0818 Belimumab (Benlysta) (2) · 2020. 9. 3. · recommended dosage for belimumab is 10 mg/kg IV over 1 hour every 2 weeks for the ﬁrst3 doses then every 4 weeksthereafter. Subcutaneous

Belimumab (Benlysta) - Medical Clinical Policy Bulletins | Aetna

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Belimumab (Benlysta)

Clinical Policy Bulletins Medical Clinical Policy Bulletins

Last Review

11/20/2018

Effective: 08/01/2011

Next

Review: 09/10/2020

Review

History

Definitions

Additional Information

Clinical Policy

Bulletin

Notes

Number: 0818

*Please see amendment for Pennsylvania Medicaid at the end of this CPB.

Note: Requires Precertification

Precertification of belimumab (Benlysta) is required of all Aetna participating providers and

members in applicable plan designs. For precertification of belimumab (Benlysta), call (866)

752-7021, or fax (866) 267-3277.

Note: Site of Care Utilization Management Policy applies to belimumab (Benlysta). For

information on site of service for Benlysta infusions, see

Utilization Management Policy on Site of Care for Specialty Drug Infusions

(https://www.aetna.com/health-care-professionals/utilization-management/drug-infusion

site-of-care-policy.html)

.

Aetna considers belimumab (Benlysta) medically necessary for the treatment of active systemic

lupus erythematosus (SLE) when all of the following criteria are met (see below: Exclusion

Criteria for Belimumab):

Prior to initiating therapy, the member is positive for autoantibodies relevant to SLE (e.g.,

anti-nuclear antibody or anti-double-stranded DNA antibody), and

The member is receiving standard treatment for SLE with any of the following (alone or

in combination):

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Glucocorticoids (e.g., prednisone, methylprednisolone, dexamethasone)

Antimalarials (e.g., hydroxychloroquine)

Immunosuppressants (e.g., azathioprine, methotrexate, mycophenolate,

cyclosporine, cyclophosphamide).

Aetna considers continuation of belimumab medically necessary for all members (including new

members) who are using belimumab for an indication outlined above and who achieve or

maintain a positive clinical response as evidenced by low disease activity or improvement in

signs and symptoms of the condition.

Exclusion Criteria for Belimumab

Benlimumab is considered experimental and investigational for persons with the following:

Severe active lupus nephritis (proteinuria greater than 6 g/24 hours or equivalent using

spot urine protein to creatinine ratio, or serum creatinine greater than 2.5 mg/dl)

Severe active central nervous system lupus (including seizures, psychosis, organic brain

syndrome, cerebrovascular accident, cerebritis, or CNS vasculitis requiring therapeutic

intervention within 60 days before initiation of belimumab)

Member is using belimumab in combination with other biologics or intravenous

cyclophosphamide.

Experimental and Investigational

Aetna considers belimumab experimental and investigational for all other indications

including the following (not an all-inclusive list) because its effectiveness for indications other

than the one listed above has not been established:

Antibody-associated vasculitis

Antibody-mediated rejection in lung transplantation and kidney transplantation

Anti-phospholipid antibody syndrome

Gout

Immunosuppressionfollowingstemcell/solidorgantransplantations

Multiple sclerosis

Myasthenia gravis

Psoriatic arthritis

Retinal vasculitis

Rheumatoid arthritis

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Sjogren syndrome

Systemic sclerosis

Uveitis

Waldenstrom macroglobulinemia

Systemic Lupus Erythematosus (SLE):

Intravenous infusion: Benlysta (belimumab) is available as 120 mg or 400mg lyophilized

powder in single-dose vials for reconstitution and dilution prior to IV infusion. The

recommended dosage for belimumab is 10 mg/kg IV over 1 hour every 2 weeks for the

first 3 doses then every 4 weeks thereafter.

Subcutaneous injection: Benlysta (belimumab) is available as a 200 mg/mL single-dose

prefilled autoinjector or single-dose prefilled syringe. The recommended dosage for

subcutaneous belimumab is 200 mg once weekly. Note: subcutaneous dosing of

Benlysta has not been evaluated and is not approved for members younger than 18

years of age.

Source: GlaxoSmithKline, 2019

Benlysta (belimumab) is a human monoclonal antibody drug that specifically recognizes and

inhibits the biological activity of B‐lymphocyte stimulator, or BLyS. BLyS is a cytokine that

belongs to the tumor necrosis factor (TNF) ligand family. It is expressed as transmembrane

protein on various cell types including monocytes, dendritic cells, and bone marrow stromal cells

and is required for the development of B‐lymphocyte cells into mature plasma B cells. Plasma B

cells produce anti‐bodies, the body's first line of defense against infection. In lupus and certain

other autoimmune diseases, elevated levels of BLyS are believed to contribute to the production

of autoantibodies –antibodies that attack and destroy the body's own healthy tissues. The

presence of autoantibodies appears to correlate with disease severity. Preclinical and clinical

studies suggest that belimumab can reduce autoantibody levels inSLE.

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Benlysta (belimumab) has been approved by the U.S. Food and Drug Administration (FDA) for

the adjunctive treatment of active, autoantibody-positive, systemic lupus erythematosus (SLE).

Belimumab has not been evaluated and is not recommended in patients with severe active lupus

nephritis or severe active central nervous system lupus or in combination with other biologic

products or cyclophosphamide.

Systemic lupus erythematosus (SLE) is a potentially fatal, autoimmune disease, which is

characterized by clinical diversity, alerations in the disease activity over time, and aberrations in

multiple components of the immune system including B cells, T cells, as well as cytokines and

growth factors, especially the presence of anti-nuclear antibodies (ANA) that are found in over 90

% of the patients. Moreover, anti-double-strand deoxyribonucleic acid (anti-dsDNA) antibodies

are found in 50 to 90 % of the patients. The prevalence of SLE worldwide is 4 to 250 per

100,000; the disease affects women disproportionately (approximately 90 % of the patients are

female). The incidence is most frequent in women aged 15 to 25 years. The disease affects

many parts of the body including the brain, heart, joints, kidneys, lungs, and the skin. When SLE

flares, it can present as chest pain, fatigue, fever, hair loss, rash, light sensitivity, as well as

swelling in the joints and joint pain (Finnish Medical Society,2007).

Conventional treatments of SLE include anti-malarials (e.g., chloroquine and

hydroxychloroquine), corticosteroids, and non-steroidal anti-inflammatory drugs (e.g., aspirin).

