Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual
Policy #:	2015011
Category:	Pharmacy
Initiated:	May 2015
Last Review:	July 2025

Vedolizumab (e.g., Entyvio) for Inflammatory Bowel Disease

Description:

Vedolizumab (e.g., Entyvio) is a humanized monoclonal antibody that inhibits adhesion and migration of leukocytes into the gastrointestinal tract by preventing the alpha4beta7 integrin subunit from binding to mucosal addressing cell adhesion molecule-1 (MAdCAM-1). It was developed as a treatment for individuals with moderate to severe ulcerative colitis (UC) or Crohn's disease (CD) who have failed at least one conventional therapy, including tumor necrosis factor (TNF) antagonists. The interaction of the α4β7 integrin with MAdCAM-1 has been implicated as an important contributor to the chronic inflammation that is a hallmark of ulcerative colitis and Crohn’s disease (Takeda Pharmaceutical, 2014).

Regulatory Status

On May 20, 2014, the U.S. Food and Drug Administration approved vedolizumab injection to treat adult individuals with moderate to severe ulcerative colitis and adult individuals with moderate to severe Crohn‘s disease (FDA , 2014).

On September 28, 2023, the U.S. Food and Drug Administration approved vedolizumab injection, for subcutaneous use, for the treatment of adults with moderately to severely active ulcerative colitis.

Coding

See CPT/HCPCS Code section below.

Policy/
Coverage:

Effective April 01, 2022 Prior Approval is required for Vedolizumab.

The use of vedolizumab subcutaneous injection is not covered under the medical benefit. Please check the member’s pharmacy benefit for coverage.

The use of vedolizumab intravenous injection is covered under the medical benefit.

Approval timeframes may differ for members/participants of Self-Insured plans.

Effective July 2025

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Vedolizumab (e.g., Entyvio) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:

For FDA labeled indications, Vedolizumab (e.g., Entyvio) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.

ULCERATIVE COLITIS

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual is 18 years of age or older; AND

2. Individual has a diagnosis of moderate to severe ulcerative colitis supported by the submitted medical records; AND

3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR

4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR

5. Individual has previously received a biologic (e.g., adalimumab, infliximab, golimumab, ustekinumab, vedolizumab, mirikizumab) or targeted synthetic drug (e.g., tofacitinib, upadacitinib, ozanimod, etrasimod) indicated for ulcerative colitis; AND

6. Individual is not using the medication in combination with other biologic intended for treatment of ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor.

CONTINUED APPROVAL for up to 1 year:

1. Individual has met initial criteria for a diagnosis of ulcerative colitis; AND

2. Individual has experienced a documented positive clinical response; AND

3. Individual is not using the medication in combination with other biologic intended for treatment of ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor.

CROHN’S DISEASE

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual is 18 years of age or older; AND

2. Individual has a diagnosis of moderate to severe Crohn’s disease supported by the submitted medical records; AND

3. Individual has an active disease with documented inadequate response (trial of ≥3 months) to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Lichtenstein, 2018); OR

4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Van Rheenen, 2021); OR

5. Individual has previously received a biologic (e.g., adalimumab, infliximab, certolizumab pegol, risankizumab, ustekinumab, natalizumab, vedolizumab) or Janus Kinase Inhibitor (e.g., updatacitinib) indicated for Crohn’s disease; OR

6. Individual has fistulizing disease (Feuerstein, 2021); AND

7. Individual is not using the medication in combination with other biologic intended for treatment of Crohn’s disease, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor.

CONTINUED APPROVAL for up to 1 year:

1. Individual has met initial criteria for a diagnosis of Crohn’s disease; AND

2. Individual has experienced a documented positive clinical response; AND

3. Individual is not using the medication in combination with other biologic intended for treatment of Crohn’s disease, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor.

POLICY GUIDELINES

Prescriber is responsible for verification that Individual does not have latent tuberculosis or serious active infection before starting the treatment.

Dosage and Administration

Dosing per FDA Guidelines unless otherwise specified below.

