Can you help more patients reduce lupus symptoms and steroids?

See how BENLYSTA may help your patients.

Icon: Symptoms

Symptoms

Up to

61%

of patients had reduced lupus symptoms (SRI-4) at Week 521-4

(primary endpoint)

See SRI-4 data

Icon: Steroids

Steroids

Real-world data

86%

of patients reduced or discontinued steroids at Week 264,5

Real-world, observational cohort study, results are descriptive. Reasons for change in steroid dose were not captured and may be unrelated to disease improvement/worsening.

See steroid data

Icon: Organ Domains

Organ domains

Patients had up to

60%

improvement in skin, joints, and kidneys at Week 524*

Post hoc, pooled analysis of 5 SLE studies. Results are descriptive.

See organ domain data

* Improvement in organ domain, as defined by SELENA-SLEDAI, at Week 52 among patients with organ involvement at baseline. Studies were designed to evaluate efficacy in overall disease activity and were not powered to evaluate efficacy in specific organ domains.

SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index; SLE = systemic lupus erythematosus; SRI = SLE Responder Index.

Study design

Study design

SRI-4 response

Organ domain improvement

Early and sustained SRI-4 response

Study design

SRI-4 response

Organ domain improvement

Early and sustained SRI-4 response

BENLYSTA: proven to reduce lupus symptoms

SRI-4 response rate at Week 52 (primary endpoint)1-4*

Bar graph: SRI-4 response rate at Week 52 (primary endpoint)¹¯³*
Bar graph: SRI-4 response rate at Week 52 (primary endpoint)¹¯³*

In patients on placebo + ST, the SRI-4 response rate at Week 52 was 48%, 44%, and 34% for BLISS-SC (n=279), BLISS-52 (n=287), and BLISS-76 (n=275), respectively.

* In BLISS-76, the difference in SRI-4 response rates was not significantly different at Week 76 (secondary endpoint).

BLISS = Belimumab International SLE Study; ST = standard therapy.

Persistent disease activity, including flares, can contribute to organ damage6-8

Find out more

What improvements were seen in skin, joints, and kidneys?4

In a post hoc, pooled analysis involving 5 SLE studies*†

Icon: Skin59%

of patients on BENLYSTA + ST had improvements in skin

(n=1585)
vs 49% of patients on ST alone (n=1039)

Measured skin domains included rash, alopecia, and mucosal ulcers.

Icon: Joints 60%

of patients on BENLYSTA + ST had improvements in joints

(n=1180)
vs 50% of patients on ST alone (n=780)

Measured joint domains included arthritis and myositis.

Icon: Renal 53%

of patients on BENLYSTA + ST had improvements in kidneys

(n=319)
vs 40% of patients on ST alone (n=223)

Measured kidney domains included urinary casts, hematuria, proteinuria, and pyuria.

Results are descriptive; use caution when interpreting data. See individual study design and limitations.

* Improvement in organ domain, as defined by SELENA-SLEDAI, at Week 52 among patients with organ involvement at baseline. Studies were designed to evaluate efficacy in overall disease activity and were not powered to evaluate efficacy in specific organ domains.

† Five randomized, controlled efficacy and safety studies included: BLISS-52, BLISS-76, NE Asia, BLISS-SC, and EMBRACE.

BLISS = Belimumab International SLE Study; EMBRACE = Efficacy and Safety of Belimumab in Adult Subjects of Black Race; NE = Northeast; SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; SRI-S2K = SLE Responder Index response rate with the modified SLEDAI-2K scoring for proteinuria; ST = standard therapy.

Early and sustained response data4,9

Graph: Reduced disease activity (SRI-4) by visit
Graph: Reduced disease activity (SRI-4) by visit

In a post hoc, pooled analysis involving 5 SLE studies.*†‡ Results are descriptive; use caution when interpreting data. See individual study design and limitations.

Set expectations with your patients that while BENLYSTA may show results as early as 8 weeks‡ for approximately 4 out of 10 patients, they should plan to commit to treatment for 6 to 9 months to see the effect of BENLYSTA on their lupus.4

* Five randomized, controlled efficacy and safety studies included: BLISS-52, BLISS-76, NE Asia, BLISS-SC, EMBRACE. The primary endpoint (SRI-S2K at Week 52) was not met in EMBRACE.

† The same patient may not have responded at each visit.

‡ Individual studies were not designed to establish onset of effect, and not all studies showed improvement at Week 8.

Sample Text

In the US open-label long-term extension trial9

Graph: Reduced disease activity (SRI-4) over 7 years
Graph: Reduced disease activity (SRI-4) over 7 years

Used with permission from Furie RA, et al. Arthritis Rheumatol. 2018;70(6):868-877. © 2018 John Wiley and Sons.

