Last Review Date: 10/03/2024

Date of Origin:  06/24/2014

Dates Reviewed:  09/2014, 03/2015, 06/2015, 09/2015, 12/2015, 03/2016, 05/2016, 09/2016, 12/2016, 03/2017, 06/2017, 09/2017, 12/2017, 03/2018, 06/2018, 10/2018, 10/2019, 10/2020, 10/2021, 04/2022, 08/2023, 10/2023, 11/2023, 05/2024, 10/2024

1. Length of Authorization

Crohn’s Disease and Ulcerative Colitis:

Initial coverage will be provided for 14 weeks and may be renewed annually thereafter unless otherwise specified.

• Dose escalation requests for Crohn’s Disease and Ulcerative Colitis: Coverage will be provided for 3 months and may be renewed annually thereafter (see Section V for therapy continuation details).
• Therapy for Crohn’s Disease and Ulcerative Colitis in patients who will be receiving subcutaneous maintenance doses: Coverage will be provided for 2 intravenous doses and 4 subcutaneous doses [see Entyvio SQ policy – Document Number: IC-0733]

Therapy for the Management of Immune Checkpoint Inhibitor-Related Diarrhea/Colitis:

Coverage will be provided for 3 doses total and may not be renewed.

Acute Graft Versus Host Disease:

Coverage will be provided for 6 months and may be renewed.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

   Loading Dose:          

• Entyvio 300 mg single use vial: 1 vial at weeks 0, 2, & 6 (3 vials total per 42 days)

  Maintenance Dose:

• Entyvio 300 mg single use vial: 1 vial every 4 weeks (28 days)

B. Max Units (per dose and over time) [HCPCS Unit]:

   Crohn’s Disease & Ulcerative Colitis:

• Loading Dose: 300 billable units (300 mg) at weeks 0, 2, & 6
• Maintenance Dose: 300 billable units (300 mg) every 4 weeks

  Management of Immune Checkpoint Inhibitor-Related Diarrhea/Colitis

• 300 billable units (300 mg) at weeks 0, 2, & 6

  Acute Graft Versus Host Disease:

• Loading Dose: 300 billable units (300 mg) at weeks 0, 2, & 6
• Maintenance Dose: 300 billable units (300 mg) every 8 weeks

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND
• Patient is up to date with all vaccinations, in accordance with current immunization guidelines, prior to initiating therapy; AND

Universal Criteria ¹

• Patient does not have an active infection, including clinically important localized infections; AND
• Patient has been evaluated and screened for the presence of latent tuberculosis (TB) infection prior to initiating treatment and will receive ongoing monitoring for presence of TB during treatment; AND
• Patient is not on concurrent treatment with another biologic therapy (e.g., integrin receptor antagonist, TNF-inhibitor, IL-inhibitor, T cell costimulation modulator, etc.) or targeted synthetic therapy (e.g., apremilast, tofacitinib, baricitinib, upadacitinib, abrocitinib, deucravacitinib, ritlecitinib, ruxolitinib, etrasimod, ozanimod, etc.); AND

Crohn’s Disease † ^1,2,16,21,25

• Physician has assessed baseline disease severity utilizing an objective measure/tool; AND
• Documented moderate to severe active disease; AND
  • Documented failure, contraindication, or ineffective response at maximum tolerated doses to a minimum 3-month trial of corticosteroids or immunomodulators (e.g., azathioprine, 6-mercaptopurine, or methotrexate, etc.); OR
  • Documented failure, contraindication, or ineffective response at maximum tolerated doses to a minimum 3-month trial of a TNF modifier such as adalimumab, certolizumab, or infliximab; OR
  • Patient has evidence of high-risk disease for which corticosteroids or immunomodulators are inadequate and biologic therapy is necessary; OR
  • Patient is already established on a biologic or targeted synthetic therapy for the treatment of CD

Ulcerative Colitis † ^1,12,18-20

• Physician has assessed baseline disease severity utilizing an objective measure/tool; AND
• Documented moderate to severe active disease; AND
  • Documented failure or ineffective response to a minimum 3-month trial of conventional therapy [aminosalicylates, corticosteroids, or immunomodulators (e.g., azathioprine, 6-mercaptopurine, methotrexate, etc.)] at maximum tolerated doses, unless there is a contraindication or intolerance to use; OR
  • Documented failure, contraindication, or ineffective response at maximum tolerated doses to a minimum 3-month trial of a TNF modifier such as adalimumab, certolizumab, or infliximab; OR
  • Patient is already established on a biologic or targeted synthetic therapy for the treatment of UC