The recommended dosage in UC and CD: 300 mg infused intravenously at week 0, 2 weeks , 6 weeks, then every 8 weeks thereafter.

Week 0: 300 mg infused intravenously over approximately 30 minutes.
Week 2: 300 mg infused intravenously over approximately 30 minutes.
Week 6: Individuals may remain on vedolizumab intravenous therapy or switch to subcutaneous injection after receiving two vedolizumab intravenous doses administered at Week 0 and Week 2.
- Intravenous Infusion: 300 mg infused over approximately 30 minutes and then every eight weeks thereafter.
- Subcutaneous Injection: 108 mg subcutaneously once every two weeks. The use of vedolizumab subcutaneous injection is not covered under the medical benefit. Please check the member’s pharmacy benefit for coverage.
Discontinue vedolizumab in individuals who do not show evidence of therapeutic benefit by Week 14.

Bring individuals up to date with all immunizations (according to current immunization guidelines) before initiating treatment with vedolizumab.

Intravenous Infusion: Vedolizumab is available as 300 mg in a single-dose vial.

Vedolizumab should be administered by as an intravenous by a healthcare professional.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Vedolizumab (e.g., Entyvio), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For individuals with contracts without primary coverage criteria, vedolizumab (e.g., Entyvio) for any indication or circumstance not described above is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.

Effective February 12, 2025 to June 2025

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

ULCERATIVE COLITIS

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual is 18 years of age or older; AND

2. Individual has a diagnosis of moderate to severe ulcerative colitis supported by the submitted medical records; AND

3. Individual has an active disease with documented inadequate response (trial of ≥3 months) to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR

4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR

5. Individual has previously received a biologic (e.g., adalimumab, infliximab, golimumab, ustekinumab, vedolizumab, mirikizumab) or targeted synthetic drug (e.g., tofacitinib, upadacitinib, ozanimod, etrasimod) indicated for ulcerative colitis; AND

6. Individual is not using the medication in combination with other biologic intended for treatment of ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND

7. Must be dosed in accordance with the FDA label.  

CONTINUED APPROVAL for up to 1 year:

1. Individual has met initial criteria for a diagnosis of ulcerative colitis; AND

2. Individual has experienced a documented positive clinical response; AND

3. Individual is not using the medication in combination with other biologic intended for treatment of ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND

4. Must be dosed in accordance with the FDA label.

CROHN’S DISEASE

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual is 18 years of age or older; AND

2. Individual has a diagnosis of moderate to severe Crohn’s disease supported by the submitted medical records; AND

3. Individual has an active disease with documented inadequate response (trial of ≥3 months) to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Lichtenstein, 2018); OR

4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Van Rheenen, 2021); OR

5. Individual has previously received a biologic (e.g., adalimumab, infliximab, certolizumab pegol, risankizumab, ustekinumab, natalizumab, vedolizumab) or Janus Kinase Inhibitor (e.g., updatacitinib) indicated for Crohn’s disease; OR

6. Individual has fistulizing disease (Feuerstein, 2021); AND

7. Individual is not using the medication in combination with other biologic intended for treatment of Crohn’s disease, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND

8. Must be dosed in accordance with the FDA label.  

CONTINUED APPROVAL for up to 1 year:

1. Individual has met initial criteria for a diagnosis of Crohn’s disease; AND

2. Individual has experienced a documented positive clinical response; AND

3. Individual is not using the medication in combination with other biologic intended for treatment of Crohn’s disease, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND

4. Must be dosed in accordance with the FDA label.

POLICY GUIDELINES

Prescriber is responsible for verification that Individual does not have latent tuberculosis or serious active infection before starting the treatment.

Dosage and Administration

Dosing per FDA Guidelines

The recommended dosage in UC and CD: 300 mg infused intravenously at week 0, 2 weeks , 6 weeks, then every 8 weeks thereafter.

