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Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: A European Scleroderma Trials and Research (EUSTAR) analysis
- Source :
- Annals of the Rheumatic Diseases, Annals of the Rheumatic Diseases, vol. 78, no. 9, pp. 1242-1248, ANNALS OF THE RHEUMATIC DISEASES, Volume 78, Issue 9, Annals of the Rheumatic Diseases, Vol. 78, No 9 (2019) pp. 1242-1248
- Publication Year :
- 2019
- Publisher :
- BMJ Publishing Group, 2019.
-
Abstract
- PubMed: 31227488<br />Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.<br />Bayer Bayer, United Kingdom Université Paris Descartes Li Ka Shing Foundation, LKSF University of Michigan, U-M<br />1Department of Rheumatology and the Centre of experimental Rheumatology, University Hospital Zurich, Zurich, switzerland 2Graf Biostatistics, Winterthur, switzerland 3Big Data institute, li Ka shing Centre for Health information and Discovery, nuffield Department of Medicine, University of Oxford, Oxford, UK 4Rheumatology a Department, Paris Descartes University, sorbonne Paris Cité, Cochin Hospital, Paris, France 5Data science and analytics, Bayer plc, Reading, UK 6UCl Division of Medicine, Royal Free Campus, london, UK 7Division of Rheumatology, Department of internal Medicine, University of Michigan scleroderma Program, University of Michigan, ann arbor, Michigan, Usa 8Department of experimental and Clinical Medicine, University of Florence, Florence, italy 9Bayer Us llC, Whippany, new Jersey, Usa 10Department of Medicine, Division of Rheumatology, University of Western Ontario, st. Joseph’s Health Care, london, Ontario, Canada Acknowledgements The R-code for the linear Mi-lassO was received from Qixuan Chen.21 Medical writing assistance was provided by adelphi Communications ltd (Bollington, UK), funded by Bayer aG (Berlin, Germany).<br />Contributors study conception and design, acquisition of data, analysis and interpretation of data and drafting and revising the article: OD and MB; analysis and interpretation of data: OD, MB, Rs and nG. all authors have critically reviewed and approved the final submitted version to be published. Funding This study was supported by a grant from Bayer aG. Bayer employees are coauthors of this paper and supported the study design and interpretation of the data, but otherwise Bayer had no influence on the study.<br />Competing interests MOB declares no conflict of interest. OD has had consultancy relationships with actelion, Bayer, Biogen idec, Boehringer ingelheim, Chemomab, espeRare foundation, Genentech/Roche, GsK, inventiva, italfarmaco, lilly, medac, Medimmune, Mitsubishi Tanabe Pharma, Pharmacyclics, novartis, Pfizer, sanofi, sinoxa and UCB in the area of potential treatments of scleroderma and its complications. OD has received research funding from actelion, Bayer, Boehringer ingelheim, Mitsubishi Tanabe Pharma and Roche in the area of potential treatments of scleroderma and its complications. OD has a patent for mir-29 licensed for the treatment of systemic sclerosis. DK has consultancy relationships and/or has received grant/research support from Bayer, Bristol-Myers squibb, Boehringer ingelheim, Genentech/Roche, niH, Pfizer, sanofi-aventis Pharmaceuticals, actelion Pharmaceuticals Us, Chemomab, Corbus, Covis, Cytori, eicos, eMD serono, Gilead, GlaxosmithKline, and UCB Pharma. He is a shareholder of eicos. CPD has consultancy relationships with and/or has received speakers’ bureau fees from actelion Pharmaceuticals Us, Bayer aG, GlaxosmithKline, Csl Behring, Merck serono, Roche Pharmaceuticals, Genentech and Biogen iDeC inc., inventiva, sanofi-aventis Pharmaceuticals and Boehringer ingelheim. JeP has consultancy relationships with and/or has received grant/research support from actelion, Bayer aG, Bristol-Myers squibb, Merck, Pfizer inc. and Roche. MM-C has consultancy relationships and/ or has received grant/research support from Pfizer, Bristol-Myers squibb, actelion, UCB Pharma, Bayer, Chemomab, Genentech/Roche, inventiva and lilly. Ya has consultancy relationships with and/or has received grant/research support from actelion, Pharmaceuticals Us, Bayer aG, Bristol-Myers squibb, inventiva, Medac, Pfizer inc., Roche Pharmaceuticals, Genentech and Biogen iDeC inc., sanofi-aventis Pharmaceuticals and servier. JdOP and JC are employees of Bayer. nTG has nothing to disclose.
- Subjects :
- INVOLVEMENT
SELECTION
BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences
diffuse
predictive factors
systemic sclerosis
2745 Rheumatology
epidemiologic methods
morbidity
Disease
Immunology
General Biochemistry, Genetics and Molecular Biology
Immunology and Allergy
Rheumatology
INTERSTITIAL LUNG-DISEASE
disease worsening, mortality, predictive factors, systemic sclerosis
predictive factor
disease worsening
DESIGN
middle aged
Medicine and Health Sciences
FIBROSIS
scleroderma
SKIN THICKNESS SCORE
mortality
skin and connective tissue diseases
Prospective cohort study
humans
lung diseases
ddc:616
education.field_of_study
heart diseases
integumentary system
clinical trials as topic
BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti
10051 Rheumatology Clinic and Institute of Physical Medicine
Interstitial lung disease
follow-up studies
ddc
female
Cohort
2723 Immunology and Allergy
europe
Life Sciences & Biomedicine
CLINICAL-TRIALS
survival rate
medicine.medical_specialty
Population
610 Medicine & health
disease progression
male
1300 General Biochemistry, Genetics and Molecular Biology
Internal medicine
Severity of illness
REGRESSION
medicine
severity of illness index
education
Survival rate
METAANALYSIS
2403 Immunology
Science & Technology
Scleroderma, Systemic
business.industry
MORTALITY
systemic
medicine.disease
prospective studies
Clinical trial
prognosis
scleroderma, diffuse
scleroderma, systemic
Scleroderma, Diffuse
business
Subjects
Details
- Language :
- English
- ISSN :
- 00034967 and 14682060
- Database :
- OpenAIRE
- Journal :
- Annals of the Rheumatic Diseases, Annals of the Rheumatic Diseases, vol. 78, no. 9, pp. 1242-1248, ANNALS OF THE RHEUMATIC DISEASES, Volume 78, Issue 9, Annals of the Rheumatic Diseases, Vol. 78, No 9 (2019) pp. 1242-1248
- Accession number :
- edsair.doi.dedup.....45d4c581e2f87ab3455d8d9e71513603