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

Herrick, Ariane L; Pan, Xiaoyan; Peytrignet, Sébastien; Lunt, Mark; Hesselstrand, Roger LU ; Mouthon, Luc; Silman, Alan; Brown, Edith; Czirják, László and Distler, Jörg H W, et al. (2017) In Annals of the Rheumatic Diseases 76(7). p.1207-1218
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)... (More)

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.

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published
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keywords
Cyclophosphamide, Methotrexate, Systemic Sclerosis, Treatment
in
Annals of the Rheumatic Diseases
volume
76
issue
7
pages
12 pages
publisher
British Medical Association
external identifiers
  • scopus:85020703821
  • wos:000403074400014
ISSN
0003-4967
DOI
10.1136/annrheumdis-2016-210503
language
English
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yes
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c78f40d0-0b38-43bf-b220-76e05526147b
date added to LUP
2017-08-09 11:27:27
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2017-09-18 11:41:13
@article{c78f40d0-0b38-43bf-b220-76e05526147b,
  abstract     = {<p>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.</p>},
  author       = {Herrick, Ariane L and Pan, Xiaoyan and Peytrignet, Sébastien and Lunt, Mark and Hesselstrand, Roger and Mouthon, Luc and Silman, Alan and Brown, Edith and Czirják, László and Distler, Jörg H W and Distler, Oliver and Fligelstone, Kim and Gregory, William J. and Ochiel, Rachel and Vonk, Madelon and Ancuta, Codrina and Ong, Voon H. and Farge, Dominique and Hudson, Marie and Matucci-Cerinic, Marco and Balbir-Gurman, Alexandra and Midtvedt, Øyvind and Jordan, Alison C. and Jobanputra, Paresh and Stevens, Wendy and Moinzadeh, Pia and Hall, Frances C. and Agard, Christian and Anderson, Marina E. and Diot, Elisabeth and Madhok, Rajan and Akil, Mohammed and Buch, Maya H and Chung, Lorinda and Damjanov, Nemanja and Gunawardena, Harsha and Lanyon, Peter and Ahmad, Yasmeen and Chakravarty, Kuntal and Jacobsen, Søren and MacGregor, Alexander J. and McHugh, Neil and Müller-Ladner, Ulf and Riemekasten, Gabriela and Becker, Michael and Roddy, Janet and Carreira, Patricia E. and Fauchais, Anne-Laure and Hachulla, Eric and Hamilton, Jennifer and Inanç, Murat and McLaren, John S. and van Laar, Jacob M. and Pathare, Sanjay and Proudman, Susannah and Rudin, Anna and Sahhar, Joanne and Coppere, Brigitte and Serratrice, Christine and Sheeran, Tom and Veale, Douglas J. and Grange, Claire and Trad, Georges Selim and Denton, Christopher P},
  issn         = {0003-4967},
  keyword      = {Cyclophosphamide,Methotrexate,Systemic Sclerosis,Treatment},
  language     = {eng},
  month        = {07},
  number       = {7},
  pages        = {1207--1218},
  publisher    = {British Medical Association},
  series       = {Annals of the Rheumatic Diseases},
  title        = {Treatment outcome in early diffuse cutaneous systemic sclerosis : The European Scleroderma Observational Study (ESOS)},
  url          = {http://dx.doi.org/10.1136/annrheumdis-2016-210503},
  volume       = {76},
  year         = {2017},
}