The Scleroderma Patient-Centered Intervention Network (SPIN ......The Scleroderma Patient-Centered...

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The University of Manchester Research The Scleroderma Patient-Centered Intervention Network (SPIN) Cohort: baseline clinical features and comparison to other large scleroderma cohorts DOI: 10.1093/rheumatology/key139 Document Version Accepted author manuscript Link to publication record in Manchester Research Explorer Citation for published version (APA): Dougherty, D. H., Kwakkenbos, L., Carrier, M-E., Salazar, G., Assassi, S., Baron, M., Bartlett, S. J., Furst, D. E., Gottesman, K., Van Den Hoogen, F., Malcarne, V. L., Mouthon, L., Nielson, W. R., Poiraudeau, S., Sauve, M., Boire, G., Bruns, A., Chung, L., Denton, C., ... Mayes, M. D. (2018). The Scleroderma Patient-Centered Intervention Network (SPIN) Cohort: baseline clinical features and comparison to other large scleroderma cohorts. Rheumatology. https://doi.org/10.1093/rheumatology/key139 Published in: Rheumatology Citing this paper Please note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscript or Proof version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version. General rights Copyright and moral rights for the publications made accessible in the Research Explorer are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Takedown policy If you believe that this document breaches copyright please refer to the University of Manchester’s Takedown Procedures [http://man.ac.uk/04Y6Bo] or contact [email protected] providing relevant details, so we can investigate your claim. Download date:02. Jan. 2021

Transcript of The Scleroderma Patient-Centered Intervention Network (SPIN ......The Scleroderma Patient-Centered...

Page 1: The Scleroderma Patient-Centered Intervention Network (SPIN ......The Scleroderma Patient-Centered Intervention Network (SPIN) Cohort: baseline clinical features and comparison to

The University of Manchester Research

The Scleroderma Patient-Centered Intervention Network(SPIN) Cohort: baseline clinical features and comparisonto other large scleroderma cohortsDOI:10.1093/rheumatology/key139

Document VersionAccepted author manuscript

Link to publication record in Manchester Research Explorer

Citation for published version (APA):Dougherty, D. H., Kwakkenbos, L., Carrier, M-E., Salazar, G., Assassi, S., Baron, M., Bartlett, S. J., Furst, D. E.,Gottesman, K., Van Den Hoogen, F., Malcarne, V. L., Mouthon, L., Nielson, W. R., Poiraudeau, S., Sauve, M.,Boire, G., Bruns, A., Chung, L., Denton, C., ... Mayes, M. D. (2018). The Scleroderma Patient-CenteredIntervention Network (SPIN) Cohort: baseline clinical features and comparison to other large scleroderma cohorts.Rheumatology. https://doi.org/10.1093/rheumatology/key139Published in:Rheumatology

Citing this paperPlease note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscriptor Proof version this may differ from the final Published version. If citing, it is advised that you check and use thepublisher's definitive version.

General rightsCopyright and moral rights for the publications made accessible in the Research Explorer are retained by theauthors and/or other copyright owners and it is a condition of accessing publications that users recognise andabide by the legal requirements associated with these rights.

Takedown policyIf you believe that this document breaches copyright please refer to the University of Manchester’s TakedownProcedures [http://man.ac.uk/04Y6Bo] or contact [email protected] providingrelevant details, so we can investigate your claim.

Download date:02. Jan. 2021

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The Scleroderma Patient-Centered Intervention Network (SPIN) Cohort: baseline 1

clinical features and comparison to other large scleroderma cohorts 2

3

Dane H. Dougherty, MD1; Linda Kwakkenbos, PhD2,3,4; Marie-Eve Carrier, MSc3; Gloria 4

Salazar, MD1; Shervin Assassi, MD1; Murray Baron, MD3,5; Susan J. Bartlett, PhD5,6,7; 5

Daniel E. Furst, MD8,9,10; Karen Gottesman, BA11; Frank van den Hoogen, MD, PhD12,13; 6

Vanessa L. Malcarne, PhD14,15; Luc Mouthon, MD, PhD16,17; Warren R. Nielson, 7

PhD18,19; Serge Poiraudeau, MD, PhD16,20,21; Maureen Sauvé, BA22,23; Gilles Boire, 8

