Effective Date

Date of Origin 

01-01-2025            

04-01-2023

Zoryve®

(roflumilast)

Cream

Cream 0.3%:

Topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older

Cream 0.15%:

Topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 6 years of age and older

1

Zoryve®

(roflumilast)

Foam

Treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older 

7

Atopic Dermatitis (AD)

Atopic dermatitis (AD), also known as atopic eczema, is a chronic, pruritic inflammatory dermatosis affecting up to 25% of children and 1-5% of adults. AD follows a relapsing course and is associated with elevated serum immunoglobulin (IgE) levels and a personal or family history of type I allergies, allergic rhinitis, and/or asthma. Onset is most common between 3 and 6 months of age, with approximately 60% of patients developing the eruption in the first year of life and 90% by age 5. While the majority of affected individuals have resolution of disease by adulthood, 10 to 30% do not, and a smaller percentage first develop symptoms as adults. AD has a complex pathogenesis involving genetic, immunologic, and environmental factors, which lead to a dysfunctional skin barrier and dysregulation of the immune system. Clinical findings include erythema, edema, xerosis, erosions/excoriations, oozing and crusting, and lichenification. These clinical findings vary by patient age and chronicity of lesions. Pruritus is a hallmark of the condition that is responsible for much of the disease burden borne by patients and their families. Typical patterns include facial, neck and extensor involvement in infants and children; flexure involvement in any age group, with sparing of groin and axillary regions.(11)

Goals of treatment are to reduce symptoms (pruritus and dermatitis), prevent exacerbations, and minimize therapeutics risks.(12) Despite its relapsing and remitting nature, the majority of patients with AD can achieve clinical improvement and disease control with topical emollient/moisturizer use and conventional topical therapies (including corticosteroids and calcineurin inhibitors).(12,13) Moisturizers reduce signs, symptoms, and inflammation in AD, and can improve severity while also increasing time between flares. Moisturizers are considered generally safe and are strongly recommended to be used as part of a treatment regimen for AD, either as monotherapy or as concurrent use with pharmacologic treatments.(14)

Topical therapies remain the mainstay of treatment due to their proven track record and generally favorable safety profile. They can be utilized individually or in combination with other topical, physical, and/or systemic treatments; as different classes of treatment have different mechanisms of action, combining therapies allows for the targeting of AD via multiple disease pathways. The American Academy of Dermatology (AAD) strongly recommends the following topical agents:(14)

• Topical corticosteroids (TCS)
• Calcineurin inhibitors (TCIs) (e.g., tacrolimus, pimecrolimus)
• Topical PDE-4 inhibitors (e.g., crisaborole) [mild to moderate AD]
• Topical JAK inhibitors (e.g., ruxolitinib) [mild to moderate AD]

TCS are the most commonly utilized FDA-approved therapies in AD and are commonly used as first-line treatment for mild-to severe dermatitis in all skin regions. TCS target a variety of immune cells and suppress the release of proinflammatory cytokines. High to very high (super) potency TCS can be used to control flares and treat severe disease, while medium potency TCS are utilized for longer courses and as maintenance therapy. Lower potency TCS may be used, and it is important to consider the anatomical site (i.e., using lower potency agents on the face, neck, genitals, and body folds) and severity of the disease when choosing a steroid potency. Most studies of TCS in AD management involve twice daily application, but some studies (particularly for potent TCS) suggest once daily use may be sufficient. Traditionally, TCS were stopped once AD signs and symptoms of an AD flare were controlled. Maintenance in between AD flares with once to twice weekly use of TCS is another approach.(14)

TCIs are a safe anti-inflammatory option for mild-to-severe AD, particularly when there is concern for adverse events secondary to corticosteroid use. Both tacrolimus and pimecrolimus have been shown to be effective in treating AD, but pimecrolimus may be more appropriate for patients who have milder disease or are sensitive to local reactions.(14) Prescribing information for pimecrolimus cream and tacrolimus ointment indicate evaluation after 6 weeks if symptoms of AD do not improve for adults and pediatrics.(15,16).