While therapeutic advances in immunosuppressive drugs (e.g., azathioprine, cyclophosphamide,

methotrexate, mycophenolate) and support therapy have markedly improved survival, SLE still

carries substantially increased rates of mortality and end stage renal disease, which are even

more elevated in younger patients. No new drugs have been approved for SLE in over 50

years. Hence, a lot of hope and excitement has been generated by the development of

biological agents designed to eliminate B cells either through direct killing (anti-B cell antibodies

such as rituximab) or attrition by inhibition of survival (anti-B-lymphocyte stimulator BLyS [also

known asBAFF] agents such as belimumab). Belimumab is a human IgG1g antibody that is the

first of the BLyS-specific inhibitor. It blocks the binding of soluble BLyS, a B-cell survival factor,

to its receptors on B cells. Belimumab does not bind B cells directly, but by binding BLyS,

belimumab inhibits the survival of B cells, including auto-reactive B cells, and reduces the

differentiation of B cells into immunoglobulin-producing plasma cells. Clinical trials of various

phases have indicated that belimumab is beneficial for patients with SLE (Furie et al, 2008;

Wallace et al, 2009; Jacobi et al, 2010; Navarra et al,2011).

In a phase I clinical study, Furie et al (2008) evaluated the safety, biological activity, and

pharmacokinetics of belimumab in patients with SLE. A total of 70 patients with mild-to-

moderate SLE were randomized to receive placebo (n = 13) or belimumab (n = 57) at 4 different

doses (1.0, 4.0, 10, and 20 mg/kg body weight) as a single infusion or two infusions 21 days

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apart. Patients were followed for 84 to 105 days to assess adverse events, pharmacokinetics,

peripheral blood B-cell counts, serology, and SLE disease activity. Data from the study were

summarized using descriptive statistics. Chi-square type tests were used to analyze discrete

variables. The Kruskal-Wallis test, the Wilcoxon test, and the analysis of co-variance were used

to analyze the continuous variables, as appropriate. The analysis was performed on all

randomized patients who received study agent. The incidences of adverse events and

laboratory abnormalities were similar among the belimumab and placebo groups. Belimumab

pharmacokinetics were linear across the 1.0 to 20 mg/kg dose range. Long terminal elimination

half-life (8.5 to 14.1 days), slow clearance (7 ml/day per kg), and small volume of distribution (69

to 112 ml/kg) were consistent with a fully human antibody. Significant reductions in median

percentages of CD20+ B cells were observed in patients treated with a single dose of belimumab

versus placebo (day 42: p = 0.0042; and day 84: p = 0.0036) and in patients treated with 2 doses

of belimumab versus placebo (day 105: p = 0.0305); SLE disease activity did not change after 1

or 2 doses of belimumab. The authors concluded that belimumab was well-tolerated and

reduced peripheral B-cell levels in SLE patients.

In a phase II, randomized, double-blind, placebo-controlled, dose-ranging study, Wallace and

colleagues (2009) evaluated the safety, tolerability, biological activity, and effectiveness of

belimumab in combination with standard of care therapy (SOC) in patients with active SLE.

Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA)

version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score greater

than or equal to 4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo

in a 52-week study. Co-primary end points were the percent change in the SELENA-SLEDAI

score at week 24 and the time to first SLE flare. Significant differences between the treatment

and placebo groups were not attained for either primary end point, and no dose response was

observed. Reductions in SELENA-SLEDAI scores from baseline were 19.5 % in the combined

belimumab group versus 17.2 % in the placebo group. The median time to first SLE flare was 67

days in the combined belimumab group versus 83 days in the placebo group. However, the

median time to first SLE flare during weeks 24 to 52 was significantly longer with belimumab

treatment (154 versus 108 days; p = 0.0361). In the subgroup (71.5 %) of serologically active

patients (ANA titer greater than or equal to 1:80 and/or anti-dsDNA greater than or equal to 30

International Units/ml), belimumab treatment resulted in significantly better responses at week 52

than placebo for SELENA-SLEDAI score (-28.8 % versus -14.2 %; p = 0.0435), physician's

global assessment (-32.7 % versus -10.7 %; p = 0.0011), and Short Form-36 physical

component score (+3.0 versus +1.2 points; p = 0.0410). Treatment with belimumab resulted in a

63 to 71 % reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4 %

reduction in anti-dsDNA titers (p = 0.0017) by week 52. The rates of adverse events and serious

adverse events were similar in the belimumab and placebo groups. The authors concluded that

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belimumab was biologically active and well-tolerated. The effect of belimumab on the reduction

of SLE disease activity or flares was not significant. However, serologically active SLE patients

responded significantly better to belimumab therapy plus SOC than to SOC alone.

Jacobi and co-workers (2010) examined the effects of long-term BLyS inhibition in patients with

SLE. A total of 17 subjects with SLE who were enrolled in a clinical trial of belimumab plus SOC

were studied. Phenotypic analysis of lymphocytes was performed using flowcytometry.

Circulating antibody-secreting cells were enumerated using enzyme-linked immunospot assay.

Serum was analyzed by enzyme-linked immunosorbent assay using an antibody that recognizes

products of the V(H)4-34 gene. Lymphocyte counts, Ig levels, and anti-dsDNA antibody levels

were available as part of the clinical trial analyses. Samples were collected on days 0, 84, 168,

365, and 532 and after day 730. The total number of B cells started to decrease from baseline

between days 84 and 168. This was due to a decrease in naive and transitional B cells.

CD27+IgD+ memory B cells and plasmablasts decreased only after 532 days, whereas

CD27+IgD- memory B cells were not affected, and there were no changes in T cells. Serum IgM

levels began to decline between days 84 and 168, but there were no changes in serum levels of

IgG, IgG anti-DNA antibodies, or V(H)4-34 antibodies during the study. Patients with SLE had

more IgM-, IgG-, and autoantibody-producing B cells than did normal controls on day 0. There

was only a modest decrease in the frequency of total IgM-producing, but not IgG-producing, cells

on days 365 and 532, consistent with the phenotypic and serologic data. The authors concluded

that these findings confirm the dependence of newly formed B cells on BLyS for survival in

humans. In contrast, memory B cells and plasma cells are less susceptible to selective BLyS

inhibition.

