Test Catalog

Test Id : RAVU

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Ravulizumab, Serum

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Overview

Test Catalog

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

Assessing the response to ravulizumab therapy

 

Assessing the need for dose escalation

 

Evaluating the potential for dose deescalation or discontinuation of therapy in remission states

 

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

 

This test is not useful as the sole basis for a diagnosis or treatment decisions

Highlights

Therapeutic drug monitoring of ravulizumab may be useful when assessing response to therapy is difficult or when patients need to be above a certain therapeutic monoclonal antibody 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.

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

Liquid Chromatography Tandem Mass Spectrometry, High Resolution Accurate Mass (LC-MS/MS HRAM)

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

Ravulizumab, S

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

RAVU

Ravulizumab

Ultomiris

Alexion

Specimen Type
Describes the specimen type validated for testing

Serum

Ordering Guidance

To measure only serum concentration of ravulizumab, order RAVU / Ravulizumab, Serum.

 

To measure the impact of ravulizumab on complement activity and its effect on complement blockage, order RAVMP / Ravulizumab Monitoring Panel, Serum which measures the alternative pathway function.

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

Patient Preparation: Suggest discontinuing natalizumab at least 4 weeks prior to testing for ravulizumab quantitation in serum. Patient should consult the healthcare provider who prescribed this drug to determine if discontinuation is an option. If not, ok to proceed with testing while taking natalizumab.

Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions:

1. Draw blood immediately before next scheduled dose.

2. Immediately after specimen collection, place the tube on wet ice.

3. After specimen has clotted on wet ice, centrifuge at 4 degrees C and aliquot serum into a plastic vial.

4. Freeze specimen within 30 minutes of centrifugation. Specimen must be placed on dry ice if not frozen immediately.

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

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 Frozen (preferred) 28 days
Ambient 28 days
Refrigerated 28 days

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

Assessing the response to ravulizumab therapy

 

Assessing the need for dose escalation

 

Evaluating the potential for dose deescalation or discontinuation of therapy in remission states

 

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

 

This test is not useful as the sole basis for a diagnosis or treatment decisions

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

Ravulizumab (Ultomiris, Alexion Pharmaceuticals) is a humanized monoclonal IgG2/4 kappa antibody therapeutic directed against the complement component 5 (C5). By association with C5, ravulizumab 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 ravulizumab demonstrated noninferiority to eculizumab in clinical trials for both paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (aHUS), there is likelihood of patients being moved from eculizumab to ravulizumab therapy. Ravulizumab is a longer-acting hybrid IgG2/IgG4 therapeutic monoclonal antibody (145 kDa). Its sequence is very similar to eculizumab (148 kDa), except for a 4 amino acid difference in the heavy chain of the molecule. Eculizumab binds to C5 in the intravascular space and, after the resulting eculizumab-C5 complex is taken up by endothelial cells, it is degraded in the endosomes. In order to increase its half-life, two changes were made to ravulizumab: 2 amino acids substituted in the constant region give ravulizumab more affinity for the Brambell receptor (FcRn), which recycles IgG instead of degrading it. The other 2 amino acid changes are in the variable region of the heavy chain, changing the affinity of the Fab fraction for C5, making it possible for C5 to be released from ravulizumab before it is recycled, so that C5 is left alone inside the endosome to be degraded.

 

Eculizumab is administered as a standard (non-weight based) dose for approved conditions. Ravulizumab's key improvements over eculizumab include a longer half-life, leading to intravenous infusions every 8 weeks instead of every 2 weeks, along with a weight-based dosing schedule that further personalizes therapy regimens. Some patients who persist with serum concentrations above therapeutic targets with complete complement blockade could benefit from dose deescalation or prolonged infusion intervals and visit the clinic for infusions less frequently than the US Food and Drug Administration-label recommendation. Therapeutic drug monitoring of ravulizumab could result in cost-savings and improved quality of life if target therapeutic concentrations can be achieved with complete complement system blockage at less frequent dosing intervals.

 

Ravulizumab trough therapeutic concentration is greater than 175 mcg/mL Complement blockage studies can aid in determining that a therapeutic concentration of the drug has blocked the complement function and subsequent production of sC5b-9. The recommended test for complement blockage evaluation in ravulizumab therapy is the alternative pathway function assay; see AH50 / Alternative Complement Pathway, Functional, Serum. A panel with both ravulizumab concentration and alternative pathway function  is available; see RAVMP / Ravulizumab Monitoring Panel, Serum.

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

 

>175 mcg/mL-Therapeutic concentration for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome

Interpretation
Provides information to assist in interpretation of the test results

Target trough therapeutic concentrations (immediately before next infusion) of ravulizumab are expected to be above 175 mcg/mL for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

 

Pharmacodynamic studies of complement blockage may also be recommended for patients undergoing therapy.

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

Results must be interpreted within the clinical context of the patient. Patients in transition between eculizumab (ECULI / Eculizumab, Serum) and ravulizumab administration will have a result that is the sum of eculizumab plus ravulizumab in circulation. This assay will not clearly differentiate between these specific analytes and must be interpreted with caution.

 

Patients actively undergoing therapy with both natalizumab and ravulizumab (extremely rare scenario) could present as assay interference. It is suggested patients discuss with their doctors the possibility of discontinuing natalizumab 4 weeks prior to testing. If discontinuation is not possible, it is ok to proceed with testing.

 

This test should not form the sole basis for a diagnosis or treatment decisions.

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

1. Willrich MA, Murray DL, Barnidge DR, Ladwig PM, Snyder MR. Quantitation of infliximab using clonotypic peptides and selective reaction monitoring by LC-MS/MS. Int Immunopharmacol. 2015;28(1):513-520. doi:10.1016/j.intimp.2015.07.007

2. 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;28(5):811-817. doi:10.1007/s13361-016-1566-y

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;24(5). doi:10.1128/CVI.00545-16

4. Sridharan M, Willrich MA, Go R. Personalized dosing of eculizumab using C5 functional activity and eculizumab level in complement-mediated thrombotic microangiopathy: A safe and cost-saving approach. Presented at XXVIII Congress of the International Society on Thrombosis and Haemostasis; July 12-14, 2020; Virtual ISTH 2020

5. Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019;133(6):540-549. doi:10.1182/blood-2018-09-876805

6. Stern RM, Connell NT. Ravulizumab: a novel C5 inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria. Ther Adv Hematol. 2019;10:2040620719874728. doi:10.1177/2040620719874728

7. Alexion Pharmaceuticals. BLA 761108-S1 Multi-disciplinary review and evaluation: Ultomiris (ravulizumab-cwvz). FDA; April 2, 2019. Accessed August 31, 2023. Available at www.fda.gov/media/135113/download

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

Ravulizumab is extracted from serum and measured by liquid chromatography high-resolution accurate-mass 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 9 days

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

14 days

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.

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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. It 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
RAVU Ravulizumab, S 97184-6
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.
609420 Ravulizumab, S 97184-6

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 | 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

Test Update Resources

Change Type Effective Date
Test Changes - Specimen Information 2023-12-07