Pharmacotherapy of Inflammatory Bowel Disorder (Coverage Criteria)
Defines medical necessity, site-of-service review, and prior authorization/step therapy expectations for pharmacologic treatment of inflammatory bowel diseases (Crohn's disease and ulcerative colitis) for Premera members and providers.
Policy Summary
PayerPremera Bluecross
PolicyPharmacotherapy of Inflammatory Bowel Disorder (Coverage Criteria)
Added coverage criteria for Rinvoq (upadacitinib) for the treatment of ulcerative colitis in individuals with an inadequate response or intolerance to one or more TNF blockers.
Added coverage for Rinvoq (upadacitinib) for the treatment of adult individuals with moderately to severely active Crohn's disease.
Updated Zeposia criteria to require prior trial and treatment failure with Amjevita (adalimumab-atto) and Humira (adalimumab) AND a trial and failure with Stelara (ustekinumab).
Updated preferred and non-preferred status for multiple adalimumab and infliximab biosimilars and reorganized preferred infliximab lineup effective 01/01/2024.
Removed references to 'first-line' and 'second-line' treatment within coverage criteria for all drugs.
Updated Zeposia criteria to require trial and treatment failure with specified adalimumab products and Stelara (ustekinumab).
Multiple adalimumab biosimilar products were added and reclassified between preferred and non-preferred status with identical coverage criteria to Amjevita.
Added coverage criteria for Velsipity (etrasimod) for ulcerative colitis and for Tyruko (natalizumab-sztn) for Crohn's disease.
Site-of-service medical necessity criteria removed for Stelara IV and Skyrizi IV; other site-of-service additions/clarifications made and some exceptions added (e.g., CRS).
Age requirements were added for many listed agents for Crohn's disease and ulcerative colitis criteria.
Re-authorization duration of approval changed from 3 years to 12 months for listed drugs.
New policy sections define different coverage criteria for multiple formulary plan types (Metallic, Essentials, Open/Preferred/Select, and plans with no pharmacy benefit).
Added coverage criteria for Rinvoq (upadacitinib) for the treatment of adult individuals with moderately to severely active Crohn's disease.
Added coverage criteria for Tremfya (guselkumab) IV/SC for the treatment of ulcerative colitis and later Crohn's disease.
Re-authorization duration updated from 3 years to 12 months.
Added site-of-service reviews for multiple agents including Skyrizi IV and Zymfentra (infliximab-dyyb) and added numerous HCPCS codes.
Added multiple new biosimilar and unbranded ustekinumab products and updated preferred/non-preferred adalimumab products and prerequisites.
Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.
~20+distinct biologic/targeted agents listed
12 monthsauthorization length
90 daysprovider notification period
Addedpolicy updates (recent)
20+document chunks in extract
Coverage Criteria — Medical Necessity and Agent-specific Rules
Medical Necessity Criteria — Examples for Crohn's Disease
Covered when ALL of the following are met for specified agents (examples from Crohn's disease criteria):
Age requirement varies by agent (examples: 6 years or older for some TNF agents; 18 years or older for many biologics)agent-dependent
See specific agent entries
Prior therapies or conditions: At least one of: trial of a corticosteroid (eg, methylprednisolone, prednisone, prednisolone, dexamethasone, or budesonide) or currently taking a corticosteroid; trial of another Crohn's agent (eg, azathioprine, 6-mercaptopurine, methotrexate, mesalamine [Pentasa]); presence of enterocutaneous or rectovaginal fistulas; prior ileocolonic resectionN/A
Agent-specific application
Prescriber: Medication is being prescribed by or in consultation with a gastroenterologistN/A
Consistently required across many agent criteria
Induction prerequisite for SC formulations: For some SC formulations, prior IV induction or a single IV induction dose is required before SC maintenance (examples: single IV induction for some ustekinumab products; 3‑dose IV induction at Weeks 0, 4, 8 for certain IL‑23 agents)single IV induction or specified IV series
Applies to specified product lines
Initial and induction coverage criteria
Covered when the following groups of conditions are met (examples by agent/group):
General eligibility for agent: Individual meets specified age requirement AND has tried one corticosteroid (examples: methylprednisolone, prednisone, prednisolone, dexamethasone, budesonide) or is currently taking a corticosteroid OR has tried one other agent for Crohn's disease (eg, azathioprine, 6‑mercaptopurine, methotrexate, mesalamine [Pentasa]) OR has enterocutaneous or rectovaginal fistulas OR has had ileocolonic resection; AND medication is prescribed by or in consultation with a gastroenterologist.age-based
Applies across many listed agents
Agents requiring IV induction: Agent has documented IV induction completed as specified (examples: single IV induction dose for some ustekinumab products; or IV infusions at Weeks 0, 4, 8 for mirikizumab, risankizumab, guselkumab, etc.) before SC maintenance or continuation.induction documented
Specific agents enumerate induction schedules
Entyvio (vedolizumab) SC — second-line criteria
Entyvio (vedolizumab) SC specific criteria:
Entyvio SC coverage: Individual is aged 18 years or older AND meets general prior therapy criteria (trial of corticosteroid or other agent, or qualifying surgical/fistula history) AND Entyvio SC is prescribed by or in consultation with a gastroenterologist AND Has had a trial and treatment failure with TWO of the following preferred/step agents: preferred adalimumab product(s), Cimzia, Omvoh SC, Rinvoq, preferred ustekinumab product(s), Skyrizi SC, Tremfya SC, Zymfentra (infliximab-dyyb); AND Has received induction therapy with Entyvio IV or is undergoing Entyvio IV induction when required.
Placement of JAK inhibitor and TNF inhibitors
Rinvoq (upadacitinib) and TNF antagonist placement:
Rinvoq coverage: Individual aged 18 years or older AND meets general prior therapy criteria AND has had trial and treatment failure with one or more TNF blockers AND Rinvoq is prescribed by or in consultation with a gastroenterologist.
TNF‑alpha antagonists coverage: Adalimumab products and biosimilars are considered medically necessary for individuals (agent-dependent minimum ages, commonly >=6 years) when general prior therapy criteria are met (corticosteroid or other agent trial, qualifying disease features) and prescriber specialty requirement is satisfied; some plans/tiering list specific prerequisite trials before other classes.
Ustekinumab family coverage logic
IL-12/23 (ustekinumab) family — first-line and second-line distinctions:
First-line ustekinumab options: Stelara (ustekinumab) IV/SC, Steqeyma IV/SC, Yesintek IV/SC may be considered medically necessary for moderately to severely active Crohn's disease when age and prior therapy criteria are met; some SC products require prior single IV induction dose.
Second-line ustekinumab products: Other ustekinumab branded/biosimilar products (Imuldosa, Otulfi, Pyzchiva, Selarsdi, Starjemza, Wezlana, etc.) may be considered medically necessary when age/prior therapy criteria met AND the individual had inadequate response or intolerance to specified first-line ustekinumab IV/SC products; IV formulations may be limited to one-time induction and SC formulations may require prior IV induction.
Ustekinumab products for Crohn's disease (SC after IV induction)
Covered when ALL of the following are met:
Age and prescribing: Individual is aged 18 years or older AND medication is prescribed by or in consultation with a gastroenterologist.
Prior therapy or disease features: Has tried one corticosteroid OR has tried one other immunomodulatory agent (eg, azathioprine, 6‑mercaptopurine, methotrexate, mesalamine [Pentasa]) OR has enterocutaneous or rectovaginal fistulas OR has had ileocolonic resection.
Failure/intolerance to prior biologics: Has had inadequate response or intolerance to ALL listed ustekinumab IV products when required (Stelara IV, Steqeyma IV, Yesintek IV) or other specified agents per policy; SC use may require documented single IV induction dose prior to maintenance.
Some products limited to IV induction only
Agents requiring IV induction before SC maintenance (Ulcerative Colitis examples)
Covered when ALL of the following are met:
Age and prescribing: Individual is aged 18 years or older AND medication is prescribed by or in consultation with a gastroenterologist.