In a randomized, multi-center, placebo-controlled, phase III trial, Navarra and associates (2011)

evaluated the safety and effectiveness of belimumab in patients with active SLE. Patients (aged

greater than or equal to 18 years) who were sero-positive with scores of at least 6 on the

SELENA-SLEDAI were enrolled in the study. Patients were randomly assigned by use of a

central interactive voice response system in a 1:1:1 ratio to belimumab 1 mg/kg or 10 mg/kg, or

placebo by intravenous infusion in 1 hr on days 0, 14, and 28, and then every 28 days until 48

weeks, with SOC. Patients, investigators, study coordinators, and sponsors were masked to

treatment assignment. Primary efficacy end point was improvement in the SLE Responder Index

(SRI) at week 52 (reduction greater than or equal to 4 points in SELENA-SLEDAI score; no new

British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new B

organ domain score; and no worsening [less than 0·3 increase] in Physician's Global

Assessment [PGA] score) versus baseline. Method of analysis was by modified intention-to-

treat. A total of 867 patients were randomly assigned to belimumab 1 mg/kg (n = 289) or 10

mg/kg (n = 290), or placebo (n = 288); 865 were treated and analyzed in the belimumab (1

mg/kg, n = 288; 10 mg/kg, n = 290) and placebo groups (n = 287). Significantly higher SRI rates

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were noted with belimumab 1 mg/kg (148 [51 %], odds ratio 1.55 [95 % confidence interval [CI]:

1.10 to 2.19]; p = 0·0129) and 10 mg/kg (167 [58 %], 1.83 [1.30 to 2.59]; p = 0·0006) than with

placebo (125 [44 %]) at week 52. More patients had their SELENA-SLEDAI score reduced by at

least 4 points during 52 weeks with belimumab 1 mg/kg (153 [53 %], 1.51 [1.07 to 2.14]; p =

0·0189) and 10 mg/kg (169 [58 %], 1.71 [1.21 to 2.41]; p = 0·0024) than with placebo (132 [46

%]). More patients given belimumab 1 mg/kg (226 [78 %], 1.38 [0.93 to 2.04]; p = 0·1064) and

10 mg/kg (236 [81 %], 1.62 [1.09 to 2.42]; p = 0·0181) had no new BILAG A or no more than 1

new B flare than did those in the placebo group (210 [73 %]). No worsening in PGA score was

noted in more patients with belimumab 1 mg/kg (227 [79 %], 1.68 [1.15 to 2.47]; p = 0·0078) and

10 mg/kg (231 [80 %], 1.74 [1.18 to 2.55]; p = 0·0048) than with placebo (199 [69 %]). Rates of

adverse events were similar in the groups given belimumab 1 mg/kg and 10 mg/kg, and placebo:

serious infection was reported in 22 (8 %), 13 (4 %), and 17 (6 %) patients, respectively, and

severe or serious hypersensitivity reactions on an infusion day were reported in 2 (less than 1

%), 2 (less than 1 %), and no patients, respectively. No malignant diseases were reported. The

authors concluded that belimumab has the potential to be the first targeted biological treatment

that is approved specifically for SLE, providing a new option for the management of this

important prototypic autoimmune disease.

On March 8, 2011, the U.S. Food and Drug Administration approved belimumab (Benlysta) for

the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus

who are receiving standard therapy, including anti-malarials, corticosteroids,

immunosuppressives, and non-steroidal anti-inflammatory drugs. The label for Benlysta includes

the following limitations of use: The efficacy of belimumab has not been evaluated in patients

with severe active lupus nephritis or severe active central nervous system lupus, and has not

been studied in combination with other biologics or intravenous cyclophosphamide. Belimumab

is administered intravenously over a 1-hour period; it should not be administered with live

vaccines. The most common side effects associated with the use of belimumab include

diarrhea, fever, and nausea. Patients also commonly experienced infusion reactions; thus, pre-

treatment with an anti-histamine should be considered. Belimumab is approved at a dosage of

10 mg/kg of body weight to be given at 2-week intervals for the first 3 doses and 4-week intervals

thereafter. In several randomized controlled trials examining the effectiveness of belimumab in

patients with SLE, the durations of therapy were 52 and 76 weeks (Phung, 2011). In a clinical

study of belimumab submitted to the FDA for approval, active SLE disease was defined as a

SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus: National Assessment-Systemic

Lupus Erythematosus Disease Activity Index) score of equal to or greater than 4, and positive

autoantibody test results (anti-nuclear antibody [ANA] and/or anti-double-stranded DNA [anti-

dsDNA]) at screening.

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Belimumab has also been studied in the treatment of other autoimmune diseases such as lupus

nephritis, multiple sclerosis, and rheumatoid arthritis (Aran and Putterman, 2008; Hawker, 2008;

Bingham, 2008). Furthermore, belimumab is being considered as one of the novel strategies in

immunosuppression following stem cell/solid organ transplantations (Webber et al, 2011).

However, in the absence of evidence based on large, randomized, placebo-controlled trials, the

role of belimumab for these indications has yet to beestablished.

The American College of Rheumatology's guidelines for screening, treatment, and management

of lupus nephritis (Hahn et al, 2012) notes that alternative therapies (e.g., rituximab, tacrolimus,

belimumab, calcineurin inhibitors) were considered but no consensus for recommendation was

reached.

Khattri and colleagues (2012) stated that the increased awareness of the role of humoral

immunophysiology in anti-phospholipid syndrome (APS) has aroused interest in B cells as

therapeutic targets in this disease. These researchers reviewed the literature on B cell-directed

therapies in human and experimental APS. The clinical data were limited to B cell depletion with

rituximab and comprised case reports and case series. Murine studies include use of

modulators of B cell function (e.g., belimumab and abatacept). In both human and murine

studies, B cell-directed therapies appeared to have clinical and serologic beneficial effects

including a decrease in the anti-phospholipid antibody titers after treatment. The authors

concluded that randomized controlled trials are needed to examine if B cell depletors and/or B

cell modulators can be effective agents for treating patients with APS.

O'Neill and Scully (2013) noted that biologic therapy has a potential to benefit patients with

orofacial manifestations of Sjogren syndrome (SS). The most appropriate use of biologics would

appear to be in patients with severe or multi-system features of SS, but their use early in the

pathogenesis has the potential to prevent disease progression. Tumor necrosis factor-alpha

blockade has not proven effective in SS. B-cell depletion using rituximab has been of benefit,

mainly in relation to extra-glandular features, and to some extent in relation to hypo-salivation

where there is still residual salivary function. Rituximab is also effective in the treatment of SS-

associated (extra-salivary) lymphomas, although the therapeutic response in salivary lymphoma

is poorer. Rituximab is given as a single or periodic intravenous infusion. Potential adverse

effects exist, notably infusion reactions and infection, and so a full risk/benefit analysis is

indicated for prospective patients. The authors concluded that further studies of rituximab in SS

are ongoing, and newer agents under trial include belimumab.