79% of patients did not have a severe flare during the 7-year follow-up9
(n/N=212/267)

Results are descriptive. Other efficacy endpoints. Exploratory results should be interpreted with additional care. See study design for data limitations.

African-American patient data

African-American patient data

Hispanic patient data

Fatigue

Flares

Steroids

African-American patient data

Hispanic patient data

Fatigue

Flares

Steroids

Efficacy data in a diverse patient population10

49% of patients in the EMBRACE trial had reduced lupus symptoms (SRI-S2K) at Week 52*
49% of patients in the EMBRACE trial had reduced lupus symptoms (SRI-S2K) at Week 52*

Numerical reduction. The primary endpoint of the EMBRACE trial was not met.

In patients on BENLYSTA + ST (n=298), 49% achieved SRI-S2K at Week 52 vs in patients on placebo + ST (n=149), 42% achieved SRI-S2K at Week 52 (primary endpoint at Week 52; P=0.107).

In previous Phase III, exploratory sub-group analyses of BENLYSTA, response rates were not consistent for African-American patients.

* The SRI-S2K is the modified SLEDAI-2K scoring for proteinuria (primary endpoint at Week 52).

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  • BENLYSTA disease severity results in African-American patientsSUP111

    Graph of BENLYSTA disease severity results in African American patients
    Graph of BENLYSTA disease severity results in African American patients

    Post hoc analysis. A real-world, observational cohort study. Results are descriptive. See study design for data limitations.

    * In the OBSErve US study, 501 patients with SLE were enrolled; 123 (24.6%) were African American. Of that, 69 (56.1%) continued to receive BENLYSTA at Month 24, 26 (21.1%) were lost to follow-up, and 28 (22.8%) discontinued BENLYSTA.

    † Analysis of African-American patients in the OBSErve US study.

    SLE = systemic lupus erythematosus; ST = standard therapy.

  • BENLYSTA disease severity results in Hispanic patientsSUP111

    Graph of BENLYSTA disease severity results in Hispanic patients
    Graph of BENLYSTA disease severity results in Hispanic patients

    Post hoc analysis. A real-world, observational cohort study. Results are descriptive. See study design for data limitations.

    * In the OBSErve US study, 501 patients with SLE were enrolled; 88 (17.6%) were Hispanic. Of that, 43 (48.9%) continued to receive BENLYSTA at Month 24, 23 (26.1%) were lost to follow-up, and 22 (25.0%) discontinued BENLYSTA.

    † Analysis of Hispanic patients in the OBSErve US study.

    SLE = systemic lupus erythematosus; ST = standard therapy.

How does fatigue impact your patients?

67%–90% of patients with lupus report experiencing fatigue12*

From a post hoc, pooled analysis of 4 SLE studies

Mean change in baseline FACIT-Fatigue score by visit4†

Line graph of mean change in baseline FACIT-Fatigue score by visit
Line graph of mean change in baseline FACIT-Fatigue score by visit

Results are descriptive. See individual study design.

* Data from a review article that analyzed over 5000 SLE outpatients from 55 articles, which included a fatigue-specific measure.12

† Pooled data from adult clinical trials of BENLYSTA (BLISS-52, BLISS-76, BLISS-SC, and EMBRACE). The individual EMBRACE and BLISS studies in SLE were not powered to detect significant differences in the FACIT-Fatigue score with BENLYSTA treatment plus standard therapy versus standard therapy alone. BLISS-52, BLISS-SC, and EMBRACE did not have scheduled FACIT-Fatigue assessments at Weeks 20, 32, 40, or 48, while BLISS-76 did not have assessments at Week 36.4

‡ MCID has not been definitively established in SLE.13

BLISS = Belimumab International SLE Study; FACIT = Functional Assessment of Chronic Illness Therapy.

Icon: Patient silhouette

Did you know?

Approximately 1 in 2 patients with lupus experience permanent organ damage within 5 years of diagnosis14,15*†

Icon: Flare

Lupus flares can contribute to organ damage.6-8,15

* Damage in SLE is defined as an irreversible tissue injury occurring after diagnosis of SLE and lasting at least 6 months. SLICC/ACR Damage Index (SDI) is the internationally agreed and validated measure of organ damage.7,16

† Cohort analysis of 298 patients followed for a minimum of 5 years by the SLICC International Research Network, comprising 27 centers from 11 countries. Year 0 represents time of enrollment. Mean age at enrollment was 35.3 years. Fifty percent of patients acquired organ damage at Year 5.15 Retrospective analysis of records from 401 patients (232 patients with ≥10 years of consistent follow-up) attending the University College London Hospital SLE clinic between 1978–2004. Year 0 represents time of diagnosis. Mean age at diagnosis was 31.2 years. Thirty-three percent of patients acquired organ damage at Year 5.14

Protection against severe flares

BENLYSTA reduced the risk of severe flares1-3*†

Reduced risk of severe flare chart
Reduced risk of severe flare chart

* As measured by the SFI, modified to exclude the single criterion of increased SELENA-SLEDAI score to >12.