Week 0: 300 mg infused intravenously over approximately 30 minutes.
Week 2: 300 mg infused intravenously over approximately 30 minutes.
Week 6: Individuals may remain on vedolizumab intravenous therapy or switch to subcutaneous injection after receiving two vedolizumab intravenous doses administered at Week 0 and Week 2.
- Intravenous Infusion: 300 mg infused over approximately 30 minutes and then every eight weeks thereafter.
- Subcutaneous Injection: 108 mg subcutaneously once every two weeks. The use of vedolizumab subcutaneous injection is not covered under the medical benefit. Please check the member’s pharmacy benefit for coverage.
Discontinue vedolizumab in individuals who do not show evidence of therapeutic benefit by Week 14.

Bring individuals up to date with all immunizations (according to current immunization guidelines) before initiating treatment with vedolizumab.

Intravenous Infusion: Vedolizumab is available as 300 mg in a single-dose vial.

Vedolizumab should be administered by as an intravenous by a healthcare professional.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Vedolizumab, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For individuals with contracts without primary coverage criteria, vedolizumab for any indication or circumstance not described above is considered investigational. Investigational services are exclusions in most member benefit certificates of coverage.

Effective August 21, 2024 to February 11, 2025

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

ULCERATIVE COLITIS

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual is 18 years of age or older; AND

2. Individual has a diagnosis of moderate to severe ulcerative colitis supported by the submitted medical records; AND

3. Individual has an active disease with documented inadequate response (trial of ≥3 months) to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR

4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR

5. Individual has previously received a biologic (e.g., adalimumab, infliximab, golimumab, ustekinumab, vedolizumab, mirikizumab) or targeted synthetic drug (e.g., tofacitinib, upadacitinib, ozanimod, etrasimod) indicated for ulcerative colitis; AND

6. Individual is not using the medication in combination with other biologic intended for treatment of ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND

7. Individual does not have latent tuberculosis or serious active infection; AND

8. Must be dosed in accordance with the FDA label.  

CONTINUED APPROVAL for up to 1 year:

1. Individual has met initial criteria for a diagnosis of ulcerative colitis; AND

2. Individual has experienced a documented positive clinical response; AND

3. Individual is not using the medication in combination with other biologic intended for treatment of ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND

4. Must be dosed in accordance with the FDA label.

CROHN’S DISEASE

INITIAL APPROVAL STANDARD REVIEW for up to 12 months: 

1. Individual is 18 years of age or older; AND

2. Individual has a diagnosis of moderate to severe Crohn’s disease supported by the submitted medical records; AND

3. Individual has an active disease with documented inadequate response (trial of ≥3 months) to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Lichtenstein, 2018); OR

4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Van Rheenen, 2021); OR

5. Individual has previously received a biologic (e.g., adalimumab, infliximab, certolizumab pegol, risankizumab, ustekinumab, natalizumab, vedolizumab) or Janus Kinase Inhibitor (e.g., updatacitinib) indicated for Crohn’s disease; OR

6. Individual has fistulizing disease (Feuerstein, 2021); AND

7. Individual is not using the medication in combination with other biologic intended for treatment of Crohn’s disease, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND

8. Individual does not have latent tuberculosis or serious active infection; AND

9. Must be dosed in accordance with the FDA label.  

CONTINUED APPROVAL for up to 1 year:

1. Individual has met initial criteria for a diagnosis of Crohn’s disease; AND

2. Individual has experienced a documented positive clinical response; AND

3. Individual is not using the medication in combination with other biologic intended for treatment of Crohn’s disease, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND

4. Must be dosed in accordance with the FDA label.

Dosage and Administration

Dosing per FDA Guidelines

The recommended dosage in UC and CD:

Week 0: 300 mg infused intravenously over approximately 30 minutes.
Week 2: 300 mg infused intravenously over approximately 30 minutes.
Week 6: Individuals may remain on vedolizumab intravenous therapy or switch to subcutaneous injection after receiving two vedolizumab intravenous doses administered at Week 0 and Week 2.
- Intravenous Infusion: 300 mg infused over approximately 30 minutes and then every eight weeks thereafter.
- Subcutaneous Injection: 108 mg subcutaneously once every two weeks. The use of vedolizumab subcutaneous injection is not covered under the medical benefit. Please check the member’s pharmacy benefit for coverage.
Discontinue vedolizumab in individuals who do not show evidence of therapeutic benefit by Week 14.

