Effective Date

Date of Origin   

01-01-2025           

Benlysta®

(belimumab)

Subcutaneous injection

Treatment of patients 5 years of age and older with active systemic lupus erythematosus (SLE) who are receiving standard therapy 

Treatment of patients 5 years of age and older with active lupus nephritis (LN) who are receiving standard therapy

Limitations of use:

• Efficacy has not been evaluated in patients with severe active central nervous system lupus. Use of Benlysta is not recommended in this situation

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:

• Safety and efficacy of Lupkynis have not been established in combination with cyclophosphamide. Use is not recommended in this situation.

9

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 2023 update of the EULAR recommendations for the management of SLE recommend the following:(5)

• Hydroxychloroquine is recommended for all patients with SLE, unless contraindicated, at a target dose of 5 mg/kg real body weight/day. Dose to be individualized based on risk for flare and retinal toxicity.
• Glucocorticoids, if needed, are dosed based on the type and severity of organ involvement, and should be reduced to maintenance dose of less than or equal to 5mg/day (prednisone equivalent) and, when possible, withdrawn; in patients with moderate-to-severe disease, pulses of intravenous methylprednisolone (125–1000mg/day, for 1–3 days) can be considered.
• In patients not responding to hydroxychloroquine (alone or in combination with glucocorticoids) or patients unable to reduce glucocorticoids below doses acceptable for chronic use, addition of immunomodulating/immunosuppressive agents (e.g., methotrexate, azathioprine, or mycophenolate) and/or biological agents (e.g., belimumab or anifrolumab) should be considered.
• In patients with organ-threatening or life-threatening disease, intravenous cyclophosphamide should be considered; in refractory cases, rituximab may be considered.
• Treatment of active skin disease should include topical agents (glucocorticoids, calcineurin inhibitors), antimalarials (hydroxychloroquine, chloroquine), and/or systemic glucocorticoids as needed, with methotrexate, mycophenolate, anifrolumab, or belimumab considered as second-line therapy.

HHS notes that the same management strategies apply to children and adolescents with SLE.(4)

Lupus Nephritis (LN)

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.(6) 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)

• Class I: minimal mesangial lupus nephritis
• Class II: mesangial proliferative lupus nephritis 
• Class III: focal lupus nephritis
• Class IV: diffuse lupus nephritis
• Class V: membranous lupus nephritis
• Class VI: advanced sclerotic lupus nephritis

Kidney Disease: Improving Global Outcomes (KDIGO) 2024 clinical practice guideline for the management of lupus nephritis recommends the following:(10)

Initial therapy of active Class III/IV:

• Patients with active Class III or IV LN, with or without a membranous component, should be treated initially with glucocorticoids plus any one of the following:
  • Mycophenolic acid analogs (MPAA)
  • Low-dose intravenous cyclophosphamide or oral cyclophosphamide
  • Belimumab and either MPAA or low-dose intravenous cyclophosphamide
    • Belimumab duration up to 2.5 years
  • MPAA and a calcineurin inhibitor (CNI) when kidney function is not severely impaired (i.e., estimated glomerular filtration rate [eGFR] less than or equal to 45 mL/min per 1.73 m^2)
    • CNI duration up to 3 years
• Initial therapy with an immunosuppressive regimen that includes a CNI (voclosporin, tacrolimus, or cyclosporine) may be preferred in patients with relatively preserved kidney function and nephrotic-range proteinuria likely due to extensive podocyte injury, as well as patients who cannot tolerate standard-dose MPAA or are unfit for or will not use cyclophosphamide-based regimens.
• A triple immunosuppressive regimen of belimumab with glucocorticoids and either MPAA or reduced-dose cyclophosphamide may be preferred in patients with repeated kidney flares or at high-risk for progression to kidney failure due to severe chronic kidney disease.

