1 Systemic Lupus Erythematosus Translating Pathophysiology into New Therapies Traduciendo fisiopatologia en nuevos tratamentos Asociacion Costarricense Medicina Interna August 7, 2015 Arthur Weinstein, MD, FACP, FRCP, MACR Professor of Medicine, Georgetown University
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Systemic Lupus Erythematosus · Systemic Lupus Erythematosus Translating Pathophysiology into New Therapies Traduciendo fisiopatologia en nuevos tratamentos Asociacion Costarricense
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Systemic Lupus ErythematosusTranslating Pathophysiology into New Therapies
Traduciendo fisiopatologia en nuevos tratamentos
Asociacion Costarricense Medicina Interna
August 7, 2015
Arthur Weinstein, MD, FACP, FRCP, MACR
Professor of Medicine, Georgetown University
Dr. Srur, Dr. Acuña, Dr. Monge
Gracias por haberme invitado
a hablar en este congreso
SLE Disclosures
Research Investigator:
Rituximab (anti-CD20) for Lupus Nephritis (Genentech)
Epratuzumab (anti-CD22) for Lupus (Immunomedics and UCB)
Lymphostat B / Belimumab [Benlysta] (anti-Blys) for SLE – phases
1, 2 and 3 and extensions (HGS/GSK) -CURRENT
Cell-bound complement activation products for SLE diagnosis
(Exagen Diagnostics)- CURRENT
Consultant /Speakers Bureau:
HGS and GSK – Benlysta for SLE - past
Consultant /Board of Directors:
Exagen Diagnostics (stock holder) - CURRENT
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SLE History Clinical/Path Features
• 1850-1900 - skin disease (Cazenave, Kaposi,
von Hebra)
• 1900 - systemic disease -”erythema
exuditavum multiforme” (Osler and others)
• 1940’s – “collagen disease”
• modern era - SLE subsets – classes of renal
disease, subacute cutaneous LE, neonatal
lupus, antiphospholipid syndrome, “borrowed“
treatments
• present – markers of diagnosis and disease
activity, large controlled clinical trials
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SLE History
Autoimmunity
• 1946 - LE cells in marrow (Hargraves)
• 1954-57 - LE cell due to antibody to nuclei (ANA) (Miescher, Friou)
• 1957 - anti-DNA in SLE (Kunkel)
• 1970’s - low complement levels (Vaughan)
• 1980’s – antiphospholipid antibodies (Hughes)
• 2000’s – genome wide association studies (GWAS)
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SLE - Systemic Autoimmune Disease
Key Features
• Multisystem organ involvement– joints, skin, kidney, brain, serositis
• Microvascular inflammation – immediate and long term consequences
• Autoantibodies – ANA, anti-DNA, antibodies to red cells, white cells, platelets, other autoantibodies (anti-phospholipid)
Frequency of SLE
manifestations
‘Lupus Spectrum Disorders’
• Skin– Subacute cutaneous lupus, bullous lupus
• CNS– Myelopathy, neuromyelitis
– “Lupoid sclerosis”
• Renal– crescentic/progressive GN (ANCA), thrombotic microangiopathy
1. Yin et al. Lupus. 2012 Sep;21(10):1088-97. Diagnostic value of serum anti-C1q antibodies in patients with lupus nephritis: a meta-analysis.
2. Hanly et al. Ann Rheum Dis. 2011 Oct;70(10):1726-32. Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus.
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SLE Survival
2000’s
• max in middle aged >45yrs
• 44% of all rheumatic disease deaths
Bernatsky S, et al. Arthritis Rheum. 2006;54:2550-2557.
General Population
Rate of Death Compared to the Age-Matched General Population
19.2 X Greater Rate
8.0 X Greater Rate
1.4 X Greater Rate
SLE Patient Age (years)
3.7 X Greater Rate
≥6040-5925-3916-24
Rate of SLE Mortality Remains HighRelative to the General Population
Percentage of Patients With Permanent Organ Damage
Chambers SA, et al. Rheumatology (Oxford). 2009;48:673-675.
One-Third of SLE Patients Accrue Permanent Organ Damage Within 5 Years of Diagnosis and
50% within 10 years
Pe
rce
nt
of
Pat
ien
ts W
ith
SD
I ≥1
5 Years(N=232)
1 Year(N=232)
10 Years(N=232)
15 Years(N=143)
20 Years(N=75)
25 Years(N=6)
0.11 0.42 0.77 1.01 1.26 2.17Mean
Damage Score
Corticosteroids use an important contributor to long
term damage accrual- up to 50% in 15 years
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Pittsburgh lupus cohortCoronary Artery Disease in SLE
• 498 women with SLE - 33 developed CAD
(f/u 13 years, ages 15-74)
• 2208 women in the Framingham study 36 developed CAD