Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

Ariane L Herrick; Sebastien Peytrignet; Mark Lunt; Xiaoyan Pan; Roger Hesselstrand; Luc Mouthon; Alan J Silman; Graham Dinsdale; Edith Brown; László Czirják; Jörg H W Distler; Oliver Distler; Kim Fligelstone; William J Gregory; Rachel Ochiel; Madelon C Vonk; Codrina Ancuţa; Voon H Ong; Dominique Farge; Marie Hudson; Marco Matucci-Cerinic; Alexandra Balbir-Gurman; Øyvind Midtvedt; Paresh Jobanputra; Alison C Jordan; Wendy Stevens; Pia Moinzadeh; Frances C Hall; Christian Agard; Marina E Anderson; Elisabeth Diot; Rajan Madhok; Mohammed Akil; Maya H Buch; Lorinda Chung; Nemanja S Damjanov; Harsha Gunawardena; Peter Lanyon; Yasmeen Ahmad; Kuntal Chakravarty; Søren Jacobsen; Alexander J MacGregor; Neil McHugh; Ulf Müller-Ladner; Gabriela Riemekasten; Michael Becker; Janet Roddy; Patricia E Carreira; Anne Laure Fauchais; Eric Hachulla; Jennifer Hamilton; Murat İnanç; John S McLaren; Jacob M van Laar; Sanjay Pathare; Susanna M Proudman; Anna Rudin; Joanne Sahhar; Brigitte Coppere; Christine Serratrice; Tom Sheeran; Douglas J Veale; Claire Grange; Georges-Selim Trad; Christopher P Denton

doi:10.1136/annrheumdis-2017-211912

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

Ariane L Herrick, Sebastien Peytrignet, Mark Lunt, Xiaoyan Pan, Roger Hesselstrand, Luc Mouthon, Alan J Silman, Graham Dinsdale, Edith Brown, László Czirják, Jörg H W Distler, Oliver Distler, Kim Fligelstone, William J Gregory, Rachel Ochiel, Madelon C Vonk, Codrina Ancuţa, Voon H Ong, Dominique Farge, Marie HudsonMarco Matucci-Cerinic, Alexandra Balbir-Gurman, Øyvind Midtvedt, Paresh Jobanputra, Alison C Jordan, Wendy Stevens, Pia Moinzadeh, Frances C Hall, Christian Agard, Marina E Anderson, Elisabeth Diot, Rajan Madhok, Mohammed Akil, Maya H Buch, Lorinda Chung, Nemanja S Damjanov, Harsha Gunawardena, Peter Lanyon, Yasmeen Ahmad, Kuntal Chakravarty, Søren Jacobsen, Alexander J MacGregor, Neil McHugh, Ulf Müller-Ladner, Gabriela Riemekasten, Michael Becker, Janet Roddy, Patricia E Carreira, Anne Laure Fauchais, Eric Hachulla, Jennifer Hamilton, Murat İnanç, John S McLaren, Jacob M van Laar, Sanjay Pathare, Susanna M Proudman, Anna Rudin, Joanne Sahhar, Brigitte Coppere, Christine Serratrice, Tom Sheeran, Douglas J Veale, Claire Grange, Georges-Selim Trad, Christopher P Denton

Department of Clinical Medicine

26 Citations (Scopus)

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Abstract

OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).

METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV).

RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%.

CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years.

TRIAL REGISTRATION NUMBER: NCT02339441.

