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Date Printed: December 18, 2017: 11:28 AM

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09-J1000-16

Original Effective Date: 02/15/10

Reviewed: 09/13/17

Revised: 10/15/17

Subject: Ustekinumab (Stelara®)

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Ustekinumab (Stelara), an interleukin (IL)-12 and IL-23 antagonist, was first approved by the US Food and Drug Administration (FDA) in September 2009 for the treatment of adults with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, and then for the treatment of active psoriatic arthritis (PsA) in September 2013. In September 2016 ustekinumab received an additional approval for the treatment of adult patients with moderately to severely active Crohn’s disease (CD) who have: (1) failed or were intolerant to treatment with immunomodulators or corticosteroids, but never failed a tumor necrosis factor (TNF) blocker, or (2) failed or were intolerant to treatment with one or more TNF blockers. Unlike for treatment of psoriasis and PsA, treatment of CD requires a single, initial weight-based IV loading dose. Ustekinumab (as sponsored by the innovator drug company) has been granted orphan drug designation by the FDA for “treatment of type 1 diabetes mellitus patients with residual beta-cell function” in November 2010, for “treatment of pediatric Crohn's disease (0 through 16 years of age)” in May 2016, for “treatment of pediatric ulcerative colitis” in February 2017, and for “treatment of pediatric systemic lupus erythematosus” in July 2017.

Psoriasis is a chronic, inflammatory disease that affects approximately 3% of the adult US population. Approximately 80% of patients with psoriasis have limited disease, and, for the majority of these patients, topical treatments are safe, effective, and convenient. However, some patients require systemic treatment. Without appropriate treatment, patients may experience substantial disease burden and decreased quality of life. The American Academy of Dermatology (AAD) guidelines state that methotrexate is a logical first choice of systemic agent, because it is the most cost-effective systemic psoriasis agent with the longest safety follow-up data. Cyclosporine is cited as particularly useful in the treatment of significant flares of psoriasis unresponsive to other therapies. Intermittent, short-term therapy (12 to 16 weeks) is the most frequently recommended regimen, with treatment withdrawn once significant improvement is achieved. When relapse occurs, cyclosporine therapy is reinstituted at the previously established effective dose, or maintenance therapy for up to 1 year can be used. Acitretin is also mentioned as an important oral option, despite is being normally less effective than other traditional systemic agents, due to its lack of immunosuppression and value in patients with known infection, active malignancy, or HIV. The use of biologic agents (TNF inhibitors and ustekinumab) is discussed as very effective treatment that can be used for patients with extensive disease. Newer biologic agents are not yet addressed in the AAD guidelines. While methotrexate must be avoided in women who are pregnant or trying to become pregnant, cyclosporine and anti-TNF biologics are considered to be low-risk options during pregnancy if systemic therapy cannot be avoided. While not a first-line agent for psoriasis, sulfasalazine has adequate data supporting safe use (pregnancy Category B), and is consider a preferred DMARD if given with folic acid when systemic treatment is clinically necessary.

Ustekinumab’s approval for Crohn’s disease was based on the results of three randomized, double-blind, placebo-controlled trials in patients with moderately to severely active Crohn’s disease (Crohn’s Disease Activity Index [CDAI] score of 220 to 450). There were two 8-week IV induction studies (CD-1 and CD-2) followed by a 44-week subcutaneous randomized withdrawal maintenance study (CD-3) representing 52 weeks of therapy. In the CD-3 maintenance study the following results were obtained.

Table 1

 

Placebo

(n = 131)

Stelara 90 mg q8 weeks

(n = 128)

Treatment difference

(95% CI)

Clinical Remission

47 (36%)

68 (53%)

17%

(5%, 29%)

Clinical Response

58 (44%)

76 (59%)

15%

(3%, 27%)

Clinical Remission in patients in remission at the start of maintenance therapy

36/79 (46%)

52/78 (67%)

21%

(6%, 36%)

