ModifiedUnitedHealthcarePolicy IEXD00116.05

Skyrizi (risankizumab-rzaa) coverage for Crohn's disease and ulcerative colitis

Defines medical necessity criteria, dosing expectations, and coding for intravenous risankizumab (Skyrizi) when used to treat moderately to severely active Crohn's disease or ulcerative colitis for UnitedHealthcare members.

Policy Summary

PayerUnitedHealthcare

PolicySkyrizi (risankizumab-rzaa) coverage for Crohn's disease and ulcerative colitis

Policy CodePolicy IEXD00116.05

Change TypeExamples of prior and concomitant targeted immunomodulators added/updated

Effective DateAug 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization for IV induction and document three planned induction doses per FDA labeling; include diagnosis severity and prior therapy history.

SourceLink

POLICY UPDATE CHANGES

Updated the examples of targeted immunomodulators with which the patient received previous treatment to add vedolizumab (Entyvio), mirikizumab (Omvoh), guselkumab (Tremfya), and others; replaced inconsistent brand/name spellings.

Updated list of examples of targeted immunomodulators the patient must not be receiving in combination with Skyrizi includes vedolizumab (Entyvio) and mirikizumab (Omvoh).

Added a Benefit Considerations section and updated References.

3induction IV doses authorized

J2327HCPCS code

Moderate–severedisease severity required

931

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618MOTIVATE enrollment

Coverage Criteria for IV Risankizumab (Skyrizi)

Initial Induction Therapy (Crohn's disease)

Covered when ALL of the following are met for Crohn's disease induction therapy:

CD Induction Coverage: Member has a diagnosis of moderately to severely active Crohn's disease

Prior therapy requirement: Either history of failure, intolerance, or contraindication to at least one conventional therapy at maximally indicated doses (examples: corticosteroids, 6-mercaptopurine, azathioprine, methotrexate) OR prior treatment with a targeted immunomodulator FDA‑approved for Crohn's disease (examples listed)

Targeted examples: adalimumab, certolizumab (Cimzia), vedolizumab (Entyvio), mirikizumab (Omvoh), upadacitinib (Rinvoq), guselkumab (Tremfya), ustekinumab.

Dosing and administration: Planned administration as three intravenous induction doses in accordance with FDA‑labeled dosing for Crohn's disease3 IV doses

Authorization will be issued for 3 induction doses.

Concomitant therapy restriction: Patient is not to receive Skyrizi in combination with another targeted immunomodulator

Examples include: adalimumab, certolizumab (Cimzia), vedolizumab (Entyvio), mirikizumab (Omvoh), upadacitinib (Rinvoq), guselkumab (Tremfya), ustekinumab.

Prescriber requirement: Prescribed by or in consultation with a gastroenterologist

Initial Induction Therapy (Ulcerative colitis)

Covered when ALL of the following are met for ulcerative colitis induction therapy:

UC Induction Coverage: Member has a diagnosis of moderately to severely active ulcerative colitis

Prior therapy requirement: Either prior or concurrent inadequate response or intolerance to a therapeutic course of oral corticosteroids and/or immunosuppressants (e.g., azathioprine, 6-mercaptopurine) OR prior treatment with a targeted immunomodulator FDA‑approved for ulcerative colitis (examples listed)

Targeted examples: adalimumab, vedolizumab (Entyvio), mirikizumab (Omvoh), upadacitinib (Rinvoq), golimumab (Simponi), guselkumab (Tremfya), tofacitinib (Xeljanz/Xeljanz XR), ustekinumab, ozanimod (Zeposia).

Prescriber requirement for UC: Prescribed by or in consultation with a gastroenterologist

Evidence-based coverage considerations

Clinical trial-based coverage considerations for moderately to severely active Crohn's disease and ulcerative colitis

Induction efficacy evidence: ADVANCE and MOTIVATE induction trials demonstrated significant improvement in CDAI clinical remission, stool frequency/abdominal pain remission, and endoscopic response at Week 12 with risankizumab versus placebo; coprimary endpoints were met (p ≤ 0.0001).

See ADVANCE/MOTIVATE trial results.

Maintenance efficacy evidence: FORTIFY (Crohn's disease) and COMMAND (ulcerative colitis) maintenance studies showed higher clinical remission and endoscopic response rates with subcutaneous risankizumab (180 or 360 mg every 8 weeks) versus withdrawal/placebo at Week 52, with acceptable tolerability.

See FORTIFY and COMMAND results.

Ulcerative colitis induction/maintenance: INSPIRE induction showed higher clinical remission (24% with risankizumab vs 8% placebo at Week 12) and COMMAND maintenance showed higher remission at Week 52 (45% vs 26% placebo).

