Last Review Date: 04/04/2024

Date of Origin: 01/01/2012

Dates Reviewed: 12/2011, 02/2013, 02/2014, 11/2014, 03/2015, 06/2015, 09/2015 12/2015, 03/2016, 06/2016, 09/2016, 12/2016, 03/2017, 06/2017, 09/2017, 12/2017, 03/2018, 06/2018, 04/2019, 05/2019, 04/2020, 01/2021, 04/2021, 04/2022, 09/2022, 04/2023, 09/2023, 04/2024

1. Length of Authorization

Coverage will be provided for 12 months and may be renewed.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

• Loading Dose (doses administered on days 1, 15 and 29):
  • Benlysta 120 mg single-dose vial for injection: 9 vials per 29 days
  • Benlysta 400 mg single-dose vial for injection: 9 vials per 29 days 
• Maintenance Dose:
  • Benlysta 120 mg single-dose vial for injection: 3 vials per 28 days
  • Benlysta 400 mg single-dose vial for injection: 3 vials per 28 days

B. Max Units (per dose and over time) [HCPCS Unit]:

• Loading Dose:
  • 120 billable units on days 1, 15 and 29
• Maintenance Dose:
  • 120 billable units per 28 days

3. Initial Approval Criteria ¹

• Patient is at least 5 years of age; AND

Universal Criteria ¹

• Patient must not have an active infection; AND
• Patient will not receive live vaccines during therapy or within 30 days prior to starting treatment; AND
• Patient does not have severe active central nervous system lupus; AND
• Will be used in combination with standard therapy (e.g., anti-malarials, corticosteroids, non-steroidal anti-inflammatory drugs, immunosuppressives); AND
• Will not be used in combination with rituximab, anifrolumab, or IV cyclophosphamide*; AND

* Note:  May be used in combination with IV cyclophosphamide for Lupus Nephritis.

Systemic Lupus Erythematosus (SLE) † ^{1,9,11,12, 22-27,29}

• Patient has a confirmed diagnosis of SLE as evidenced by all of the following:
  • Confirmed SLE classification criteria score >10* (Note: must include clinical and immunologic domains criteria)
  • 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
• Patient has documented active disease; AND
• Physician has assessed baseline disease severity utilizing an objective measure/tool (i.e., Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K), British Isles Lupus Assessment Group-2004 (BILAG 2004), and/or Physician’s Global Assessment (PGA) score); AND
• Patient has failed to respond adequately to at least one (1) standard therapy such as anti-malarials, corticosteroids, non-steroidal anti-inflammatory drugs, immunosuppressives**

** Note:  For patients already established on biologic therapy, trial and failure of standard therapy is not required.

Lupus Nephritis (LN) † ^{1,9,11,12,19,22,28-30}

• Patient has active lupus nephritis Class III, IV, or V as confirmed by renal biopsy; AND
• Patient has a confirmed diagnosis of SLE as evidenced by all of the following**:
  • Confirmed SLE classification criteria score >10* (Note: must include clinical and immunologic domains criteria)
  • 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
• Physician has obtained a baseline measurement of one or more of the following: urine protein:creatinine ratio (uPCR), estimated glomerular filtration rate (eGFR), or urine protein

**Patients with class III, IV, or V disease that do not meet the SLE diagnostic criteria will be reviewed on a case-by-case basis

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage can be renewed based on the following criteria:

• Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: depression, suicidal thoughts, serious infections, suspected or confirmed progressive multifocal leukoencephalopathy (PML), malignancy, severe hypersensitivity reactions/anaphylaxis, serious infusion-related reactions, etc.; AND

Systemic Lupus Erythematosus (SLE) ^1,9,21-27,29

• Adequate documentation of disease stability and/or improvement as indicated by one or more of the following when compared to pre-treatment baseline:

• Improvement in the SELENA-SLEDAI-2K; OR
• Reduction of baseline BILAG-2004 (e.g. reduction from A to B or from B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥2 new BILAG-2004 B or ≥1 new BILAG A); OR
• No worsening (<0.30-point increase) in Physician’s Global Assessment (PGA) score; OR
• Seroconverted (negative)

Lupus Nephritis (LN) ^1,19,22,30

• Adequate documentation of disease stability and/or improvement as indicated by one or more of the following when compared to pre-treatment baseline:

• Urine protein:creatinine ratio (uPCR); OR
• Estimated glomerular filtration rate (eGFR); OR
• Urine protein

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J0490 – Injection, belimumab, 10 mg; 1 billable unit = 10 mg

NDC(s):

• Benlysta 120 mg/5 mL single-dose vial for injection: 49401-0101-xx
• Benlysta 400 mg/20 mL single-dose vial for injection: 49401-0102-xx