Bring individuals up to date with all immunizations (according to current immunization guidelines) before initiating treatment with vedolizumab.

Intravenous Infusion: Vedolizumab is available as 300 mg in a single-dose vial.

Vedolizumab should be administered by as an intravenous by a healthcare professional.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Due to the detail of the policy statement, the document containing the coverage statements for dates prior to August 21, 2024 is not online. If you would like a hardcopy print, please email: codespecificinquiry@arkbluecross.com

Rationale:

This policy was enacted with searches of the MEDLINE database with literature reviewed through April 2015. Following is a summary of the key literature.

The safety and effectiveness of Vedolizumab (VDZ) for ulcerative colitis (UC) was established in two induction and maintenance clinical trials (GEMINI I) conducted by Feagan et al (2013) involving 895 patients who had not responded adequately to corticosteroids, immunomodulators, or tumor necrosis factor blocker medications. The 2 trials were integrated randomized, double-blind, placebo-controlled trials of VDZ in patients with active UC.

In the trial of induction therapy, 374 patients (cohort 1) received VDZ (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label VDZ at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to VDZ at week 6 were randomly assigned to continue receiving VDZ every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score of at least 3 points and a decrease of at least 30 % from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Mayo clinic score is an evaluation and measurement of stool frequency, rectal bleeding, endoscopic findings and a physician‘s overall assessment. Score ranges from 0 to 12, with higher scores indicating more active disease. Response rates at week 6 were 47.1 % and 25.5 % among patients in the VDZ group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95 % confidence interval [CI]: 11.6 to 31.7; p < 0.001). At week 52, 41.8 % of patients who continued to receive VDZ every 8 weeks and 44.8 % of patients who continued to receive VDZ every 4 weeks were in clinical remission (Mayo Clinic score less than or equal to 2 and no subscore greater than 1), as compared with 15.9 % of patients who switched to placebo (adjusted difference, 26.1 percentage points for VDZ every 8 weeks versus placebo [95 % CI: 14.9 to 37.2; p < 0.001] and 29.1 percentage points for VDZ every 4 weeks versus placebo [95 % CI: 17.9 to 40.4; p < 0.001]). The frequency of adverse events was similar in the VDZ and placebo groups (Feagan et al, 2013).

Findings from GEMINI I showed that VDZ met primary endpoints for improvements in clinical response at six weeks and clinical remission at 52 weeks. A statistically significant number of UC patients achieved corticosteroid-free clinical remission and showed mucosal healing (Mayo endoscopic subscore of 0 or 1) compared with placebo. Therefore, the authors concluded that VDZ was more effective than placebo as induction and maintenance therapy for UC (Feagan et al, 2013 and FDA, 2014).

The safety and effectiveness of Vedolizumab (VDZ) for Crohn‘s (CD) disease was established in three induction and maintenance clinical trials (GEMINI II) conducted by Sandborn et al (2013) involving 1,576 patients who had not responded adequately to corticosteroids, immunomodulators, or tumor necrosis factor blocker medications. The study was integrated with separate induction and maintenance trials that assessed intravenous VDZ therapy (300 mg) in adults with active Crohn’s disease.

In the induction trial, 368 patients were randomly assigned to receive VDZ or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label VDZ at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to VDZ were randomly assigned to receive placebo or VDZ every 8 or 4 weeks until week 52. At week 6, a total of 14.5 % of the patients in cohort 1 who received VDZ and 6.8 % who received placebo were in clinical remission (i.e., had a score on the Crohn’s Disease Activity Index (CDAI) of less than or equal to 150) (p = 0.02); a total of 31.4 % and 25.7 % of the patients, respectively, had a CDAI-100 response (greater than or equal to 100-point decrease in the CDAI score) (p = 0.23). CDAI scores range from 0 to 600, with higher scores indicating greater disease activity. Among VDZ patients in cohorts 1 and 2 who had a response to induction therapy, 39.0 % and 36.4 % of those assigned to VDZ every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6 % assigned to placebo (p < 0.001 and p = 0.004 for the 2 VDZ groups, respectively, versus placebo). Antibodies against VDZ developed in 4.0 % of the patients. Naso-pharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving VDZ than in patients receiving placebo. VDZ, as compared with placebo, was associated with a higher rate of serious adverse events (24.4 % versus 15.3 %), infections (44.1 % versus 40.2 %), and serious infections (5.5 % versus 3.0 %).