See INSPIRE and COMMAND results.

Skyrizi must not be administered in combination with another targeted immunomodulator. Concurrent therapy with listed biologic or targeted agents is excluded from coverage. Examples of prohibited concomitant agents include adalimumab, certolizumab (Cimzia), vedolizumab (Entyvio), mirikizumab (Omvoh), upadacitinib (Rinvoq), guselkumab (Tremfya), and ustekinumab.

The policy's examples of targeted immunomodulators that members must not be receiving in combination with Skyrizi have been updated to explicitly add vedolizumab (Entyvio) and mirikizumab (Omvoh). These agents are now listed alongside other targeted therapies when assessing concurrent-use exclusions for Skyrizi.

Policy revisions clarify prior-treatment requirements and have operational implications for prior authorization and step-therapy logic. The updated prior/concomitant agent lists add agents such as vedolizumab (Entyvio), mirikizumab (Omvoh), upadacitinib (Rinvoq), and guselkumab (Tremfya), which will be used when determining whether documented prior targeted immunomodulator therapy meets the policy’s criteria. Additionally, prior authorization for IV induction will be issued for 3 induction doses in accordance with FDA-labeled dosing, and reviewers will verify that the member is not concurrently receiving any newly listed prohibited agents.

Coding

Applicable HCPCS CodesHCPCS

J2327

Injection, risankizumab-rzaa, intravenous, 1 mg

Applicable ICD-10 Diagnosis CodesICD-10

K50.00	Crohn's disease of small intestine without complications.
K50.011	Crohn's disease of small intestine with rectal bleeding.
K50.012	Crohn's disease of small intestine with intestinal obstruction.
K50.013	Crohn's disease of small intestine with fistula.
K50.014	Crohn's disease of small intestine with abscess.
K50.018	Crohn's disease of small intestine with other complication.
K50.019	Crohn's disease of small intestine with unspecified complications.
K50.10	Crohn's disease of large intestine without complications.
K50.111	Crohn's disease of large intestine with rectal bleeding.
K50.112	Crohn's disease of large intestine with intestinal obstruction.

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Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Skyrizi IV induction (three doses). Authorization will be issued for three induction doses. Prescriptions must be by or in consultation with a gastroenterologist.

HCPCS J2327 referenced in Applicable Codes

Documentation Required

Document Diagnosis Severity and History

Coverage requires documentation of diagnosis severity (moderately to severely active Crohn's disease or ulcerative colitis) and a clear prior therapy history. Document the member’s disease severity (for example: modified Mayo score, endoscopic severity, or other validated measures), current symptoms, and prior response to therapies.

Document objective disease severity (e.g., mMS, endoscopic score)
Document prior conventional therapies and doses, reasons for failure or intolerance

Background

Skyrizi (risankizumab-rzaa) is a humanized IgG1 monoclonal antibody that selectively binds the p19 subunit of interleukin-23 (IL-23), inhibiting downstream pro-inflammatory cytokine signaling. It is indicated for treatment of moderately to severely active Crohn's disease and ulcerative colitis when medical necessity criteria are met; phase 3 induction and maintenance trials demonstrated higher clinical remission and endoscopic response rates with risankizumab versus placebo.

Definitions and Clinical Endpoints

Skyrizi (risankizumab-rzaa) — Key drug definition

Generic namerisankizumab-rzaa

Brand nameSkyrizi

Drug classHumanized IgG1 monoclonal antibody targeting the IL-23 p19 subunit

Mechanism of actionBinds the p19 subunit of interleukin‑23 (IL‑23) and inhibits its interaction with the IL‑23 receptor, reducing release of pro‑inflammatory cytokines and chemokines.

Indications in this policyTreatment of moderately to severely active Crohn's disease or ulcerative colitis when coverage criteria are met.

Clinical remission endpoints (CD trials)

Coprimary endpoints (CD induction trials)

Revision History

2025-08-01Policy revision — coverage rationale updatedLatest

Updated examples of targeted immunomodulators the patient must not be receiving in combination with Skyrizi; Entyvio (vedolizumab) and Omvoh (mirikizumab) were added to the exclusion list for Crohn's disease and ulcerative colitis.

Policy revision — operational prior-treatment examples updated

Revised and expanded examples of prior/concomitant targeted immunomodulators used in prior-therapy and step-therapy logic (added guselkumab/Tremfya, upadacitinib/Rinvoq, ozanimod/Zeposia; standardized brand/agent spellings), which may affect prior-treatment determinations.

