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Risankizumab (e.g., Skyrizi) | |
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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:
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.
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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 infusion 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 or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 6 months.
Effective July 24, 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
STANDARD REVIEW for up to 3 doses:
ULCERATIVE COLITIS
STANDARD REVIEW for up to 3 doses:
Dosage and Administration
Dosing per FDA Guidelines
Note: Please refer to the risankizumab package insert for detailed induction and maintenance dosing.
Crohn’s Disease
Ulcerative Colitis
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:
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:
CONTINUED APPROVAL for up to 1 year:
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
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:
For members with contracts without primary coverage criteria, risankizumab, for any indication or circumstance not described above, is considered investigational. This includes the following:
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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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. (FDA, 2024)
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CPT/HCPCS: | |
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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 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. Risankizumab: Skyrizi [package insert]. North Chicago (IL): AbbVie, 2023. 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. |
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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 © 2024 American Medical Association. |