MD24; Alessandra Bruns, MD24; Lorinda Chung, MD25; Christopher Denton, MD26; 9

James V. Dunne, MB,CHB27,28; Paul Fortin, MD29; Tracy Frech, MD30; Anna Gill, MD27; 10

Jessica Gordon, MD31; Ariane L Herrick, MD32; Monique Hinchcliff, MD33; Marie 11

Hudson, MD5,34; Sindhu R. Johnson, MD35,36; Niall Jones, MD37; Suzanne Kafaja, MD8; 12

Maggie Larche, MD38; Joanne Manning, HNC39; Janet Pope, MD40; Robert Spiera, 13

MD31; Virginia Steen, MD41; Evelyn Sutton, MD42; Carter Thorne, MD43; Pearce Wilcox, 14

MD28,29, Brett D. Thombs, PhD2,3,5,44-47; Maureen D. Mayes, MD, MPH1; on behalf of the 15

SPIN Investigators 16

17

1Department of Internal Medicine, Division of Rheumatology, University of Texas 18

McGovern Medical School, Houston, Texas, USA; 2Department of Psychiatry, McGill 19

University, Montreal, Quebec, Canada; 3Lady Davis Institute for Medical Research, 20

Jewish General Hospital, Montreal, Quebec, Canada; 4Behavioural Science Institute, 21

Clinical Psychology, Radboud University, Nijmegen, the Netherlands; 5Department of 22

Medicine, McGill University, Montreal, Quebec, Canada; 6Division of Rheumatology, 23

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Johns Hopkins School of Medicine, Baltimore, Maryland, USA; 7McGill University 1

Health Center, Montréal, Québec, Canada; 8Division of Rheumatology, Geffen School of 2

Medicine at the University of California, Los Angeles, Los Angeles, USA; 9University of 3

Washington,Seattle Washington; 10University of Florence, Florence, Italy; 11Scleroderma 4

Foundation, USA; 12Department of Rheumatology, Radboud University Medical Center, 5

Nijmegen, The Netherlands; 13Department of Rheumatology, Sint Maartenskliniek, 6

Nijmegen, The Netherlands; 14Department of Psychology, San Diego State University, 7

San Diego, California, USA; 15San Diego State University/ University of California, San 8

Diego Joint Doctoral Program in Clinical Psychology, San Diego, California, USA; 9

16Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Paris, 10

France; 17Service de Médecine Interne, Centre de Référence Maladies Systémiques 11

Autoimmunes Rares, vascularites nécrosantes et sclérodermie systémique, Hôpital 12

Cochin, Paris, France; 18Beryl & Richard Ivey Rheumatology Day Programs, St Joseph's 13

Health Care, London, Ontario, Canada; 19Lawson Health Research Institute, London, 14

Ontario, Canada; 20Service de Médecine Physique et Réadaptation, Hôpital Cochin, Paris, 15

France; 21IFR Handicap INSERM, Paris, France; 22Scleroderma Society of Ontario, 16

Hamilton, Ontario, Canada; 23Scleroderma Society of Canada, Ottawa, Ontario, 17

Canada; 24Sherbrooke University, Sherbrooke, Québec, Canada; 25Stanford University, 18

Stanford, California, USA; 26Royal Free London Hospital, London, UK; 27St. Paul's 19

Hospital, Vancouver, British Columbia, Canada; 28University of British Columbia, 20

Vancouver, British Columbia, Canada; 29Université Laval, Québec, Québec, 21

Canada; 30University of Utah, Salt Lake City, Utah, USA; 31Hospital for Special Surgery, 22

New York City, New York, USA; 32University of Manchester, Salford Royal NHS 23

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Foundation Trust, Manchester, UK; 33Northwestern University, Chicago, Illinois, 1

USA; 34Jewish General Hospital, Montréal, Québec, Canada; 35Toronto Scleroderma 2

Program, Mount Sinai Hospital, Toronto Western Hospital, Toronto, Ontario, 3

Canada; 36University of Toronto, Toronto, Ontario, Canada; 37University of Alberta, 4

