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09-J2000-62

Original Effective Date: 06/15/16

Reviewed: 09/13/17

Revised: 10/15/17

Subject: Ixekizumab (Taltz®) Injection

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:

Ixekizumab (Taltz) was approved by the US Food and Drug Administration (FDA) in March 2016 for moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Ixekizumab is a humanized IgG4 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. Secukinumab (Cosentyx), approved by the FDA in January 2015 for moderate to severe plaque psoriasis, was the first-in-class biologic agent to target IL-17. Interleukin-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated concentrations of IL-17A are found in psoriatic plaques. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.

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 it 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.

The safety and efficacy of ixekizumab were evaluated in three, double-blind, multicenter, phase 3 studies (UNCOVER-1, UNCOVER-2 and UNCOVER-3) in a total of 3,866 adult patients with moderate to severe chronic plaque psoriasis. In all three trials, subjects were randomized to either placebo or ixekizumab (80 mg every two weeks [Q2W]) for 12 weeks, following a 160 mg starting dose. In the two active comparator trials (UNCOVER-2 and UNCOVER-3), subjects were also randomized to etanercept (Enbrel) 50 mg twice weekly for 12 weeks. All three trials assessed the changes from baseline to Week 12 in two co-primary endpoints: (1) PASI 75 [the proportion of subjects who achieved at least a 75% reduction in the Psoriasis Area and Severity Index (PASI) composite score], and (2) sPGA of “0” (clear) or “1” (minimal) [the proportion of subjects with an static Physician Global Assessment (sPGA) score of 0 or 1 and at least a 2-point improvement]. Other evaluated outcomes included the proportion of subjects with a sPGA score of 0, PASI 90, and PASI 100. Subjects in all treatment groups had a median baseline PASI score ranging from about 17 to 18. Of all subjects, 44% had received prior phototherapy, 49% had received prior conventional systemic therapy, and 26% had received prior biologic therapy for the treatment of psoriasis.

The results of UNCOVER-1, UNCOVER-2 and UNCOVER-3 in the intent-to-treat (ITT) population are presented in Table 1 below.

Table 1

 

UNCOVER-1

UNCOVER-2

UNCOVER-3

Taltz

(n=433)

Placebo

(n=431)

Taltz

(n=351)

Placebo

(n=168)

Taltz

(n=385)

Placebo

(n=193)

sPGA of 0 or 1

82%

3%

83%

2%

81%

7%

sPGA of 0

37%

0%

42%

1%

40%

0%

PASI 75

89%

4%

90%

4%

87%

7%

PASI 90

71%

1%

71%

1%

68%

3%

PASI 100

35%

0%

40%

1%

38%

0%

In an integrated analysis of the US sites in the two active comparator studies using etanercept, ixekizumab demonstrated superiority to etanercept 50 mg twice weekly on sPGA and PASI scores during the 12 week treatment period. The respective response rates for ixekizumab and etanercept were: sPGA of 0 or 1 (73% vs. 27%); PASI 75 (87% vs. 41%); sPGA of 0 (34% vs. 5%); PASI 90 (64% vs. 18%), and PASI 100 (34% vs. 4%).

POSITION STATEMENT:

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

NOTE: Members initiating provider-administered (i.e., submitted as a medical claim with J3590 or C9399 with NDC) ixekizumab therapy are NOT required to have had an inadequate response to two preferred self-administered (i.e., subcutaneous) biologic products. However, members transitioning to self-administered treatment after a single provider-administered first dose must still meet the preferred self-administered biologic product requirement.

NOTE: If the member has had an inadequate response to previous biologic therapy, other than ixekizumab, 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). However, members self-administering ixekizumab must still meet the two preferred self-administered (i.e., subcutaneous) biologic product requirement.

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

1. Ixekizumab 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. Ixekizumab 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. sarilumab (Kevzara)

l. secukinumab (Cosentyx)

m. tocilizumab (Actemra)

n. tofacitinib (Xeljanz, Xeljanz XR)

o. ustekinumab (Stelara)

p. vedolizumab (Entyvio)

3. The member is 18 years of age or older

Table 2

Indications and Specific Criteria

Indication

Criteria

Max Allowable Dosage

Plaque psoriasis

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

1. 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)

2. 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)