Management of Immune Checkpoint Inhibitor-Related Diarrhea/Colitis ‡ ^13,14

• Patient has been receiving therapy with an immune checkpoint inhibitor (e.g., nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, cemiplimab, ipilimumab, tremelimumab, dostarlimab, retifanlimab, nivolumab/relatlimab, tislelizumab, toripalimab, etc.); AND
  • Patient has mild (G1) diarrhea or colitis related to their immunotherapy with persistent or progressive symptoms and a positive lactoferrin/calprotectin; OR
  • Patient has moderate (G2) to severe (G3-4) diarrhea or colitis related to their immunotherapy

Acute Graft Versus Host Disease ‡ ^13,22

• Patient has received an allogeneic hematopoietic stem cell transplant; AND
• Used for steroid-refractory acute GVHD; AND
• Used in combination with systemic corticosteroids as additional therapy following no response to first-line therapies

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the universal and indication-specific criteria as identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: anaphylaxis or other serious allergic, severe infusion-related or hypersensitivity reactions, severe infections, progressive multifocal leukoencephalopathy (PML), jaundice or other evidence of significant liver injury, etc.; AND

Crohn’s Disease ^16,26,27

• Disease response as indicated by improvement in signs and symptoms compared to baseline such as endoscopic activity, number of liquid stools, presence and severity of abdominal pain, presence of abdominal mass, body weight regain, hematocrit, presence of extra intestinal complications, use of anti-diarrheal drugs, tapering or discontinuation of corticosteroid therapy, improvement in biomarker levels [i.e., fecal calprotectin or serum C-reactive protein (CRP)] and/or an improvement on a disease activity scoring tool [e.g., an improvement on the Harvey-Bradshaw Index score, etc].

Ulcerative Colitis ^9-11,20,28

• Disease response as indicated by improvement in signs and symptoms compared to baseline such as stool frequency, rectal bleeding, endoscopic activity, tapering or discontinuation of corticosteroid therapy, normalization of C-reactive protein (CRP) or fecal calprotectin (FC), and/or an improvement on a disease activity scoring tool.

Management of Immune Checkpoint Inhibitor-Related Diarrhea/Colitis ‡ ^13,14

• May not be renewed.

Acute Graft Versus Host Disease ^22-24

• Response to therapy with an improvement in one or more of the following:
  • Clinician assessments (e.g., NIH Skin Score, Upper GI Response Score, NIH Lung Symptom Score, etc.)
  • Patient-reported symptoms (e.g., Lee Symptom Scale, etc.)

5. Dosage/Administration ^{1,14,17,22-24}

6. Billing Code/Availability Information

HCPCS Code:

• J3380 – Injection, vedolizumab, intravenous, 1 mg; 1 billable unit = 1 mg

NDC:

• Entyvio 300 mg single use vial: 67464-0300-xx

7. References

1. Entyvio [package insert]. Lexington, MA 02421; Takeda Pharmaceuticals U.S.A., Inc.; May 2024. Accessed August 2024.
2. Lichtenstein GR, Loftus EV, Isaacs K, et al. American College of Gastroenterology Clinical Guideline: Management of Crohn’s Disease in Adults. Am J Gastroenterol. 2018;113: 481-517. doi: 10.1038/ajg.2018.27; published online 27 March 2018.
3. 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 Mar;105(3):501-23.
4. Dignass A, Lindsay JO, Sturm A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis. 2012 Dec;6(10):991-1030.
5. Terdiman JP, Gruss CB, Heidelbaugh JJ, et al. American Gastroenterological Association Institute guideline on the use of thiopurines, methotrexate, and anti-TNF-α biologic drugs for the induction and maintenance of remission in inflammatory Crohn's disease. Gastroenterology. 2013 Dec;145(6):1459-63. doi: 10.1053/j.gastro.2013.10.047.
6. Gomollón F, Dignass A, Annese V, et al. EUROPEAN Evidence-based consensus on the diagnosis and management of Crohn's disease 2016: Part 1: Diagnosis and medical management. J Crohns Colitis. 2016 Sep 22. pii: jjw168.
7. Harbord M, Eliakim R, Bettenworth D, et al. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 2: Current Management. J Crohns Colitis. 2017 Jan 28. doi: 10.1093/ecco-jcc/jjx009.
8. National Institute for Health and Care Excellence. NICE 2012. Crohn’s Disease: Management. Published 10 October 2012. Clinical Guideline [CG152]. https://www.nice.org.uk/guidance/cg152/resources/crohns-disease-management-pdf-35109627942085.
9. Lewis JD, Chuai S, Nessel L, et al. Use of the Non-invasive Components of the Mayo Score to Assess Clinical Response in Ulcerative Colitis. Inflamm Bowel Dis. 2008 Dec; 14(12): 1660–1666. doi:  10.1002/ibd.20520
10. Paine ER. Colonoscopic evaluation in ulcerative colitis. Gastroenterol Rep (Oxf). 2014 Aug; 2(3): 161–168.
11. Walsh AJ, Bryant RV, Travis SPL. Current best practice for disease activity assessment in IBD. Nature Reviews Gastroenterology & Hepatology13, 567–579 (2016) doi:10.1038/nrgastro.2016.128
12. Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019 Mar;114(3):384-413.
13. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) vedolizumab. National Comprehensive Cancer Network, 2024. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc.” To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed August 2024.
14. Bergqvist, V, Hertervig E, Gedeon P, et al. Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis. Cancer Immunology Immunotherapy 66: 581-592, No. 5, May 2017.
15. Torres J, Bonovas S, Doherty G, et al. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohn’s Colitis. 2020 Jan 1;14(1):4-22. doi: 10.1093/ecco-jcc/jjz180. PMID: 31711158.
16. National Institute for Health and Care Excellence. NICE 2019. Crohn’s Disease: Management. Published 03 May 2019. Clinical Guideline [NG129]. https://www.nice.org.uk/guidance/ng129/resources/crohns-disease-management-pdf-66141667282885
17. Vermeire S, Loftus EV, Colombel JF, et al. Long-term Efficacy of Vedolizumab for Crohn’s Disease, Journal of Crohn's and Colitis, Volume 11, Issue 4, 1 April 2017, Pages 412–424, https://doi.org/10.1093/ecco-jcc/jjw176
18. National Institute for Health and Care Excellence. NICE 2019. Ulcerative colitis: management. Published 03 May 2019. NICE guideline [NG130]. https://www.nice.org.uk/guidance/ng130
19. Feuerstein JD, Isaacs KL, Schneider Y, et al. AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis. Gastroenterology. 2020;158(5):1450-1461. doi:10.1053/j.gastro.2020.01.006.
20. Raine T, Bonovas S, Burisch J, et al. ECCO Guidelines on therapeutics in ulcerative colitis: medical treatment. J Crohns Colitis. 2022 Jan 28. 16 (1):2-17. Doi: 10.1093/ecco-jcc/jjab178
21. Feuerstein JD, Ho EY, Shmidt E, et al. AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn's Disease. Gastroenterology. 2021 Jun;160(7):2496-2508. doi: 10.1053/j.gastro.2021.04.022. PMID: 34051983; PMCID: PMC8988893.
22. Li AC, Dong C, Tay ST, et al. Vedolizumab for acute gastrointestinal graft versus-host disease: A systematic review and meta-analysis. Front Immunol 2022;13:1025350.
23. Chen YB, Shah NN, Renteria AS, et al. Vedolizumab for prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood Adv. 2019 Dec 10;3(23):4136-4146. doi: 10.1182/bloodadvances.2019000893. PMID: 31821456; PMCID: PMC6963235.
24. Metha, RS, Saliba RM, Jan A, et al. Vedolizumab for Steroid Refractory Lower Gastrointestinal Tract Graft-Versus-Host Disease. Transplant Cell Ther 2021;27:272.e1-272.e5.
25. Gordon H, Minozzi S, Kopylov U et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Medical Treatment, Journal of Crohn's and Colitis, 2024; jjae09. https://doi.org/10.1093/ecco-jcc/jjae091.
26. Ranasinghe IR, Tian C, Hsu R. Crohn Disease. [Updated 2024 Feb 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK436021/.
27. Ananthakrishnan AN, Alder J, Chachu KA, et al. AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn’s Disease. Gastroenterology. 2023 Dec;165(6):1367-1399. doi: 10.1053/j.gastro.2023.09.029. PMID: 37981354.
28. Singh S, Ananthakrishnan AN, Nguyen NH, et al. AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis. Gastroenterology. 2023 Mar;164(3):344-372. doi: 10.1053/j.gastro.2022.12.007. PMID: 36822736.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A