Coverage Policy Manual
Policy #: 2022031
Category: Pharmacy
Initiated: July 2022
Last Review: July 2026
Risankizumab (e.g., Skyrizi)
Description:
Risankizumab, an interleukin-23 (IL-23) antagonist, is a humanized immunoglobulin G1 (IgG1) monoclonal antibody. Risankizumab works by binding to the p19 subunit of human IL-23 cytokine and inhibits its interaction with the IL-23 receptor, thereby inhibiting the inflammatory and immune responses to IL-23 (Skyrizi, 2022).
 
Regulatory Status
 
Risankizumab (e.g., Skyrizi) is approved by the U.S. Food and Drug Administration (FDA) for treatment of the following:
⦁ Moderate to severe plaque psoriasis (Ps) in adults who are candidates for systemic therapy or phototherapy.
⦁ Active psoriatic arthritis (PsA) in adults.
⦁ Moderately to severely active Crohn’s disease (CD) in adults
 
Risankizumab solution for intravenous infusion is indicated for the induction phase in CD.
 
Risankizumab subcutaneous injection is indicated for Ps, PsA and the maintenance phase of CD.
 
On June 18, 2024, the U.S. Food and Drug Administration approve risankizumab-rzaa (e.g., Skyrizi) for the treatment of moderately to severely active ulcerative colitis in adults.
 
Coding
 
See CPT/HCPCS Code section below.
Policy/
Coverage:
Prior Approval is required for risankizumab (e.g., Skyrizi).
 
STANDARD REVIEW FOR DURATION OF TREATMENT COURSE OR 12 MONTHS (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.
 
Effective October 28, 2026
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Risankizumab (e.g., Skyrizi) meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes or for members with contracts without Primary Coverage Criteria, is considered Medically Necessary and is covered when member receives a “recommended” determination from criteria review in InterQual® for Risankizumab (e.g., Skyrizi) based on diagnosis and requested product.
 
Click the following link to view the specific criteria in InterQual®: https://prod.ds.interqual.com/service/connect/transparency?tid=27b0a724-ca06-4b22-846b-598b8dae52fc
 
See Criteria below.
 
CROHN’S DISEASE
 
INITIAL APPROVAL
 
1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of moderate to severe Crohn’s disease supported by the submitted medical records; AND
3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Lichtenstein, 2018); OR
4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Van Rheenen, 2021); OR
5. Individual has previously received a biologic (e.g., adalimumab, infliximab, certolizumab pegol, risankizumab, ustekinumab, natalizumab, vedolizumab) or Janus Kinase Inhibitor (e.g., upadacitinib) indicated for moderate to severe Crohn’s disease; OR
6. Individual has disease with high-risk features (see policy guidelines, ACG, 2025); AND
7. Individual is not using the medication in combination with any other biologic, including but not limited to: TNF inhibitor, IL-36 inhibitor, integrin inhibitor, any other IL inhibitor, or Janus kinase inhibitor.
 
AUTHORIZATION RENEWAL
 
1. Individual has experienced a documented positive clinical response; AND
2. Manageable or no side effects; AND
3. Individual is not using the medication in combination with any other biologic intended to treat Crohn’s disease, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor.
 
ULCERATIVE COLITIS
 
INITIAL APPROVAL
 
1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of moderate to severe ulcerative colitis supported by the submitted medical records AND meets one of the following:
a. Inadequate response, loss of response, or intolerance to at least one conventional therapy (ECCO 2022); OR
b. Contraindication to conventional therapy (ECCO 2022); OR
c. Previously received an FDA-approved biologic or targeted synthetic therapy for ulcerative colitis; OR
d. Treating provider documents that advanced therapy is clinically appropriate due to disease severity, prognostic factors, or anticipated inadequate response to conventional therapy (ACG, 2025); AND
3. Individual is not using the medication in combination with any other biologic intended to treat ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor.
 
AUTHORIZATION RENEWAL
 
1. Individual has experienced a documented positive clinical response; AND
2. Manageable or no side effects; AND
3. Individual is not using the medication in combination with any other biologic intended to treat ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor.
 
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
 
Risankizumab (e.g., Skyrizi) does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes and is not covered for any indication or circumstance not described above.
 
