Clinical Policy: Reference Number: CP.MP.HN255 Effective Date: 02/06 Last Review Date: 7/17 Coding Implications Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Celiac disease is a disorder of the small bowel disorder with mucosal inflammation, villous atrophy, and crypt hyperplasia, when gluten is ingested and improves with gluten is eliminated from the diet. Celiac disease can be categorized into degrees such as asymptomatic, silent with no evident malabsorption or other disease manifestations or potential, positive celiac-specific serology with normal histology. Serological testing is useful in the diagnosis and management of celiac disease. Asymptomatic patients without a family history of celiac disease or laboratory or clinical evidence for malabsorption can be considered to be low risk. The benefit of population screening for asymptomatic celiac disease has not yet been demonstrated. Policy/Criteria I. It is the policy of Health Net of California that the following serological tests for Celiac Disease are considered medically necessary for any of the following: A. Immunoglobulin A (IgA) anti-tissue transglutaminase (TTG), (also referred to as TTG-IgA) testing, or IgA anti-endomysial antibodies (IgA-EMA) testing for detection of celiac disease (CD) in individuals over the age of 2 years is considered medically necessary in any of the following: 1.Individuals with symptoms, signs, or laboratory evidence suggestive of malabsorption, (e.g., chronic diarrhea with weight loss, steatorrhea, postprandial abdominal pain, bloating) 2.Individuals with symptoms, signs, or laboratory evidence for which CD is a treatable cause 3.Individuals with a first-degree family member who has a confirmed diagnosis of CD when the individual shows possible signs or symptoms or laboratory evidence of CD. 4.Individuals with elevated serum aminotransferase levels when no other etiology is found 5.Individuals with Type I diabetes mellitus (DM) if there are any digestive symptoms, or signs, or laboratory evidence suggestive of CD. B. Measurement of total IgA, when there exists a high probability of CD and the ossibility of IgA deficiency. (IgA deficiency is more common in CD than in the general population). An alternative approach is to include both IgA and IgG-based testing, such as IgG-deamidated gliadin peptides (DGPs), in these high-probability individuals. C. IgG-based testing (IgG DGPs and IgG TTG) in individuals when a low IgA or selective IgA deficiency is identified Page 1 of 10
D. IgA TTG test in combination with DGP (IgA and IgG) in children younger than 2 years of age when CD is suspected E. HLA-DQ2 / DQ8 genotyping testing to rule out the disease in selected clinical situations. (HLA-DQ2 / DQ8 testing should not be used routinely in the initial diagnosis of CD). Examples of such clinical situations include but are not limited to: 1.Equivocal small-bowel histological finding (Marsh I-II) in seronegative individuals 2. Evaluation of individuals on a gluten free diet (GFD) in whom no testing for CD was done before GFD 3. Individuals with discrepant celiac-specific serology and histology 4. Individuals with suspicion of refractory CD where the original diagnosis of celiac remains in question 5. Individuals with Down's syndrome F. Serologic testing is also useful in monitoring the response to gluten-free diet. (Serum levels of IgA-EMA and IgA-TTG fall on a gluten-free diet and the test often becomes negative in treated patients) II. It is the policy of Health Net of California to consider screening for asymptomatic celiac disease, using the IgA endomysial or IgG ttg assays, investigational, as studies have noted lower sensitivity and specificity, and their benefit has not yet been demonstrated. Although potential advantages of screening for asymptomatic celiac disease exist, additional peerreviewed studies are needed to determine if this type of testing should be advocated. Background Celiac disease, also referred to as Celiac Sprue or gluten-sensitive enteropathy, is a chronic malabsorption disorder of the small intestine caused by exposure to dietary gluten in genetically predisposed individuals. Although celiac disease has been considered rare, studies suggest its prevalence is much greater than previous estimates, and may affect as many as 3 million Americans. The genetic predisposition to celiac disease is attributed to the specific genetic markers known as HLA-DQ2 and HLA-DQ8 that are present in affected individuals. Of the patients with celiac disease, 95% are human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 positive. When these individuals are exposed to dietary proteins present in wheat, barley, and rye, known as glutens, they interact with these HLA molecules to activate an abnormal mucosal immune response and induce tissue damage Certain populations have an increased prevalence of celiac disease, including first and seconddegree relatives of individuals with biopsy-proven celiac disease. In addition, individuals with type 1 diabetes mellitus, Down syndrome, Turner syndrome, Williams syndrome, selective IgA deficiency, and autoimmune disorders have an increased prevalence. Celiac disease is characterized by chronic inflammation of the small intestinal mucosa that may result in atrophy of intestinal villi, a lowering of the villous height to crypt depth ratio, an Page 2 of 10