Induction-only/induction then maintenance: Medication is used only for a one-time IV induction dose OR IV therapy used for induction at Week 0, Week 4, and Week 8 (examples: Omvoh, Skyrizi, Tremfya) where SC maintenance is permitted only after documented IV induction.documented IV induction
SC maintenance permitted only after induction where specified
JAK inhibitors, S1P modulators, and second-line sequencing for Ulcerative Colitis
Covered when ALL of the following are met:
Age and prior therapy: Individual is 18 years or older AND has had a trial and treatment failure with one or more TNF blockers for eligibility for JAK inhibitors (eg, Rinvoq, Xeljanz) and S1P modulators per policy; AND medication is prescribed by or in consultation with a gastroenterologist.age >=18
Applies to adult UC criteria
Second-line trial requirement: For certain second-line agents (eg, Entyvio SC, Zeposia), patient must have had trial and treatment failure with TWO agents from a specified list (includes preferred adalimumab products, Omvoh SC, Rinvoq, Simponi SC, Skyrizi SC, preferred ustekinumab products, Tremfya SC, Velsipity, Xeljanz).2
Varies by agent and formulary tier
Zeposia (ozanimod) for ulcerative colitis
Covered when ALL of the following are met
Zeposia UC criteria: Individual is aged 18 years or older AND has had trial and treatment failure with TWO specified agents from the policy list (eg, designated preferred adalimumab products, Omvoh SC, Rinvoq, Simponi, Skyrizi, preferred ustekinumab products, Tremfya, Velsipity, Xeljanz, Zymfentra) AND Zeposia is prescribed by or in consultation with a gastroenterologist AND dose is < 0.92 mg per day.age >=18; dose < 0.92 mg/day; failure of 2 agents
Check member plan for custom-formulary exceptions
Adalimumab products for ulcerative colitis
Covered when ALL of the following are met
Adalimumab-class UC criteria: Individual is aged 5 years or older AND has had trial and treatment failure with ALL the following listed comparators (eg, Cyltezo or equivalent adalimumab biosimilars per criterion) as specified by plan AND medication is prescribed by or in consultation with a gastroenterologist.age >=5
Applies to multiple branded/biosimilar adalimumab products and plan-specific sequencing
Infliximab biosimilars (Avsola, Renflexis) for ulcerative colitis
Covered when ALL of the following are met
Avsola/Renflexis UC criteria: Individual is aged 6 years or older AND has had inadequate response or intolerance to Inflectra, Janssen infliximab, or Remicade AND medication is prescribed by or in consultation with a gastroenterologist; site-of-service administration review may apply.age >=6
Site-of-service review applies
Ustekinumab-class agents for ulcerative colitis (IV induction or single IV dose/SC maintenance)
Covered when ALL of the following are met
IV ustekinumab criteria: Individual is aged 18 years or older AND has had inadequate response or intolerance to ALL specified IV ustekinumab agents (eg, Steqeyma IV, Yesintek IV, Stelara IV) when required AND medication is prescribed by or in consultation with a gastroenterologist AND IV form is used only as a one-time induction dose.age >=18
Induction-only IV formulations
SC ustekinumab maintenance criteria: Individual is aged 18 years or older AND has received a single IV induction dose AND medication is prescribed by or in consultation with a gastroenterologist.age >=18; prior single IV induction
SC formulations permitted only after induction where specified
Crohn's disease agents by plan section (Section 2 Essentials plans examples)
Covered when ALL of the following are met (per agent-specific rules)
TNF‑alpha (Essentials) criteria: For certain adalimumab products: individual is aged 6 years or older AND has tried one corticosteroid or is currently taking a corticosteroid OR has tried one other agent for Crohn's disease OR has enterocutaneous/rectovaginal fistulas OR has had ileocolonic resection; AND medication is prescribed by or in consultation with a gastroenterologist.age >=6
Applies to Section 2 Essentials formulary plans
Infliximab‑family (Essentials) criteria: Inflectra, Janssen infliximab, Remicade: individual is aged 6 years or older AND meets prior therapy/disease feature criteria AND medication is prescribed by or in consultation with a gastroenterologist; site-of-service review applies.age >=6
Site-of-service review applies
Entyvio (vedolizumab) criteria:
Medical necessity criteria by agent/class (selected examples from excerpt)
Coverage considered medically necessary when the specified AND/OR criteria for age, prior therapies, induction dosing, and prescriber/consultation are met.
General recurring criteria: Agents generally require: individual meets age requirement (commonly >=18 yrs; some agents >=6 yrs), trial of a corticosteroid or current corticosteroid use OR trial of one other conventional agent for Crohn's disease (eg, azathioprine, 6‑mercaptopurine, methotrexate, mesalamine [Pentasa]) OR presence of enterocutaneous/rectovaginal fistulas OR prior ileocolonic resection; and gastroenterologist prescriber/consult documented.
Applies across multiple agent entries
IV induction before SC maintenance: Omvoh, Skyrizi, Tremfya, Entyvio, certain ustekinumab products and others specify SC maintenance or on-body injector use only after IV induction therapy (eg, Week 0, 4, 8 regimen) or a single IV induction dose as noted.documented IV induction
Explicit IV induction requirement repeated for several agents
TNF‑alpha first‑line general: Patient is aged 5 years or older AND medication is prescribed by or in consultation with a gastroenterologist (applies to listed adalimumab biosimilars on Essentials plans).age >=5 years
Zymfentra SC criteria: Patient is aged 18 years or older AND has received an intravenous infliximab induction regimen (eg, Remicade, Avsola, Inflectra, or Renflexis) before SC Zymfentra; medication is prescribed by or in consultation with a gastroenterologist.age >=18; prior IV induction
Subject to site-of-service review
Ustekinumab (Steqeyma/Yesintek/Stelara and biosimilars) induction and SC maintenance
Covered when ALL of the following are met
IV induction use: Steqeyma/Yesintek IV may be considered medically necessary when patient is aged 18+ AND used only as a one-time induction dose.age >=18
IV induction only
SC maintenance after IV: Steqeyma/Yesintek SC may be considered medically necessary when patient is aged 18+ AND has received a single IV induction dose AND is prescribed by or in consultation with a gastroenterologist.age >=18; prior single IV induction
SC only after IV induction
IL-23 inhibitors (Omvoh, Skyrizi, Tremfya) induction then SC
Covered when ALL of the following are met
Omvoh IV induction: Omvoh IV may be considered medically necessary for adults aged 18+ when prescribed by or in consultation with a gastroenterologist AND used only for induction at Week 0, Week 4, and Week 8 (3 IV infusions); Omvoh SC covered only after IV induction.age >=18; IV at Weeks 0/4/8
Omvoh SC requires prior IV induction
Skyrizi IV induction (Weeks 0, 4, 8) for adults 18+ when prescribed by/with a gastroenterologist; SC on‑body injector allowed only after IV induction.age >=18; 3 IV infusions
Induction then SC maintenance
Tremfya IV induction: Tremfya IV may be considered medically necessary for adults 18+ when used only for induction (Weeks 0, 4, 8); SC permitted thereafter per criteria.age >=18; induction at Weeks 0/4/8
Janus kinase inhibitors and S1P modulators (Rinvoq, Xeljanz, Velsipity)
Covered when ALL of the following are met
JAK inhibitors: Patient is aged 18+ AND has had trial and treatment failure with one or more TNF blockers AND medication is prescribed by or in consultation with a gastroenterologist (applies to Rinvoq, Xeljanz, Xeljanz XR).age >=18; prior TNF failure
JAK placement per policy
S1P modulators: Patient is aged 18+ AND medication is prescribed by or in consultation with a gastroenterologist; dose limits apply where specified (eg, Velsipity <=2 mg/day).age >=18; dose limits where specified
Velsipity dosing constraint
Entyvio (vedolizumab) SC/IV second-line
Covered when ALL of the following are met
Entyvio IV/SC criteria: Patient is aged 18+ AND has had trial and treatment failure with TWO specified agents from the policy list (preferred adalimumab products or other listed biologics) AND has received or is undergoing Entyvio IV induction when indicated AND Entyvio is prescribed by or in consultation with a gastroenterologist.age >=18; failure of 2 agents; Entyvio IV induction when required
Applies to Essentials plan examples
Zeposia (ozanimod) second-line
Covered when ALL of the following are met
Zeposia criteria: Patient is aged 18+ AND has had trial and treatment failure with TWO specified agents from policy lists AND Zeposia is prescribed by or in consultation with a gastroenterologist AND dose is < 0.92 mg per day.age >=18; >=2 prior failures; dose <0.92 mg/day
Applies to Essentials plan examples; check formulary exceptions
Second-line adalimumab group: Patient is aged 5 years or older AND has had trial and treatment failure with ALL specified listed adalimumab comparators per criterion AND medication is prescribed by or in consultation with a gastroenterologist.age >=5; failure of listed agents
Applies to Essentials plans; check for custom-formulary exceptions
Avsola and Renflexis (infliximab biosimilars) criteria
Covered when ALL of the following are met
Avsola/Renflexis criteria: Patient is aged 6 years or older AND has had inadequate response or intolerance to Inflectra, Janssen infliximab, or Remicade AND medication is prescribed by or in consultation with a gastroenterologist; site-of-service review may apply.age >=6; prior inadequate response to listed infliximab products
Subject to site-of-service review
Ulcerative Colitis — Essentials Formulary (Section 2) medical necessity
