07-01-2024            

Cibinqo®

(abrocitinib)

Tablet

Treatment of adults and pediatric patients 12 years of age and older with refractory, moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

• Limitations of use: 
  • Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants

1

Atopic Dermatitis

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.(2)

Goals of treatment are to reduce symptoms (pruritus and dermatitis), prevent exacerbations, and minimize therapeutics risks.(6) 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, wet wrap therapy), conventional topical therapies (including corticosteroids and calcineurin inhibitors) and environmental and occupational modifications, when necessary.(4,6) 

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:(4)

• Calcineurin inhibitors (TCIs) (e.g., tacrolimus, pimecrolimus)
• Topical corticosteroids (TCS)
• Topical PDE-4 inhibitors (e.g., crisaborole)
• Topical JAK inhibitors (e.g., ruxolitinib)

Targeting a variety of immune cells and suppressing the release of proinflammatory cytokines, 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. When choosing a steroid potency, it is important to consider the anatomical site (i.e., using lower potency agents on the face, neck, genitals, and body folds).  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. TCIs are a safe anti-inflammatory option for AD, particularly when there is concern for adverse events secondary to corticosteroid use. Topical tacrolimus has shown flare prevention and disease control when used intermittently from 2 to 3 times per week in in patients with stable disease.(4) Prescribing information for pimecrolimus cream and tacrolimus ointment indicate evaluation after 6 weeks if symptoms of AD do not improve for adults and pediatrics.(8,9). 

When AD is more severe or refractory to topical treatment, advanced treatment with phototherapy or systemic medications can be considered. Phototherapy is conditionally recommended by the AAD as a treatment for AD based on low certainty evidence. The AAD strongly recommends the following systemic therapies:(5)

• Monoclonal antibodies (biologics) (e.g., dupilumab, tralokinumab)
• JAK inhibitors (e.g., upadacitinib, abrocitinib, baricitinib)

In a change from the 2014 AAD AD guidelines the use of systemic antimetabolites such as methotrexate, immunosuppressants such as systemic corticosteroids, mycophenolate mofetil, azathioprine, and cyclosporine are now conditionally recommended  for AD only in a small number of select patients due to low or very low certainty of evidence and need for monitoring. The most favored first-line systemic is dupilumab.(5)

There is no clear consensus on how to operationalize a definition of the FDA indication for treatment of patients with "moderate to severe" AD. The severity of AD can vary substantially over time and, from a patient's perspective, can include a complex combination of intensity of itch, location, body surface area (BSA) involvement, and degree of skin impairment. Given the variability of patient phenotype and lack of familiarity among clinicians with scoring systems used in clinical trials, it is advisable to create a broad clinically relevant definition inclusive of multiple specific measures of disease intensity for example:(11)

One of the following:

• Affected BSA greater than or equal to 10%
• Investigator Global Assessment (IGA) greater than or equal to 3
• Eczema Area and Severity Index (EASI) greater than or equal to 16

OR

One of the following:

• Affected BSA greater than or equal to 10%
• Involvement of body sites that are difficult to treat with prolonged topical corticosteroid therapy (e.g., hands, feet, face, neck, scalp, genitals/groin, skin folds)
• Severe itch that has been unresponsive to topical therapies

Efficacy

The efficacy of Cibinqo as monotherapy and in combination with background topical corticosteroids was evaluated in 3 randomized, double-blind, placebo-controlled trials [Trial-AD-1 (NCT03349060), Trial-AD-2 (NCT03575871), and Trial-AD-3 (NCT03720470)] in 1615 subjects 12 years of age and older (Cibinqo is not approved for use in pediatric patients) with moderate-to-severe atopic dermatitis as defined by Investigator’s Global Assessment (IGA) score greater than or equal to 3, Eczema Area and Severity Index (EASI) score greater than or equal to 16, body surface area (BSA) involvement greater than or equal to 10%, and Peak Pruritus Numerical Rating Scale (PP-NRS) greater than or equal to 4 at the baseline visit prior to randomization.(1)

Overall, 53% of subjects were male, 69% of subjects were white, 64% of subjects had a baseline IGA score of 3 (moderate AD), and 36% of subjects had a baseline IGA score of 4 (severe AD). The baseline mean EASI score was 30. The baseline mean age was 36 years old with 8% of subjects 12 to less than 18 years old and 92% of subjects 18 years of age or older. Subjects in these trials were those who had inadequate response to previous topical therapy or were subjects for whom topical treatments were medically inadvisable, or who had received systemic therapies including dupilumab. In each of the trials, over 40% of subjects had prior exposure to systemic therapy. In Trial-AD-1 and Trial-AD-2, 6% of the subjects had received dupilumab, whereas prior use of dupilumab was not allowed in Trial-AD-3.(1)

