Commercial

Medical Policy

Notification

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

Notification Issue Date:

This version of the policy went through a code update process effective 04/01/2020, and 0164U was added to this policy on that date.

Title:

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

Policy #:

06.02.17h

Policy

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 antineutrophilic 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 (e.g., 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. Although 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, whereas 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 fourth-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. 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 antineutropholic 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

Alkhatry M, Al-Rifai A, Annese V, et al. First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases: A 2020 Delphi consensus. World J Gastroenterol. 2020;26(43):6710-6769.

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. Clin Chem. 2006;52(2):171-181.

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.

Kucharzik T, Taylor S, Allocca M, et al. ECCO-ESGAR-ESP-IBUS Guideline on Diagnostics and Monitoring of Patients with Inflammatory Bowel Disease: Part 1. J Crohns Colitis. 2025;19(7):jjaf106.

Lichtenstein GR, Loftus EV, Afzali A, et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2025;120(6):1225-1264.

Lichtenstein GR, Loftus EV, Isaacs KL, et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2018 Apr;113(4):481-517. Erratum in: Am J Gastroenterol. 2018;113(7):1101.

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.

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.

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, Pogány 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.

Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG Clinical Guideline Update: Ulcerative Colitis in Adults. Am J Gastroenterol. 2025;120(6):1187-1224.

Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol. 2019;114(3):384-413.

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.

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.

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].

Thompson 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

CPT Procedure Code Number(s)

0164U, 83516, 83520, 88350

ICD - 10 Procedure Code Number(s)

N/A

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

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 06.02.17h:

06/10/2026	This policy has been reviewed and reissued to communicate the Company's continued position on serodiagnosis of inflammatory bowel disease (IBD) and the Prometheus® IBD sgi Diagnostic™ Test.
07/09/2025	This policy has been reissued in accordance with the Company's annual review process.
03/20/2024	This policy has been reissued in accordance with the Company's annual review process.
08/23/2023	The policy has been reviewed and reissued to Communicate the Company's continued position on Serodiagnosis of Inflammatory Bowel Disease (IBD) and the Prometheus® IBD sgi Diagnostic™ Test.
02/23/2022	This policy has been reissued in accordance with the Company's annual review process.
04/01/2020	This version of the policy went through a code update process effective 04/01/2020, and 0164U was added to this policy on that date.

Revisions From 06.02.17g:

03/25/2020	This policy has been reissued in accordance with the Company's annual review process.
01/01/2020	This version of the policy will become effective on 01/01/2020 due to a coding update. The following code is being deleted from the policy: 0085U

Revisions From 06.02.17f:

07/01/2019

This version of the policy went through a code update process effective 07/01/2019, and 0085U was added to this policy on that date.

Revisions From 06.02.17e:

08/29/2018

The 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:

4/1/2020

Version Issued Date:

4/2/2020

Version Reissued Date:

6/10/2026