May be considered medically necessary when ALL of the following are met (formulary Section 2: Rx Plan E1, E3, E4):
UC Essentials criteria: 1) Individual meets age requirement as specified by agent (eg, >=6 yrs for certain infliximab products; >=18 yrs for many biologics); 2) Has had inadequate response or intolerance to specified prior agents where listed; 3) Medication is prescribed by or in consultation with a gastroenterologist; 4) For some ustekinumab/Steqeyma/Yesintek pathways, prior inadequate response to Steqeyma and Yesintek may be required before other ustekinumab products are used.age and prior-therapy conditions per agent
Site-of-service review may apply to some infliximab products
May be considered medically necessary when ALL of the following are met (Section 3: Rx Plan M1, M2, M4):
Crohn's first‑line TNF‑alpha criteria: 1) Individual meets specified age (commonly >=6 yrs for certain TNF agents or >=18 yrs for others); 2) Has tried one corticosteroid or is currently taking a corticosteroid OR has tried one other conventional agent OR has qualifying disease features (fistulas, ileocolonic resection); 3) Medication is prescribed by or in consultation with a gastroenterologist; 4) Specific sequencing by drug class applies per formulary (eg, TNF‑alpha first‑line, IL‑12/23 and IL‑23 placements, integrin inhibitors, oral agents later).age and prior-therapy conditions as above
Some agents subject to site‑of‑service review or induction-only IV rules
Induction-only and induction-to-maintenance criteria (examples)
Specific products require defined induction regimens before maintenance/SC use:
Omvoh induction/maintenance: Omvoh IV is used only for induction (Weeks 0, 4, 8; total 3 infusions); Omvoh SC is considered medically necessary only after completing the IV induction series and meeting other prior‑therapy/disease criteria.IV induction at Weeks 0/4/8
Omvoh SC requires prior IV induction
Steqeyma/Yesintek SC induction note: Steqeyma (ustekinumab-stba) SC and Yesintek (ustekinumab-kfce) SC are considered medically necessary only when the individual has received a single IV induction dose and meets prior‑therapy conditions.single IV induction dose for SC use
Single‑dose IV induction required prior to SC maintenance for certain ustekinumab products
Agent-specific medical necessity (examples)
Covered when ALL of the following are met (examples for specific agents):
Adult age requirement: Patient is aged 18 years or older (some agents allow age >=6 years depending on product).age >=18 or >=6 as specified
Age varies by agent
Prior corticosteroid or other agent trial: Has tried one corticosteroid (eg, methylprednisolone, prednisone, prednisolone, dexamethasone, budesonide) OR is currently taking a corticosteroid OR has tried one other Crohn's agent (eg, azathioprine, 6‑MP, methotrexate, mesalamine [Pentasa]).1 agent or steroid
Many criteria allow alternative qualifying conditions such as fistulas or prior ileocolonic resection
Qualifying disease features: Has enterocutaneous or rectovaginal fistulas OR has had ileocolonic resection to reduce recurrence (may substitute for medication trials in some cases).
Entyvio (vedolizumab) SC criteria
Entyvio (vedolizumab) SC specific coverage:
Age and prior trials: Patient is 18 years or older AND has tried one corticosteroid or one other agent OR qualifying surgical/fistula history; AND Entyvio SC is prescribed by or in consultation with a gastroenterologist.age >=18
Entyvio SC requires trial and treatment failure with TWO preferred adalimumab products unless Entyvio IV induction has been given
Failure requirement: Has had trial and treatment failure with TWO of the following preferred adalimumab products or alternatives (eg, Cyltezo, Simlandi, Hyrimoz, etc.) as specified in the policy.failure with 2 adalimumab products
Also may require prior Entyvio IV induction or current induction
Ustekinumab class criteria
Ustekinumab (IL-12/23) induction and maintenance rules:
Induction dose rule: Some ustekinumab products are limited to a one‑time IV induction dose; subsequent SC formulations require prior IV induction or documentation that a single IV induction has been given.single IV induction documented
Multiple branded and biosimilar preparations referenced
Prior therapy failure for certain formulations: For some SC formulations, patient must have had inadequate response or intolerance to ALL the following (eg, Steqeyma, Yesintek) before other ustekinumab formulations are considered.failure to listed agents
Used to define second‑line use for some biosimilars/brands
Rinvoq (upadacitinib) criteria
Rinvoq (upadacitinib) criteria (example of JAK inhibitor placement):
Age and prior trials: Patient is 18 years or older AND has tried one corticosteroid or one other conventional agent OR qualifying fistula/surgical history; AND Rinvoq is prescribed by or in consultation with a gastroenterologist.age >=18
Additionally requires trial and treatment failure with one or more TNF blockers per Crohn's criteria
TNF blocker failure: Has had a trial and treatment failure with one or more TNF blockers (documented).failure with >=1 TNF blocker
Specifically cited for Rinvoq placement in Crohn's disease
Adalimumab biosimilars - first-line
Covered when ALL of the following are met
Adalimumab biosimilars criteria: Individual is aged 5 years or older AND medication is prescribed by or in consultation with a gastroenterologist; listed adalimumab biosimilars (Cyltezo, Simlandi, Hyrimoz, etc.) may be considered medically necessary per product‑specific criteria.age >=5
First‑line adalimumab biosimilars examples
Infliximab biosimilars - site-of-service and induction requirement
Covered when ALL of the following are met
Zymfentra and infliximab induction/site-of-service: Zymfentra (infliximab‑dyyb) SC: individual aged 18 years or older who has received an IV infliximab induction regimen (eg, Remicade, Avsola, Inflectra, Renflexis) AND medication is prescribed by or in consultation with a gastroenterologist; subject to site‑of‑service review. Inflectra/Remicade/Janssen infliximab IV: individual aged 6 years or older and prescriber specialty requirement applies.age >=18 for Zymfentra; >=6 for IV infliximab
Site‑of‑service review applies to listed infliximab products
IL-12/23 and IL-23 inhibitors - induction-only IV then SC
Covered when ALL of the following are met
IL‑12/23 and IL‑23 IV induction rules: Omvoh, Skyrizi, Tremfya IV formulations are used only for induction (Weeks 0, 4, 8); SC maintenance or on‑body injector use is allowed only after documented IV induction; prescriber must be or consult a gastroenterologist.IV induction at Weeks 0/4/8
Induction‑only IV then SC maintenance
JAK inhibitors (Rinvoq, Xeljanz) - prior TNF failure
Covered when ALL of the following are met
JAK inhibitor criteria (prior TNF failure): Individual is aged 18 years or older AND has had trial and treatment failure with one or more TNF blockers AND medication is prescribed by or in consultation with a gastroenterologist (applies to Rinvoq, Xeljanz).age >=18; prior TNF failure
Prior TNF failure required for JAK agents in Crohn's/UC contexts
S1P receptor modulators and Entyvio SC - step and failure requirements
Covered when ALL of the following are met
Velsipity criteria: Individual is aged 18 years or older; Velsipity (etrasimod) prescribed by or in consultation with a gastroenterologist; dose <= 2 mg/day where specified.age >=18; dose <=2 mg/day
S1P modulators dosing constraint
Entyvio SC prior‑failure requirement: Entyvio SC may be considered medically necessary when the adult has trial and treatment failure with TWO agents from the specified list (includes preferred adalimumab product, Omvoh SC, Rinvoq, Simponi SC, Skyrizi SC, preferred ustekinumab SC, Tremfya SC, Velsipity, Xeljanz).failure with >=2 agents
Prescriber must be or consult a gastroenterologist
Second‑line IL‑12/23 IV agents: Individual is aged 18 years or older; has had inadequate response or intolerance to ALL the following agents (eg, Steqeyma IV, Yesintek IV) as specified; medication is prescribed by or in consultation with a gastroenterologist; IV form used only as a one‑time induction dose.age >=18; failure/intolerance to ALL specified agents
Exhaustive failure requirement for second‑line IL‑12/23 IV agents
Second‑line IL‑12/23 SC agents: Individual is aged 18 years or older; has received a single IV induction dose; medication prescribed by or in consultation with a gastroenterologist; SC formulations covered after IV induction.age >=18; prior single IV induction
SC maintenance after induction
Zeposia (ozanimod) - prior failures and dose limit
Covered when ALL of the following are met
Zeposia criteria: Individual is aged 18 years or older; has had trial and treatment failure with TWO agents from the specified list (includes preferred adalimumab product, Omvoh SC, Rinvoq, Simponi, Skyrizi SC, preferred ustekinumab SC, Tremfya SC, Velsipity, Xeljanz, Zymfentra) AND medication is prescribed by or in consultation with a gastroenterologist; dose is < 0.92 mg/day.age >=18; >=2 prior failures; dose <0.92 mg/day
Criteria excludes certain custom formularies per policy 5.01.647
TNF-α inhibitors - second-line and required prior biosimilar trial
Covered when ALL of the following are met
TNF‑alpha required biosimilar trial: Individual is aged 5 years or older; has had trial and treatment failure with ALL specified adalimumab biosimilar comparators per policy; medication is prescribed by or in consultation with a gastroenterologist.age >=5; failure with specified biosimilars
Required prior biosimilar trials before some second‑line TNF listings
Ustekinumab (Stelara) — Induction and Maintenance
Evidence from randomized controlled trials supports ustekinumab for induction and maintenance in moderately to severely active Crohn's disease in adults meeting study populations' characteristics.
