Subject: Opzelura (Atopic Dermatitis) PA with Limit 5556-C UDR 04-2023 v2

Drug

OPZELURA  (ruxolitinib cream)

Note: *Drugs that are listed in the target drug box include both brand and generic and all dosage forms and strengths unless otherwise stated. OTC products are not included unless otherwise stated.

Policy:

FDA-APPROVED INDICATIONS
Opzelura is indicated for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adult and pediatric patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

Limitation of Use:
Use of Opzelura in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants such as azathioprine or cyclosporine is not recommended.


COVERAGE CRITERIA
The requested drug will be covered with prior authorization when the following criteria are met:
•   The requested drug is NOT being prescribed in combination with
     therapeutic biologics, other janus kinase (JAK) inhibitors, or potent
     immunosuppressants such as azathioprine or cyclosporine
AND
     •   The requested drug is being prescribed for topical short-term
          and non-continuous chronic treatment of mild to moderate
          atopic dermatitis in a non-immunocompromised patient
          AND
          º   The request is for an adult or pediatric patient 12 years of
               age or older
          AND
                    •   The request is NOT for continuation of therapy
                              AND
                              •   The patient’s disease is not adequately
                                   controlled with other topical prescription
                                   therapies (e.g., medium or higher potency
                                   topical corticosteroid, topical calcineurin
                                   inhibitor)
                              OR
                              •   Other topical prescription therapies are not
                                   advisable (e.g., medium or higher potency
                                   topical corticosteroid, topical calcineurin
                                   inhibitor)
               OR
                    •   The request is for continuation of therapy
                         AND
                         •   The patient has achieved or maintained a positive
                              clinical response as evidenced by improvement
                              [(e.g., improvement in or resolution of any of the
                              following signs and symptoms: erythema
                              (redness), edema (swelling), xerosis (dry skin),
                              erosions, excoriations (evidence of scratching),
                              oozing and crusting, lichenification (epidermal
                              thickening), OR pruritus (itching)]
               AND
               º   The requested drug will NOT be applied to affected areas
                    of greater than 20% body surface area (BSA)
AND
•   If additional quantities are being requested, then the requested drug
     is being prescribed to treat a body surface area that requires more
     than 60 grams per 28 days

Quantity Limits apply.
60 grams per 21 days* or 180 grams per 63 days**
For larger BSA: 240 grams per 21 days* or 720 grams per 63 days**

*The duration of 21 days is used for a 28-day fill period and 63 days is used for an 84-day fill period to allow time for refill processing.
**For new starts, the mail limit will be the same as the retail limit. The intent is for prescriptions of the requested drug to be filled one month at a time for new starts, even if filled at mail order; there should be no 3-month supplies filled for new starts. The duration of 21 days is used for a 28-day fill period to allow time for refill processing.

     Duration of Approval (DOA):
               •   5556-C: Initial therapy DOA: 3 months; Continuation of
                    therapy DOA: 12 months

RATIONALE
The intent of the criteria is to provide coverage consistent with product labeling, FDA guidance, standards of medical practice, evidence-based drug information, and/or published guidelines. Opzelura is indicated for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adult and pediatric patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.¹

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease that occurs most frequently in children, but also affects many adults. It follows a relapsing course. Notable clinical findings of AD include erythema, edema, xerosis, erosions/excoriations, oozing and crusting, and lichenification. Pruritis is a hallmark of the condition that is responsible for much of the disease burden borne by patients and their families.⁴

Per the American Academy of Dermatology’s Guidelines of Care for the Management of Atopic Dermatitis, topical agents are the mainstay of AD therapy. Topical agents from several classes are frequently used in combination, in part because they address different aspects of AD pathogenesis. Topical corticosteroids (TCS) are used in the management of AD in both adults and children and are the mainstay of anti-inflammatory therapy. They are typically introduced into the treatment regimen after failure of lesions to respond to good skin care and regular use of moisturizers alone. TCS are generally the standard to which other topical anti-inflammatory therapies are compared and are used for both active inflammatory disease and for prevention of relapses. During significant flares, mid – or higher-potency TCS for short courses may be appropriate to gain control of symptoms; however, for long-term management, the least-potent corticosteroid that is effective should be used to minimize risk of adverse effects. Comparative trials are limited in duration and scope, and as a result, there are no data to support any agent as being more efficacious than others. Patient vehicle preference, along with cost and availability, often determine their selection.⁵ A list of medium or higher potency topical corticosteroids are listed below in Table 1 for reference.

