Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Serodiagnosis of Inflammatory Bowel Disease (IBD) and the Prometheus® IBD sgi Diagnostic™ Test

Policy #:06.02.17e

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

EXPERIMENTAL INVESTIGATIONAL

Serodiagnosis of inflammatory bowel disease (IBD) is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published literature. Serodiagnostic tests of IBD include, but are not limited to, the following:
  • Anti-neutrophilic cytoplasmic antibody (ANCA), perinuclear anti-neutrophilic cytoplasmic antibody (pANCA)
  • Anti-saccharomyces cerevisiae antibody (ASCA)
  • Anti-outer membrane porin C (anti-OmpC) antibody
  • Anti-CBir1 flagellin (anti-CBir1) antibody

IBD diagnostic testing combining serologic, genetic, and inflammatory markers (eg, Prometheus® IBD Sgi Diagnostic™) is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published literature.
Guidelines

Prometheus Laboratories offers a variety of proprietary diagnostic tests for a multitude of disorders, including one for the serodiagnosis of inflammatory bowel disease (IBD). The IBD First Step™ and IBD Diagnostic System tests are frequently requested by providers as "Prometheus Testing."

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, serodiagnosis of IBD is not eligible for payment under the medical benefits of the Company's products because the service is considered experimental/investigational and, therefore, not covered.

Description

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract of unknown etiology. IBD falls into two major categories: ulcerative colitis (UC) and Crohn's disease (CD), both of which present with abdominal pain and diarrhea. Even though these two groups share many of the same clinical manifestations, important differences exist. UC primarily causes inflammation of the mucosal lining and is generally limited to the colon and rectum, while CD affects the entire digestive system and can produce ulcers that extend deep into the intestinal wall. A definitive diagnosis can usually be established with a combination of endoscopic, radiographic, and histologic criteria. However, in 10 to 15 percent of the cases, a distinction between UC and CD is not definitive.

The goal of treatment for UC and CD is to control inflammation and other symptoms. Initially, medications are commonly used to treat IBD. If medications fail to work or no longer alleviate symptoms, surgery may be required. Individuals who undergo surgery for CD may experience many symptom-free years; however, the disease frequently recurs, and there is no long-term cure.

Serodiagnosis is defined as a diagnosis of disease based on antigen-antibody reactions in the blood serum or other serum fluids in the body (serologic tests). Perinuclear anti-neutrophilic cytoplasmic antibodies (p-ANCA) and anti-saccharomyces cytoplasmic antibodies (ASCA) are two serum antibodies that have been associated with IBD and can potentially be used in diagnostic tests. Although p-ANCA and ASCA are present in individuals with CD and UC, the tests used to detect these antibodies have low sensitivities, and neither test is completely specific for the disease. P-ANCA and ASCA remain the most widely investigated markers for UC and CD, respectively. The suboptimal sensitivity levels of these serological tests do not support their use for screening for IBD or for routine clinical use. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD. Currently, the efficacy of serodiagnosis for IBD cannot be established by review of the available published peer-reviewed literature.

Prometheus® Laboratories Inc. (San Diego, CA) has developed a proprietary testing system that uses a two-step process with a combination of laboratory tests to aid in the diagnosis of IBD and to differentiate between CD and UC. Prometheus® IBD sgi Diagnostic™ is a 4th-generation IBD diagnostic test that combines serologic, genetic, and inflammatory markers using the proprietary Smart Diagnostic algorithm, proposed to improve the predictive accuracy. This algorithm uses measurements of 17 biologic markers to determine whether an individual has IBD. Then if it is determined the individual has IBD, the algorithm examines the marker measurements to differentiate CD from UC. Prometheus® IBD sgi Diagnostic™ includes the serological markers ASCA immunoglobulin A (IgA), ASCA immunoglobulin G (IgG), ANCA IgG, perinuclear anti-neutropholic cytoplasmic antibody (pANCA), DNAse pANCA, anti-outer membrane porin C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), Fla-X flagellin, and A4-Fla2 flagellin. Genetic susceptibility is believed to influence immune response, and this assay includes evaluation of genes ATG16L1, ECM1, NKX2-3, and STAT3. Inflammatory markers tested include intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), vascular growth factor (VEGF), C-reactive protein (CRP), and serum amyloid A protein (SAA). Currently, despite the inclusion of serologic, genetic, and inflammation markers combined with a diagnostic algorithm to interpret patterns among assay values, the efficacy of Prometheus® IBD sgi Diagnostic™ for the diagnosis of IBD and to distinguish CD from UC cannot be established by review of the available published peer-reviewed literature because currently there is insufficient evidence to evaluate this test.