Original language	English
Journal	Annals of the Rheumatic Diseases
Volume	77
Issue number	4
Pages (from-to)	563-570
Number of pages	8
ISSN	0003-4967
DOIs	https://doi.org/10.1136/annrheumdis-2017-211912
Publication status	Published - Apr 2018

Keywords

Adult
Area Under Curve
Disease Progression
Early Diagnosis
Female
Humans
Logistic Models
Male
Predictive Value of Tests
Prospective Studies
RNA Polymerase III/analysis
ROC Curve
Scleroderma, Diffuse/diagnosis
Severity of Illness Index
Skin/pathology
Skin Tests/statistics & numerical data

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Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational StudyFinal published version, 691 KBLicence: CC BY-NC

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Herrick, A. L., Peytrignet, S., Lunt, M., Pan, X., Hesselstrand, R., Mouthon, L., Silman, A. J., Dinsdale, G., Brown, E., Czirják, L., Distler, J. H. W., Distler, O., Fligelstone, K., Gregory, W. J., Ochiel, R., Vonk, M. C., Ancuţa, C., Ong, V. H., Farge, D., ... Denton, C. P. (2018). Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study. Annals of the Rheumatic Diseases, 77(4), 563-570. https://doi.org/10.1136/annrheumdis-2017-211912

Herrick, AL, Peytrignet, S, Lunt, M, Pan, X, Hesselstrand, R, Mouthon, L, Silman, AJ, Dinsdale, G, Brown, E, Czirják, L, Distler, JHW, Distler, O, Fligelstone, K, Gregory, WJ, Ochiel, R, Vonk, MC, Ancuţa, C, Ong, VH, Farge, D, Hudson, M, Matucci-Cerinic, M, Balbir-Gurman, A, Midtvedt, Ø, Jobanputra, P, Jordan, AC, Stevens, W, Moinzadeh, P, Hall, FC, Agard, C, Anderson, ME, Diot, E, Madhok, R, Akil, M, Buch, MH, Chung, L, Damjanov, NS, Gunawardena, H, Lanyon, P, Ahmad, Y, Chakravarty, K, Jacobsen, S, MacGregor, AJ, McHugh, N, Müller-Ladner, U, Riemekasten, G, Becker, M, Roddy, J, Carreira, PE, Fauchais, AL, Hachulla, E, Hamilton, J, İnanç, M, McLaren, JS, van Laar, JM, Pathare, S, Proudman, SM, Rudin, A, Sahhar, J, Coppere, B, Serratrice, C, Sheeran, T, Veale, DJ, Grange, C, Trad, G-S & Denton, CP 2018, 'Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study', Annals of the Rheumatic Diseases, vol. 77, no. 4, pp. 563-570. https://doi.org/10.1136/annrheumdis-2017-211912

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title = "Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study",

abstract = "OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV).RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%.CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years.TRIAL REGISTRATION NUMBER: NCT02339441.",

keywords = "Adult, Area Under Curve, Disease Progression, Early Diagnosis, Female, Humans, Logistic Models, Male, Predictive Value of Tests, Prospective Studies, RNA Polymerase III/analysis, ROC Curve, Scleroderma, Diffuse/diagnosis, Severity of Illness Index, Skin/pathology, Skin Tests/statistics & numerical data",

author = "Herrick, {Ariane L} and Sebastien Peytrignet and Mark Lunt and Xiaoyan Pan and Roger Hesselstrand and Luc Mouthon and Silman, {Alan J} and Graham Dinsdale and Edith Brown and L{\'a}szl{\'o} Czirj{\'a}k and Distler, {J{\"o}rg H W} and Oliver Distler and Kim Fligelstone and Gregory, {William J} and Rachel Ochiel and Vonk, {Madelon C} and Codrina Ancu{\c t}a and Ong, {Voon H} and Dominique Farge and Marie Hudson and Marco Matucci-Cerinic and Alexandra Balbir-Gurman and {\O}yvind Midtvedt and Paresh Jobanputra and Jordan, {Alison C} and Wendy Stevens and Pia Moinzadeh and Hall, {Frances C} and Christian Agard and Anderson, {Marina E} and Elisabeth Diot and Rajan Madhok and Mohammed Akil and Buch, {Maya H} and Lorinda Chung and Damjanov, {Nemanja S} and Harsha Gunawardena and Peter Lanyon and Yasmeen Ahmad and Kuntal Chakravarty and S{\o}ren Jacobsen and MacGregor, {Alexander J} and Neil McHugh and Ulf M{\"u}ller-Ladner and Gabriela Riemekasten and Michael Becker and Janet Roddy and Carreira, {Patricia E} and Fauchais, {Anne Laure} and Eric Hachulla and Jennifer Hamilton and Murat İnan{\c c} and McLaren, {John S} and {van Laar}, {Jacob M} and Sanjay Pathare and Proudman, {Susanna M} and Anna Rudin and Joanne Sahhar and Brigitte Coppere and Christine Serratrice and Tom Sheeran and Veale, {Douglas J} and Claire Grange and Georges-Selim Trad and Denton, {Christopher P}",

