Print

Date Printed: August 18, 2017: 10:15 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-J2000-19

Original Effective Date: 09/15/14

Reviewed: 08/10/16

Revised: 02/01/17

Subject: Apremilast (Otezla®) Tablet

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:

Apremilast (Otezla®) was approved by the US Food and Drug Administration (FDA) for the treatment of adults with active psoriatic arthritis (PsA) in March 2014 and then moderate-to-severe plaque psoriasis in September 2014. Apremilast exerts its therapeutic activity through inhibition of phosphodiesterase-4 (PDE-4). PDE-4 inhibition promotes intracellular accumulation of cyclic adenosine monophosphate; this accumulation results in a downregulation of inflammatory responses and ultimately reduces inflammation.

FDA-approval for PsA was based on three similarly designed clinical trials, PALACE-1, -2, and -3 (i.e., PsA-1, PsA-2, and PsA-3). All three trials were multi-center, randomized, double-blind, placebo-controlled trials and enrolled a total of 1,493 subjects. Subjects were enrolled if they were diagnosed with active PsA despite previous or current treatment with a disease modifying anti-rheumatic drug (DMARD). Of note, previous treatment with a biologic, including anti-tumor necrosis factor (TNF) agents was allowed and up to 10% of subjects could be previous anti-TNF failures. The primary efficacy endpoint was the proportion of subjects achieving a 20% reduction in the American College of Rheumatology (ACR) response criteria for rheumatoid arthritis, modified for psoriatic arthritis (i.e., ACR20) at 16 weeks. Apremilast treatment resulted in significantly more subjects achieving an ACR20 response at week 16 (38%, 32% and 41% in PsA-1, -2, and -3 respectively) when compared to placebo (19%, 19%, 18%). Additionally, the number of tender and swollen joints, pain assessment and Health Assessment Questionnaire Disability Index were also improved at week 16.

FDA-approval for plaque psoriasis was based on two multicenter, randomized, double-blind, placebo-controlled trials (PSOR-1 and PSOR-2) in which 1,257 subjects 18 years of age and older with moderate to severe plaque psoriasis were enrolled. Approximately 30% of subjects had received prior phototherapy and 54% had received prior conventional systemic and/or biologic therapy for the treatment of psoriasis. The primary efficacy endpoint was the proportion of subjects achieving a Psoriasis Area and Severity Index (PASI)-75 response. Apremilast treatment resulted in significantly more subjects achieving a PASI-75 response at week 16 (33.1% and 28.8% in PSOR-1 and PSOR-2, respectively) vs. placebo (5.3% and 5.8%). Also, more patients on apremilast had a Static Physician Global Assessment (sPGA) of clear or almost clear (21.7% and 20.4% vs. 3.9% and 4.4%).

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 Food and Drug Administration 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: If the member has failed previous biologic therapy that is FDA-approved for the requested indication listed below, the member is not required to try and fail additional non-biologic prerequisite therapy (e.g., for psoriasis, if member has previously tried and failed etanercept, but does not have a history of methotrexate failure, they do not have to try and fail methotrexate to meet medical necessity criteria).

Initiation of apremilast (Otezla®) meets the definition of medical necessity for members diagnosed with ANY of the following conditions when ALL associated criteria are met:

1. Psoriatic Arthritis (PsA) [including both axial and non-axial (peripheral) PsA]

a. Member’s disease is active

b. EITHER of the following based on the dominate disease type:

i. Axial PsA: Member has tried and failed or has a contraindication to at least TWO different NSAID therapies (e.g., celecoxib, diclofenac, ibuprofen, meloxicam naproxen)

ii. Peripheral PsA: Member has previously tried and failed or has a contraindication to methotrexate, or, if methotrexate is contraindicated, to another DMARD (e.g., cyclosporine, leflunomide, sulfasalazine)

c. Apremilast use is NOT in combination with ANY of the following:

i. Abatacept (Orencia)

ii. Adalimumab (Humira)

iii. Anakinra (Kineret)

iv. Certolizumab (Cimzia)