The American College of Gastroenterology (ACG) states that for CD, serological studies are evolving to provide adjunctive support for the diagnosis of CD but are not sufficiently sensitive or specific to be recommended for use as screening tools. Similarly, as reported in published ACG practice guidelines for UC, pANCA, and ASCA currently are neither a first step nor a definitive step in differential diagnosis or clinical decision making. Furthermore, the ACG states that the measurement of genetic mutations of CD has not yet been proven to be of clinical benefit for the general assessment of diagnosis, guidance of individual care, or prediction of response to specific medical therapies. Thompson (2011) reports that advances in genetic contributions for UC will not in the short term provide additional diagnostic or prognostic value.
References


Abreu MT. Serologies in Crohn's disease: can we change the gray zone to black and white? Gastroenterology. 2006;131(2):664-667. Also available at: http://www.gastrojournal.org/article/PIIS0016508506014326/fulltext. Accessed February 21, 2013.

American Gastroenterology Association. American Gastroenterological Association medical position statement: Irritable bowel syndrome. Gastroenterology. 2002;123(6):2105-2107.

Annese V, Andreoli A, Andriulli A, et al. Familial expression of anti-Saccharomyces cerevisiae Mannan antibodies in Crohn's disease and ulcerative colitis: A GISC study. Am J Gastroenterol. 2001;96(8):2407-2412.

Bossuyt, X. Serologic markers in inflammatory bowel disease. Clinical Chemistry. 2006;52(2)171-181. Also available at: http://www.clinchem.org/content/52/2/171.full. Accessed February 21, 2013.

Gupta A, Derbes C, Sellin J. Clinical indications of the use of antineutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies in the evaluation of inflammatory bowel disease at an Academic Medical Center. Inflamm Bowel Dis. 2005;11(10):898-902.

Gupta SK, Fitzgerald JF, Croffie JM, et al. Comparison of serological markers of inflammatory bowel disease with clinical diagnosis in children. Inflamm Bowel Dis. 2004;10(3):240-244.

Hayes, Inc. Hayes Genetic Testing Evaluation (Report). Lansdale, PA: Hayes, Inc.; IBD sgi Diagnostic Test (Prometheus Inc.). February 2012.

Joossens S, Reinisch W, Vermeire S, et al. The value of serologic markers in indeterminate colitis: a prospective follow-up study. Gastroenterology. 2002;122(5):1242-1247.

Kornbluth A, Sachar DB. Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105(3):501-523.

Lichtenstein GR, Hanauer SB, Sandborn WJ. Practice Parameters Committee of the American College of Gastroenterology. Management of Crohn’s disease in adults. Am J Gastroenterol. 2009;104(2):465-83.

Lombardi G, Annese V, Piepoli A, et al. Antineutrophil cytoplasmic antibodies in inflammatory bowel disease: Clinical role and review of the literature. Dis Colon Rectum.
2000;43(7):999-1007.

Mayo Reference Services. Communiqué. The appropriate use of laboratory testing for verification and differentiation of ulcerative colitis and Crohn's disease. [Mayo Reference Services Web site]. 08/01/03. Available at: http://www.mayomedicallaboratories.com/media/articles/communique/mc2831-0803.pdf. Accessed February 21, 2013.