Edmonton, Alberta, Canada; 38McMaster University, Hamilton, Ontario, 5

Canada; 39Salford Royal NHS Foundation Trust, Salford, UK; 40University of Western 6

Ontario, London, Ontario, Canada; 41Georgetown University, Washington, DC, 7

USA; 42Dalhousie University, Halifax, Nova Scotia, Canada; 43Southlake Regional 8

Health Centre, Newmarket, Ontario, Canada; 44Department of Epidemiology, 9

Biostatistics, and Occupational Health, McGill University, Montréal, Québec, 10

Canada; 45Department of Educational and Counselling Psychology, McGill University, 11

Montréal, Québec, Canada; 46Department of Psychology; and McGill University, 12

Montréal, Québec, Canada; 47School of Nursing, McGill University, Montréal, Québec, 13

Canada 14

15

Declaration of Conflicts of Interest: All authors reported that there are no conflicts of 16

interest to declare. 17

18

Word Count: 1987 19

20

Address for Correspondence: Linda Kwakkenbos, PhD; Jewish General Hospital; 4333 21

Côte-Sainte-Catherine Road; Montréal, Québec H3T 1E4; Tel: (514) 340-8222 ext. 8578; 22

Email: [email protected] 23

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FUNDING 1

SPIN is funded by the Canadian Institutes of Health Research (CIHR; PI = Thombs, 2

TR3-119192; PI = Thombs, PJT-148504; PIs = Thombs, Mouthon, Poiraudeau, PJT-3

149073) and the Arthritis Society (SOG-16-380, PI = Thombs). In addition, SPIN has 4

received institutional contributions from the Lady Davis Institute for Medical Research of 5

the Jewish General Hospital, Montreal, Quebec, Canada and from McGill University, 6

Montreal, Canada. SPIN has also received support from the Scleroderma Society of 7

Ontario, Scleroderma Canada, and Sclérodermie Quebec. Dr. Kwakkenbos was 8

supported by a CIHR Banting Postdoctoral Fellowship. Dr. Thombs was supported by an 9

Investigator Salary Award from the Arthritis Society. 10

11

ACKNOWLEDGEMENTS 12

SPIN Investigators: Alexandra Albert, Université Laval, Québec, Québec, Canada; 13

Guylaine Arsenault, Sherbrooke University, Sherbrooke, Québec, Canada; Lyne 14

Bissonette, Sherbrooke University, Sherbrooke, Québec, Canada; Isabelle Boutron, 15

Université Paris Descartes, and Assistance Publique-Hôpitaux de Paris, Paris, France; 16

Patricia Carreira, Servicio de Reumatologia del Hospital 12 de Octubre, Madrid, Spain; 17

Angela Costa Maia, University of Minho, Braga, Portugal; Pierre Dagenais, Sherbrooke 18

University, Sherbrooke, Québec, Canada; Robyn Domsic, University of Pittsburgh, 19

Pittsburgh, Pennsylvania, USA; Ghassan El-Baalbaki, Université du Québec à Montréal, 20

Montréal, Québec, Canada; Carolyn Ells, McGill University, Montréal, Québec, Canada; 21

Cornelia van den Ende, Sint Maartenskliniek, Nijmegen, The Netherlands; Kim 22

Fligelstone, Scleroderma Society, London, UK; Catherine Fortune, Scleroderma Society 23

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of Ontario, Hamilton, Ontario, Canada; Dominique Godard, Association des 1

Sclérodermiques de France, Sorel-Moussel, France; Genevieve Gyger, Department of 2

Medicine, McGill University, Montreal, Quebec, Canada; Daphna Harel, New York 3

University, New York, New York, USA; Alena Ikic, Université Laval, Québec, Québec, 4

Canada; Ann Impens, Midwestern University, Downers Grove, Illinois, USA; Yeona 5

Jang, McGill University, Montréal, Québec, Canada; Artur Jose de B. Fernandes, 6

Sherbrooke University, Sherbrooke, Québec, Canada; Ann Tyrell Kennedy, Federation of 7

