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Ustekinumab is a recombinant, human monoclonal antibody directed against IL-12 and IL-23, both proinflammatory cytokines. Ustekinumab binds to a protein subunit used by both the IL-12 and IL-23 cytokines and inhibits their interaction with receptors, thereby suppressing inflammation and immune cell activation. Ustekinumab is administered by subcutaneous injection or intravenous infusion.

The U.S. Food and Drug Administration (FDA) has approved ustekinumab (Stelara®) for the following indications:

• Psoriasis
  • Treatment of patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
• Psoriatic Arthritis
  • Treatment of adults with active psoriatic arthritis. Ustekinumab can be used alone or in combination with methotrexate.
• Crohn’s Disease
  • Treatment of adults with moderately to severely active Crohn’s disease.
• Ulcerative Colitis 
  • Treatment of adults with moderately to severely active ulcerative colitis. 

Serious adverse reactions have occurred in patients receiving ustekinumab, including serious infections and malignancy. Concurrent administration of ustekinumab with other immunosuppressive agents or phototherapy has not been well-studied in patients with psoriasis.

NOTE: When ustekinumab (Stelara®) will be self-administered by subcutaneous injection, please refer to applicable pharmacy benefit plan.

I.   Initial Review for Ustekinumab (Stelara®)

Ustekinumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Diagnosis of ONE of the following:
  • Moderate to severe plaque psoriasis in a patient 6 years of age or older AND ONE of the following:
    • Previously failed another biologic therapy with FDA approval for the same indication; or
    • Used one conventional agent prerequisite for the indication (see table 2 below); or
    • Documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL conventional agents for the indication; or
    • First line treatment for severe plaque psoriasis (e.g., greater than 10% body surface area involvement, occurring on select locations [i.e., hands, feet, scalp, face, or genitals], intractable pruritis); or
    • First line treatment for moderate to severe plaque psoriasis with concomitant severe active psoriatic arthritis (e.g., erosive disease, elevated markers of inflammation [e.g., ESR, CRP] attributable to psoriatic arthritis, long term damage that interferes with function [i.e., joint deformities], rapid progressive); OR
  • Active psoriatic arthritis in a patient 18 years of age or older AND ONE of the following:
    • Previously failed another biologic therapy with FDA approval for the same indication; or 
    • Used one conventional agent prerequisite for the indication (see table 2 below); or
    • Documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL conventional agents for the indication; or
    • First line treatment for severe active psoriatic arthritis (e.g., erosive disease, elevated markers of inflammation [e.g., ESR, CRP] attributable to psoriatic arthritis, long term damage that interferes with function [i.e., joint deformities], rapid progressive); or
    • First line treatment for active psoriatic arthritis with concomitant severe plaque psoriasis (e.g., greater than 10% body surface area involvement, occurring on select locations [i.e., hands, feet, scalp, face, or genitals], intractable pruritis); OR
  • Moderately to severely active Crohn’s disease in a patient 18 years of age or older AND ONE of the following:
    • Previously failed another biologic therapy with FDA approval for the same indication; or
    • Used one conventional agent prerequisite for the indication (see table 2 below); or
    • Documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL conventional agents for the indication; OR
  • Moderately to severely active ulcerative colitis in a patient 18 years of age or older AND ONE of the following: 
    • Previously failed another biologic therapy with FDA approval for the same indication; or 
    • Used one conventional agent prerequisite for the indication (see table 2 below); or 
    • Documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL conventional agents for the indication; 
• AND
• No FDA labeled contraindications to ustekinumab (see table 1 below); AND
• Not currently being treated with another biologic therapy; AND
• For patients not currently receiving ustekinumab, the patient has been screened for latent tuberculosis (TB) and started on TB therapy if the patient tests positive; AND
• Requested dose is within the FDA labeled dose for the labeled indications (see table 3 below); AND
• For commercial health plan members only, ustekinumab is administered in accordance with site of service criteria (see policy XI-06); AND
• For commercial health plan members only, step therapy supplement criteria may apply for select conditions (see policy II-242: Step Therapy Supplement).
  

II.  Renewal Review for Ustekinumab (Stelara®)

Ustekinumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Previously approved for ustekinumab through the initial review process; AND
• Demonstrated positive clinical response to ustekinumab therapy (e.g., stabilization and/or slowing of disease progression, or decrease in symptom severity and/or frequency); AND
• No FDA labeled contraindications to ustekinumab (see table 1 below); AND
• Not currently being treated with another biologic therapy; AND
• Requested dose is within the FDA labeled dose for the labeled indications (see table 3 below); AND
• For commercial health plan members only, ustekinumab is administered in accordance with site of service criteria (see policy XI-06).

III.  Experimental/Investigative Uses

All other uses of ustekinumab are considered EXPERIMENTAL/INVESTIGATIVE due to the lack of clinical evidence demonstrating an impact on improved health outcomes.

Table 1.  FDA Labeled Contraindications

Table 2.  Conventional Agent Prerequisites

Table 3.  Dosing

NOTE:  See documentation submission requirements below if the requested dose is higher or more frequent than the dosing criteria provided in this table.

IV (intravenous), SC (subcutaneous)

Documentation Submission:

Documentation supporting the medical necessity criteria described in the policy must be included in the prior authorization, when prior authorization is required. In addition, the following documentation must also be submitted:

Initial Review

1. Clinical notes describing the diagnosis and clinical features of the diagnosis.
2. For patients not currently receiving the ustekinumab, laboratory results for latent tuberculosis (TB) screening. If the test was positive, describe follow-up therapy.
3. Clinical notes describing current and past medications for the diagnosis, including response to the medications.
4. The dose being requested, including the patient’s weight if the diagnosis requires weight-based dosing. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
5. For commercial health plan members only, the site of service for ustekinumab administration is specified, including CMS place of service code (see policy XI-06). If ustekinumab is administered in a hospital outpatient facility, a clear explanation for the medical necessity of the site of service MUST be submitted, including documentation for one or more of the site of service criteria provided in policy XI-06.
6. For commercial health plan members only, when step therapy requirements apply for the requested indication, documentation for one or more of the step therapy supplement criteria MUST be provided (see policy II-242).
   

Renewal Review  

1. Documentation of prior approval for ustekinumab through the initial review process.
2. Documentation supporting positive clinical response with ustekinumab therapy (e.g., slowing of disease progression or decrease in symptom severity and/or frequency).
3. Clinical notes describing current and past medications for the diagnosis, including response to the medications.
4. The dose being requested, including the patient’s weight if the diagnosis requires weight-based dosing. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
5. For commercial health plan members only, the site of service for ustekinumab administration is specified, including CMS place of service code (see policy XI-06).  If ustekinumab is administered in a hospital outpatient facility, a clear explanation for the medical necessity of the site of service MUST be submitted, including documentation for one or more of the site of service criteria provided in policy XI-06.