Ustekinumab’s approval for plaque psoriasis was based on the results of two multicenter, randomized, double-blind, placebo-controlled phase III trials (PHOENIX 1 and PHOENIX 2). Subjects were randomized to receive ustekinumab 45 mg, ustekinumab 90 mg, or placebo every 12 weeks with crossover to ustekinumab at week 12. The primary efficacy endpoint was the proportion of subjects achieving 75% reduction in Psoriasis Area and Severity Index (PASI 75) and Physician Global Assessment (PGA) of "cleared or minimal" at week 12. In PHOENIX 1, 67% of patients achieved a PASI 75 response and 59% achieved a PGA of "cleared or minimal" in the 45 mg ustekinumab group; similar rates of response were seen in the 90 mg ustekinumab group (66% achieved a PASI 75 response and 61% achieved a PGA of "cleared or minimal"). The results were similar in PHOENIX 2: 67% achieved a PASI 75 and 76% a desired PGA score in the 45 mg group, and 68% in PASI 75 and 73% a PGA score in the 90 mg group.

Based on the manufacturer’s labeling, the recommended dose of ustekinumab is weight-based. A study by Lebwohl et al, analyzed data pooled from PHOENIX 1 and 2 to assess the impact of body weight on the efficacy, safety, and pharmacokinetics of ustekinumab. This analysis was based on previous analyses that have suggested that adjusting the dose of biologic agents based on weight may be useful in achieving optimal drug concentrations associated with efficacy, and may prevent excessive drug exposure in lighter weight patients. The differences in PASI 75 response rates between the 45 mg and 90 mg doses were calculated for each 10 kg weight category across studies. In the clinical response evaluation, PASI 75 response rates were similar among subjects receiving 45 mg or 90 mg dose in subpopulations weighing 100 kg or less: 76.9% vs. 80.8% (P = 0.1823). However, in subgroups weighing more than 100 kg, PASI 75 response rates were approximately 20% higher in subjects receiving 90 mg when compared those receiving 45 mg (74.2% vs. 54.6%, p < 0.0001). While PASI 75 response rates were higher in patients >100 kg receiving a 90 mg dosage, the majority of patients (55%) were still able to achieve a PASI 75 with a 45 mg dosage. In addition, over one-quarter (28%) of patients >100 kg were able to achieve a PASI 90 with a 45 mg dosage. This indicates that a starting dose of 45 mg, regardless of weight, is adequate for many patients, and more cost-effective than a 90 mg starting dose. Patients >100 kg with an inadequate response can be increased to a dose of 90 mg.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the subcutaneous formulations of the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) of the subcutaneus formulations in certain provider-administered setting such as an outpatient hospital, ambulatory surgical suite, or emergency facility is not considered medically necessary.

 

Certificate of Medical Necessity

Submit a completed Certificate of Medical Necessity (CMN) along with your request to expedite the medical review process.

1. Click the link Ustekinumab (Stelara®) - Certificate of Medical Necessity (MS Word) to open the form.

2. Complete all fields on the form thoroughly.

3. Print and submit a copy of the form with your request.

Note: Florida Blue regularly updates CMNs. Ensure you are using the most current copy of a CMN before submitting to Florida Blue. For a complete list of available CMNs, visit the Certificates of Medical Necessity page.

NOTE: Adalimumab (Humira), etanercept (Enbrel), golimumab (Simponi), and ustekinumab (Stelara) are the preferred self-administered biologic products

NOTE: If the member has had an inadequate response to previous biologic therapy, other than ustekinumab, that is FDA-approved for the requested indication listed in Table 2 or 3, the member is not required to have had an inadequate response to non-biologic prerequisite therapy (e.g., for psoriasis, if member has previously had an inadequate response to etanercept, but does not have a history of inadequate response to methotrexate, they do not have to try methotrexate to meet medical necessity criteria)

Initiation of intravenous ustekinumab (Stelara) meets the definition of medical necessity when ALL of the following criteria are met (“1”, “2”, and “3”):

1. Ustekinumab will be used for the treatment of an indication listed in Table 2 and ALL of the indication-specific and maximum-allowable dose criteria are met