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

a. Member has had an inadequate response, has persistent and intolerable adverse effect(s), or has a contraindication to TWO or more of the following self-administered biologic therapies (the specific adverse effect(s) and/or contraindications must be provided):

etanercept (Enbrel)

adalimumab (Humira)

ustekinumab (Stelara)

b. BOTH of the following (“i” and “ii”):

i. Member has had an inadequate response to, has persistent and intolerable adverse effect(s), or has a contraindication to ustekinumab (Stelara) (the specific adverse effect and/or contraindication must be provided)

ii. Member should consider alternatives to the use of an anti-TNF biologic due to a product warning and precaution for EITHER of the following (the specific condition must be provided):

Demyelinating disease (e.g., multiple sclerosis)

Current or worsening congestive heart failure

Initial:

• 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12

Maintenance:

• 80 mg every 4 weeks starting on week 16

Approval duration:12 weeks

 

BSA, body surface area

*NOTE: Members initiating provider-administered (i.e., submitted as a medical claim with J3590 or C9399 with NDC) ixekizumab therapy are NOT required to have had an inadequate response to two preferred self-administered (i.e., subcutaneous) biologic products. However, members transitioning to self-administered treatment after a single provider-administered first dose must still meet the preferred self-administered biologic product requirement.

†NOTE: If the member has had an inadequate response to previous biologic therapy, other than ixekizumab, 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). However, members self-administering ixekizumab must still meet the two preferred self-administered (i.e., subcutaneous) biologic product requirement.

Continuation of ixekizumab (Taltz) 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 ixekizumab 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 2, OR the member previously met ALL indication-specific initiation criteria

2. Member has demonstrated a beneficial clinical response to ixekizumab therapy

3. Ixekizumab is NOT 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. sarilumab (Kevzara)

l. secukinumab (Cosentyx)

m. tocilizumab (Actemra)

n. tofacitinib (Xeljanz, Xeljanz XR)

o. ustekinumab (Stelara)

p. vedolizumab (Entyvio)

4. The dosage of ixekizumab does not exceed the following:

a. First 12 week of treatment – 80 mg every 2 weeks (weeks 2, 4, 6, 8, 10, and 12)

b. After 12 weeks of treatment - 80 mg every 4 weeks starting on week 16

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

• Indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

• Administered by subcutaneous injection. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.

• Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in subcutaneous injection technique using the autoinjector or prefilled syringe. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis. Administration the upper, outer arm may be performed by a caregiver or healthcare provider.

• Before injection, remove ixekizumab from the refrigerator and allow to reach room temperature (30 minutes) without removing the needle cap.

Dose Adjustments

• Specific guidelines for dosage adjustments in hepatic or renal impairment are not available; it appears no dosage adjustments are needed

Drug Availability

• Autoinjector - 80 mg/mL solution in a single-dose prefilled autoinjector (cartons of 1, 2, or 3)

• Prefilled Syringe - 80 mg/mL solution in a single-dose prefilled syringe (cartons of 1, 2, or 3)

PRECAUTIONS:

Boxed Warning

• None

Contraindications

• Patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients

Precautions/Warnings

Infections: Serious infections have occurred. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue ixekizumab until the infection resolves.

Tuberculosis (TB): Evaluate for TB prior to initiating treatment. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering ixekizumab. Consider anti-TB therapy prior to initiating in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment

Hypersensitivity: Serious hypersensitivity reactions, including angioedema and urticaria (each ≤0.1%), occurred in clinical trials. Anaphylaxis, including cases leading to hospitalization, has been reported in post marketing use. If a serious allergic reaction occurs, discontinue ixekizumab immediately and initiate appropriate therapy.

Inflammatory Bowel Disease: Crohn's disease and ulcerative colitis, including exacerbations, occurred during clinical trials. Patients who are treated with ixekizumab and have inflammatory bowel disease should be monitored closely.

Adverse Reactions: Most common (≥1%) adverse reactions associated with ixekizumab treatment are injection site reactions, upper respiratory tract infections, nausea, and tinea infections

Immunizations: Prior to initiating therapy with ixekizumab, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with ixekizumab. No data are available on the response to live or inactive vaccines.

Pregnancy: There are no available data on ixekizumab use in pregnant women to inform any drug associated risks. Human IgG is known to cross the placental barrier; therefore, ixekizumab may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus.

Pediatric Use: The safety and effectiveness of ixekizumab in pediatric patients (<18 years of age) have not been evaluated.