Jin and Ding (2013) summarized up-to-date pharmacological and clinical data of belimumab in

the treatment of rheumatoid arthritis (RA). A literature search was performed on PubMed using

keywords, including belimumab, LymphoStat-B, benlysta, BLyS inhibitor, rheumatoid arthritis and

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autoimmune disease. References of relevant studies were searched by hand. Abstracts of

international conferences up to October 2012 were also included. Belimumab was well-tolerated

in the treatment of RA over 24 weeks. It significantly increased American College of

Rheumatology (ACR)20 responses at week 24, especially in patients with high disease activity,

positive rheumatoid factor, no anti-tumor necrosis factor (TNF) treatment experience and those

who had failed methotrexate therapy. However, belimumab failed to demonstrate significantly

improved ACR50 and ACR70 responses in the single phase II clinical trial of RA. The authors

concluded that these results suggested that the clinical effectiveness of belimumab for RA needs

to be further investigated in future clinical trials. Careful patient selection may be necessary for

belimumab to achieve optimal clinical outcomes in RA.

In a single-arm, phase II clinical trial, Bishton et al (2013) evaluated the safety and activity of

belimumab in 12 patients with Waldenstrom macroglobulinemia (WM). A total of 10 patients had

stable disease with therapy, although no objective responses were seen. Correlative studies

showed patients to have low or undetectable baseline serum levels of B-lymphocyte stimulator,

with the administration of belimumab having no effect on B-cell numbers. The authors concluded

that belimumab cannot be recommended as a single-agent therapy for the treatment of

symptomatic WM, although further evaluation in combination with other agents would be

justified.

Furuta and Jayne (2014) noted that the current standard therapy for anti-neutrophil cytoplasm

antibody-associated vasculitis (AAV), high-dose glucocorticoid and cyclophosphamide followed

by azathioprine, has improved the disease prognosis. However, there are still unmet needs. For

example, reducing relapse risk and glucocorticoid toxicity; newer therapies are needed. These

researchers stated that potential newer drugs are emerging following a better understanding of

disease mechanisms and the availability of targeted therapies to B cells, T cells, pro-

inflammatory cytokines and complement. Rituximab has proven efficacy in remission induction

therapy for AAV, and 2 trials with rituximab as remission maintenance therapy are ongoing.

Clinical trials evaluating mycophenolate mofetil as remission induction therapy, gusperimus,

belimumab and complement factor C5a inhibition are also ongoing, and many other potential

candidates are being investigated both clinically and experimentally. The authors concluded that

B-cell therapy is now an established treatment in AAV and several other therapies are under

evaluation. However, the unmet need in vasculitis therapy remains large and newer therapies

either alone or in combination will need to both improve efficacy and permit reductions in

glucocorticoid and immunosuppressive exposure.

Schwartz et al (2014) stated that renal involvement is a major cause of morbidity and mortality in

SLE. These researchers provided an update on recent discoveries in the pathogenesis,

diagnosis, and treatment of lupus nephritis. Localized long-lived plasma cells have been

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identified as playing an important role in lupus nephritis. In addition, the roles of aberrant

expression of microRNAs and pro-inflammatory cytokines have been explored. Early diagnosis

is important for effective treatment and multiple biomarkers have been identified; however, none

has been yet validated for clinical use. Biomarker panels may turn out to be more accurate than

each individual component. Biologic agents for the treatment of lupus nephritis are being

studied, including belimumab which was recently approved for non-renal SLE. Rituximab has

not proven itself in large, placebo-controlled trials, although it is still being used in refractory

cases of lupus nephritis. The authors concluded that lupus nephritis is a potentially devastating

complication of SLE. Immune cells, cytokines, and epigenetic factors have all been recently

implicated in lupus nephritis pathogenesis. These recent discoveries may enable a paradigm

shift in the treatment of this complex disease, allowing the tailoring of treatment to target specific

pathogenic mediators at specific points in time in the progression of disease.

In a review on “The future of uveitis treatment”, Lin and colleagues (2014) listed belimumab as

one of the emerging therapies for the treatment of uveitis. Furthermore, an UpToDate review on

“Uveitis: Treatment” (Rosenbaum, 2014) does not mention belimumab as a therapeutic option.

Selmi and colleagues (2014) stated that as the understanding of the pathogenesis of

autoimmune diseases is growing, new therapies are being developed to target disease-specific

pathways. Since the introduction of etanercept in 1998, several biotechnological agents have

been developed, most of them indicated in the treatment of RA, but also psoriatic arthritis. Most

currently available molecules target TNF-alpha with different strategies (i.e., etanercept,

infliximab, adalimumab, golimumab, and certolizumab pegol), interleukin (IL)-6 (tocilizumab),

CTLA-4 (abatacept), and B cells (rituximab, belimumab) as they are key mediators in the

cascade of inflammation. Further, small molecules have been recently developed to target intra-

cellular signaling, such as janus kinases for tofacitinib, the first FDA-approved small molecule for

RA. Most novel treatments are being developed for arthritis with specific differences between RA

and psoriatic arthritis, as well as for SLE, following the approval of belimumab. Finally, biologic

therapies are effective also in gout, mainly targeting IL-1 to block the inflammasome. These

researchers described the new and upcoming treatment options for RA, psoriatic arthritis, SLE,

and gout to dissect what one should be aware of when discussing these new and promising

molecules.

In a phase II clinical trial, De Vita and colleagues (2015) examined the safety and effectiveness

of long-term treatment of SS with belimumab. Patients with primary SS were included in the

BELISS study, a 1-year open-label trial, if they were positive for anti-SSA or anti-SSB antibodies

and had systemic complications or persistent salivary gland enlargement or early disease or

biomarkers of B-cell activation. They received intravenous belimumab, 10 mg/kg, at weeks 0, 2

and 4 and then every 4 weeks; if response was observed at week 28, or if the clinician and the

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patient agreed to continue the study in the absence of side effects, treatment was continued for 1

year. Safety and effectiveness were analyzed during the 1-year period of treatment. Among the

30 patients recruited, 28 were evaluated at week 28 as already reported; 19 terminated the 52-

week study, 15 of them being responders and 4 non-responders at week 28; 13 of the 15

responders at week 28 also responded at week 52 (86.7 %). The improvement in the EULAR

Sjogren's Syndrome Disease Activity Index and EULAR Sjogren's Syndrome Patient Reported

Index scores observed at week 28 showed a trend to further improvement at week 52, and the

amelioration of peculiar EULAR Sjogren's Syndrome Disease Activity Index domains (glandular,

lymphadenopathy, articular) appeared of particular relevance. The decrease in biomarkers of B-

cell activation observed at week 28 persisted unchanged until week 52, with RF decreasing

further. Salivary flow, Schirmer's test and the focus score of salivary biopsy did not change.

