Organ Damage | BENLYSTA (belimumab) for HCPs

In pivotal lupus trials, BENLYSTA demonstrated significant disease activity reduction (SRI-4) at Week 52^1-3

In pivotal Phase III lupus trials, the primary endpoint was defined as SRI-4 response rate at Week 52. The SRI-4 response rate at Week 52 for BENLYSTA + ST vs placebo + ST was 61% (n=554) vs 48% (n=279) for BLISS-SC, 58% (n=290) vs 44% (n=287) for BLISS-52, and 43% (n=273) vs 34% (n=275) for BLISS-76, P<0.05 for each.^1-3

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80%of patients had no change in their organ damage score over 7–8 years of treatment with BENLYSTA⁴

Post hoc analysis of pooled data from 3 open-label LTE studies (Phase 2 LTE, BLISS-76 LTE, and BLISS-52 + BLISS-76 LTE). Results are descriptive. See study design for data limitations.

See the data

For patients on BENLYSTA + ST, organ damage progression was less than half of ST alone⁵

Real-world, post hoc, propensity score-matched analysis. Results are descriptive. See study design for data limitations.

See the data

BLISS = Belimumab International SLE Study; LTE = long-term extension; SC = subcutaneous; SDI = SLICC/ACR Damage Index; SLE = systemic lupus erythematosus; SLICC/ACR = Systemic Lupus International Collaborating Clinics/American College of Rheumatology; SRI = SLE Responder Index; ST = standard therapy.

LTE organ damage

Organ damage progression

Time to organ damage progression

Rate of organ damage progression

Study designs

The long-term impact of BENLYSTA + ST on organ damage progression over 7–8 years⁴

Patients with no change in SDI score from baseline

80% of patients had no change in their organ damage score over 7-8 years of treatment with BENLYSTA

Post hoc analysis of pooled data from 3 open-label LTE studies (Phase 2 LTE, BLISS-76 LTE, and
BLISS-52 + BLISS-76 LTE). Results are descriptive. See study design for data limitations.

Reduction of organ damage progression⁵

The impact of BENLYSTA was evaluated in a real-world analysis of organ damage progression.

Reduction of organ damage progression based on mean change in organ damage (SDI) from baseline to Year 5* (primary endpoint)

Real-world evidence: organ damage progression was less than half of ST alone

Real-world, post hoc, propensity score-matched analysis. Results are descriptive. See study design for data limitations.

* Includes all patients with ≥5 years of follow-up.

TLC = Toronto Lupus Cohort.

Time to organ damage progression⁵

Patients treated with BENLYSTA + ST were less likely to progress to a higher organ damage score over any given year of follow-up⁵

Difference in time to organ damage progression*

As early as Year 1, more patients on BENLYSTA + ST were observed to have no change in their SDI score

Real-world, post hoc, propensity score-matched analysis. Results are descriptive. See study design for data limitations.

* Time to organ damage progression was a secondary endpoint, assessed in patients with ≥1 year of follow-up.

† Years are 48 weeks in length.

CI = confidence interval; HR = hazard ratio; KM = Kaplan-Meier.

Reduction in rate of organ damage progression⁵

Annual probability of progression is based on the increase in SDI score per year (secondary endpoint)

Patients on BENLYSTA were 61% less likely to progress to a higher organ damage score (SDI) (HR=0.39; 95% CI: 0.25, 0.61)

Real-world, post hoc, propensity score-matched analysis. Results are descriptive. See study design for data limitations.

* Based on SDI score increases per year in patients with ≥1 year follow-up.

Persistent disease activity, including flares and chronic
high-dose steroid use, are some of the drivers of
organ damage.^1-3,6-10

See how BENLYSTA impacts these drivers

Study designs

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PSM study designSUP5
A post hoc, PSM comparative analysis was performed to assess the difference in organ damage (SDI) progression between patients in BLISS-76 LTE* and from the TLC.^†
KEY LIMITATIONS OF THIS PSM STUDY⁵

Post hoc analysis

Patients matched based on known variables only

Patients could not be matched by year of entry into the study

Differences in patient populations

* To be eligible, patients on BENLYSTA had to be in the United States; regimen was BENLYSTA IV 10 mg/kg + ST.

† Chosen based on its size, the extent of organ damage in patients, and the severity of disease activity. Regimen was ST alone.

IV = intravenous; PSM = propensity score matching.

What patient characteristics were used in the PSM analysis?

