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Lupus Prior Authorization with Quantity Limit Program Summary
Policy Number: PH-1166
This program applies to Blue Partner, Commercial, NetResults A series, SourceRx and Health Insurance Marketplace formularies.
POLICY REVIEW CYCLE
Effective Date |
Date of Origin |
07-01-2024 |
|
FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Benlysta® (belimumab) Subcutaneous solution Injection powder |
Treatment of patients 5 years and older with systemic lupus erythematosus (SLE) who are receiving standard therapy Treatment of patients 5 years and older with active lupus nephritis (LN) who are receiving standard therapy Limitations of use: |
|
1 |
Lupkynis® (voclosporin) Capsule |
In combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis Limitations of use: |
|
9 |
See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm
CLINICAL RATIONALE
Systemic Lupus Erythematosus (SLE) |
Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown cause. It has a broad range of clinical and serological manifestations and can affect many organs. Clinical symptoms of SLE include fatigue, fever, arthralgia, myalgia, changes in weight, skin and mucus membrane lesions and ulcers, and vascular disease. SLE can also include cardiac, renal, pulmonary, and neurologic involvement. Due to its multisystem involvement and likelihood of changes in presentation, the diagnosis of SLE may be difficult.(2) The American College of Rheumatology (ACR) recommends referral to a rheumatologist and/or another appropriate specialist to establish the diagnosis of SLE; assess activity and severity level; and management of the disease.(3) The 2019 update of the EULAR recommendations for the management of SLE recommend the following(5):
HHS notes that the same management strategies apply to children and adolescents with SLE.(4) |
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Lupus Nephritis |
Lupus nephritis (LN) is a common cause of kidney injury and failure in patients with SLE. Roughly 50% of patients with SLE will develop LN at some point in their SLE disease course and between 10% to 30% of those patients will progress to kidney failure requiring kidney transplant. Mortality in patients with LN is significantly higher than those that do not develop LN, with death occurring in 5% to 25% of patients with proliferative LN. LN typically develops early in SLE disease course and can often be present at initial diagnosis of SLE. LN results due to an accumulation of immune complex in the glomeruli. Intrarenal inflammation occurs leading to permanent damage to the kidney.(6) Diagnosis of LN can be challenging, especially if the patient has not been initially diagnosed with SLE. Serum creatinine levels, urine dipstick testing, and urine sediment are necessary tools for LN evaluation. Proteinuria in patients with SLE is suggestive of a diagnosis of LN.(5) The American College of Rheumatology (ACR) indicates that all patients with clinical evidence of LN should undergo a renal biopsy to determine disease classification and confirm diagnosis of LN. The ACR also indicates that treatment should be based off of the International Society of Nephrology/Renal Pathology Society (ISN/RPS) LN classification. The ISN/RPS breaks down LN into the following 6 classes:(8)
Kidney Disease Improving Global Outcomes (KDIGO) 2023 draft guidelines recommend the following for lupus nephritis Class III or IV initial treatment:(10)
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Efficacy |
Benlysta SLE trials(1) The safety and efficacy of belimumab was evaluated in two randomized, double-blind, placebo-controlled, phase III studies involving patients age 18 and older with SLE (BLISS-52 and BLISS-76 study). The design of these studies was based on the results of a phase II study which identified that patients who were autoantibody-positive had a better response to belimumab. As a result, BLISS-52 and BLISS-76 limited the study population to only include autoantibody-positive SLE patients. Patients were on a standard of care SLE treatment regimen comprising of at least one of the following: corticosteroids, antimalarials, nonsteroidal anti-inflammatory drugs (NSAIDS), and/or immunosuppressives (azathioprine, methotrexate, or mycophenolate). Patients with severe active lupus nephritis and severe central nervous system (CNS) lupus were excluded. Patients using other biologics