For contracts without Primary Coverage Criteria, Risankizumab (e.g., Skyrizi) is considered not Medically Necessary and is not covered or is investigational for any indication or circumstance not described above. Not Medically Necessary or Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Click the following link to view the specific criteria in InterQual®: https://prod.ds.interqual.com/service/connect/transparency?tid=27b0a724-ca06-4b22-846b-598b8dae52fc
 
POLICY GUIDELINES
 
Prescriber is responsible for verification that Individual does not have latent tuberculosis or serious active infection before starting the treatment.
 
High-risk features of adult Crohn’s disease when objective active inflammation is present:
1. Penetrating, fistulizing, stricturing, or stenosing phenotype​; OR
2. Perianal or severe rectal disease​; OR
3. Deep ulcers or severe endoscopic disease; OR​
4. Extensive small bowel, ileal, ileocolonic, or proximal GI involvement​; OR
5. Age less than 30 at onset; OR
6. Extraintestinal manifestations (e.g., peripheral arthritis, axial spondyloarthritis, erythema nodosum, perianal fistulas, uveitis, scleritis, episcleritis, pyoderma gangrenosum, primary sclerosing cholangitis), or high inflammatory burden​; OR
7. Prior surgical resection.
 
The American College of Gastroenterology (ACG) recognizes cigarette smoking as a modifiable risk factor associated with more aggressive manifestations of Crohn’s disease and poorer clinical outcomes. This risk factor should be considered by the medical provider when selecting the most appropriate therapeutic agent for the individual.
 
Moderate to severe ulcerative colitis is characterized by the following:
1. Frequent stools (6 or more per day)
2. Frequent blood in stools
3. Frequent urgency
4. Hemoglobin less than 75% of normal
5. Erythropoietin Sedimentation Rate greater than 30
6. Elevated C-reactive protein
7. Fecal calprotectin greater than 150-200
8. Ulcerative Colitis Endoscopic Index of Severity of 5-8
 
Ulcerative Colitis activity index according to American College of Gastroenterology:
1. Remission: daily formed stools, no blood in stool, no urgency, normal hemoglobin, less than 30 erythrocyte sedimentation rate (ESR), normal C-reactive protein (CRP), less than 150-000 fecal calprotectin (FC), 0-1 Ulcerative Colitis Endoscopic Index of Severity (UCEIS).
2. Mild: less than 4 stools per day, intermittent bloody stools, occasional urgency, normal hemoglobin, less than 30 ESR, elevated CRP, greater than 150-200 RC, 2-4 UCEIS.
3. Moderate Severe: greater than 6 stools per day, frequent blood in stools, urgency often, less than 75% of normal hemoglobin, greater than 30 ESR, elevated CRP, greater than 150-200 FC, 5-8 UCEIS.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Please refer to a separate policy on Maximum Dosage and Frequency (policy #2025031) for pharmacologic/biologic medications.
 
Effective February 11, 2026 to October 27, 2026
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Risankizumab (e.g., Skyrizi) meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes or for members with contracts without Primary Coverage Criteria, is considered Medically Necessary and is covered when member receives a “recommended” determination from InterQual® criteria review for (service/procedure) based on diagnosis and requested product.
 
 
See Criteria below.
 
For FDA labeled indications, Risankizumab (e.g., Skyrizi) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.
 
CROHN’S DISEASE
 
STANDARD REVIEW for up to 3 doses:
 
1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of moderate to severe Crohn’s disease (Skyrizi, 2024) supported by the submitted medical records; AND
3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Lichtenstein, 2018); OR
4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Van Rheenen, 2021); OR
5. Individual has previously received a biologic (e.g., adalimumab, infliximab, certolizumab pegol, risankizumab, ustekinumab, natalizumab, vedolizumab) or Janus Kinase Inhibitor (e.g., upadacitinib) indicated for moderate to severe Crohn’s disease; OR
6. Individual has fistulizing disease (Feuerstein, 2021); AND
7. Individual is not using the medication in combination with any other biologic, including but not limited to: TNF inhibitor, IL-36 inhibitor, integrin inhibitor, any other IL inhibitor, or Janus kinase inhibitor.  
 
ULCERATIVE COLITIS
 
STANDARD REVIEW for up to 3 doses:
 
1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of moderate to severe ulcerative colitis (Skyrizi, 2024) supported by the submitted medical records; AND
3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR
4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR
5. Individual has previously received a biologic (e.g., adalimumab, infliximab, golimumab, ustekinumab, vedolizumab, mirikizumab) or targeted synthetic drug (e.g., tofacitinib, upadacitinib, ozanimod, etrasimod) indicated for ulcerative colitis; AND
6. Individual is not using the medication in combination with other biologic intended for treatment of ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor.
 