† The incidence of severe flare over 52 weeks was a secondary endpoint.

‡ Reduction of severe flares was not significant in BLISS-76.

BLISS = Belimumab International SLE Study; CI = confidence interval; HR = hazard ratio; SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index; SFI = SELENA-SLEDAI Flare Index; ST = standard therapy.

Clinical trials

Clinical trials

Real-world data

Early use

Clinical trials

Real-world data

Early use

Icon: Organ Damage

Did you know that chronic use of high-dose steroids can lead to organ damage?1-3,6,14

BENLYSTA: steroid-sparing efficacy results

Across 3 pivotal studies:

Approximately 1 in 5 patients reduced steroid dose by ≥25% to ≤ 7.5 mg/day at week 52

Approximately 1 in 5
patients reduced steroid dose
by ≥25% to ≤7.5 mg/day at Week 521-3*†

  BLISS-SC
P=0.0732		 BLISS-52
P=0.0526		 BLISS-76
P=0.4253
BENLYSTA + ST 18% (n=335) 19% (n=204) 18% (n=120)
Placebo + ST 12% (n=168) 12% (n=192) 13% (n=126)

There were no statistically significant differences between treatment groups in any trial.

* In patients who were receiving >7.5 mg/day at baseline. Overall, 60%, 69%, and 46% of patients were receiving doses >7.5 mg/day at baseline in BLISS-SC, BLISS-52, and BLISS-76, respectively.

† In BLISS-SC, BLISS-52, and BLISS-76, this was a secondary endpoint evaluating steroid dose reduction during Weeks 40–52.1-3

BLISS = Belimumab International SLE Study; ST = standard therapy.

Steroid-sparing efficacy results in a real-world setting4,5*

At Week 26, 86% of patients reduced or discontinued steroids* with a mean reduction in daily dose* by 58% vs baseline
At Week 26, 86% of patients reduced or discontinued steroids* with a mean reduction in daily dose* by 58% vs baseline
Data from US patients prescribed steroids at baseline (n=386) ITT, LOCF†‡
  Baseline 6 Months 12 Months 18 Months 24 Months
% of patients who reduced steroid dose vs baseline - 77%
(297)		 60%
(232)		 55%
(212)		 55%
(211)
% of patients who discontinued steroids vs baseline - 9%
(35)		 29%
(110)		 33%
(126)		 34%
(131)
% of patients whose dose remained the same vs baseline - 12%
(46)		 8%
(30)		 8%
(32)		 8%
(31)
% of patients who increase steroid dose vs baseline - 2%
(8)		 4%
(14)		 4%
(16)		 3%
(13)
Average daily steroid dose, mg (of patients on steroids) 19.9 8.4 6.3 6.5 6.1
Data from US patients prescribed steroids at baseline (n=386) ITT, LOCF†‡
  Baseline 6 Months
% of patients who reduced steroid dose vs baseline - 77%
(297)
% of patients who discontinued steroids vs baseline - 9%
(35)
% of patients whose dose remained the same vs baseline - 12%
(46)
% of patients who increase steroid dose vs baseline - 2%
(8)
Average daily steroid dose, mg (of patients on steroids) 19.9 8.4
  Baseline 12 Months
% of patients who reduced steroid dose vs baseline - 60%
(232)
% of patients who discontinued steroids vs baseline - 29%
(110)
% of patients whose dose remained the same vs baseline - 8%
(30)
% of patients who increase steroid dose vs baseline - 4%
(14)
Average daily steroid dose, mg (of patients on steroids) 19.9 6.3
  Baseline 18 Months
% of patients who reduced steroid dose vs baseline - 55%
(212)
% of patients who discontinued steroids vs baseline - 33%
(126)
% of patients whose dose remained the same vs baseline - 8%
(32)
% of patients who increase steroid dose vs baseline - 4%
(16)
Average daily steroid dose, mg (of patients on steroids) 19.9 6.5
  Baseline 24 Months
% of patients who reduced steroid dose vs baseline - 55%
(211)
% of patients who discontinued steroids vs baseline - 34%
(131)
% of patients whose dose remained the same vs baseline - 8%
(31)
% of patients who increase steroid dose vs baseline - 3%
(13)
Average daily steroid dose, mg (of patients on steroids) 19.9 6.1

A real-world, observational cohort study. Results are descriptive. See study design for data limitations.

