Scleroderma Lung Involvement, Autoantibodies, and Outcome Prediction: The Confounding Effect of Time

Nihtyanova, Svetlana I.; Denton, Christopher P.

doi:10.3899/jrheum.170055

Cited by 13 publications

(12 citation statements)

References 19 publications

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“…Some studies have suggested that anti‐RNAP+ SSc patients tend to develop PF later in the disease course, in contrast to SSc patients with anti–topo I antibodies, in whom PF is an early complication . A major caveat for these types of analyses would be that the disease duration differs between subjects at study entry, which could significantly bias the estimation of time to event .…”

Section: Introductionmentioning

confidence: 99%

Using Autoantibodies and Cutaneous Subset to Develop Outcome‐Based Disease Classification in Systemic Sclerosis

Nihtyanova

Sarı

Harvey

et al. 2020

Arthritis & Rheumatology

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164

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Objective To describe the associations between autoantibodies, clinical presentation, and outcomes among patients with systemic sclerosis (SSc) in order to develop a novel SSc classification scheme that would incorporate both antibodies and the cutaneous disease subset as criteria. Methods Demographic and clinical characteristics, including cutaneous subset, time of disease and organ complication onset, and autoantibody specificities, were determined in a cohort of SSc subjects. Survival analysis was used to assess the effect of the autoantibodies on organ disease and death. Results The study included 1,325 subjects. Among the antibody/skin disease subsets, anticentromere antibody–positive patients with limited cutaneous SSc (lcSSc) (n = 374) had the highest 20‐year survival (65.3%), lowest incidence of clinically significant pulmonary fibrosis (PF) (8.5%) and scleroderma renal crisis (SRC) (0.3%), and lowest incidence of cardiac SSc (4.9%), whereas the frequency of pulmonary hypertension (PH) was similar to the mean value in the SSc cohort overall. The anti–Scl‐70+ groups of patients with lcSSc (n = 138) and patients with diffuse cutaneous SSc (dcSSc) (n = 149) had the highest incidence of clinically significant PF (86.1% and 84%, respectively, at 15 years). Anti‐Scl‐70+ patients with dcSSc had the lowest survival (32.4%) and the second highest incidence of cardiac SSc (12.9%) at 20 years. In contrast, in anti‐Scl‐70+ patients with lcSSc, other complications were rare, and these patients demonstrated the lowest incidence of PH (6.9%) and second highest survival (61.8%) at 20 years. Anti–RNA polymerase antibody–positive SSc patients (n = 147) had the highest incidence of SRC (28.1%) at 20 years. The anti–U3 RNP+ SSc group (n = 56) had the highest incidence of PH (33.8%) and cardiac SSc (13.2%) at 20 years. Among lcSSc patients with other autoantibodies (n = 295), the risk of SRC and cardiac SSc was low at 20 years (2.7% and 2.4%, respectively), while the frequencies of other outcomes were similar to the mean values in the full SSc cohort. Patients with dcSSc who were positive for other autoantibodies (n = 166) had a poor prognosis, demonstrating the second lowest survival (33.6%) and frequent organ complications. Conclusion These findings highlight the importance of autoantibodies, cutaneous subset, and disease duration when assessing morbidity and mortality in patients with SSc. Our novel classification scheme may improve disease monitoring and benefit future clinical trial designs in SSc.

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Section: Introductionmentioning

confidence: 99%

Using Autoantibodies and Cutaneous Subset to Develop Outcome‐Based Disease Classification in Systemic Sclerosis

Nihtyanova

Sarı

Harvey

et al. 2020

Arthritis & Rheumatology

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164

150

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“…Analyses of patient cohorts in the past few years has provided further insights into the timing and frequency of clinically important lung fibrosis development in SSc. Up to half of patients with dcSSc eventually develop severe lung fibrosis and many of these patients develop this complication within the first 3 years following diagnosis and can have considerable lung involvement at initial presentation [52,100]. This finding has important implications for treatment strategies aiming to prevent or attenuate worsening of disease.…”