POLICY GUIDELINES
 
Prescriber is responsible for verification that Individual does not have latent tuberculosis or serious active infection before starting the treatment.
 
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
 
Risankizumab (e.g., Skyrizi) does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes and is not covered for any indication or circumstance not described above.
 
For contracts without Primary Coverage Criteria, Risankizumab (e.g., Skyrizi) is considered not Medically Necessary and is not covered or is investigational for any indication or circumstance not described above. Not Medically Necessary or Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Please refer to a separate policy on Maximum Dosage and Frequency (policy #2025031) for pharmacologic/biologic medications.
 
Effective July 2025 to February 10, 2026
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Risankizumab (e.g., Skyrizi) intravenous infusion meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
For FDA labeled indications, Risankizumab (e.g., Skyrizi) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.
 
CROHN’S DISEASE
 
STANDARD REVIEW for up to 3 doses:
 
1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of moderate to severe Crohn’s disease (Skyrizi, 2024) supported by the submitted medical records; AND
3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Lichtenstein, 2018); OR
4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Van Rheenen, 2021); OR
5. Individual has previously received a biologic (e.g., adalimumab, infliximab, certolizumab pegol, risankizumab, ustekinumab, natalizumab, vedolizumab) or Janus Kinase Inhibitor (e.g., upadacitinib) indicated for moderate to severe Crohn’s disease; OR
6. Individual has fistulizing disease (Feuerstein, 2021); AND
7. Individual is not using the medication in combination with any other biologic, including but not limited to: TNF inhibitor, IL-36 inhibitor, integrin inhibitor, any other IL inhibitor, or Janus kinase inhibitor.  
 
ULCERATIVE COLITIS
 
STANDARD REVIEW for up to 3 doses:
 
1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of moderate to severe ulcerative colitis (Skyrizi, 2024) supported by the submitted medical records; AND
3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR
4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR
5. Individual has previously received a biologic (e.g., adalimumab, infliximab, golimumab, ustekinumab, vedolizumab, mirikizumab) or targeted synthetic drug (e.g., tofacitinib, upadacitinib, ozanimod, etrasimod) indicated for ulcerative colitis; AND
6. Individual is not using the medication in combination with other biologic intended for treatment of ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor.
 
Policy guidelines
 
Prescriber is responsible for verification that Individual does not have latent tuberculosis or serious active infection before starting the treatment.
 
Dosage and Administration
Dosing per FDA Guidelines unless otherwise specified below.
 
Note:  Please refer to the risankizumab package insert for detailed induction and maintenance dosing.
 
Crohn’s Disease
    •  The recommended induction dose of risankizumab is 600 mg given as an intravenous infusion at weeks 0, 4 and 8.
    •  This is followed by 180 mg or 360 mg given as a self-administered subcutaneous injection at week 12, and every 8 weeks thereafter.
 
Ulcerative Colitis
    •  The recommended induction dose of risankizumab is 1,200 mg administered by intravenous infusion over at least two hours at week 0, week 4, and week 8.
    •  This is followed by 180 mg or 360 mg administered by subcutaneous injection at week 12, and every 8 weeks thereafter.
 
Risankizumab for IV infusion is available as a 600mg/10ml solution for injection.
 
Risankizumab IV infusion should be administered by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Risankizumab, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members  with contracts without primary coverage criteria, risankizumab, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective January 29, 2025 to June 2025
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Risankizumab intravenous infusion meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
CROHN’S DISEASE
 
STANDARD REVIEW for up to 3 doses:
1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of moderate to severe Crohn’s disease supported by the submitted medical records; AND
3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Lichtenstein, 2018); OR
4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Van Rheenen, 2021); OR
5. Individual has previously received a biologic (e.g., adalimumab, infliximab, certolizumab pegol, risankizumab, ustekinumab, natalizumab, vedolizumab) or Janus Kinase Inhibitor (e.g., upadacitinib) indicated for moderate to severe Crohn’s disease; OR
6. Individual has fistulizing disease (Feuerstein, 2021); AND
7. Individual is not using the medication in combination with any other biologic, including but not limited to: TNF inhibitor, IL-36 inhibitor, integrin inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
8. Must be dosed in accordance with the FDA label.  
 