Safety of treatment was good. The authors concluded that long-term treatment with belimumab

may be beneficial in SS; randomized, double-blind, controlled studies in larger populations are

encouraged.

In April 2019, Benlysta, for intravenous use, was FDA-approved for use in pediatric patients

aged 5 years and older with active, autoantibody positive, systemic lupus erythematosus (SLE)

who are receiving standard therapy. (GSK, 2019).

Sjogren's Syndrome

Mariette et al (2015) evaluated the safety and effectiveness of belimumab in patients with

primary Sjogren's syndrome (pSS). Patients were included in this bi-centric prospective 1-year

open-label trial if they fulfilled American European Consensus group criteria, were anti-Sjogren's

syndrome A-positive and had current systemic complications or salivary gland enlargement, or

early disease (less than 5 years), or biomarkers of B cell activation. They received belimumab,

10 mg/kg, at weeks 0, 2 and 4 and then every 4 weeks to week 24. The primary end-point,

assessed at week 28, was improvement in 2 of 5 items: reduction in greater than or equal to 30

% in dryness score on a visual analog scale (VAS), greater than or equal to 30 % in fatigue VAS

score, greater than or equal to 30 % in VAS pain score, greater than or equal to 30 % in systemic

activity VAS assessed by the physician and/or greater than 25 % improvement in any B cell

activation biomarker values. Among 30 patients included, the primary end-point was achieved in

18 (60 %). The mean (SD) European League Against Rheumatism (EULAR) Sjogren's

Syndrome Disease Activity Index decreased from 8.8 (7.4) to 6.3 (6.6) (p = 0.0015) and EULAR)

Sjogren's Syndrome Patient Reported Index from 6.4 (1.1) to 5.6 (2.0) (p = 0.0174). The mean

dryness, fatigue and pain VAS varied from 7.8 (1.8) to 6.2 (2.9) (p = 0.0021), 6.9 (1.8) to 6.0 (2.2)

(p = 0.0606) and 4.6 (2.6) to 4.7 (2.4) (p = 0.89), respectively. Salivary flow and Schirmer's test

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did not change. The authors concluded that these encouraging results justified future

randomized controlled trials of belimumab in a selected target population of pSS patients most

likely to benefit from treatment.

In a systematic review and meta-analysis, Letaief and colleagues (2018) examined the clinical

safety and effectiveness of B-cell targeted therapies for pSS. These investigators performed a

systematic literature review using databases including Medline, Embase and Cochrane. Only

articles reporting controlled or prospective studies of biological disease-modifying anti-rheumatic

drugs (b-DMARDs) modulating B cells in treatment of pSS were selected. The highest-quality

studies were selected for meta-analysis. The primary outcome of interest was clinical efficacy at

week 24 on fatigue, dryness, Schirmer test, salivary flow rate and the full EULAR Sjogren's

syndrome disease activity index (ESSDAI) score including biological domain. For the efficacy

criteria used, the difference between rituximab and placebo groups was expressed as mean

difference (MD). A total of 18 articles (13 of rituximab, 3 of belimumab, 1 of epratuzumab and 1

of baminercept) were identified for detailed evaluation; 4 randomized controlled trials (RCTs) of

rituximab treatment versus placebo involving 300 patients were included for quantitative

analysis. No significant differences were observed between groups in the meta-analysis of mean

improvements between baseline and week 24 in fatigue VAS [MD -3,24 95 % CI: -30,21 to

23.72], oral dryness VAS [MD -8.41 95 % CI: -35.06 to 18.24], salivary flow rate [MD 0.04 95 %

CI: -0.03 to 0.11] and Schirmer test [MD 0.35 95 % CI: -2.13 to 2.82)]. Rituximab was relatively

safe compared to placebo. The authors concluded that the findings of this review showed that

rituximab is not effective in pSS with the designs and outcomes proposed in the trials; RCTs are

needed to prove the effectiveness of belimumab and epratuzumab in this indication. The RCT

evaluating baminercept failed to achieve its primary end-point.

Cutaneous Lupus

Vashisht and colleagues (2017) presented their experience of using belimumab for the

management of cutaneous lupus at their center. These researchers studied 5 patients with

significant SLE skin manifestations. All patients met 1997 ACR SLE criteria and had failed

multiple medications to control their skin disease; PGA, SLEDAI, and Cutaneous LE disease

Area and Severity Index (CLASI) were recorded before and 16 weeks after belimumab

treatment. Belimumab was added to concomitant standard therapy. All 5 patients demonstrated

marked clinical improvement following belimumab treatment. The average time to clinical

improvement after treatment initiation was 8 to 12 weeks; SLEDAI scores (median, range)

improved in all the patients ((2, 2 to 6) to (0, 0 to 4); p = 0.025); PGA scores (median, range)

were better in all patients ((3, 2 to 3) to (1, 0 to 1); p = 0.039); CLASI activity scores (median,

range) improved dramatically in all patients ((17, 9 to 31) to (3, 2 to 14); p = 0.043). There was

no worsening of the CLASI damage scores. The mean daily prednisone dose decreased

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significantly from 31 mg (± 18.8) at baseline to 3 mg (± 2.7) (p = 0.042). The authors concluded

that in this case series, the addition of belimumab to standard therapy improved the signs and

symptoms of refractory cutaneous lupus. This was one of the first reports highlighting the

potential utility of this medication for the treatment of severe skin involvement in SLE refractory

to conventional therapies. Moreover, they stated that additional studies are needed to evaluate

the use of belimumab in the treatment of cutaneous lupus.

Retinal Vasculitis

De Scheerder and colleagues (2016) reported the case of a 26-year old African female who was

treated successfully with belimumab in a case of severe membranous lupus nephritis and retinal

vasculitis, resistant to 1st line therapy. She presented initially with chronic dacryoadenitis and

screening showed nephrotic-range proteinuria. Biopsy of the kidney confirmed the diagnosis of

membranous lupus nephritis. Clinical features (joint pain, dacryoadenitis, retinal vasculitis and

lupus nephritis) in combination with serology (positive anti-double-stranded DNA (ds-DNA)

antibodies, hypocomplementemia) confirmed the diagnosis of SLE. Treatment was immediately

initiated with glucocorticosteroids (GCS), mycophenolate mofetil (MMF) and hydroxychloroquine

sulphate (Plaquenil). Tacrolimus was associated but no effect was observed with the proteinuria

remaining in the nephrotic range and secondary effects of the glucocorticoids becoming a real

concern. The patient was started on add-on belimumab with quasi-immediate effect on the

proteinuria, making it possible to decrease the dosage of the other immunosuppressants and

gradually stop them, even the GCS. The patient is currently in complete remission after 3 years

of treatment with belimumab. The authors were able to stop immunosuppressive treatment but

kept the patient on anti-malarial treatment as the most recent guidelines in treatment of SLE

recommend. This was a single-case study; its findings need to be validated by well-designed

studies.