The authors concluded that VDZ-treated patients with active Crohn’s disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive VDZ (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with VDZ (Sandborn, 2013).

In a Mayo Clinic article (2013), gastroenterologist Dr. Edward V. Loftus, interpreted the Gemini I and II results to indicate that VDZ is better for treating UC than Crohn’s. Loftus stated that VDZ met its primary endpoint for Crohn's disease but not all of its secondary endpoints and that, “the induction data are not as robust as the maintenance data. So it's possible these drugs--the lymphocyte trafficking blockers-- have a slower onset of action in Crohn's. The efficacy-to-safety ratio may also not be as good for Crohn's as for UC."

In 2015, Garnock-Jones published the results of a study on the pharmacological properties of intravenous infusions of VDZ and its clinical efficacy in adult patients with UC and Crohn’s. In phase III clinical trials, patients with UC had significantly higher rates of clinical response and clinical remission when treated with VDZ than when receiving placebo at both 6 and 52 weeks. However, outcomes with VDZ in patients with Crohn's disease were mixed. In a study that evaluated both clinical remission rate and CDAI-100 response rate as primary endpoints, only the clinical remission rate at 6 weeks was significantly higher with vedolizumab than placebo. In another trial, there was no significant between-group difference in the clinical remission rate in TNF-antagonist failure patients at 6 weeks (primary endpoint), although there was a significant difference at 10 weeks. In the Crohn's disease study that included maintenance treatment, VDZ was significantly more effective at 52 weeks than placebo in both endpoints (clinical remission was the only primary endpoint in the maintenance study). VDZ was generally well tolerated in these trials. Also, vedolizumab is a specific α4β7 integrin antagonist, with gut-specific effects, and is unlikely to be associated with the development of progressive multifocal leukoencephalopathy, a risk observed with the less selective α4β7/α4β1 integrin antagonist natalizumab. Overall, current research supports vedolizumab as a useful treatment option for patients with moderately to severely active ulcerative colitis. The evidence for use of vedolizumab as a cost effective treatment option for Crohn’s disease is insufficient.

In 2023, Pannacione et al have published a Bayesian Network Meta-Analysis evaluation efficacy and safety of advanced therapies for moderately to severely active ulcerative colitis. Vedolizumab maintenance 300 mg every 8 weeks had a slightly better clinical response rate (absolute rate 55%, range 30-79%) than vedolizumab 300 mg every 4 weeks (absolute rate 52%, range 24-79%) with identical rate of clinical remission (45% absolute rate for both). Vedolizumab 300 mg every 4 weeks was also more frequently discontinued due to adverse events.

Updated Prescribing Insert states that vedolizumab every four-week dosing regimen did not demonstrate additional clinical benefit over every eight-week dosing regimen. Manufacturer states that every four-week dosing regimen is not recommended.

Mechanistically, the α4β7 binding saturation studies that evaluated serum inhibition of MAdCAM-1-Fc binding to α4β7 revealed that maximum (100%) α4β7 binding saturation was achieved within an hour after the first dose, at all doses over a range of 2-10 mg/kg. This level of inhibition was sustained for a substantial period of time: 84, 126 and 112 days for 2 mg/kg, 6 mg/kg, and 10 mg/kg dose cohorts, respectively. The serum concentration associated with dropping below 100% ranged 2-6 micrograms/mL. Based on this, every 8-week dosing schedule (every 56 days) is expected to result in sustained maximum binding of vedolizumab to α4β7.