ULCERATIVE COLITIS
 
STANDARD REVIEW for up to 3 doses:
1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of moderate to severe ulcerative colitis supported by the submitted medical records; AND
3. Individual has an active disease with documented inadequate response (trial of ≥3 months) to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR
4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR
5. Individual has previously received a biologic (e.g., adalimumab, infliximab, golimumab, ustekinumab, vedolizumab, mirikizumab) or targeted synthetic drug (e.g., tofacitinib, upadacitinib, ozanimod, etrasimod) indicated for ulcerative colitis; AND
6. Individual is not using the medication in combination with other biologic intended for treatment of ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
7. Must be dosed in accordance with the FDA label.
 
Policy guidelines
 
Prescriber is responsible for verification that Individual does not have latent tuberculosis or serious active infection before starting the treatment.
 
Dosage and Administration
Dosing per FDA Guidelines
 
Note:  Please refer to the risankizumab package insert for detailed induction and maintenance dosing.
 
Crohn’s Disease
    • The recommended induction dose of risankizumab is 600 mg given as an intravenous infusion at weeks 0, 4 and 8.
    • This is followed by 180 mg or 360 mg given as a self-administered subcutaneous injection at week 12, and every 8 weeks thereafter.
 
Ulcerative Colitis
    • The recommended induction dose of risankizumab is 1,200 mg administered by intravenous infusion over at least two hours at week 0, week 4, and week 8.
    • This is followed by 180 mg or 360 mg administered by subcutaneous injection at week 12, and every 8 weeks thereafter.
 
Risankizumab for IV infusion is available as a 600mg/10ml solution for injection.
 
Risankizumab IV infusion should be administered by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Risankizumab, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members  with contracts without primary coverage criteria, risankizumab, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective July 24, 2024 to January 28, 2025
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Risankizumab intravenous infusion meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
CROHN’S DISEASE
 
STANDARD REVIEW for up to 3 doses:
 
1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of moderate to severe Crohn’s disease supported by the submitted medical records; AND
3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Lichtenstein, 2018); OR
4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Van Rheenen, 2021); OR
5. Individual has previously received a biologic (e.g., adalimumab, infliximab, certolizumab pegol, risankizumab, ustekinumab, natalizumab, vedolizumab) or Janus Kinase Inhibitor (e.g., upadacitinib) indicated for moderate to severe Crohn’s disease; OR
6. Individual has fistulizing disease (Feuerstein, 2021); AND
7. Individual is not using the medication in combination with any other biologic, including but not limited to: TNF inhibitor, IL-36 inhibitor, integrin inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
8. Individual does not have latent tuberculosis or serious active infection; AND
9. Must be dosed in accordance with the FDA label.  
 
ULCERATIVE COLITIS
 
STANDARD REVIEW for up to 3 doses:
 
1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of moderate to severe ulcerative colitis supported by the submitted medical records; AND
3. Individual has an active disease with documented inadequate response (trial of ≥3 months) to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR
4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone, hydrocortisone, budesonide, corticotropin) (ECCO 2022); OR
5. Individual has previously received a biologic (e.g., adalimumab, infliximab, golimumab, ustekinumab, vedolizumab, mirikizumab) or targeted synthetic drug (e.g., tofacitinib, upadacitinib, ozanimod, etrasimod) indicated for ulcerative colitis; AND
6. Individual is not using the medication in combination with other biologic intended for treatment of ulcerative colitis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
7. Individual does not have latent tuberculosis or serious active infection; AND
8. Must be dosed in accordance with the FDA label.
 
Dosage and Administration
Dosing per FDA Guidelines
 
Note:  Please refer to the risankizumab package insert for detailed induction and maintenance dosing.
 
Crohn’s Disease
    • The recommended induction dose of risankizumab is 600 mg given as an intravenous infusion at weeks 0, 4 and 8.
    • This is followed by 180 mg or 360 mg given as a self-administered subcutaneous injection at week 12, and every 8 weeks thereafter.
 
Ulcerative Colitis
    • The recommended induction dose of risankizumab is 1,200 mg administered by intravenous infusion over at least two hours at week 0, week 4, and week 8.
    • This is followed by 180 mg or 360 mg administered by subcutaneous injection at week 12, and every 8 weeks thereafter.
 
Risankizumab for IV infusion is available as a 600mg/10ml solution for injection.
 