Maintenance therapy for Class III/IV:

• After completion of initial therapy, patients should be placed on MPAA for maintenance
  • Azathioprine (AZA) is an alternative to MPAA after completion of initial therapy in patients who do not tolerate MPAA, who do not have access to MPAA, or who are considering pregnancy
• Patients treated with triple immunosuppressive regimens that include belimumab or a CNI in addition to standard immunosuppressive therapy can continue with a triple immunosuppressive regimen as maintenance therapy
• If MPAA and azathioprine cannot be used for maintenance, CNIs or mizoribine or leflunomide can be considered

Pure Class V:

• Patients with low-level proteinuria:
  • Renin-angiotensin system blockade and blood pressure control
  • Immunosuppressive treatment guided by extrarenal manifestations of systemic lupus erythematosus
  • Hydroxychloroquine
• Patients with nephrotic-range proteinuria:
  • Renin-angiotensin system blockade and blood pressure control
  • Combined immunosuppressive treatment with glucocorticoid and one other agent (e.g., mycophenolic acid analogs, cyclophosphamide, CNI, rituximab, AZA)
  • Hydroxychloroquine

Lupus nephritis in children:

• Treat pediatric patients with LN using immunosuppression regimens similar to those used in adults, but consider issues relevant to this population, such as dose adjustment, growth, fertility, and psychosocial factors, when devising the therapy plan

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(1,7)

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 1) mycophenolate mofetil (MMF) for induction followed by MMF for maintenance therapy, or 2) IV cyclophosphamide for induction followed by azathioprine (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).

Safety

Benlysta is contraindicated in patients that have experienced anaphylaxis with belimumab.(1)

Lupkynis is contraindicated in the following:(9)

• Patients concomitantly using strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) because these medications can significantly increase exposure to Lupkynis which may increase the risk of acute and/or chronic nephrotoxicity
• Patients who have a known serious or severe hypersensitivity reaction to Lupkynis or any of its excipients

Lupkynis has a boxed warning due to the increased risk for developing malignancies and serious infections with Lupkynis or other immunosuppressants that may lead to hospitalization or death.(9)

1

Benlysta prescribing information. GlaxoSmithKline LLC. June 2024.

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, Andersen J, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Annals of the Rheumatic Diseases. 2023;83(1):15-29. doi:10.1136/ard-2023-224762

6

Parikh SV, Almaani S, Brodsky S, Rovin BH. Update on Lupus Nephritis: Core Curriculum 2020. Am J Kidney Dis 2020; 76:265.

7

Furie R, Rovin BH, Houssiau F, et al. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med. 2020;383(12):1117-1128. doi:10.1056/nejmoa2001180

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. May 2024.

10

Rovin BH, Ayoub IM, Chan TM, Liu ZH, Mejía-Vilet JM, Floege J. KDIGO 2024 Clinical Practice Guideline for the Management of Lupus Nephritis. Kidney International. 2024;105(1):S1-S69. doi:10.1016/j.kint.2023.09.002

