Print

Date Printed: October 23, 2017: 02:08 AM

Private Property of Blue Cross and Blue Shield of Florida.
This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J2000-79

Original Effective Date: 06/15/17

Reviewed: 05/10/17

Revised: 00/00/00

Subject: Brodalumab (Siliq®) 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:

Brodalumab (Siliq) is an injectable human monoclonal IgG2κ antibody directed against interleukin-17 receptor A (IL-17RA). Blocking IL-17RA inhibits IL-17 cytokine-induced responses including the release of pro-inflammatory cytokines and chemokines. Brodalumab was approved by the US Food and Drug Administration (FDA) in February 2017 for “the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies.” Because of an observed risk of suicidal ideation and behavior during clinical trials, the labeling includes a Boxed Warning and the drug is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), the SILIQ REMS Program. Brodalumab is the third biologic agent that specifically targets the IL-17 pathway to be approved by the FDA for treatment of psoriasis. Secukinumab (Cosentyx), approved in January 2015, was the first followed by ixekizumab (Taltz) approved in March 2016.

The safety and efficacy of brodalumab was assessed in 4,373 adults with moderate to severe plaque psoriasis during three multicenter, randomized, double-blind, controlled trials (AMAGINE-1, -2, and -3). Subjects had at least a 6-month history of moderate to severe plaque psoriasis, defined as having a minimum affected body surface area (BSA) of 10%, a Psoriasis Area and Severity Index (PASI) score ≥12, a static Physician’s Global Assessment (sPGA) score ≥3 in the overall assessment of psoriasis on a severity scale of 0 to 5. In all three trials, subjects were randomized to subcutaneous treatment with placebo or brodalumab 210 mg at Weeks 0, 1, and 2, followed by treatments every 2 weeks through Week 12. In the two active comparator trials (AMAGINE-2 and -3), subjects randomized to ustekinumab (Stelara) received either a 45 mg dose (if ≤100 kg) or 90 mg dose (if >100 kg) at Weeks 0, 4, and 16, followed by the same dose every 12 weeks. All three trials assessed the change from baseline to Week 12 vs. placebo for two co-primary endpoints: [1] PASI 75 (the proportion of subjects who achieved at least a 75% reduction in the PASI composite score), and [2] the proportion of subjects with an sPGA of 0 (clear) or 1 (almost clear), and at least a 2-point improvement from baseline. In AMAGINE-2 and -3, comparisons were also made to ustekinumab for the primary endpoint of the proportion of subjects who achieved a reduction in PASI score of 100% (PASI 100) from baseline at Week 12. Baseline demographics were generally consistent across all treatment groups in all three trials. Subjects were predominantly men (69%) and white (91%), with a mean age of 45 years. The baseline PASI score ranged from 9.4 to 72 (median 17.4) and the baseline affected BSA ranged from 10% to 97% (median 21%). Baseline sPGA scores ranged from “3 (moderate)” (58%) to “5 (very severe)” (5%). Approximately 21% of subjects had a history of psoriatic arthritis. Approximately 30% of subjects had previously received a biologic therapy and 12% of subjects had failed previous biologic therapy.

In all three studies brodalumab vs. placebo significantly increased the proportion of patients achieving a PASI-75, a PASI-100, and a sPGA score of clear or almost clear at 12 weeks. In AMAGINE-2 and -3, brodalumab 210 mg vs. ustekinumab significantly improved the proportion of patients achieving a PASI-75, PASI-100, and a sPGA score of 0 or 1 at 12 weeks. See Table 1 for a summary of the trial results. The 210 mg dose was ultimately approved by the FDA due to the greater efficacy and similar safety profile as compared to the 140 mg dose. Regarding adverse effects, rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. There were 2 deaths from suicide in brodalumab-treated patients in AMAGINE-2 and 2 suicides in AMAGINE-1.

Table1

Week 12 Results

Trial

Treatment

PASI-75

PASI-100

sPGA 0/1

AMAGINE-1

brodalumab 140 mg (n=219)

60.3%

23.3%

53.9%

brodalumab 210 mg (n=222)

83.3%

41.9%

75.7%

placebo (n=220)

2.7%

0.5%

1.4%

AMAGINE-2

brodalumab 140 mg (n=610)

67%

26%

58%

brodalumab 210 mg (n=612)

86%

44%

79%

ustekinumab (n=300)

70%

22%

61%

placebo (n=309)

8%

1%

4%

AMAGINE-3

brodalumab 140 mg (n=629)

69%

27%

60%

brodalumab 210 mg (n=624)

85%

37%

80%

ustekinumab (n=313)

69%

19%

57%

placebo (n=315)

6%

0.3%

4%

PASI = Psoriasis Area and Severity Index % improvement; sPGA = static Physician's Global Assessment score of 0 or 1

Regarding the use of prerequisite therapy, 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.

