scleroderma associated lung disease
TRANSCRIPT
2016 Patient Forum
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Jane Dematte MD, MBADirector, ILD program
Division of Pulmonary and Critical CareNorthwestern Feinberg School of Medicine
October 15, 2016
SclerodermaAssociated Lung
Disease
Northwestern Medicine
ILD Program
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
How does SSc affect the lungs?
• Interstitial Lung Disease• Aspiration Lung Injury• Pulmonary Vascular Disease
» Pulmonary arterial hypertension• Pulmonary Edema
» Pulmonary hypertension—Pulmonary arterial hypertension—Pulmonary venous hypertension
–
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Northwestern Medicine
ILD Program
What is Interstitial Lung Disease
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
How Common is ILD in SSc?
Prevalence ILD Serology
RA 19% +RF, +CCP
Scleroderma 25-85% +Scl 70 (30%)ACA 40-80% lc
SLE 3-33% dsDNA 50-80%Primary Sjogrens 9-75% antiSSa/SSb
(ro/la)
DM/PM/(AS syndrome) 20-65%
U1RNPAntisynthetase ABs (anti Jo-1)
40-80%MCTD 80% nRNP 100
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Northwestern Medicine
ILD Program
Pathologic and Radiographic Corrleates
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Interstitial Lung Disease vs Pulmonary Fibrosis
Northwestern Medicine
ILD Program
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Causes of SSc related deaths
Steen et al Annals of the Rheumatic Diseases 2007;66:940-944
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Severity of Disease
NSIP
Need a PFT in here
2/2012 Result % predictedFVC 2.06 55FEV1 1.60 62FEV1/FVC NL NLTLC 3.90 69FRC 2.36 86 (BMI 32)RV 1.84 84Dlco 11.9 52 Hgb range (10.1-
12)
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
What is the Impact of ILD
Northwestern Medicine
ILD Program
Association between severity of ILD and survival in patients with SSc. FVC, forced vital capacity; PF, pulmonary fibrosis; SSc, systemic sclerosis.
Steen et al. Arthritis Rheum 1994
N=890
University of Pittsburg Scleroderma databank
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Steen et al Annals of the Rheumatic Diseases 2007;66:940-944
Survival in Scleroderma
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Limited vs Extensive Ds: SSc ? RA
N=215
Northwestern Medicine
ILD ProgramGoh et al Am J Resp Crit Care Med; 177:1248-54 (2008)
Ds progressionDecline in FVC >10%Dlco >5%
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Who is at RiskKhanna et al; Arthritis Rheum Oct 2011; 63(10):3078
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Available Treatments
• Mycophenolate vs Cytoxan
• Rituxan
• Stem Cell transplant
• Lung transplant
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Scleroderma Lung Study II: Cytoxan v MMF
FVC mRSS
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Rituxin in SSc2 year fu study
Dauossis et al; Clin Exp Rheumatol 2012; 30 (Suppl. 71): S17-S22.
24m median inc 12.8% 24m median inc 19.5%
Northwestern Medicine
ILD Program
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
ASTIS SCOTN
randomized156 75
Transplant regimen
CYC 200 mg/kg, rabbit ATG 7.5 mg/kg, graft
manipulation CD4 selection
CYC 120 mg/kg, equine ATG 90 mg/kg, TBI 800 cGY lung shield, graft manipulation
CD4 selectionControl Arm 12x monthly CYC 750
mg/m212x monthly CYC 750
mg/m2
Primary endpoint
Event free Survival Composite, death & end stage organ failure at 56
monthsSecondary endpoints
TRM/toxicitymRSS
OSF/HAQ-DI
Deaths in both arms, no unexpected toxicity
Current status
Published Recruitment completed May 2011 in follow up
Prospective Randomized Trials of Stem Cell Txplant in SSc: SCOT and ASTIS
Tyndall, A. Nat. Rev. Rheumatol. Adc online pub 13 Sept 2011; doi:10.1038/nrrheum.2011.136
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
ASTISAutologous Stem cell Transplantation International Scleroderma
• 156 pts enrolled between March 2001 and Oct 2009
• Similar protocol and endpoint as SCOT
• Major differences are » No TBI» rabbit ATG
JAMA 2014;311(24):2490-98
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
HRs: (time varying): 3m 2.40 (p=.14), 6m 1.50 p=.38, 1yr .48 p=.02, 2yr .29 p=.002, thru 10 yr HR .29 p=.002
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Causes of Death
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Lung Transplant
2006 ISHLT endorsed Lung Transplantation for CT associated ILD
Respiratory Medicine (2013) 107, 2081-2087
Transplantation 2013; 95: 975-980Northwestern Medicine
ILD Program
N O R T H W E S T E R N U N I V E R S I T Y F E I N B E R G S C H O O L O F M E D I C I N E
Results: 5 year follow up
Northwestern Medicine
ILD Program
thank you!