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Interleukin-13 (IL-13) Antagonist Prior Authorization with Quantity Limit Program Summary
Policy Number: PH-1170
This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.
POLICY REVIEW CYCLE
Effective Date |
Date of Origin |
10-01-2024 |
|
FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
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. Adbry can be used with or without topical corticosteroids. |
|
1 |
See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm
CLINICAL RATIONALE
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 topical emollient/moisturizer use and conventional topical therapies (including corticosteroids and calcineurin inhibitors).(5,6) 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.(4) 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)
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.(4) 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.(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)
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:
OR One of the following:
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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)
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) |
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Safety |
Tralokinumab is contraindicated in patients who have known hypersensitivity to tralokinumab-ldrm or any excipients in Adbry.(1) |
REFERENCES
Number |
Reference |
1 |
Adbry prescribing information. LEO Pharma Inc. December 2023. |
2 |
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. |
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 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 |
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. August 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. |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Available MSC |
Final Age Limit |
Preferred Status |
|
||||||
Adbry |
tralokinumab-ldrm subcutaneous soln auto-injector ; tralokinumab-ldrm subcutaneous soln prefilled syr |
150 MG/ML ; 300 MG/2ML |
M ; N ; O ; Y |
N |
|
|
POLICY AGENT SUMMARY QUANTITY LIMIT
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
QL Amount |
Dose Form |
Day Supply |
Duration |
Addtl QL Info |
Allowed Exceptions |
Targeted NDCs When Exclusions Exist |
|
|||||||||
Adbry |
tralokinumab-ldrm subcutaneous soln auto-injector |
300 MG/2ML |
2 |
Pens |
28 |
DAYS |
|
|
|
Adbry |
Tralokinumab-ldrm Subcutaneous Soln Prefilled Syr |
150 MG/ML |
4 |
Syringes |
28 |
DAYS |
|
|
|
CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Adbry |
tralokinumab-ldrm subcutaneous soln auto-injector ; tralokinumab-ldrm subcutaneous soln prefilled syr |
150 MG/ML ; 300 MG/2ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
CLIENT SUMMARY – QUANTITY LIMITS
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Adbry |
tralokinumab-ldrm subcutaneous soln auto-injector |
300 MG/2ML |
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 |
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
||
|
Initial Evaluation Target Agent(s) will be approved when ALL of the following are met:
Compendia Allowed: AHFS, DrugDex 1 or 2a level of evidence, or NCCN 1 or 2a recommended use Length of Approval: 6 months Note: Initial loading dose is allowed for Adbry and may require a Quantity Limit review. The loading dose plus maintenance dose may be approved for 1 month, followed by maintenance dosing for the remainder of the length of approval. 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:
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 CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
|
Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:
Length of Approval: up to 12 months Note: If approving initial loading dose for Adbry, approve quantity for loading dose plus maintenance for 1 month followed by maintenance dose for the remainder of the length of approval. Maintenance dosing begins 2 weeks after patient receives the loading dose. |
CONTRAINDICATION AGENTS
Contraindicated as Concomitant Therapy |
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) |
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 Blue Cross and Blue Shield of Alabama’s 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.
Commercial _ PS _ IL-13_Antagonist_PAQL _ProgSum_ 10-01-2024