POSITION STATEMENT:

Comparative Effectiveness

The FDA has deemed 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) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

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

Initiation of brodalumab (Siliq) meets the definition of medical necessity when ALL of the following criteria are met:

1. Brodalumab will be used for the treatment of an indication listed in Table 2, and ALL indication-specific criteria are met

2. The member is 18 years of age or older

3. The member does NOT have a comorbid diagnosis of Crohn’s disease

4. Brodalumab will NOT be administered in combination with ANY of the following:

a. abatacept (Orencia)

b. adalimumab (Humira)

c. anakinra (Kineret)

d. apremilast (Otezla)

e. certolizumab (Cimzia)

f. etanercept (Enbrel)

g. golimumab (Simponi, Simponi Aria)

h. infliximab products (Remicade, Inflectra, Renflexis)

i. ixekizumab (Taltz)

j. secukinumab (Cosentyx)

k. tocilizumab (Actemra)

l. tofacitinib (Xeljanz, Xeljanz XR)

m. ustekinumab (Stelara)

n. vedolizumab (Entyvio)

Table 2

Indications and Specific Criteria

Indication

Criteria

Maximum Allowable Dosage (IV)

Plaque psoriasis

ALL of the following:

1. Member’s disease is moderate to severe as evidenced by documentation of EITHER of the following (“a” or “b”):

a. Psoriasis covers more than 10% of member’s body surface area (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. Member has had an inadequate response to or has a contraindication to methotrexate, or, if methotrexate is contraindicated, the member has had an inadequate response to EITHER cyclosporine or acitretin, OR has a contraindication to BOTH cyclosporine and acitretin (the specific contraindications must be provided)*

3. Member has had an inadequate response to or has a contraindication to TWO or more of the following (the specific contraindication(s) must be provided):

a. adalimumab (Humira)

b. etanercept (Enbrel)

c. ustekinumab (Stelara)

Initial:

• 210 mg at Weeks 0, 1, and 2

(i.e., 3 doses in the first 28 days)

Maintenance:

• 210 mg every 2 weeks starting no sooner than week 4

(i.e., 2 doses per 28 days)

Approval duration: 16 weeks

 

*NOTE: if the member has had an inadequate response to previous biologic therapy, other than brodalumab, that is FDA-approved for the requested indication listed in Table 2, the member is NOT required to have had an inadequate therapeutic response to additional 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 brodalumab (Siliq) meets the definition of medical necessity when ALL of the following criteria are met:

1. An authorization or reauthorization for brodalumab 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 has previously met ALL indication-specific initiation criteria

2. Member has demonstrated a beneficial response to therapy with brodalumab

3. Brodalumab will NOT be administered in combination with ANY of the following:

a. abatacept (Orencia)

b. adalimumab (Humira)

c. anakinra (Kineret)

d. apremilast (Otezla)

e. certolizumab (Cimzia)

f. etanercept (Enbrel)

g. golimumab (Simponi, Simponi Aria)

h. infliximab products (Remicade, Inflectra, Renflexis)

i. ixekizumab (Taltz)

j. secukinumab (Cosentyx)

k. tocilizumab (Actemra)

l. tofacitinib (Xeljanz, Xeljanz XR)

m. ustekinumab (Stelara)

n. vedolizumab (Entyvio)

4. The member does NOT have a comorbid diagnosis of Crohn’s disease

5. The dosage of brodalumab does not exceed 210 mg every 2 weeks

Approval duration: 12 months

Brodalumab is considered investigational and experimental for all other conditions including, but not limited to asthma, Crohn's disease, psoriatic arthritis, and rheumatoid arthritis.

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 moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies.

• The recommended dose is 210 mg administered by subcutaneous injection at Weeks 0, 1, and 2 followed by 210 mg every 2 weeks. If an adequate response has not been achieved after 12 to 16 weeks of treatment, consider discontinuing therapy. Continued treatment beyond 16 weeks in patients who have not achieved an adequate response is not likely to result in greater success.

