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

被引：112

作者：

Herrick, Ariane L. ^{[1
,2
]}

Pan, Xiaoyan ^{[3
]}

Peytrignet, Sebastien ^{[3
]}

Lunt, Mark ^{[3
]}

Hesselstrand, Roger ^{[4
]}

Mouthon, Luc ^{[5
]}

Silman, Alan ^{[6
]}

Brown, Edith ^{[7
]}

Czirjak, Laszlo ^{[8
]}

Distler, Joerg H. W. ^{[9
]}

Distler, Oliver ^{[10
]}

Fligelstone, Kim ^{[11
]}

Gregory, William J. ^{[12
]}

Ochiel, Rachel ^{[11
]}

Vonk, Madelon ^{[13
]}

Ancuta, Codrina ^{[14
]}

Ong, Voon H. ^{[15
]}

Farge, Dominique ^{[16
]}

Hudson, Marie ^{[17
,18
]}

Matucci-Cerinic, Marco ^{[19
]}

Balbir-Gurman, Alexandra ^{[20
]}

Midtvedt, Oyvind ^{[21
]}

Jordan, Alison C. ^{[22
]}

Jobanputra, Paresh ^{[22
]}

Stevens, Wendy ^{[23
]}

Moinzadeh, Pia ^{[24
]}

Hall, Frances C. ^{[25
]}

Agard, Christian ^{[26
]}

Anderson, Marina E. ^{[27
]}

Diot, Elisabeth ^{[28
]}

Madhok, Rajan ^{[29
]}

Akil, Mohammed ^{[30
]}

Buch, Maya H. ^{[31
,32
]}

Chung, Lorinda ^{[33
]}

Damjanov, Nemanja ^{[34
]}

Gunawardena, Harsha ^{[35
]}

Lanyon, Peter ^{[36
,37
]}

Ahmad, Yasmeen ^{[38
]}

Chakravarty, Kuntal ^{[39
]}

Jacobsen, Soren ^{[40
]}

MacGregor, Alexander J. ^{[41
]}

McHugh, Neil ^{[42
]}

Mueller-Ladner, Ulf ^{[43
]}

Riemekasten, Gabriela ^{[44
]}

Becker, Michael ^{[45
]}

Roddy, Janet ^{[46
]}

Carreira, Patricia E. ^{[47
]}

Fauchais, Anne Laure ^{[48
]}

Hachulla, Eric ^{[49
]}

Hamilton, Jennifer ^{[50
]}

机构：

[1] Univ Manchester, Salford Royal NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Ctr Musculoskeletal Res, Manchester, Lancs, England

[2] Cent Manchester NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, NIHR Manchester Musculoskeletal Biomed Res Unit, Manchester, Lancs, England

[3] Univ Manchester, Manchester Acad Hlth Sci Ctr, Ctr Musculoskeletal Res, Manchester, Lancs, England

[4] Lund Univ, Dept Rheumatol, Lund, Sweden

[5] Univ Paris 05, Hop Cochin, AP HP,Serv Med Interne, Ctr Reference Vasc Necrosantes & Sclerodermie Sys, Paris, France

[6] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England

[7] Univ Manchester, Steering Comm, Via Prof Herrick, Manchester, Lancs, England

[8] Univ Pecs, Med Ctr, Dept Rheumatol & Immunol, Pecs, Hungary

[9] Univ Erlangen Nurnberg, Dept Internal Med 3, Erlangen, Germany

[10] Univ Zurich, Dept Rheumatol, Zurich, Switzerland

[11] Royal Free London NHS Fdn Trust, London, England

[12] Salford Royal NHS Fdn, Rehabil Serv, Salford, Lancs, England

[13] Radboud Univ Nijmegen, Med Ctr, Dept Rheumat Dis, Nijmegen, Netherlands

[14] Grigore T Popa Univ Med & Pharm, Clin Rehabil Hosp, Rheumatol Dept 2, Iasi, Romania

[15] Ctr Rheumatol & Connect Tissue Dis, UCL Div Med, London, England

[16] Paris Denis Diderot Univ, Hop St Louis, AP HP,Vasc,UF 04,INSERM,UMRS 1160, Unite Clin Med Interne Malad Autoimmunes & Pathol, Paris, France

[17] Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada

[18] McGill Univ, Montreal, PQ, Canada

[19] Univ Florence, Dept Expt & Clin Med, Div Rheumatol AOUC, Florence, Italy

[20] Rappaport Fac Med, Shine Rheumatol Unit, Rambam Heath Care Campus, Haifa, Israel

