BENLYSTA EARLY

Add BENLYSTA early

  • After hydroxychloroquine in lupus* 
  • As part of initial therapy in lupus nephritis
* As part of standard therapy.

The only biologic in lupus and lupus nephritis backed by over a decade of comprehensive clinical and real-world evidence.

Up to 61% of patients had reduced lupus symptoms (SRI-4) at Week 521–4

(Primary endpoint)

SEE SRI-4 DATA

SLE = systemic lupus erythematosus; SRI = SLE Responder Index.

BENLYSTA: proven to reduce lupus symptoms1–4

SRI-4 response rate at Week 52 (primary endpoint)1–3*

In pivotal Phase III lupus trials, BENLYSTA demonstrated significantly higher SRI-4 response rates at Week 52 vs standard therapy alone

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

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

Sustained response data in the US open-label long-term extension trial5

SRI-4 responders over 7 years

76% of patients were observed to achieve SRI-4 at Year 7

Severe flare data

BENLYSTA reduced the risk of severe flares1–3*†

Up to

49%

reduced risk of severe flares over 52 weeks1–3

Patients having ≥1 severe flare over 52 weeks1-3*†

Up to 49% reduced risk of severe flares over 52 weeks

* 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.

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.

During the 7-year follow-up,

79%

of patients did not have a severe flare

(n/N=212/267)5

Results are descriptive. Other efficacy endpoints. Exploratory results should be interpreted with additional care.

 

See study limitations.

 

See study design.

BENLYSTA: steroid reduction results

Steroid reduction was not mandated across 3 pivotal studies, and:

Approximately 1 in 5 patients reduced steroid dose at Week 52

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-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)

Why wait to add BENLYSTA?

Add BENLYSTA sooner, after hydroxychloroquine (HCQ) in SLE*

* As part of standard therapy in lupus.

RWE analysis: impact of initiating BENLYSTA + ST prior to immunosuppressants* on steroid discontinuation6

Median time to OCS discontinuation in a real-world setting6*

Real-world evidence: median time to OCS discontinuation was observed to decrease when BENLYSTA was started earlier than an immunosuppressant

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.6

See study limitations.

See study design.

Average daily OCS dose in patients with no immunosuppressant use and after use of 1 immunosuppressant, stratified by baseline disease severity6

  No IS 1 IS
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

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.6

 

No immunosuppressant: patients initiating BENLYSTA without prior immunosuppressant use during the baseline period.6

 

1 immunosuppressant: patients initiating BENLYSTA with the use of 1 prior immunosuppressant during the baseline period.6

 

The sample size of patients with mild baseline SLE among patients initiating BENLYSTA after immunosuppressant use was too small to be meaningful (n=8), and thus was not evaluated.6

 

* BENLYSTA cohort did not receive immunosuppressants at baseline or for 24 months prior.6

† 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.6

‡ Regardless of baseline disease severity.6

§ 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.6

IS = immunosuppressant; OCS = oral corticosteroid.

RWE analysis: impact of BENLYSTA + ST before IS on flares6*†

In patients with moderate SLE at baseline6

Real-world evidence: reduction of flares when BENLYSTA + ST were used prior to IS over 24 months in moderate SLE

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.6

 

See study limitations.

 

See study design.

Moderate baseline SLE: mean rate of mild and severe flares (per person-year)†‡§

  BENLYSTA + ST before IS
(N=1909)		 BENLYSTA + ST with IS
(N=3252)
Mild flares
6 months 4.63 5.20
12 months 4.33 4.87
24 months 4.27 4.76
Severe flares
6 months 0.35 0.5
12 months 0.32 0.44
24 months 0.28 0.4

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.6

* BENLYSTA cohort did not receive immunosuppressants at baseline.

† The modified definition categorized the initiation of IS as filling a prescription for an immunosuppressant >60 days after the previous day’s prescription supply ended.

‡ SLE flare episodes were identified and classified by severity based on a previously published claims-based algorithm, which considers relevant medications and HCRU associated with an SLE diagnosis or an SLE-related condition flare.