PSM: A method to match and compare patients from different studies⁵

Demographics
Age Age squared Gender Race/Ethnicity Black Asian/other Current smoker
Clinical characteristics
History of: Hypertension Dyslipidemia Proteinuria
SLE-specific characteristics
SLE duration Number of ACR criteria at diagnosis Baseline SLEDAI score Baseline SDI SDI = 1 SDI ≥ 2
Medications
Steroids Immunosuppressant Antimalarials

Demographics	Clinical characteristics	SLE-specific characteristics	Medications
Age Age squared Gender Race/Ethnicity Black Asian/other Current smoker	History of: Hypertension Dyslipidemia Proteinuria	SLE duration Number of ACR criteria at diagnosis Baseline SLEDAI score Baseline SDI SDI = 1 SDI ≥ 2	Steroids Immunosuppressant Antimalarials

Demographics

Clinical characteristics

SLE-specific characteristics

Medications

Age
Age squared
Gender
Race/Ethnicity
- Black
- Asian/other
Current smoker

History of:

Hypertension
Dyslipidemia
Proteinuria

SLE duration
Number of ACR criteria at diagnosis
Baseline SLEDAI score
Baseline SDI
- SDI = 1
- SDI ≥ 2

Steroids
Immunosuppressant
Antimalarials

Once matched, any observed differences between patients are presumed to be a result of the treatment.⁵

ACR = American College of Rheumatology; PSM = propensity score matching; SDI = SLICC/ACR Damage Index; SLE = systemic lupus erythematosus; SLEDAI = SLE Disease Activity Index; SLICC/ACR = Systemic Lupus International Collaborating Clinics/American College of Rheumatology.

Long-term extension study designSUP4
This was a post hoc analysis of pooled data from 3 open-label LTE studies (LBSL02 Phase 2 LTE, BLISS-76 LTE, and BLISS-52 + BLISS-76 LTE, excluding US patients from BLISS-76).

Patients received BENLYSTA IV 10 mg/kg + ST every 28 days and must have completed treatment through Week 72 of LBSL02 and BLISS-76, or Week 48 of BLISS-52.

The SDI score was assessed among eligible patients in the BLISS-76 and BLISS-52 + BLISS-76 LTE studies, within the high disease activity population (anti-dsDNA positive and low C3/C4), and the 5-year completer population (patients with ≥5 years of follow-up after their first dose of BENLYSTA).

Patients in the originator studies who received BENLYSTA 1 mg/kg were transitioned to BENLYSTA 10 mg/kg upon entering the LTE. BENLYSTA 1 mg/kg is not an approved dose and not included in the data shown.

KEY DATA LIMITATIONS

As the studies were open-label and did not have a control arm, causal inferences about the effect of BENLYSTA cannot be made

There was an increased number of withdrawals in later years, resulting in a small study population as compared to baseline

The Phase 2 study included some patients who were autoantibody negative at baseline. In the Phase 3 trials, all patients were autoantibody-positive

The baseline SDI scores varied among patients and are not reflected in this figure
anti-dsDNA = anti-double–stranded DNA.

Did you know?

Organ damage in lupus can be severe and irreversible

1 in 3 patients

experience irreversible organ damage within 1 year of diagnosis^6,9*^†‡

1 in 2 patients

experience irreversible organ damage within 5 years of diagnosis^6,9*^†‡

* 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.^10,11

† 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 5.⁶

‡ 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. Nearly 50% of patients acquired organ damage at Year 5.⁹

Organ damage in patients with lupus can affect multiple organ systems¹²

Damage most commonly occurs in the mucocutaneous, musculoskeletal, and immune systems.

Constitutional

Respiratory

Hematological

Kidney

Dermatological

Musculoskeletal

Circulatory

Gastrointestinal

Select overarching principle from the 2023 EULAR recommendations:

Assess lupus disease activity at each clinic visit and evaluate organ damage at least annually, using validated instruments (frequency for both at physician’s discretion).¹³

Find out more

Select overarching principle from the 2023 EULAR recommendations:

Assess lupus disease activity at each clinic visit and evaluate organ damage at least annually, using validated instruments (frequency for both at physician’s discretion).¹³

Find out more

Hear the story of a patient experiencing organ damage*

Meet Maria

* Hypothetical patient profile. Not representative of all BENLYSTA patients.

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BENLYSTA for lupus

BENLYSTA improved key clinical outcomes for appropriate patients.

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Safety profile

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

Find out more

Slow the progression of organ

damage in your patients with lupus

See what BENLYSTA could do

Slow the progression of

organ damage in your

patients with lupus

See what BENLYSTA could do

INDICATION & IMPORTANT SAFETY INFO

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.

CONTRAINDICATION

Previous anaphylaxis with BENLYSTA.

WARNINGS AND PRECAUTIONS

Serious Infections: Serious and sometimes fatal infections have been reported and occurred more frequently with BENLYSTA.

