Effective Date

Date of Origin 

07-01-2024            

Adbry®

(tralokinumab-ldrm)

Subcutaneous injection

Treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

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 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 Adbry was assessed in three randomized, double-blind, placebo-controlled trials [ECZTRA 1 (NCT03131648), ECZTRA 2 (NCT03160885), and ECZTRA 3 (NCT03363854)]. Efficacy was assessed in a total of 1934 subjects 18 years of age and older with moderate-to-severe atopic dermatitis (AD) not adequately controlled by topical medication(s). Disease severity was defined by an Investigator’s Global Assessment (IGA) score greater than or equal to 3 in the overall assessment of AD lesions on a severity scale of 0 to 4, an Eczema Area and Severity Index (EASI) score greater than or equal to 16 on a scale of 0 to 72, and a minimum body surface area (BSA) involvement of greater than or equal to 10%. At baseline, 58% of subjects were male, 69% of subjects were white, 50% of subjects had a baseline IGA score of 3 (moderate AD), and 50% of subjects had a baseline IGA score of 4 (severe AD). The baseline mean EASI score was 32 and the baseline weekly averaged Worst Daily Pruritus Numeric Rating Scale (NRS) was 8 on a scale of 0-10.(1)

In all three trials, subjects received subcutaneous injections of Adbry 600 mg or placebo on Day 0, followed by 300 mg every other week or placebo for 16 weeks. Responders were defined as achieving an IGA 0 or 1 (“clear” or “almost clear”) or EASI-75 (improvement of at least 75% in EASI score from baseline) at week 16.(1)

To evaluate maintenance of response in the monotherapy trials (ECZTRA 1 and ECZTRA 2), subjects responding to initial treatment with Adbry 300 mg every other week were re-randomized to Adbry 300 mg every other week, Adbry 300 mg every 4 weeks or placebo every other week for another 36 weeks following first dose administration. Subjects randomized to placebo in the initial treatment period who achieved a clinical response at week 16 continued to receive placebo every other week for another 36 weeks. Non-responders at week 16, and subjects who lost clinical response during the maintenance period were placed on open-label treatment with Adbry 300 mg every other week and optional use of TCS.(1)

The ECZTRA 3 trial studied the use of Adbry in combination with either a topical corticosteroid or topical calcineurin inhibitor. Subjects received either Adbry 300 mg every other week with TCS or placebo with TCS and as needed topical calcineurin inhibitors (TCI) until week 16. Subjects in the Adbry 300 mg with TCS group who achieved clinical response at week 16 were re-randomized to Adbry 300 mg every other week with TCS or Adbry every 4 weeks with TCS for another 16 weeks following first dose administration. Subjects in the placebo with TCS group who achieved clinical response at week 16 continued on placebo with TCS for another 16 weeks. Subjects who did not achieve clinical response at week 16 received Adbry 300 mg every other week for another 16 weeks. A mid-potency TCS (i.e., mometasone furoate 0.1% cream) was dispensed at each dosing visit. Subjects were instructed to apply a thin film of the dispensed TCS as needed once daily to active lesions from week 0 to week 32 and were to discontinue treatment with TCS when control was achieved. An additional, lower potency TCS or TCI could be used at the investigator’s discretion on areas of the body where use of the supplied TCS was not advisable, such as areas of thin skin.(1)

All three trials assessed the primary endpoints of the proportion of subjects with an IGA 0 or 1 at week 16 and the proportion of subjects with EASI-75 at week 16. Secondary endpoints included the reduction of Worst Daily Pruritus NRS (weekly average) of at least 4 points on the 11-point itch NRS from baseline to week 16.(1)

1. Full Analysis Set (FAS) includes all subjects randomized and dosed
2. Responders was defined as a subject with an IGA 0 or 1 (“clear” or “almost clear”)
3. Subjects who received rescue treatment or with missing data were considered as non-responders

Note: Difference and 95% CI are based on the CMH test stratified by region and baseline IGA score

Examination of age, gender, race, body weight, and previous treatment, including immunosuppressants, did not identify differences in response to Adbry 300 mg every other week among these subgroups.(1)

In ECZTRA 1, 179 Adbry 300 mg every other week responders (IGA 0/1 or EASI-75) were re-randomized (and dosed) at week 16 to Adbry 300 mg every other week (68 subjects), Adbry 300 mg every 4 weeks (76 subjects) or placebo (35 subjects). Among these subjects, 39 subjects in Adbry 300 mg every other week arm, 36 subjects in Adbry 300 mg every 4 weeks arm and 19 subjects in placebo arm were IGA 0/1 responders at week 16. Maintenance of IGA 0/1 response at week 52 was as follows: 20 subjects (51%) in the every other week arm, 14 subjects (39%) in the every 4 weeks arm and 9 subjects (47%) in the placebo arm. Among the re-randomized subjects, 47 subjects in Adbry 300 mg every other week arm, 57 subjects in Adbry 300 mg every 4 weeks arm and 30 subjects in placebo arm were EASI-75 responders at week 16. Maintenance of EASI-75 response at week 52 was as follows: 28 subjects (60%) in the every other week arm, 28 subjects (49%) in the every 4 weeks arm and 10 subjects (33%) in the placebo arm.(1)