Risankizumab IV infusion should be administered by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Risankizumab, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members  with contracts without primary coverage criteria, risankizumab, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective April 24, 2024 to July 23, 2024
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Risankizumab intravenous infusion meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
STANDARD REVIEW for up to 3 doses:
 
1. Individual is greater than or equal to 18 years of age; AND
2. Individual has a diagnosis of moderate to severe Crohn’s disease supported by the submitted medical records; AND
3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Lichtenstein, 2018); OR
4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Van Rheenen, 2021); OR
5. Individual has previously received a biologic (e.g., adalimumab, infliximab, certolizumab pegol, risankizumab, ustekinumab, natalizumab, vedolizumab) or Janus Kinase Inhibitor (e.g., upadacitinib) indicated for moderate to severe Crohn’s disease; OR
6. Individual has fistulizing disease (Feuerstein, 2021); AND
7. Individual is not using the medication in combination with any other biologic, including but not limited to: TNF inhibitor, IL-36 inhibitor, integrin inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
8. Individual does not have latent tuberculosis or serious active infection; AND
9. Must be dosed in accordance with the FDA label.  
 
Dosage and Administration
Dosing per FDA Guidelines
 
Note:  Please refer to the risankizumab package insert for detailed induction and maintenance dosing.
 
The recommended induction dose of risankizumab is 600 mg given as an IV infusion at weeks 0, 4 and 8.
This is followed by 180 mg or 360 mg given as a self-administered subcutaneous injection at week 12, and every 8 weeks thereafter.
 
Risankizumab for IV infusion is available as a 600mg/10ml solution for injection.
 
Risankizumab IV infusion should be administered by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Risankizumab, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members  with contracts without primary coverage criteria, risankizumab, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective January 2024 to April 23, 2024
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Risankizumab intravenous infusion meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
CROHN'S DISEASE
INITIAL APPROVAL STANDARD REVIEW for up to 3 doses:
1. Individual is greater than or equal to 18 years of age; AND
2. Individual has a diagnosis of moderate to severe Crohn’s disease supported by the submitted medical records; AND
3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Lichtenstein, 2018); OR
4. Individual has an active disease with intolerance or contraindication to at least one conventional therapy option (e.g., betamethasone, methylprednisolone, prednisolone, prednisone, budesonide, hydrocortisone, azathioprine, mercaptopurine, sulfasalazine, mesalamine, methotrexate) (Van Rheenen, 2021); OR
5. Individual has previously received a biologic (e.g., adalimumab, infliximab, certolizumab pegol, risankizumab, ustekinumab, natalizumab, vedolizumab) or Janus Kinase Inhibitor (e.g., upadacitinib) indicated for moderate to severe Crohn’s disease; OR
6. Individual has fistulizing disease (Feuerstein, 2021); AND
7. Individual is not using the medication in combination with any other biologic, including but not limited to: TNF inhibitor, IL-36 inhibitor, integrin inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
8. Individual does not have latent tuberculosis or serious active infection; AND
9. Must be dosed in accordance with the FDA label.  
 
CONTINUED APPROVAL for up to 1 year:
1. Individual has met initial criteria for a diagnosis of Crohn’s disease; AND
2. Individual has experienced a documented positive clinical response; AND
3. Individual is not using the medication in combination with any other biologic, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor.
4. Must be dosed in accordance with the FDA label.
 
Dosage and Administration
Dosing per FDA Guidelines
 
Note:  Please refer to the risankizumab package insert for detailed induction and maintenance dosing.
 
The recommended induction dose of risankizumab is 600 mg given as an IV infusion at weeks 0, 4 and 8.
This is followed by 180 mg or 360 mg given as a self-administered subcutaneous injection at week 12, and every 8 weeks thereafter.
 
Risankizumab for IV infusion is available as a 600mg/10ml solution for injection.
 
Risankizumab IV infusion should be administered by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Risankizumab, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members  with contracts without primary coverage criteria, risankizumab, for any indication or circumstance not described above, is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective July 27, 2022 - December 31, 2023
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Initial Approval Standard Review for up to 3 doses:
 
Risankizumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
Moderately to Severely Active CD
 
    1. Individual has a diagnosis of moderately to severely active CD; AND
    2. Individual is 18 years of age or older; AND
    3. Individual is dosed in accordance with the FDA label; AND
    4. Individual has documentation of one of the following:  
a.  Individual has previously met criteria for and received a FDA approved biologic indicated for moderately to severely active Crohn’s disease OR    
b.  Individual has had an inadequate response to at least one conventional therapy option (i.e. azathioprine, mercaptopurine, sulfasalazine, methotrexate, or corticosteroids) OR  
c.  Individual has an intolerance or contraindication to all conventional therapy options (i.e., azathioprine, mercaptopurine, sulfasalazine, methotrexate, or corticosteroids) (FDA, 2020).
 