Ustekinumab Induction/Eligibility: Adults with moderately to severely active Crohn's disease (CDAI 220–450) who match trial populations (including prior TNF exposure status) may be eligible for ustekinumab induction; induction efficacy demonstrated vs placebo with clinical response at Week 6 and remission by Week 8 in trials.CDAI 220-450
Study CD‑1 included TNF‑failed subjects; CD‑2 included primarily TNF‑naive subjects.
Ustekinumab Maintenance: Individuals achieving clinical response at Week 8 may continue maintenance with 90 mg SC every 8 weeks as per Study CD‑3, which showed higher corticosteroid‑free remission rates vs placebo at Week 44/47.Clinical response at Week 8 (>=100 point CDAI reduction)
Maintenance benefit observed in multiple subgroups including prior TNF failures.
Biologic agents — evidence summaries
Clinical trial evidence summaries for infliximab, adalimumab, certolizumab, natalizumab, vedolizumab, golimumab, and others that inform coverage for moderate to severe Crohn's disease and ulcerative colitis.
Infliximab (Remicade): Randomized trials in moderate‑to‑severe UC and CD demonstrated reduced symptoms, improved quality of life, mucosal healing, and reduced recurrence; biosimilars (Inflectra, Avsola, etc.) share indications with noted pediatric exceptions.study‑specific dosing
Remicade evidence summarized in policy
Adalimumab (Humira): RCTs show induction and maintenance efficacy in Crohn's disease and UC with dosing‑dependent responses; nonresponders at 12 weeks were unlikely to later respond in trials.trial dosing regimens
CLASSIC/Gain/CHARM studies summarized
Vedolizumab (Entyvio): GEMINI trials showed vedolizumab induction and maintenance efficacy in CD and UC with improved remission and steroid‑free remission in maintenance responders; induction efficacy variable in heavily pretreated populations.
Updated coverage criteria and step therapy requirements
Coverage updates and criteria (summarized from updates and drug-specific trial populations).
Rinvoq (upadacitinib) updates: Coverage criteria were added for Rinvoq for UC in individuals with inadequate response or intolerance to one or more TNF blockers and later added for Crohn's disease per policy updates.
Added in 2022–2023 updates
Zeposia prior therapy update: Zeposia criteria were updated to require prior trial and treatment failure with specified adalimumab products (eg, Amjevita and Humira NDC groupings) and with Stelara (ustekinumab) before Zeposia coverage in some updates.trial and failure of listed agents
Updated 2023
Biosimilar step/try‑fail: Step therapy updated to require trial and failure of preferred adalimumab and infliximab biosimilars before coverage of non‑preferred agents; preferred‑nonpreferred statuses were revised effective Jan 1, 2024 and later updates.try preferred products first
Summary of updated coverage and step therapy criteria
Policy contains distinct criteria sets that were updated by drug and by formulary plan type; examples of criteria-level changes follow.
Rinvoq for Crohn's disease: Coverage criteria were added for adult individuals with moderately to severely active Crohn's disease (age requirements introduced in later updates).adults
Added in 2023 with subsequent age clarifications
Zeposia step therapy: Requires prior trial and treatment failure with specified adalimumab products (including Amjevita and Humira NDC blocks) and Stelara (ustekinumab) before use in some plan types; dosing limit applied (<0.92 mg/day).trial and failure of listed agents; dose <0.92 mg/day
Updated 2023–2025
Adalimumab biosimilar hierarchy: Multiple adalimumab biosimilars were added and reclassified between preferred and non‑preferred; coverage criteria align to Amjevita with updated NDC group references and try‑fail sequencing.
General agent-specific coverage
Coverage is provided when agent-specific medical necessity criteria are met, including trials of required prerequisite agents, age requirements where specified, and adherence to site-of-service rules.
General coverage requirements: Member meets agent‑specific indication (Crohn's disease or UC), meets age requirements where specified, has documented trial and inadequate response or intolerance to required prerequisite medications (preferred agents/biosimilars) and requests conform to site‑of‑service rules when applicable.
Re‑authorization generally 12 months unless otherwise specified
The policy’s site‑of‑service medical necessity provisions do not apply to fully‑insured members in Alaska pursuant to Alaska HB 226. For Alaska fully‑insured members, site‑of‑service exceptions described elsewhere in the policy (for example, cytokine release syndrome) are not constrained by the site‑of‑service rules in this document; providers should follow the member’s plan booklet or ID card and applicable state requirements when determining whether site‑of‑service review is required.
Certain custom Open and Preferred formulary members are excluded from the coverage criteria in this policy. Specifically, members assigned to the identified custom Open formulary (Formulary ID: 6062; Rx Plan F1) and the identified custom Preferred formulary (Formulary ID: 6064; Rx Plan G3) follow separate medical necessity rules. Providers must verify the member’s formulary and apply the alternative criteria described in the referenced custom‑formulary policy.
Members on the custom formularies referenced above should be evaluated using policy 5.01.647 — Medical Necessity Criteria for Custom Open and Preferred Formularies. That policy contains the alternative coverage and step‑therapy rules that apply to Formulary ID 6062 (Rx Plan F1) and Formulary ID 6064 (Rx Plan G3).
The policy explicitly notes that some medical necessity criteria do not apply for the two custom formularies (Formulary ID: 6062; Rx Plan F1 and Formulary ID: 6064; Rx Plan G3). When a member belongs to one of these plans, the custom formulary exclusions and alternative requirements take precedence and should be followed instead of the criteria in this document.
The custom‑formulary exception is referenced repeatedly across formulary sections (Section 1, Section 2, Section 3 examples). For any request, providers must check member plan details to determine whether the standard policy criteria or the custom‑formulary criteria in policy 5.01.647 apply.
The policy refers to two specific custom formularies (Open formulary ID 6062; Rx Plan F1 and Preferred formulary ID 6064; Rx Plan G3) that are excluded from the standard criteria. These two formularies are handled under the separate custom formulary policy; do not apply the standard step‑therapy or site‑of‑service rules to those members.
The custom formulary exceptions are reiterated in multiple places and affect which prerequisite trials and step‑therapy sequencing apply. For members in the listed custom Open/Preferred formularies, follow the alternative coverage pathways in policy 5.01.647 rather than the standard plan section rules shown in this policy.
The policy identifies the relevant custom formulary identifiers (Formulary ID: 6062; Rx Plan F1 and Formulary ID: 6064; Rx Plan G3) wherever those exceptions affect drug‑specific criteria (for example, Entyvio, Zeposia, Zymfentra). Verify these formulary IDs on the member’s benefit information to determine applicability.
Uses of the listed agents outside the indications, dosage/administration, or combinations described in this policy are considered investigational and may be denied. This includes use in combinations not outlined here or for indications not included in the policy; providers should reference the specific drug entries and supporting related policies when requesting coverage for off‑label uses.
Reiterating the investigational position: any proposed use that falls outside FDA‑labeled dosing/administration or outside the conditions set forth in this policy (including agent combinations not listed) is treated as investigational and may result in denial. Providers should supply supporting clinical evidence if requesting coverage for such uses.