2. Member has not received a previous dose of ustekinumab (IV or SC) in the past 12 months

3. Ustekinumab will NOT be used in combination with any of the following:

a. abatacept (Orencia)

b. adalimumab (Humira)

c. anakinra (Kineret)

d. apremilast (Otezla)

e. brodalumab (Siliq)

f. certolizumab (Cimzia)

g. etanercept (Enbrel)

h. golimumab (Simponi, Simponi Aria)

i. guselkumab (Tremfya)

j. infliximab products (Remicade, Inflectra, Renflexis)

k. ixekizumab (Taltz)

l. sarilumab (Kevzara)

m. tocilizumab (Actemra)

n. tofacitinib (Xeljanz, Xeljanz XR)

o. ustekinumab (Stelara)

p. vedolizumab (Entyvio)

Table 2

Indication

Criteria

Max Allowable Dosage

Crohn’s disease (CD)

[FDA-approved indication for adults; orphan indication for pediatrics]

When ALL of the following are met (“1”, “2”, and “3”):

1. Member is 18 years of age or older

2. Member has a diagnosis of moderately to severely active CD [e.g., Crohn’s Disease Activity Index (CDAI) greater than 220 points]

3. Member has had an inadequate response to at least ONE or has contraindications to ALL of the following treatments* (the specific contraindication(s) must be provided):

a. azathioprine

b. mercaptopurine (6-MP)

c. methotrexate

d. systemic corticosteroid (e.g. oral prednisone, IV methylprednisolone)

≤55 kg: 260 mg (two 130 mg vials) X 1 dose

>55 to 85 kg: 390 mg (three 130 mg vials) X 1 dose

>85 kg: 520 mg (four 130 mg vials) X 1 dose

Orphan Indications (non-FDA approved)

Pediatric systemic lupus erythematosus (SLE)

When ALL of the following are met (“1”, “2”, and “3”):

1. Member is less than 18 years of age

2. Member has moderate-to-severe, refractory disease

3. Member has had an inadequate response to a combination of hydroxychloroquine and a corticosteroid

≤55 kg: 260 mg (two 130 mg vials) X 1 dose

>55 to 85 kg: 390 mg (three 130 mg vials) X 1 dose

>85 kg: 520 mg (four 130 mg vials) X 1 dose

Pediatric ulcerative colitis (UC)

When ALL of the following are met (“1”, “2”, “3”, and “4”):

1. Member is less than 18 years of age

2. Member’s disease is moderately to severely active

3. EITHER of the following* (“a” or “b”):

a. Member has had an inadequate response to, or has a contraindication to systemic corticosteroid therapy (the specific contraindication must be provided)

b. Member is dependent on systemic corticosteroids [i.e., unable to successfully taper corticosteroids to less than 10 mg of prednisone (or equivalent) within 3 months of initiation without return of symptoms]

4. Member has had an inadequate response to ANY, or has a contraindication to ALL of the following* (the specific contraindications must be provided):

a. Oral aminosalicylates (i.e., sulfasalazine, olsalazine, mesalamine, or balsalazide)

b. Topical aminosalicylates (e.g., enema or suppository)

c. Thiopurine therapy (e.g., azathioprine or 6-mercaptopurine [6-MP])

≤55 kg: 260 mg (two 130 mg vials) X 1 dose

>55 to 85 kg: 390 mg (three 130 mg vials) X 1 dose

>85 kg: 520 mg (four 130 mg vials) X 1 dose

Approval duration: Single IV dose

*NOTE: If the member has had an inadequate response to previous biologic therapy, other than ustekinumab, that is FDA-approved for the requested indication listed in Table 2, the member is not required to have had an inadequate response to non-biologic prerequisite therapy (e.g., for psoriasis, if member has previously had an inadequate response to etanercept, but does not have a history of inadequate response to methotrexate, they do not have to try methotrexate to meet medical necessity criteria)

Initiation of subcutaneous ustekinumab (Stelara) meets the definition of medical necessity when ALL of the following criteria are met (“1” and “2”):

1. Ustekinumab will be used for the treatment of an indication listed in Table 3 and ALL of the indication-specific and maximum-allowable dose criteria are met