Dosage and Administration
Dosing per FDA Guidelines
 
Note:  Please refer to risankizumab’s package insert for detailed induction and maintenance dosing.
 
The recommended induction dose of risankizumab is 600 mg given as an IV infusion at weeks 0, 4 and 8. This is followed by 180 mg or 360 mg given as a self-administered subcutaneous injection at week 12, and every 8 weeks after that.
 
 
Risankizumab for IV infusion is available as a 600mg/10ml solution for injection.
 
Risankizumab IV infusion should be administered by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Risankizumab, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. This includes the following:
1. All other indications not included above; OR
2. In the presence of Tuberculosis, other active serious infections, or a history of recurrent infections; OR
3. In combination with other biologic drugs (e.g. TNF antagonists, abatacept, vedolizumab, IL-23 inhibitors or IL-17 inhibitors and others).
 
For members  with contracts without primary coverage criteria, risankizumab, for any indication or circumstance not described above, is considered investigational. This includes the following:
1. All other indications not included above; OR
2. In the presence of Tuberculosis, other active serious infections, or a history of recurrent infections; OR
3. In combination with other biologic drugs (e.g. TNF antagonists, abatacept, vedolizumab, IL-23 inhibitors or IL-17 inhibitors and others).
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Rationale:
There were three phase III trials studying risankizumab vs placebo that led to the added indication for treatment of adults with moderately to severely active CD. Of the three trials, there were two induction studies, ADVANCE and MOTIVATE, and one maintenance study, FORTIFY.
 
In the two 12-week induction studies, subjects with moderately to severely active Crohn’s disease were randomized to receive SKYRIZI 600 mg, SKYRIZI 1,200 mg, or placebo as an intravenous infusion at Week 0, Week 4, and Week 8. Subjects with inadequate response, loss of response, or intolerance to oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapy were enrolled.  
 
In ADVANCE, 58% (491/850) of subjects had failed or were intolerant to treatment with one or more biologic therapies (prior biologic failure). All subjects in MOTIVATE had prior biologic failure. ADVANCE and MOTIVATE combined, the median age was 36 years (ranging from 16 to 80 years).
 
In ADVANCE and MOTIVATE, the co-primary endpoints were clinical remission and endoscopic response at Week 12. Secondary endpoints included clinical response and endoscopic remission. The SKYRIZI 1,200 mg dosage did not demonstrate additional treatment benefit over the 600 mg dosage and is not a recommended regimen.
 
Onset of clinical response and clinical remission based on CDAI occurred as early as Week 4 in a greater proportion of subjects treated with the SKYRIZI 600 mg induction regimen compared to placebo. CDAI clinical remission rate at week 12 were as follows for ADVANCE and MOTIVATE respectively: 45% at 600 mg dosage and 25% for placebo, 42% at 600 mg dosage and 20% for placebo.
 
Reductions in stool frequency and abdominal pain were observed in a greater proportion of subjects treated with the SKYRIZI 600 mg induction regimen compared to placebo. Stool frequency and abdominal pain scores at week 12 were as follow for ADVANCE and MOTIVATE respectively: 43% at 600 mg dosage and 22% placebo, 35% 600 mg dosage and 19% placebo (D'Haens, 2022).
The maintenance study FORTIFY evaluated subjects who achieved clinical response defined as a reduction in CDAI of at
least 100 points from baseline after 12 weeks of induction treatment with intravenous SKYRIZI in studies ADVANCE and MOTIVATE. Subjects were randomized to receive a maintenance regimen of SKYRIZI 360 mg or placebo at Week 12 and every 8 weeks thereafter for up to an additional 52 weeks.
 
The co-primary endpoints in FORTIFY were CDAI clinical remission and endoscopic response at Week 52. Both endpoints were met. CDAI clinical remission at week 52 was 52% at the 360 mg dosage and 41% for placebo. Endoscopic response at week 52 was 47% at the 360 mg dosage and 22% for placebo (Ferrante, 2022).
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2023. No new literature was identified that would prompt a change in the coverage statement.
 