increase in intraepithelial lymphocytes, extensive surface cell damage and infiltration of the lamina propria with inflammatory cells leading to malabsorption, and exhibit a variety of clinical manifestations. Although previously thought to be a disease of childhood, it may occur at any age, with the classic presentation of diarrhea and malabsorption occurring less often, while atypical and silent presentations increasing. Presenting symptoms of adults include weight loss, diarrhea, lassitude, and anemia. Symptoms in children include failure to thrive, vomiting, diarrhea, muscle wasting, signs of hypoproteinemia and general irritability. It is not uncommon for celiac disease to present with extraintestinal manifestations, with little or no gastrointestinal symptoms, as in the case of dermatitis herpetiformis. Other presentations are unexplained short stature, delayed puberty, infertility, recurrent fetal loss, osteoporosis, vitamin deficiencies, fatigue, protein calorie malnutrition, recurrent aphthous stomatitis, elevated transaminases, and dental enamel hypoplasia. Untreated celiac disease may lead to vitamin and mineral deficiencies, an increased risk of gastrointestinal malignancies and intestinal lymphoma, osteoporosis, and other extraintestinal problems. Treatment of celiac disease is a lifelong gluten-free diet, omitting wheat, rye, and barley from the diet, which results in remission for most individuals. Even small quantities of gluten may be harmful. Oats may be permitted, however, their inclusion in a gluten-free diet is limited by potential contamination with gluten during processing. Compliance with the glutenfree diet is extremely challenging due to the poor palatability of gluten-free foods and confusing food-labels. The diagnosis of celiac disease is established by serological testing, biopsy evidence of villous atrophy, and improvement of symptoms on a gluten-free diet. According to a NIH Consensus Panel Statement on celiac disease (2004), testing should begin with serologic evaluation. Current serum immunologic markers for celiac disease have increased the sensitivity and specificity for diagnosing the disease. Because 2 to 3 percent of individuals with celiac sprue have selective IgA deficiency, IgA levels should also be measured. Serologic testing may not be as accurate in children less than age five. Based on very high sensitivities and specificities, the best available tests are the IgA antihuman tissue transglutaminase (TTG) and IgA endomysial antibody immunofluorescence (EMA) tests. Endomysial antibodies bind to connective tissue surrounding smooth muscle cells and are moderately sensitive and highly specific for untreated celiac disease. Even low titers of serum IgA endomysial antibodies are indicative of celiac disease. Serum levels of IgA endomysial antibody fall on a gluten-free diet and the test often becomes negative in treated patients. The IgA and IgG antigliadin antibody tests have lower diagnostic accuracy with frequent false positive results. Per the NIH Consensus Panel Statement, the IgA and IgG antigliadin antibody tests are no longer recommended for the initial diagnostic evaluation or screening, however, they may be useful for monitoring the response to a gluten-free diet. Page 3 of 10
According to the NIH Consensus Statement, when the diagnosis of celiac disease is uncertain because of indeterminate results, testing for certain genetic markers (HLA haplotypes) can stratify individuals to high or low risk for celiac disease. The consensus statement noted that greater than 97% of patients with celiac disease have the DQ2 and/or DQ8 marker, compared to about 40% of the general population. Therefore, an individual negative for DQ2 or DQ8 is extremely unlikely to have celiac disease (high negative predictive value). Serum IgA endomysial and tissue transglutaminase antibody testing have the highest diagnostic accuracy. The IgA and IgG antigliadin antibody tests have lower diagnostic accuracy with frequent false positive results as compared with IgA ttg and IgA DGP assays and are therefore no longer recommended for initial