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Test Code ECULI Eculizumab, Serum


Advisory Information


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


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.


Secondary ID

65676

Useful For

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

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

Reporting Name

Eculizumab, S

Specimen Type

Serum

Specimen Minimum Volume

0.5 mL

Specimen Stability Information

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

Reject Due To

Hemolysis

Mild OK; Gross Reject

Lipemia

Mild Reject; Gross Reject

Icterus

Mild OK; Gross OK

Other

NA

Clinical Information

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

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

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.

Clinical Reference

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)

Day(s) and Time(s) Performed

Wednesday

Analytic Time

3 days

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

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 U.S. Food and Drug Administration.

CPT Code Information

80299

LOINC Code Information

Test ID Test Order Name Order LOINC Value
ECULI Eculizumab, S In Process

 

Result ID Test Result Name Result LOINC Value
65676 Eculizumab, S In Process