2024 Update
Ulcerative Colitis
Induction Trial (Study UC-1)
In the 12-week induction study (UC-1; NCT03398148), 966 subjects with moderately to severely active ulcerative colitis were randomized and received SKYRIZI 1,200 mg or placebo as an intravenous infusion at Week 0, Week 4, and Week 8. Disease activity was assessed by the modified Mayo score (mMS), a 3-component Mayo score (0-9) which consists of the following subscores (0 to 3 for each subscore): stool frequency (SFS), rectal bleeding (RBS), and findings on centrally read endoscopy score (ES). An ES of 2 was defined by marked erythema, lack of vascular pattern, any friability, and/or erosions; an ES of 3 was defined by spontaneous bleeding and ulceration. Enrolled subjects had a mMS between 5 and 9, with an ES of 2 or 3. Subjects with inadequate response, or intolerance to oral aminosalicylates, corticosteroids, immunomodulators, biologics, Janus Kinase inhibitors (JAKi), and/or sphingosine-1-phospate receptor modulators (S1PRM) were enrolled.
 
At baseline in UC-1, the median mMS was 7; 37% had severely active disease (mMS >7); 69% had an ES of 3. In UC-1, 52% (499/966) of subjects had failed (inadequate response or intolerance) treatment with one or more biologics, JAKi or S1PRM. Of these 499 subjects, 484 (97%) failed biologics and 90 (18%) failed JAK inhibitors. Enrolled subjects were permitted to use a stable dose of oral corticosteroids (up to 20 mg/day prednisone or equivalent), immunomodulators, and aminosalicylates. At baseline, 36% of subjects were receiving corticosteroids, 16% of subjects were receiving immunomodulators (including azathioprine, 6-mercaptopurine, methotrexate), and 73% of subjects were receiving aminosalicylates in UC-1. In UC-1, the primary endpoint was clinical remission defined using the mMS at Week 12 Key secondary endpoints included clinical response, endoscopic improvement, and histologic endoscopic mucosal improvement.
 
Maintenance Study UC-2
The maintenance study (UC-2; NCT03398135) evaluated 547 subjects who received one of three SKYRIZI induction regimens, including the 1,200 mg regimen, for 12 weeks in Studies UC-1 or UC-3 and demonstrated clinical response per mMS after 12 weeks. Subjects were randomized to receive a maintenance regimen of subcutaneous (SC) SKYRIZI 180 mg or SKYRIZI 360 mg or placebo at Week 12 and every 8 weeks thereafter for up to an additional 52 weeks. In UC-2, 75% (411/547) of subjects had failed (inadequate response or intolerance) treatment with one or more biologics, JAKi, or S1PRM. Of these 411 subjects, 407 (99%) failed biologics and 78 (19%) failed JAK inhibitors.
 
The primary endpoint in UC-2 was clinical remission using mMS at Week 52. Key secondary endpoints included corticosteroid-free clinical remission, endoscopic improvement, and histologic endoscopic mucosal improvement. (Skyrizi, 2024)
 
2025 Update
In the 12-week phase 3 INSPIRE induction study, patients were randomized to intravenous risankizumab 1200 mg or placebo. Clinical responders were randomized to subcutaneous risankizumab 180 mg, risankizumab 360 mg, or placebo (risankizumab withdrawal) in the 52-week phase 3 COMMAND maintenance study. This post hoc analysis assessed outcomes by AT-IR status, number, and mechanism of action. AT included biologics, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators.
 
Efficacy analyses included 472 non-AT-IR and 503 AT-IR patients (induction), and 137 non-AT-IR and 411 AT-IR patients (maintenance). More patients achieved clinical remission per Adapted Mayo score with risankizumab 1200 mg versus placebo at induction week 12 (non-AT-IR, 29.7% versus 8.4%, nominal P < .0001; AT-IR, 11.4% versus 4.3%, nominal P = .0083); consistent with risankizumab 180 mg or risankizumab 360 mg versus placebo (withdrawal) at maintenance week 52 (non-AT-IR, 50.9% or 61.7% versus 31.1%, nominal P = .057 or P = .0033, respectively; AT-IR, 36.6% or 29.5% versus 23.2%, nominal P = .0159 or P = .2334, respectively). Risankizumab had increased efficacy over placebo, regardless of AT-IR number or mechanism of action, with higher efficacy rates for non-AT-IR compared to AT-IR. Safety results in non-AT-IR and AT-IR patients were generally comparable in both induction and maintenance.
 