diagnostic evaluation or screening. The newer antideamidated gliadin peptide (DGP) assays show high diagnostic accuracy. IgA EMA, IgA ttg, IgA DGP and IgG DGP levels fall with treatment; as a result, these assays can be used as a noninvasive means of monitoring the response to a gluten-free diet. The recent guidelines from the American College of Gastroenterology on the diagnosis and management of Celiac Disease (2013) make the following recommendations regarding serologic testing: 1. Patients with symptoms, signs, or laboratory evidence suggestive of malabsorption, such as chronic diarrhea with weight loss, steatorrhea, postprandial abdominal pain, and bloating, should be tested for CD. (Strong recommendation, high level of evidence) 2. Patients with symptoms, signs, or laboratory evidence for which CD is a treatable cause should be considered for testing for CD. (Strong recommendation, moderate level of evidence) 3. Patients with a first-degree family member who has a confirmed diagnosis of CD should be tested if they show possible signs or symptoms or laboratory evidence of CD. (Strong recommendation, high level of evidence) 4. Consider testing of asymptomatic relatives with a first degree family member who has a confirmed diagnosis of CD. (Conditional recommendation, high level of evidence) 5. CD should be sought among the explanations for elevated serum aminotransferase levels when no other etiology is found. (Strong recommendation, high level of evidence) 6. Patients with Type I diabetes mellitus (DM) should be tested for CD if there are any digestive symptoms, or signs, or laboratory evidence suggestive of CD. (Strong recommendation, high level of evidence) 7. Immunoglobulin A (IgA) anti-tissue transglutaminase (TTG) antibody is the preferred single test for detection of CD in individuals over the age of 2 years. (Strong recommendation, high level of evidence) 8. When there exists a high probability of CD wherein the possibility of IgA deficiency is considered, total IgA should be measured. An alternative approach is to include both IgA and IgG-based testing, such as IgG-deamidated gliadin peptides (DGPs), in these highprobability patients. (Strong recommendation, moderate level of evidence) Page 4 of 10
9. In patients in whom low IgA or selective IgA deficiency is identified, IgG-based testing (IgG DGPs and IgG TTG) should be performed. (Strong recommendation, moderate level of evidence) 10. If the suspicion of CD is high, intestinal biopsy should be pursued even if serologies are negative. (Strong recommendation, moderate level of evidence) 11. All diagnostic serologic testing should be done with patients on a gluten-containing diet. (Strong recommendation, high level of evidence) 12. Antibodies directed against native gliadin are not recommended for the primary detection of CD. (Strong recommendation, high level of evidence) 13. Combining several tests for CD in lieu of TTG IgA alone may marginally increase the sensitivity for CD but reduces specificity and therefore are not recommended in low-risk populations. (Conditional recommendation, moderate level of evidence) 14. When screening children younger than 2 years of age for CD, the IgA TTG test should be combined with DGP (IgA and IgG). (Strong recommendation, moderate level of evidence) 15. The confirmation of a diagnosis of CD should be based on a combination of findings from the medical history, physical examination, serology, and upper endoscopy with histological analysis of multiple biopsies of the duodenum. (Strong recommendation, high level of evidence) 16. HLA-DQ2 / DQ8 testing should not be used routinely in the initial diagnosis of CD. (Strong recommendation, moderate level of evidence) 17. While standard diagnostic tests (specific serology and intestinal biopsy) have a high PPV for CD, they should not be relied upon to exclude CD in patients already adhering to a GFD. (Strong recommendation, high level of evidence) 18. HLA-DQ2 / DQ8 genotyping should be used to try to exclude CD prior to embarking on a formal gluten challenge. (Strong recommendation, high level of evidence) 19. Monitoring of adherence to GFD should be based on a combination of history and serology (IgA TTG or IgA (or IgG) DGP antibodies). (Strong recommendation, moderate level of evidence) Coding Implications This clinical policy references Current Procedural Terminology (CPT ). CPT is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2015, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services. Not an all inclusive list CPT Codes Description Page 5 of 10