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

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.
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.
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.
Touma Z, Arriens C, Henning C, et al. SLE medication usage and organ damage among adult SLE patients with SLE treated with belimumab (BEL): pooled data from three open-label extension studies over 11+ years [abstract]. Arthritis Rheumatol. 2023;75(Suppl 9).
Urowitz MB, Oshfeldt RL, Wielage RC, et al. Organ damage in patients treated with belimumab versus standard of care: a propensity score-matched comparative analysis. Ann Rheum Dis. 2019;78(3):372-379.
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;48:673-675.
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. Rheum. 2012;51(3):491-498.
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.
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. 2012;64(1):132-137.
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.
Gladman D, Ginzler E, Goldsmith C, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 1996;39(3):363-369.
Aringer M, Johnson SR. Classifying and diagnosing systemic lupus erythematosus in the 21st century. Rheumatology (Oxford). 2020;59(Suppl5):v4-v11.
Fanouriakis A, Kostopoulou M, Andersen J, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2024;83(1):15-29.

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exit-intent

Organ damage from lupus may be putting your patients at risk

What can you do to help them?

In pivotal lupus trials, BENLYSTA demonstrated significant disease activity reduction (SRI-4) at Week 521-3

80%of patients had no change in their organ damage score over 7–8 years of treatment with BENLYSTA4

For patients on BENLYSTA + ST, organ damage progression was less than half of ST alone5

The long-term impact of BENLYSTA + ST on organ damage progression over 7–8 years4

Patients with no change in SDI score from baseline

Reduction of organ damage progression5

The impact of BENLYSTA was evaluated in a real-world analysis of organ damage progression.

Reduction of organ damage progression based on mean change in organ damage (SDI) from baseline to Year 5* (primary endpoint)

Time to organ damage progression5

Patients treated with BENLYSTA + ST were less likely to progress to a higher organ damage score over any given year of follow-up5

Difference in time to organ damage progression*

Reduction in rate of organ damage progression5

Annual probability of progression is based on the increase in SDI score per year (secondary endpoint)

Persistent disease activity, including flares and chronic high-dose steroid use, are some of the drivers of organ damage.1-3,6-10

Study designs

A post hoc, PSM comparative analysis was performed to assess the difference in organ damage (SDI) progression between patients in BLISS-76 LTE* and from the TLC.†

PSM: A method to match and compare patients from different studies5

Did you know?

Organ damage in lupus can be severe and irreversible

1 in 3 patients

1 in 2 patients

Organ damage in patients with lupus can affect multiple organ systems12

Damage most commonly occurs in the mucocutaneous, musculoskeletal, and immune systems.

Constitutional

Respiratory

Hematological

Kidney

Dermatological

Musculoskeletal

Circulatory

Gastrointestinal

Select overarching principle from the 2023 EULAR recommendations:

Assess lupus disease activity at each clinic visit and evaluate organ damage at least annually, using validated instruments (frequency for both at physician’s discretion).13

Select overarching principle from the 2023 EULAR recommendations:

Assess lupus disease activity at each clinic visit and evaluate organ damage at least annually, using validated instruments (frequency for both at physician’s discretion).13

Hear the story of a patient experiencing organ damage*

Learn more

BENLYSTA for lupus

Safety profile

Slow the progression of organ

damage in your patients with lupus

Slow the progression of

organ damage in your

patients with lupus

CONTRAINDICATION

CONTRAINDICATION

WARNINGS AND PRECAUTIONS

CONTRAINDICATION

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

USE IN SPECIFIC POPULATIONS

References

In pivotal lupus trials, BENLYSTA demonstrated significant disease activity reduction (SRI-4) at Week 52^1-3

80%of patients had no change in their organ damage score over 7–8 years of treatment with BENLYSTA⁴

For patients on BENLYSTA + ST, organ damage progression was less than half of ST alone⁵

The long-term impact of BENLYSTA + ST on organ damage progression over 7–8 years⁴

Reduction of organ damage progression⁵

Time to organ damage progression⁵

Patients treated with BENLYSTA + ST were less likely to progress to a higher organ damage score over any given year of follow-up⁵

Reduction in rate of organ damage progression⁵

Persistent disease activity, including flares and chronic
high-dose steroid use, are some of the drivers of
organ damage.^1-3,6-10

A post hoc, PSM comparative analysis was performed to assess the difference in organ damage (SDI) progression between patients in BLISS-76 LTE* and from the TLC.^†

PSM: A method to match and compare patients from different studies⁵

Organ damage in patients with lupus can affect multiple organ systems¹²

Assess lupus disease activity at each clinic visit and evaluate organ damage at least annually, using validated instruments (frequency for both at physician’s discretion).¹³

Assess lupus disease activity at each clinic visit and evaluate organ damage at least annually, using validated instruments (frequency for both at physician’s discretion).¹³