[21] Oslo Univ Hosp, Rikshosp, Rheumatol Unit, Oslo, Norway

[22] UHB Fdn Trust, Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England

[23] St Vincents Hosp, Melbourne, Vic, Australia

[24] Univ Cologne, Dept Dermatol, Kerpenerstr 62, Cologne, Germany

[25] Cambridge Univ NHS Hosp Fdn Trust, Cambridge, England

[26] Univ Nantes, Hotel Dieu Hosp, Dept Internal Med, Nantes, France

[27] Univ Liverpool, Univ Hosp Aintree, Liverpool, Merseyside, England

[28] Hop Bretonneau Tours, Serv Med Interne, Tours, France

[29] Glasgow Royal Infirm, Ctr Rheumat Dis, Glasgow, Lanark, Scotland

[30] Sheffield Teaching Hosp, Sheffield, S Yorkshire, England

[31] Univ Leeds, Leeds Inst Rheumat & Musculoskeletal Med, Leeds, W Yorkshire, England

[32] Leeds Teaching Hosp NHS Trust, NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England

[33] Stanford Univ, Stanford, CA 94305 USA

[34] Univ Belgrade, Sch Med, Inst Rheumatol, Belgrade, Serbia

[35] North Bristol NHS Trust, Clin & Acad Rheumatol, Bristol, Avon, England

[36] Nottingham Univ Hosp NHS Trust, Nottingham, England

[37] Nottingham NHS Treatment Ctr, Nottingham, England

[38] Peter Maddison Rheumatol Ctr, Llandudno, England

[39] Queens Hosp, Romford, Essex, England

[40] Univ Copenhagen, Ctr Rheumatol & Spine Dis, Rigshosp, Copenhagen Lupus & Vasculitis Clin, Copenhagen, Denmark

[41] Univ East Anglia, Norwich Med Sch, Norwich, Norfolk, England

[42] Royal Natl Hosp Rheumat Dis, Bath, Avon, England

[43] Justus Liebig Univ Giessen, Dept Rheumatol & Clin Immunol, Bad Nauheim, Germany

[44] Univ Lubeck, Dept Rheumatol, Lubeck, Germany

[45] Univ Hosp Charite Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany

[46] Royal Perth Hosp, Dept Rheumatol, Perth, WA, Australia

[47] Hosp Univ 12 Octubre, Serv Reumatol, Madrid, Spain

[48] Limoges Univ Hosp, Internal Med Unit, Limoges, France

[49] Univ Lille, Ctr Natl Reference Malad Syst & Autoimmunes Rares, FHU Immune Mediated Inflammatory Dis & Targeted T, U995,Dept Med,Interne & Immunol Clin,INSERM, Lille, France

[50] Gateshead Hosp Fdn Trust, Gateshead, England

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2017年 / 76卷 / 07期

关键词：

HEALTH-ASSESSMENT QUESTIONNAIRE; SKIN THICKNESS SCORE; PROPENSITY SCORE; CYCLOPHOSPHAMIDE; PLACEBO; TRIALS; SURVIVAL; THERAPY;

D O I：

10.1136/annrheumdis-2016-210503

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1207 / 1218

页数：12

共 31 条

[1] Conditioning on the propensity score can result in biased estimation of common measures of treatment effect: A Monte Carlo study (p n/a) [J].

Austin, Peter C. ;

Grootendorst, Paul ;

Normand, Sharon-Lise T. ;

Anderson, Geoffrey M. .

STATISTICS IN MEDICINE, 2007, 26 (16) :3208-3210

[2] Variable selection for propensity score models [J].

Brookhart, M. Alan ;

Schneeweiss, Sebastian ;

Rothman, Kenneth J. ;

Glynn, Robert J. ;

Avorn, Jerry ;

Sturmer, Til .

AMERICAN JOURNAL OF EPIDEMIOLOGY, 2006, 163 (12) :1149-1156

[3]

CLEMENTS P, 1995, J RHEUMATOL, V22, P1281

[4]

Clements PJ, 2000, ARTHRITIS RHEUM-US, V43, P2445, DOI 10.1002/1529-0131(200011)43:11<2445::AID-ANR11>3.0.CO

[5]

2-Q

[6] Constructing inverse probability weights for marginal structural models [J].

Cole, Stephen R. ;

Hernan, Miguel A. .

AMERICAN JOURNAL OF EPIDEMIOLOGY, 2008, 168 (06) :656-664

[7]

Denton CP, 2007, ARTHRITIS RHEUM-US, V56, P323, DOI 10.1002/art.22289

[8] Controlling for time-dependent confounding using marginal structural models [J].

Fewell, Zoe ;

Hernan, Miguel A. ;

Wolfe, Frederick ;

Tilling, Kate ;

Choi, Hyon ;

Sterne, Jonathan A. C. .

STATA JOURNAL, 2004, 4 (04) :402-420

[9] Innovative research methods for studying treatments for rare diseases: methodological review [J].

Gagne, Joshua J. ;

Thompson, Lauren ;

O'Keefe, Kelly ;

Kesselheim, Aaron S. .

BMJ-BRITISH MEDICAL JOURNAL, 2014, 349

[10] The continuing unethical conduct of underpowered clinical trials [J].

Halpern, SD ;

Karlawish, JHT ;

Berlin, JA .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2002, 288 (03) :358-362

← 1 2 3 4 →