2. Ustekinumab will NOT be used concomitantly with any of the following:

a. abatacept (Orencia)

b. adalimumab (Humira)

c. anakinra (Kineret)

d. apremilast (Otezla)

e. brodalumab (Siliq)

f. certolizumab (Cimzia)

g. etanercept (Enbrel)

h. golimumab (Simponi, Simponi Aria)

i. guselkumab (Tremfya)

j. infliximab products (Remicade, Inflectra, Renflexis)

k. ixekizumab (Taltz)

l. sarilumab (Kevzara)

m. tocilizumab (Actemra)

n. tofacitinib (Xeljanz, Xeljanz XR)

o. ustekinumab (Stelara)

p. vedolizumab (Entyvio)

Table 3

Indications and Specific Criteria

Indication

Criteria

Max Allowable Dosage

Crohn’s disease (CD)

[FDA-approved indication for adults; orphan indication for pediatrics]

When ALL of the following are met (“1”, “2”, and “3”):

1. Member is 18 years of age or older

2. Member has a diagnosis of moderately to severely active CD [e.g., Crohn’s Disease Activity Index (CDAI) greater than 220 points]

3. Member has had an inadequate response to at least ONE or has contraindications to ALL of the following treatments* (the specific contraindication(s) must be provided):

a. azathioprine

b. mercaptopurine (6-MP)

c. methotrexate

d. systemic corticosteroid (e.g. oral prednisone, IV methylprednisolone)

• 90 mg given 8 weeks after the initial IV dose, then every 8 weeks thereafter (i.e., week 8, week 16, week 24, etc.).The dose to be given on week 32 requires reauthorization.

Psoriatic arthritis (PsA)

[including both axial and non-axial (peripheral) PsA]

When ALL of the following are met (“1”, “2”, and “3”):

1. Member is 18 years of age or older

2. Member’s disease is active (i.e., persistent joint inflammation)

3. EITHER of the following based on the dominate disease type (“a” or “b”):

a. Axial PsA: Member has had an inadequate response to, or has a contraindication to at least TWO different NSAID therapies taken continuously for at least 4 weeks each* (e.g., celecoxib, diclofenac, ibuprofen, meloxicam, naproxen) (the specific contraindications must be provided)

b. Peripheral PsA: Member has had an inadequate response to, or has a contraindication to at least ONE NSAID therapy taken continuously for at least 4 weeks* (e.g., celecoxib, diclofenac, ibuprofen, meloxicam, naproxen) (the specific contraindication must be provided)

AND

Member has had an inadequate response to, or has a contraindication to methotrexate, OR, if methotrexate is contraindicated, to another csDMARD* (e.g., cyclosporine, leflunomide, sulfasalazine) (the specific contraindication must be provided)

• 45 mg every 4 weeks for 2 doses (weeks 0 and 4) during the first 12 weeks of treatment. The dose to be given on week 16 requires reauthorization.

• Exception: members with co-existent moderate-to-severe plaque psoriasis weighing >100 kg (220 lbs.) may receive the 90 mg dose every 4 weeks for 2 doses (weeks 0 and 4) during the first 12 weeks of treatment.

Plaque psoriasis

When ALL of the following are met (“1”, “2”, and “3”):

1. Member is 18 years of age or older

2. Member’s disease is moderate to severe as evidenced by EITHER of the following before or after systemic drug therapy (‘a” or “b”):

a. Psoriasis covers 10% or more of member’s BSA

b. Psoriasis covers less than 10% of member’s BSA, but affects crucial body areas necessary for daily living activities (i.e., face, palms of hands, soles of feet, or genitals)

3. EITHER of the following* (“a” or “b”):

a. Member has had an inadequate response to at least 3 months of continuous treatment with methotrexate, or has a contraindication to methotrexate

b. If methotrexate is contraindicated, the member has had an inadequate response to at least 3 months of continuous treatment with EITHER cyclosporine or acitretin, or has a contraindication to BOTH cyclosporine and acitretin (the specific contraindications must be provided; pregnancy is not considered a contraindication to the use of cyclosporine)

• 45 mg every 4 weeks for 2 doses (weeks 0 and 4) during the first 12 weeks of treatment. The dose to be given on week 16 requires reauthorization.

• Exception: members with co-existent psoriatic arthritis weighing >100 kg (220 lbs.) may receive the 90 mg dose every 4 weeks for 2 doses (weeks 0 and 4) during the first 12 weeks of treatment.