Myasthenia Gravis

Diaz-Manera et al (2012) stated that new treatments for immune mediated diseases have

increased notably in the last 10 years. Monoclonal antibodies directed against different

components of the immune system have appeared, along with new drugs from the hematology

field. In the case of myasthenia gravis (MG), many of these new treatments have been used in

experimental animal models and also in patients. These investigators reviewed the progress in

the field of MG treatment achieved in the last 5 years. Firstly, the current treatment protocol was

introduced. Secondly, new data from recent randomized trials and case series of patients

treated with methotrexate, cyclophosphamide, rituximab or improved systems of apheresis was

reported. Finally, all future treatments that are currently under evaluation in pre-clinical animal

models of experimental autoimmune MG were discussed. Evidence supporting the use of

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methotrexate and rituximab in MG has been published recently, in addition to conflicting

randomized trials that were not successful, evaluating the use of tacrolimus as a steroid sparing

agent. New promising therapies (e.g., belimumab and eculizumab) are currently under

evaluation in clinical trials.

In a phase-II, multi-center, placebo-controlled, double-blind study, Hewett and colleagues (2018)

examined the safety and efficacy of belimumab in patients with generalized MG who remained

symptomatic despite standard of care (SoC) therapy. Eligible participants with MG were

randomized 1:1 to receive IV belimumab 10 mg/kg or placebo. Participants received SoC

therapies throughout the 24-week treatment phase and 12-week follow-up period. The primary

efficacy end-point was mean change from baseline in the Quantitative Myasthenia Gravis (QMG)

scale at week 24; safety assessments included the frequency and severity of adverse events

(AEs) and serious AEs. A total of 40 subjects were randomized (placebo n = 22; belimumab n =

18). The mean change in QMG score from baseline at week 24 was not significantly different for

belimumab versus placebo (p = 0.256). There were no statistically significant differences

between treatment groups for secondary end-points, including the MG Composite and MG-

Activity of Daily Living scores. Acetylcholine receptor antibody levels decreased over time in

both treatment groups. No unexpected AEs were identified and occurrence was similar in the

belimumab (78 %) and placebo (91 %) groups; 1 subject receiving placebo died (severe sepsis)

during the treatment phase. The authors concluded that the primary end-point was not met for

belimumab in participants with generalized MG receiving SoC. There was no significant

difference in mean change in the QMG score at week 24 for belimumab versus placebo. The

safety profile of belimumab was consistent with previous SLE studies. This study provided Class

I evidence that for participants with generalized MG, belimumab did not significantly improve

QMG score compared with placebo.

Antibody-Mediated Rejection in Lung Transplantation

Hulbert and colleagues (2018) stated that there is increasing recognition of the importance of

antibody-mediated rejection (AMR) after lung transplantation. The development of donor-specific

antibodies, a key feature of AMR, occurs in approximately 30 % of lung transplant recipients and

is associated with poor post-transplant outcomes. These investigators high-lighted recently

developed AMR diagnostic criteria in lung transplantation, potential mechanisms that mediate

the development of AMR, and discusses current and emerging treatment strategies for this

significant, graft-limiting complication. A major advance is the development of consensus

guidelines to precisely define AMR among lung transplant. Regimens for the treatment of AMR

continue to evolve with varying success reported with regards to antibody clearance and

improving clinical outcomes. A multi-modality treatment approach was common, typically

involving a combination of intravenous immune globulin (IVIG), plasmapheresis (PP), rituximab,

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and bortezomib or carfilzomib. The authors concluded that recent studies suggested several

new agents including tocilizumab, belimumab, daratumumab, plerixafor, and C1 esterase

inhibitor as potentially novel and effective therapies to employ in AMR treatment. These

investigators noted that despite advancements in the diagnosis of AMR through well-defined

consensus guidelines, there is limited evidence to guide treatment. Current data suggests that

conventional approaches are of sub-optimal efficacy, but emerging therapeutic agents with

diverse biological mechanisms offer promise for improved AMR treatment.

Antibody-Mediated Rejection in Kidney Transplantation

Banham and colleagues (2018) stated that B cells produce allo-antibodies and activate allo-

reactive T cells, negatively affecting kidney transplant survival. By contrast, regulatory B cells

are associated with transplant tolerance. Immunotherapies are needed that inhibit B-cell effector

function, including antibody secretion, while sparing regulators and minimizing infection risk. B

lymphocyte stimulator (BLyS) is a cytokine that promotes B-cell activation and has not previously

been targeted in kidney transplant recipients. These researchers examined the safety and

activity of an anti-BLyS antibody, belimumab, in addition to standard-of-care immunosuppression

in adult kidney transplant recipients. They used an experimental medicine study design with

multiple secondary and exploratory end-points to gain further insight into the effect of belimumab

on the generation of de-novo IgG and on the regulatory B-cell compartment. In a randomized,

double-blind, placebo-controlled, phase-II clinical trial, these researchers employed belimumab,

in addition to standard-of-care immunosuppression (basiliximab, mycophenolate mofetil,

tacrolimus, and prednisolone) at 2 centers. Subjects were eligible if they were aged 18 to 75

years and receiving a kidney transplant and were planned to receive standard-of-care

immunosuppression. They were randomly assigned (1:1) to receive either intravenous

belimumab 10 mg/kg body weight or placebo, given at day 0, 14, and 28, and then every 4

weeks for a total of 7 infusions. The co-primary end-points were safety and change in the

concentration of naive B cells from baseline to week 24, both of which were analyzed in all

patients who received a transplant and at least 1 dose of drug or placebo (the modified intention-

to-treat [mITT] population). Between September 13, 2013, and February 8, 2015, of 303 patients

assessed for eligibility, 28 kidney transplant recipients were randomly assigned to receive

belimumab (n = 14) or placebo (n = 14); 25 patients (12 [86 %] patients assigned to the

belimumab group and 13 [93 %] patients assigned to the placebo group) received a transplant

and were included in the mITT population. These investigators observed similar proportions of

adverse events (AEs) in the belimumab and placebo groups, including serious infections (1 [8 %]

of 12 in the belimumab group and 5 [38 %] of 13 in the placebo group during the 6-month on-

treatment phase; and none in the belimumab group and 2 [15 %] in the placebo group during the

6-month follow-up). In the on-treatment phase, 1 patient in the placebo group died because of

fatal myocardial infarction (MI) and acute cardiac failure. The co-primary end-point of a reduction

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in naive B cells from baseline to week 24 was not met. Treatment with belimumab did not

significantly reduce the number of naive B cells from baseline to week 24 (adjusted MD between

the belimumab and placebo treatment groups -34.4 cells/μL, 95 % CI: -109.5 to 40.7). The

authors concluded that belimumab might be a useful adjunct to standard-of-care

immunosuppression in renal transplantation, with no major increased risk of infection and

potential beneficial effects on humoral allo-immunity. These preliminary findings need to be

validated by well-designed studies.