In ECZTRA 2, 218 Adbry 300 mg every other week responders (IGA 0/1 or EASI-75) were re-randomized (and dosed) at week 16 to Adbry 300 mg every other week (90 subjects), Adbry 300 mg every 4 weeks (84 subjects) or placebo (44 subjects). Among these subjects, 53 subjects in Adbry 300 mg every other week arm, 44 subjects in Adbry 300 mg every 4 weeks arm and 26 subjects in placebo arm were IGA 0/1 responders at week 16. Maintenance of IGA 0/1 response at week 52 was as follows: 32 subjects (60%) in the every other week arm, 22 subjects (50%) in the every 4 weeks arm and 6 subjects (23%) in the placebo arm. Among the re-randomized subjects, 76 subjects in Adbry 300 mg every other week arm, 69 subjects in Adbry 300 mg every 4 weeks arm and 40 subjects in placebo arm were EASI-75 responders at week 16. Maintenance of EASI-75 response at week 52 was as follows: 43 subjects (57%) in the every other week arm, 38 subjects (55%) in the every 4 weeks arm and 8 subjects (20%) in the placebo arm.(1)

In ECZTRA 3, 131 Adbry 300 mg every other week + TCS responders (IGA 0/1 or EASI-75) were re-randomized (and dosed) at week 16 to Adbry 300 mg every other week + TCS (65 subjects) or Adbry 300 mg every 4 weeks + TCS (66 subjects). Among these subjects, 45 subjects in Adbry 300 mg every other week + TCS arm and 46 subjects in Adbry 300 mg every 4 weeks + TCS arm were IGA 0/1 responders at week 16. Maintenance of IGA 0/1 response at week 32 was as follows: 40 subjects (89%) in the every other week arm and 35 subjects (76%) every 4 weeks arm. Among the re-randomized subjects, 65 subjects in Adbry 300 mg every other week arm and 62 subjects in Adbry 300 mg every 4 weeks arm were EASI-75 responders at week 16. Maintenance of EASI-75 response at week 32 was as follows: 60 subjects (92%) in the every other week arm and 56 subjects (90%) in the every 4 weeks arm.(1)

Safety

Tralokinumab is contraindicated in patients who have known hypersensitivity to tralokinumab-ldrm or any excipients in Adbry.(1)

1

Adbry prescribing information. LEO Pharma Inc. 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 (ICER). JAK Inhibitors and Monoclonal Antibodies for the Treatment of Atopic Dermatitis: Effectiveness and Value. Final Evidence Report. August 2021. Updated February 2023.

Adbry

tralokinumab-ldrm subcutaneous soln prefilled syr

150 MG/ML

M ; N ; O ; Y

N

Adbry

Tralokinumab-ldrm Subcutaneous Soln Prefilled Syr

150 MG/ML

4

Syringes

28

DAYS

Adbry

tralokinumab-ldrm subcutaneous soln prefilled syr

150 MG/ML

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

Adbry

Tralokinumab-ldrm Subcutaneous Soln Prefilled Syr

150 MG/ML

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 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. BOTH of the following:
            1. ONE of the following:
               1. The patient has tried and had an inadequate response to at least a mid-potency topical steroid 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 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
            2. 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) 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
         3. The prescriber has assessed 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
         4. The patient will be using standard maintenance therapy (e.g., topical emollients, 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. ONE of the following:
   1. The patient is initiating therapy with the requested agent OR
   2. The patient has been treated with the requested agent for less than 16 consecutive weeks OR
   3. The patient has been treated with the requested agent for at least 16 consecutive weeks AND ONE of the following:
      1. The patient weighs less than 100 kg and ONE of the following:
         1. The patient has achieved clear or almost clear skin AND the patient’s dose will be reduced to 300 mg every 4 weeks OR
         2. The patient has NOT achieved clear or almost clear skin OR
         3. There is support for of therapy using 300 mg every 2 weeks OR
      2. The patient weighs greater than or equal to 100 kg 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: Approve Adbry subcutaneous loading dose for 1 month, then maintenance dose can be approved for the remainder of 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. ONE of the following:
   1. The patient is initiating therapy with the requested agent OR
   2. The patient has been treated with the requested agent for less than 16 consecutive weeks OR
   3. The patient has been treated with the requested agent for at least 16 consecutive weeks AND ONE of the following:
      1. The patient weighs less than 100 kg and ONE of the following:
         1. The patient has achieved clear or almost clear skin AND the patient’s dose will be reduced to 300 mg every 4 weeks OR
         2. The patient has NOT achieved clear or almost clear skin OR
         3. There is support for therapy using 300 mg every 2 weeks OR
      2. The patient weighs greater than or equal to 100 kg AND
4. 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
5. 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
6. 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 approval - up to 6 months; Renewal approval - up to 12 months

Note: Approve Adbry subcutaneous loading dose for 1 month, then maintenance dose can be approved for the remainder of 6 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)