Entyvio access guide: IV vs SC vedolizumab coverage, IBD step therapy, reauthorization, and support routing

Entyvio (vedolizumab, Takeda) is an integrin receptor antagonist that blocks alpha-4-beta-7 binding to MAdCAM-1 in gut-associated lymphoid tissue. First approved by the FDA in May 2014 as an intravenous infusion for moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD), Entyvio gained a subcutaneous formulation in September 2023 for UC maintenance and in April 2024 for CD maintenance. The SC option has triggered a major benefit-channel shift: payers including Blue Cross Blue Shield of Michigan moved Entyvio SC from medical benefit to pharmacy benefit starting January 2026, creating new PA workflows and specialty-pharmacy routing requirements.

This guide is for access teams, gastroenterology coordinators, and hub personnel navigating vedolizumab coverage in a market where the IV-to-SC transition is reshaping benefit adjudication, step-therapy logic, and reauthorization documentation.

Short answer

Indication-by-indication PA requirements

Ulcerative colitis

Payers uniformly require moderately to severely active UC confirmed by a gastroenterologist. The typical step-therapy ladder before Entyvio requires:

1. Conventional therapy failure: trial and failure, intolerance, or contraindication to at least one conventional agent (corticosteroids, azathioprine, 6-mercaptopurine, or methotrexate). Some plans accept disease severity that warrants a biologic as first-line without conventional trial.
2. Anti-TNF positioning: Blue Shield of California requires trial and failure of infliximab (or a biosimilar such as Avsola, Inflectra, or Renflexis) before Entyvio for UC. Other payers such as UHC and Cigna do not universally require anti-TNF failure first but may list preferred anti-TNFs as step-therapy agents.

Crohn's disease

Step-therapy requirements for CD are typically more stringent:

1. Conventional therapy failure: trial and failure of corticosteroids, immunomodulators (azathioprine, 6-MP, methotrexate), or aminosalicylates.
2. Biologic step edits: many plans require failure of at least one anti-TNF (adalimumab or infliximab, including biosimilars) before Entyvio for CD. Mass General Brigham Health Plan requires trial and failure, contraindication, or intolerance to two of the following: Humira (or adalimumab biosimilars Hadlima, Simlandi, Yuflyma), Omvoh, Rinvoq, Skyrizi, Stelara (or biosimilars Selarsdi, Steqeyma, Yesintek), Tremfya, Xeljanz, or Simponi — unless the patient is continuing from at least two IV induction doses of Entyvio.

IV vs SC benefit routing

The 2026 coverage landscape is defined by a benefit-channel split between IV and SC formulations:

Medical benefit (IV)

Entyvio IV 300 mg is billed under medical benefit using HCPCS code J3590 (unclassified biologics) or via a plan-specific billing code. Site-of-care policies apply: many plans require infusion at a designated specialty infusion center rather than a hospital outpatient department. Buy-and-bill practices submit the drug cost plus administration fees.

Pharmacy benefit (SC)

Entyvio SC 108 mg is dispensed through specialty pharmacies under the pharmacy benefit. Key developments in 2026:

• Blue Cross Blue Shield of Michigan transitioned all commercial members from Entyvia IV (medical benefit) to Entyvio SC (pharmacy benefit) effective January 1, 2026. Members with active IV authorizations could continue through December 31, 2025. Proactive SC authorizations were issued for pharmacy benefit coverage through December 31, 2026.
• BCBSM requires Walgreens Specialty Pharmacy as the sole dispensing pharmacy for Entyvio SC on its commercial plans.
• Members without pharmacy coverage through their BCBSM plan must obtain new prescriptions and PA through their separate pharmacy benefit provider.

Maryland Physicians Care (SC formulation)

Maryland Physicians Care designates the SC formulation as non-preferred. Prescribers must supply clinical documentation supporting medical necessity of SC over IV. The PA criteria state: "Coverage for subcutaneous formulations are not preferred. Prescriber must supply clinical documentation to support why the subcutaneous formulation is medically necessary over the preferred IV formulation."

