OBJECTIVE

The intent of the Injectable Atopic Dermatitis Agent(s) Prior Authorization (PA) program is to ensure that patients prescribed therapy meet the selection requirements defined in product labeling and/or clinical guidelines and/or clinical studies. The PA defines appropriate use as the Food and Drug Administration (FDA) labeled indication or as supported by guidelines and/or clinical evidence.

 

TARGET AGENT

Dupixent^® (dupilumab)

 

QUANTITY LIMIT TARGET AGENT- RECOMMENDED LIMIT

Brand (generic)	GPI	Multisource Code	Quantity Limit
Dupixent (dupilumab)
300mg/2 mL pre-filled syringe	9027302000E520	M, N, O, Y	2 syringes (4 mL)/28 days

* The recommended dose of Dupixent for adult patients is an initial loading dose of 600 mg (two 300 mg injections) subcutaneously, followed by 300 mg given every other week for maintenance

 

PRIOR AUTHORIZATION CRITERIA FOR APPROVAL

Initial Evaluation

Targeted Agent will be approved when ALL of the following are met:

1. ONE of the following:
   1. There is documentation that the patient is currently being treated with the requested agent (starting on samples is not approvable) within the past 90 days

     OR

1. 2. The prescriber states the patient is currently being treated with the requested agent within the past 90 days (starting on samples is not approvable) AND is at risk if therapy is changed

OR

1. 3. The patient has the diagnosis of moderate-to-severe atopic dermatitis AND ALL of the following:
      1. ONE of the following:
         1. The patient has at least 10% body surface area involvement

                    OR

1. 1. 1. 2. The patient has involvement of the palms and/or soles of the feet

AND

1. 1. 2. The patient is 18 years of age or over

                         AND

1. 1. 3. ONE of the following:
         1. There is documentation the patient has tried and had an inadequate response to a systemic immunosuppressant (e.g., methotrexate, azathioprine, CellCept, cyclosporine) for a minimum of 3 months

                    OR

1. 1. 1. 2. There is documentation the patient has tried and had an inadequate response to BOTH at least a mid- potency topical steroid for a minimum of 4 weeks AND a topical calcineurin inhibitor (e.g., pimecrolimus, tacrolimus) for a minimum of 6 weeks

                    OR

1. 1. 1. 3. The patient has a documented intolerance, FDA labeled contraindication, or hypersensitivity to ALL systemic immunosuppressants, a mid- potency topical steroid AND a topical calcineurin inhibitor

                         AND

1. 1. 4. ONE of the following:
         1. There is documentation that the patient has tried and had an inadequate response to use of a high potency topical steroid OR oral steroids for the treatment of flares for a minimum of 1 week

OR

1. 1. 1. 2. The patient has a documented intolerance, FDA labeled contraindication, or hypersensitivity to BOTH a high potency topical steroid AND an oral steroid  *Will accept that the patient has face/neck, skin folds, intertriginous, and/or genital area involvement for topical steroids

                              AND

1. 1. 5. The prescriber has documented the patient’s baseline pruritus and other symptom severity (e.g., erythema, edema, xerosis, erosions/excoriations, oozing and crusting, and/or lichenification)

          AND

1. 1. 6. The patient will continue the use of topical emollients and good skin care practices along with the requested agent

                    OR

1. 4. The patient has another FDA approved indication for the requested agent

AND

2. The prescriber is a specialist in the area of the patient’s diagnosis or the prescriber has consulted with a specialist in the area of the patient’s diagnosis (e.g., dermatologist, allergist, immunologist)

AND

3. The patient does NOT have any FDA labeled contraindications to the requested agent

AND

4. ONE of the following:
   1. The quantity requested is less than or equal to the program quantity limit

          OR

1. 2. The quantity (dose) requested is within FDA approved labeling and the prescribed dose cannot be achieved using a lesser quantity of a higher strength

         

Length of Approval:  6 months

 

Renewal Evaluation

1. The patient has been previously approved for the requested agent through Prime Therapeutics Prior Authorization Review process