The policy history notes a prior revision to the section on toxicities of TNF inhibitors, clarifying that the toxicities section was revised to exclude non‑IBD disease states in a 2018 update. This reflects a historical narrowing of that subsection to IBD‑specific contexts.
Per the 2025 update, site‑of‑service medical necessity criteria do not apply to Alaska fully‑insured members under Alaska HB 226. The history and update notes document this statewide exception; providers caring for Alaska fully‑insured members must follow state requirements and the member’s plan documents rather than the site‑of‑service rules in this policy.
This medical policy does not apply to Medicare Advantage members. Coverage determinations for Medicare Advantage should be made according to the member’s Medicare Advantage benefit documents and applicable Medicare rules.
The policy includes a site‑of‑service review for selected IV/infusion agents. When site‑of‑service review applies, failure to meet the policy’s site‑of‑service criteria (for example, lack of documented access issues, absence of clinical justification for hospital outpatient vs office setting, or not meeting listed CRS criteria) may result in services being considered not medically necessary. Providers should document the clinical reason for the requested site and include supporting notes.
Some agents require documented prior IV induction before coverage of follow‑on subcutaneous maintenance dosing; use of SC formulations without the required induction may be considered not medically necessary. Examples include agents with a one‑time IV induction (ustekinumab variants) or IV induction series at Weeks 0, 4, and 8 (Omvoh, Skyrizi, Tremfya). Prior IV induction must be clearly documented for SC maintenance approvals.
For several IL‑12/23 agents and related products, the policy distinguishes IV induction‑only formulations. If a product’s approval in the policy requires a one‑time IV induction dose or an induction series, use of that agent outside the induction context (for example, continuing IV beyond the one‑time induction dose or using SC maintenance without prior IV induction where required) may not meet medical necessity.
Certain IL‑12/23 IV agents are designated for induction only; the policy requires those IV administrations to be used as the induction dose(s) and not as ongoing maintenance. Requests for continued IV administration beyond the defined induction regimen are not supported by the policy unless the product’s specific criteria allow it.
Zeposia (ozanimod) coverage requires meeting step‑therapy prerequisites and the policy sets a dose constraint: dosing must be 0.92 mg per day. Requests for dosing at or above 0.92 mg/day do not meet the policy dosing criterion and may be considered not medically necessary.
Where required prior trials, documented treatment failures, or gastroenterologist prescribing/consultation are not provided, the policy indicates a high risk of denial. Providers should include clear documentation of prior medication trials, dates, dosages, and clinical response to avoid denials for insufficient documentation.
Age requirements are agent‑specific. Many TNF agents allow pediatric use (examples: some adalimumab/infliximab products ≥ 6 years or ≥ 5 years for certain adalimumab entries), whereas most IL‑12/23, IL‑23, JAK, and S1P agents require adults (≥ 18 years). Always confirm the minimum age specified for the requested product in the policy.
Some SC formulations are permitted only after a qualifying induction course; for certain products the SC use is effectively limited to one‑time induction or to maintenance only after documented IV induction. If the SC item is indicated by the policy as limited to an induction‑only or post‑induction use, requests outside those constraints may be considered not medically necessary.
The policy does not support continuing IV administrations beyond the defined induction schedules for agents where IV is specified solely for induction (for example, Omvoh, Skyrizi, Tremfya IV inductions given at Week 0, Week 4, and Week 8). IV beyond induction is not consistent with the stated coverage logic.
The policy treats any uses of the listed drugs that are not consistent with the specified coverage criteria (including step‑therapy sequencing, induction requirements, age limits, and prescriber requirements) as not medically necessary. Providers should align requests with the policy criteria or provide compelling clinical justification and supporting evidence for exceptions.
Step therapy and tiering are enforced: where the policy requires trials and failures of preferred agents or biosimilars before escalation to non‑preferred products, failure to document those prerequisite trials may render a request not medically necessary. The policy’s NMN rules apply across plan sections unless a custom‑formulary exception is documented.
The excerpted text does not introduce additional explicit new items classified as not medically necessary in the recent updates shown here. Historical reviews referenced found no new studies requiring NMN changes in some prior updates.
Policy changes to product preference and step therapy imply that certain non‑preferred agents will be denied without prior trials of preferred products. Providers must follow the updated step‑therapy sequencing and preferred‑before‑nonpreferred rules (including required trials of specified adalimumab and infliximab biosimilars) when initiating therapy.
Coding — HCPCS, NDC, and Product Groupings
Named Biologic and Related Productsmixed
Avsola
infliximab-axxq IV
Entyvio
vedolizumab IV
Inflectra
infliximab-dyyb IV
Infliximab (Janssen unbranded)
infliximab IV
Remicade
infliximab IV
Renflexis
infliximab-abda IV
Tyruko
natalizumab-sztn IV
Tysabri
natalizumab IV
Zymfentra
infliximab-dyyb SC
Stelara/ustekinumab
IV and SC formulations listed
1–10 of 14
1/2
Products listed (no explicit billing codes in this segment)mixed
NDC/HCPCS not listed
The document lists product names but did not include explicit CPT/HCPCS/NDC codes in these chunks.
Drug products listed (no billing codes)mixed
No CPT/HCPCS listed in this chunk set
Document lists branded biologic and biosimilar product names; no procedure or billing codes provided in these chunks.
Drugs listed (brand/generic names)mixed
NDC/HCPCS not specified in these chunks
Document lists brand and biosimilar drug names; no explicit numeric codes provided in these chunks.
Named products (no numeric codes provided in this excerpt)mixed
N/A
Document lists product names and routes but does not provide specific CPT/HCPCS/ICD-10/NDC codes in this segment.
Drugs listed (by product name/biosimilar)mixed
NDC/HCPCS not listed
No explicit procedure or billing codes present in this excerpt; drugs are identified by brand and biosimilar names.
Infliximab productsNDC|mixed
infliximab-axxq
Avsola (infliximab-axxq) IV
infliximab-abda
Renflexis (infliximab-abda) IV
infliximab-dyyb
Inflectra (infliximab-dyyb) IV / Zymfentra (infliximab-dyyb) SC
infliximab
Infliximab (Janssen unbranded) IV / Remicade (infliximab) IV
Ustekinumab and biosimilars / IL-12/23 agentsNDC|mixed
Injection; ustekinumab-auub (Wezlana), biosimilar; IV, mg
Q5140
Injection; adalimumab-fkjp, biosimilar; mg (new code effective 01/01/25)
1–10 of 13
1/2
Referenced NDC groupings for adalimumab productsNDC
NDCs starting with 55513
Amjevita (adalimumab-atto) NDC group referenced for prior trial requirements
NDCs starting with 72511
Humira/adalimumab NDC group referenced for biosimilar preference groupings
Referenced NDC identifier groupsNDC
NDCs starting with 55513
Amjevita (adalimumab-atto) reference NDC block
NDCs starting with 72511
Humira (adalimumab) reference NDC block
NDCs starting with 83457
Humira (Cordavis) NDC block
NDCs starting with 00074
Humira (AbbVie) NDC block
NDCs starting with 61314
Hyrimoz (adalimumab-adaz) NDC block
Policy HCPCS/Codes mentionedHCPCS
J3590
Unclassified biologic (used in policy to report Avsola, Simlandi, etc.)
J2327
Skyrizi (risankizumab-rzaa)
J1628
Tremfya (guselkumab)
Q5131
HCPCS code added July 1, 2023 (policy reference)
Q5134
HCPCS code for Tyruko
J1748
HCPCS code added for Zymfentra
inv-95: Age — minimum ages by product group
Age groups referencedSome TNF agents: >= 6 years; Many biologics (IL-12/23, IL-23, JAK, S1P, integrin inhibitors): >= 18 years
Essentials (Section 2) examplesEntyvio, Omvoh, Skyrizi, Tremfya and many IL-23/IL-12/23 agents: age >= 18 years
Provider Actions — Prior Authorization, Documentation, and Step Therapy
Prior Authorization
Site-of-Service and Medical Necessity Review Required
Site-of-Service (SOS) medical necessity review applies to medical-benefit administered IV/infusion drugs and selected injectable agents. SOS review evaluates whether administration in a hospital-based outpatient setting, infusion center, physician office, or home is clinically appropriate for the individual and the drug being given. SOS criteria apply to all ages, and for members age 13 and older the site-of-service is reviewed for medical necessity. SOS medical necessity criteria applies ONLY to medical benefit reviews and does NOT apply to Alaska fully‑insured members (see Alaska HB 226).