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

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

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

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

Initial Evaluation

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

1. ONE of the following:
   1. The patient has a diagnosis of active systemic lupus erythematosus (SLE) disease WITHOUT active lupus nephritis (LN) AND ALL of the following:
      1. The requested agent is FDA labeled for SLE AND
      2. BOTH of the following:
         1. The patient has a history of positive anti-nuclear antibody (ANA) titer of >1:80 measured via indirect immunofluorescence (IIF) on human epithelial (HEp-2) cells (or an equivalent ANA positive test) at least once AND
         2. The patient has a confirmed SLE classification criteria score greater than 10 (Note: must include clinical and immunologic domains criteria) AND
      3. ONE of the following:
         1. The patient has tried and had an inadequate response to TWO of the following: corticosteroids, antimalarials (e.g., hydroxychloroquine), nonsteroidal anti-inflammatory drugs (e.g., NSAIDs), and/or immunosuppressives (e.g., azathioprine, methotrexate, oral cyclophosphamide, or mycophenolate) OR
         2. The patient has an intolerance or hypersensitivity to at least TWO of the standard of care drug classes (i.e., corticosteroids, antimalarials [e.g., hydroxychloroquine], nonsteroidal anti-inflammatory drugs [e.g., NSAIDs] and immunosuppressives [e.g., azathioprine, methotrexate, oral cyclophosphamide, or mycophenolate]) OR
         3. The patient has an FDA labeled contraindication to ALL the standard of care drug classes (i.e., corticosteroids, antimalarials [e.g., hydroxychloroquine], nonsteroidal anti-inflammatory drugs [e.g., NSAIDs] and immunosuppressives [e.g., azathioprine, methotrexate, oral cyclophosphamide, or mycophenolate]) AND
      4. The patient has moderate to severe active disease defined as a Physician’s Global Assessment (PGA) score of  >1 AND at least ONE of the following:
         1. The patient has a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) score of greater than 6 OR
         2. The patient has disease activity with greater than or equal to 2 systems with British Isles Lupus Assessment Group (BILAG) B scores OR
         3. The patient has disease activity with greater than or equal to 1 system with BILAG A scores OR
   2. The patient has a diagnosis of active lupus nephritis (LN) AND ALL of the following:
      1. The requested agent is FDA labeled for LN AND
      2. The patient has Class III, IV, or V lupus nephritis confirmed via kidney biopsy AND
      3. If the requested agent is Benlysta, then ALL of the following:
         1. The patient has a history of positive anti-nuclear antibody (ANA) titer of >1:80 measured via indirect immunofluorescence (IIF) on human epithelial (HEp-2) cells (or an equivalent ANA positive test) at least once AND
         2. The patient has a confirmed SLE classification criteria score greater than 10 (Note: must include clinical and immunologic domains criteria) AND
         3. ONE of the following:
            1. The patient has tried and had an inadequate response to the following: corticosteroids AND either cyclophosphamide or mycophenolate mofetil OR
            2. The patient has an intolerance or hypersensitivity to the following: corticosteroids AND either cyclophosphamide or mycophenolate mofetil OR
            3. The patient has an FDA labeled contraindication to ALL of the following: corticosteroids, cyclophosphamide and mycophenolate mofetil OR
   3. The patient has another FDA labeled indication for the requested agent and route of administration OR
   4. The patient has another indication that is supported in compendia 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 and route of administration OR
   2. The prescriber has provided information in support of using the requested agent for the patient’s age for the requested indication and route of administration AND
3. ONE of the following:
   1. The patient has a diagnosis of active systemic lupus erythematosus (SLE) disease WITHOUT active LN AND the patient will continue standard SLE therapy (i.e., corticosteroids, antimalarials [e.g., hydroxychloroquine], nonsteroidal anti-inflammatory drugs [e.g., NSAIDs], and/or immunosuppressives [e.g., azathioprine, methotrexate, oral cyclophosphamide, or mycophenolate]) OR
   2. The patient has a diagnosis of active LN AND the patient will continue standard lupus nephritis therapy (i.e., corticosteroids, cyclophosphamide or mycophenolate mofetil) OR
   3. The patient has another FDA labeled indication for the requested agent AND 
4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., rheumatologist, nephrologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
5. The patient does NOT have an active infection AND
6. The patient has NOT received a live vaccine within 30 days prior to starting therapy with the requested agent AND will NOT receive a live vaccine concurrently with the requested agent AND
7. The patient does NOT have severe active central nervous system lupus AND
8. If the requested agent is Benlysta, then BOTH of the following:
   1. The patient will NOT be using the requested agent in combination with Lupkynis AND
   2. 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 (submitted copy of clinical trials, phase III studies, guidelines required) AND
9. If the requested agent is Lupkynis, the patient will NOT be using the requested agent in combination with cyclophosphamide, Benlysta, OR Saphnelo AND
10. The patient does NOT have any FDA labeled contraindications to the requested agent

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

Length of Approval:  12 months

*NOTE: An initial loading dose is allowed for subcutaneous Benlysta and may require a Quantity Limit review. The loading dose may be approved for 1 month, followed by the maintenance dose for the remainder of the length of approval.