Reauthorization criteria

Across UHC, Cigna, BCBS, and Medicaid plans, reauthorization follows a consistent pattern:

1. Documentation of positive clinical response evidenced by at least one of:
   • Improvement in intestinal inflammation (mucosal healing on endoscopy)
   • Improvement in laboratory values (decreased CRP, ESR, or platelet counts)
   • Reversal of high fecal output state
   • Chart-documented clinical improvement by the prescriber
2. No concurrent targeted immunomodulators: Entyvio must not be combined with anti-TNF agents, IL inhibitors, JAK inhibitors, or other targeted immunomodulators. UHC explicitly lists prohibited combinations including adalimumab, Cimzia, Enbrel, Omvoh, Rinvoq, Simponi, Skyrizi, Stelara, and Xeljanz.
3. 12-month reauthorization cycle: most plans approve continuation for 12 months at a time.

Arkansas Blue Cross and Blue Shield

Effective February 26, 2026, initial and continuation approval is for the duration of the treatment course or 12 months, whichever comes first. The SC injection is not covered under the medical benefit and must be adjudicated through the pharmacy benefit.

Step-therapy hierarchy in IBD

Entyvio sits within a competitive IBD biologic landscape. The typical payer step-therapy sequence for ulcerative colitis in 2026:

For Crohn's disease, the hierarchy is similar but fewer agents are FDA-approved at each level. Entyvio's gut-selective mechanism (no systemic immunosuppression signal) is a differentiator that access teams can cite when justifying Entyvio over anti-TNFs in patients with infection risk.

Express Scripts and PBM positioning

On the Express Scripts 2026 National Preferred Formulary, Entyvio IV is a preferred alternative in the Infused Non-TNF Biologics class. It is listed alongside Omvoh, Skyrizi, and Tremfya as a preferred option for patients who might otherwise use excluded ustekinumab products (Stelara IV, Otulfi IV, Pyzchiva IV, Steqeyma IV, Starjemza IV, Wezlana IV). The preferred ustekinumab alternatives are IMULDOSA IV, SELARSDI IV, USTEKINUMAB-TTWE IV (by Quallent), and YESINTEK IV. The SC formulation routes through pharmacy benefit PA criteria separately.

EntyvioConnect support program

Takeda's EntyvioConnect program provides the following services:

Co-pay assistance

• Commercially insured patients may pay as little as $0 per dose through the Co-Pay Program
• Maximum annual benefit of $20,000 per year regardless of whether the patient receives IV or SC
• If the patient's plan uses a copay maximizer or similar program, the maximum annual benefit is reduced to $9,000 per calendar year
• Not available for Medicare, Medicaid, TRICARE, or other government-funded programs

Bridge program

For patients whose commercial insurance denies coverage, EntyvioConnect provides free medication during the appeals process. This requires an active prescription and submission of an appeal within the program's specified timeframe.

Patient Assistance Program

Uninsured patients or those whose benefits are insufficient to cover Entyvio may receive treatment at no cost through Takeda's Help At Hand program. Eligibility is income-based.

Injection training for Entyvio Pen

EntyvioConnect provides a training kit for patients prescribed the SC formulation, including a practice pen, training guide, alcohol wipes, and a portable cooler. Virtual or in-home injection education is available.

Start Program (bridge during appeals)

For patients whose prior authorization was denied, the EntyvioConnect Start Program offers Entyvio IV or SC at no cost for up to 3 years while the appeals process is pending. Eligibility requirements apply.

Bridge Program (coverage gap)

For patients with a temporary gap in commercial coverage (job loss, insurance transition), the Bridge Program offers Entyvio at no cost for up to 6 months for either IV infusions or SC injections.

Billing and coding

Per Takeda's Entyvio Coding Guide (available at EntyvioHCP.com/Access-Support), the most common NDC codes are:

• Entyvio IV: 64764-300-20 (300 mg single-dose vial)
• Entyvio Pen SC: 64764-108-21 (108 mg single-dose prefilled pen)
• HCPCS: J3590 (unclassified biologics) for medical benefit billing

Incorrect billing codes are one of the most common reasons for PA denial, per Takeda's PA checklist.