Psoriasis (PS)

Psoriasis (PS) is a chronic inflammatory skin and systemic disorder. It is a complex disease that affects the skin and joints and is associated with numerous comorbidities, including obesity and inflammatory bowel disease. Psoriasis vulgaris, or plaque psoriasis, is a cutaneous form that often presents with pink plaques with silvery scale on the scalp, elbows, knees, or presacral region, but any area of the skin may be involved.(2,3) Plaque psoriasis is the most common form (affecting 90% of adults with psoriasis), but others include guttate, erythrodermic, pustular, inverse, nail, and psoriatic arthritis. PS is clinically diagnosed based on the presence of cutaneous and systemic symptoms, and treatment is similar for most forms but is guided by the body surface area (BSA) involved.(6)

The American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) categorize psoriasis severity as mild (less than 3% of body surface area [BSA]), moderate (3% to 10% of BSA), or severe (greater than 10% of BSA). The AAD/NPF guidelines also note that psoriasis can be considered severe irrespective of BSA when it occurs in select locations (e.g., hands, feet, scalp, face, or genital area) or when it causes intractable pruritus.(4)

Topical therapies are most commonly used to treat mild to moderate PS, but they may be used in combination with phototherapy, systemic, or biologic therapies for the treatment of moderate to severe PS.(4) Topical therapies alone can be sufficient for managing limited disease and also have fewer significant adverse effects compared to systemic treatment options.(3)

Topical corticosteroids (TCS) have high efficacy and good safety for the treatment of PS, especially localized disease.(4) TCS have shown to be the most effective topical treatment for psoriasis plaques.(10) Moderate to high potency TCS are generally recommended as initial therapy, but very high (super) potency TCS may be required for thick, chronic plaques. Lower potency TCS should be used to treat PS on the face or intertriginous areas, or areas that are susceptible to skin atrophy and adverse effects.(4) It is important to consider the anatomical site, BSA of application, patient age, and severity of the disease when choosing a steroid potency and vehicle.(4,5) Studies have shown that different potency TCS were effective and safe at 2 to 4 weeks in the treatment of mild to severe plaque psoriasis. To decrease the risk of corticosteroid adverse effects, TCS may be used short term (e.g., 2 to 4 weeks) to treat flares, while vitamin D analogues, topical retinoids, and calcineurin inhibitors can be used as maintenance treatment.(4)

Topical calcineurin inhibitors (TCIs), such as tacrolimus and pimecrolimus, are often used in the treatment of psoriasis.(4) The use of TCIs can lead to the avoidance of adverse effects secondary to long term TCS use, and can be beneficial for prolonged treatment of areas of thinner skin, the face, and intertriginous areas.(4,10)

Vitamin D analogues (e.g., calcipotriene and calcitriol) have been shown to be safe and effective for the treatment of mild to moderate PS.(4) Vitamin D analogues may be used as monotherapy, but combination therapy with a TCS has shown superior efficacy.(4,10) Calcipotriene ointment combined with topical tacrolimus is also more efficacious than tacrolimus alone.(4)

Tazarotene is a topical retinoid that is recommended for the treatment of mild to moderate PS. Tazarotene has been shown to be efficacious as monotherapy, but adding a TCS as combination therapy increases efficacy. The combination use with a medium to high potency TCS has been shown to increase the duration of treatment effect and the time of remission. Tazarotene can also be beneficial for the treatment of palmar-plantar psoriasis and nail psoriasis. Studies have shown topical tazarotene has similar efficacy to fluocinonide cream, crude coal tar 5% ointment, and calcipotriene 0.005% ointment.(4)

Other topical medications that can be used for the treatment of PS include salicylic acid and coal tar, and both are recommended for the treatment of mild to moderate psoriasis.(4) Salicylic acid is an effective treatment as monotherapy, or it can be combined with a TCS or TCI to increase efficacy and the penetration of the combined agent.(4,10) Coal tar may be combined with phototherapy to reduce the time of clearance and improve therapeutic outcomes compared to phototherapy alone. Topical anthralin is also an effective treatment for mild to moderate psoriasis.(4)

For the treatment of PS in the pediatric patient population, topical corticosteroids are the mainstay option based on extensive clinical experience that supports efficacy. Topical calcineurin inhibitors are also a treatment option and may be preferred for psoriasis of the face, genitalia, and body folds. Vitamin D analogues are recommended as a treatment option for childhood plaque psoriasis and are considered safe, effective, and generally well tolerated. Vitamin D analogues are frequently used in combination with TCS. Other topical therapies that may be used for the treatment of pediatric psoriasis include tazarotene, anthralin, and coal tar.(5)

Seborrheic Dermatitis (SD)

