Impact of SSc-ILD

Interstitial lung disease (ILD) is an important cause of mortality in patients with systemic sclerosis (SSc) and can have a negative impact on quality of life1-6

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ILD IS THE LEADING CAUSE OF DEATH IN SSc1

Pulmonary fibrosis is the leading cause of mortality in SSc, accounting for ~35% of SSc-related deaths1,2
Pulmonary fibrosis is the leading cause of morality in SSc, accounting for ~35% of SSc-related deaths

Causes of SSc-related deaths (1997–2001).
Adapted from: Steen VD and Mediger TA Ann Rheum Dis. 2007;66;944 and Tyndall AJ, et al. Ann Rheum Dis. 2010;69(10):1809-1815

 

1-, 5- and 10-year survival rates for SSc-ILD patients vs. SSc patients without ILD7

In a Canadian cohort of SSc-ILD patients, 5- and 10-year survival rates were 44.4% and 22% respectively7

Increased mortality / lower percentage survival rates for SSc-ILD patients compared to SSc patients

Adapted from: Pope JE, et al. Poster presented at the 6th Systemic Sclerosis World E-Congress 2020.

 

LUNG FIBROSIS AT BASELINE IS ASSOCIATED WITH INCREASED MORTALITY COMPARED WITH NO LUNG FIBROSIS IN PATIENTS WITH SSc-ILD8

In the Norwegian SSc-ILD cohort, fibrosis per se confers increased mortality risk in SSc-ILD8

Any extent of lung fibrosis at baseline has been shown to carry increased mortality risk in patients with SSc-ILD compared with the general population.8 This standard mortality rate increases with increasing extent of fibrosis.8

Norwegian SSc-ILD cohort cumulative survival was lower for patients with lung fibrosis

Cumulative survival rates at 1, 5 and 10 years after ILD diagnosis shown by Kaplan-Meier curves in a Norwegian cohort. Time to death in patients with normal ranged FVC% (FVC 80–100%) stratified by presence or absence of lung fibrosis by HRCT p<0.001.
Adapted from: Hoffmann-Vold A-M, et al. Am J Respir Crit Care Med. 2019;200:1258–1266.

 

In a Norwegian SSc-ILD patient cohort, >10% extent of fibrosis on HRCT was associated with significantly higher standard mortality rates8

Lung fibrosis per se confers increased mortality risk in SSc, shown for the first time in a Norwegian cohort study of patients with SSc (N=630).8 The SMR correlated with extent of fibrosis, with the highest SMR seen in patients with >10% fibrosis (SMR increased from 2.2 with no fibrosis to 8.0 with >25% fibrosis).8

Standard mortality rates in Norwegian SSc-ILD cohort positively correlate with extent of lung fibrosis

Adapted from: Hoffmann-Vold A-M, et al. Am J Respir Crit Care Med. 2019;200:1258–1266.

Extensive lung disease, classified as >20% disease extent on HRCT, is associated with higher mortality (HR 2.48, 95% CI 1.57–3.92, p<0.0005)9

A threshold of 20% disease extent on HRCT is associated with a substantial increase in mortality9

Extent of lung fibrosis on HRCT for SSc-ILD is a predictor of mortality

Kaplan-Meier survival curve of SSc-ILD patients with HRCT disease extent >20% (n=64) and patients with HRCT and patients with HRCT disease extent ≤20% (n=151).
Adapted from Goh NS, et al. AM J Respir Crit Care Med. 2008;177:1248-1254.

>10% extent of fibrosis on HRCT is associated with significantly higher mortality8

Ensure your SSc patients undergo baseline lung HRCT screening for ILD8,10,11

 

EVEN SMALL ANNUAL FVC DECLINES OF <5% PREDICTED CAN LEAD TO MORTALITY WITHIN 4–8 YEARS IN PATIENTS WITH SSc-ILD12

Some studies have suggested FVC decline is most rapid early in the course of SSc-ILD and may stabilize after the first 4 years.12 However, recent evidence indicates that FVC decline in SSc-ILD does not plateau after an initial period of progression but instead progresses at distinct rates that correlate with different mortality time frames.12

SSc-ILD shows heterogenous rates of progression but is fundamentally progressive over the long term12,13

Progression of FVC % predicted in patients with SSc-ILD categorized by prognostic groups12
FVC percentage predicted progression was significantly lower in patients

Progression of FVC (% predicted) in 171 patients with SSc-ILD categorized by prognostic groups.
Adapted from: Guler SA, et al. Ann Am Thorac Soc. 2018;15,1427–1433.

Low FVC (% predicted) and decline in FVC are predictors of mortality in SSc-ILD14

In a long-term UK study, annual relative FVC declines of ≥10% predicted over 12 months were strongly associated with mortality of SSc-ILD patients over 15 years (HR 1.84, 95% CI 1.14–2.97, p=0.01)14

FVC decline predicted / FVC decline of 10% or more is a greater predictor of SSc-ILD mortality

Kaplan-Meier survival curve for a cohort of 162 SSc-ILD patients according to FVC decline <10% and FVC decline ≥10%.
Adapted from: Goh NS, et al. Arthritis Rheumatol. 2017;69;1670–1678.

