scholarly journals Biomarkers in systemic sclerosis-associated interstitial lung disease: review of the literature

Rheumatology ◽  
2019 ◽  
Vol 58 (9) ◽  
pp. 1534-1546 ◽  
Author(s):  
Olivier Bonhomme ◽  
Béatrice André ◽  
Fanny Gester ◽  
Dominique de Seny ◽  
Catherine Moermans ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Wide Spectrum ◽  
Unknown Origin ◽  
Multiple Organ ◽  
Correct Identification ◽  
Review Of The Literature ◽  
Clinical Value ◽  
Diagnosis And Prognosis ◽  
Risk Of Progression

Abstract SSc is a rare disease of unknown origin associated with multiple organ involvement. One of the major complications that drives the mortality of SSc patients is interstitial lung disease. The course of SSc-interstitial lung disease progression has a wide spectrum. Since the treatment is based on aggressive immunosuppression it should not be given to stable or non-progressing disease. The correct identification of disease with high risk of progression remains a challenge for early therapeutic intervention, and biomarkers remain urgently needed. In fact, eight categories of biomarkers have been identified and classified according to the different biological pathways involved. The purpose of this article is to describe the main biomarkers thought to be of interest with clinical value in the diagnosis and prognosis of SSc-interstitial lung disease.

scholarly journals OP0269 A COMBINED CLINICAL AND BIOMARKER ALGORITHM TO PREDICT FVC DECLINE IN SYSTEMIC SCLEROSIS ASSOCIATED INTERSTITIAL LUNG DISEASE: RESULTS FROM AN INTERNATIONAL MULTICENTRE OBSERVATIONAL COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 163.2-164
Author(s):  
M. Hutchinson ◽  
G. Abignano ◽  
J. Blagojevic ◽  
S. L. Bosello ◽  
Y. Allanore ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Predictive Value ◽  
Large Population ◽  
Healthy Controls ◽  
Research Support ◽  
Clinical Value ◽  
Linear Predictor ◽  
Risk Of Progression