Orphan Indications (non-FDA approved)

Pediatric systemic lupus erythematosus (SLE)

When ALL of the following are met (“1”, “2”, and “3”):

1. Member is less than 18 years of age

2. Member has moderate-to-severe, refractory disease

3. Member has had an inadequate response to a combination of hydroxychloroquine and a corticosteroid

90 mg given 8 weeks after the initial IV dose, then every 8 weeks thereafter (i.e., week 8, week 16, week 24, etc.). The dose to be given on week 32 requires reauthorization.

Pediatric ulcerative colitis (UC)

When ALL of the following are met (“1”, “2”, “3”, and “4”):

1. Member is less than 18 years of age

2. Member’s disease is moderately to severely active

3. EITHER of the following* (“a” or “b”):

a. Member has had an inadequate response to, or has a contraindication to systemic corticosteroid therapy (the specific contraindication must be provided)

b. Member is dependent on systemic corticosteroids [i.e., unable to successfully taper corticosteroids to less than 10 mg of prednisone (or equivalent) within 3 months of initiation without return of symptoms]

4. Member has had an inadequate response to ANY, or has a contraindication to ALL of the following* (the specific contraindications must be provided):

a. Oral aminosalicylates (i.e., sulfasalazine, olsalazine, mesalamine, or balsalazide)

b. Topical aminosalicylates (e.g., enema or suppository)

c. Thiopurine therapy (e.g., azathioprine or 6-mercaptopurine [6-MP])

90 mg given 8 weeks after the initial IV dose, then every 8 weeks thereafter (i.e., week 8, week 16, week 24, etc.). The dose to be given on week 32 requires reauthorization.

Type 1 diabetes mellitus in patients with residual beta-cell function

Member has a confirmed diagnosis

90 mg at week 0 and week 4, then 90 mg every 12 weeks starting on week 16

Approval duration:

Crohn’s disease, pediatric SLE, and pediatric UC: 24 weeks (to allow three SC doses after the initial IV loading dose)

Type 1 diabetes mellitus: 6 months

Other indications: 12 weeks

NSAID, non-steroidal anti-inflammatory drug

*NOTE: If the member has had an inadequate response to previous biologic therapy, other than ustekinumab, that is FDA-approved for the requested indication listed in Table 3, the member is not required to have had an inadequate response to non-biologic prerequisite therapy (e.g., for psoriasis, if member has previously had an inadequate response to etanercept, but does not have a history of inadequate response to methotrexate, they do not have to try methotrexate to meet medical necessity criteria).

Continuation of subcutaneous ustekinumab meets the definition of medical necessity when ALL of the following criteria are met (“1”,”2”,”3” and “4”):

1. An authorization or reauthorization for ustekinumab has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of a condition listed in Table 3, OR the member previously met ALL indication-specific initiation criteria.

2. EITHER of the following (“a” or “b”):

a. Member has demonstrated a beneficial response to therapy for the treatment of moderate to severe Crohn’s disease, moderate to severe plaque psoriasis or active psoriatic arthritis, pediatric SLE, pediatric UC, or DM1 in patients with residual beta-cell function.

b. ALL of the following (applicable to the psoriasis and psoriatic arthritis indications ONLY):

i. Member’s weight is >100 kg

ii. Member is currently receiving a dose of 45 mg

iii. Member had an inadequate treatment response after the first 90 days

iv. Member’s dose will be increased to 90 mg

3. Ustekinumab is NOT administered concomitantly with ANY of the following:

a. abatacept (Orencia)

b. adalimumab (Humira)

c. anakinra (Kineret)

d. apremilast (Otezla)

e. brodalumab (Siliq)

f. certolizumab (Cimzia)

g. etanercept (Enbrel)

h. golimumab (Simponi, Simponi Aria)

i. guselkumab (Tremfya)

j. infliximab products (Remicade, Inflectra, Renflexis)

k. ixekizumab (Taltz)

l. sarilumab (Kevzara)

m. secukinumab (Cosentyx)

n. tocilizumab (Actemra)

o. tofacitinib (Xeljanz, Xeljanz XR)

p. vedolizumab (Entyvio)