2016 Update

A literature search conducted through August 2016 did not reveal any new information that would prompt a change in the coverage statement.

2017 Update

A literature search conducted through August 2017 did not reveal any new information that would prompt a change in the coverage statement.

2018 Update

A literature search conducted through August 2018 did not reveal any new information that would prompt a change in the coverage statement.

2019 Update

A literature search conducted through July 2019 did not reveal any new information that would prompt a change in the coverage statement.

2020 Update

Annual policy review completed with a literature search using the MEDLINE database through August 2020. No new literature was identified that would prompt a change in the coverage statement.

2021 Update

Annual policy review completed with a literature search using the MEDLINE database through August 2021. No new literature was identified that would prompt a change in the coverage statement.

2022 Update

Annual policy review completed with a literature search using the MEDLINE database through August 2022. No new literature was identified that would prompt a change in the coverage statement.

2023 Update

Annual policy review completed with a literature search using the MEDLINE database through August 2023. No new literature was identified that would prompt a change in the coverage statement.

March 2024 Update

Rationale has been updated based on the Pannacione (2023) meta-analysis and updated package insert.

2024 Update

A subgroup analysis was conducted in Japanese patients with moderate to severe ulcerative colitis (UC) enrolled in the phase 3 VISIBLE 1 study, which evaluated the safety and efficacy of a new vedolizumab subcutaneous (SC) formulation.

Eligible patients received open-label infusions of vedolizumab 300 mg intravenous (IV) at weeks 0 and 2 in the induction phase. Patients with clinical response by complete Mayo score at week 6 entered the double-blind maintenance phase and were randomized to vedolizumab 108 mg SC every 2 weeks, placebo, or vedolizumab 300 mg IV every 8 weeks. The primary endpoint was clinical remission (complete Mayo score ≤ 2 points; no individual subscore > 1 point) at week 52.

Of 49 patients who entered the induction phase, 22 out of 49 patients (45%) had clinical response at week 6 and were randomized to vedolizumab 108 mg SC (n = 10), placebo (n = 10), or vedolizumab 300 mg IV (n = 2). At week 52, 4 out of 10 patients (40%) who received vedolizumab SC had clinical remission versus 2 out of 10 patients (20%) who received placebo (difference: 20% [95% confidence interval, -27.9 to 61.8]). Two patients (2/10, 20%) who received vedolizumab SC experienced an injection-site reaction versus none who received placebo.

Results indicate that the efficacy of vedolizumab SC in a subgroup of Japanese patients with UC are similar with those in the overall VISIBLE 1 study population, and with those established with vedolizumab IV. The safety and tolerability of vedolizumab SC were generally similar to that established for vedolizumab IV. (ClinicalTrials.gov ID NCT02611830; EudraCT 2015-000480-14). (Kobayashi T, Ito H, Ashida T, et.al., 2021)

The safety and efficacy of subcutaneous ENTYVIO was evaluated in a randomized, doubleblind, placebo-controlled trial (SC CD Trial; NCT02611817) in adult patients with moderately to severely active Crohn’s disease defined as CDAI score of 220 to 450. At baseline, the median CDAI score was 316 (range: 198 to 559).

The trial included patients who had experienced an inadequate response to, loss of response to, or intolerance to at least one of the following: corticosteroids, immunomodulators (azathioprine, 6-mercaptopurine, or methotrexate), or TNF blockers (including primary nonresponders). Patients were permitted to use concomitant stable doses of oral aminosalicylates, oral corticosteroids (prednisone ≤30 mg/day, budesonide ≤9 mg/day, or equivalent steroid), immunomodulators, probiotics, antidiarrheals, and/or antibiotics. Concomitant biologic therapies, rectal treatment with 5-aminosalicylic acid or corticosteroid enemas/suppositories were prohibited.

All patients received open-label intravenous ENTYVIO 300 mg at Week 0 and Week 2. In order to be randomized to treatment in SC CD Trial, patients had to be in clinical response (defined as a ≥70-point decrease in the CDAI score from baseline) at Week 6. A total of 409 patients were randomized at Week 6 in a double-blind fashion (2:1) to ENTYVIO 108 mg administered by subcutaneous injection or placebo every 2 weeks. Efficacy assessments were at Week 52.