* Reasons for change in steroid dose were not captured and may be unrelated to disease improvement/worsening.

† Intent-to-treat (ITT) consisting of all patients enrolled at baseline followed through 24 months using the last observation carried forward (LOCF) method to account for patients who were lost to follow-up and/or discontinued BENLYSTA during follow-up.

‡ Total percentage may not add up to 100% due to rounding.

Why wait to add BENLYSTA?

Median time to OCS discontinuation in a real-world setting17*

Graph: Median time to OCS discontinuation in a real-world setting
Graph: Median time to OCS discontinuation in a real-world setting

Results are descriptive. Data from a real-world, retrospective, longitudinal cohort study based on administrative claims. Data from the Komodo Health Database of de-identified patient-level claims.17

Average daily OCS dose in patients with no immunosuppressant use and after use of 1 immunosuppressant, stratified by baseline disease severity17
  No immunosuppressant 1 immunosuppressant
Average daily OCS dose [mg], mean Moderate SLE Severe SLE Moderate SLE Severe SLE
Index‡ 3.1 6.7 3.9 9.5
6 months 3.4 6.2 4.4 8.4
12 months 2.9 5.9 4.0 7.3
24 months 2.6 4.4 3.5 5.8
Average daily OCS dose in patients with no immunosuppressant use and after use of 1 immunosuppressant, stratified by baseline disease severity17
  No immunosuppressant
Average daily OCS dose [mg], mean Moderate SLE Severe SLE
Index‡ 3.1 6.7
6 months 3.4 6.2
12 months 2.9 5.9
24 months 2.6 4.4
  1 immunosuppressant
Index‡ 3.9 9.5
6 months 4.4 8.4
12 months 4.0 7.3
24 months 3.5 5.8

Results are descriptive. Data from a real-world, retrospective, longitudinal cohort study based on administrative claims. Data from the Komodo Health Database of de-identified patient-level claims.17

The sample size of patients with mild baseline SLE among patients initiating BENLYSTA after ISS use was too small to be meaningful (n=8), thus was not evaluated.

See study design for data limitations.

* Discontinuation of OCS therapy was identified as a patient with ≥1 prescription for OCS who did not fill another prescription for OCS for 120 days after the previous prescription ran out according to the fill date and days supplied on the previous prescription. The date of discontinuation was assumed to be the date that the previous prescription ran out based on the fill date and days supplied.17

† Regardless of baseline disease severity.17

‡ Average daily dose of OCS at index is calculated as the average daily dose of OCS over the 3-month period prior to the index date.17

CI = confidence interval; ISS = immunosuppressant; OCS = oral corticosteroid; SLE = systemic lupus erythematosus.

Steroid-sparing efficacy results in African-American patients11*

Graph: Mean steroid dose over 24 months in African American patients still receiving BENLYSTA at 24 months (n=69)

Mean steroid dose over 24 months in patients still receiving BENLYSTA at 24 months (n=69)†

Graph: Mean steroid dose over 24 months in African American patients still receiving BENLYSTA at 24 months (n=69)

Post hoc analysis. A real-world, observational cohort study. Results are descriptive. See study design for data limitations.

 

Reasons for change in steroid dose were not captured and may be unrelated to disease improvement/worsening. Care should be taken when interpreting the present findings due to patient attrition, small sample size, and the lack of a control group.

* Analysis of African-American patients in the OBSErve US study.

† In the OBSErve US study, 501 patients with SLE were enrolled; 123 (24.6%) were African-American. Of that, 69 (56.1%) continued to receive BENLYSTA at Month 24, 26 (21.1%) were lost to follow-up, and 28 (22.8%) discontinued BENLYSTA.

SD = standard deviation.

Steroid-sparing efficacy results in Hispanic patients11*

Graph: Mean steroid dose over 24 months in Hispanic patients still receiving BENLYSTA at 24 months (n=43)

Mean steroid dose over 24 months in patients still receiving BENLYSTA over 24 months (n=43)†

Graph: Mean steroid dose over 24 months in Hispanic patients still receiving BENLYSTA at 24 months (n=43)

Post hoc analysis. A real-world, observational cohort study. Results are descriptive. See study design for data limitations.

Reasons for change in steroid dose were not captured and may be unrelated to disease improvement/worsening. Care should be taken when interpreting the present findings due to patient attrition, small sample size, and the lack of a control group.

* Analysis of Hispanic patients in the OBSErve US study.

