Serum Antibodies for the Diagnosis and Management of Inflammatory Bowel Disease: ANCA for Ulcerative Colitis and ASCA for Crohn's Disease
DESCRIPTION
Inflammatory bowel disease (IBD) can be subdivided into ulcerative colitis (UC) and Crohn's disease (CD), both of which present with symptoms of diarrhea and abdominal pain. The definitive diagnosis can usually be established by a combination of radiographic, endoscopic, and histologic criteria, although in 10% - 15% of cases, the distinction between UC and CD cannot be made with certainty. Two serum antibodies, anti-neutrophilic cytoplasmic antibodies (ANCA) and anti-Saccharomyces cerevisiae (ASCA) have been associated with IBD. A number of subtypes of these markers have also been identified based on the specific antigen that is targeted. Testing for ANCA is currently available in most clinical laboratories. Testing for ASCA is becoming more available, but its reliability is questionable.
These serum antibodies have several potential uses. It has been proposed that they can be used as diagnostic tests to improve the efficiency and accuracy of diagnosing IBD, in order to decrease the extent of the diagnostic work-up or to avoid invasive tests. As a diagnostic test, it's thought they might also prove useful in differentiating between UC and CD in cases of indeterminate colitis. A second potential use is to classify subtypes of IBD in location of disease (i.e., proximal versus distal bowel involvement) or by disease severity, thereby providing prognostic information.
The IBD First Step™ and IBD Diagnostic System (Prometheus Laboratories, Inc.) are two commercially available diagnostic tests that use combinations of tests for ANCA and/or ASCA to aid in the diagnosis of IBD. They utilize a 2-step process to diagnose IBD and to differentiate between UC and CD. The IBD First Step™ is a panel of 4 markers intended to maximize the sensitivity and negative predictive value of the test. Individuals who test positive on the initial screen are further analyzed by the IBD Diagnostic System, a set of proprietary markers and enzyme reagents, to distinguish between true positive results and artifacts of fixation. The intention is to increase the specificity of the test compared to tests offered by other laboratories.
POLICY
Determination of anti-neutrophil cytoplasmic antibody (ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) as an aid in the diagnosis and/or management of individuals with inflammatory bowel disease is considered investigational.
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
No published studies demonstrate the use of the markers addressed in this policy in lieu of a standard work-up for IBD. A number of authors claim that these markers can be used to avoid invasive testing, but no studies demonstrated an actual decrease in the number of invasive tests through use of serum markers. Available evidence does not indicate the use of these tests will likely alter the diagnostic work-up, the final diagnosis made, or the treatment provided for individuals with suspected IBD. The studies available do not determine the impact of these tests on the final health outcome.
SOURCES
Anand, V., Russell, A., Tsuyuki, R., & Fedorak, R. (2008). Perinuclear antineutrophil cytoplasmic autoantibodies and anti-saccharomyces cerevisiae antibodies as serological markers are not specific in the identification of crohn’s disease and ulcerative colitis. Canadian Journal of Gastroenterology, 22 (1), 33 - 36. (Level 5 evidence)
BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2009). Serum antibodies for the diagnosis of inflammatory bowel disease (2.04.17). Retrieved November 17, 2009 from BlueWeb.
Forcione, D. G., Rosen, M. J., Kisiel, J. B., & Sands, B. E. (2004). Anti-Saccharomyces cerevisiae antibody (ASCA) positivity is associated with increased risk for early surgery in Crohn's disease. Gut, 53 (8), 1117 - 1122. (Level 4 Evidence)
Hayes. Medical Technology Directory. (2003, July). Serologic assays for the diagnosis and management of inflammatory bowel disease. Retrieved October 3, 2006 from www.Hayesinc.com/subscribers. (30 articles and/or guidelines reviewed)
Institute for Clinical Systems Improvement. (2002, November). Serum antibodies for the diagnosis of inflammatory bowel disease (IBD): ANCA for ulcerative colitis (UC) and ASCA for Crohn's disease (CD). Retrieved November 17, 2006 from http://www.icsi.org/technology_assessment_reports__active/ta_serum_antibodies_for_the_diagnosis_of_inflammatory_bowel_disease__ibd___panca_for_ulcerative_colitis__uc__and_asca_for_crohn_s_disease__cd_.html.
Jaskowski, T., Litwin, C., & Hill, H. (2006). Analysis of serum antibodies in patients suspected of having inflammatory bowel disease. Clinical and Vaccine Immunology, 13 (6), 655 - 660. (Level 5 Evidence)
Marrero, F., Qadeer, M., & Lashner, B. (2008). Severe complications of inflammatory bowel disease. Medical Clinics of North America, 92 (3), 671 - 686. (Level 5 Evidence)
Sabery, N., & Bass, D. (2007). Use of serologic markers as a screening tool in inflammatory bowel disease compared with elevated erythrocyte sedimentation rate and anemia. Pediatrics, 119 (1), e193 - 199. (Level 2 Evidence)
Schoepfer, A., Trummler, M., Seeholzer, P., Seibold-Schmid, B. & Seibold F. (2008). Discriminating IBD from IBS: comparison of the test performance of fecal markers, Blood leukocytes, CRP, and IBD antibodies. Inflammatory Bowel Diseases, 14 (1), 32 - 39. (Level 5 Evidence)
The Technology Evaluation Center. (1999, July). Serum antibodies for the diagnosis of inflammatory bowel disease: ANCA for ulcerative colitis and ASCA for Crohn's disease (Vol. 14, No. 12). Chicago: BlueCross BlueShield Association. (26 articles and/ or guidelines reviewed)
U. S. Food and Drug Administration. (2003, May). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K030704. Retrieved November 17, 2009 from http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=11105.
U. S. Food and Drug Administration. (2006, April). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K051927. Retrieved November 17, 2009 from http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=18928.
Vermeire, S., Vermeulen, N., Assche, G., Bossuyt, X., & Rutgeerts, P. (2008). (Auto) Antibodies in inflammatory bowel diseases. Gastroenterology Clinics of North America, 37 (2), 429 - 438. (Level 5 Evidence)
Zisman, T., & Rubin, D. (2009). Novel diagnostic and prognostic modalities in inflammatory bowel disease. Gastroenterology Clinics of North America, 38 (4), 729 - 752. (Level 5 Evidence)
ORIGINAL EFFECTIVE DATE: 7/1/2004
MOST RECENT REVIEW DATE: 1/14/2010
ID_BT
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