note = "{\textcopyright} Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.",

year = "2018",

month = apr,

doi = "10.1136/annrheumdis-2017-211912",

language = "English",

volume = "77",

pages = "563--570",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "B M J Group",

number = "4",

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TY - JOUR

T1 - Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

AU - Herrick, Ariane L

AU - Peytrignet, Sebastien

AU - Lunt, Mark

AU - Pan, Xiaoyan

AU - Hesselstrand, Roger

AU - Mouthon, Luc

AU - Silman, Alan J

AU - Dinsdale, Graham

AU - Brown, Edith

AU - Czirják, László

AU - Distler, Jörg H W

AU - Distler, Oliver

AU - Fligelstone, Kim

AU - Gregory, William J

AU - Ochiel, Rachel

AU - Vonk, Madelon C

AU - Ancuţa, Codrina

AU - Ong, Voon H

AU - Farge, Dominique

AU - Hudson, Marie

AU - Matucci-Cerinic, Marco

AU - Balbir-Gurman, Alexandra

AU - Midtvedt, Øyvind

AU - Jobanputra, Paresh

AU - Jordan, Alison C

AU - Stevens, Wendy

AU - Moinzadeh, Pia

AU - Hall, Frances C

AU - Agard, Christian

AU - Anderson, Marina E

AU - Diot, Elisabeth

AU - Madhok, Rajan

AU - Akil, Mohammed

AU - Buch, Maya H

AU - Chung, Lorinda

AU - Damjanov, Nemanja S

AU - Gunawardena, Harsha

AU - Lanyon, Peter

AU - Ahmad, Yasmeen

AU - Chakravarty, Kuntal

AU - Jacobsen, Søren

AU - MacGregor, Alexander J

AU - McHugh, Neil

AU - Müller-Ladner, Ulf

AU - Riemekasten, Gabriela

AU - Becker, Michael

AU - Roddy, Janet

AU - Carreira, Patricia E

AU - Fauchais, Anne Laure

AU - Hachulla, Eric

AU - Hamilton, Jennifer

AU - İnanç, Murat

AU - McLaren, John S

AU - van Laar, Jacob M

AU - Pathare, Sanjay

AU - Proudman, Susanna M

AU - Rudin, Anna

AU - Sahhar, Joanne

AU - Coppere, Brigitte

AU - Serratrice, Christine

AU - Sheeran, Tom

AU - Veale, Douglas J

AU - Grange, Claire

AU - Trad, Georges-Selim

AU - Denton, Christopher P

PY - 2018/4

Y1 - 2018/4

N2 - OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV).RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%.CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years.TRIAL REGISTRATION NUMBER: NCT02339441.

AB - OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV).RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%.CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years.TRIAL REGISTRATION NUMBER: NCT02339441.

KW - Adult

KW - Area Under Curve

KW - Disease Progression

KW - Early Diagnosis

KW - Female

KW - Humans

KW - Logistic Models

KW - Male

KW - Predictive Value of Tests

KW - Prospective Studies

KW - RNA Polymerase III/analysis

KW - ROC Curve

KW - Scleroderma, Diffuse/diagnosis

KW - Severity of Illness Index

KW - Skin/pathology

KW - Skin Tests/statistics & numerical data

U2 - 10.1136/annrheumdis-2017-211912

DO - 10.1136/annrheumdis-2017-211912

M3 - Journal article

C2 - 29306872

SN - 0003-4967

VL - 77

SP - 563

EP - 570

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 4

ER -

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

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Keywords

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