Characteristics of lupus

Lupus is a complex, chronic, multisystem autoimmune disease in which many patients experience irreversible organ damage.1-3

Lupus is characterized by:

Pathological production of autoantibodies such as ANA1,4

Waxing and waning disease activity1

Inflammation in multiple organ systems5

Abnormal activation of B and T cells6,7

ANA = antinuclear antibodies.

Persistent disease activity, including flares, can contribute to organ damage8-10

Graph showing how long-term persistent lupus disease activity can lead to irreversible organ damage progression

Graphical representation of a hypothetical disease course of a patient with lupus

Did you know?

Approximately 1 in 2 patients experience irreversible organ damage within 5 years of diagnosis2,3*†‡

Organ damage in patients with lupus can affect multiple organ systems2,11-13

Musculoskeletal

Pulmonary

Renal

Cardiovascular

Ocular

List of organ systems is not all-inclusive.

Increased difference in the occurrence of organ damage, as defined by SDI, between steroid-exposed (n=173) and steroid-naïve (n=86) patients with lupus14§

8% within 3 years, 17% within 5 years, and 20% within 8 years
  • *

    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.2,9

  • †

    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 5.3

  • ‡

    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 5.2

  • §

    A study of 259 patients (glucocorticosteroid-naïve group [86] and glucocorticosteroid-exposed group [173]) with SLE enrolled in the University of Toronto Lupus Clinic. Organ damage was measured using the SDI at 3, 5, and 8 years. The average baseline steroid dose was 34.6 mg/day in the steroid-exposed group. The average cumulative steroids in the first 3, 5, and 8 years (baseline SDI = 0) were 16.11 g, 22.61 g, and 36.71 g, respectively.14

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

2023 EULAR recommendations

Early lupus diagnosis, prompt treatment initiation aiming for remission (or low disease activity if not possible), and strict adherence to treatment are essential to prevent flares and organ damage, improve prognosis, and enhance quality of life.15

SEE THE GUIDELINES

Trademarks are property of their respective owners.
EULAR = European Alliance of Associations for Rheumatology.

Lupus disease activity

Disease activity includes all signs and symptoms or laboratory abnormalities due to lupus-related pathophysiology.5,8

 

Clinical and/or serological disease activity may be present. Selected features may include8:

  • Inflammatory/non-inflammatory symptoms in any system
  • Autoantibodies (eg, ANA)
  • Low complement C3 and/or C4
  • Increased gamma globulin serum levels

Flares

A flare is a measurable increase in disease activity and includes new or worse clinical symptoms and/or laboratory abnormalities.5

 

Lupus flares, persistent disease activity, and the prolonged use of corticosteroids in the long-term management of lupus can all contribute to organ damage.3,8-10,17

Various tools, including SELENA-SLEDAI, can be used to measure disease activity.

VIEW THE SELENA-SLEDAI TOOL

SELENA-SLEDAI = Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index.

Lupus nephritis is a real risk for many patients with lupus

Up to 5 of the next 10 patients with lupus a doctor sees may develop lupus nephritis

31-48% of patients will develop lupus nephritis at some point after their initial lupus diagnosis18*

Approximately 20% of patients with lupus nephritis will progress to ESKD within 10 years of diagnosis19

* Data from a pragmatic review of 26 publications involving patients with lupus nephritis with or without a proven biopsy.
ESKD = end-stage kidney disease.

Just one renal flare could shorten a kidney’s lifespan by decades20-22*

Renal flares are associated with irreversible nephron loss, shortening the kidney's lifespan and increasing the risk of ESKD3,8-10,17

Potential impact of lupus nephritis on kidney lifespan 

Chart showing how just one renal flare could shorten a kidney's lifespan by decades

Adapted with permission from Anders HJ, et al., 2020.

45% of patients with lupus nephritis experience renal flares despite receiving immunosuppressive therapy20,23*

It is critical to reduce the number of renal flares to prevent progression to ESKD and the need for dialysis20,22

* Renal flares are defined as a rise in serum creatine level and/or proteinuria, abnormal urinary sediment, or reduction in creatine clearance.20,22

CKD = chronic kidney disease; GFR = glomerular filtration rate.

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Efficacy for lupus

BENLYSTA helped appropriate patients with lupus.

SEE EFFICACY DATA

How BENLYSTA works

Discover the mechanism of action of BENLYSTA, designed to target BLyS, an underlying cause of lupus.

LEARN ABOUT THE MOA

The risk of organ damage is real.
Act now—talk to your patients about the risk.

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. Guidelines for referral and management of systemic lupus erythematosus in adults. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheumatol. 1999;42(9):1785-1796.

  2. 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.

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

  4. Arbuckle MR, McClain MT, Rubertone MW, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349(16):1526-1533.

  5. Ruperto N, Hanrahan LM, Alarcón GS, et al. International consensus for a definition of disease flare in lupus. Lupus. 2011;20(5):453-462.

  6. Zharkova O, Celhar T, Cravens PD, et al. Pathways leading to an immunological disease: systemic lupus erythematosus. Rheumatology (Oxford). 2017;56(suppl_1):i55-i66.

  7. Mok C, Lau C. Pathogenesis of systemic lupus erythematosus. J Clin Path. 2003;56(7):481-490.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Bertsias G, Cervera R, Boumpas DT. Systemic lupus erythematosus: pathogenesis and clinical features. In: Bijlsma JWJ, Hachulla E, eds. EULAR textbook on rheumatic diseases. 2012;5:476-505.

  13. Al Sawah S, Zhang X, Zhu B, et al. Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus – the Hopkins Lupus Cohort. Lupus Sci Med. 2015;2(1):e000066.

  14. Sheane BJ, Gladman DD, Su J, et al. Disease outcomes in glucocorticosteroid-naive patients with systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2017;69(2):252-256.

  15. 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.

  16. Yen EY, Singh RR. Lupus: an unrecognized leading cause of death in young females: a population-based study using nationwide death certificates, 2000–2015. Arthritis Rheumatol. 2018;70(8):1251-1255.

  17. Stoll T, Sutcliffe N, Mach J, et al. Analysis of the relationship between disease activity and damage in patients with systemic lupus erythematosus—a 5-yr prospective study. Rheumatology (Oxford). 2004;43(8):1039-1044.

  18. Mahajan A, Amelio J, Gairy K, et al. Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: a pragmatic review mapping disease severity and progression. Lupus. 2020;29(9):1011-1020.

  19. Tektonidou MG, Dasgupta A, Ward MM. Risk of end-stage renal disease in patients with lupus nephritis, 1971-2015: a systematic review and Bayesian meta-analysis. Arthritis Rheumatol. 2016;68(6):1432-1441.

  20. Anders HJ, Saxena R, Zhao MH, et al. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):7.

  21. Rijnink EC, Teng YKO, Wilhelmus S, et al. Clinical and histopathologic characteristics associated with renal outcomes in lupus nephritis. Clin J Am Soc Nephrol. 2017;12(5):734-743.

  22. Sprangers B, Monahan M, Appel GB. Diagnosis and treatment of lupus nephritis flares—an update. Nat Rev Nephrol. 2012;8(12):709-717.

  23. Illei GG, Takada K, Parkin D, et al. Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term followup of a cohort of 145 patients participating in randomized controlled studies. Arthritis Rheum. 2002;46(4):995-1002.