, the half-life of tocilizumab is also concentration-dependent and varies depending on the serum concentration level. Population pharmacokinetic analyses in any patient population tested so far indicate no relationship between apparent clearance and the presence of anti-drug antibodies.(1)

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Tocilizumab limit of quantitation =0.5 mcg/mL

Interpretation Provides information to assist in interpretation of the test results

Measured concentrations of tocilizumab will be impacted by the route of administration, the dosage, and the time interval between drug administration and blood collection. Measured concentrations should be interpreted in the context of the last administered dose of tocilizumab.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Therapeutic concentrations for tocilizumab have not been defined for any of the approved clinical indications.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. ACTEMRA (tocilizaumab). Medication Guide and Instructions for Use. Genetech, Inc; 05/2020. Available at: www.gene.com/download/pdf/actemra_prescribing.pdf

2. Tanaka T, Narazaki M, Kishimoto T: IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295

3. Sheppard M, Laskou F, Stapleton PP, Hadavi S, Dasgupta B: Tocilizumab (Actemra). Hum Vaccin Immunother. 2017;13(9):1972-1988