Section: [H1] Classification Of Lung Involvement [H2] Classification mentioning

confidence: 99%

“…Other less common antinuclear antibodies (ANA) such as anti-U11/U12 ribonucleoprotein (RNP) antibodies or anti-Th/To RNP antibodies are also associated with lung fibrosis [101]. Interestingly, the presence of anti-centromere antibodies (ACA) or anti-RNA polymerase III antibodies (ARA) seems to be negatively associated with severe lung fibrosis [100,101] and so presence of these can be used to identify cases at lower risk in clinical practice and encourage further investigation of respiratory symptoms.…”

Section: [H1] Classification Of Lung Involvement [H2] Classification mentioning

confidence: 99%

“…Change in lung function, assessed by fall in FVC, is an important component of the newly developed composite response index for SSc clinical trials [113], and a decrease in lung function is associated with worse outcomes [114]. Finally, as discussed above, particular ANAs are also associated with an increased or decreased risk of lung fibrosis [100,101].…”

Section: [H2] Stratification By Lung Fibrosis Severitymentioning

confidence: 99%

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Major lung complications of systemic sclerosis

2018

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Systemic sclerosis (SSc) is associated with high mortality owing to internal organ complications, and lung disease is the leading cause of SSc-associated death. The most notable lung complications in SSc are fibrosis and pulmonary arterial hypertension (PAH). A major challenge for the management of lung disease in SSc is detecting those patients with severe pathology and those patients who are likely to benefit from available treatments. In the past few years, strategies for managing lung fibrosis and pulmonary hypertension, including PAH, have greatly progressed. For lung fibrosis, the tools to assess risk of progression and severity of the disease have been refined. Clinical trial results support the use of immunosuppression, including high-intensity regimens with autologous stem cell transplantation. New trials are underway to test other potential therapies including treatments that are approved for use in idiopathic lung fibrosis. For PAH, identifying individuals at high risk of disease development is critical. In addition, individuals who have borderline elevation of pulmonary arterial pressure need to be appropriately managed and followed up. Many approved drugs targeting PAH are now available, and results from large-scale clinical trials provide robust evidence that various treatments for SSc-associated PAH are associated with good long-term outcomes.

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“…50 Those with subclinical ILD at present but with a high-risk trajectory for developing progressive lung disease (e.g. early diffuse cutaneous disease with progressive skin involvement, positive SCL-70 antibody, or elevated CRP) should be initiated on immunomodulatory therapy that can be TCZ 20,21,51,52 or MMF based on our unpublished experience.…”

Section: Management Strategies: Goals Of Treatment In 2019mentioning

confidence: 99%

Treatment of systemic sclerosis–associated interstitial lung disease: Lessons from clinical trials

Roofeh

Distler

Allanore

et al. 2020

Journal of Scleroderma and Related Disorders

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Systemic sclerosis–associated interstitial lung disease remains a leading cause of mortality. Despite decades of clinical trials, the treatment effects of disease modifying anti-rheumatic drugs continue to be modest and there remains a great need for therapies that attenuate and hopefully ameliorate parenchymal lung disease. In this review, we highlight the key clinical trials that have shaped the management strategies employed by the authors, providing their strength of recommendation based on level of evidence. We also review lessons learned in more recent years, suggesting a benefit in targeting patients with subclinical interstitial lung disease with high risk for progression early in the disease course, as well as the benefit seen in a large clinical trial leading to the first Food and Drug Administration–approved treatment for systemic sclerosis–associated interstitial lung disease. These lessons come in a context of heterogeneity of patient populations and response to therapy, as well as the inherent constraints of time-limited studies to detect meaningful outcomes for patients.

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Scleroderma Lung Involvement, Autoantibodies, and Outcome Prediction: The Confounding Effect of Time

Cited by 13 publications

References 19 publications

Using Autoantibodies and Cutaneous Subset to Develop Outcome‐Based Disease Classification in Systemic Sclerosis

Using Autoantibodies and Cutaneous Subset to Develop Outcome‐Based Disease Classification in Systemic Sclerosis

Major lung complications of systemic sclerosis

Treatment of systemic sclerosis–associated interstitial lung disease: Lessons from clinical trials

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