Beginning at Week 6, patients who were receiving corticosteroids were required to begin a corticosteroid tapering regimen.

At the time of randomization into the double-blind phase (Week 6), patients were receiving corticosteroids (45%), immunomodulators (32%), and aminosalicylates (45%). Fifty-one percent of patients had an inadequate response, loss of response, or intolerance to a TNF blocker therapy prior to enrollment.

Patients in the double-blind phase had a mean age of 38 years (range 18 to 76 years); 55% were male; 91% identified as White, 6% as Asian, and 3% identified as another racial group.

The primary endpoint was the proportion of patients with clinical remission (CDAI score ≤150) at Week 52.

Among patients using oral corticosteroids at baseline (Week 0) and achieving clinical response at Week 6, 45% (43/95) treated with subcutaneous ENTYVIO compared to 18% (8/44) treated with placebo discontinued corticosteroids and were in clinical remission at Week 52. This result was not statistically significant under the prespecified multiple testing procedure. (FDA, 2024)

2025 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2025. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:

References:

Bressler B, Marshall JK, Bernstein CN , Bitton A, Jones J, Leontiadis GI, Panaccione R, Steinhart AH, Tse F, Feagan B , Toronto Ulcerative Colitis Consensus Group.(2015) Clinical Practice Guidelines for the Medical Management of Nonhospitalized Ulcerative Colitis: The Toronto Consensus Gastroenterology. 2015 May;148(5):1035-1058.

Entyvio(2024) package insert Takeda Pharmaceuticals U.S.A., Inc., Lexington, MA. 2024

Feagan BG, et al(2013) GEMINI 1 Study Group Vedolizumab as induction and maintenance therapy for ulcerative colitis. New England Journal of Medicine. 2013;369:699.

Garnock-Jones KP.(2015) Vedolizumab: a review of its use in adult patients with moderately to severely active ulcerative colitis or Crohn's disease. BioDrugs. 2015 Feb;29(1):57-67. PMID: 25502899

Hazlewood GS, Rezaie A, Borman M., et al.(2015) Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: a network meta-analysis. Gastroenterology. 2015 Feb;148(2):344-54.

Kobayashi T, Ito H, Ashida T, Yokoyama T, Nagahori M, Inaba T, Shikamura M, Yamaguchi T, Hori T, Pinton P, Watanabe M, Hibi T.(2021) Efficacy and safety of a new vedolizumab subcutaneous formulation in Japanese patients with moderately to severely active ulcerative colitis. Intest Res. 2021 Oct;19(4):448-460. doi: 10.5217/ir.2020.00026. Epub 2020 Aug 18. PMID: 32806876; PMCID: PMC8566830.

Loftus, EV.(2015) Vedolizumab better for UC than Crohn’s disease in trials. Mayo Clinic Website at http://www.mayoclinic.org/medical-professionals/clinical-updates/digestive-diseases/vedolizumab-better-for-uc-than-crohns-disease-in-trials.

Mosli MH, MacDonald JK, Bickston SJ, et al.(2015) Vedolizumab for Induction and Maintenance of Remission in Ulcerative Colitis: A Cochrane Systematic Review and Meta-analysis. . Inflamm Bowel Dis. 2015 Apr 3. [Epub ahead of print].

Sandborn WJ, et al.(2013) GEMINI 2 Study Group: Vedolizumab as induction and maintenance therapy for Crohn's disease. New England Journal of Medicine. 2013;369:711.

Takeda Pharmaceuticals America Inc.(2014) Entyvio (vedolizumab) for injection, for intravenous use. Prescribing Information. Deerfield, IL: Takeda Pharmaceuticals America; 2014.

U.S. Food and Drug Administration (FDA).(2014) FDA approves Entyvio to treat ulcerative colitis and Crohn's disease. FDA News. Silver Spring, MD: FDA; May 20. 2014.

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.