§ Rate of PPY is calculated as the total number of visits across all patients divided by the total person-time of observation.

∥ The SE of the population incidence rate is calculated as √(total number of events/total follow-up time).

In patients with severe SLE at baseline6

Real-world evidence: reduction of flares when BENLYSTA + ST were used prior to IS over 24 months in severe SLE

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.6

 

See study limitations.

 

See study design.

Severe baseline SLE: mean rate of mild and severe flares (per person-year)†‡§

  BENLYSTA + ST before IS
(N=386)		 BENLYSTA + ST with IS
(N=862)
Mild flares
6 months 4.91 5.27
12 months 4.56 5.09
24 months 4.40 5.02
Severe flares
6 months 0.99 2.07
12 months 0.89 1.71
24 months 0.70 1.48

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.6

 

* BENLYSTA cohort did not receive immunosuppressants at baseline.

† The modified definition categorized the initiation of IS as filling a prescription for an immunosuppressant >60 days after the previous day’s prescription supply ended.

‡ SLE flare episodes were identified and classified by severity based on a previously published claims-based algorithm, which considers relevant medications and HCRU associated with an SLE diagnosis or an SLE-related condition flare.

§ Rate of PPY is calculated as the total number of visits across all patients divided by the total person-time of observation.

∥ The SE of the population incidence rate is calculated as √(total number of events/total follow-up time).

HCRU = healthcare resource utilization; PPY = per person-year.

Patients using BENLYSTA + ST without IS had fewer flares4*

Post hoc analysis of pooled data from five Phase III trials for BENLYSTA

Patients using BENLYSTA + ST were observed to have 27 percent fewer on-study flares

Results are descriptive.

 

See study limitations.

 

See study design.

* BENLYSTA cohorts did not receive IS at baseline.

GC = glucocorticoid; IV = intravenous.

Post hoc pooled data analysis: efficacy outcomes in patients treated with BENLYSTA + ST without IS4*

Post hoc analysis of pooled data from five Phase III trials for BENLYSTA

Proportion of patients achieving SRI-4 response

When BENLYSTA + ST were used without IS, 6 in 10 patients were observed to achieve an SRI-4 response by Week 52

Patients with a baseline SELENA-SLEDAI score of <4 or with a missing PGA score at baseline were excluded from the SRI-4 response analysis.

Results are descriptive.

 

See study limitations.

 

See study design.

* BENLYSTA cohort did not receive immunosuppressants.

BENLYSTA: additional data on lupus disease activity

    Steroid reduction results in a real-world setting4,10*

    In a real-world setting

    Real-world evidence: at Week 26, 86% of patients were observed to reduce or discontinue steroids with a mean reduction in daily dose by 58% vs baseline

    A real-world observational study. Results are descriptive.

     

    See study limitations.

     

    See study design.

     

    Data from US patients prescribed steroids at baseline (n=386) ITT, LOCF†‡

    % of patients who reduced steroid dose vs baseline
    Baseline 6 months 12 months 18 months 24 months
    - 77% (297) 60% (232) 55% (212) 55% (211)
    % of patients who discontinued steroids vs baseline
    Baseline 6 months 12 months 18 months 24 months
    - 9% (35) 29% (110) 33% (126) 34% (131)
    % of patients whose dose remained the same vs baseline
    Baseline 6 months 12 months 18 months 24 months
    - 12% (46) 8% (30) 8% (32) 8% (31)
    % of patients who increased steroid dose vs baseline
    Baseline 6 months 12 months 18 months 24 months
    * 2% (8) 4% (14) 4% (16) 3% (13)
    Average daily steroid dose, mg (of patients on steroids)
    Baseline 6 months 12 months 18 months 24 months
    19.9 8.4 6.3 6.5 6.1

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

    † ITT consisting of all patients enrolled at baseline followed through 24 months using the 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.

    ITT = intent-to-treat; LOCF = last observation carried forward.