4. The member’s dosage of ustekinumab does not exceed ANY of the following:

a. Crohn’s disease, type 1 DM, pediatric UC, and pediatric SLE

i. 90 mg every 8 weeks (regardless of weight)

b. Psoriatic arthritis

i. Members without co-existent moderate to severe plaque psoriasis (independent of weight): 45 mg every 12 weeks starting 12 weeks after the previous dose

ii. Members with co-existent moderate to severe plaque psoriasis and less than or equal to 100 kg: 45 mg every 12 weeks starting 12 weeks after the previous dose

iii. Members with co-existent moderate to severe plaque psoriasis and greater than 100 kg: 90 mg every 12 weeks starting 12 weeks after the previous dose, AND the member previously had an inadequate response to an initial dose of 45 mg*

c. Plaque psoriasis

i. Members greater than 100 kg: 90 mg every 12 weeks starting 12 weeks after the previous dose, AND the member previously had an inadequate response to an initial dose of 45 mg*

ii. Members less than or equal to 100 kg: 45 mg every 12 weeks starting 12 weeks after the previous dose

*Members who have been previously approved for a dose of 90 mg are NOT required to have tried a 45 mg dose.

Approval duration: 1 year

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved: ustekinumab is indicated for: (1) the treatment of adults with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, for the treatment of adults with active psoriatic arthritis, alone or in combination with methotrexate, and for the treatment of adult patients with moderately to severely active Crohn’s disease who have: (a) failed or were intolerant to treatment with immunomodulators or corticosteroids, but never failed treatment with a tumor necrosis factor (TNF) blocker or (b) failed or were intolerant to treatment with one or more TNF blockers . The recommended dose is based on weight for the treatment of plaque psoriasis:

• 100 kg or less: 45 mg every 4 weeks at weeks 0 and 4, followed by 45 mg every 12 weeks beginning at week 16.

• Greater than 100 kg: 90 mg every 4 weeks at weeks 0 and 4, followed by 90 mg every 12 weeks beginning at week 16.

The recommended dose for the treatment of active psoriatic arthritis is 45 mg every 4 weeks at weeks 0 and 4, followed by 45 mg every 12 weeks beginning at week 16. In persons with co-existent moderate to severe plaque psoriasis who weight greater than 100 kg, the recommended dose is 90 mg every 4 weeks at weeks 0 and 4, followed by 90 mg every 12 weeks beginning at week 16.

The recommended dosage for the treatment of Crohn’s disease is weight-based for the initial IV loading dose but then a fixed maintenance dosage. The loading dose is: ≤55 kg: 260 mg (two 130 mg vials) X 1 dose; >55 to 85 kg: 390 mg (three 130 mg vials) X 1 dose; >85 kg: 520 mg (four 130 mg vials) X 1 dose (on week 0) given as an IV infusion in 250 mL (using normal saline) over at least one hour. The maintenance dose is 90 mg given as a subcutaneous injection 8 weeks after the initial IV dose (week 8), then every 8 weeks thereafter.

Ustekinumab should be administered as a subcutaneous injection with the exception of the initial IV infusion loading dose for Crohn’s disease. Although initially approved only for administration by a healthcare professional, ustekinumab was approved for subcutaneous self-administration in June 2013.

Drug availability: ustekinumab is supplied in the following dosage forms and strengths

• Single-dose prefilled syringe: 45 mg/0.5 mL, 90 mg/1 mL (both for SQ use)

• Single-dose vial: 45 mg/0.5 mL (for SQ use), 130 mg/26 mL (5 mg/mL) (for IV infusion)

PRECAUTIONS:

Contraindication: ustekinumab is contraindicated in persons with clinically significant hypersensitivity to ustekinumab or any of the excipients.

Warnings

• Infections: Serious infections have occurred. Do not start ustekinumab during any clinically important active infection. If a serious infection develops, discontinue therapy until the infection resolves.

• Theoretical Risk for Particular Infections: Serious infections from mycobacteria, salmonella and Bacillus Calmette-Guerin (BCG) vaccinations have been reported in persons genetically deficient in IL-12/IL-23. Diagnostic tests for these infections should be considered as dictated by clinical circumstances.