† In the OBSErve US study, 501 patients with SLE were enrolled; 88 (17.6%) were Hispanic. Of that, 43 (48.9%) continued to receive BENLYSTA at Month 24, 23 (26.1%) were lost to follow-up, and 22 (25.0%) discontinued BENLYSTA.

SD = standard deviation.

The most comprehensive clinical trial program in lupus to date

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  • Study design for adult lupus trials

    Study design

    Phase III trials in adults were randomized, double-blind, and placebo-controlled, and assessed intravenous and subcutaneous methods of administration.

    BLISS-SC (52-week duration)3
    Treatment arms
    • BENLYSTA SC 200 mg + ST (n=556)
    • Placebo + ST (n=280)
    Regions
    177 centers throughout North America, South America, Europe, and Asia
    BLISS-52 (52-week duration)1
    Treatment arms
    • BENLYSTA IV 1 mg/kg* + ST (n=288)
    • BENLYSTA IV 10 mg/kg + ST (n=290)
    • Placebo + ST (n=287)
    Regions
    92 centers throughout South America, Asia, Eastern Europe, and Australia
    BLISS-76 (76-week duration, primary endpoint measured at Week 52)2
    Treatment arms
    • BENLYSTA IV 1 mg/kg* + ST (n=271)
    • BENLYSTA IV 10 mg/kg + ST (n=273)
    • Placebo + ST (n=275)
    Regions
    136 centers throughout North America and Europe
    EMBRACE (52-week duration)10
    Treatment arms
    • BENLYSTA IV 10 mg/kg + ST (n=299)
    • Placebo + ST (n=149)
    Regions
    96 centers throughout North America, South America, South Africa, and Europe
    NE Asia (52-week duration)18
    Treatment arms
    • BENLYSTA IV 10 mg/kg + ST (n=451)
    • Placebo + ST (n=226)
    Regions
    49 centers throughout China, Japan, and South Korea
    BLISS-SC (52-week duration)3
    Treatment arms Regions
    • BENLYSTA SC 200 mg + ST (n=556)
    • Placebo + ST (n=280)
    		 177 centers throughout North America, South America, Europe, and Asia
    BLISS-52 (52-week duration)1
    Treatment arms Regions
    • BENLYSTA IV 1 mg/kg* + ST (n=288)
    • BENLYSTA IV 10 mg/kg + ST (n=290)
    • Placebo + ST (n=287)
    		 92 centers throughout South America, Asia, Eastern Europe, and Australia
    BLISS-76 (76-week duration, primary endpoint measured at Week 52)2
    Treatment arms Regions
    • BENLYSTA IV 1 mg/kg* + ST (n=271)
    • BENLYSTA IV 10 mg/kg + ST (n=273)
    • Placebo + ST (n=275)
    		 136 centers throughout North America and Europe
    EMBRACE (52-week duration)10
    Treatment arms Regions
    • BENLYSTA IV 10 mg/kg + ST (n=299)
    • Placebo + ST (n=149)
    		 96 centers throughout North America, South America, South Africa, and Europe
    NE Asia (52-week duration)18
    Treatment arms Regions
    • BENLYSTA IV 10 mg/kg + ST (n=451)
    • Placebo + ST (n=226)
    		 49 centers throughout China, Japan, and South Korea

     

    Key inclusion criteria1-4,10

    • Patients were ≥18 years of age
    • Patients were self-identified as Black race (EMBRACE)
    • Patients were diagnosed with SLE according to the ACR criteria
    • Patients met ≥1 of the following:
      • ANA titer ≥1:80
      • Anti-dsDNA autoantibodies ≥30 IU/mL
    • Patients were receiving stable doses of any of the following, alone or in combination, for ≥30 days:
      • Antimalarial
      • Immunosuppressant
      • Corticosteroid
      • NSAID
    • Patients had active disease†
      • SELENA-SLEDAI score ≥8 (BLISS-SC, EMBRACE, NEA)
      • SELENA-SLEDAI score ≥6 (BLISS-52 and BLISS-76)

     

    Key exclusion criteria1-4

    • Severe active lupus nephritis
      • Proteinuria >6 g over 24 hours or equivalent with spot urine protein:creatinine ratio
      • Serum creatinine >2.5 mg/dL
      • Required hemodialysis within 90 days of study entry
      • Required high-dose prednisone (>100 mg/day) within 90 days of study entry
    • Severe active CNS lupus
      • Patient required therapeutic intervention for any of the following within 60 days of study entry:
        • Seizures, psychosis, organic brain syndrome, CVA, cerebritis, or CNS vasculitis
    • Use of other biologics or IV cyclophosphamide was not permitted

    * The 1-mg/kg dose is not recommended.

    † Can include clinical (eg, arthritis, rash, and hair loss) and serological (eg, decreased complement and anti-dsDNA) SLE manifestations.