Seborrheic dermatitis (SD) is a common skin condition in infants, adolescents, and adults. The characteristic symptoms of scaling, erythema, and itching occur most often on the scalp, face, chest, back, axilla, and groin. SD is a clinical diagnosis based on the location and appearance of the lesions. Although some environmental triggers (e.g., low temperature and humidity in winter) are likely to promote its development, several other factors including fungal colonization by Malassezia spp, sebaceous gland activity, as well as immunosuppression, endocrine, neurologic and iatrogenic factors have been postulated.(8,9)

Treatment of SD is aimed at modulating sebum production, reducing skin colonization by Malassezia spp and controlling inflammation. In mild-to moderate SD forms, topical antifungals and/or topical corticosteroids are first-line therapy. Topical calcineurin inhibitors are effective, well tolerated second-line treatments. In Severe and/or resistant cases the off-label use of some topical and systemic drugs, as well as physical treatment with ultraviolet blue (UVB) phototherapy may be considered. Topical treatments include:(8,9)

• SD on scalp
  • Topical antifungal agents 
    • Ciclopirox shampoo
    • Ketoconazole shampoo
  • Topical corticosteroids
    • Betamethasone valerate foam
    • Clobetasol shampoo
    • Fluocinolone shampoo
    • Fluocinolone solution
  • Over the counter preparations
    • Coal tar shampoo
    • Selenium sulfide shampoo
    • Tea tree oil shampoo
    • Zinc pyrithione shampoo
• SD on face and body 
  • Topical antifungals
    • Ciclopirox gel or cream
    • Clotrimazole cream
    • Ketoconazole cream, foam
    • Sertaconazole cream
  • Calcineurin inhibitors
    • Pimecrolimus cream
    • Tacrolimus ointment
  • Topical corticosteroids
    • Betamethasone valerate cream or lotion
    • Desonide cream, foam, gel, or ointment
    • Fluocinolone cream, oil, or solution
    • Hydrocortisone cream or ointment

Systemic antifungals (terbinafine, itraconazole) are mainly indicated in acute and/or severe and/or resistant SD forms.(8)

Efficacy

Plaque psoriasis

Two multicenter, randomized, double-blind, vehicle-controlled trials (DERMIS-1 [NCT04211363] and DERMIS-2 [NCT04211389]) enrolled a total of 881 subjects with mild to severe plaque psoriasis and an affected BSA of 2% to 20%. At baseline, 16% of subjects had an Investigator’s Global Assessment (IGA) score of 2 (mild), 76% had an IGA score of 3 (moderate), and 8% had an IGA score of 4 (severe). One hundred seventy-nine (20%) subjects had an intertriginous IGA (I-IGA) score of 2 or higher (mild) at baseline, and 678 (77%) subjects had a baseline Worst Itch-Numeric Rating Score (WI-NRS) score of 4 or higher on a scale of 0 to 10.(1)

Subjects were randomized 2:1 to receive Zoryve or vehicle applied once daily for 8 weeks. The primary endpoint was the proportion of subjects who achieved IGA treatment success at week 8. Success was defined as a score of “Clear” (0) or “Almost Clear” (1), plus a 2-grade improvement from baseline. Secondary endpoints included the proportion of subjects that achieved I-IGA success at week 8 and WI-NRS success sequentially at weeks 8, 4, and 2. WI-NRS success was defined as a reduction of at least 4 points from baseline in subjects with a baseline WI-NRS score of at least 4.(1) 

Patients treated with Zoryve achieved greater IGA success at week 8 compared to patients treated with vehicle (41.5% vs 5.8% [difference of 39.7% for DERMIS-1], 36.7% vs 7.1% [difference of 29.5% for DERMIS-2]. Among subjects with an I-IGA score of at least 2 (mild) at baseline (approximately 22% of subjects in DERMIS-1 and 19% in DERMIS-2), there was a higher percentage of subjects who achieved I-IGA success at week 8 in the group who received Zoryve compared to the group who received vehicle (DERMIS-1: 71.5% vs. 13.8%; DERMIS-2: 67.5% vs. 17.4%). Secondary endpoints were not statistically significant.(1)

