Test Catalog

Test Id : ECULI

Eculizumab, Serum

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

Assessing the response to eculizumab therapy

 

Assessing the need for dose escalation

 

Evaluating the potential for dose de-escalation or discontinuation of therapy in remission states

 

Monitoring patients who need to be above a certain eculizumab concentration in order to improve the odds of a clinical response for therapy optimization

Method Name
A short description of the method used to perform the test

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Eculizumab, S

Aliases
Lists additional common names for a test, as an aid in searching

ECULI

ECUMP

Soliris

Eculizumab

Specimen Type
Describes the specimen type validated for testing

Serum

Ordering Guidance

Therapeutic drug monitoring of eculizumab may be useful when assessing response to therapy is difficult or patients need to be above a certain therapeutic monoclonal antibody (mAb) concentration in order to improve the odds of a clinical response for therapy optimization, including potential dose de-escalation or discontinuation of therapy in remission states. Pharmacodynamic studies of complement blockage are also common, see ECUMP / Eculizumab Monitoring Panel, Serum for more information on related testing.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: Pembrolizumab/Keytruda must be discontinued at least 4 weeks prior to testing for eculizumab quantitation in serum.

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 1 mL

Collection Instructions:

1. Draw blood immediately before next scheduled dose.

2. Spin down within 2 hours of draw.

Forms

If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-Renal Diagnostics Test Request (T830)

-Coagulation Test Request (T753)

-Therapeutics Test Request (T831)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.5 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 28 days
Frozen 30 days
Ambient 4 days

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

Assessing the response to eculizumab therapy

 

Assessing the need for dose escalation

 

Evaluating the potential for dose de-escalation or discontinuation of therapy in remission states

 

Monitoring patients who need to be above a certain eculizumab concentration in order to improve the odds of a clinical response for therapy optimization

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

Eculizumab (Soliris, Alexion Pharmaceuticals), a humanized monoclonal IgG2/4 kappa antibody therapeutic directed against complement component C5, has been heralded as a breakthrough treatment for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). By association with C5, eculizumab inhibits the terminal complement pathway through simultaneous blockade of the generation of the potent prothrombotic and proinflammatory molecule, C5a, and the formation of membrane attack complex initiator, C5b. Since all 3 arms of the complement cascade converge at the point of C5 activation, targeted by eculizumab, this drug may have broad potential application and is being clinically evaluated in other disorders with complement overactivation. In PNH, eculizumab has become the standard of care, proving to be a safe and effective therapy with long-lasting effects, potentially enabling patients to become transfusion-independent and extending their survival.

 

Eculizumab is administered as an IV infusion, and the dosing regimen prescribed for an average adult diagnosed with PNH is 600 mg weekly for the first 4 weeks, followed by 900 mg for the fifth dose 1 week later; then, 900 mg every 2 weeks thereafter. Eculizumab has been evaluated in aHUS patients through 2 prospective, open-label, single-arm studies (C08-002 and C08-003) as well as a single-arm retrospective study. In aHUS, it is prescribed for an average adult at 900 mg weekly for the first 4 weeks, followed by 1200 mg for the fifth dose 1 week later, then 1200 mg every 2 weeks thereafter. Eculizumab was generally well tolerated and no significant adverse effects were attributed to drug treatment; some adverse reactions included upper respiratory tract infections and diarrhea in prospective and retrospective studies, hypertension, headache, and leucopenia (C08-002/C08-003), and fever (C09-001R). Additional case reports suggest that eculizumab may prevent posttransplantation recurrence of aHUS, even in those patients harboring CFH/CFHR1 hybrid gene variants, who are at very high risk of recurrence. Further research is needed to determine the duration of eculizumab therapy in the context of the genetic background of aHUS cases and risk of disease relapse.

 

The drawbacks of eculizumab therapy are associated with its potentially life-threatening side-effects, variations in response profiles, and the cost of treatment. Patients treated with eculizumab are at an increased risk of susceptibility towards life-threatening infections such as Neisseria meningitides; to prevent such infections, vaccinations and, in some cases, prophylactic antibiotic treatment is recommended. A number of serious and potentially treatment-related adverse effects were observed including pyrexia, headache, abdominal distension, viral infection, renal impairment, and anxiety. It is important to note that there is variability among individuals towards eculizumab response, and some patients may not benefit from this therapy. This is potentially a life-long therapy with a high cost of administration. The cost of eculizumab may limit its use in routine clinical practice worldwide.

 

Therapeutic drug monitoring of eculizumab is typically not performed during treatment regimens due to the low toxicity of biologics. Measurement of therapy efficacy is usually based on clinical presentation and improvement of symptoms, although this landscape is changing, as it is recognized that patients undergoing life-long therapy with eculizumab who are in complete remission without significant evidence or pathogenic genetic variants leading to increased risk of relapse may benefit from dose de-escalation or discontinuing therapy.

 

Pharmacodynamic studies of complement blockage may also be recommended, see ECUMP / Eculizumab Monitoring Panel, Serum for more information.

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.

Lower limit of quantitation =5.0 mcg/mL

>35 Therapeutic concentration for paroxysmal nocturnal hemoglobinuria (PNH)

>50 Therapeutic concentration for atypical hemolytic uremic syndrome (aHUS)

Interpretation
Provides information to assist in interpretation of the test results

Minimum trough therapeutic concentrations (immediately before next infusion) of eculizumab are expected to be above 35 mcg/mL for paroxysmal nocturnal hemoglobinuria (PNH) and above 50 mcg/mL for aHUS.

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

Patients actively undergoing therapy with both pembrolizumab and eculizumab (extremely rare scenario) should not have their therapeutic eculizumab level assessed using this test. If the patient has taken pembrolizumab in the past, they should wait for 4 weeks after therapy with pembrolizumab has ended before being tested for eculizumab quantitation using this method.

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

1. Ladwig PM, Barnidge DR, Willrich MA: Quantification of the IgG2/4 kappa Monoclonal Therapeutic Eculizumab from Serum Using Isotype Specific Affinity Purification and Microflow LC-ESI-Q-TOF Mass Spectrometry. J Am Soc Mass Spectrom 2017 May;28(5):811-817

2. Willrich MA, Murray DL, Barnidge DR, et al: Quantitation of infliximab using clonotypic peptides and selective reaction monitoring by LC-MS/MS. International immunopharmacology 2015 Sep;28(1):513-520

3. Ladwig PM, Barnidge DR, Willrich MA: Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory. Clin Vaccine Immunol 2017 May 5;24(5)

Method Description
Describes how the test is performed and provides a method-specific reference

Eculizumab is extracted from serum and measured by liquid chromatography (high-resolution accurate-mass, HRAM) mass spectrometry.(Unpublished Mayo Method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Wednesday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 7 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

2 weeks

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

80299

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
ECULI Eculizumab, S 90240-3
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
65676 Eculizumab, S 90240-3

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Create a PDF

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports