162 Form

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Pharmacy Medical Policy Entyvio (vedolizumab) Policy Table of Contents • Policy: Commercial • Coding Information • Information Pertaining to All Policies • Policy: Medicare
• Background • Forms
• Prior Authorization Information • Policy History • References
Policy Number: 162 BCBSA Reference Number: N/A Related Policies • Formulary Exception Form #434

Prior Authorization Information Policy ☒ Prior Authorization ☐ Step Therapy ☐ Quantity Limit ☐ Administrative Reviewing Department Pharmacy Operations: Tel: 1-800-366-7778 Fax: 1-800-583-6289 Policy Effective Date 10/2024 Pharmacy (Rx) or Medical (MED) benefit coverage ☒ Rx (Specialty Network); OR ☒ MED To request for coverage: Providers may call, fax, or mail the attached form (Formulary Exception/Prior Authorization form) to the address below.
Blue Cross Blue Shield of Massachusetts Pharmacy Operations Department 25 Technology Place Hingham, MA 02043
Tel: 1-800-366-7778 Fax: 1-800-583-6289

Individual Consideration for the atypical patient: Policy for requests that do not meet clinical criteria of this policy, see section labeled Individual Consideration
Policy applies to Commercial Members:
• Managed Care (HMO and POS),
• PPO and Indemnity • MEDEX with Rx plan • Managed Major Medical with Custom BCBSMA Formulary • Comprehensive Managed Major Medical with Custom BCBSMA Formulary • Managed Blue for Seniors with Custom BCBSMA Formulary Policy does NOT apply to: • Medicare Advantage

Summary This is a comprehensive policy covering prior authorization, requirements for Entyvio (vedolizumab) for the treatment of moderate to severe Ulcerative Colitis (UC) and Crohn’s Disease (CD).
Pathogenesis
Inflammatory Bowel Disease (IBD) is a condition characterized by chronic inflammation of the gastrointestinal (GI) tract. While the cause of IBD is unknown, it is however the result of the immune

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system gone awry, triggered by either environmental factors or a genetic component. There are two main types of IBD conditions – UC and CD:

Ulcerative Colitis Chron’s Disease Location Large intestine and rectum Any part of GI tract from the mouth to the anus Damage Continuous damage usually starting at the rectum spreading into the colon Patchy – damaged areas next to areas of health tissue Inflammation Present only in the innermost layer of the colon May reach multiple layers of the walls of the GI tract Entyvio (vedolizumab) is an integrin receptor antagonist approved for the use of moderate to severe Ulcerative Colitis and Crohn’s Disease. It’s FDA approved dosing is 300mg at week zero, two and six, then every 8 weeks thereafter. Entyvio (vedolizumab) should be discontinued in patients who do not show evidence of therapeutic benefit by week 14. Formulary status of Integrin inhibitor agents: Drug Formulary Status
(BCBSMA Commercial Plan) FDA-approved Indication Entyvio (vedolizumab), Intravenous Covered, QCD, PA required Moderate to severely active Ulcerative Colitis; Moderate to severely active Crohn’s disease Entyvio (vedolizumab), Pen Injector Covered, QCD, PA required Moderate to severely active Ulcerative Colitis Moderate to severely active Crohn’s disease PA – Prior Authorization; QCD – Quality Care Dosing/Quantity limit

Policy
No Coverage Requirements For mild Crohn’s Disease in low-risk patients, the recommended treatment approach is step up therapy up therapy with less potent drugs. These drugs have extensive evidence with good safety profiles such as: • Oral 5-aminosalicylates (e.g., sulfasalazine, mesalamine) • Glucocorticoids—topical or systemic (e.g., prednisone, budesonide) • Immunomodulators (e.g., azathioprine, 6-mercaptopurine, methotrexate) Please note that quantity limits may apply – please see limits found in Medical Policy #621B) Entyvio ® (vedolizumab)
Length of Approval Initial: 16 weeks; continuation of therapy: 12 months or 6 months for escalated dosing Formulary status
Prior Authorization is required as per this medical policy. See section on individual consideration if an exception is required for the atypical patient. Dosage considerations Dosage considerations Standard Dosing Initiation: 3 single use vials (300 mg/vial) in the first 6 weeks or 42 days

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Continuation: 1 single use vial every 8 weeks or 56 days OR 1 pen injector every 2 weeks beginning at Week 6 post initiation. Note: We may approve an escalated dosing frequency of 1 single use vial (300 mg) every 4 weeks if additional criteria is met. Initial Approval Criteria APPROVAL duration – 16 weeks Entyvio ® (vedolizumab) may be MEDICALLY NECESSARY when ALL of the following criteria are met: Moderate to Severe Ulcerative Colitis

1. A documented diagnosis of moderate to severe Ulcerative Colitis; AND
2. Age is equal to or greater than 18 years; AND
3. The drug is prescribed by a board-certified or eligible gastroenterologist; AND
4. Documented history of failure, contraindication, or intolerance to at least one of the following conventional therapies: a. Tumor necrosis factor (TNF) blocker (e.g., infliximab, adalimumab, or golimumab); OR b. Immunomodulator (e.g., azathioprine, 6-mercaptopurine); OR c. Corticosteroid; AND
5. Not receiving in combination with any of the following: a. Biologic DMARD (e.g., JAK inhibitors, TNF inhibitors, IL-1 inhibitor, IL-6 inhibitor, etc.); OR b. Other Integrin Inhibitors (e.g., natalizumab); AND
6. For Subcutaneous Entyvio ONLY, there is clinical response or remission beyond week 6 following the first two Entyvio intravenous doses administered at Week 0 and Week 2; AND

7. Documented Dose and Frequency must be submitted and must be within the FDA approved
   Dosing and Frequency.

   *The recommended titration dosage of ENTYVIO in adults with Ulcerative Colitis:
   Intravenous Entyvio - 300 mg administered by intravenous infusion at Week 0, Week 2 and Week 6 and then every 8 weeks thereafter: OR
   Subcutaneous Pen Injector: 300 mg administered by intravenous infusion at Week 0 and Week 2 and then 108 mg subcutaneously at Week 6 and every 2 weeks thereafter

   Moderate to Severe Crohn’s Disease

8. A documented diagnosis of moderate to severe Crohn’s Disease; AND
9. Age is equal to or greater than 18 years; AND
10. The drug is prescribed by a board-certified or eligible gastroenterologist; AND
11. Not receiving in combination with either of the following: 1 1

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a. Potent Immunosuppressives (e.g., JAK inhibitors, TNF inhibitors, IL-1 inhibitor, IL-6 inhibitor, etc.); OR Natalizumab.
AND

5. For Subcutaneous Entyvio ONLY, there is clinical response or remission beyond week 6 following the first two Entyvio intravenous doses administered at Week 0 and Week 2; AND

6. Documented Dose and Frequency must be submitted and must be within the FDA approved
   Dosing and Frequency.

   *The recommended titration dosage of ENTYVIO in adults with Ulcerative Colitis:
   Intravenous Entyvio - 300 mg administered by intravenous infusion at Week 0, Week 2 and Week 6 and then every 8 weeks thereafter: OR
   Subcutaneous Pen Injector: 300 mg administered by intravenous infusion at Week 0 and Week 2 and then 108 mg subcutaneously at Week 6 and every 2 weeks thereafter Renewal Criteria RE-AUTHORIZATION duration – 12 months We may renew coverage of Entyvio® if ALL the following criteria are met:

7. Individual continues to meet initial approval criteria; AND
8. Absence of unacceptable toxicity from the medication or serious allergic reactions, or severe infections; AND

9. Continued diagnosis and documentation of positive clinical response to Entyvio where a response to treatment as indicated by improvement in signs and symptoms compared to baseline including but not limited to: a. Reduction in stool frequency/bloody stools; OR b. Improvement abdominal pain; OR c. Endoscopic and laboratory response (e.g., C-reactive Protein); AND

10. Documented Dose and Frequency must be submitted and must be within the FDA approved
    Dosing and Frequency.

    *FDA-labeled dosing - The recommended dosage of ENTYVIO in adults with ulcerative colitis or Crohn's disease is 300 mg administered by intravenous infusion at zero, two and six weeks and then every eight weeks thereafter: OR
    Subcutaneous Pen Injector: 300 mg administered by intravenous infusion at Week 0 and Week 2 and then 108 mg subcutaneously at Week 6 and every 2 weeks thereafter

    Renewal Criteria

    Dose Escalation Criteria INITIAL APPROVAL duration – 16 weeks

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An escalated dosing regimen for Entyvio ® (vedolizumab) may be approved for one vial (300 mg) every 4 weeks if the following criteria are met:

1. Individual has been treated with standard maintenance dosing (i.e., every 8 weeks) for at least 2 doses or 16 weeks; AND
2. The increased dosing is being prescribed by or in consultation with a gastroenterologist; AND
3. Individual is not requesting dose escalation based solely on therapeutic drug levels or antibody testing alone in the absence of signs and symptoms of disease; AND
4. Partial or inadequate response to standard dosing characterized by: a. Individual initially achieved an adequate response to standard maintenance dosing but has subsequently lost response, as determined by the prescriber; OR b. Individual partially responded but had an inadequate response to standard maintenance dosing as determined by the prescriber; AND
5. Absence of unacceptable toxicity from the medication or serious allergic reactions, or severe infections; AND

6. Dose escalation does not exceed one vial (300 mg) every 4 weeks.

7. Documented Dose and Frequency must be submitted with dose escalation.

   Dose Escalation Renewal Criteria RE-AUTHORIZATION duration – 6 months We may renew coverage of escalated dosing of Entyvio ® (vedolizumab) if ALL the following criteria are met:

8. Escalated dosage does not exceed one vial (300 mg) every 4 weeks; AND
9. Individual subsequently regained response or documentation of positive clinical response following increased dosing, as indicated by improvement in signs and symptoms of the disease including but not limited to: a. Reduction in stool frequency/bloody stools; OR b. Improvement abdominal pain; OR c. Endoscopic and laboratory response (e.g., C-reactive Protein); AND
10. Individual is not experiencing unacceptable adverse effects or serious allergic reactions, or severe infections; AND
11. Individual is being assessed regularly (at least annually) for dose de-escalation.
12. Documented Dose and Frequency must be submitted with dose escalation. Use of Entyvio ® (vedolizumab) may be considered INVESTIGATIONAL for all other indications not specifically mentioned above.

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Individual Consideration Our medical policies are written for most people with a given condition. Each policy is based on peer reviewed clinical evidence. We also take into consideration the needs of atypical patient populations and diagnoses.
If the coverage criteria outlined is unlikely to be clinically effective for the prescribed purpose, the health care provider may request an exception to cover the requested medication based on an individual’s unique clinical circumstances. This is also referred to as “individual consideration” or an “exception request.”
Some reasons why you may need us to make an exception include: therapeutic contraindications; history of adverse effects; expected to be ineffective or likely to cause harm (physical, mental, or adverse reaction).
To facilitate a thorough and prompt review of an exception request, we encourage the provider to include additional supporting clinical documentation with their request. This may include: • Clinical notes or supporting clinical statements; • The name and strength of formulary alternatives tried and failed (if alternatives were tried) and specifics regarding the treatment failure, if applicable; • Clinical literature from reputable peer reviewed journals; • References from nationally recognized and approved drug compendia such as American Hospital Formulary Service® Drug Information (AHFS-DI), Lexi-Drug, Clinical Pharmacology, Micromedex or Drugdex®; and • References from consensus documents and/or nationally sanctioned guidelines.

Providers may call, fax or mail relevant clinical information, including clinical references for individual patient consideration, to:

Blue Cross Blue Shield of Massachusetts Pharmacy Operations Department 25 Technology Place Hingham, MA 02043
Phone: 1-800-366-7778 Fax: 1-800-583-6289

We may also use prescription claims records to establish prior use of formulary alternatives or to show if step therapy criteria has been met. We will require the provider to share additional information when prescription claims data is either not available or the medication fill history fails to establish use of preferred formulary medications or that step therapy criteria has been met.
CPT Codes / HCPCS Codes / ICD Codes The following codes are included below for informational purposes. Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage as it applies to an individual member. Providers should report all services using the most up-to-date industry-standard procedure, revenue, and diagnosis codes, including modifiers where applicable. HCPCS Codes HCPCS Code Code Description

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ICD-10 Diagnosis Codes ICD10 Diagnosis Code Code Description K50.00 Crohn's disease of small intestine without complications K50.011 Crohn's disease of small intestine with rectal bleeding K50.012 Crohn's disease of small intestine with intestinal obstruction K50.013 Crohn's disease of small intestine with fistula K50.014 Crohn's disease of small intestine with abscess K50.018 Crohn's disease of small intestine with other complication K50.019 Crohn's disease of small intestine with unspecified complications K50.10 Crohn's disease of large intestine without complications K50.111 Crohn's disease of large intestine with rectal bleeding K50.112 Crohn's disease of large intestine with intestinal obstruction K50.113 Crohn's disease of large intestine with fistula K50.114 Crohn's disease of large intestine with abscess K50.118 Crohn's disease of large intestine with other complication K50.119 Crohn's disease of large intestine with unspecified complications K50.80 Crohn's disease of both small and large intestine without complications K50.811 Crohn's disease of both small and large intestine with rectal bleeding K50.812 Crohn's disease of both small and large intestine with intestinal obstruction K50.813 Crohn's disease of both small and large intestine with fistula K50.814 Crohn's disease of both small and large intestine with abscess K50.818 Crohn's disease of both small and large intestine with other complication K50.819 Crohn's disease of both small and large intestine with unspecified complications K50.90 Crohn's disease, unspecified, without complications K50.911 Crohn's disease, unspecified, with rectal bleeding K50.912 Crohn's disease, unspecified, with intestinal obstruction K50.913 Crohn's disease, unspecified, with fistula K50.914 Crohn's disease, unspecified, with abscess K50.918 Crohn's disease, unspecified, with other complication K50.919 Crohn's disease, unspecified, with unspecified complications K51.00 Ulcerative (chronic) pancolitis without complications K51.011 Ulcerative (chronic) pancolitis with rectal bleeding K51.012 Ulcerative (chronic) pancolitis with intestinal obstruction K51.013 Ulcerative (chronic) pancolitis with fistula K51.014 Ulcerative (chronic) pancolitis with abscess K51.018 Ulcerative (chronic) pancolitis with other complication K51.019 Ulcerative (chronic) pancolitis with unspecified complications K51.20 Ulcerative (chronic) proctitis without complications K51.211 Ulcerative (chronic) proctitis with rectal bleeding K51.212 Ulcerative (chronic) proctitis with intestinal obstruction K51.213 Ulcerative (chronic) proctitis with fistula K51.214 Ulcerative (chronic) proctitis with abscess K51.218 Ulcerative (chronic) proctitis with other complication J3380 Injection, vedolizumab, 1 mg J3590 Unclassified drugs or biologics, Vedolizumab (SC)

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K51.219 Ulcerative (chronic) proctitis with unspecified complications K51.30 Ulcerative (chronic) rectosigmoiditis without complications K51.311 Ulcerative (chronic) rectosigmoiditis with rectal bleeding K51.312 Ulcerative (chronic) rectosigmoiditis with intestinal obstruction K51.313 Ulcerative (chronic) rectosigmoiditis with fistula K51.314 Ulcerative (chronic) rectosigmoiditis with abscess K51.318 Ulcerative (chronic) rectosigmoiditis with other complication K51.319 Ulcerative (chronic) rectosigmoiditis with unspecified complications K51.40 Inflammatory polyps of colon without complications K51.411 Inflammatory polyps of colon with rectal bleeding K51.412 Inflammatory polyps of colon with intestinal obstruction K51.413 Inflammatory polyps of colon with fistula K51.414 Inflammatory polyps of colon with abscess K51.418 Inflammatory polyps of colon with other complication K51.419 Inflammatory polyps of colon with unspecified complications K51.50 Left sided colitis without complications K51.511 Left sided colitis with rectal bleeding K51.512 Left sided colitis with intestinal obstruction K51.513 Left sided colitis with fistula K51.514 Left sided colitis with abscess K51.518 Left sided colitis with other complication K51.519 Left sided colitis with unspecified complications K51.80 Other ulcerative colitis without complications K51.811 Other ulcerative colitis with rectal bleeding K51.812 Other ulcerative colitis with intestinal obstruction K51.813 Other ulcerative colitis with fistula K51.814 Other ulcerative colitis with abscess K51.818 Other ulcerative colitis with other complication K51.819 Other ulcerative colitis with unspecified complications K51.90 Ulcerative colitis, unspecified, without complications K51.911 Ulcerative colitis, unspecified with rectal bleeding K51.912 Ulcerative colitis, unspecified with intestinal obstruction K51.913 Ulcerative colitis, unspecified with fistula K51.914 Ulcerative colitis, unspecified with abscess K51.918 Ulcerative colitis, unspecified with other complication K51.919 Ulcerative colitis, unspecified with unspecified complications T45.1X5A Adverse effect of antineoplastic and immunosuppressive drugs, initial encounter T45.1X5D Adverse effect of antineoplastic and immunosuppressive drugs, subsequent encounter T45.1X5S Adverse effect of antineoplastic and immunosuppressive drugs, sequela

Policy History Date Action 10/2024 Updated to add SubQ dosing to Crohns 3/2024 Updated to require dose and frequency for Prior Authorization. 7/2023 Updated to align with 118E MGL § 51A 6/2023 Updated to new format, updated criteria for UC & CD coverage, references.
8/2022 Updated Criteria for both Crohn’s and UC. 4/2021 Implement new standalone policy for Entyvio ® J3380 or J3380.

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Information Pertaining to All Blue Cross Blue Shield Medical Policies Click on any of the following terms to access the relevant information: Medical Policy Terms of Use ref Managed Care Guidelines Indemnity/PPO Guidelines Clinical Exception Process Medical Technology Assessment Guidelines

Forms To request prior authorization using the Massachusetts Standard Form for Medication Prior Authorization Requests (eForm), click the link below: Formulary Exception Form #434 Endnotes

1. FDA-approved indications
2. From National Blue Cross Blue Shield Association policy 5.01.05

3. Local Medicare policy http://www.medicarenhic.com/ and CMS guidelines http://www.hcfa.gov/pubforms/14%5Fcar/3b2049.htm#_1_7.

   References

4. Entyvio ® [Product Information]. Lexington, MA. Takeda Pharmaceuticals U.S.A., Inc.; June 2022.
5. Medical Management of Low-Risk Adult Patients with Mild to Moderate Ulcerative Colitis. UptoDate Accessed: 6/1/2023
6. Management of Moderate to Severe Ulcerative Colitis in Adults. UptoDate Accessed: 6/1/2023
7. Overview of Drug Dosing and Monitoring of Biologic Agents and Small Molecule for Treatment of Ulcerative Colitis in Adults. UptoDate Accessed: 6/1/2023
8. Overview of Medical Management of High-risk, Adult Patients with Moderate to Severe Chron’s Disease. UptoDate Accessed: 6/6/2023
9. GR Lichtenstein et al. ACG Clinical Guideline: Management of Chron’s Disease in Adults. Am J Gastroenterology 2018;113:481-517.
10. JD Feuerstein et al. AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Chron’s Disease. Gastroenterology 2021;160:2496–2508.