SOS review applies to IV/injectable drugs administered under the medical benefit (not pharmacy).
Alaska fully‑insured members are exempt from SOS criteria; contact Customer Service for details.
Denial Risk
Site-of-Service administration is subject to review for selected agents
Certain agents and administration settings are specifically subject to SOS review. Examples include many infliximab products, vedolizumab (Entyvio) IV/SC, natalizumab (Tyruko, Tysabri), some ustekinumab and risankizumab IV formulations, and other agents identified in the policy. Failure to meet SOS criteria may impact medical necessity determinations and lead to denial of coverage for the administration site.
Background and Definitions
Requests submitted without documentation of required prerequisite trials, induction completion, or prescriber specialty (gastroenterologist or documented consult) may be denied. The policy specifically lists these missing items as common denial risks and requires complete prior‑therapy documentation to support medical necessity determinations.
inv-162: Inflammatory bowel disorder — definition
Clinical featuresInflammation may cause ulcers, abdominal pain, cramping, diarrhea, bleeding, fatigue, and weight loss
ScopeThis policy addresses pharmacologic treatment and pre-approval requirements for these disorders
inv-163: Site of service — definition
DefinitionSite of service = location where the drug is administered (hospital outpatient, infusion center, physician office, or home)
Review applicabilitySite-of-service medical necessity criteria applies to medical benefit reviews and, historically, to age 13+ site-of-service review cohort
Revision History and Policy Changes
2023-07-01addition
Added coverage criteria for Rinvoq (upadacitinib) for treatment of adult individuals with moderately to severely active Crohn's disease.
2024-11-01addition
Added coverage criteria for Tremfya (guselkumab) IV/SC for treatment of ulcerative colitis (later expanded to include certain Crohn's disease individuals).
2024-01-03formulary_update
Policy Summary
PayerPremera Bluecross
PolicyPharmacotherapy of Inflammatory Bowel Disorder (Coverage Criteria)
For certain agents (eg, some JAK inhibitors, vedolizumab SC), documentation of trial and treatment failure with specified agents is required (eg, trial and failure of one or more TNF blockers or failure of listed ustekinumab products).
prior biologic failure documented
Varies by product and formulary tier
Individual is aged 18 years or older AND has tried one corticosteroid or is currently taking one OR has tried one other agent OR has qualifying disease features; AND prescribed by or in consultation with a gastroenterologist.
age >=18
Site-of-service review may apply
IL‑12/23 and IL‑23 agents (Essentials): For agents like Steqeyma, Yesintek, Omvoh, Skyrizi, Tremfya: individual is aged 18 years or older AND has tried one corticosteroid or is currently taking one OR has tried one other agent OR has qualifying disease features; additional induction-only or prior IV induction rules apply for some products (eg, IV induction then SC maintenance).age >=18
Many agents limited to induction dosing or require IV induction before SC maintenance
For some TNF agents, coverage requires trials and treatment failures with specific adalimumab biosimilars/products or infliximab products per formulary step therapy; other agents require failure of all listed comparators before approval.
documented failures per product list
Examples include specified adalimumab or infliximab prerequisites
Entyvio SC special requirement: Entyvio SC coverage requires adult age >=18, prior corticosteroid or conventional agent trial or qualifying surgical/fistula history AND trial and treatment failure with TWO preferred adalimumab products or specified alternatives AND receipt or ongoing induction with Entyvio IV when indicated, and gastroenterologist prescriber/consult.failure with 2 agents; Entyvio IV induction when required
Detailed multi-step requirement
Ustekinumab sequencing: Certain ustekinumab IV products may be medically necessary for adults >=18 after trials of corticosteroids/conventional agents or qualifying disease features; SC formulations may be used after single IV induction dose and may require prior inadequate response/intolerance to specified ustekinumab agents per policy.age >=18; single IV induction for SC where specified
Can substitute for prior medication trials in some cases
Specialty/prescriber requirement: Medication is being prescribed by or in consultation with a gastroenterologist.prescriber = gastroenterologist or consult documented
Repeated across many agent‑specific criteria
Induction requirement for IV agents: For specified agents (eg, Omvoh, Skyrizi, Tremfya), IV is used only for induction administered at Week 0, 4, and 8 (total 3 infusions); SC maintenance allowed only after documented IV induction.IV at Weeks 0,4,8
Applies to several IL‑23/IL‑12/23 agents
induction response required for maintenance
Antibody formation associated with lower drug concentrations and reduced remission
Effective dates noted in history
try preferred adalimumab products first
Effective date changes Jan 1, 2024 and later
Infliximab sequencing: Preferred infliximab products were updated (eg, Avsola moved to preferred list effective 01/01/2024 with subsequent reclassifications); some criteria require trial and failure with Inflectra, Janssen infliximab, or Remicade before Avsola/Renflexis.trial and failure of listed infliximab agents
Sequencing updated across 2023–2025
Site-of-service criteria: Site‑of‑service medical necessity criteria were added, removed, or modified for specific IV agents (eg, site‑of‑service removed for Stelara IV; added for Skyrizi IV and selected infliximab products); exceptions added for cytokine release syndrome and Alaska fully‑insured members per state law.agent‑specific
Alaska fully‑insured members exempt per Alaska HB 226
Age requirements were added or updated for many agents (adalimumab products, infliximab products, Entyvio IV/SC, Stelara, Skyrizi, Rinvoq, Cimzia, Tyruko/Tysabri, Simponi, Omvoh, Tremfya) in 2024–2025 updates.agent‑specific age limits
See agent entries for exact ages
Re‑authorization duration updated from 3 years to 12 months for approvals under this policy.12 months
Operational change effective in 2025 update
Formulary‑specific criteria: Different coverage criteria were established for Metallic, Essentials, Open/Preferred/Select formulary plans and plans with no pharmacy benefit for numerous drugs listed in the policy.plan‑type specific
See plan section entries
ISHIP METALLIC (Section 3) examplesCertain TNF‑α antagonists (adalimumab biosimilars) and infliximab products: may be considered for ages >= 6 years per plan-specific criteria
inv-96: Zeposia (ozanimod) dose limit
Zeposia maximum daily doseDose must be less than 0.92 mg per day
Plan exceptions noteCustom Open/Preferred formularies (Formulary ID 6062, 6064) may have differing criteria — check member plan
Associated prior-failure requirementZeposia criteria additionally require prior trials/failures with specified agents in some plan sections
inv-97: Zeposia daily dose
Daily dosing constraintZeposia (ozanimod) daily dose must be < 0.92 mg/day
Clinical contextDose requirement appears in multiple formulary sections (Section 1/2/3) for ulcerative colitis criteria
Formulary exceptionCustom formulary plans (IDs 6062, 6064) are exempt from this specific criterion — see policy 5.01.647
inv-98: Minimum age for some agents
Pediatric allowancesSome infliximab and adalimumab products may be used in individuals aged 6 years or older
Adult-only agentsMany IL-12/23, IL-23, JAK, S1P and integrin inhibitors list age >= 18 years
Plan-specific variationsAge minima are specified per agent and per formulary section — verify plan details
inv-99: Velsipity dose
Velsipity (etrasimod) dosingDose is 2 mg or less per day
Prescriber requirementVelsipity must be prescribed by or in consultation with a gastroenterologist
Indication contextListed as an S1P modulator for ulcerative colitis in adult individuals
inv-100: Zeposia dose constraint
Zeposia dosing constraintZeposia (ozanimod) must be prescribed at a dose < 0.92 mg per day to meet medical necessity criteria
Applies across sectionsDose requirement appears in multiple formulary sections (Essentials, ISHIP) for UC criteria
Custom-formulary exceptionNot applicable to specified custom formularies (Formulary ID 6062, 6064); check policy 5.01.647
inv-101: CDAI (clinical threshold used in trials)
CDAI entry range for trialsInduction trial populations used CDAI score 220–450 for enrollment
Clinical response definitionClinical response defined as >=100‑point reduction in CDAI or CDAI <150
Maintenance eligibilityParticipants achieving clinical response at induction could enter maintenance (Study CD‑3)
inv-102: Clinical trial timing
Trial examplesUstekinumab induction studies evaluated response at Week 6 and remission at Week 8; vedolizumab and others report maintenance at Week 52
inv-103: Provider notification period
Provider notification period for changes90-day provider notification prior to certain policy changes (effective dates referenced)
Operational noteSeveral coding and site‑of‑service changes referenced as effective following a 90‑day notification period
Check history entriesPolicy history documents effective/change dates and related provider notice timelines
SOS review may be applied to individual drugs listed in the policy (see drug-specific criteria).