Risankizumab was effective and well tolerated, regardless of prior AT-IR status. (Panaccione, 2025)
 
2026 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2026. No new literature was identified that would prompt a change in the coverage statement.
 
August 2026 Update
The risankizumab (Skyrizi®) Crohn’s disease coverage criteria are being updated to align with the most recent American College of Gastroenterology (ACG) Clinical Guideline for the Management of Crohn’s Disease in Adults (2025), which emphasizes an individualized, risk-based treatment strategy and early use of advanced therapies in patients at elevated risk for disease progression. The updated criteria incorporate contemporary high-risk features associated with aggressive disease, including penetrating, fistulizing, stricturing, or stenosing disease; perianal involvement; extensive ileal or ileocolonic disease; deep ulcerations; extraintestinal manifestations; prior intestinal resection; and other predictors of poor long-term outcomes. These revisions ensure that the policy reflects current evidence-based standards of care and supports timely access to risankizumab for appropriately selected patients with moderate-to-severe Crohn’s disease in order to reduce complications, preserve bowel function, and improve long-term disease control.
 
The ulcerative colitis criteria are likewise being updated to maintain consistency with current ACG recommendations and the evolving therapeutic landscape for inflammatory bowel disease. The revised criteria recognize the role of advanced biologic therapies, including IL-23 inhibitors such as risankizumab, in achieving key treatment goals such as clinical remission, endoscopic improvement, corticosteroid-free remission, and reduction of disease-related complications in patients with moderate-to-severe ulcerative colitis. Aligning the policy with the newest ACG guidance promotes evidence-based utilization management, ensures that coverage determinations reflect current expert consensus and available clinical evidence, and supports appropriate patient access to effective therapies when medically necessary. These updates strengthen the clinical foundation of the policy while maintaining consistency with contemporary gastroenterology practice and treatment expectations.
CPT/HCPCS:
J2327Injection, risankizumab-rzaa, intravenous, 1 mg
References:
ACIP(2025) Advisory Committee on Immunization Practices (ACIP). Centers for Disease Control and Prevention www.cdc.gov/acip/index.html

D'Haens, G. et al.(2022) Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022 May 28;399(10340):2015-2030. doi: 10.1016/S0140-6736(22)00467-6. PMID: 35644154.

Ferrante, M. et al.(2022) Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maint. trial. Lancet. 2022 May 28;399(10340):2031-2046. doi: 10.1016/S0140-6736(22)00466-4. PMID: 35644155.

Feuerstein JD, Ho EY, Shmidt E, et. al.(2021) AGA clinical practice guidelines on the medical management of moderate to severe luminal and perianal fistulizing Crohn’s disease. Gastroenterology. 2021 Jun 1;160(7):2496-508.

Lichtenstein GR, Loftus EV, Afzali A, Long MD, Barnes EL, Isaacs KL, Ha CY.(2025) ACG clinical guideline: management of Crohn's disease in adults American Journal of Gastroenterology. 2025 Jun;120(6):1225-64.

Panaccione R, Louis E, Colombel JF, et.al.,(2025) Risankizumab efficacy and safety based on prior inadequate response or intolerance to advanced therapy: post hoc analysis of the INSPIRE and COMMAND phase 3 studies. J Crohns Colitis. 2025 Jan 11;19(1):jjaf005. doi: 10.1093/ecco-jcc/jjaf005. PMID: 39804294; PMCID: PMC11772864.

Risankizumab: Skyrizi [package insert]. North Chicago (IL): AbbVie, 2023.

Rubin DT, Ananthakrishnan AN, Siegel CA, Barnes EL, Long MD.(2025) ACG clinical guideline update: ulcerative colitis in adults Official journal of the American College of Gastroenterology | ACG. 2025 Jun 1;120(6):1187-224.

Skyrizi (risankizumab)(2024) package insert North Chicago, IL: AbbVie Inc. 2024.

Skyrizi [package insert]. North Chicago (IL): AbbVie, 2024.

Skyrizi® (risankizumab) [package insert]. North Chicago, IL: AbbVie Inc. 2022.

Van Rheenen PF, Aloi M, Assa A, Bronsky J, et. al.(2021) The medical management of paediatric Crohn’s disease: an ECCO-ESPGHAN guideline update. Journal of Crohn's and Colitis. 2021 Feb 1;15(2):171-94.
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.
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