Clinical Burden of Systemic Lupus Erythematosus (SLE

Clinical Burden of Systemic Lupus

Erythematosus (SLE): Organ Damage and Mortality

©2020 AstraZeneca. All rights reserved. US-46887 Last Updated 10/20

©2020 AstraZeneca. All rights reserved.US-46887 Last Updated 10/20

Patients With SLE Can Experience Significant Clinical Burden

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References: 1. Urowitz MB, Gladman DD, Ibanez, et al. Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort. Arthritis Care Res (Hoboken). 2012;64(1):132-137. 2. Peschken CA, Wang Y, Abrahamowicz M, et al. Persistent disease activity remains a burden for patients with systemic lupus erythematosus. J Rheumatol. 2019;46(2):166-175. 3. Giannakou I, Chatzidionysiou K, Magder LS, Gyori N, van Vollenhoven R, Petri MA. Predictors of persistent disease activity and long quiescence in systemic lupus erythematosus: results from the Hopkins Lupus Cohort. Lupus Sci Med. 2018;5(1):e000287. 4. Segura BT, Bernstein BS, McDonnell T, et al. Damage accrual and mortality over long-term follow-up in 300 patients with systemic lupus erythematosus in a multi-ethnic British cohort. Rheumatology (Oxford). 2020;59(3):524-533.

Organ damage accrual1

High corticosteroid usage2,3

Increased mortality4

SLE is often associated with:

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Organ Damage Accrues Over Time in Patients With SLE

• A multicenter inception systemic lupus erythematosus cohort registry consisting of a diverse population of patients with SLE from 27 centers in 11 countries within 15 months of a diagnosis of SLE, based on the presence of American College of Rheumatology (ACR) classification criteria1

• Only patients followed for at least 5 years were included in this study1

• SDI assessed accumulated organ damage annually, since the onset of SLE, stemming from the disease and/or sequaelae1

• In a separate study of a Swedish SLE population (N=543), with a mean disease duration of 17 years, 59% of patients had acquired organ damage involving at least 1 organ domain2

1

2

1.5

0.5

0 54321

ACCRUAL OF ORGAN DAMAGE IN PATIENTS WITH SLE (n=298)1

Mea

n SL

ICC/

ACR

Dam

age

Inde

x (S

DI)

Sco

re*

Years in Registry

Irreversible organ damage continues to be a concern1,2

SLICC = Systemic Erythematosus International Collaborating Clinics.

* According to the SDI, damage in SLE is defined as an irreversible tissue injury occurring after diagnosis of SLE and lasting at least 6 months. Damage is assessed in 12 organ systems.1,3

References: 1. Urowitz MB, Gladman DD, Ibanez D, et al. Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort. Arthritis Care Res (Hoboken). 2012;64(1):132-137. 2. Frodlund M, Reid S, Wettero J, et al. The majority of Swedish systemic lupus erythematosus patients are still affected by irreversible organ impairment: factors related to damage accrual in two regional cohort. Lupus. 2019;28(10):1261-1272. 3. 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.

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The Importance of Limiting the Use of Corticosteroids

Increased corticosteroid use, especially in high doses, could result in long-term toxicity and organ damage1-4

— In an analysis of a prospective, longitudinal cohort study of 2265 patients with SLE followed over 26 years (mean follow-up of 6.2 years), the risks associated with a mean prednisone dose of ≥7.5 mg/day include an increase in the probability of cataracts, osteoporotic fractures, and cardiovascular damage4

References: 1. Mosca M, Tani C, Aringer M. Withdrawal of therapy in non-renal systemic lupus erythematosus: is this an achievable goal? Clin Exp Rheumatol. 2013;31(4 suppl 78):s71-s74. 2. Lateef A, Petri M. Unmet medical needs in systemic lupus erythematosus. Arthritis Res Ther. 2012;14(suppl 4):S4. 3. Thamer M, Hernan MA, Zhang Y, Cotter D, Petri M. Prednisone, lupus activity, and permanent organ damage. J Rheumatol. 2009;36(3):560-564. 4. 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.