In the U.S., Topical Calcineurin Inhibitors (TCI) are approved as second-line therapy for the short-term and noncontinuous treatment of AD in non-immunocompromised individuals who have failed to respond to other topical prescription treatments for AD or when those treatments are not advisable. TCI have the benefit of not carrying risk for cutaneous atrophy, with little negative effect on collagen synthesis and skin thickness. TCI can therefore be used as steroid-sparing agents. Clinical situations in which topical calcineurin inhibitors may be preferable to topical steroids include recalcitrance to steroids, sensitive areas (e.g., face, anogenital, skin folds), steroid-induced atrophy and long-term uninterrupted steroid use. TCI may also be combined with TCS.⁵

The safety and efficacy of Opzelura for atopic dermatitis was evaluated by the Topical Ruxolitinib Evaluation in Atopic Dermatitis studies (TRuE-AD) which was comprised of 2 randomized, double-blind, vehicle-controlled, phase 3 studies of identical design. The current study data compares ruxolitinib cream to vehicle making it difficult to compare efficacy to either class of agents (TCI or TCS) recommended in the American Academy of Dermatology Guidelines.⁶ Therefore, coverage for ruxolitinib cream will be considered if the patient’s disease is not adequately controlled with other topical prescription therapies or when those therapies are not advisable (e.g., medium or higher potency topical corticosteroid, topical calcineurin inhibitor).¹

 

TABLE 1:  EXAMPLES OF TOPICAL CORTICOSTEROIDS FOR TREATMENT OF ATOPIC DERMATITIS 2,3,5
Medium Potency	betamethasone dipropionate lotion, spray 0.05%
	betamethasone valerate cream/lotion 0.1%/foam 0.12%
	clocortolone pivalate cream 0.1%
	desonide lotion, ointment 0.05%
	desoximetasone cream 0.05%
	fluocinolone acetonide cream/ointment/kit 0.025%
	flurandrenolide cream/ointment/lotion 0.05%
	fluticasone propionate cream/lotion 0.05%/ointment 0.005%
	hydrocortisone butyrate cream/lipocream/lotion/ointment/solution 0.1%
	hydrocortisone probutate cream 0.1%
	hydrocortisone valerate cream/ointment 0.2%
	mometasone furoate cream/lotion/solution 0.1%
	prednicarbate cream/ointment 0.1%
	triamcinolone acetonide cream/ointment/lotion/kit 0.1%
	triamcinolone acetonide cream/ointment/lotion 0.025%
	triamcinolone acetonide ointment 0.05%
High Potency	amcinonide cream/ointment/lotion 0.1%
	betamethasone dipropionate cream/ointment 0.05%
	betamethasone dipropionate augmented cream/lotion 0.05%
	betamethasone valerate ointment 0.1%
	desoximetasone cream/ointment/spray 0.25%/gel/ointment 0.05%
	diflorasone diacetate cream (emollient base) 0.05% diflorasone cream 0.05%
	halcinonide cream/ointment 0.1%
	fluocinonide cream/emulsified cream/ointment/gel/solution 0.05%
	mometasone furoate ointment 0.1%
	triamcinolone acetonide aerosol solution 0.147 mg/g
	triamcinolone acetonide cream/ointment 0.5%
Very High Potency	betamethasone dipropionate augmented ointment/gel 0.05%
	clobetasol propionate cream/ointment/foam/shampoo/gel/lotion/solution/spray 0.05%/cream 0.025%
	diflorasone diacetate ointment 0.05%
	flurandrenolide tape 4mcg/cm2
	halobetasol propionate cream/ointment/lotion/kit 0.05%
	fluocinonide cream 0.1%