    ACR = American College of Rheumatology; ANA = antinuclear antibody; anti-dsDNA = anti-double–stranded DNA; BLISS = Belimumab International SLE Study; CNS = central nervous system; CVA = cerebrovascular accident; EMBRACE = Efficacy and Safety of Belimumab in Adult Subjects of Black Race; IV = intravenous; NEA = Northeast Asia; NSAID = nonsteroidal anti-inflammatory drug; SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index; SC = subcutaneous; SLE = systemic lupus erythematosus; ST = standard therapy.

  • Pivotal study endpoints

    Study endpoints1-3
    Endpoints were analyzed in a hierarchical manner – if at any point statistical significance was not met, subsequent endpoints could not be considered significant

    Primary endpoint
    SRI-4 at Week 52

    • ≥4-point reduction in the SELENA-SLEDAI score, and
    • No new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores, and
    • No worsening (<0.30-point increase) in PGA score

    Secondary endpoint
    Severe flare
    The incidence of severe flares over 52 weeks.
    SFI modified to include the single criterion of increased SELENA-SLEDAI score to >12 as defining severe flare.
    Steroid reduction
    Percentage of patients with a ≥25% mean prednisone dose decrease from baseline to ≤7.5 mg/day from Weeks 40–52.

    PGA = Physician’s Global Assessment; SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index; SFI = SELENA-SLEDAI Flare Index; SRI = SLE Responder Index.

  • Definition of primary endpoint

    SRI-4 at Week 52 (primary endpoint)

    To be considered a responder, patients must meet all three components3:

    • SELENA-SLEDAI: ≥4-point reduction
    • BILAG: No new BILAG A or 2 new BILAG B organ domain scores
    • PGA: No worsening of ≥0.30 points

    BILAG = British Isles Lupus Assessment Group; PGA = Physician’s Global Assessment; SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index; SRI = SLE Responder Index.

  • Definition of severe flare

    Using a modified SELENA-SLEDAI Flare Index, severe flares were defined as at least one of the following19,20*:

    To be considered a responder, patients must meet all 3 components:

    • Hospitalization for SLE activity
    • New/worse (requiring doubling of prednisone, or prednisone increase to >0.5 mg/kg/day, or hospitalization):

      - CNS SLE
      - Vasculitis
      - Nephritis
      - Myositis
      - Platelets <60,000
      - Hemolytic anemia (Hb <7 g/dL or decrease in Hb of >3 g/dL)

    • Any manifestation that required an increase in prednisone to >0.5 mg/kg/day or initiation of a new immunosuppressant
    • Increase in PGA score to >2.5

    * The modified SELENA-SLEDAI excludes severe flares triggered only by an increase of the SELENA-SLEDAI score to >12.

    CNS = central nervous system; Hb = hemoglobin; PGA = Physician’s Global Assessment; SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index; SLE = systemic lupus erythematosus.

  • Study parameters for Be-SLESUP4

    Post hoc pooled analysis of 5 double-blind placebo-controlled studies evaluating BENLYSTA
    Comparison for all efficacy endpoints:

    • Pooled BENLYSTA (10 mg/kg IV + 200 mg SC) vs pooled placebo (IV + SC)

     

    Analysis parameters

    Studies Patients evaluated Endpoints
    • BLISS-52
    • BLISS-76
    • EMBRACE*
    • BLISS-SC
    • NE Asia

     

    BENLYSTA (n=1869)

    Placebo (n=1217)

    		 SRI-4 + subgroups
    • Severe flares and subgroups
    • Organ domains
    • Steroid outcomes
    Studies included
    • BLISS-52
    • BLISS-76
    • EMBRACE*
    • BLISS-SC
    • NE Asia
    Patients evaluated
    BENLYSTA + ST (n=1869)
    Placebo + ST (n=1217)
    Endpoints

    SRI-4 + subgroups

    • Severe flares and subgroups
    • Organ domains
    • Steroid outcomes

     

     

    Key limitations:

    • Post hoc analysis
    • Pooled dosage groups
    • Results not adjusted for multiple comparisons
    • Individual endpoints may not have been achieved in all clinical studies pooled for this analysis

     

    * The primary endpoint (SRI-S2K at Week 52) was not met in EMBRACE.

    BLISS = Belimumab International SLE Study; IV = intravenous; EMBRACE = Efficacy and Safety of Belimumab in Adult Subjects of Black Race; NE = Northeast; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; SRI = SLE Responder Index; SRI-S2K = SLE Responder Index response rate with the modified SLEDAI-2K scoring for proteinuria; SC = subcutaneous.

