Statistical and Molecular Genetic Analysis of Systemic Lupus Erythematosus(SLE)
Clinical Burden of Systemic Lupus Erythematosus (SLE ...
Transcript of 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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©2020 AstraZeneca. All rights reserved.US-46887 Last Updated 10/20
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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©2020 AstraZeneca. All rights reserved.US-46887 Last Updated 10/20
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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©2020 AstraZeneca. All rights reserved.US-46887 Last Updated 10/20
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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©2020 AstraZeneca. All rights reserved.US-46887 Last Updated 10/20
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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©2020 AstraZeneca. All rights reserved.US-46887 Last Updated 10/20
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