Seborrheic dermatitis

Two randomized double-blind, vehicle-controlled trials (STRATUM [NCT04973228]) and Trial 203 [NCT04091646] enrolled patients with seborrheic dermatitis involving the scalp, face, and/or body with an Investigator Global Assessment (IGA) of moderate or severe (IGA of 4 or 3 on a 5 point scale from 0 to 4). The primary endpoint in both studies was the proportion of patients who achieved IGA treatment success at Week 8. Success was defined as a score of "Clear" (0) or "Almost Clear" (1), plus a 2-grade improvement from baseline. IGA was achieved in 79.5% and 71.1% of patients in STRATUM and Trial 203 respectively, with a 95% confidence interval in both trials.(7)

Atopic dermatitis

Two multicenter, randomized, double-blind, vehicle-controlled trials (INTEGUMENT-1 [NCT04773587] and INTEGUMENT-2 [NCT04773600]) enrolled a total of 1337 adult and pediatric subjects 6 years of age and older (615 subjects were 6 to 17 years of age) with mild to moderate atopic dermatitis. Subjects were randomized 2:1 to receive ZORYVE cream, 0.15%, or vehicle cream applied once daily for 4 weeks. The median age of the trial population was 20 years (range 6 to 91 years of age). At baseline, subjects had a mean affected BSA of 14% (range of 3% to 88%), and 42% had facial involvement. At baseline, 24% of subjects had a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 2 (mild), and 76% had a vIGA-AD score of 3 (moderate).(1)

The primary endpoint was the proportion of subjects who achieved vIGA-AD treatment success at Week 4. Success was defined as a score of "Clear" (0) or "Almost Clear" (1), plus a 2-grade improvement from baseline.(1)

*The difference in percent and related 95% CIs are Mantel-Haenszel estimates stratified by pooled study site and vIGA-AD randomization strata.

Safety

Zoryve is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C).(1,7) 

1

Zoryve cream prescribing information. Arcutis Biotherapeutics, Inc. July 2024. 

2

Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. Journal of the American Academy of Dermatology. 2019;80(4):1029-1072. doi:10.1016/j.jaad.2018.11.057

3

Menter A, Gelfand JM, Connor C, et al. Joint American Academy of Dermatology–National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. Journal of the American Academy of Dermatology. 2020;82(6):1445-1486. doi:10.1016/j.jaad.2020.02.044

4

Elmets CA, Korman NJ, Prater EF, et al. Joint AAD–NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures. Journal of the American Academy of Dermatology. 2021;84(2):432-470. doi:10.1016/j.jaad.2020.07.087

5

Menter A, Cordoro KM, Davis DMR, et al. Joint American Academy of Dermatology–National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients. Journal of the American Academy of Dermatology. 2020;82(1):161-201. doi:10.1016/j.jaad.2019.08.049

6

Garner KK, Hoy KDS, Carpenter AM. Psoriasis: Recognition and Management Strategies. Am Fam Physician. 2023;108(6):562-573.

7

Zoryve foam prescribing information. Arcutis Biotherapeutics, Inc. December 2023.

8

Dall'Oglio F, Nasca MR, Gerbino C, Micali G. An Overview of the Diagnosis and Management of Seborrheic Dermatitis. Clin Cosmet Investig Dermatol. 2022 Aug 6;15:1537-1548. doi: 10.2147/CCID.S284671. PMID: 35967915; PMCID: PMC9365318.

9

Clark GW, Pope SM, Jaboori K. Diagnosis and Treatment of Seborrheic Dermatitis. Am Fam Physician. 2015;91(3):185-190.

10

Shreiber AM, Friery E. Psoriasis: Update on topical therapy from the American Academy of Dermatology. Am Fam Physician. 2022;105(5):558-560.

11

Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of Care for the Management of Atopic Dermatitis: Section 1. Diagnosis and Assessment of Atopic Dermatitis. J Am Acad Dermatol. 2014 Feb;70(2):338-51.

12

Sidbury R, Tom WL, Bergman JN, et al. Guidelines of care for the management of atopic dermatitis: Section 4. Prevention of disease flares and use of adjunctive therapies and approaches. J Am Acad Dermatol. 2014 Dec;71(6):1218-33.

13

Davis DM, Drucker AM, Alikhan A, et al. Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies. Journal of the American Academy of Dermatology. 2024;90(2):e43-e56. doi:10.1016/j.jaad.2023.08.102

14

Sidbury R, Alikhan A, Bercovitch L, et al. Guidelines of care for the management of atopic dermatitis in adults with topical therapies. J Am Acad Dermatol. 2023;89(1):e1-e20.

15

Pimecrolimus cream prescribing information. Oceanside Pharmaceuticals. September 2020.

