Ustekinumab (Stelara®) and Ustekinumab Biosimilars

Restricted Product(s):

• *ustekinumab (Stelara^®) intravenous infusion and subcutaneous injection for administration by a healthcare professional
• ustekinumab-aauz (Otulfi^™) intravenous infusion and subcutaneous injection for administration by a healthcare professional
• ustekinumab-ttwe (Pyzchiva^®) intravenous infusion and subcutaneous injection for administration by a healthcare professional
• ustekinumab-aekn (Selarsdi^™) intravenous infusion and subcutaneous injection for administration by a healthcare professional
• ustekinumab-stba (Steqeyma^®) intravenous infusion and subcutaneous injection for administration by a healthcare professional
• ustekinumab-auub (Wezlana^™) intravenous infusion and subcutaneous injection for administration by a healthcare professional
• ustekinumab-kfce (Yesintek^™) intravenous infusion and subcutaneous injection for administration by a healthcare professional

*preferred agent

FDA Approved Use:

• For patients 6 years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
• For patients 6 years and older with active psoriatic arthritis
• For adults with moderately to severely active Crohn’s disease
• For adults with moderately to severely active ulcerative colitis

Criteria for Medical Necessity:

The restricted product(s) may be considered medically necessary when the following criteria are met:

1. The patient has a diagnosis of moderate to severe plaque psoriasis (PS); AND 
   1. The patient is 6 years of age or older; AND 
   2. The patient has tried and had an inadequate response to ONE conventional agent (i.e., acitretin, anthralin, calcipotriene, calcitriol, coal tar products, cyclosporine, methotrexate, pimecrolimus, PUVA [phototherapy], tacrolimus, tazarotene, topical corticosteroids) used in the treatment of PS for at least 3-months [medical record documentation required]; OR 
   3. The patient has an intolerance or hypersensitivity to ONE of the conventional agents used in the treatment of PS [medical record documentation required]; OR 
   4. The patient has an FDA labeled contraindication to ALL of the conventional agents used in the treatment of PS [medical record documentation required]; OR 
   5. The patient has severe active PS (e.g., greater than 10% body surface area involvement, occurring on select locations [i.e., hands, feet, scalp, face, or genitals], intractable pruritus, serious emotional consequences) [medical record documentation required]; OR 
   6. The patient has concomitant severe psoriatic arthritis (PsA) (e.g., erosive disease, elevated markers of inflammation [e.g., ESR, CRP] attributable to PsA, long-term damage that interferes with function [i.e., joint deformities], rapidly progressive) [medical record documentation required]; OR 
2. The patient has a diagnosis of active psoriatic arthritis (PsA); AND 
   1. The patient is 6 years of age or older; AND 
   2. The patient has tried and had an inadequate response to ONE conventional agent (i.e., cyclosporine, leflunomide, methotrexate, sulfasalazine) used in the treatment of PsA for at least 3-months [medical record documentation required]; OR
   3. The patient has an intolerance or hypersensitivity to ONE of the conventional agents used in the treatment of PsA [medical record documentation required]; OR 
   4. The patient has an FDA labeled contraindication to ALL of the conventional agents used in the treatment of PsA [medical record documentation required]; OR 
   5. The patient has severe active PsA (e.g., erosive disease, elevated markers of inflammation [e.g., ESR, CRP] attributable to PsA, long-term damage that interferes with function [i.e., joint deformities], rapidly progressive) [medical record documentation required]; OR 
   6. The patient has concomitant severe psoriasis (PS) (e.g., greater than 10% body surface area involvement, occurring on select locations [i.e., hands, feet, scalp, face, or genitals], intractable pruritus, serious emotional consequences) [medical record documentation required]; OR
3. The patient has a diagnosis of moderately to severely active Crohn’s disease (CD); AND 
   1. The patient is 18 years of age or older; AND
   2. The patient has tried and had an inadequate response to ONE conventional agent (i.e., 6-mercaptopurine, azathioprine, corticosteroids [e.g., prednisone, budesonide EC capsule], methotrexate) used in the treatment of CD for at least 3-months [medical record documentation required]; OR
   3. The patient has an intolerance or hypersensitivity to ONE of the conventional agents used in the treatment of CD [medical record documentation required]; OR
   4. The patient has an FDA labeled contraindication to ALL of the conventional agents used in the treatment of CD [medical record documentation required]; AND
   5. If the request is for initiation of ustekinumab therapy, an initial intravenous infusion of an ustekinumab product will be administered; OR
