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 & 45 others 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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

LanguageEnglish
Pages1-8
JournalAnnals of the Rheumatic Diseases
Early online date6 Jan 2018
DOIs
StatusE-pub ahead of print - 6 Jan 2018

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Diffuse Scleroderma
Observational Studies
Skin
Area Under Curve
Randomized Controlled Trials
RNA Polymerase III
ROC Curve
Logistics
Logistic Models
Clinical Trials

Keywords

  • Journal Article

Cite this

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

In: Annals of the Rheumatic Diseases, 06.01.2018, p. 1-8.

Research output: Contribution to journalArticle

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, pp. 1-8. https://doi.org/10.1136/annrheumdis-2017-211912
Herrick, Ariane L ; Peytrignet, Sebastien ; Lunt, Mark ; Pan, Xiaoyan ; Hesselstrand, Roger ; Mouthon, Luc ; Silman, Alan J ; Dinsdale, Graham ; Brown, Edith ; Czirják, László ; Distler, Jörg H W ; Distler, Oliver ; Fligelstone, Kim ; Gregory, William J ; Ochiel, Rachel ; Vonk, Madelon C ; Ancuţa, Codrina ; Ong, Voon H ; Farge, Dominique ; Hudson, Marie ; Matucci-Cerinic, Marco ; Balbir-Gurman, Alexandra ; Midtvedt, Øyvind ; Jobanputra, Paresh ; Jordan, Alison C ; Stevens, Wendy ; Moinzadeh, Pia ; Hall, Frances C ; Agard, Christian ; Anderson, Marina E ; Diot, Elisabeth ; Madhok, Rajan ; Akil, Mohammed ; Buch, Maya H ; Chung, Lorinda ; Damjanov, Nemanja S ; Gunawardena, Harsha ; Lanyon, Peter ; Ahmad, Yasmeen ; Chakravarty, Kuntal ; Jacobsen, Søren ; MacGregor, Alexander J ; McHugh, Neil ; Müller-Ladner, Ulf ; Riemekasten, Gabriela ; Becker, Michael ; Roddy, Janet ; Carreira, Patricia E ; Fauchais, Anne Laure ; Hachulla, Eric ; Hamilton, Jennifer ; İnanç, Murat ; McLaren, John S ; van Laar, Jacob M ; Pathare, Sanjay ; Proudman, Susanna M ; Rudin, Anna ; Sahhar, Joanne ; Coppere, Brigitte ; Serratrice, Christine ; Sheeran, Tom ; Veale, Douglas J ; Grange, Claire ; Trad, Georges-Selim ; Denton, Christopher P. / Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study. In: Annals of the Rheumatic Diseases. 2018 ; pp. 1-8.
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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.",
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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

N1 - © 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.

PY - 2018/1/6

Y1 - 2018/1/6

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 - Journal Article

U2 - 10.1136/annrheumdis-2017-211912

DO - 10.1136/annrheumdis-2017-211912

M3 - Article

SP - 1

EP - 8

JO - Annals of the Rheumatic Diseases

T2 - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

ER -