Coverage Policy Manual
Policy #: 2022031
Category: Pharmacy
Initiated: July 2022
Last Review: July 2023
  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., SkyriziTM) 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.
 
Coding
 
See CPT/HCPCS Code section below.

Policy/
Coverage:
The use of risankizumab subcutaneous injection is not covered under the medical benefit. Please check member’s pharmacy benefit for coverage of risankizumab subcutaneous injection.
 
The use of risankizumab intravenous injection is covered under the medical benefit.
 
Prior Approval is required for risankizumab (e.g., Skyrizi).
 
The use of this drug requires documentation of direct physician involvement and signature in the ordering and evaluation as documented in the medical records submitted for prior approval.  
 
The Step Therapy Medication Act is applicable to fully insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart, Tyson, or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.
 
Effective July 27, 2022
 
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.

CPT/HCPCS:
C9399Unclassified drugs or biologicals
J2327Injection, risankizumab-rzaa, intravenous, 1 mg
J3490Unclassified drugs
J3590Unclassified biologics

References: 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 the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet. 2022 May 28;399(10340):2031-2046. doi: 10.1016/S0140-6736(22)00466-4. PMID: 35644155.

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


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2023 American Medical Association.