• Tuberculosis (TB): Evaluate individuals for TB prior to initiating treatment with ustekinumab. Initiate treatment of latent TB before administering ustekinumab

• Malignancies: ustekinumab may increase risk of malignancy. The safety of ustekinumab in persons with a history of or a known malignancy has not been evaluated.

• Anaphylaxis or other clinically significant hypersensitivity reactions may occur.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): One case was reported. If suspected, treat promptly and discontinue ustekinumab.

• Immunization: do not administer live vaccines with ustekinumab.

• Reversible Posterior Leukoencephalopathy Syndrome (RPLS): One case was reported. If suspected, treat promptly and discontinue ustekinumab.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

J3357

Ustekinumab, for subcutaneous injection, 1 mg

Q9989

Ustekinumab, for intravenous injection, 1 mg

ICD-10 Diagnosis Codes That Support Medical Necessity of Intravenous Injection (Q9989):

K50.00 – K50.919

Crohn’s disease [regional enteritis]

K51.00 – K51.919

Ulcerative colitis

M32.0 – M32.9

Systemic lupus erythematosus (SLE)

ICD-10 Diagnosis Codes That Support Medical Necessity of Subcutaneous Injection (J3357):

E10.10 - E10.9

Type 1 diabetes mellitus

K50.00 – K50.919

Crohn’s disease [regional enteritis]

K51.00 – K51.919

Ulcerative colitis

L40.0

Psoriasis vulgaris

L40.50

Arthropathic psoriasis, unspecified

L40.51

Distal interphalangeal psoriatic arthropathy

L40.52

Psoriatic arthritis mutilans

L40.53

Psoriatic spondylitis

L40.59

Other psoriatic arthropathy

M32.0 – M32.9

Systemic lupus erythematosus (SLE)

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline review date.

Medicare Part D: Florida Blue has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

DEFINITIONS:

Axial PsA (a.k.a., psoriatic spondylitis): a subset of psoriatic arthritis that affects the spine (i.e., spondylitis) and/or spinal joints (e.g., the sacroiliac joint between the sacrum and ilium of pelvis). Axial PsA shares similar clinical findings to patients with ankylosing spondylitis (AS); however, patients with axial PsA are often less symptomatic, have asymmetric disease, and tend to have less severe disease. In addition, the psoriatic plaques or nail changes present in patients with axial PsA are absent in patients with AS. About 5% of PsA patients have exclusively axial involvement, and 20 to 50% have both spinal and peripheral involvement, with peripheral joint involvement being the predominant pattern.

Bacillus Calmette-Guérin (BCG): a vaccine against tuberculosis that is prepared from a strain of the attenuated (weakened) live bovine tuberculosis bacillus, Mycobacterium bovis.

DMARDs: An acronym for disease-modifying antirheumatic drugs. These are drugs that modify the rheumatic disease processes, and slow or inhibit structural damage to cartilage and bone. These drugs are unlike symptomatic treatments such as NSAIDs that do not alter disease progression. DMARDs can be further subcategorized. With the release of biologic agents (e.g., anti-TNF drugs), DMARDs were divided into either: (1) conventional, traditional, synthetic, or non-biological DMARDs; or as (2) biological DMARDs. However, with the release of newer targeted non-biologic drugs and biosimilars, DMARDs are now best categorized as: (1) conventional synthetic DMARDs (csDMARD) (e.g., MTX, sulfasalazine), (2) targeted synthetic DMARDs (tsDMARD) (e.g., tofacitinib, apremilast), and (3) biological DMARDs (bDMARD), which can be either a biosimilar DMARD (bsDMARD) or biological originator DMARD (boDMARD).

Non-axial or peripheral PsA: a subset of psoriatic arthritis that does NOT affect the spine or spinal joints [e.g. elbow, wrist, knees, hands, feet, and digits (dactylitis)]. Peripheral involvement may be polyarticular (5 or more joints affected) or oligoarticular (a.k.a., pauciarticular) (4 or fewer joints affected). Approximately 95% of patients with PsA have involvement of the peripheral joints, predominantly the polyarticular form, whereas a minority has the oligoarticular form.

Plaque psoriasis: It is the most common form of psoriasis. It affects 80 to 90% of people with psoriasis. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery white scaly skin. These areas are called plaques.