16

Tacrolimus ointment prescribing information. Glenmark Pharmaceuticals Inc., USA. August 2023.

Zoryve

roflumilast cream

0.15 %

M ; N ; O ; Y

N

Zoryve

roflumilast cream

0.3 %

M ; N ; O ; Y

N

Zoryve

roflumilast foam

0.3 %

M ; N ; O ; Y

N

Zoryve

roflumilast cream

0.15 %

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zoryve

roflumilast cream

0.3 %

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zoryve

roflumilast foam

0.3 %

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PA

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The patient has a diagnosis of mild to moderate atopic dermatitis (AD) AND ALL of the following:
      1. ONE of the following:
         1. The patient has tried and had an inadequate response to at least a low-potency topical corticosteroid used in the treatment of AD after at least a 4-week duration of therapy OR
         2. The patient has an intolerance or hypersensitivity to at least a low-potency topical corticosteroid used in the treatment of AD OR
         3. The patient has an FDA labeled contraindication to ALL topical corticosteroids used in the treatment of AD AND
      2. ONE of the following:
         1. The patient has tried and had an inadequate response to a topical calcineurin inhibitor used in the treatment of AD after at least a 6-week duration of therapy OR
         2. The patient has an intolerance or hypersensitivity to a topical calcineurin inhibitor used in the treatment of AD OR
         3. The patient has an FDA labeled contraindication to ALL topical calcineurin inhibitors used in the treatment of AD AND
      3. BOTH of the following:
         1. The patient is currently treated with topical emollients and practicing good skin care AND
         2. The patient will continue the use of topical emollients and good skin care practices in combination with the requested agent OR
   2. The patient has a diagnosis of plaque psoriasis AND ALL of the following:
      1. The patient's affected body surface area (BSA) is less than or equal to 20% AND
      2. ONE of the following:
         1. The patient has tried and had an inadequate response to a topical corticosteroid used in the treatment of plaque psoriasis after at least a 2-week duration of therapy OR
         2. The patient has an intolerance or hypersensitivity to therapy with a topical corticosteroid used in the treatment of plaque psoriasis OR
         3. The patient has an FDA labeled contraindication to ALL topical corticosteroids used in the treatment of plaque psoriasis AND
      3. ONE of the following:
         1. The patient has tried and had an inadequate response to another topical psoriasis agent with a different mechanism of action (e.g., vitamin D analogs, calcineurin inhibitors, tazarotene) OR
         2. The patient has an intolerance or hypersensitivity to another topical psoriasis agent with a different mechanism of action OR
         3. The patient has an FDA labeled contraindication to ALL other topical psoriasis agents with a different mechanism of action OR
   3. The patient has a diagnosis of seborrheic dermatitis AND BOTH of the following:
      1. ONE of the following:
         1. The patient has tried and had an inadequate response to ONE topical antifungal OR ONE topical corticosteroid used in the treatment of seborrheic dermatitis OR
         2. The patient has an intolerance or hypersensitivity to ONE topical antifungal OR ONE topical corticosteroid used in the treatment of seborrheic dermatitis OR
         3. The patient has an FDA labeled contraindication to ALL topical antifungals AND topical corticosteroids used in the treatment of seborrheic dermatitis AND
      2. ONE of the following:
         1. The patient has seborrheic dermatitis of the scalp OR
         2. The patient has tried and had an inadequate response to ONE topical calcineurin inhibitor (e.g., pimecrolimus, tacrolimus) used in the treatment of seborrheic dermatitis OR
         3. The patient has an intolerance or hypersensitivity to ONE topical calcineurin inhibitor (e.g., pimecrolimus, tacrolimus) used in the treatment of seborrheic dermatitis OR
         4. The patient has an FDA labeled contraindication to ALL topical calcineurin inhibitors used in the treatment of seborrheic dermatitis OR
   4. The patient has another FDA labeled indication for the requested agent and route of administration AND
2. If the patient has an FDA labeled indication, then BOTH of the following:
   1. ONE of the following:
      1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
      2. There is support for using the requested agent for the patient’s age for the requested indication AND
   2. The requested dosage form and strength of Zoryve is FDA labeled for the requested indication AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., dermatologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: diagnosis of plaque psoriasis 12 months; diagnosis of atopic dermatitis or seborrheic dermatitis 3 months; all other FDA labeled indications 12 months

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., dermatologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months