Organ Damage | BENLYSTA (belimumab) for HCPs

In pivotal lupus trials, BENLYSTA demonstrated significant disease activity reduction (SRI-4) at Week 52^3-5

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.^3-5

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

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

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

* 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.^8,9

† 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 5.² 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 5.¹

SLE = systemic lupus erythematosus; SLICC/ACR = Systemic Lupus International Collaborating Clinics/American College of Rheumatology.

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.

References

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.

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.

Navarra SV, Guzman 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.

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;78:372-379.

Bertsias G, Cervera R, Boumpas DT. Systemic lupus erythematosus: pathogenesis and clinical features. EULAR textbook on rheumatic diseases. 2012;5:476-505.

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.

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.

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.

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

Irreversible organ damage is a consequence of lupus1,2

What can you do for your patients?

In pivotal lupus trials, BENLYSTA demonstrated significant

disease activity reduction (SRI-4) at Week 523-5

In pivotal lupus trials, BENLYSTA demonstrated significant disease activity reduction (SRI-4) at Week 523-5

For patients on BENLYSTA + ST, organ damage progression was less than half of ST alone6

For patients on BENLYSTA + ST, organ damage progression wasless than half of ST alone6

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

Reduction of organ damage progression6

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)

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

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

Reduction in rate of organ damage progression6

Reduction in rate of organ damage progression6

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

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

What was the study design?

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 studies6

Did you know?

Approximately 1 in 2 patients experience irreversible organ damage within 5 years of diagnosis1,2*†

Did you know?

Approximately 1 in 2 patients experience irreversible organ damage within 5 years of diagnosis1,2*†

Organ damage in patients with lupus can affect multiple organ systems1,7,8

Musculoskeletal

Pulmonary

Renal

Cardiovascular

Ocular

Persistent disease activity, including flares, can contribute to organ damage9-11

Chronic steroid use can be a contributing factor in organ damage accrual2,10

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).12

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).12

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

Irreversible organ damage is a consequence of lupus^1,2

disease activity reduction (SRI-4) at Week 52^3-5

In pivotal lupus trials, BENLYSTA demonstrated significant disease activity reduction (SRI-4) at Week 52^3-5

For patients on BENLYSTA + ST,
organ damage progression was
less than half
of ST alone⁶

For patients on BENLYSTA + ST, organ damage progression was
less than half
of ST alone⁶

Reduction of organ damage progression⁶

Reduction in rate of organ damage progression⁶

Reduction in rate of organ damage progression⁶

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 studies⁶

Approximately 1 in 2 patients experience irreversible organ damage within 5 years of diagnosis^1,2*^†

Approximately 1 in 2 patients experience irreversible organ damage within 5 years of diagnosis^1,2*^†

Organ damage in patients with lupus can affect multiple organ systems^1,7,8

Persistent disease activity, including flares, can contribute to organ damage^9-11

Chronic steroid use can be a contributing factor in organ damage accrual^2,10

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).¹²

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).¹²