  • Study design for BLISS-76 LTESUP9

    US patients who completed the BLISS-76 Phase III trial were eligible for the BLISS-76 LTE open-label trial

    Trial parameters

    Study details Patients enrolled Endpoints

    Multicenter US extension study (up to 8 years)

    • BENLYSTA IV 10 mg/kg + ST*

     

    		 N=268 (US sites only)

    Assessed every 48 weeks

    • Primary: safety
      • AEs, AESI, vital signs, laboratory measures, SDI
    • Other
      • Efficacy by SRI-4
      • Disease activity scores
      • Flare rates
      • Steroid use
    Study details
    Multicenter US extension study (up to 8 years)
    • BENLYSTA IV 10 mg/kg + ST*
    Patients enrolled
    N=268 (US sites only)
    Endpoints
    Assessed every 48 weeks
    • Primary: safety
      • AEs, AESI, vital signs, laboratory measures, SDI
    • Other:
      • Efficacy by SRI-4
      • Disease activity scores
      • Flare rates
      • Steroid use

     

    Key limitations:

    • Open-label design with lack of comparator arm
    • Selection bias and responder bias may be present
    • Pooled dosage groups
    • Small group of patients at later time points

    * Patients who received placebo in BLISS-76 received 10 mg/kg BENLYSTA in the LTE study, and patients who received BENLYSTA continued to receive the same dose (1 or 10 mg/kg IV every 28 days) plus standard therapy. Following a protocol amendment in March 2011, patients receiving 1 mg/kg BENLYSTA had their dose increased to 10 mg/kg.

    AE = adverse event; AESI = adverse events of special interest; BLISS = Belimumab International SLE Study; IV = intravenous; LTE = long-term extension; SDI = SLICC/ACR Damage Index; SRI = SLE Responder Index; ST = standard therapy.

  • OBSErve study designSUP5,11

    An observational cohort study assessed the effectiveness of BENLYSTA 10 mg/kg + ST in adult patients with SLE over a 24-month period in US clinical practices across 27 states and included 92 rheumatologists (N=501). To qualify for enrollment, patients were required to have at least 8 infusions of BENLYSTA. The baseline was the date of first infusion. Physician-assessed clinical response was reviewed at 6-month intervals using medical charts and data collected using case report forms.

    Primary objective: Physician-assessed clinical response to BENLYSTA at 6 months. Between baseline and Month 6, ≥50% improvement in overall clinical response was reported for 48.7% of participants.

    Selected other objective: Changes in steroid use at 6-month intervals over a 24-month period.

    Study discontinuation: During the 2-year observation, 45% (n=224) were lost to follow-up or discontinued use of BENLYSTA. Common reasons for discontinuing BENLYSTA (n=122; 22.5%) include: patient request (40.2%), medication not effective (29.5%), and adverse event (12.5%).

    Key data limitations:

    • Lack of control group
    • Risk of selection bias
    • Validated disease assessment tool not consistently used
    • Patient attrition
    • Potential measurement error based on non-uniform categorization or interpretation of disease severity and treatment response
    • Reasons for change in steroid dose were not captured and may be unrelated to disease improvement/worsening

    Post hoc analysis in African-American and Hispanic patients
    The primary outcome measure was overall clinical response to belimumab at the end of a 24-month period, based on physician’s assessment over the last 6-month period.

    Other clinical outcomes (assessed versus index at Month 6, 12, 18, and 24 post-index) included:

    • Physician-assessed SLE disease severity
    • Oral corticosteroid use
    • Utilization of assessment tools
    • Reasons for, and rate of, belimumab discontinuation

     

    Study discontinuation:
    • In the OBSErve US study, 501 patients with SLE were enrolled; 123 (24.6%) were African American and 88 (17.6%) were Hispanic, of whom 69 (56.1%) and 43 (48.9%), respectively, continued to receive belimumab at Month 24
    • Of those patients who did not continue belimumab use over the 24 months, 26 (21.1%) African-American and 23 (26.1%) Hispanic patients were lost to follow-up, and 28 (22.8%) and 22 (25.0%), respectively, discontinued belimumab
    • The most common reasons for discontinuation in the African-American group were patient request (n=13) and medication inefficacy (n=7), and 2 patients discontinued belimumab due to an adverse event, while in the Hispanic group, the most common reasons for discontinuation were lost to follow-up (n=8) and loss of insurance or reimbursement (n=7)

     

    Care should be taken when interpreting the present findings due to the following limitations:
    • Patient attrition
    • Small sample size
    • Lack of a control group
    • Varied experience of participating clinicians with the clinical SLE tools
    • Analysis-by-responder bias
    • Use of subjective, non-validated assessments
    • Assessment tools not consistently used in approximately half of cases

    SLE = systemic lupus erythematosus; ST = standard therapy.