CPT Codes Description 81382 HLA Class II typing, high resolution (ie, alleles or allele groups); one locus (eg, HLA-DRB1, -DRB3/4/5, -DQB1, -DQA1, -DPB1, or -DPA1), each 82784 Gammaglobulin; IgA, IgD, IgG, IgM, each 83516 Immunoassay for analyte other than infectious agent antibody or infectious agent antigen, qualitative or semiquantitative; multiple step method [covered for IgG and IgA deamidated gliadin antibodies (DGP)] [not covered for IgA 83520 Immunoassay, analyte, quantitative; not otherwise specified 86255-86356 Fluorescent noninfectious agent antibody; screen, each antibody [covered for genetic testing for HLA-DQ2 and HLA-DQ8 haplotypes] [not covered for serological testing of antireticulin antibodies (ARA)] 86828-86829 Antibody to human leukocyte antigens (HLA), solid phase assays (eg, microspheres or beads, ELISA, flow cytometry); qualitative assessment of the presence or absence of antibody(ies) to HLA Class I and/or Class II HLA antigens HCPCS Codes Description ICD-10-CM Diagnosis Codes that Support Coverage Criteria ICD-10-CM Description Code K90.0 Celiac disease Initial Approval 02/06 Update. Revision Diagnostic tests should be performed before the 3/08 initiation of gluten restriction begins, added to the policy statement. To monitor response to a gluten-free diet was removed from policy statement. (American Gastroenterological Association) Annual review no changes 2/11 9/12 Revised policy statement, removing testing of anti-gliadin antibodies, and 9/13 anti-reticulin antibodies as these tests are no longer recommended. Added 2013 recommendations from ACG guidelines on Celiac Disease. Code updates. Annual review no changes 4/14 4/15 4/16 Page 6 of 10
Update to new format 7/17 References 1. Armstrong D, Don-Wauchope AC, Verdu EF. Testing for gluten-related disorders in clinical practice: The role of serology in managing the spectrum of gluten sensitivity. Can J Gastroenterol. 2011; 25(4):193-197. 2. Barakauskas VE, Lam GY, Estey MP. Digesting all the options: laboratory testing for celiac disease. Crit Rev Clin Lab Sci. 2014 Dec;51(6):358-78. 3. Bufler P, Heilig G, Ossiander G, et al. Diagnostic performance of three serologic tests in childhood celiac disease. Z Gastroenterol. 2015 Feb;53(2):108-114. 4. Bürgin-Wolff A, Mauro B, Faruk H. Intestinal biopsy is not always required to diagnose celiac disease: a retrospective analysis of combined antibody tests. BMC Gastroenterol. 2013 Jan 23;13:19. 5. Ciclitira PJ. Management of celiac disease in adults. UpToDate. May 14, 2012. 6. Delgado JF, Amengual MJ, Veraguas A, et al. Pediatric celiac patients carrying the HLA-DR7-DQ2 and HLA-DR3-DQ2 haplotypes display small clinical differences. Acta Paediatr. 2014 Jun;103(6):e238-42. 7. Garnier-Lengliné H, Brousse N, Candon S, et al. Have serological tests changed the face of childhood coeliac disease? A retrospective cohort study. BMJ Open. 2012 Nov 22;2(6). 8. Hayes. Celiac Disease. GTE Report. January 4, 2010, Updated January 11, 2012. Update Jan 2013. Updated January 14, 2014. Archived Feb 2015 9. Hayes. Medical Technology Directory. Serologic Assays for the Diagnosis and Management of Inflammatory Bowel Disease. July 28, 2003, Updated August 28, 2008 10. Hojsak I, Mozer-Glassberg Y, Segal GN, et al. Celiac Disease Screening Assays for Children Younger than 3 Years of Age: The Performance of Three Serological Tests. Dig Dis Sci. 2011 Aug 17. [Epub ahead of print]. 11. Hope BC, Ameratunga R, Austin PM, et al. Diagnostic utility of modified gliadin Peptide antibody assays in new zealand children. J Pediatr Gastroenterol Nutr. 2013 Jul;57(1):43-8. 12. Hostoffer RW. Selective IgA deficiency: Clinical manifestations, pathophysiology, and diagnosis. UpToDate. August 3, 2015. 13. Husby S, Murray JA. Diagnosing celiac disease and the potential for serological markers. Nat Rev Gastroenterol Hepatol. 2014 Nov;11(11):655-63. 14. Katz KD, Rashtak S, Lahr BD, et al. Screening for celiac disease in a north american population: sequential serology and gastrointestinal symptoms. Am J Gastroenterol. 2011 Jul;106(7):1333-9. Epub 2011 Mar 1. 15. Kelly CP. Diagnosis of celiac disease. UpToDate. 2011. Updated June 18, 2015. 16. Lewis NR, Scott BB. Meta-analysis: Deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease. Aliment Pharmacol Ther. 2010;31(1):73-81. Page 7 of 10
