STELARA (USTEKINUMAB) - Oxford Health Plans

Policy Number: PHARMACY 218.2 T2
Effective Date: February 15, 2013
Table of Contents
STELARA (USTEKINUMAB)
CONDITIONS OF COVERAGE...................................
COVERAGE RATIONALE………………………………
BENEFIT CONSIDERATIONS....................................
BACKGROUND...........................................................
CLINICAL EVIDENCE.................................................
U.S. FOOD AND DRUG ADMINISTRATION...............
APPLICABLE CODES.................................................
REFERENCES............................................................
POLICY HISTORY/REVISION INFORMATION..........
Policy History Revision Information
Stelara (Ustekinumab): Clinical Policy (Effective 02/15/2013)
©1996-2013, Oxford Health Plans, LLC
CLINICAL POLICY
The services described in Oxford policies are subject to the terms, conditions and limitations of the
Member's contract or certificate. Unless otherwise stated, Oxford policies do not apply to Medicare
Advantage enrollees. Oxford reserves the right, in its sole discretion, to modify policies as necessary without
prior written notice unless otherwise required by Oxford's administrative procedures or applicable state law.
The term Oxford includes Oxford Health Plans, LLC and all of its subsidiaries as appropriate for these
policies.
Certain policies may not be applicable to Self-Funded Members and certain insured products. Refer to the
Member's plan of benefits or Certificate of Coverage to determine whether coverage is provided or if there
are any exclusions or benefit limitations applicable to any of these policies. If there is a difference between
any policy and the Member’s plan of benefits or Certificate of Coverage, the plan of benefits or Certificate of
Coverage will govern.
CONDITIONS OF COVERAGE
Applicable Lines of Business/
Products
Benefit Type
Referral Required
(Does not apply to non-gatekeeper
products)
Authorization Required
(Precertification always required for
inpatient admission)
Precertification with Medical
Director Review Required
Applicable Site(s) of Service
(If site of service is not listed, Medical
Director review is required)
Special Considerations
This policy applies to Oxford Commercial plan membership
Pharmacy 1
General Benefits Package 3
No
Yes 1,2
No
Other
Page
1
2
2
3
3
7
7
7
8
Related Policies:
Biologics in the
Treatment of Skin,
Joint and
Gastrointestinal
Conditions
Orencia (abatacept)
Prescription Drug
Quantity Duration
(QD) and Quantity
Level Limitations
(QLL)
1 Providers must call Oxford's Pharmacy Benefit Manager
(PBM) to obtain precertification when obtained at a pharmacy
for self administration.
2 New Jersey Small and Individual Commercial Members should
refer to their certificate of coverage for precertification
guidelines and quantity limit guidelines.
1

Special Considerations
(continued)
COVERAGE RATIONALE
Stelara (Ustekinumab): Clinical Policy (Effective 02/15/2013)
3
Precertification is not required when provided in an office or
outpatient setting.
Ustekinumab is considered medically necessary for the treatment of plaque psoriasis when all
of the following criteria are met:
Initial Therapy
Member has a diagnosis of moderate to severe plaque psoriasis; and
Member is not receiving ustekinumab (Stelara) in combination with another infused or
self-injected biologic agent (e.g., tocilizumab (Actemra), belimumab (Benlysta),
etanercept (Enbrel), adalimumab (Humira), certolizumab (Cimzia), golimumab (Simponi),
alefacept (Amevive), rituximab (Rituxan), infliximab (Remicade), or abatacept (Orencia)
Initial Approval: 12 months
Reauthorization
Documentation that Member continues to receive clinical benefit from ongoing treatment with
Stelara
Reauthorization Approval: 12 months
Additional information from the manufacturer’s labeling:
Stelara (ustekinumab) is indicated for the treatment of adult patients (18 years or older) with
moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. 1
Ustekinumab is NOT medically necessary for the treatment of
1. Psoriatic arthritis
2. Crohn’s disease
3. Multiple sclerosis
The findings of available studies are limited by short duration and/or relatively small patient
population. Larger and longer term phase III studies are needed to further characterize
ustekinumab efficacy and safety for treatment of psoriatic arthritis and Crohn’s disease.
In available studies, ustekinumab does not demonstrate efficacy in the treatment of multiple
sclerosis.
BENEFIT CONSIDERATIONS
Not all Oxford Members have a pharmacy benefit.
For coverage of outpatient prescription drugs and specific exclusions, exceptions, and
dispensing limitations, refer to the Member's pharmacy plan, if applicable.