AND

2. If the patient has a diagnosis of moderate-to-severe atopic dermatitis, then BOTH of the following
   1. The patient has a reduction or stabilization from baseline in at least ONE of the following:
      1. Affected body surface area
      2. Flares
      3. Pruritus, erythema, edema, xerosis, erosions/excoriations, oozing and crusting, and/or lichenification

               AND

1. 2. The patient will continue the use of topical emollients and good skin care practices along with the requested agent

AND

3. The prescriber is a specialist in the area of the patient’s diagnosis or the prescriber has consulted with a specialist in the area of the patient’s diagnosis (e.g. dermatologist, allergist, immunologist)

AND

4. The patient does NOT have an FDA labeled contraindication to the requested agent

AND

5. ONE of the following:
   1. The quantity requested is less than or equal to the program quantity limit

               OR

1. 2. The quantity (dose) requested is within FDA approved labeling and the prescribed dose cannot be achieved using a lesser quantity of a higher strength

              

Length of Approval:  12 months

 

FDA APPROVED INDICATIONS AND DOSAGE¹

Agent	Indication	Dosing
Dupixent® (dupilumab) subcutaneous injection	Treatment of adult patients with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable	Initial dose: 600 mg (two 300 mg injections in different injection sites), followed by 300 mg given every other week

 

CLINICAL RATIONALE

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.^2,3 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.²

Goals of treatment are to reduce symptoms (pruritus and dermatitis), prevent exacerbations, and minimize therapeutics risks. Despite its relapsing and remitting nature, the majority of patients with AD can achieve clinical improvement and disease control with nonpharmacological interventions (e.g. emollient use), conventional topical therapies (including corticosteroids and calcineurin inhibitors) and environmental and occupational modifications, when necessary.⁴ The American Academy of Dermatology guidelines suggest application of moisturizers should be an integral part of the treatment of patients with AD as there is strong evidence that their use reduces disease severity and need for pharmacologic intervention. They are an important component of maintenance treatment and prevention of flares.⁵  The AAD recommends topical corticosteroids for patients who fail to respond to good skin care and regular use of emollients alone. Proactive, intermittent use of topical corticosteroids as maintenance therapy (1-2 times/weekly) on areas that commonly flare is recommended to help prevent relapses and is more effective than use of emollients alone. Monitoring by physical exam for cutaneous side effects during long-term, potent steroid use is suggested. Proactive, once to twice weekly application of mid-potency TCS for up to 40 weeks has not demonstrated adverse events (e.g., purpura, telangiectasia, striae, focal hypertichosis, acneiform/rosacea-like eruptions, skin atrophy) in clinical trials.⁵ It is suggested that patients with acute flares use super high or high potency topical corticosteroids for up to two weeks and then replace these with lower potency preparations until the lesions resolve.⁴ Maintenance therapy includes use of moderate to high potency topical corticosteroids or topical calcineurin inhibitors. Medium to high potency topical corticosteroids applied once daily for 2 consecutive days per week for up to 16 weeks is recommended over topical calcineurin inhibitors.⁴

Topical calcineurin inhibitors (TCIs) (e.g., pimecrolimus, tacrolimus) are recommended by the AAD and are effective for acute and chronic treatment.  They are particularly useful in selected clinical situations, such as recalcitrance to steroids; for sensitive areas (face, anogenital, skin folds); for steroid-induced atrophy; and when there is long-term uninterrupted topical steroid use. TCIs are recommended for use on actively affected areas as a steroid-sparing agent.  Proactive, intermittent use of TCIs as maintenance therapy (2-3 times per week) on areas that commonly flare is recommended to help prevent relapses while reducing need for topical corticosteroids, and is more effective than use of emollients alone.²

Prescribing information for Elidel^® (pimecrolimus) cream indicates evaluation after 6 weeks if symptoms of AD do not improve.⁷