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:

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 active systemic lupus erythematosus (SLE) disease WITHOUT active lupus nephritis (LN) AND ALL of the following:
      1. The requested agent is FDA labeled for SLE AND
      2. The patient is currently using standard SLE therapy (i.e., corticosteroids, antimalarials [e.g., hydroxychloroquine], nonsteroidal anti-inflammatory drugs [e.g., NSAIDs], and/or immunosuppressives [e.g., azathioprine, methotrexate, cyclophosphamide, or mycophenolate]) AND
      3. The patient will continue standard SLE therapy (i.e., corticosteroids, antimalarials [e.g., hydroxychloroquine], nonsteroidal anti-inflammatory drugs [e.g., NSAIDs], and/or immunosuppressives [e.g., azathioprine, methotrexate, cyclophosphamide, or mycophenolate]) AND
      4. The patient has had a decrease in symptoms or stabilization as indicated by at least ONE of the following:
         1. Improvement in the SELENA-SLEDAI-2K score OR
         2. No new BILAG-A organ domain score or 2 new BILAG-B organ domain scores OR
         3. No worsening (less than 0.30-point increase) in Physician’s Global Assessment (PGA) score OR
         4. Seroconverted (negative) OR
   2. The patient has a diagnosis of active lupus nephritis (LN) AND ALL of the following:
      1. The requested agent is FDA labeled for LN AND
      2. The patient is currently using standard LN therapy (i.e., corticosteroids, cyclophosphamide or mycophenolate mofetil) AND
      3. The patient will continue standard LN therapy (i.e., corticosteroids, cyclophosphamide or mycophenolate mofetil) AND
      4. The patient has had clinical benefit with the requested agent AND
      5. If the requested agent is Benlysta, the patient has had a decrease in symptoms or stabilization as indicated by improvement in at least ONE of the following:
         1. Urine protein:creatinine ratio (uPCR) OR
         2. Estimated glomerular filtration rate (eGFR) OR
         3. Urine protein OR
   3. The patient has a diagnosis other than active SLE or active LN 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., rheumatologist, nephrologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have an active infection AND
5. The patient has NOT received a live vaccine within 30 days prior to starting therapy with the requested agent AND will NOT receive a live vaccine concurrently with the requested agent AND
6. The patient does NOT have severe active central nervous system lupus AND
7. If the requested agent is Benlysta, then BOTH of the following:
   1. The patient will NOT be using the requested agent in combination with Lupkynis AND
   2. 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 (submitted copy of clinical trials, phase III studies, guidelines required) AND
8. If the requested agent is Lupkynis, the patient will NOT be using the requested agent in combination with cyclophosphamide, Benlysta, OR Saphnelo AND
9. The patient does NOT have any FDA labeled contraindications to the requested agent

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

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. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why 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: up to 12 months

Note: If approving initial loading dose for subcutaneous Benlysta, approve the loading dose for 1 month, followed by maintenance dosing for the remainder of the length of approval.

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)
Leqselvi (deuruxolitinib)
Litfulo (ritlecitinib)
Nemluvio (nemolizumab-ilto)
Nucala (mepolizumab)
Olumiant (baricitinib)
Omvoh (mirikizumab-mrkz)
Opzelura (ruxolitinib)
Orencia (abatacept)
Otezla (apremilast)
Pyzchiva (ustekinumab-ttwe)
Remicade (infliximab)
Renflexis (infliximab-abda)
Riabni (rituximab-arrx)
Rinvoq (upadacitinib)
Rituxan (rituximab)
Rituxan Hycela (rituximab/hyaluronidase human)
Ruxience (rituximab-pvvr)
Saphnelo (anifrolumab-fnia)
Selarsdi (ustekinumab-aekn)
Siliq (brodalumab)
Simlandi (adalimumab-ryvk)
Simponi (golimumab)
Simponi ARIA (golimumab)
Skyrizi (risankizumab-rzaa)
Sotyktu (deucravacitinib) 
Spevigo (spesolimab-sbzo) subcutaneous injection
Stelara (ustekinumab)
Taltz (ixekizumab)
Tezspire (tezepelumab-ekko)
Tofidence (tocilizumab-bavi)
Tremfya (guselkumab)
Truxima (rituximab-abbs)
Tyenne (tocilizumab-aazg)
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)