Oxford's Pharmacy Benefit Manager (PBM) provides a nationwide network of
participating pharmacies that administer prescription drugs on a retail level. Groups that
purchase the Outpatient Prescription Drug Rider will have their retail pharmacy benefit
administered by the PBM.
For information regarding any quantity level limitations, refer to Prescription Drug
Quantity Duration (QD) and Quantity Level Limitations (QLL)
For information on coverage for Orencia intravenous infusion, refer to: Orencia
(abatacept).
©1996-2013, Oxford Health Plans, LLC
2

For Information regarding coverage for Enbrel, Humira, Kineret, Cimzia, Simponi, and
Orencia (subcutaneous formulation), refer to: Biologics in the Treatment of Skin, Joint
and Gastrointestinal Conditions.
Some states mandate benefit coverage for off-label use of medications for some
diagnoses or under some circumstances. Some states also mandate usage of other
Compendium references. Where such mandates apply, they supersede language in the
benefit document or in the notification criteria.
BACKGROUND
Ustekinumab is a human IgG1κ monoclonal antibody that binds with high affinity and specificity to
the p40 protein subunit used by both the interleukin (IL)-12 and IL-23 naturally occurring
cytokines. IL-12 and IL-23 are involved in inflammatory and immune responses, such as natural
killer cell activation and CD4+ T-cell differentiation and activation. 1
CLINICAL EVIDENCE
Medically Necessary Use:
Plaque Psoriasis
Two multicenter, randomized, double-blind, placebo-controlled studies (PHOENIX-1 and
PHOENIX-2) were considered in the approval of ustekinumab for the treatment of plaque
psoriasis. 1 Enrollment consisted of a total of 1996 subjects 18 years of age and older with plaque
psoriasis who had a minimum body surface area involvement of 10%, and Psoriasis Area and
Severity Index (PASI) score ≥12, and who were candidates for phototherapy or systemic therapy.
Subjects with guttate, erythrodermic, or pustular psoriasis were excluded from the studies.
Leonardi et al. conducted a phase III, parallel, double-blind, placebo-controlled study (PHOENIX-
1) in 766 patients with moderate-to-severe psoriasis. 8 Subjects were randomly assigned to
receive ustekinumab 45 mg (n=255) or 90 mg (n=256) at weeks 0 and 4 and then every 12
weeks; or placebo (n=255) at weeks 0 and 4, with subsequent crossover to ustekinumab at week
12. Patients who were initially randomized to receive ustekinumab at week 0 and achieved longterm
response (at least 75% improvement in psoriasis area and severity index [PASI 75] at weeks
28 and 40) were randomized a second time at week 40 to maintenance ustekinumab or
withdrawal from treatment until loss of response. The primary endpoint was the proportion of
patients achieving PASI 75 at week 12. Analyses were by intent to treat and resulted in the
following: 171 (67·1%) patients receiving ustekinumab 45 mg, 170 (66·4%) receiving ustekinumab
90 mg, and eight (3·1%) receiving placebo achieved PASI 75 at week 12 (difference in response
rate vs placebo 63·9%, 95% CI 57·8–70·1, p

y intent to treat and resulted in the following: 273 (66.7%) patients receiving ustekinumab 45 mg,
311 (75.7%) receiving ustekinumab 90 mg, and 15 (3.7%) receiving placebo achieved the primary
endpoint (difference in response rate 63.1%, 95% CI 58.2–68.0, p

function and HRQoL in patients with PsA and psoriasis involving at least 3% BSA. However, the
findings of this study are limited by its short duration and relatively small patient population.
Gottlieb et al. conducted a phase II double-blind, randomized, placebo-controlled, crossover
study at 24 sites in North America and Europe. 3 Patients with active psoriatic arthritis were
randomly assigned to receive subcutaneous injections of either ustekinumab 90 mg every week
for 4 weeks (weeks 0–3; total dose 360 mg) followed by placebo at weeks 12 and 16 (Group 1),
or placebo (weeks 0–3) followed by ustekinumab 90 mg at weeks 12 and 16 (total dose 180 mg;
Group 2). The first 12 weeks of the study were placebo-controlled. Masking was maintained to
week 16, and patients were followed up to week 36.