   6. If the request is for ustekinumab maintenance therapy, the patient has received an initial intravenous infusion of an ustekinumab product; AND
   7. The patient will be treated with the 90 mg injection; OR
4. The patient has a diagnosis of moderately to severely active ulcerative colitis (UC); AND 
   1. The patient is 18 years of age or older; AND
   2. The patient has tried and had an inadequate response to ONE conventional agent (i.e., 6-mercaptopurine, azathioprine, balsalazide, corticosteroids, cyclosporine, mesalamine, sulfasalazine) used in the treatment of UC for at least 3-months [medical record documentation required]; OR
   3. The patient has severely active ulcerative colitis [medical record documentation required]; OR
   4. The patient an intolerance or hypersensitivity to ONE of the conventional agents used in the treatment of UC [medical record documentation required]; OR
   5. The patient has an FDA labeled contraindication to ALL of the conventional agents used in the treatment of UC [medical record documentation required]; AND
   6. If the request is for initiation of ustekinumab therapy, an initial intravenous infusion of an ustekinumab product will be administered; OR
   7. If the request is for ustekinumab maintenance therapy, the patient has received an initial intravenous infusion of an ustekinumab product; AND
   8. The patient will be treated with the 90 mg injection; AND
5. If ustekinumab 90 mg is requested, ONE of the following: 
   1. The patient has a diagnosis of psoriasis; AND 
      1. The patient has tried and had an inadequate response to 45 mg for at least 3-months [medical record documentation required]; OR 
      2. The patient weighs >100 kg [medical record documentation required]; OR 
   2. The patient has a dual diagnosis of psoriasis AND psoriatic arthritis; AND 
      1. The patient has tried and had an inadequate response to 45 mg for at least 3-months [medical record documentation required]; OR 
      2. The patient weighs >100 kg [medical record documentation required]; OR 
   3. The patient has a diagnosis of Crohn’s disease or ulcerative colitis; AND 
6. If the request is for Otulfi^™ (ustekinumab-aauz), Pyzchiva^® (ustekinumab-ttwe), Selarsdi^™ (ustekinumab-aekn), Steqeyma^® (ustekinumab-stba), Wezlana^™ (ustekinumab-auub), Yesintek^™ (ustekinumab-kfce), or a non-preferred ustekinumab product, BOTH of the following:
   1. ONE of the following:
      1. The patient has tried and had an inadequate response to the following preferred ustekinumab product: Stelara® (ustekinumab) [medical record documentation required]; OR
      2. The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to Stelara® (ustekinumab) that is NOT expected to occur with the requested agent [medical record documentation required]; AND
   2. ONE of the following:
      1. The patient has tried and had an inadequate response to TWO of the following agents FDA approved for treatment of the requested indication: an adalimumab product, Cosentyx, Enbrel, Entyvio, Skyrizi, Tremfya, Otezla, Sotyktu, Rinvoq, Xeljanz/Xeljanz XR [medical record documentation required]; OR
      2. The patient has an intolerance or hypersensitivity to TWO of the following agents FDA approved for treatment of the requested indication: an adalimumab product, Cosentyx, Enbrel, Entyvio, Skyrizi, Tremfya, Otezla, Sotyktu, Rinvoq, Xeljanz/Xeljanz XR [medical record documentation required]; OR
      3. The patient has an FDA labeled contraindication to ALL of the following agents FDA approved for treatment of the requested indication: an adalimumab product, Cosentyx, Enbrel, Entyvio, Skyrizi, Tremfya, Otezla, Sotyktu, Rinvoq, Xeljanz/Xeljanz XR [medical record documentation required]; AND
7. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., dermatologist for PS; rheumatologist for PsA; gastroenterologist for CD, UC) or has consulted with a specialist in the area of the patient’s diagnosis; AND
8. The patient will NOT be using the requested agent in combination with another biologic immunomodulator agent, Otezla® or Zeposia®; AND
9. The patient does NOT have any FDA labeled contraindications to ustekinumab (Stelara^®), ustekinumab-aauz (Otulfi^™), ustekinumab-ttwe (Pyzchiva^®), ustekinumab-aekn (Selarsdi^™), ustekinumab-stba (Steqeyma^®), ustekinumab-auub (Wezlana^™), or ustekinumab-kfce (Yesintek^™); AND
10. The patient has been tested for latent tuberculosis (TB) when required by the prescribing information for the requested agent AND if positive the patient has begun therapy for latent TB; AND
11. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
12. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval:
Crohn’s disease and ulcerative colitis induction (IV): 60 days (one-time approval)
Crohn’s disease and ulcerative colitis maintenance (SC): 365 days (1 year)
All other indications: 365 days (1 year)