The proportion of subjects achieving PP-NRS4 at week 2 (defined as an improvement of greater than or equal to 4 points from baseline in PP-NRS) was higher in subjects treated with Cibinqo monotherapy 200 mg once daily (28% in Trial-AD-1 and 24% in Trial-AD-2) and 100 mg once daily (11% in both trials) compared to placebo (2% in both trials). A higher proportion of subjects in the Cibinqo monotherapy 100 mg or 200 mg once daily arm compared to placebo achieved improvement in itching at week 12.(1)

The proportions of subjects achieving PP-NRS4 at week 2 was higher in subjects treated with Cibinqo 200 mg once daily (30%) and 100 mg once daily (14%) in combination with background medicated topical therapies compared to placebo (8%). Examination of age, gender, race, weight, and previous systemic AD therapy treatment did not identify differences in response to Cibinqo 100 mg or 200 mg once daily among these subgroups in Trial-AD-1, Trial- AD-2, and Trial-AD-3.(1)

Safety

Abrocitinib carries the following boxed warnings:(1)

• Increased risk of serious bacterial, fungal, viral, and opportunistic infections leading to hospitalization or death, including tuberculosis (TB). Discontinue treatment with Cibinqo if serious or opportunistic infection occurs. Test for latent TB before and during therapy, and if positive, start treatment for TB prior to use. Monitor all patients for active TB during treatment, even if initial latent TB test is negative.
• Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus Kinase (JAK) inhibitor vs tumor necrosis factor (TNF) blockers in RA patients
• Malignancies have occurred in patients treated with Cibinqo. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs TNF blockers in RA patients
• MACE (defined as cardiovascular death, myocardial infarction, and stroke) has occurred with Cibinqo. Higher rate of MACE with another JAK inhibitor vs TNF blockers in RA patients
• Thrombosis has occurred in patients treated with Cibinqo. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs TNF blockers.

Abrocitinib is contraindicated in patients taking antiplatelet therapies, except for low dose aspirin (less than or equal to 81 mg daily), during the first 3 months of treatment.(1)

1

Cibinqo prescribing information. Pfizer Labs. December 2023.

2

Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, 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.

3

Reference no longer used

4

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.

5

Davis DMR, Drucker AM, Alikhan A, et al. Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies. J Am Acad Dermatol 2023;e1-e14.

6

Sidbury R, Tom WL, Bergman JN, Cooper KD, Silverman RA, Berger TG, 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.

7

Reference no longer used

8

Pimecrolimus cream prescribing information. Oceanside Pharmaceuticals. September 2020.

9

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

10

Reference no longer used

11

Institute For Clinical and Economic Review (CER). JAK Inhibitors and Monoclonal Antibodies for the Treatment of Atopic Dermatitis: Effectiveness and Value. Final Evidence Report. August 2021. Updated February 2023.

Cibinqo

abrocitinib tab

100 MG ; 200 MG ; 50 MG

M ; N ; O ; Y

N

Cibinqo

abrocitinib tab

100 MG ; 200 MG ; 50 MG

30

Tablets

30

DAYS

Cibinqo

abrocitinib tab

100 MG ; 200 MG ; 50 MG

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

Cibinqo

abrocitinib tab

100 MG ; 200 MG ; 50 MG

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

Initial Evaluation

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

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
3. BOTH of the following:
   1. ONE of the following:
      1. The patient has a diagnosis of moderate-to-severe atopic dermatitis (AD) AND ALL of the following: 
         1. ONE of the following:
            1. The patient has at least 10% body surface area involvement OR
            2. The patient has involvement of body sites that are difficult to treat with prolonged topical corticosteroid therapy (e.g., hands, feet, face, neck, scalp, genitals/groin, skin folds) OR
            3. The patient has an Eczema Area and Severity Index (EASI) score of greater than or equal to 16 OR
            4. The patient has an investigator Global Assessment (IGA) score of greater than or equal to 3 AND
         2. ONE of the following:
            1. The patient has tried and had an inadequate response to at least a mid- potency topical steroid 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 mid- potency topical steroid used in the treatment of AD OR
            3. The patient has an FDA labeled contraindication to ALL mid-, high-, and super-potency topical steroids used in the treatment of AD AND
         3. ONE of the following:
            1. The patient has tried and had an inadequate response to a topical calcineurin inhibitor (e.g., Elidel/pimecrolimus, Protopic/tacrolimus) 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 OR
            3. The patient has an FDA labeled contraindication to ALL topical calcineurin inhibitors AND
         4. The prescriber has documented the patient’s baseline (prior to therapy with the requested agent) pruritus and other symptom severity (e.g., erythema, edema, xerosis, erosions/excoriations, oozing and crusting, and/or lichenification) AND
         5. 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 another FDA labeled indication for the requested agent and route of administration AND
   2. If the patient has an FDA labeled indication, then 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 OR
4. The patient has another indication that is supported in compendia for the requested agent and route of administration AND
5. The patient has been tested for latent tuberculosis (TB) AND if positive the patient has begun therapy for latent TB AND
6. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., dermatologist, allergist, immunologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
7. ONE of the following (Please refer to “Agents NOT to be used Concomitantly” table): 
   1. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR
   2. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following:
      1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND
      2. There is support for the use of combination therapy (copy of support required, e.g., clinical trials, phase III studies, guidelines) AND
8. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS, DrugDex 1 or 2a level of evidence, or NCCN 1 or 2a recommended use