RISK OF DAMAGE AT MEAN CORTICOSTEROID DOSES ≥7.5 MG/DAY VS <7.5 MG/DAY4

Renal damage 1.440 (0.863-2.403)

Cardiovascular damage 1.544 (1.018-2.341)P=0.041

P=0.163

Cataracts

Osteoporotic fractures 2.161 (1.546-3.022)

0 0.5 1 1.5 2 2.5 3

Hazard Ratio (95% CI)

2.412 (1.778-3.273)P<0.001

P<0.001

A reduction of ≥1 mg/day in mean prednisone dose reduces the estimated risk of future organ damage4

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Damage Accrual Correlates With Corticosteroid Dose1,2

• An observational study reported on 230 newly diagnosed patients with SLE3

• Damage was assessed using SDI scores calculated first at 6 months after SLE diagnosis, and then on a yearly basis, with 5 years of follow-up3

HR = hazard ratio.

*Received in the first year of follow-up.3

References: 1. Thamer M, Hernan MA, Zhang Y, Cotter D, Petri M. Prednisone, lupus activity, and permanent organ damage. J Rheumatol. 2009;36(3):560-564. 2. 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. 3. Ruiz-Arruza I, Ugarte A, Cabezas-Rodriguez I, Medina JA, Moran MA, Ruiz-Irastorza G. Glucocorticoids and irreversible damage in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2014;53(8):1470-1476.

SURVIVAL FREE-OF-DAMAGE CURVES IN PATIENTS WITH SLE WITHOUT EARLY ORGAN DAMAGE ACCORDING TO PREDNISONE DOSE (N=230)3*

0.25

0

0.50

1.00

0.75

0 1 2 3 4 5

Dam

age-

Free

Sur

viva

l

Years

Cumulative free-of- damage survival

No prednisone: 0.86 Low: 0.73Med: 0.64High: 0.44

HR of damage (95% CI)

1.7 (0.6-4.87)2.4 (0.96-6.2)7.2 (2.2-23.1)

No prednisoneMedium dose (≤30 mg/day)

Low dose (≤7.5 mg/day)High dose (>30 mg/day)

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Organ Damage as a Predictor of Mortality in Patients With SLE

Organ damage contributes to increased and early mortality in patients with SLE1-3

In a retrospective analysis of medical records and SDI scores of 300 patients in the United Kingdom for up to 40 years (median follow-up of 13.3 years)3:

• At the 1-year follow-up, signs of organ damage were observed in 13% of patients; 1.3% had an SDI >1

• Overall, 231 patients (N=300) developed damage:

-124 (53.7%) developed damage by year 5

-107 (46.3%) developed damage later

• The mean time to onset of damage was 9.5 years from diagnosis of SLE

• 35% of patients (81/231) with SLE who exhibited organ damage died during their follow-up compared with 8.7% without organ damage

*SDI scores were determined by chart review of both deceased and alive patients.3

References: 1. Doria A, Gatto M, Iaccarino L, Punzi L. Value and goals of treat-to-target in systemic lupus erythematosus: knowledge and foresight. Lupus. 2015;24(4-5):507-515. 2. Yee CS, Su L, Toescu V, et al. Birmingham SLE cohort: outcomes of a large inception cohort followed for up to 21 years. Rheumatology (Oxford). 2015;54(5):836-843. 3. Segura BT, Bernstein BS, McDonnell T, et al. Damage accrual and mortality over long-term follow-up in 300 patients with systemic lupus erythematosus in a multi-ethnic British cohort. Rheumatology (Oxford). 2020;59(3):524-533.

0.25

0

0.5

1.0

0.75

0 10 20 30 40

Surv

ival

Pro

babi

lity

Disease Duration (years)

Damage

Without damage

Without damage (n=69)

Damage (n=231)

ORGAN DAMAGE LEADS TO DECREASED PROBABILITY OF SURVIVAL IN PATIENTS WITH SLE (n=300)3*

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Clinical Burden of Systemic Lupus Erythematosus (SLE