Quantity Limit Exception Criteria:

1. The quantity (dose) requested is for documented titration purposes at the initiation of therapy (authorization for a 90 day titration period); AND 
2. The prescribed dose cannot be achieved using a lesser quantity of a higher strength; AND 
3. The quantity (dose) requested does not exceed the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert; OR 
4. If the quantity (dose) requested exceeds the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert, then the prescriber must submit documentation in support of therapy with a higher dose for the intended diagnosis (submitted documentation may include medical records OR fax form which reflects medical record documentation that shows the length of time the requested dose has been used, and what other medications and doses have been tried and failed).

*Site of Care Medical Necessity Criteria

1. For requests for injection or infusion administration in an inpatient setting, the injection or infusion may be given if the above medical necessity criteria are met AND the inpatient admission is NOT for the sole purpose of administering the injection or infusion; OR 
2. For requests for injection or infusion administration in an outpatient hospital setting, the injection or infusion may be given if the above medical necessity criteria are met AND ONE of the following must be met: 
   1. History of mild adverse events that have not been successfully managed through mild pre-medication (e.g., diphenhydramine, acetaminophen, steroids, fluids, etc.); OR 
   2. Inability to physically and cognitively adhere to the treatment schedule and regimen complexity; OR 
   3. New to therapy, defined as initial injection or infusion OR less than 3 months since initial injection or infusion; OR 
   4. Re-initiation of therapy, defined as ONE of the following: 
      1. First injection or infusion after 6 months of no injections or infusions for drugs with an approved dosing interval less than 6 months duration; OR 
      2. First injection or infusion after at least a 1-month gap in therapy outside of the approved dosing interval for drugs requiring every 6 months dosing duration; OR 
   5. Requirement of a change in the requested restricted product formulation; AND 
3. If the Site of Care Medical Necessity Criteria in #1 or #2 above are not met, the injection or infusion will be administered in a home-based infusion or physician office setting with or without supervision by a certified healthcare professional.

References:

All information referenced is from FDA package insert unless otherwise noted below.

Policy Implementation/Update Information:

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q1 annually.

March 2025v2: Criteria change: Added new to market ustekinumab biosimilar Otulfi (ustekinumab-aauz) to policy for the same FDA approved indications as Stelara and with the same coverage criteria requirements. For Otulfi, added additional corresponding criteria as a non-preferred ustekinumab biosimilar product with requirement of trial and failure of Stelara; and requirement of trial and failure of two of the following agents FDA approved for the requested indication: an adalimumab product, Cosentyx, Enbrel, Entyvio, Skyrizi, Tremfya, Otezla, Sotyktu, Rinvoq, Xeljanz/Xeljanz XR. Added Otulfi to SOC criteria and added associated dosing, maximum units, and HCPCS code Q9999 (effective 4/1/2025) to FDA label reference table.

March 2025: Criteria change: Added new to market ustekinumab biosimilar Selarsdi (ustekinumab-aekn) to policy for the same FDA approved indications as Stelara and with the same coverage criteria requirements. For Selarsdi, added additional corresponding criteria as a non-preferred ustekinumab biosimilar product with requirement of trial and failure of Stelara; and requirement of trial and failure of two of the following agents FDA approved for the requested indication: an adalimumab product, Cosentyx, Enbrel, Entyvio, Skyrizi, Tremfya, Otezla, Sotyktu, Rinvoq, Xeljanz/Xeljanz XR. Added Selarsdi to SOC criteria and added associated dosing, maximum units, and HCPCS code Q9998 to FDA label reference table.

