|MP 5.01.110||Belimumab (Benlysta® )|
|Original Policy Date
|Last Review Status/Date
Local Policy created with literature search/11:2011
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Belimumab (Benlysta®, previously known as LymphoStat-B) is a recombinant, fully human, IgG monocolnal antibody that binds and inhibits the biological activity of soluble B lymphocyte stimulator, or BLyS, protein. BLyS is a member of the tumor necrosis factor (TNF) ligan family and is also known as B-cell activating factor belonging to the tumor necrosis factor family (BAFF). It plays a role in B cell selection and survival and is expressed by a variety of cell types, including neutrophils, monocytes, macrophages, dendritic cells, and T cells. (8) There are 3 receptors for BLyS. BLyS receptor 3 (BR3) is the only BLyS receptor found on newly formed and mature primary B cells, and BLyS is its only ligand. Blockade by belimumab (Benlysta® ) is expected to affect these cells more than memory B cells and plasma cells, which have other ligand activators.
Belimumab (Benlysta®) is a new molecular entity that targets a novel pathway for the treatment of systemic lupus erythematosus (SLE). The scope of this review is the clinical effectiveness and safety of belimumab (Benlysta®) for reducing disease activity in adult patients with active, autoantibody-positive SLE who are receiving standard therapy. No studies assessing the use of belimumab (Benlysta®) in other autoimmune diseases have been published. A list of currently active clinical trials of belimumab (Benlysta®) in other diseases is included.
Belimumab (Benlysta®) may be considered medically necessary if:
- all inclusion criteria are met,
- no exclusion criterion applies,
- the dosing is appropriate, and,
- follow-up assessments occur during ongoing treatment.
Each of these elements is defined below.
- Patients are adults at least 18 years of age diagnosed with SLE by American College of Rheumatology criteria.
- Patients have tested positive for serum antibodies at 2 independent time points of 30 days or greater. Positive serum antibody tests are:
- Anti-nuclear antibody (ANA) titer ≥ 1:80
- Anti-double-stranded DNA ≥ 30 IU/mL
- Patients have active disease as indicated by a score on the Safety of Estrogens in Lupus Erythematosus National Assessment modification of the SLE Disease Activity Index (SELENA-SLEDAI) of at least 6.
- Patients are receiving a stable standard of care treatment regimen for SLE for at least 30 days. Standard of care treatment regimens comprise any of the following drug classes, alone or in combination:
- non-biologic immunosuppressives
- Severe active lupus nephritis, defined as either:
- Proteinuria > 6 g/24 hour, or
- Serum creatinine > 2.5 mg/dL
- Hemodialysis within 90 days prior to the first dose of study drug
- Severe active central nervous system (CNS) lupus, including seizures, psychosis, organic brain syndrome, cerebrovascular accident, cerebritis or CNS vasculitis requiring therapeutic intervention within 60 days before initiation of belimumab (Benlysta®)
- Any chronic infection (e.g., chronic hepatitis, tuberculosis, pneumocystis carinii jiroveci pneumonia [PCP], cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria)
- Hospitalization for treatment of infection or use of parenteral (intravenous or intramuscular) antibiotics (i.e., antibacterials, antivirals, antifungals, or anti-parasitic agents) within 60 days before initiation of belimumab (Benlysta®)
- Significant unstable or uncontrolled acute or chronic comorbid disease (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurologic, or infectious disease); for example, 3 or more courses of oral or intravenous steroids for asthma or atopic dermatitis within 1 year
- Malignant neoplasm within the last 5 years, excluding adequately-treated basal or squamous cell skin cancers and cervical carcinoma-in-situ
- Current treatment with other biologics or intravenous cyclophosphamide
- Live vaccine within 30 days before initiation of belimumab (Benlysta®)
- Pregnancy or breast-feeding
- Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to first dose of study drug
- Belimumab (Benlysta®) is administered by intravenous infusion.
- The recommended dosage regimen is 10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter.
- Belimumab (Benlysta®) is administered by healthcare providers prepared to manage anaphylaxis.
- Prophylaxis for infusion reactions, including antihistamines and corticosteroids, may be considered.
- If an infusion reaction develops, the infusion rate may be slowed or interrupted.
- If a serious hypersensitivity reaction develops, the infusion must be discontinued immediately.
- Women of childbearing potential should use adequate contraception during treatment with belimumab (Benlysta®) and for at least 4 months after the final treatment.
- Live vaccines should not be administered for 30 days before or concurrently with belimumab (Benlysta®).
- For any new infection that develops during treatment with belimumab (Benlysta®), consideration should be given to interrupting or discontinuing belimumab (Benlysta®) therapy.
- After treatment with belimumab (Benlysta®) for 6 months, treatment response should be assessed. If there has been deterioration in clinical status, as defined by any of the following, discontinuation of belimumab (Benlysta®) should be considered:
- Increase in SELENA-SLEDAI of 8 or more points, or
- Increase in BILAG of 8 or more points, or
- New or worsening BILAG A or 2 BILAG B organ domain scores
- Periodic assessments for new or worsening depression, suicidal thoughts, and other mood changes should be performed during belimumab (Benlysta®) treatment.
