Scleroderma Associated Lung Disease is presented by Jane Dematte MD, MBA, Director, ILD program Division of Pulmonary and Critical Care, Northwestern Feinberg School of Medicine

1. 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, MBA
Director, ILD program
Division of Pulmonary and Critical Care
Northwestern Feinberg School of Medicine
October 15, 2016
Scleroderma
Associated Lung
Disease
Northwestern Medicine
ILD Program

2. 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
–

3. 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

4. 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%
U1RNP
Antisynthetase ABs
(anti Jo-1)
40-80%
MCTD 80% nRNP 100

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
Northwestern Medicine
ILD Program
Pathologic and Radiographic Corrleates

6. 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

7. 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

8. 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 % predicted
FVC 2.06 55
FEV1 1.60 62
FEV1/FVC NL NL
TLC 3.90 69
FRC 2.36 86 (BMI 32)
RV 1.84 84
Dlco 11.9 52 Hgb range (10.1-12)

9. 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

10. 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

11. 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 Program
Goh et al Am J Resp Crit Care Med; 177:1248-54 (2008)
Ds progression
Decline in
FVC >10%
Dlco >5%

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
Fig 1. Survival of total IIP v.
CVD-IP
Park et al American Journal of Respiratory and Critical Care Medicine Vol 175. pp. 705-711, 2007
Fig 2. Comparison of the survival curves
of all subject groups CVD- UIP v. CVD-
NSIP; I- NSIP v. UIP
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=362, IIP 269, CT associated 93
UIP 203/269, 66/269 i-NSIP/36/93 UIP, 57 NSIP
CV :Younger, F, nonsmokers, no diff in baseline PFT
Northwestern Medicine
ILD Program

13. 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 Risk
Khanna et al; Arthritis Rheum Oct 2011; 63(10):3078

14. 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

15. 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

16. 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 SSc
2 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

17. 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 SCOT
N randomized 156 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
selection
Control Arm 12x monthly CYC 750 mg/m2 12x monthly CYC 750 mg/m2
Primary
endpoint
Event free Survival Composite, death & end stage
organ failure at 56 months
Secondary
endpoints
TRM/toxicity
mRSS
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

18. 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
Autologous 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

19. 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

20. 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

21. 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

22. 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

23. thank you!