• Brodalumab is intended for use under the guidance and supervision of a healthcare professional. Patients may self-inject when deemed appropriate by a healthcare professional and after proper training in subcutaneous injection technique using the prefilled syringe.

Dose Adjustments

• No specific guidelines for dosage adjustments for renal or hepatic impairment are available. It appears that no dosage adjustments are needed.

Drug Availability

• Injection: 210 mg/1.5 mL solution in a single-dose prefilled syringe. Each prefilled syringe is for single-dose only.

PRECAUTIONS:

Boxed Warning

• Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with brodalumab. Prior to prescribing brodalumab, weigh the potential risks and benefits in patients with a history of depression and/or suicidal ideation or behavior. Patients with new or worsening suicidal ideation and behavior should be referred to a mental health professional, as appropriate. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation or behavior, new onset or worsening depression, anxiety, or other mood changes.

• Because of the observed suicidal behavior in subjects treated with brodalumab, brodalumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the SILIQ REMS Program.

Contraindications

• Patients with Crohn’s disease because brodalumab may cause worsening of disease

Precautions/Warnings

• SILIQ REMS Program: Notable requirements of the program include the following:

o Prescribers must be certified with the program.

o Patients must sign a Patient-Prescriber Agreement Form.

o Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive brodalumab.

Further information, including a list of qualified pharmacies, is available at www.SILIQREMS.com or by calling the SILIQ REMS Program Call Center at 855-511-6135.

• Infections: Serious infections have occurred. Consider the risks and benefits prior to initiating brodalumab in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue brodalumab until the infection resolves.

• Tuberculosis (TB): Evaluate patients for TB infection prior to initiating treatment with brodalumab.

• Crohn’s Disease: Crohn’s disease occurred during clinical trials. Discontinue brodalumab if patient develops Crohn’s disease while taking brodalumab.

• Immunizations: Avoid using live vaccines concurrently with brodalumab.

• CYP450 Substrates: The formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation, and treatment with brodalumab may modulate serum levels of some cytokines. Therefore, upon initiation or discontinuation of brodalumab 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.

• Pregnancy: There are no human data on brodalumab use in pregnant women to inform a drug associated risk. Human IgG antibodies are known to cross the placental barrier; therefore, brodalumab may be transmitted from the mother to the developing fetus. See the package insert for additional information.

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 Diagnoses 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 guideline creation.

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

Certolizumab (Cimzia), 09-J0000-77

Etanercept (Enbrel), 09-J0000-38

Golimumab (Simponi), 09-J1000-11

Infliximab (Remicade), 09-J0000-39

Ixekizumab (Taltz) Injection, 09-J2000-62

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

Secukinumab (Cosentyx), 09-J2000-30

Ustekinumab (Stelara), 09-J1000-16

OTHER:

None

REFERENCES:

  1. Attia A, Abushouk AI, Ahmed H, et al. Safety and Efficacy of Brodalumab for Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Meta-Analysis. Clin Drug Investig. 2017 Feb 14.
  2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 2017 Apr 1]. Available from: http://www.clinicalpharmacology.com/
  3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; April 2017 [cited 2017 Apr 1]. Available from: http://clinicaltrials.gov/.
  4. DRUGDEX System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017 Apr 1]. Available from: http://www.thomsonhc.com/.
  5. 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.
  6. Hsu S, Papp KA, Lebwohl MG, et al. Consensus guidelines for the management of plaque psoriasis. Arch Dermatol 2012;148 (1):95-102.
  7. Lebwohl M, Strober B, Menter A, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med 2015; 373(14):1318-1328.
  8. 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.
  9. 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.
  10. 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.
  11. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 2017 Apr 1]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  12. Papp KA, Reich K, Paul C, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol 2016; 175(2):273-286.
  13. 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.
  14. Siliq (brodalumab) [prescribing information]. Valeant; Bridgewater, NJ. February 2017.
  15. Targan SR, Feagan B, Vermeire S, et al. A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Brodalumab in Patients With Moderate-to-Severe Crohn's Disease. Am J Gastroenterol. 2016 Nov;111(11):1599-1607.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 05/10/17.

GUIDELINE UPDATE INFORMATION:

06/15/17

New Medical Coverage Guideline.

Date Printed: October 23, 2017: 02:08 AM