v. Etanercept (Enbrel)

vi. Golimumab (Simponi, Simponi Aria)

vii. Secukinumab (Cosentyx)

viii. Infliximab products (Remicade, Inflectra)

ix. Ixekizumab (Taltz)

x. Tocilizumab (Actemra)

xi. Tofacitinib (Xeljanz, Xeljanz XR)

xii. Ustekinumab (Stelara)

xiii. Vedolizumab (Entyvio)

d. Member is 18 years of age or older

e. Dosage does not exceed 30 mg twice daily

2. Plaque Psoriasis

a. Member has moderate to severe chronic plaque psoriasis evidenced by either of the following:

i. Psoriasis covers more than 5% of body surface area (BSA)

ii. Psoriasis covers less than or equal to 5% of BSA but affects crucial body areas (e.g., face, hands, feet, genitals)

b. Member has previously tried and failed or has a contraindication to methotrexate, or, if methotrexate is contraindicated, the member has tried and failed 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)

c. Apremilast use is NOT in combination with ANY of the following:

i. Abatacept (Orencia)

ii. Adalimumab (Humira)

iii. Anakinra (Kineret)

iv. Certolizumab (Cimzia)

v. Etanercept (Enbrel)

vi. Golimumab (Simponi, Simponi Aria)

vii. Infliximab products (Remicade, Inflectra)

viii. Ixekizumab (Taltz)

ix. Secukinumab (Cosentyx)

x. Tocilizumab (Actemra)

xi. Tofacitinib (Xeljanz, Xeljanz XR)

xii. Ustekinumab (Stelara)

xiii. Vedolizumab (Entyvio)

d. Member is 18 years of age or older

e. Dosage does not exceed 30 mg twice daily

Approval duration: 6 months

Continuation of apremilast (Otezla) meets the definition of medical necessity when ALL of the following criteria are met:

1. An authorization/reauthorization for apremilast has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of plaque psoriasis or PsA, OR the member previously met ALL indication-specific initiation criteria.

2. The member has demonstrated a beneficial response to apremilast therapy.

3. The dosage does not exceed 30 mg twice daily.

4. Use is NOT in combination with ANY of the following:

a. Abatacept (Orencia)

b. Adalimumab (Humira)

c. Anakinra (Kineret)

d. Certolizumab (Cimzia)

e. Etanercept (Enbrel)

f. Golimumab (Simponi, Simponi Aria)

g. Infliximab products (Remicade, Inflectra)

h. Ixekizumab (Taltz)

i. Secukinumab (Cosentyx)

j. Tocilizumab (Actemra)

k. Tofacitinib (Xeljanz, Xeljanz XR)

l. Ustekinumab (Stelara)

m. Vedolizumab (Entyvio)

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.

Apremilast is indicated for the treatment of adults with active psoriatic arthritis and patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. To reduce the risk of gastrointestinal symptoms, the following titration schedule is recommended:

• Day 1: 10 mg in the morning

• Day 2: 10 mg in morning and 10 mg in evening

• Day 3: 10 mg in morning and 20 mg in evening

• Day 4: 20 mg in morning and 20 mg in evening

• Day 5: 20 mg in morning and 30 mg in evening

• Day 6: 30 mg twice daily

Dose Adjustments: Reduce the dose to 30 mg once daily for persons with severe renal impairment (i.e., creatinine clearance less than 30 ml/min). For initial dose titration, titrate using only the morning schedule and skip evening doses. No dose adjustment is necessary in patients with hepatic impairment.

Product Availability: apremilast is supplied as 10-, 20-, and 30-mg tablets.

PRECAUTIONS:

Contraindication:

Known hypersensitivity to apremilast or any excipients in the formulation.

Warnings:

Depression: Advise patients, their caregivers, and families to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes and if such changes occur to contact their healthcare provider. Carefully weigh risks and benefits of treatment with apremilast in persons with a history of depression and/or suicidal thoughts or behavior.

Weight Decrease: Monitor weight regularly. If unexplained or clinically significant weight loss occurs, evaluate weight loss and consider discontinuation of apremilast.