Policy Summary

PayerUnitedHealthcare

PolicySkyrizi (risankizumab-rzaa) coverage for Crohn's disease and ulcerative colitis

Policy CodePolicy IEXD00116.05

Change TypeExamples of prior and concomitant targeted immunomodulators added/updated

Effective DateAug 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization for IV induction and document three planned induction doses per FDA labeling; include diagnosis severity and prior therapy history.

SourceLink

On This Page

Safety considerations: Overall incidence of treatment‑emergent adverse events was similar across treatment groups in trials; common adverse events included worsening disease, arthralgia, and headache; deaths during induction were assessed as unrelated to study drug in trial reports where applicable.

See trial safety summaries.

Prior/concomitant therapy impact: Policy lists examples of targeted immunomodulators that members must not be receiving in combination with Skyrizi and examples of prior targeted immunomodulators that constitute prior treatment; these example lists were updated to add agents including vedolizumab (Entyvio), mirikizumab (Omvoh), guselkumab (Tremfya), ozanimod (Zeposia), and upadacitinib (Rinvoq).

Operational criteria for coverage decisions updated in policy history.

Step Therapy

Prior Failure / Step Therapy Requirements

Coverage requires prior failure, intolerance, or contraindication to conventional therapies (e.g., corticosteroids, azathioprine, 6-mercaptopurine, methotrexate) unless the patient has previously received an FDA‑approved targeted immunomodulator for the condition. Alternatively, prior treatment with an approved targeted immunomodulator for the indication may satisfy step requirements.

Examples of conventional therapies: corticosteroids (prednisone, methylprednisolone, budesonide), azathioprine, 6‑mercaptopurine, methotrexate
Examples of prior targeted immunomodulators (non‑exhaustive): adalimumab, vedolizumab (Entyvio), mirikizumab (Omvoh), upadacitinib (Rinvoq), guselkumab (Tremfya), ustekinumab

Documentation Required

Documentation to Support Medical Necessity

Provide clinical trial and evidence details as relevant to support medical necessity — e.g., INSPIRE, COMMAND, ADVANCE, MOTIVATE, FORTIFY results showing induction and maintenance efficacy and safety in moderately to severely active UC and CD. Include prior biologic/JAKi/S1PRM exposure and outcomes when applicable.

Summarize trial evidence (study name, population severity, prior treatment exposure, key endpoints)
Document prior biologic, JAK inhibitor, or S1PRM failures if applicable

Denial Risk

Denial and Potential Denial Triggers

Denial may be triggered if diagnosis severity or prior therapy history are not documented per policy requirements. Denial may also occur if the patient is concurrently receiving prohibited targeted immunomodulators listed in the policy.

Potential denial triggers: incomplete documentation of disease severity or lack of evidence of prior failure/intolerance to required therapies
Concurrent use of listed targeted immunomodulators (e.g., adalimumab, vedolizumab, mirikizumab, upadacitinib, guselkumab, ustekinumab) is prohibited and may lead to denial

Clinical remission defined by Crohn's Disease Activity Index (CDAI) or patient‑reported outcome criteria (average daily stool frequency and abdominal pain score) and endoscopic response at Week 12.

TimingWeek 12 for co‑primary endpoint assessment in ADVANCE and MOTIVATE induction studies.

PopulationPatients with moderately to severely active Crohn's disease enrolled in ADVANCE and MOTIVATE trials (aged 16–80 years).

Administration regimen in trialsIntravenous risankizumab at weeks 0, 4, and 8 (600 mg or 1200 mg doses studied).

mMS — modified Mayo score definition

DefinitionModified Mayo score (mMS): a 3‑component Mayo score (range 0–9) consisting of stool frequency subscore (SFS), rectal bleeding subscore (RBS), and centrally read endoscopy score (ES).

Component scoringEach subscore (SFS, RBS, ES) scored 0–3 and summed to give total mMS (0–9).

Endoscopy score (ES) descriptorsES of 2 = marked erythema, lack of vascular pattern, any friability, and/or erosions; ES of 3 = spontaneous bleeding and ulceration.

Eligibility range in INSPIREEnrolled subjects had mMS between 5 and 9 (median 7); 37% had mMS > 7 (severely active).

CDAI / stool frequency & abdominal pain score — Remission endpoint definitions

Definition of remission endpoints in maintenance trialsClinical remission at Week 52 was defined by CDAI in the US protocol or by stool frequency and abdominal pain score in the non‑US protocol.

CDAI useCDAI was used as the clinical remission measure in the US protocol for FORTIFY maintenance study.

Stool frequency & abdominal pain score useAverage daily stool frequency and abdominal pain score were used as the clinical remission measures in the non‑US protocol for FORTIFY.

ContextEndpoints applied to patients who had clinical response to risankizumab in ADVANCE or MOTIVATE and entered FORTIFY maintenance study.