February 2025v2: Criteria change: Added new to market ustekinumab biosimilar Pyzchiva (ustekinumab-ttwe) to policy for the same FDA approved indications as Stelara and with the same coverage criteria requirements. For Pyzchiva, added additional corresponding criteria as a non-preferred ustekinumab biosimilar product with requirement of trial and failure of Stelara; and requirement of trial and failure of two of the following agents FDA approved for the requested indication: an adalimumab product, Cosentyx, Enbrel, Entyvio, Skyrizi, Tremfya, Otezla, Sotyktu, Rinvoq, Xeljanz/Xeljanz XR. Added Pyzchiva to SOC criteria and added associated dosing, maximum units, and HCPCS codes Q9996 (SC) and Q9997 (IV) to FDA label reference table.

February 2025: Criteria change: Added new to market ustekinumab biosimilars Steqeyma (ustekinumab-stba) and Yesintek (ustekinumab-kfce) to policy for the same FDA approved indications as Stelara and with the same coverage criteria requirements. For Steqeyma and Yesintek, added additional corresponding criteria as a non-preferred ustekinumab biosimilar product with requirement of trial and failure of Stelara; and requirement of trial and failure of two of the following agents FDA approved for the requested indication: an adalimumab product, Cosentyx, Enbrel, Entyvio, Skyrizi, Tremfya, Otezla, Sotyktu, Rinvoq, Xeljanz/Xeljanz XR. Added Steqeyma and Yesintek to SOC criteria and added associated dosing, maximum units, and HCPCS codes C9399, J3490, J3590 for each product to FDA label reference table.

January 2025: Criteria change: Added new to market ustekinumab biosimilar Wezlana (ustekinumab-auub) to policy for the same FDA approved indications as Stelara and with the same coverage criteria requirements. For Wezlana, added additional corresponding criteria as a non-preferred ustekinumab biosimilar product with requirement of trial and failure of Stelara; and requirement of trial and failure of two of the following agents FDA approved for the requested indication: an adalimumab product, Cosentyx, Enbrel, Entyvio, Skyrizi, Tremfya, Otezla, Sotyktu, Rinvoq, Xeljanz/Xeljanz XR. Added Wezlana to SOC criteria and added associated dosing, maximum units, and HCPCS codes Q5137 (SC) and Q5138 (IV) for Wezlana to FDA label reference table. Changed policy name to “Ustekinumab (Stelara®) and Ustekinumab Biosimilars” from “Ustekinumab (Stelara®)”.

January 2024: Criteria update: Updated criteria related to specific dosing for Crohn’s disease and ulcerative colitis indications to state “patient will be treated with the 90 mg injection” for clarity.

September 2023: Criteria change: For psoriatic arthritis: Removed hydroxychloroquine from list of conventional agents. For Crohn’s disease: Removed aminosalicylates, mesalamine, and sulfasalazine from list of conventional agents. For ulcerative colitis: Updated policy to allow bypassing conventional agents for severely active ulcerative colitis; removed steroid suppositories from list of conventional agents. Separated out intolerance/hypersensitivity criteria from FDA labeled contraindication criteria for clarity. Added Zeposia as agent not to be used in combination with another biologic immunomodulator agent for clarity.

January 2023: Criteria change: Expanded psoriatic arthritis indication to patients 6 years and older, updated corresponding dosage in dosing reference table.

October 2021: Criteria change: Added Site of Care medical necessity criteria. Policy notification given 8/2/2021 for effective date 10/1/2021.

August 2021: Criteria change: Removed criteria points regarding medication history indicating use of another biologic immunomodulator agent FDA labeled for the treatment of the same condition. Policy notification given 6/1/2021 for effective date 8/1/2021.

June 2021: Criteria change: Medical record documentation required for all indications.

April 2021: Criteria change: Addition of criteria for history of use of another biologic immunomodulator agent (or Otezla) for the same indication; PS: BSA requirement changed to 10%, added option for concomitant severe PsA; PsA: added requirement for trial of one conventional agent, added option for severe active PsA or concomitant severe psoriasis; added requirements to be prescribed by or in consultation with a specialist, that patient has no FDA labeled contraindications, and for TB testing; added maximum units; medical policy formatting change. Policy notification given 2/26/2021 for effective date 4/28/2021.

*Further historical criteria changes and updates available upon request from Medical Policy and/or Corporate Pharmacy.