Background:Interstitial lung disease (ILD) is the leading cause of mortality in patients with Systemic Sclerosis (SSc). Forced Vital Capacity (FVC) is a major indicator of severity in SSc ILD. The ELF serum test and its constituent biomarkers (HA, PIIINP and TIMP-1) have shown to correlate with FVC in two large, independent multicentre cohorts of 457 patients, but also showed a correlation with age.Objectives:Here we aimed to investigate the relationship of the ELF biomarkers and age in a large population of healthy controls and to identify a combined clinical and biomarkers model to stratify for risk of ILD progression in a multicentre longitudinal cohort of patients with SSc.Methods:ELF score was measured in sera from 925 healthy controls in one centre and 869 longitudinal samples from 254 SSc patients from 6 centres across 4 European countries. Clinical data were recorded according to EUSTAR Minimal Essential dataset. FVC% change over time was estimated by Mixed-effects modelling. Patients were then divided in two groups: progressors, with a %FVC drop > 3%/year (according to published MCID) and a group of patients with stable or improving FVC. Lasso penalised regression was carried out with biomarkers and the available clinical and demographic variables at patient’s first visit as potential predictors. The resulting linear predictor was used to derive two thresholds, one for optimal sensitivity (rule-out) and one for optimal specificity (rule-in). Patients within thresholds were further selected according to the ratio of TIMP-1: PIIINP (Figure 1).Results:HA was the only ELF biomarker that correlated significantly with age in the healthy control cohort. Therefore, we defined by linear regression a “residual HA” which accounted for age. TIMP1, PIIINP and residual HA were then considered as distinct biomarkers in the analysis of the SSc cohort. 189 SSc patients with 785 time-points had complete datasets and were included in the analysis. Median follow up was 33 months (IQR 18-48). One-hundred and forty patients (74%) were classified as non progressors, 94 (50%) with no change or improving FVC and 46 (24%) with FVC drop <3% year. 49 patients (26%) were classed as progressors (drop of 3%/year or more in FVC, median slope -4.7%/year). Variable selection via Lasso penalised logistic regression resulted in a model with a c-index of 0.69 (95% CI: 0.60-0.78)) and contained age, disease duration (from first non-Raynaud’s symptom), residual HA, anti-centromere antibodies (ACA) status, previous diagnosis of ILD, joint synovitis and history of protein pump inhibitor use. A two-step process was developed using the linear predictor from the model and the ratio of TIMP-1 and PIIINP (Figure 1). The stratification tool increased by nearly two-fold the ability to predict progressors in any 12 months interval (46 to 49% predictive value vs 26% probability) identifying an 82 to 91% negative predictive value for progression.Conclusion:Building on the face and content validity of the biomarkers included in the ELF score, here we identify an easy to assess combined clinical and biomarker model to stratify patients for their risk of ILD progression. Despite its derivation from a large multicentre cohort, independent validation will determine the clinical value of Scleroscore as a stratification tool for risk of progression of SSc ILD.Disclosure of Interests:Michelle Hutchinson: None declared, Giuseppina Abignano: None declared, Jelena Blagojevic: None declared, Silvia Laura Bosello: None declared, Yannick Allanore Grant/research support from: Alpine, Boehringer Ingelheim, Genentech/Roche, Medsenic, and Sanofi, Christopher Denton Consultant of: Corbus, Actelion, GlaxoSmithKline, Bayer, Sanofi, Galapagos, Inventiva, Boehringer Ingelheim, Roche, CSL Behring, Acceleron, Horizon, Arxx Therapeutics, Grant/research support from: Corbus, Actelion, GlaxoSmithKline, Bayer, Sanofi, Galapagos, Inventiva, Boehringer Ingelheim, Roche, CSL Behring, Acceleron, Horizon, Arxx Therapeutics, Oliver Distler Consultant of: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB, Grant/research support from: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB, Paul Emery Consultant of: Lilly, Abbvie, Roche, Grant/research support from: Lilly, Marco Matucci-Cerinic Consultant of: Chemomab, Lilly, Abbvie, Actelion, Francesco Del Galdo Speakers bureau: Astra-Zeneca, Boehringer Ingelheim, Actelion, Consultant of: Astra-Zeneca, Mitsubishi-Tanabe, Capella Biosciences, Chemomab, Actelion, Boehringer-Ingelheim, Grant/research support from: Capella Biosciences, Chemomab, Kymab, Mitsubishi-Tanabe

scholarly journals Ongoing clinical trials and treatment options for patients with systemic sclerosis–associated interstitial lung disease

Rheumatology ◽  
2018 ◽  
Vol 58 (4) ◽  
pp. 567-579 ◽  
Author(s):  
Dinesh Khanna ◽  
Donald P Tashkin ◽  
Christopher P Denton ◽  
Martin W Lubell ◽  
Cristina Vazquez-Mateo ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Treatment Guidelines ◽  
Treatment Options ◽  
Multiple Organ ◽  
Organ Systems ◽  
The Uk ◽  
Disease Modifying Treatment ◽  
Substantial Morbidity

Abstract SSc is a rare CTD that affects multiple organ systems, resulting in substantial morbidity and mortality. Evidence of interstitial lung disease (ILD) is seen in ∼80% of patients with SSc. Currently there is no approved disease-modifying treatment for ILD and few effective treatment options are available. CYC is included in treatment guidelines, but it has limited efficacy and is associated with toxicity. MMF is becoming the most commonly used medication in clinical practice in North America and the UK, but its use is not universal. Newer agents targeting the pathogenic mechanisms underlying SSc-ILD, including fibrotic and inflammatory pathways, lymphocytes, cell–cell and cell–extracellular membrane interactions, hold promise for better treatment outcomes, including improved lung function, patient-related outcomes and quality of life. Here we review ongoing trials of established and novel agents that are currently recruiting patients with SSc-ILD.