Mow WS, Vasiliauskas EA, Lin YC, et al. Association of antibody responses to microbial antigens and complications of small bowel Crohn's disease. Gastroenterology. 2004;126(2):414-424.

Papp M, Norman GL, Altojay I et al. Utility of serological markers in inflammatory bowel diseases: gadget or magic? World Gastroenterol. 2007;13(14):2028-2036.

Peeters M, Joossens S, Vermeire S, et al. Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease. Am J Gastroenterol. 2001;96(3):730-734.

Prometheus Laboratories. Prometheus® IBS Diagnostic is the first blood-based biomarker test for IBS. [Prometheus Laboratories Web site]. Available at: http://www.ibsbloodtest.com/. Accessed February 21, 2013.

Prometheus Therapeutics & Diagnostics. Prometheus® IBD sgi Diagnostic. Product description. [Prometheus Laboratories Web site]. Available at: http://www.prometheuslabs.com/Resources/IBDDiagnostic/IBD-sgi-Product-Detail.pdf. Accessed February 21, 2013.

Reese GE, Constantinides VA, Simillis C, et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol. 2006;101(10):2410-2422.

Reumaux D, Colombel JF, Masy E, et al. Anti-neutrophil cytoplasmic auto-antibodies (ANCA) in ulcerative colitis (UC): No relationship with disease activity. Inflamm Bowel Dis.
2000;6(4):270-274.

Roozendaal C, Pogany K, Hummel EJ, et al. Titres of anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease are not related to disease activity. QJM. 1999;92(11):651-658.

Sabery N, Bass D. Use of serologic markers as a screening tool in inflammatory bowel disease compared with elevated erythrocyte sedimentation rate and anemia. Pediatrics.2007;119(1):193-199. Also available at: http://pediatrics.aappublications.org/content/119/1/e193.full.pdf. Accessed February 21, 2013.

Schoepfer AM, Trummler M, Seeholzer P, et al. Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies. Inflamm Bowel Dis. 2008;14(1)32-39.

Sutton CL, Yang H, Li Z, et al. Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in affected and unaffected relatives of patients with Crohn's disease. Gut. 2000;46(1):58-63. Also available at: http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1727768&blobtype=pdf. Accessed February 21, 2013.

Taddei C, Audrain MA, Reumaux D, et al. Alpha1-antitrypsin phenotypes and anti-neutrophil cytoplasmic auto-antibodies in inflammatory bowel disease. Eur J Gastroenterol Hepatol. 1999;11(11):1293-1298.

Teml A, Kratzer V, Schneider B, et al. Anti-Saccharomyces cerevisiae antibodies: a stable marker for Crohn's disease during steroid and 5-aminosalicylic acid treatment. Am J Gastroenterol. 2003;98(10):2226-2231.

The Institute for Clinical Systems Improvement (ICS) Technology Assessment. Serum Antibodies for the Diagnosis of Inflammatory Bowel Disease (IBD): pANCA for Ulcerative Colitis (UC) and ASCA for Crohn's Disease (CD). Released November 2002 [via subscription only]. Accessed April 2009.

Thomson AI, Lees CW. Genetics of ulcerative colitis. Inflamm Bowel Dis. 2011;17(3):831-848.

Zholudev A, Zurakowski D, Young W, et al. Serologic testing with ANCA, ASCA, and anti-OmpC in children and young adults with Crohn's disease and ulcerative colitis: Diagnostic value and correlation with disease phenotype. Am J Gastroenterol. 2004;99(11):2235-2241.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

83516, 83520, 88350


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

This service is experimental/investigational for all diagnoses.


HCPCS Level II Code Number(s)

N/A


Revenue Code Number(s)

N/A

Coding and Billing Requirements



Policy History

Revisions from 06.02.17e
08/29/2018The policy has been reviewed and reissued to communicate the Company’s continuing position on Serodiagnosis of Inflammatory Bowel Disease (IBD) and the Prometheus® IBD sgi Diagnostic™ Test.

Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 01/01/2016
Version Issued Date: 01/04/2016
Version Reissued Date: 08/29/2018

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