Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)

Ariane L Herrick; Xiaoyan Pan; Sébastien Peytrignet; Mark Lunt; Roger Hesselstrand; Luc Mouthon; Alan Silman; Edith Brown; László Czirják; Jörg H W Distler; Oliver Distler; Kim Fligelstone; William J Gregory; Rachel Ochiel; Madelon Vonk; Codrina Ancuţa; Voon H Ong; Dominique Farge; Marie Hudson; Marco Matucci-Cerinic; Alexandra Balbir-Gurman; Øyvind Midtvedt; Alison C Jordan; Paresh Jobanputra; Wendy Stevens; Pia Moinzadeh; Frances C Hall; Christian Agard; Marina E Anderson; Elisabeth Diot; Rajan Madhok; Mohammed Akil; Maya H Buch; Lorinda Chung; Nemanja 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 Inanc; John S McLaren; Jacob M van Laar; Sanjay Pathare; Susannah 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-2016-210503

Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)

Ariane L Herrick, Xiaoyan Pan, Sébastien Peytrignet, Mark Lunt, Roger Hesselstrand, Luc Mouthon, Alan Silman, Edith Brown, László Czirják, Jörg H W Distler, Oliver Distler, Kim Fligelstone, William J Gregory, Rachel Ochiel, Madelon Vonk, Codrina Ancuţa, Voon H Ong, Dominique Farge, Marie Hudson, Marco Matucci-CerinicAlexandra Balbir-Gurman, Øyvind Midtvedt, Alison C Jordan, Paresh Jobanputra, Wendy Stevens, Pia Moinzadeh, Frances C Hall, Christian Agard, Marina E Anderson, Elisabeth Diot, Rajan Madhok, Mohammed Akil, Maya H Buch, Lorinda Chung, Nemanja 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 Inanc, John S McLaren, Jacob M van Laar, Sanjay Pathare, Susannah Proudman, Anna Rudin, Joanne Sahhar, Brigitte Coppere, Christine Serratrice, Tom Sheeran, Douglas J Veale, Claire Grange, Georges-Selim Trad, Christopher P Denton

Institut for Klinisk Medicin

57 Citationer (Scopus)

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Abstract

Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.

Originalsprog	Engelsk
Tidsskrift	Annals of the Rheumatic Diseases
Vol/bind	76
Udgave nummer	7
Sider (fra-til)	1207-1218
ISSN	0003-4967
DOI	https://doi.org/10.1136/annrheumdis-2016-210503
Status	Udgivet - 1 jul. 2017

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10.1136/annrheumdis-2016-210503Licens: CC BY-NC

1207.fullForlagets udgivne version, 1,02 MBLicens: CC BY-NC

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Herrick, A. L., Pan, X., Peytrignet, S., Lunt, M., Hesselstrand, R., Mouthon, L., Silman, A., Brown, E., Czirják, L., Distler, J. H. W., Distler, O., Fligelstone, K., Gregory, W. J., Ochiel, R., Vonk, M., Ancuţa, C., Ong, V. H., Farge, D., Hudson, M., ... Denton, C. P. (2017). Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS). Annals of the Rheumatic Diseases, 76(7), 1207-1218. https://doi.org/10.1136/annrheumdis-2016-210503

Herrick, AL, Pan, X, Peytrignet, S, Lunt, M, Hesselstrand, R, Mouthon, L, Silman, A, Brown, E, Czirják, L, Distler, JHW, Distler, O, Fligelstone, K, Gregory, WJ, Ochiel, R, Vonk, M, Ancuţa, C, Ong, VH, Farge, D, Hudson, M, Matucci-Cerinic, M, Balbir-Gurman, A, Midtvedt, Ø, Jordan, AC, Jobanputra, P, Stevens, W, Moinzadeh, P, Hall, FC, Agard, C, Anderson, ME, Diot, E, Madhok, R, Akil, M, Buch, MH, Chung, L, Damjanov, N, 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, Inanc, M, McLaren, JS, van Laar, JM, Pathare, S, Proudman, S, Rudin, A, Sahhar, J, Coppere, B, Serratrice, C, Sheeran, T, Veale, DJ, Grange, C, Trad, G-S & Denton, CP 2017, 'Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)', Annals of the Rheumatic Diseases, bind 76, nr. 7, s. 1207-1218. https://doi.org/10.1136/annrheumdis-2016-210503

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title = "Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)",

abstract = "Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.",

keywords = "Adult, Antibodies, Antinuclear/immunology, Autoantibodies/immunology, Cohort Studies, Cyclophosphamide/therapeutic use, Early Medical Intervention, Europe, Female, Humans, Immunosuppressive Agents/therapeutic use, Male, Methotrexate/therapeutic use, Middle Aged, Mycophenolic Acid/therapeutic use, Nuclear Proteins/immunology, Prospective Studies, RNA Polymerase III/immunology, Scleroderma, Diffuse/drug therapy, Severity of Illness Index, Survival Rate, Treatment Outcome",

author = "Herrick, {Ariane L} and Xiaoyan Pan and S{\'e}bastien Peytrignet and Mark Lunt and Roger Hesselstrand and Luc Mouthon and Alan Silman 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 Madelon Vonk 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 Jordan, {Alison C} and Paresh Jobanputra 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 Nemanja Damjanov 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 Inanc and McLaren, {John S} and {van Laar}, {Jacob M} and Sanjay Pathare and Susannah Proudman 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 = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.",

year = "2017",

month = jul,

day = "1",

doi = "10.1136/annrheumdis-2016-210503",

language = "English",

volume = "76",

pages = "1207--1218",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "B M J Group",

number = "7",

}

TY - JOUR

T1 - Treatment outcome in early diffuse cutaneous systemic sclerosis

T2 - the European Scleroderma Observational Study (ESOS)

AU - Herrick, Ariane L

AU - Pan, Xiaoyan

AU - Peytrignet, Sébastien

AU - Lunt, Mark

AU - Hesselstrand, Roger

AU - Mouthon, Luc

AU - Silman, Alan

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

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 - Jordan, Alison C

AU - Jobanputra, Paresh

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

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 - Inanc, Murat

AU - McLaren, John S

AU - van Laar, Jacob M

AU - Pathare, Sanjay

AU - Proudman, Susannah

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 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.

AB - Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.

KW - Adult

KW - Antibodies, Antinuclear/immunology

KW - Autoantibodies/immunology

KW - Cohort Studies

KW - Cyclophosphamide/therapeutic use

KW - Early Medical Intervention

KW - Europe

KW - Female

KW - Humans

KW - Immunosuppressive Agents/therapeutic use

KW - Male

KW - Methotrexate/therapeutic use

KW - Middle Aged

KW - Mycophenolic Acid/therapeutic use

KW - Nuclear Proteins/immunology

KW - Prospective Studies

KW - RNA Polymerase III/immunology

KW - Scleroderma, Diffuse/drug therapy

KW - Severity of Illness Index

KW - Survival Rate

KW - Treatment Outcome

U2 - 10.1136/annrheumdis-2016-210503

DO - 10.1136/annrheumdis-2016-210503

M3 - Journal article

C2 - 28188239

SN - 0003-4967

VL - 76

SP - 1207

EP - 1218

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 7

ER -

Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)

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