FVC <80% predicted at baseline is a predictor of mortality in SSc-ILD1
FVC decline predicted / FVC decline of 10% or more is a greater predictor of SSc-ILD mortality

Kaplan-Meier graphs for SSc survival on the basis of the follow-up data of 2,940 patients of whom 294 died. SSc mortality is plotted according to the presence or absence of pulmonary restrictions.
Adapted from: Tyndall AJ, et al. Ann Rheum Dis. 2010;69(10);1809-1815

Aim to slow decline in FVC as part of the treatment goal to delay ILD progression in SSc-ILD10

 

OLDER AGE AT PRESENTATION, MALE SEX, EXTENT OF LUNG FIBROSIS, LOW BASELINE VALUES AND DECLINES IN FVC AND DLCO ARE ALL RISK FACTORS FOR MORTALITY IN SSc-ILD1,8,14-16

 

 

Risk factors for mortality in SSc-ILD

Age

Older age at presentation15,17

Sex

Male15,17

FVC

<80%1

DLCO

Baseline DLCO % predicted <40%18

DLCO % predicted <40%1

Decline DLCO predicted <15%19

Extent of fibrosis on HRCT

>10% disease extent on HRCT8

Smoking

Active smoking and history of smoking12,15

Older age at diagnosis has been shown to negatively affect survival
(HR 1.04, 95% CI 1.03–1.05)17

Older age at diagnosis has been shown to negatively affect survival (HR 1.04, 95% CI 1.03–1.05)17
Male sex is associated with early mortality in SSc-ILD
(HR 1.81, 95% CI 1.29–2.55)17,20

Male sex is associated with early mortality in SSc-ILD (HR 1.81, 95% CI 1.29–2.55)17,20

SYMPTOMS OF ILD CAN HAVE A NEGATIVE IMPACT ON QUALITY OF LIFE IN PATIENTS WITH SSc-ILD3-6

Symptoms of cough and dyspnea may compromise patients’ quality of life and adversely affect patients’ ability to perform activities central to their daily lives21

Symptoms of SSc-ILD can be significant contributors to reduced quality of life21,22
Social impact

Social impact
Impacts sleep and health

Impacts sleep and health
Impact on well-being and productivity

Impact on well-being and productivity
Emotional impact

Emotional impact

SSc-ILD patients experience fatigue, depression as well as significant impacts on their well-being and productivity.22

Symptoms of ILD can have negative effects on patients’ quality of life22

Impact on well-being

Productivity loss

Need for support

22.6% of SSc-ILD patients have depression

40.4% of SSc-ILD patients retire early

2.0% of SSc-ILD patients need paid caregiver
support (e.g. nurse)

40.3% of SSc patients experience fatigue

11.9 Years between actual retirement and legal
age for it

37.7% of SSc-ILD patients need support from an
unpaid caregiver (e.g. family memeber)

44.7% of extensive SSc-ILD have permanent
            disability (8.5% of limited SSc-ILD)

22.3 Hours of work unpaid carers dedicate to a
SSc-ILD patient, weekly

29.3% of extensive SSc-ILD lost their job due to
their disease (5% of limited SSc-ILD)

100% of panelists agree that unpaid caregivers
have impacted quality of life

Adapted from: Wuyts W, et al. 2020. Poster presented at the 6th Systemic Sclerosis World E-Congress 2020.

 

ACUTE EXACERBATION OF ILD IS A SIGNIFICANT PREDICTOR OF POOR OUTCOME AND SHORTER SURVIVAL IN SSc-ILD23

In a Japanese cohort, 4 out of 35 patients with SSc-ILD developed acute exacerbation of ILD during the follow-up period and all 4 died23

In a Japanese cohort, 4 out of 35 patients with SSc-ILD developed acute exacerbation of ILD during the follow-up period and all 4 died23
Survival curves for acute exacerbation of ILD in SSc-ILD in a Japanese study23

AE-ILD was a significant predictor of poor outcome in SSc-ILD (p=0.0013).

Survival of patients with SSc-ILD is lower following acute exacerbation of ILD

Adapted from: Okamoto M, et al. 2016;54;445–453.

 
 

How can you identify, treat and manage ILD in patients with SSc?

Footnotes
  • AE, acute exacerbation; CI, confidence interval; DLCO, diffusing capacity of the lung for carbon monoxide; DM, dermatomyositis; FVC, forced vital capacity; HR, hazard ratio; HRCT, high-resolution computed tomography; ILD, interstitial lung disease; KL-6, Krebs von den Lungen-6; PM, polymyositis; SMR, standard mortality rate; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease; UIP, usual interstitial pneumonia.

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  7. Pope JE, Quansah K, Kolb M, et al. Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) in Canada’s largest province: an estimate of the prevalence and survival of SSc and SSc-ILD in Ontario over 10 years. Poster presented at the 6th Systemic Scelerosis World E-Congress 2020.
  8. Hoffmann-Vold AM, Fretheim H, Halse AK, et al. Tracking impact of interstitial lung disease in systemic sclerosis in a complete nationwide cohort. Am J Respir Crit Care Med. 2019;200;1258–1266.
  9. Goh NS, Desai SR., Veeraraghavan S, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008;177:1248–1254.
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  12. Guler, S.A., Winstone, T.A., Murphy, D., et al. Does systemic sclerosis–associated interstitial lung disease burn out? Specific phenotypes of disease progression. Annals ATS. 2018;15;1427–1433.
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  22. Wuyts W, Romild Davidson J, Kilpelainen M et al. Management and burden of disease of SSc-ILD in eight European countries: Results of the BUILDup project. Poster presented at the 6th Systemic Sclerosis World E-Congress 2020.
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