The clinical value of surgical lung biopsy in 166 patients with suspected interstitial lung disease

2015 ◽  
Author(s):  
Lisa Nicol ◽  
David McAllister ◽  
Catriona Graham ◽  
Pauline McFarlane ◽  
Gareth Stewart ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Lung Biopsy ◽  
Clinical Value ◽  
Surgical Lung Biopsy

scholarly journals Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage

Thorax ◽  
2019 ◽  
Vol 75 (1) ◽  
pp. 92-95 ◽  
Author(s):  
Marie-Louise Frémond ◽  
Marie Legendre ◽  
Michael Fayon ◽  
Annick Clement ◽  
Emilie Filhol-Blin ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
T Lymphocytes ◽  
Lung Disease ◽  
Renal Dysfunction ◽  
Unknown Origin ◽  
Alveolar Haemorrhage ◽  
Healthy Controls ◽  
Functional Tests ◽  
Life Threatening ◽  
Copa Syndrome

COPA (coatomer subunit α) syndrome is a newly recognised cause of interstitial lung disease in children and adults, frequently associated with arthritis and renal dysfunction. We report a 11-year-old girl with disease limited to major pulmonary haemosiderosis manifesting at the age of 2 years, due to a heterozygous p.(Arg233His) mutation in COPA. Her interferon (IFN) signature was elevated (10.312 and 12.429, healthy <2.466), as was the level of serum IFNα (211 fg/mL, healthy <10 fg/mL). STAT1 phosphorylation in T lymphocytes and monocytes was increased as compared with healthy controls. Based on these results she was treated with the JAK1/2 inhibitor ruxolitinib, which resulted in reduction in IFN signalling and appeared to be associated with partial though incomplete decrease in the severity of her pulmonary disease. Patients with alveolar haemorrhage of unknown origin should be considered for COPA screening. Functional tests can help to personalise patient therapy.

scholarly journals Association between immunosuppressive therapy and course of mild interstitial lung disease in systemic sclerosis

Rheumatology ◽  
2019 ◽  
Vol 59 (5) ◽  
pp. 1108-1117 ◽  
Author(s):  
Sabrina Hoa ◽  
Sasha Bernatsky ◽  
Russell J Steele ◽  
Murray Baron ◽  
Marie Hudson ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Disease Duration ◽  
Immunosuppressive Drugs ◽  
Baseline Visit ◽  
Impaired Lung Function ◽  
Risk Of Progression ◽  
One Year ◽  
The One

Abstract Objective Interstitial lung disease (ILD) is a leading cause of mortality in SSc. Little is known about the benefits of immunosuppressive drugs in mild ILD. Our aim was to determine whether use of CYC or MMF was associated with an improved ILD course in patients with normal or mildly impaired lung function. Methods A retrospective cohort of SSc subjects with ILD, disease duration below seven years and no exposure to CYC or MMF prior to the baseline visit was constructed from the Canadian Scleroderma Research Group registry. Subjects were categorized as having mild ILD if baseline forced vital capacity (FVC % predicted) was &gt;85%. The primary exposure was any use of CYC or MMF at the baseline visit. FVC at one year was compared between exposed and unexposed subjects, using multivariate linear regression. Results Out of 294 eligible SSc-ILD subjects, 116 met criteria for mild ILD. In this subgroup, mean (s.d.) disease duration was 3.7 (2.0) years. Thirteen (11.2%) subjects were exposed to CYC or MMF at baseline. The one-year FVC was higher in exposed subjects compared with unexposed subjects, by a difference of 8.49% (95% CI: 0.01–16.98%). None of the exposed subjects experienced clinically meaningful progression over two years, whereas 24.6% of unexposed subjects did. Conclusion In this real-world setting, CYC/MMF exposure at baseline was associated with higher FVC values and a lower risk of progression among subjects with mild ILD. These data suggest a window of opportunity to preserve lung function in SSc-ILD.

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