Psoriatic arthritis: joint inflammation that occurs in about 5% to 10% of people with psoriasis (a common skin disorder). It is a severe form of arthritis accompanied by inflammation, psoriasis of the skin or nails, and a negative test for rheumatoid factor. Enthesitis refers to inflammation of entheses, the site where ligaments or tendons insert into the bones. It is a distinctive feature of PsA and does not occur with other forms of arthritis. Common locations for enthesitis include the bottoms of the feet, the Achilles' tendons, and the places where ligaments attach to the ribs, spine, and pelvis.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): a neurological disorder, which is not caused by demyelination or a known infectious agent. RPLS can present with headache, seizures, confusion and visual disturbances. Conditions with which it has been associated include preeclampsia, eclampsia, acute hypertension, cytotoxic agents and immunosuppressive therapy. Fatal outcomes have been reported.

RELATED GUIDELINES:

Adalimumab (Humira®), 09-J0000-46

Apremilast (Otezla®) Tablet), 09-J2000-19

Brodalumab (Siliq®) Injection, 09-J2000-74

Certolizumab Pegol (Cimzia®), 09-J0000-77

Etanercept (Enbrel®), 09-J0000-38

Golimumab (Simponi®, Simponi® Aria™), 09-J1000-11

Guselkumab (Tremfya), 09-J2000-87

Infliximab Products [infliximab (Remicade®), infliximab-dyyb (Inflectra®), and infliximab-abda (Renflexis®)], 09-J0000-39

Ixekizumab (Taltz) Injection, 09-J2000-62

Natalizumab (Tysabri) IV, 09-J0000-73

Psoralens with Ultraviolet A (PUVA), 02-10000-16

Secukinumab (Cosentyx®), 09-J2000-30

Vedolizumab (Entyvio), 09-J2000-18

OTHER:

Conventional Synthetic DMARDs

Generic Name

Brand Name

Auranofin (oral gold)

Ridaura

Azathioprine

Imuran

Cyclosporine

Neoral, Sandimmune

Hydroxychloroquine

Plaquenil

Leflunomide

Arava

Methotrexate

Rheumatrex, Trexall

Sulfasalazine

Azulfidine, Azulfidine EN-Tabs

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COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 09/13/17.

GUIDELINE UPDATE INFORMATION:

02/15/10

New Medical Coverage Guideline.

04/15/10

Revision to guideline; consisting of adding specific continuation criteria.

01/01/11

Revision to guideline; consisting of updating coding.

09/15/11

Review and revision to guideline; consisting of updating position statement, coding and references.

09/15/12

Review and revision to guideline; consisting of modifying continuation criteria, reformatting position statement and updating precautions and references.

09/15/13

Review and revision to guideline; consisting of revising description, position statement, dosage/administration, and precautions; updated program exceptions and references.

01/01/14

Revision to guideline; consisting of revising position statement, updating coding and references.

04/15/14

Revision to guideline; consisting of revising position statement.

09/15/14

Review and revision to guideline; consisting of updating position statement and references.

09/15/15

Review and revision to guideline; consisting of revising position statement, updating coding and references.

11/01/15

Revision: ICD-9 Codes deleted.

11/15/15

Revision to guideline consisting of updating maximum starting dosage in the position statement.

02/24/16

Revision to guideline consisting of updating the position statement.

09/15/16

Review and revision to guideline consisting of updating position statement, related guidelines, and references.

11/15/16

Revision to guideline, based on a new FDA-approved indication and IV formulation, consisting of updating the description section, position statement, dosage/administration section, billing/coding, related guidelines, and references.

01/01/17

Revision: updated HCPCS code J3357 description.

01/15/17

Revision to guideline to separate the authorizations for the IV and SC formulations for Crohn’s disease.

04/01/17

Revision to guideline consisting of adding HCPCS code C9487.

07/01/17

Addition of HCPCS code Q9989 that replaces codes C9487 and J3590

07/15/17

Revision to guideline consisting of updating the position statement.

10/15/17

Review and revision to guideline consisting of updating description, position statement, coding/billing, definitions, related guidelines, and references.

Date Printed: December 18, 2017: 11:28 AM