Phototherapy is recommended as a treatment for both acute and chronic AD in children and adults, after failure of the mentioned above. Systemic immunomodulator agents are indicated and recommended for the subset of adult and pediatric patients in whom optimized topical regimens using emollients, topical anti-inflammatory therapies, adjunctive methods, and/or phototherapy do not adequately control the signs and symptoms of disease. Photo therapy and systemic immunomodulating agents may also be used in patients whose medical, physical, and/or psychological states are greatly affected by their skin disease.⁶ Oral cyclosporine or corticosteroids are short term treatment options for moderate to severe dermatitis with rapid onset or bridging therapy. Oral cyclosporine is suggested over oral corticosteroid. AD symptoms begin to resolve as quickly with the use of cyclosporine within the first week and dramatic improvement can be seen in 8 weeks. Long term (e.g. beyond one year) use of oral cyclosporine is limited by its side effects, mainly hypertension and kidney toxicity. Oral corticosteroids are recommended for patients whom cannot use cyclosporine. Dose for corticosteroid recommended is 40 to 60 mg per day for one week then taper over the following two to three weeks. While patients are being tapered off, patients are transitioned to another immunosuppressive agent with better safety profile for long term use. Second-line systemic immunosuppressive agents include methotrexate, azathioprine, and mycophenolate mofetil. The maximum benefit of methotrexate may not be seen for several months after start of therapy. Azathioprine and mycophenolate mofetil benefits maybe seen for 6 to 8 weeks.^3,4 

Dupilumab was FDA approved through two randomized, double blind, placebo-controlled phase 3 trials (SOLO 1 and SOLO 2).  All patients in both trials were at least 18 years old, had chronic AD (according to American Academy of Dermatology Consensus Criteria Eichenfield 2014) that had been present for at least 3 years, and had ≥10% body surface area (BSA) involvement at the screening and baseline visits.  Additionally, all patients had a documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or whom topical treatments are otherwise medically inadvisable.  The primary outcome measure in both trails was proportion of patients with both IGA (Investigator Global Assessment) 0 to 1 (on a 5-point scale) and a reduction from baseline of ≥2 points at week 16. There were several secondary endpoints included.  Some examples include: proportion of patients with Eczema Area and Severity Index (EASI) -75 (≥75% improvement from baseline) at week 16, percent change from baseline to week 16 in pruritus numerical rating scale (NRS), change from baseline to week 16 in % BSA, and changes in quality of life, anxiety, and depression. 

The manufacturer reports the following results from SOLO 1 and SOLO 2. In SOLO 1, the primary outcome (an IGA of 0-1 and a reduction of ≥2 points from baseline at week 16) occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo).  The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons).  In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons).  Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life.^7-9

 

REFERENCES

1. Dupixent prescribing information.  Regeneron Pharmaceuticals, Inc. April 2018.
2. Eichenfield L, Tom W, Chamlin S, et al. Guidelines of care for the management of atopic dermatitis: Part 1: Diagnosis and Assessment of Atopic Dermatitis. J Am Acad Dermatol. 2014;70(2): 338–351.
3. Berger, Timothy G., MD., et al. Management of Severe Refractory Atopic Dermatitis (eczema) in Adults. UpToDate. Last updated May 3, 2018.
4. Weston, William L., MD., et al. Treatment of Atopic Dermatitis (eczema). UpToDate. Last updated April 2018.
5. Eichenfield L, Tom W, Berger T, 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(1):116-32. http://www.jaad.org/article/S0190-9622(14)01257-2/pdf.
6. Sidbury, Robert, MD., et al. Guidelines of Care for the Management of Atopic Dermatitis. Section 3. Management and Treatment with Phototherapy and Systemic Agents. J Am Acad Dermatol 2014; 71 (2): 327-349.
7. Elidel prescribing information. Valeant Pharmaceuticals. December 2017.
8. Study of Dupilumab (REGN668/SAR231893) Monotherapy Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis (SOLO 1). NCT02277743. ClinicalTrials.gov.
9. Study of Dupilumab (REGN668/SAR231893) Monotherapy Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis (SOLO 2). NCT02277769. ClinicalTrials.gov.
10. Simpson, Eric, et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 2016; 375:2335-2348. December 15, 2016. DOI: 10.1056/NEJMoa1610020.

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

 

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