Use of listed agents for indications or settings not supported by the policy (or FDA labeling) may be considered investigational or not medically necessary.
Site-of-service review may affect medical necessity determinations and can lead to claim denials if criteria are not met.
Note
Certain criteria do not apply to custom formulary plans
Certain SOS criteria and step-therapy requirements do not apply to members enrolled in specific custom formularies. The policy includes an explicit exception: one Open formulary (Formulary ID: 6062; Rx Plan F1) and one Preferred formulary (Formulary ID: 6064; Rx Plan G3) have separate criteria; refer to policy 5.01.647 for custom Open and Preferred formulary members.
Check the member plan booklet or member ID card to determine whether custom formulary criteria apply.
Custom-formulary members follow criteria specified in policy 5.01.647 rather than the standard criteria in this policy.
Denial Risk
Site-of-service and prior therapy risks
Providers should be aware of denial risks related to both SOS and step‑therapy/prior‑therapy requirements. Common denial triggers include missing documentation of required prior trials, lack of prescriber specialty or consultation (when required), failure to demonstrate induction dosing when IV induction is mandated, and failure to meet SOS access exceptions.
Denial triggers for missing step-therapy trials: absence of documented trial and treatment failure with required preferred agents (e.g., preferred adalimumab products before non-preferred agents like Zeposia).
Denial triggers for site-of-service review: missing documentation supporting medical necessity for a higher-cost site (e.g., no local infusion center within 50 miles, inability of home infusion vendor to travel, or lack of documented access barriers).
Site-of-service review may affect medical necessity and therefore claim payment.
Failure to document induction (IV) when an IV induction regimen is required may result in denial.
Billing Rule
Claims for drugs administered via IV must be processed through the medical benefit
Claims for drugs administered via an intravenous route must be billed and processed under the medical benefit (not the pharmacy benefit). When drugs are IV‑administered, providers must use appropriate HCPCS/CPT/medical billing codes as listed in the policy coding section.
Examples of HCPCS used for IV biologics are listed in the policy coding table (e.g., J1745, J1748, J3380, J3357, J2327, J2267, C9399, J3590).
Unlisted biologics or certain brand products may require reporting with C9399 or J3590 per the coding guidance.
Documentation Required
Medication must be prescribed by or in consultation with the required specialty
Medication must be prescribed by or in consultation with the required specialty when specified in the drug-specific criteria (commonly a gastroenterologist for Crohn's disease and ulcerative colitis agents). Where the policy requires a specialist prescriber or consultation, documentation must appear in the medical record or prior-authorization submission.
Common requirement: Prescribed by or in consultation with a gastroenterologist for IBD agents (e.g., infliximab products, ustekinumab, vedolizumab, mirikizumab, risankizumab).
When consultation is used, include consult notes or ordering provider documentation in the request.
Documentation Required
Prescriber and prior-therapy documentation required
Prescriber specialty and prior‑therapy documentation are required for prior authorization and medical‑necessity determinations. The submission should include prescriber specialty, dates and durations of prior medication trials, reasons for discontinuation (lack of efficacy or intolerance), evidence of corticosteroid use or taper (when relevant), and documentation of induction dosing if applicable.
Required clinical documentation examples: prescriber specialty or consult note; chart notes documenting prior trials with dates, doses, and clinical response or intolerance; endoscopy or imaging reports if relevant to diagnosis/severity.
Prior-therapy documentation required may include trials of corticosteroids, immunomodulators (azathioprine, 6‑MP, methotrexate), preferred biologics, or specific preferred biosimilars depending on formulary and step-therapy rules.
Documentation Required
Prescriber specialty and chart documentation requirements for continuation/re-authorization
Prescriber specialty and prior‑therapy documentation must support age eligibility, indication, prior failures/intolerances, and induction/maintenance therapy use. Chart notes are required to demonstrate continued clinical response for re‑authorization requests (e.g., symptom improvement, steroid tapering, objective markers when available).
For re-authorization, include chart notes showing ongoing benefit and clinical response.
Chart documentation must show adherence to the drug-specific induction schedule when an IV induction is required (for example, Omvoh or Skyrizi IV induction at Weeks 0, 4, and 8).
Step Therapy
Step therapy tiers define sequencing by drug class
Step‑therapy tiers define preferred sequencing by drug class and may require trials of preferred biologics or biosimilars before use of non‑preferred agents. The policy contains formulary‑specific tiering and IV→SC sequencing rules: many IV agents are required for induction and an SC formulation (when available) is used only after IV induction per plan rules.
Step therapy tiers and sequencing differ by formulary section (Section 1: Open/Preferred/Select; Section 2: Essentials; Section 3: ISHIP Metallic).
IV-to-SC sequencing: Several IL‑12/23 and IL‑23 agents require IV induction followed by SC maintenance; SC use is often permitted only after documented IV induction.
Formulary-specific step therapy tiers list first-line and subsequent options (e.g., TNF‑α inhibitors, IL‑12/23 inhibitors, IL‑23 inhibitors, integrin inhibitors, JAK inhibitors, S1P modulators).
Preferred-before-nonpreferred biologic step therapy: prior authorization may require trials of specified preferred biosimilars or preferred biologic products (for example, preferred adalimumab biosimilars/products must be tried and failed before non‑preferred adalimumab products or oral alternatives in some plan sections). Check the policy's updates for current preferred/non‑preferred designations and effective dates.
2023–2025 updates changed preferred adalimumab biosimilar designations and moved some infliximab products between preferred/non‑preferred tiers; refer to the policy history and 2024/2025 updates for effective dates.
Operational note: prior‑auth reviews will require documentation of trials with the currently preferred biosimilars (e.g., Cyltezo, Simlandi, specified Humira biosimilars) before approving non‑preferred adalimumab agents or other step options.