    Did you know that persistent disease activity, including flares and chronic use of high-dose steroids, can lead to organ damage?1–3,11–15

    LEARN HOW BENLYSTA CAN HELP

    Lupus disproportionately affects Black and Hispanic populations, who experience a significantly higher burden of the disease compared to white populations.16

    Efficacy data in a diverse patient population17

    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).

      Organ damage may be a real risk for your patients with lupus

      SEE WHAT BENLYSTA COULD DO

      Learn more

      Real-world evidence

      See the effect of BENLYSTA on organ damage progression.

      SEE THE EFFECT ON ORGAN DAMAGE

      Safety profile

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

      SEE SAFETY PROFILE

      Add BENLYSTA after hydroxychloroquine for your patients with lupus*

      Add BENLYSTA sooner, after HCQ in SLE

      * As part of standard therapy.

      Indication & Safety Info

      Indication

      Important Safety Information

      Indication

      BENLYSTA is indicated for patients aged ≥5 with active systemic lupus erythematosus (SLE) or active lupus nephritis who are receiving standard therapy. BENLYSTA is not recommended in patients with severe active central nervous system lupus.

      Important Safety Information

      CONTRAINDICATION

      Previous anaphylaxis with BENLYSTA.

      WARNINGS AND PRECAUTIONS

      Serious Infections: Serious and sometimes fatal infections have been reported and occurred more frequently with BENLYSTA. Use caution in patients with severe or chronic infections, and consider interrupting therapy in patients with a new infection.

       

      Progressive Multifocal Leukoencephalopathy (PML): Cases of JC virus-associated PML resulting in neurological deficits, including fatal cases, have been reported. If PML is suspected, immunosuppressant therapy, including BENLYSTA, must be suspended until PML is excluded. If confirmed, stop immunosuppressant therapy, including BENLYSTA.

       

      Hypersensitivity Reactions (Including Anaphylaxis): Acute hypersensitivity reactions, including anaphylaxis and death, and infusion-related reactions have been reported. Generally, reactions occurred within hours of the infusion but may occur later, including in patients who have previously tolerated BENLYSTA. Non-acute hypersensitivity reactions (eg, rash, nausea, fatigue, myalgia, headache, and facial edema) typically occurred up to a week after infusion. Monitor patients during and after treatment and be prepared to manage anaphylaxis and infusion-related reactions. Be aware of the risk of hypersensitivity reactions, which may present as infusion-related reactions. Discontinue immediately in the event of a serious reaction. With intravenous administration, if an infusion reaction develops, slow or interrupt the infusion.

       

      Depression and Suicidality: Depression and suicidality were reported in patients receiving BENLYSTA. Before adding BENLYSTA, assess patients’ risk of depression and suicide and monitor them during treatment. Instruct patients/caregivers to contact their HCP if they experience new/worsening depression, suicidal thoughts/behavior, or other mood changes.

       

      Malignancy: There is an increased risk of malignancies with the use of immunosuppressants. The impact of BENLYSTA on the development of malignancies is unknown.

       

      Immunization: Live vaccines should not be given for 30 days before or concurrently with BENLYSTA as clinical safety has not been established.

       

      Use With Biologic Therapies: Available data do not support the safety and efficacy of concomitant use of BENLYSTA with rituximab in patients with SLE. An increased incidence of serious infections and post-injection systemic reactions in patients receiving BENLYSTA concomitantly with rituximab compared to patients receiving BENLYSTA alone has been observed. The safety and efficacy of BENLYSTA concomitantly with other biologic therapies, including B-cell-targeted therapies, have not been established. Caution should be exercised if BENLYSTA is administered in combination with other biologic therapies.

       

      ADVERSE REACTIONS

      The most common serious adverse reactions in adult SLE clinical trials were serious infections; some were fatal. The most common adverse reactions (≥5%) were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, pharyngitis, and injection site reactions (subcutaneous injection).

       

      Adverse reactions reported in clinical trials with SLE pediatric patients (≥5 years) and adult patients with lupus nephritis were consistent with those observed in adult SLE trials.

