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Test Catalog

Test ID: ECUMP    
Eculizumab Monitoring Panel, Serum

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

Therapeutic drug monitoring of eculizumab

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

Eculizumab (Soliris, Alexion Pharmaceuticals) is a humanized hybrid monoclonal antibody (IgG2/IgG4) that blocks complement C5 cleavage, thereby preventing the activation of the proinflammatory effects of C5a and the cytolytic effects of the membrane attack complex (MAC) formed by C5b-C9. It is FDA-approved for atypical hemolytic uremic syndrome(1) and paroxysmal nocturnal hemoglobinuria,(2) and it is also prescribed for other conditions such as C3 glomerulopathies.(3) The dosing regimen for an average adult may vary from 300 to 1,200 mg intravenously every 2 weeks during the maintenance stages, according to the condition for which the drug is prescribed. Therapy efficacy may be monitored by measuring efficiency of complement blockade.(4) Eculizumab will affect complement function assays that rely on the formation of the MAC to generate cell lysis. Although total complement (CH50) and soluble membrane attack complex (sMAC) have been recommended for eculizumab monitoring, the measurement of C5 function and C5 antigen more specifically indicate the impact of eculizumab on the complement system blockage and may help guide the next dose of the drug.

 

This panel measures the pharmacodynamics effects of eculizumab on the complement system.

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.

C5 COMPLEMENT ANTIGEN

10.6-26.3 mg/dL

 

C5 COMPLEMENT FUNCTIONAL

29-53 U/mL

Interpretation Provides information to assist in interpretation of the test results

The panel will measure the pharmacodynamic effects of eculizumab on the complement system. Total complement (CH50) function, alternative pathway (AH50) function, and C5 function assays will be decreased to a similar extent in the presence of eculizumab. The function of C5 may be completely absent when eculizumab is present at therapeutic concentrations. C5 antigen, on the other hand, will be normal or elevated. C5 complement function drops on average 30% with 25 mcg/mL of eculizumab, and 70% with 50 mcg/mL. In the presence of 100 mcg/mL of eculizumab in serum, there is on average 20% residual C5 function.

 

Decreased C5 function in the presence of normal or elevated C5 antigen concentrations suggests eculizumab is partially blocking C5 activity.

 

Absent C5 function in the presence of normal or elevated C5 antigen concentrations suggests eculizumab is completely blocking C5 activity.

 

Normal C5 function in the presence of normal or elevated C5 antigen concentrations suggests eculizumab concentration is not sufficient to block C5 activity.

 

If C5 function and C5 antigen concentrations are all decreased, it may be due to a secondary consumption process, poor hepatic synthesis of complement proteins or C5 deficiency. Clinical correlation recommended. If indicated, resubmit samples to confirm results.

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

As with all complement assays, proper sample handling is of utmost importance to ensure that the complement system is not activated before clinical testing

 

This panel of assays will not quantitate eculizumab concentrations.

 

If patient is on ravulizumab therapy, the best assay to monitor complement blockage is the alternative pathway (AH50). Test RAVUM / Ravulizumab Complement Blockage Monitoring, Serum offers appropriate interpretation for AH50 decreases in association with the expected ravulizumab drug concentration.

 

This panel will not measure the soluble membrane attack complex (sMAC).

Supportive Data

In a Mayo Clinic study with samples from individual subjects with normal complement activity defined by the total complement (CH50) assay and spiked with varying concentrations of eculizumab,(5) there was a significant decrease in CH50, alternative pathway function (AH50), and C5 functional results with eculizumab. Considering that the therapeutic target concentrations are expected to be above 50 mcg/mL, the results showed that eculizumab is partially blocking the complement cascade at 25 mcg/mL, with a complete blockage for C5 functional at 100 mcg/mL.

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

1. Wong EK, Goodship TH, Kavanagh D: Complement therapy in atypical haemolytic uraemic syndrome (aHUS). Mol Immunol. 2013;56:199-212

2. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L: Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007;25:1256-1264

3. Zuber J, Le Quintrec M, Krid S, et al: Eculizumab for atypical hemolytic uremic syndrome recurrence in renal transplantation. Am J Transplant. 2012;12:3337-3354

4. Volokhina EB, van de Kar NC, Bergseth G, et al: Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome. Clin Immunol. 2015;160(2):237-243

5. Andreguetto B, Murray D, Snyder M, et al: The impact of eculizumab in complement assays. Mol Immunol. 2015;67:119-120