including B-cell targeted therapies such as rituximab or intravenous cyclophosphamide in the previous six months were also excluded. BLISS-52 (N=865) and BLISS-76 (N=826) had similar designs with the exception of duration. BLISS-76 was 76 weeks in duration and BLISS-52 was 52 weeks in length. Eligible patients had active SLE disease which was defined as a Safety of Estrogen in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score greater than or equal to 6. Patients were randomly assigned to receive belimumab 1 mg/kg, 10 mg/kg, or placebo in addition to standard of care. The study medication was administered on Days 0, 14, 28, and then every 28 days for 48 weeks in BLISS-52 and 72 weeks in BLISS-76. In both BLISS-52 and BLISS-76, the proportion of SLE patients achieving a SLE Responder Index-4 (SRI-4) response was significantly higher in the belimumab 10 mg/kg group than placebo while the effect on SRI-4 was not consistently significantly different for the belimumab 1 mg/kg group. The safety and efficacy of Benlysta in pediatric patients was evaluated in an international, randomized, double-blind, placebo-controlled, 52-week study conducted in 93 patients with a clinical diagnosis of SLE according to the ACR classification criteria. Patients had a SELENA-SLEDAI score greater than or equal to 6 and positive autoantibodies at screening. Patients were on stable SLE treatment regimen and had similar inclusion and exclusion criteria as in the adult studies. The primary endpoint was the same as the adult trials, and there was a numerically higher proportion of pediatric patients achieving a response in SRI-4 and its components in patients receiving Benlysta plus standard therapy compared with placebo plus standard therapy (53% vs 44%, odds ratio 1.49 [CI 0.64, 3.46]). Benlysta LN clinical trials(1) The safety and efficacy of Benlysta in patients with lupus nephritis was evaluated in a 104 week, randomized, double-blind, placebo controlled trial that included 448 patients with active proliferative and/or membranous lupus nephritis. Patients had to be at least 18 years of age and ANA positive SLE that fulfilled the ACR classification criteria. Patients were required to have a urine protein to creatinine ratio of 1 or more and biopsy-proven lupus nephritis ISN/RPS class III, IV, or V. Induction therapy had to be initiated within 60 days before randomization and therapies had to include either induction with glucocorticoids in combination with MMF or IV cyclophosphamide, followed by MMF or AZA for maintenance therapy. The primary efficacy endpoint was Primary Efficacy Renal Response (PERR) at week 104, defined as a response at Week 100 confirmed by a repeat measurement at week 104 of the following parameters: urine protein:creatinine ratio (uPCR) less than or equal to 0.7 g/g and estimated glomerular filtration rate (eGFR) greater than or equal to 60 mL/min/1.73 m2 or no decrease in eGFR of greater than 20% from pre-flare value. The major secondary endpoints included Complete Renal Response (CRR) (defined as a response at week 100 confirmed by a repeat measurement at week 104 of the following parameters: uPCR less than 0.5 g/g and eGFR greater than or equal to 90 mL/min/1.73 m2 or no decrease in eGFR of greater than 10% from pre-flare value); PERR at week 52; and time to renal-related event or death (renal-related event defined as first event of end-stage renal disease, doubling of serum creatinine, renal worsening [defined by quantified increase in proteinuria and/or impaired renal function], or receipt of renal disease-related prohibited therapy due to inadequate lupus nephritis control or renal flare management). The proportion of patients achieving PERR at Week 104 was significantly higher in patients receiving Benlysta plus standard therapy compared with placebo plus standard therapy (43% vs 32%, p=0.031). The subgroup analysis of PERR and CRR by biopsy class indicated the odds ratios for patients with class 5 without combined class III or class IV favored placebo plus standard therapy over Benlysta plus standard therapy. The odds ratio for all other classes or combinations favored Benlysta plus standard therapy. Most of the secondary endpoint were statistically significant (CRR at week 100 p=0.017 [30% vs 20% Benlysta vs placebo], PERR at week 52 p=0.025 [47% vs 35% Benlysta vs placebo]). The table below shows the time to renal related event or death.