An effective therapeutic regimen for the treatment of SLE first requires the accurate determination of both disease activity and severity. Disease activity usually refers to the degree of inflammation, while severity implies that organ function and perhaps its underlying structure is quantitatively impaired. The ability to differentiate between these two possibilities is extremely important because immunosuppressive therapy is not indicated in the absence of inflammation.¹ The American College of Rheumatology (ACR) defines mild disease as outlined in Table 1.
Table 1. Characteristics of Patients with Mild SLE
|1. Diagnosis of SLE is confirmed or highly suspected.|
2. Disease is clinically stable.
|3. Disease is not life threatening.|
4. Body systems that can be a target of SLE have normal and stable function, including:
|5. There are no significant toxicities of the therapies for SLE.|
Most physicians rely on classification criteria developed by the American Rheumatism Association (now the American College of Rheumatology [ACR]) that use history, physical examination, and laboratory data for diagnosis (see Table 2). These criteria were developed to differentiate SLE patients from patients with other rheumatic diseases in clinical trials, and were established primarily in Caucasian patients. Whether the criteria apply to other populations has not been established.(5)
If a patient has, at any time in his or her medical history, 4 of the 11 criteria documented, the diagnosis of SLE can be made with 95% specificity and 85% sensitivity. If the patient meets fewer than 4 criteria, the diagnosis of SLE is possible, and the diagnosis depends upon clinical judgment. If ANA are negative, the patient has a very low probability of having SLE. Patients with positive ANA alone, without organ system involvement or typical laboratory findings, are unlikely to have SLE.(9)
|1. Malar rash||Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds|
|2. Discoid rash||Erythematosus raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions|
|3. Photosensitivity||Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation|
|4. Oral ulcers||Oral or nasopharyngeal ulceration, usually painless, observed by a physician|
|5. Arthritis||Nonerosive arthritis involving 2 or more peripheral joints, characterized by tenderness, swelling, or effusion|
|6. Serositis||Pleuritis - convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion, OR
Pericarditis - documented by EKG, rub or evidence of pericardial effusion
|7. Renal disorder||Persistent proteinuria greater than 0.5 grams per day or greater than 3+ if quantitation not performed OR
Cellular casts - may be red cell, hemoglobin, granular, tubular, or mixed
|8. Neurologic disorder||Seizures OR psychosis - in the absence of offending drugs or known metabolic derangements (uremia, ketoacidosis, or electrolyte imbalance)|
|9. Hemtologic disorder||Hemolytic anemia - with reticulocytosis, OR
Leukopenia - less than 4,000/mm3 total on two or more occasions, OR
Lymphopenia - less than 1,500/mm3 on two or more occasions, OR
Thrombocytopenia - less than 100,000/mm3 in the absence of offending drugs
|10. Immunologic disorders||Positive antiphospholipid antibody, OR
Anti-DNA - antibody to native DNA in abnormal titer, OR
Anti-Sm - presence of antibody to Sm nuclear antigen, OR
False-positive serologic test for syphilis known to be positive for at least six months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test
|11. Antinuclear antibody||An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with 'drug-induced lupus' syndrome|
ACR = American College of Rheumatology, anti-dsDNA = anti-double stranded DNA autoantibody, anti-Sm = anti-Smith antigen autoantibody,
EKG = electrocardiogram, SLE = systemic lupus erythematosus
- 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. The Lancet 2011;377(9767):721-731.
- van Vollenhoven RF, Zamani O, Wallace DJ et al. European League Against Rheumatism Abstract Archive. Belimumab, a BLyS-specific inhibitor, reduces disease activity and severe flares in seropositive SLE patients: BLISS-76 study. Available at: http://www.abstracts2view.com/eular/view.php?nu=EULAR10L_OP0068. Accessed December 2010.
- 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 2009;61(9):1168-1178.
- UpToDate. Overview of the clinical manifestations of systemic lupus erythematosus in adults. Available at: http://www.uptodate.com/home/index.html. Accessed December 2010.
- UpToDate. Diagnosis and differential diagnosis of systemic lupus erythematosus in adults. Available at: http://www.uptodate.com/home/index.html. Accessed December 2010.
- UpToDate. Epidemiology and pathogenesis of systemic lupus erythematosus. Available at: http://www.uptodate.com/home/index.html. Accessed December 2010.
- Wang J, Pan HF, Ye DQ, Su H, Li XP. Moderate alcohol drinking might be protective for systemic lupus erythematosus: a systematic review and meta-analysis. Clin Rheumatol 2008;27(12):1557-1563.
- Townsend MJ, Monroe JG, Chan AC. B-cell targeted therapies in human autoimmune diseases: An updated perspective. Immunological Reviews 2010;237(1):264-283.
- 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.
- Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25(11):1271-1277.
- Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40(9):1725.
- FDA. Center for Drug Evaluation and Research. FDA briefing information, belimumab (Benlysta®), for the November 16, 2010 meeting of the Arthritis Advisory Committee. Available at:
|Q2044||Injection, belimumab, 10mg|
|11/07/11||Add to Prescription Drug section||New policy|