In the TRuE-AD study, patients were randomized 2:2:1 to twice-daily 0.75% RUX cream, 1.5% RUX cream, or vehicle cream for 8 continuous weeks. Subjects had affected body surface area (BSA) of 3 to 20%. The primary endpoint was Investigator’s Global Assessment treatment success at week 8 (Investigator’s Global Assessment score of 0/1 and ≥ 2-grade improvement from baseline).  Significantly more patients achieved Investigator’s Global Assessment treatment success with 0.75% RUX cream and 1.5% RUX cream versus vehicle at week 8. Significant itch reductions versus vehicle were reported within 12 hours of first application of 1.5% RUX cream.⁶ The Opzelura prescribing information notes that if signs and symptoms of atopic dermatitis do not improve within 8 weeks of Opzelura use, patients should be re-examined by their healthcare provider.¹ Therefore, to allow the patient a sufficient trial period of 8 weeks with consideration of additional time needed for follow-up with their provider, initial approval will be for 3 months.  For continuation of therapy, if the patient is showing a positive clinical response [e.g., improvement in or resolution of any of the following signs and symptoms: erythema (redness), edema (swelling), xerosis (dry skin), erosions, excoriations (evidence of scratching), oozing and crusting, lichenification (epidermal thickening), OR pruritus (itching)], then the request will be approved for 12 months.

For atopic dermatitis, patients should be instructed to apply a thin layer of Opzelura twice daily to affected areas of up to 20% body surface area (BSA). Patients should stop using Opzelura when signs and symptoms (e.g., itch, rash, and redness) of atopic dermatitis resolve.¹

Use of Opzelura should not exceed one 60 gram tube per week or one 100 gram tube per 2 weeks. Opzelura is available in a 60 gram and 100 gram tube.¹  No universal standard exists for quantity of application, although suggested methods include use of the adult fingertip unit (the amount from the distal interphalangeal joint to the fingertip or approximately 0.5 grams, being applied over an area equal to 2 adult palms), following the rule of 9’s that measures the percent affected area, and use of charts that propose amounts based on patient age and body site.⁵ Palmar hand surface is approximately equal to 1% body surface area (BSA)⁷; therefore, one fingertip unit treats 2% of BSA.

The initial quantity limit for Opzelura will be 60 grams per 28 days. This quantity will allow a treatment area of approximately 4% BSA. If additional quantities are being requested, treatment of a body surface area (BSA) that requires more than 60 grams per 28 days will be required. The post quantity limit will allow up to 240 grams per 28 days, which allows for up to the max dosing of 60 grams per week according to the package insert.

 

 

Place of Service:

Outpatient

The above policy is based on the following references:

1. Opzelura [package insert]. Wilmington, DE: Incyte Corporation; September 2023.
2. Lexicomp Online, AHFS DI (Adult and Pediatric) Online. Waltham, MA: UpToDate, Inc.; 2023. https://online.lexi.com. Accessed February 21, 2023.
3. Micromedex (electronic version). Merative, Ann Arbor, Michigan, USA. Available at: https://www.micromedexsolutions.com/ (cited: February/21/2023).
4. Eichenfield LF, Tom WL, et. al. Guidelines of care for the management of atopic dermatitis: Section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol 2014; 70:338-51.
5. Eichenfield LF, Tom WL, et. al. Guidelines of care for the management of atopic dermatitis: Section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol 2014; 71:116-32.
6. Papp K, Szepietowski JC, Kircik L, et. al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol 2021;85:863-72.
7. S. Department of Health & Human Services. Burn Triage and Treatment – Thermal Injuries. Chemical Hazards Emergency Medical Management. November 16, 2022. Available at: https://chemm.hhs.gov/burns.htm. Accessed April 6, 2022.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

December 31, 2023