The primary study endpoint was ACR20 response at week 12. In the intent to treat analysis, 32
(42%) patients in Group 1 and ten (14%) in Group 2 achieved the primary endpoint (difference
28% [95% CI 14.0-41.6]; p=0.0002). Of 124 (85%) participants with psoriasis affecting 3% or
more body surface area, 33 of 63 (52%) in Group 1 and three of 55 (5%) in Group 2 had a 75% or
greater improvement in psoriasis area and severity index score at week 12 (47% [33.2-60.6];
p

associated with CD in the colon and ileum as reflected by higher CRP concentrations. The
investigators stated that potential benefit of ustekinumab in CD is supported by serum CRP
reductions. Evidence suggests that increased systemic inflammation as manifested by higher
baseline CRP values leads to larger treatment effects with ustekinumab, especially in infliximabexperienced
patients. Despite these conclusions, further study is needed to confirm whether
change in serum CRP correlates with long-term clinical efficacy in the treatment of Crohn’s
disease.
Multiple Sclerosis
Kasper et al. conducted a phase I, double-blind, placebo-controlled, sequential dose escalation
study in 20 subjects with multiple sclerosis (MS). 9 Subjects were randomized (4:1) to receive a
single subcutaneous injection of either ustekinumab (0.3, 0.75, 1.5, and 3 mg/kg) or placebo.
Clinical and laboratory evaluations were performed through 16 weeks following administration.
Single subcutaneous administrations of ustekinumab in this first study of relapsing MS were
generally well tolerated. Adverse events were generally mild or moderate, with no apparent doserelated
trends. There was a large degree of variability in T2 lesion volume and total number of
gadolinium-positive lesions, both unaffected by dose escalation. Three relapses of MS occurred
in two placebo-treated subjects. Over the range of single doses studied, the median Tmax ranged
from 9.0 to 16.5 days, and the median T1/2 ranged from 20.2 to 30.9 days. The authors concluded
that safety of ustekinumab in MS needs to be tested in a study of longer duration and involving a
larger cohort of subjects.
In a phase II, multicenter, randomized, double-blind, placebo-controlled trial, Segal et al. studied
repeated injections of ustekinumab in patients (n=249) with relapsing-remitting multiple sclerosis
(RRMS). 10 Subjects aged 18-65 years were assigned to one of five groups: placebo (n=49) or
four different ustekinumab dosages (n=50 for all) at weeks 0, 1, 2, 3, 7, 11, 15, and 19.
Ustekinumab doses were 27 mg, 90 mg q8w, 90 mg, or 180 mg; the 90 mg q8w dosage group
received placebo substitute at weeks 7 and 15. The primary endpoint was the cumulative number
of new gadolinium-enhancing T1-weighted lesions on serial cranial MRI through week 23.
Patients were followed up through week 37. In the intent to treat analysis, ustekinumab treatment
did not show a significant reduction in the primary endpoint for any dosage groups versus
placebo. At week 37, adverse events occurred in 38 (78%) placebo-treated patients and 170
(85%) ustekinumab-treated patients, with infections most commonly reported. Serious adverse
events occurred in one (2%) placebo-treated patient and six (3%) ustekinumab-treated patients.
Malignant diseases were reported in two patients shortly after the initiation of ustekinumab
treatment; both patients were withdrawn from the trial and given appropriate treatment, which
resulted in complete remission. No serious infections, cardiovascular events, or exacerbation of
demyelinating events occurred. A dose-dependent increase in serum concentrations of
ustekinumab was recorded. The investigators concluded that ustekinumab is generally well
tolerated but does not show efficacy in reducing the cumulative number of gadolinium-enhancing
T1-weighted lesions in multiple sclerosis.
Professional Societies
The American Academy of Dermatology guidelines of care for the management of psoriasis
and psoriatic arthritis (PsA) state that patients with limited skin disease should not automatically
be treated with systemic treatment if they do not improve, because treatment with systemic
therapy may carry more risk than the disease itself. 11
The strength of AAD recommendations for the treatment of moderate to severe plaque psoriasis
using ustekinumab is A (highest recommendation; level I evidence). Compared with the TNF-alfa
inhibitors, the most comprehensive ustekinumab safety data to date come from a pooled analysis
of phase II and phase III clinical trials involving slightly more than 3,000 patients with just over 3
years of continuous therapy. Therefore, the use of registries to monitor the long-term safety of
ustekinumab and other new agents currently under development, and to monitor the long-term
safety of all of the systemic agents available, is an essential step in defining the long-term
adverse effects of ustekinumab and other new agents. 12
Stelara (Ustekinumab): Clinical Policy (Effective 02/15/2013)
©1996-2013, Oxford Health Plans, LLC
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When considering the use of ustekinumab for PsA, the AAD states that until the results of
ongoing phase III trials of ustekinumab for PsA become available, the TNF-alfa inhibitors should
be considered the biologic class of choice for these patients. 12
U.S. FOOD AND DRUG ADMINISTRATION (FDA)
Stelara (ustekinumab) is indicated for the treatment of adult patients (18 years or older) with
moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. 1
APPLICABLE CODES
The codes listed in this policy are for reference purposes only. Listing of a service or device code
in this policy does not imply that the service described by this code is a covered or non-covered
health service. Coverage is determined by the Member’s plan of benefits or Certificate of
Coverage. This list of codes may not be all inclusive.