       

      USE IN SPECIFIC POPULATIONS

      Pregnancy: There are insufficient data in pregnant women to establish whether there is drug-associated risk for major birth defects or miscarriage. After a risk/benefit assessment, if prevention is warranted, women of childbearing potential should use contraception during treatment and for ≥4 months after the final treatment.

       

      Pregnancy Registry: HCPs are encouraged to refer patients and pregnant women are encouraged to enroll themselves by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/benlysta-belimumab/.

       

      Please see full Prescribing Information and Medication Guide for BENLYSTA.

      To report SUSPECTED ADVERSE REACTIONS, contact GSK at gsk.public.reportum.com or 1-888-825-5249, or
      FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

      References

      1. Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721-731.

      2. Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918-3930.

      3. Stohl W, Schwarting A, Okada M, et al. Efficacy and safety of subcutaneous belimumab in systemic lupus erythematosus: a fifty-two–week randomized, double-blind, placebo-controlled study. Arthritis Rheumatol. 2017;69(5):1016-1027.

      4. Data on file, GSK.

      5. Furie RA, Wallace DJ, Aranow C, et al. Long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus: a continuation of a seventy-six-week phase III parent study in the United States. Arthritis Rheumatol. 2018;70(6):868-877.

      6. Rubin B, Chen Y, Worley K, et al. Improved health outcomes in patients with systemic lupus erythematosus following early belimumab initiation without prior immunosuppressant use: a real-world descriptive study. Rheumatol Ther. 2024;11(4):947-962.

      7. Parodis I, Lindblom J, Levy RA, et al. Attainment of remission and low disease activity after treatment with belimumab in patients with systemic lupus erythematosus: a post-hoc analysis of pooled data from five randomised clinical trials. Lancet Rheumatol. 2024;6(11):e751-e761.

      8. Cleanthous S, Tyagi M, Isenberg DA, et al. What do we know about self-reported fatigue in systemic lupus erythematosus? Lupus. 2012;21(5):465-476.

      9. Lai JS, Beaumont JL, Ogale S, et al. Validation of the functional assessment of chronic illness therapy-fatigue scale in patients with moderately to severely active systemic lupus erythematosus, participating in a clinical trial. J Rheumatol. 2011;38(4):672-679.

      10. Collins CE, Dall’Era M, Kan H, et al. Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA. Lupus Sci Med. 2016;3(1):e000118.

      11. Lopez R, Davidson JE, Beeby MD, et al. Lupus disease activity and the risk of subsequent organ damage and mortality in a large lupus cohort. Rheumatology (Oxford). 2012;51(3):491-498.

      12. Gladman DD, Urowitz MB, Rahman P, et al. Accrual of organ damage over time in patients with systemic lupus erythematosus. J Rheumatol. 2003;30(9):1955-1959.

      13. Chambers SA, Allen E, Rahman A, et al. Damage and mortality in a group of British patients with systemic lupus erythematosus followed up for over 10 years. Rheumatology (Oxford). 2009;48(6):673-675.

      14. Urowitz MB, Gladman DD, Ibañez D, et al. Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort. Arth Care Res (Hoboken). 2012;64(1):132-137.

      15. Doria A, Gatto M, Zen M, et al. Optimizing outcome in SLE: treating-to-target and definition of treatment goals. Autoimmun Rev. 2014;13(7):770-777.

      16. Izmirly PM, Parton H, Wang L, et al. Prevalence of systemic lupus erythematosus in the United States: estimates from a meta-analysis of the Centers for Disease Control and Prevention National Lupus Registries. Arthritis Rheumatol. 2021;73(6):991-996.

      17. Ginzler E, Guedes Barbosa LS, D'Cruz D, et al. Phase III/IV, randomized, fifty-two–week study of the efficacy and safety of belimumab in patients of Black African ancestry with systemic lupus erythematosus. Arthritis Rheumatol. 2022;74(1):112-123.

      18. Bell C, Chung J, Rubin B. Real-world clinical outcomes in belimumab-treated US African American and Hispanic patients with systemic lupus erythematosus: a retrospective, observational study. Rheumatol Ther. 2023;10(2):447-462.