17. Ludvigsson JF, Zingone F, Tomson T, et al. Increased risk of epilepsy in biopsy-verified celiac disease: a population-based cohort study. Neurology 2012; 78:1401 18. Makovicky P, Rimarova K, Boor A, et al. Correlation between antibodies and histology in celiac disease: Incidence of celiac disease is higher than expected in the pediatric population. Mol Med Rep. 2013 Aug 13. 19. Mooney PD, Wong SH, Johnston AJ, et al. Increased Detection of Celiac Disease With Measurement of Deamidated Gliadin Peptide Antibody Before Endoscopy. Clin Gastroenterol Hepatol. 2015;13(7):1278. 20. Mubarak A, Spierings E, Wolters VM, et al. Children with celiac disease and high ttga are genetically and phenotypically different. World J Gastroenterol. 2013 Nov 7;19(41):7114-20.. 21. Neves MM, Gonzalez-Garcia MB, Nouws HP, et al. An electrochemical deamidated gliadin antibody immunosensor for celiac disease clinical diagnosis. Analyst. 2013;138(7):1956-1958. 22. NIH Consensus Development Conference on Celiac Disease. National Institutes of Health Consensus Development Conference Statement. June 28 30, 2004 Available at: http://consensus.nih.gov/2004/2004celiacdisease118html.htm 23. Pallav K, Kabbani T, Tariq S, et al. Clinical utility of celiac disease-associated HLA testing. Dig Dis Sci. 2014 Sep;59(9):2199-206. 24. Plantier S, Harlé JR, Gautier M, et al. Immunological screening and follow-up of celiac disease: Experience of the University Hospital of Marseille. Rev Med Interne. 2013 Aug 9. 25. Rozenberg O, Lerner A, Pacht A, et al. A new algorithm for the diagnosis of celiac disease. Cell Mol Immunol. 2011 Mar;8 (2):146-9. Epub 2011 Feb 14. 26. Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013 May;108(5):656-76. Available at: http://gi.org/guideline/diagnosis-and-management-of-celiac-disease/ 27. Sandström O, Rosén A, Lagerqvist C, et al. Transglutaminase Iga Antibodies in A Celiac Disease Mass Screening and the Role of Hla-Dq Genotyping and Endomysial Antibodies in Sequential Testing. J Pediatr Gastroenterol Nutr. 2013 Jun 17. 28. Schuppan D, Dietrich W. Pathogenesis, epidemiology, and clinical manifestations of celiac disease in adults. UpToDate. June 13, 2012. 29. Schyum AC, Rumessen JJ. Serological testing for celiac disease in adults. 30. Shahnaz A, Maguire G, Parker R, et al. Tissue transglutaminase antibody levels predict IgA deficiency. Arch Dis Child. 2013 Aug 8. 31. Srinivas M, Basumani P, Podmore G, et al. Utility of testing patients, on presentation, for serologic features of celiac disease. Clin Gastroenterol Hepatol. 2014 Jun;12(6):946-52 32. United European Gastroenterol J. 2013 Oct;1(5):319-25. 33. van der Windt DA, Jellema P, Mulder CJ, et al. Diagnostic testing for celiac disease among patients with abdominal symptoms: A systematic review. JAMA. 2010;303(17):1738-1746. Page 8 of 10
34. Vaquero L, Caminero A, Nuñez A, et al. Coeliac disease screening in first-degree relatives on the basis of biopsy and genetic risk. Eur J Gastroenterol Hepatol. 2013 Dec 2. 35. Vermeersch P, Geboes K, Mariën G, et al. Serological diagnosis of celiac disease: comparative analysis of different strategies. Clin Chim Acta. 2012 Nov 12;413(21-22):1761-7. 36. Vermeersch P, Geboes K, Mariën G, et al. Diagnostic performance of IgG antideamidated gliadin peptide antibody assays is comparable to IgA anti-ttg in celiac disease. Clin Chim Acta. 2010 Jul 4;411(13-14):931-5. Epub 2010 Feb 19. 37. Villalta D, Tonutti E, Prause C, et al. IgG antibodies against deamidated gliadin peptides for diagnosis of celiac disease in patients with IgA deficiency. Clin Chem. 2010;56(3):464-468. 38. Wakim-Fleming J, Pagadala MR, Lemyre MS, et al. Diagnosis of celiac disease in adults based on serology test results, without small-bowel biopsy. Clin Gastroenterol Hepatol. 2013 May;11(5):511-6. 39. World Gastroenterology Organisation Global Guidelines. Celiac disease. April 2012. Available at: http://www.worldgastroenterology.org/assets/export/userfiles/2012_celiac%20disease_l ong_final.pdf Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. Health Plan means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan s affiliates, as applicable. The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures. This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to Page 9 of 10
applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time. This clinical policy does not constitute medical advice, medical treatment or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions. Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan. This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services. Note: For Medicaid members, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy. Note: For Medicare members, to ensure consistency with the Medicare National Coverage Determinations (NCD) and Local Coverage Determinations (LCD), all applicable NCDs, LCDs, and Medicare Coverage Articles should be reviewed prior to applying the criteria set forth in this clinical policy. Refer to the CMS website at http://www.cms.gov for additional information. 2016 Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. No part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright or other notice contained herein. Centene and Centene Corporation are registered trademarks exclusively owned by Centene Corporation. Page 10 of 10