7. References

1. Benlysta [package insert]. Philadelphia, PA; GlaxoSmithKline LLC; February 2024. Accessed February 2024.
2. Boyce EG, Fusco BE.  Belimumab: review of use in systemic lupus erythematosus.  Clin Ther. 2012 May;34(5):1006-22. doi: 10.1016/j.clinthera.2012.02.028. Epub 2012 Mar 30.
3. Navarra SV, Guzmán RM, Gallacher AE, et al.  Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Feb;377(9767):721-31. doi: 10.1016/SO140-6736(10)61354-2. Epub 2011 Feb 4.
4. Furie R, Petri M, Zamani O, et al.  A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus.  Arthritis Rheum. 2011 Dec;63(12):3918-30. doi: 10.1002/art.30613.
5. Petri M, Orbai AM, Alarcón GS, et al.  Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug;64(8):2677-86. doi: 10.1002/art.34473.
6. Furie R, Stohl W, Ginzler EM, et al. Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus. Arthritis Res Ther. 2008;10(5):R109. doi: 10.1186/ar2506. Epub 2008 Sep 11.
7. Kim SS, Kirou KA, Erkan D. Belimumab in systemic lupus erythematosus: an update for clinicians. Ther Adv Chronic Dis. 2012 Jan;3(1):11-23. doi: 10.1177/2040622311424806.
8. Calvo-Alén J1, Silva-Fernández L, Úcar-Angulo E, et al. SER consensus statement on the use of biologic therapy for systemic lupus erythematosus. Reumatol Clin. 2013 Sep-Oct;9(5):281-96.
9. Gordon C, Amissah-Arthur MB, Gayed M, et al. The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. See comment in PubMed Commons belowRheumatology (Oxford). 2018 Jan 1;57(1):e1-e45. doi: 10.1093/rheumatology/kex286.
10. NICE. Belimumab for treating active autoantibody-positive systemic lupus erythematosus: Technology Appraisal Guidance [TA397]. https://www.nice.org.uk/guidance/ta397.  Published: 22 June 2016. Accessed March 2021.
11. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis Rheum. 1999;42(9):1785–1796.
12. Lam NC, Ghetu MV, Bieniek ML. Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management. Am Fam Physician. 2016 Aug 15;94(4):284-94.
13. Wallace DJ, Stohl W, Furie RA, et al. A Phase II, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of Belimumab in Patients With Active Systemic Lupus Erythematosus. Arthritis Rheum, 61 (9), 1168-78, 2009 Sept 15. doi: 10.1002/art.24699
14. D’Cruz D, Maksimowicz-McKinnon K, Oates J, et al. Efficacy and safety of belimumab in patients of black race with systemic lupus erythematosus: results from the EMBRACE study. 10.1136/lupus-2019-lsm.199
15. Brunner HI, Abud-Mendoza C, Viola DI, et al. Efficacy and Safety of Intravenous Belimumab in Children with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-intravenous-belimumab-in-children-with-systemic-lupus-erythematosus/
16. Stohl W, Schwarting A, Okada M, et al. Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty-Two-Week Randomized, Double-Blind, Placebo-Controlled Study. Arthritis Rheumatol, 69 (5), 1016-1027; May 2017. DOI: 10.1002/art.40049.
17. Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 2019;78: 736–745.
18. Furie R, Rovin BH, Houssiau F, et al. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med 2020; 383:1117-1128. DOI: 10.1056/NEJMoa2001180.
19. Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012;64(6):797-808. doi:10.1002/acr.21664.
20. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771-1782. doi:10.1136/annrheumdis-2012-201940.
21. NICE. Belimumab for treating active autoantibody-positive systemic lupus erythematosus: Technology appraisal guidance [TA752]. https://www.nice.org.uk/guidance/ta752. Published: 15 December 2021.
22. Aringer M, Costenbader K, Daikh D, et al. 2019 European League against Rheumatism/American College of rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol 2019;71:1400–12.
23. Fanouriakis A, Tziolos N, Bertsias G, et al. Update on the diagnosis and management of systemic lupus erythematosus. Ann Rheum Dis 2021; 80:14-25. doi:10.1136/annrheumdis-2020-218272
24. Lam NC, Brown JA, Sharma R. Systemic Lupus Erythematosus: Diagnosis and Treatment. Am Fam Physician. 2023 Apr 107(4):383-395.
25. Yee CS, Cresswell L, Farewell V, Rahman A, Teh LS, Griffiths B et al. Numerical scoring for the BILAG-2004 index. Rheumatology (Oxford) 2010; 49(9):1665-9.
26. Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29(2):288-91. 
27. Chessa E, Piga M, Floris A, Devilliers H, Cauli A, Arnaud L. Use of Physician Global Assessment in systemic lupus erythematosus: a systematic review of its psychometric properties. Rheumatology (Oxford). 2020 Dec 1;59(12):3622-3632. doi: 10.1093/rheumatology/keaa383.
28. Fanouriakis A, Kostopoulou M, Cheema K, et al: 2019 update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis 2020; 79(6):713-723
29. Fanouriakis A, Kostopoulou M, Andersen J, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2024 Jan 2;83(1):15-29. doi: 10.1136/ard-2023-224762.
30. Kidney Disease: Improving Global Outcomes (KDIGO) Lupus Nephritis Work Group. KDIGO 2024 Clinical Practice Guideline for the Management of Lupus Nephritis. Kidney Int. 2024;105(1S):S1–S69.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A