Lupkynis LN trial(9) The safety and efficacy of Lupkynis were investigated in a 52-week, randomized, double-blind, placebo-controlled trial in patients with a diagnosis of systemic lupus erythematosus and with International Society of Nephrology/Renal Pathology Society (ISN/RPS) biopsy-proven active Class III or IV LN (alone or in combination with Class V LN) or Class V LN. A total of 357 patients with LN were randomized in a 1:1 ratio to receive either Lupkynis 23.7 mg twice daily or placebo. Patients in both arms received background treatment with MMF and corticosteroids. The primary efficacy endpoint was the proportion of patients achieving complete renal response at week 52. In order to be considered a responder, the patient must not have received more than 10 mg prednisone for greater than or equal to 3 consecutive days or for greater than or equal to 7 days in total during weeks 44 through 52. Patients who received rescue medication or withdrew from the study were considered non-responders. A higher proportion of patients in the Lupkynis arm than the placebo arm achieved complete renal response at week 52 (Lupkynis 40.8% vs placebo 22.5%, p less than 0.001). A higher proportion of patients in the Lupkynis arm than the placebo arm achieved complete renal response at week 24 (32.4% vs. 19.7%; odds ratio: 2.2; 95% CI: 1.3, 3.7). Time to UPCR of less than or equal to 0.5 mg/mg was shorter in the Lupkynis arm than the placebo arm (median time of 169 days vs. 372 days; hazard ratio: 2.0; 95% CI: 1.5, 2.7). |
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Safety |
Benlysta is contraindicated in patients that have experienced anaphylaxis with belimumab.(1) Lupkynis is contraindicated in the following:(9)
|
REFERENCES
Number |
Reference |
1 |
Benlysta Prescribing Information. GlaxoSmithKline LLC. February 2023. |
2 |
Lam NC, Ghetu MV, Bieniek ML. Systemic lupus erythematosus: primary care approach to diagnosis and management. Am Fam Physician. 2016;94(4):284–294. |
3 |
Guidelines for referral and management of systemic lupus erythematosus in adults. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999; 42(9):1785–1796. |
4 |
Levy, D. M., & Kamphuis, S. (2012). Systemic lupus erythematosus in children and adolescents. Pediatric clinics of North America, 59(2), 345–364. doi:10.1016/j.pcl.2012.03.007. |
5 |
Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Annals of the Rheumatic Diseases 2019;78:736-745. |
6 |
Parikh SV, Almaani S, Brodsky S, Rovin BH. Update on Lupus Nephritis: Core Curriculum 2020. Am J Kidney Dis 2020; 76:265. |
7 |
Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, Karpouzas GA, Merrill JT, Wallace DJ, Yazdany J, Ramsey-Goldman R, Singh K, Khalighi M, Choi SI, Gogia M, Kafaja S, Kamgar M, Lau C, Martin WJ, Parikh S, Peng J, Rastogi A, Chen W, Grossman JM; American College of Rheumatology. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012 Jun;64(6):797-808. doi: 10.1002/acr.21664. PMID: 22556106; PMCID: PMC3437757. |
8 |
Weening JJ, D'Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 2004; 65:521. |
9 |
Lupkynis prescribing information. Aurinia Pharmaceuticals, Inc. January 2021. |
10 |
Kidney Disease Improving Global Outcomes (KDIGO) KDIGO 2023 Clinical Practice Guideline for the Management of Lupus Nephritis. Public Review Draft. March 2023. |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Available MSC |
Final Age Limit |
Preferred Status |
|
||||||
Benlysta |
belimumab subcutaneous solution auto-injector |
200 MG/ML |
M ; N ; O ; Y |
N |
|
|
Benlysta |
belimumab subcutaneous solution prefilled syringe |
200 MG/ML |
M ; N ; O ; Y |
N |
|
|
Lupkynis |
voclosporin cap |
7.9 MG |
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 |
|
|||||||||
Benlysta |
belimumab subcutaneous solution auto-injector |
200 MG/ML |
4 |
Injectors |
28 |
DAYS |
|
|
|
Benlysta |
belimumab subcutaneous solution prefilled syringe |
200 MG/ML |
4 |
Syringes |
28 |
DAYS |
|
|
|
Lupkynis |
voclosporin cap |
7.9 MG |
180 |
Capsules |
30 |
DAYS |
|
|
|
CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Benlysta |
belimumab subcutaneous solution auto-injector |
200 MG/ML |
Blue Partner ; Commercial ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Benlysta |
belimumab subcutaneous solution prefilled syringe |
200 MG/ML |
Blue Partner ; Commercial ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Lupkynis |
voclosporin cap |
7.9 MG |
Blue Partner ; Commercial ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
CLIENT SUMMARY – QUANTITY LIMITS
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
Benlysta |
belimumab subcutaneous solution auto-injector |
200 MG/ML |
Blue Partner ; Commercial ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Benlysta |
belimumab subcutaneous solution prefilled syringe |
200 MG/ML |
Blue Partner ; Commercial ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
Lupkynis |
voclosporin cap |
7.9 MG |
Blue Partner ; Commercial ; 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:
Length of Approval: 12 months *NOTE: Approve Benlysta subcutaneous loading dose for 1 month, then maintenance dose can be approved for the remainder of 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria *Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.
Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met:
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 |
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.
ALBP _ Commercial _ CS _ Lupus__PAQL _ProgSum_ 07-01-2024 _ © Copyright Prime Therapeutics LLC. May 2024 All Rights Reserved