Cytochrome P450 Substrates: The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation. Thus, ixekizumab, an antagonist of IL-17A, could normalize the formation of CYP450 enzymes. Therefore, upon initiation or discontinuation in patients who are receiving concomitant drugs which are CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for effect (e.g., for warfarin) or drug concentration (e.g., for cyclosporine) and consider dosage modification of the CYP450 substrate.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

C9399

Unclassified drugs or biologicals (Hospital outpatient use ONLY)

J3590

Unclassified biologics

ICD-10 Diagnosis Codes That Support Medical Necessity

L40.0

Psoriasis vulgaris

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

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

DEFINITIONS:

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.

RELATED GUIDELINES:

Adalimumab (Humira®), 09-J0000-46
Apremilast (Otezla), 09-J2000-19

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

Etanercept (Enbrel®), 09-J0000-38

Guselkumab (Tremfya), 09-J2000-87

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

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

Secukinumab (Cosentyx®), 09-J2000-30

Ustekinumab (Stelara), 09-J1000-16

OTHER:

None

REFERENCES:

  1. Armstrong AW, Siegel MP, Bagel J, et al. From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017 Feb;76(2):290-298.
  2. Blauvelt A, Papp KA, Griffiths CEM, et al. Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3). Am J Clin Dermatol. 2017 Apr;18(2):273-280.
  3. Canadian Psoriasis Guidelines Addendum Committee. 2016 Addendum to the Canadian Guidelines for the Management of Plaque Psoriasis 2009. J Cutan Med Surg. 2016 Sep;20(5):375-431.
  4. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2017. Available at: www.clinicalpharmacilogy-ip.com. Accessed 8/8/17.
  5. Coates LC, Kavanaugh A, Mease PJ et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis: Treatment Recommendations for Psoriatic Arthritis 2015. Arthritis Rheumatol 2016;68:1060–71
  6. Dogra S, Jain A, Kanwar AJ. Efficacy and safety of acitretin in three fixed doses of 25, 35 and 50 mg in adult patients with severe plaque type psoriasis: a randomized, double blind, parallel group, dose ranging study. J Eur Acad Dermatol Venereol. 2013 Mar;27(3):e305-11.
  7. Dogra S, Krishna V, Kanwar AJ. Efficacy and safety of systemic methotrexate in two fixed doses of 10 mg or 25 mg orally once weekly in adult patients with severe plaque-type psoriasis: a prospective, randomized, double-blind, dose-ranging study. Clin Exp Dermatol. 2012 Oct;37(7):729-34.
  8. FDA Orphan Drug Designations and Approvals [Internet]. Washington, D.C. [cited 2017 August 8]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/.
  9. Gordon KB, Blauvelt A, Papp KA, et al.; UNCOVER-1 Study Group; UNCOVER-2 Study Group; UNCOVER-3 Study Group. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med. 2016 Jul 28;375(4):345-56.
  10. Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008 May;58(5):851-64. doi: 10.1016/j.jaad.2008.02.040.
  11. Griffiths C, Reich K, Lebwohl M, et al: Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet 2015; 386(9993):541-551.
  12. Hsu S, Papp KA, Lebwohl MG, et al. Consensus guidelines for the management of plaque psoriasis. Arch Dermatol 2012;148(1):95-102.
  13. Krause ML, Amin A, and Makol A. Use of DMARDs and biologics during pregnancy and lactation in rheumatoid arthritis: what the rheumatologist needs to know. Ther Adv Musculoskelet Dis. 2014 Oct; 6(5): 169–184.
  14. 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. Am Acad Dermatol. May 2008; 58(5):826-850.
  15. Menter A, Korman, NJ, Elmets, CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: Case-based presentations and evidence-based conclusions. J Am Acad Dermatol 2011; 65:137-74.
  16. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 8/8/17.
  17. Nast A, Gisondi P, Ormerod AD, et al. European S3-Guidelines on the systemic treatment of psoriasis vulgaris--Update 2015--Short version--EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol. 2015 Dec;29(12):2277-94.
  18. Rahimi R, Nikfar S, Rezaie A, et al. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis. Reprod. Toxicol;2008:25,271–275.
  19. Taltz (ixekizumab) [prescribing information]. Eli Lilly and Company; Indianapolis, IN. July 2017.

COMMITTEE APPROVAL:

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

GUIDELINE UPDATE INFORMATION:

06/15/16

New Medical Coverage Guideline.

10/15/17

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

Date Printed: October 17, 2017: 04:19 PM