Length of Approval: 6 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

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. ONE of the following:
   1. The patient has a diagnosis of moderate-to-severe atopic dermatitis AND BOTH of the following:
      1. The patient has had a reduction or stabilization from baseline (prior to therapy with the requested agent) of ONE of the following:
         1. Affected body surface area OR
         2. Flares OR
         3. Pruritus, erythema, edema, xerosis, erosions/excoriations, oozing and crusting, and/or lichenification OR
         4. A decrease in the Eczema Area and Severity Index (EASI) score OR
         5. A decrease in the Investigator Global Assessment (IGA) score AND
      2. The patient will continue standard maintenance therapies (e.g., topical emollients, good skin care practices) in combination with the requested agent OR
   2. The patient has a diagnosis other than moderate-to-severe atopic dermatitis AND 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, allergist, immunologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. ONE of the following (Please refer to “Agents NOT to be used Concomitantly” table): 
   1. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR
   2. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following:
      1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND
      2. There is support for the use of combination therapy (copy of support required, e.g., clinical trials, phase III studies, guidelines) AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS, DrugDex 1 or 2a level of evidence, or NCCN 1 or 2a recommended use

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. ALL of the following:
   1. The requested quantity (dose) exceeds the program quantity limit AND
   2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
   3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit

Length of Approval: Initial - up to 6 months, Renewal - up to 12 months

Agents NOT to be used Concomitantly

Abrilada (adalimumab-afzb)

Actemra (tocilizumab)

Adalimumab

Adbry (tralokinumab-ldrm)

Amjevita (adalimumab-atto)

Arcalyst (rilonacept)

Avsola (infliximab-axxq)

Benlysta (belimumab)

Bimzelx (bimekizumab-bkzx)

Cibinqo (abrocitinib)

Cimzia (certolizumab)

Cinqair (reslizumab)

Cosentyx (secukinumab)

Cyltezo (adalimumab-adbm)

Dupixent (dupilumab)

Enbrel (etanercept)

Entyvio (vedolizumab)

Fasenra (benralizumab)

Hadlima (adalimumab-bwwd)

Hulio (adalimumab-fkjp)

Humira (adalimumab)

Hyrimoz (adalimumab-adaz)

Idacio (adalimumab-aacf)

Ilaris (canakinumab)

Ilumya (tildrakizumab-asmn)

Inflectra (infliximab-dyyb)

Infliximab

Kevzara (sarilumab)

Kineret (anakinra)

Litfulo (ritlecitinib)

Nucala (mepolizumab)

Olumiant (baricitinib)

Omvoh (mirikizumab-mrkz)

Opzelura (ruxolitinib)

Orencia (abatacept)

Otezla (apremilast)

Remicade (infliximab)

Renflexis (infliximab-abda)

Riabni (rituximab-arrx)

Rinvoq (upadacitinib)

Rituxan (rituximab)

Rituxan Hycela (rituximab/hyaluronidase human)

Ruxience (rituximab-pvvr)

Siliq (brodalumab)

Simponi (golimumab)

Simponi ARIA (golimumab)

Skyrizi (risankizumab-rzaa)

Sotyktu (deucravacitinib) 

Stelara (ustekinumab)

Taltz (ixekizumab)

Tezspire (tezepelumab-ekko)

Tremfya (guselkumab)

Truxima (rituximab-abbs)

Tysabri (natalizumab)

Velsipity (etrasimod)

Wezlana (ustekinumab-auub)

Xeljanz (tofacitinib)

Xeljanz XR (tofacitinib extended release)

Xolair (omalizumab)

Yuflyma (adalimumab-aaty)

Yusimry (adalimumab-aqvh)

Zeposia (ozanimod)

Zymfentra (infliximab-dyyb)