Discoid Lupus

Chong et al (2014) stated that B-cell activating factor of the TNF family (BAFF) promotes the

maturation and survival of B cells. Because BAFF levels are elevated in systemic lupus

erythematosus (SLE) patients, BAFF has been the target of emerging therapies for SLE, such as

belimumab. Levels of BAFF and its receptors in discoid lupus erythematosus (DLE) patients are

unknown. These researchers compared skin and blood mRNA and protein levels of BAFF and

its receptors BAFF-R, TACI, and BCMA in DLE subjects with (DLE+/SLE+ (n = 28)) and without

SLE (DLE+/SLE- (n = 35)), psoriasis subjects (n = 11), and normal subjects (n = 42). They used

quantitative real-time PCR to measure blood and skin BAFF, BAFF-R, TACI, and BCMA mRNA,

sandwich ELISAs to measure sera BAFF, and immunohistochemistry to evaluate BAFF and

BAFF-R skin protein expression. BAFF mRNA and protein levels were highest in DLE+/SLE+

blood, followed by DLE+/SLE-, psoriasis, and normal blood. BAFF protein also correlated with

anti-nuclear antibodies, and auto-antibodies against double-stranded DNA, single-stranded DNA,

and ribonucleoprotein, and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)

scores in DLE patients. While showing no difference between DLE+/SLE+ and DLE+/SLE- skin,

BAFF and its receptors mRNA were up-regulated in DLE skin versus normal and psoriasis skin;

DLE skin had higher percentages of BAFF-R⁺ inflammatory cells, likely T cells and

macrophages, than psoriasis and normal skin. The authors concluded that BAFF may be a

serologic marker of systemic disease in DLE patients; BAFF and its receptors were elevated in

DLE skin, suggesting that targeted therapies against these proteins could treat refractory DLE

patients.

Ugarte and colleagues (2018) evaluated the clinical response to combined therapy with

hydroxychloroquine and mepacrine in patients with SLE and refractory joint and/or skin disease.

Mepacrine was added to 46 SLE patients unresponsive to treatment with the following drug

combinations: hydroxychloroquine + prednisone + immunosuppressive drugs (n = 24),

hydroxychloroquine + prednisone (n = 16), hydroxychloroquine + prednisone + retinoids (n = 2),

hydroxychloroquine alone (n = 1), hydroxychloroquine + 1 immunosuppressive drug (n = 1),

hydroxychloroquine + prednisone + 1 immunosuppressive drug + belimumab (n = 1) or

hydroxychloroquine + prednisone + belimumab (n = 1). The outcome variable was the clinical

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response, either complete or partial, based on clinical judgement. The Cutaneous Lupus

Erythematosus Disease Area and Severity Index (CLASI) and the SLEDAI score were

additionally used. A total of 91 % patients showed complete/partial response, with similar rates

among those with joint or skin disease. In patients with cutaneous activity, a statistically

significant decrease in the CLASI was seen. There also was a statistically significant decrease

in the SLEDAI. The mean daily dose of prednisone decreased from 5.8 to 3.4 mg/day (p = 0.001).

Prednisone could be discontinued in 20 % of patients. No serious adverse events (AEs)

were seen. Smoking was the only predictor of complete response. The authors concluded that

in the setting of refractory skin and/or joint disease, the addition of mepacrine to previous therapy

including hydroxychloroquine was safe and effective in reducing disease activity and decreasing

prednisone doses. The fact that smokers responded better opened the door to further studying

the combination of mepacrine-hydroxychloroquine as a 1st-line therapy in such patients.

(Discoid lupus was one of the keywords listed in the present study).

An UpToDate review on “Initial management of discoid lupus and subacute cutaneous lupus”

(Clarke, 2018a) does not mention belimumab as a therapeutic option. Furthermore, an

UpToDate review on “Management of refractory discoid lupus and subacute cutaneous lupus”

(Clarke, 2018b) states that “Multiple other medications have been used for subacute cutaneous

lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE). With the exception of

clofazimine, data supporting these therapies [including belimumab] are limited … The effect of

belimumab in cutaneous LE has not been well studied; however, in a series of 5 patients with

SLE and acute cutaneous lupus erythematosus, SCLE, and/or DLE, all had significant

improvement in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)

disease activity scores with the addition of intravenous belimumab to standard treatment. The

average time to clinical improvement was 4 months, and marked improvement occurred as early

as 8 weeks. Serious potential adverse effects of belimumab include hypersensitivity reactions,

infections, and depression”.

Early Diffuse Cutaneous Systemic Sclerosis

In a randomized, double-blind, placebo-controlled, pilot trial, Gordon and colleagues (2018)

evaluated the safety and efficacy of treatment with belimumab in patients with early diffuse

cutaneous systemic sclerosis (dcSSc) treated with background mycophenolate mofetil (MMF).

In this 52-week, investigator-initiated, single-center, double-blind, placebo-controlled, pilot study,

a total of 20 patients with dcSSc recently started on MMF were randomized 1:1 to additionally

receive belimumab at 10 mg/kg intravenously or placebo. These investigators assessed safety,

efficacy, and differential gene expression. In the belimumab group, the median modified Rodnan

skin thickness score (MRSS) decreased from 27 (interquartile range [IQR] 26.5 to 31) to 18 (IQR

11 to 23) (p = 0.039). In the placebo group, the median MRSS decreased from 28 (IQR 22 to 28)

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to 21 (IQR 14 to 25) (p = 0.023). The median change in MRSS was -10 (IQR -13 to -9) in the

belimumab group and -3.0 (IQR -15 to -1) in the placebo group (p = 0.411). There were no

significant differences between the groups in the number of AEs. A significant decrease in

expression of B cell signaling and pro-fibrotic genes and pathways was observed in patients with

improved MRSS in the belimumab group but not in the placebo group. The authors concluded

that patients in both treatment groups experienced significant improvements in MRSS. The

median difference was greater in the belimumab group but did not achieve statistical significance

in this small pilot study; AEs were similar between the groups. Changes in gene expression

were consistent with mechanism of action and showed that clinical response to treatment with

belimumab was associated with a significant decrease in pro-fibrotic genes and pathways.