Contact

• Phone: 1-844-ENTYVIO (1-844-368-9846), Monday to Friday 8 AM to 8 PM ET
• HCP Access Support: EntyvioHCP.com/Access-Support (includes PA checklist, letter of medical necessity template, and coding guide)

Documentation checklist for PA submission

Access teams should prepare the following before submitting a vedolizumab prior authorization:

1. Diagnosis confirmation: ICD-10 code (K51.x for UC, K50.x for CD), gastroenterologist attestation of moderate-to-severe disease
2. Disease severity documentation: endoscopy findings, CRP/ESR, fecal calprotectin, CDAI score (CD) or Mayo score (UC)
3. Prior treatment history: drug name, dose, start/stop dates, and reason for discontinuation for each prior conventional agent and biologic
4. TB screening: negative TB test (skin test or IGRA) within 12 months prior to initiation
5. Infection screening: documentation of no active infection
6. SC medical necessity letter (if requesting SC): explain why SC formulation is medically necessary when the payer designates IV as preferred — cite patient inability to attend infusion visits, needle phobia, travel distance, or occupational constraints
7. IV induction confirmation (for SC maintenance): dates of at least two IV infusions at weeks 0 and 2 before transitioning to SC

ICER and CMS negotiation context

In March 2026, the Institute for Clinical and Economic Review (ICER) published a special assessment of Entyvio to inform CMS drug price negotiations under the Inflation Reduction Act. The report evaluated vedolizumab against therapeutic alternatives including infliximab, adalimumab, and ustekinumab, finding that Entyvio showed some advantages over infliximab for ulcerative colitis remission but not over ustekinumab. Access teams should monitor the negotiated price outcome, as it may shift Medicare Part D formulary positioning and create downstream commercial plan changes.

Key takeaways for access teams

• IV-to-SC transitions require benefit-channel switching: confirm whether the SC formulation routes through pharmacy or medical benefit on the patient's specific plan before prescribing.
• SC is non-preferred on some formularies: prepare a medical-necessity letter documenting why SC is required over IV for patients who cannot comply with infusion schedules.
• Step therapy typically demands anti-TNF failure first for CD; for UC, the ladder varies by plan. Check plan-specific PA criteria.
• Reauthorization needs objective evidence: mucosal healing, improved inflammatory markers, or chart-documented clinical improvement at each 12-month cycle.
• EntyvioConnect provides robust support: co-pay assistance ($0 per dose, $20,000 annual maximum), bridge programs during appeals, and injection training for the SC pen.

Sources

• Takeda Pharmaceuticals. FDA Approves Subcutaneous Administration of ENTYVIO for Maintenance Therapy in Crohn's Disease. Press release, April 19, 2024. takeda.com/newsroom/newsreleases/2024/fda-approves-subcutaneous-administration-of-entyvio
• FDA. Entyvio (vedolizumab) Prescribing Information. BLA 125476. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125476s060s061lbl.pdf
• FDA. BLA 761359 Multi-disciplinary Review. Entyvio SC for Crohn's Disease. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/761359Orig1s000MultidisciplineR.pdf
• Maryland Physicians Care. Entyvio (Vedolizumab) Prior Authorization Policy RX.PA.008.MPC. Revised 02/2026. marylandphysicianscare.com
• Mass General Brigham Health Plan. Entyvio SC (vedolizumab) Prior Authorization Policy. Effective 01/01/2026. resources.massgeneralbrighamhealthplan.org
• Cigna. Inflammatory Conditions – Entyvio Subcutaneous Prior Authorization Policy. Coverage Policy Number IP0675. Effective 03/15/2026. static.cigna.com
• UnitedHealthcare. Entyvio (vedolizumab) for Subcutaneous Use – Prior Authorization/Medical Necessity. uhcprovider.com
• Blue Shield of California. Vedolizumab (Entyvio) Medi-Cal Medical Benefit Drug Policy. Effective 12/01/2025. blueshieldca.com
• Blue Cross Blue Shield of Michigan. Provider Alert: Changes to Entyvio Management for Commercial Members. Effective January 1, 2026. providerinfo.bcbsm.com
• EntyvioConnect. Co-Pay Program and Patient Support. entyvio.com/copay-support; entyviohcp.com/patient-support
• Express Scripts. 2026 National Preferred Formulary Exclusions. express-scripts.com/pdf/formulary/NPF_Preferred_Formulary_Exclusions2026.pdf
• ICER. Special Assessment to Inform CMS Drug Price Negotiations: Entyvio. March 2026. icer.org
• Moda Health / Prime Therapeutics. Vedolizumab Medical Necessity Criteria. Document IC-0733. modahealth.com