  • Early use study designSUP17

    Immunosuppressant use analysis17

    Immunosuppressant use analysis
    Immunosuppressant use analysis
    • Retrospective, real-world, longitudinal cohort study based on administrative claims
    • Data from the Komodo Health Database of de-identified claims between January 2015 and December 2022 were used
    • A total of 6841 eligible adults with a diagnosis of lupus were identified at index on January 1, 2017
    • Patient follow-up was over a maximum of 60 months post-index
    • Patients were stratified into 2 cohorts: those initiating BENLYSTA before or after ISS use. Patients were then further stratified by their baseline SLE disease severity, defined using a previously published algorithm based on measures of SLE disease activity and expert clinical opinion. This analysis excluded patients with mild disease activity and those with history of use of >2 ISS during the baseline period
    • ISSs of interest were: azathioprine, cyclophosphamide, cyclosporine, leflunomide, methotrexate, mycophenolate mofetil/mycophenolic acid, tacrolimus, and voclosporin
    • Results were reported descriptively and the time to OCS discontinuation was assessed using Kaplan–Meier methodology

    Endpoints:

    • Rate and severity of SLE flares
    • Time to organ damage occurrence
    • OCS use
    • All-cause HCRU

    Inclusion criteria:

    • A lupus diagnosis before or on the index date based on:
      • ≥2 outpatient medical claims, OR
      • ≥1 inpatient/emergency department claim
    • Filled ≥1 prescription for BENLYSTA from January 2017 to May 2022
    • ≥18 years of age on the index date
    • ≥24 months of continuous enrollment before index date

    Exclusion criteria:

    • Diagnosis of drug-induced lupus before the index date based on ≥1 outpatient, inpatient, or emergency department claim
    • Prescription of BENLYSTA or a Janus kinase inhibitor (ie, baricitinib, tofacitinib, upadacitinib, ruxolitinib, and fedratinib) during the baseline period (other biologic treatments were permitted)
    • Patients who had received ≥2 prior ISS during the baseline period

    Key data limitations:

    • All results presented here are based on descriptive analyses and numerical differences are presented without statistical hypothesis testing
    • The 24-month baseline period may have resulted in small sample sizes
    • Medication usage:
      • The presence of a dispensed medication does not guarantee that the medication was taken as prescribed
      • Adherence to medication(s) was not measured
    • Difference between baseline clinical characteristics between cohorts
    • Reasons for change in steroid dose were not captured and may be unrelated to disease improvement/worsening

  • EMBRACE trial parametersSUP110

    Trial parameters

    Studies included Patients evaluated Endpoints
    • Randomized
    • Double-blind
    • Placebo-controlled
    • 52-week duration
    		 BENLYSTA IV 10 mg/kg
    
+ ST (n=299)
    Placebo + ST (n=149)    		 96 centers throughout North
    America, South America, South
    Africa, and Europe
    Studies included
    • Randomized
    • Double-blind
    • Placebo-controlled
    • 52-week duration
    Patients evaluated
    BENLYSTA IV 10 mg/kg
    + ST (n=299)
    Placebo + ST (n=149)
    Endpoints
    96 centers throughout North America, South America, South Africa, and Europe

     

    mITT population: all patients who were randomized and received at least one dose of study treatment (48 patients from 3 sites were excluded due to non-compliance).

    mITT = modified intention-to-treat.

  • EMBRACE study endpointsSUP110,21

    Endpoints were analyzed in a hierarchical manner – if at any point statistical significance was not met, subsequent endpoints could not be considered significant.

    Primary endpoint
    SRI–SLEDAI-2K at Week 52

    • ≥4-point reduction in the modified SELENA-SLEDAI score using S2K scoring for proteinuria, and
    • No new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores, and
    • No worsening (≥0.30-point increase) in PGA score

    Secondary endpoint
    Severe flare
    Time to first severe SLE flare as measured by the SFI.
    Steroid reduction
    Percentage of patients with a ≥25% mean prednisone dose decrease from baseline to ≤7.5 mg/day from Weeks 40–52.

    PGA = Physician’s Global Assessment; SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; SFI = SELENA-SLEDAI Flare Index; SRI = SLE Responder Index.

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Real-world evidence

See the effect of BENLYSTA on organ damage progression.

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Safety profile

Well-established safety profile based on the largest clinical trial program in lupus and lupus nephritis.

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Add BENLYSTA after hydroxychloroquine for your patients with lupus*

* As part of standard therapy.

Add BENLYSTA after hydroxychloroquine for your patients with lupus*

* As part of standard therapy.