These researchers stated that additional studies are needed to determine the role of belimumab

in the treatment of dcSSc.

Lupus Nephritis

Margiotta and colleagues (2018) stated that the treatment of lupus nephritis (LN) is an unmet

need in the management of patients with SLE. These investigators reported 2 cases of women

affected by LN (Society of Nephrology/Renal Pathology Society (ISN/RPS) Class IV) with

serological active disease, high disease activity and marked fatigue. In both cases, MMF, as

induction therapy, was poorly tolerated because of gastro-intestinal (GI) toxicity. Belimumab,

together with low-doses of MMF, was effective as induction treatment leading to early

achievement of complete renal response in these 2 selected cases of LN. The authors also

presented a literature review concerning the safety and efficacy of belimumab in LN. They

stated that further studies are needed to evaluate the use of belimumab to manage the renal

involvement in patients with SLE.

Systemic Sclerosis

Katsiar and colleagues (2018) noted that systemic sclerosis (SSc) is a chronic systemic disease

characterized by microvasculopathy, immune activation, and extensive collagen deposition.

Microvasculopathy and immune activation occur very early in the disease process. Evidence

from animal models and in-vitro studies indicated that T-cells and B-cells activate fibroblasts to

produce collagen. Traditional immuno-suppressants, cyclophosphamide(CyP),

methotrexate(MTX), and more recently mycophenolate mofetil (MMF), may prove more effective

if used very early in the disease course. These drugs showed some benefit in skin (MTX, CyP,

MMF) and lung function (CyP, MMF). Biologicals, such as intravenous immunoglobulin (IVIG),

belimumab (Beli), tocilizumab(TCZ), abatacept (Aba), rituximab (RTX) and fresolimumab (Fresu)

appeared promising as they exhibited some benefit in skin (IVIG, Beli, TCZ, Aba, RTX, Fresu),

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hand function (IVIG), and joints (IVIG, TCZ, Aba). Autologous stem cell transplantation showed

the best therapeutic efficacy on skin and internal organs, and looks very promising, as

modification of transplantation immunosuppression is decreasing the early high mortality.

CPT Codes / HCPCS Codes / ICD-10 Codes

Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+":

Code Code Description

Other CPT codes related to the CPB:

86038 Antinuclear antibodies (ANA)

96365 Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or

drug); initial, up to 1 hour

96372 Therapeutic, prophylactic, or diagnostic injection (specify substance or drug);

subcutaneous or intramuscular

HCPCS codes covered if selection criteria are met:

J0490 Injection, Belimumab, 10 mg

Other HCPCS codes related to the CPB:

J0390 Injection, chloroquine hydrochloride

J0456 Injection, azithromycin, 500 mg

J1020 Injection, methylprednisolone acetate, 20 mg

J1030 Injection, methylprednisolone acetate, 40 mg

J1094 Injection, dexamethasone acetate, 1 mg

J1100 Injection, dexamethasone sodium phosphaste, 1 mg

J1700 Injection, hydrocortisone acetate, up to 25 mg

J1710 Injection, hydrocortisone sodium phosphate, up to 50 mg

J1720 Injection, hydrocortisone sodium succinate, up to 100 mg

J7312 Injection, dexamethasone, intravitreal implant, 0.1 mg

J7500 Azathioprine, oral, 50 mg

J7501 Azathioprine, parenteral, 100 mg

J7502 Cyclosporine, oral, 100 mg

J7509 Methylprednisolone oral, per 4 mg

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J7512 Prednisone, immediate release or delayed release, oral, 1 mg

J7515 Cyclosporine, oral, 25 mg

J7516 Cyclosporine, parenteral, 250 mg

J7517 Mycophenolate mofetil, oral, 250 mg

J7637 Dexamethasone, inhalation solution, compounded product, administered through

dme, concentrated form, per milligram

J7638 Dexamethasone, inhalation solution, compounded product, administered through

dme, unit dose form, per milligram

J8540 Dexamethasone, oral 0.25 mg

J8610 Methotrexate; oral, 0.25 mg

J9070 Cyclophosphamide, 100 mg [not covered when used in combination with Benlysta]

Q0144 Azithromycin dihydrate, oral, capsules/powder, 1 gram

ICD-10 codes covered if selection criteria are met:

M32.0 - M32.9 Systemic lupus erythematosus (SLE)

ICD-10 codes not covered for indications listed in the CPB :

C88.0 Waldenstrom macroglobulinemia

D68.61 Antiphospholipid syndrome

G35 Multiple sclerosis

G70.00 Myasthenia gravis without (acute) exacerbation

H20.00 - H21.9 Disorders of iris and ciliary body

H35.061 - H35.069 Retinal vasculitis

L40.50 - L40.59 Psoriatic arthritis

M05.00 - M06.9 Rheumatoid arthritis

M1A.00x+ - M10.9 Gout

M30.0 Polyarteritis nodosa [antibody-associated vasculitis]

M31.30 - M31.31 Wegener's granulomatosis [antibody-associated vasculitis]

M34.0 - M34.9 Systemic sclerosis

M35.00 - M35.09 Sicca syndrome [Sjögren]

N18.4 - N18.6 Chronic kidney disease, stage 4 (severe), stage 5, ESRD

T86.810 Lung transplant rejection [antibody-mediated rejection]

Z94.0 Kidney transplant status

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Z94.1 Heart transplant status

Z94.2 Lung transplant status

Z94.3 Heart and lungs transplant status

Z94.4 Liver transplant status

Z94.82 Intestine transplant status

Z94.83 Pancreas transplant status

Z94.84 Stem cells transplant status

Z99.2 Dependence on renal dialysis

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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and

constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or

program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any

results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna

or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be

updated and therefore is subject to change.

Copyright © 2001-2019 Aetna Inc.

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AETNA BETTER HEALTH® OF PENNSYLVANIA

Amendment to Aetna Clinical Policy Bulletin Number: 0818

Belimumab (Benlysta)

There are no amendments for Medicaid.

www.aetnabetterhealth.com/pennsylvania revised 11/12/2019

Proprietary

http://www.aetnabetterhealth.com/pennsylvania

Documents

0818 Belimumab (Benlysta) (2) · 2020. 9. 3. · recommended dosage for belimumab is 10 mg/kg IV over 1 hour every 2 weeks for the ﬁrst3 doses then every 4 weeksthereafter. Subcutaneous