HCPCS Code Description
J3357 Injection, ustekinumab, 1 mg
ICD-9 Code Description
696.1 Other psoriasis
ICD-10 Codes (Preview Draft)
In preparation for the transition from ICD-9 to ICD-10 medical coding on October 1, 2014 * , a
sample listing of the ICD-10 CM and/or ICD-10 PCS codes associated with this policy has been
provided below for your reference. This list of codes may not be all inclusive and will be updated
to reflect any applicable revisions to the ICD-10 code set and/or clinical guidelines outlined in this
policy. *The effective date for ICD-10 code set implementation is subject to change.
ICD-10 Diagnosis Code
(Effective 10/01/14)
Description
L40.0 Psoriasis vulgaris
L40.1 Generalized pustular psoriasis
L40.2 Acrodermatitis continua
L40.3 Pustulosis palmaris et plantaris
L40.4 Guttate psoriasis
L40.8 Other psoriasis
L40.9 Psoriasis, unspecified
REFERENCES
The foregoing Oxford policy has been adapted from an existing UnitedHealthcare Pharmacy
Clinical Pharmacy Program that was researched, developed and approved by the UnitedHealth
Group National Pharmacy & Therapeutics Committee
1. Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc; August 2011.
2. Kavanaugh A, Menter A, Mendelsohn A, et al. Effect of ustekinumab on physical function
and health-related quality of life in patients with psoriatic arthritis: a randomized, placebocontrolled,
phase II trial. Curr Med Res Opin. 2010 Oct;26(10):2385-92.
3. Gottlieb A, Menter A, Mendelsohn A, et al. Ustekinumab, a human interleukin 12/23
monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled,
crossover trial. Lancet. 2009 Feb 21;373(9664):633-40. Epub 2009 Feb 11.
4. Sandborn WJ, Feagan BG, Fedorak RN, et al. A randomized trial of Ustekinumab, a
human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe
Crohn's disease. Gastroenterology. 2008 Oct;135(4):1130-41. Epub 2008 Jul 17.
Stelara (Ustekinumab): Clinical Policy (Effective 02/15/2013)
©1996-2013, Oxford Health Plans, LLC
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5. Toedter GP, Blank M, Lang Y, et al. Relationship of C-reactive protein with clinical
response after therapy with ustekinumab in Crohn's disease. Am J Gastroenterol. 2009
Nov;104(11):2768-73. Epub 2009 Aug 11.
6. Kasper, L.H., D. Everitt, T.P. Leist, et al. A phase I trial of an interleukin-12/23
monoclonal antibody in relapsing multiple sclerosis. Curr Med Res Opin. 2006
Sep;22(9):1671-8.
7. Segal BM, Constantinescu CS, Raychaudhuri A, et al. Repeated subcutaneous injections
of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting
multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging
study. Lancet Neurol. 2008 Sep;7(9):796-804.
8. Leonardi CL, Kimball AB, Yeilding N, et al. Efficacy and safety of ustekinumab, a human
interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a
randomized, double-blind, placebo-controlled trial (PHOENIX-1). Lancet 2008;371:1665–
74.
9. Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human
interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a
randomized, double-blind, placebo-controlled trial (PHOENIX-2). Lancet 2008;371:1675–
84.
10. Griffiths CEM, Strober BE, van de Kerkhof P, et al. Comparison of ustekinumab and
etanercept for moderate-to-severe psoriasis. N Engl J Med 2010;362:118-28.
11. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of
psoriasis and psoriatic arthritis section 1. Overview of psoriasis and guidelines of care for
the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826-50.
12. Menter, A, Korman N, Elmets C, et al. Guidelines of care for the management of
psoriasis and psoriatic arthritis section 6. Case-based presentations and evidence-based
conclusions. J Am Acad Dermatol. Doi:10.1016/j.jaad.2010.11.055 [publication date: July
2012].
POLICY HISTORY/REVISION INFORMATION
Date Action/Description
Revised coverage rationale:
02/15/2013
o
o
Removed criteria for patients currently on therapy
Added reauthorization criteria and approval period
Archived previous policy version PHARMACY 218.1 T2
Stelara (Ustekinumab): Clinical Policy (Effective 02/15/2013)
©1996-2013, Oxford Health Plans, LLC
8