Drug Interactions: Use with strong cytochrome P450 enzyme inducers (e.g. rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended because loss of efficacy may occur.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J8499

Prescription drug, oral, non-chemotherapeutic, NOS

ICD-10 Diagnoses Codes That Support Medical Necessity (Effective 10/01/15)

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

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 revised 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.

DMARDs: An acronym for disease-modifying antirheumatic drugs.

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.

RELATED GUIDELINES:

Adalimumab (Humira®), 09-J0000-46

Certolizumab (Cimzia®), 09-J0000-77

Etanercept (Enbrel®), 09-J0000-38

Golimumab (Simponi™), 09-J1000-11

Infliximab (Remicade®) and Infliximab-dyyb (Inflectra®), 09-J0000-39

Ixekizumab (Taltz) Injection, 09-J2000-62

Psoralens with Ultraviolet A (PUVA), 09-10000-16

Secukinumab (Cosentyx®), 09-J2000-30

Ustekinumab (Stelara), 09-J1000-16

OTHER:

Table 1: DMARDs

DMARD Generic Name

DMARD Brand Name

Auranofin (oral gold)

Ridaura

Azathioprine

Imuran

Chlorambucil

Leukeran

Cyclophosphamide

Cytoxan

Cyclosporine

Neoral, Sandimmune

Gold sodium thiomalate (injectable gold)

Myochrysine

Hydroxychloroquine sulfate

Plaquenil

Leflunomide

Arava

Methotrexate

Rheumatrex, Trexall

Minocycline

Minocin

Penicillamine

Cuprimine, Depen

Sulfasalazine

Azulfidine, Azulfidine EN-Tabs

REFERENCES:

  1. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2016 [cited 2016 Jun 23]. Available from: http://www.clinicalpharmacology.com/.
  2. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2016 Jun 10]. Available from: http://www.thomsonhc.com/.
  3. Gossec L, Smolen JS, Ramiro S, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016 Mar;75(3):499-510.
  4. 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.jaad2008.02.040.
  5. Hsu S, Papp KA, Lebwohl MG, et al. Consensus guidelines for the management of plaque psoriasis. Arch Dermatol 2012;148(1):95-102.
  6. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Treatment of psoriatic arthritis in a phase 3 randomized, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis. Mar 4 2014.
  7. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Supplemental Data: Treatment of psoriatic arthritis in a phase 3 randomized, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Available at: http://ard.bmj.com/content/suppl/2014/03/04/annrheumdis-2013-205056.DC1/annrheumdis-2013-205056supp.docx.
  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. J Am Acad Dermatol. 2008 May;58(5):826-50.
  10. Mentor A, Korman NJ, Elmets CA, et al. Guidelines for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol 2011;65:137-74.
  11. National Institute for Health and Clinical Excellence (NICE). Psoriasis: the assessment and management of psoriasis. London (UK): National Institute for Health and Clinical Excellence (NICE); 2012 Oct. 61 p. (NICE clinical guideline; no. 153).
  12. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2016 [cited 2016 Jun 23]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  13. Otezla (apremilast) [package insert]. Celgene Corp. Summit (NJ): March 2016.
  14. 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.
  15. Schett G, Wollenhaupt J, Papp K, et al. Oral apremilast in the treatment of active psoriatic arthritis: Results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2012;64(10):3156-3167.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 01/11/17.

GUIDELINE UPDATE INFORMATION:

09/15/14

New Medical Coverage Guideline.

12/15/14

Revision to guideline; consisting of

04/15/15

Revision of guideline; consisting of position statement to exclude combination therapy.

09/15/15

Review and revision of guidelines; consisting of updating description section, position statement, dosage/administration, billing/coding, related guidelines, definitions, and references.

11/01/15

Revision: ICD-9 Codes deleted.

09/15/16

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

02/01/17

Revision to guideline consisting of removing the two preferred agent prerequisite requirement.

Date Printed: August 18, 2017: 10:15 AM