State exceptionSite-of-service criteria does NOT apply to Alaska fully‑insured members (see policy note)
inv-164: IV induction — definition
DefinitionIV induction = an initial induction regimen administered intravenously (examples include 3 IV infusions at Weeks 0, 4, and 8 for some agents)
Agent examplesOmvoh, Skyrizi, Tremfya and other IL‑23/IL‑12/23 agents specify Week 0/4/8 IV induction schedules
PurposeIV induction is required prior to some SC maintenance/on‑body injector formulations per policy
inv-165: Induction dose — definition
DefinitionInduction dose = a single IV induction dose required for some agents (e.g., certain ustekinumab products) prior to SC maintenance
Use caseSome ustekinumab IV products are described as one‑time induction doses; SC use follows documented single IV induction
DocumentationInduction dosing must be recorded to meet medical necessity for subsequent SC maintenance formulations
inv-166: Trial and treatment failure — definition
DefinitionTrial and treatment failure = documented inadequate response or intolerance to specified prior agents required before advancing to other classes
Common prerequisitesExamples include prior trials of corticosteroids, immunomodulators (azathioprine, 6‑MP, methotrexate) or prior biologics (TNF blockers)
Policy consequenceFailure to document required trials/failures may trigger denial of prior authorization
inv-167: IV induction dose — definition duplicate
Definition (duplicate)IV induction dose = a specified initial intravenous dosing regimen (e.g., single IV induction or Week 0/4/8 schedule) required before certain SC maintenance formulations
Agent examplesSteqeyma/Yesintek/ustekinumab IV single induction; Omvoh/Skyrizi/Tremfya Week 0/4/8 induction
Coverage implicationSC formulations often require prior IV induction documented to meet medical necessity
inv-168: Induction therapy — definition
DefinitionInduction therapy = initial dosing course of IV infusions (example Week 0, Week 4, Week 8) required for certain agents before SC maintenance
Typical scheduleMany IL‑23/IL‑12/23 agents use a three‑dose IV induction (Weeks 0/4/8)
Maintenance transitionSC maintenance allowed only after completion of specified IV induction where required
inv-169: Trial and treatment failure — definition duplicate
Definition (duplicate)Trial and treatment failure = insufficient response or intolerance to specified prior agents (corticosteroids, immunomodulators, prior biologics) as a criterion to advance therapy
Policy impactMany agent criteria require documented failure of specified comparators before approval
Denial riskLack of documented prior failures is identified as a common denial trigger
inv-170: induction therapy (product examples)
Examples of induction therapy productsOmvoh, Skyrizi, Tremfya listed as IV induction (Week 0,4,8) with SC maintenance only after induction
Ustekinumab pathwaySome ustekinumab products require a single IV induction dose prior to SC maintenance (Steqeyma/Yesintek examples)
DocumentationInduction completion must be documented in the chart to support SC maintenance requests
inv-171: trial and treatment failure — definition (another reference)
Definition (alternate reference)Trial and treatment failure = documented inadequate response or intolerance to specified prior agents; some agents require two prior failures
Entyvio exampleEntyvio SC often requires documented failure of TWO specified preferred agents before approval
Policy consequenceFailure to demonstrate required prior failures may result in denial
inv-172: Induction therapy (Omvoh example)
Omvoh induction exampleOmvoh IV induction defined as Week 0, Week 4, and Week 8 (three IV infusions); subsequent Omvoh SC requires prior IV induction
Coverage limitationOmvoh IV is indicated for induction only per policy language
Prescriber requirementPrescribed by or in consultation with a gastroenterologist
inv-173: Prior therapy requirement — definition
Prior therapy requirementCommon requirement that individual has tried a corticosteroid (or is currently taking one) OR another conventional agent (azathioprine, 6‑MP, methotrexate, mesalamine) before biologic approval
Alternative qualifying featuresEnterocutaneous or rectovaginal fistulas or prior ileocolonic resection may substitute in some criteria
Prescriber requirementMany criteria require prescription by or consultation with a gastroenterologist
inv-174: Induction therapy — definition duplicate
Definition (duplicate)Induction therapy = specified initial IV regimen (often Week 0,4,8) required before transitioning to maintenance SC formulations
Agent examplesMirikizumab, risankizumab, guselkumab induction schedules cited as Week 0,4,8
Coverage implicationSC formulations contingent on documented IV induction completion
DefinitionFirst-line/Second-line tiers = formulary-defined sequencing where certain drug classes are designated first-line and others second-line
ExamplesTNF‑α inhibitors often positioned first-line with IL‑12/23, IL‑23, JAK, S1P modulators placed in subsequent tiers depending on plan
Plan specificityTier placement varies by formulary section (Section 1, Section 2, Section 3) and affects prerequisite trial requirements
inv-176: Induction-only IV — definition
DefinitionInduction-only IV = IV administration used only for induction (examples: Omvoh, Skyrizi, Tremfya), typically Week 0, 4, 8 for a total of three infusions
SC follow-upSC maintenance/on‑body injector permitted only after documented IV induction where specified
Coverage noteUse of IV beyond induction for these agents is not supported per policy language
inv-177: Single IV induction then SC maintenance — definition
DefinitionSingle IV induction then SC maintenance = for certain ustekinumab products a one‑time IV induction dose is required before switching to SC maintenance dosing
Product examplesSteqeyma, Yesintek, Stelara IV may be used as single IV induction prior to SC formulations
Documentation requirementSingle IV induction must be documented to support SC maintenance approvals
Clinical remission (UC) definitionClinical remission often defined as total Mayo score <2 with no subscore >1 (or modified 3‑component Mayo definitions used in some trials)
Clinical response (UC)Typical trial response defined as >=30% and >=3‑point decrease in Mayo score plus rectal bleeding improvement or rectal bleeding subscore 0/1
Trial timingPrimary induction endpoints in UC trials commonly at Week 6–12; maintenance outcomes at Week 52
inv-180: Clinical remission (UC) duplicate
Clinical remission (UC) (duplicate)Often defined as total Mayo score <2 with no subscore >1; modified/3‑component Mayo score used in some trials
Use in policyThese trial definitions inform clinical response/remission thresholds referenced in agent evidence summaries
DocumentationClinical status and steroid tapering may be required when supporting maintenance authorization
Clinical response (UC)Defined variably; example: decrease from baseline in Mayo score by >=30% and >=3 points with rectal bleeding improvement or rectal bleeding subscore 0/1
Endpoint timingInduction endpoints usually evaluated at Weeks 6–12 in UC trials
RelevancePolicy uses these trial definitions to interpret clinical response for coverage considerations
Site-of-service review — definitionA section of the policy that evaluates medical necessity of IV administration location (facility vs office) for applicable agents; historically applied to individuals age 13+ with later modifications
Operational noteSite‑of‑service reviews and HCPCS additions/changes are documented in policy history and may be plan‑specific
State exceptionAlaska fully‑insured members are exempt from site‑of‑service criteria per Alaska HB 226
Site-of-service review — operational definitionA requirement that certain IV‑administered therapies undergo review to determine appropriate outpatient infusion setting or need for hospital administration, with specific exceptions
ExceptionsExceptions include documented access issues or cytokine release syndrome considerations; check plan specifics
DocumentationLack of site‑of‑service justification (eg, access within 50 miles) may result in denial
Effective Jan 3, 2025 planning noted: changed Avsola to second-line, reorganized preferred infliximab products and updated adalimumab biosimilar preferred/non-preferred classifications to align step therapy prerequisites (effective dates starting 01/01/2024 and later updates).
2025-01-03policy_change
Policy clarified site-of-service rules and added multiple agent-specific age requirements and formulary plan–specific sections (Metallic, Essentials, Open/Preferred/Select); non-formulary exception approvals standardized to 12 months.
Added numerous HCPCS/Q-codes (including Q5131, Q5134 and others) and added site-of-service reviews for multiple agents (Skyrizi IV, Zymfentra) with planned effective dates and provider notification periods noted.
2023-02-01addition
Added coverage criteria for Rinvoq (upadacitinib) for Crohn's disease and updated Zeposia criteria to require prior trial and treatment failure with specified adalimumab products and ustekinumab (Stelara).
2023-03-01formulary_update
Added multiple adalimumab biosimilars and reclassified several as preferred or non-preferred, updating prerequisite lists used in step therapy prior-to-nonpreferred requirements; moved Avsola into preferred infliximab list effective 01/01/2024.
2024-01-03addition
Added coverage criteria for Tyruko (natalizumab-sztn) and Entyvio (vedolizumab) SC and Omvoh (mirikizumab) for ulcerative colitis; updated step therapy requirements and added Tremfya as a brand step option for Entyvio SC and Zeposia.
2024-03-01reclassification
Changed Avsola to a second-line agent and updated coverage criteria for Avsola and Renflexis to require prior trial and failure with Inflectra, Janssen infliximab, or Remicade; implemented additional preferred/non-preferred adalimumab changes effective Jan 1, 2024.
2025-01-03site_of_service_revision
Removed certain site-of-service requirements (Stelara IV and Skyrizi IV) and added exemptions and clarifications including Alaska fully-insured member exception per Alaska HB 226; standardized non-formulary exception approvals to up to 12 months.
2025-07-01comprehensive_updateLatest
Expanded formulary-specific criteria (Metallic, Essentials, Open/Preferred/Select), added age requirements across many agents, updated re-authorization duration from 3 years to 12 months, and added numerous HCPCS/Q-codes with effective dates and provider notification periods.
2023-03-01coding_update
Added HCPCS code Q5131 (policy coding update) and added Amjevita to HCPCS J3590 for prerequisite lists used in step therapy.
2024-10-08coding_addition
Added HCPCS code J1628 for Tremfya and HCPCS code Q5134 for Tyruko as part of interim reviews and site-of-service additions.
Added numerous HCPCS and Q-codes (examples include Q5098/Q5099 group additions effective 07/01/25) and updated the Reviewed-for-Medical-Necessity HCPCS/J-code group used for prior authorization processing.
2023-03-01addition
Added coverage criteria for Rinvoq (upadacitinib) for Crohn's disease and positioned Rinvoq in the JAK inhibitor group requiring prior TNF failure where specified.
2024-01-03addition
Added Tremfya (guselkumab) coverage (IV/SC) for ulcerative colitis and later expanded to include certain Crohn's disease individuals; Tremfya designated as a brand step therapy option for Entyvio SC and Zeposia.
2025-07-01policy_updateLatest
Updated agent-specific coverage to add age requirements and to include new ustekinumab biosimilars and formulations (multiple Steqeyma/Yesintek/Imuldosa/etc.) with clarified induction-to-maintenance sequencing and prerequisite trial expectations.
Notes in the policy history and the not‑medically‑necessary summary emphasize that no new explicit NMN items were added in several document reviews; however, coverage and step‑therapy updates continue to change preferred/non‑preferred status and prerequisites, which indirectly affect NMN determinations when prerequisite trials are not met.