European Scleroderma Associations, Dublin, Ireland; Nader Khalidi, McMaster 8

University, Hamilton, Ontario, Canada; Benjamin Korman, Northwestern University, 9

Chicago, Illinois, USA; Catarina Leite, University of Minho, Braga, Portugal; Patrick 10

Liang, Sherbrooke University, Sherbrooke, Québec, Canada; Carlo Marra, Memorial 11

University, St. John’s, Newfoundland, Canada; Ariel Masetto, Sherbrooke University, 12

Sherbrooke, Québec, Canada; Karen Nielsen, Scleroderma Society of Ontario, Hamilton, 13

Ontario, Canada; Alexandra Portales, Asociación Española de Esclerodermia, Madrid, 14

Spain; Robert Riggs, Scleroderma Foundation, USA; David Robinson, University of 15

Manitoba, Winnipeg, Manitoba, Canada; Tatiana Sofia Rodriguez Reyna, Instituto 16

Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 17

Sophie Roux, Sherbrooke University, Sherbrooke, Québec, Canada; Anne A. Schouffoer, 18

Leiden University Medical Center, Leiden, The Netherlands; Doug Smith, University of 19

Ottawa, Ottawa, Ontario, Canada; Russell J. Steele, Jewish General Hospital and McGill 20

University, Montréal, Québec, Canada; Maria E. Suarez-Almazor, University of Texas 21

MD Anderson Cancer Center, Houston, Texas, USA; John Varga, Northwestern 22

University, Chicago, Illinois, USA; Joep Welling, NVLE Dutch patient organization for 23

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systemic autoimmune diseases, Utrecht, The Netherlands; Fredrick Wigley, Division of 1

Rheumatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA; Durhane 2

Wong-Rieger, Canadian Organization for Rare Disorders, Toronto, Ontario, Canada; 3

Julie Cumin, Jewish General Hospital; Vanessa C. Delisle, Jewish General Hospital and 4

McGill University, Montréal, Québec, Canada; Claire Fedoruk, Jewish General Hospital, 5

Montréal, Québec, Canada; Rina S. Fox, San Diego State University and University of 6

California, San Diego, San Diego, California, USA; Shadi Gholizadeh, San Diego State 7

University and University of California, San Diego, San Diego, California, USA; Lisa R. 8

Jewett, Jewish General Hospital and McGill University, Montréal, Québec, Canada; 9

Brooke Levis, Jewish General Hospital and McGill University, Montréal, Québec, 10

Canada; Sarah D. Mills, San Diego State University and University of California, San 11

Diego, San Diego, California, USA; Mia R. Pepin, Jewish General Hospital, Montréal, 12

Québec, Canada; Jennifer Persmann, Université du Québec à Montréal, Montréal, 13

Québec, Canada; Kimberly Turner, Jewish General Hospital. 14

15

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ABSTRACT 1

Objective: The Scleroderma Patient-centered Intervention Network Cohort is a web-2

based cohort designed to collect patient-reported outcomes at regular intervals as a 3

framework to conduct trials of psychosocial, educational, self-management, and 4

rehabilitation interventions for patients with systemic sclerosis (SSc). The aim of this 5

study was to present baseline demographic, medical, and patient-reported outcome data 6

of the SPIN Cohort and to compare it with other large SSc cohorts. 7

Methods: Descriptive statistics were used to summarize SPIN Cohort characteristics; 8

these were compared to published data of the European Scleroderma Trials and Research 9

(EUSTAR) and Canadian Scleroderma Research Group (CSRG) cohorts. 10

Results: Demographic, organ involvement, and antibody profile data for SPIN (N=1125) 11

were generally comparable to the EUSTAR (N=7319) and CSRG (N=1390) cohorts. 12

There was a high proportion of women and White patients in all cohorts, though relative 13

proportions differed. Scl70 antibody frequency was highest in EUSTAR, somewhat lower 14

in SPIN, and lowest in CSRG, consistent with the higher proportion of interstitial lung 15

disease among diffuse cutaneous SSc patients in SPIN compared to CSRG (48.5% vs 16

40.3%). RNA polymerase III antibody frequency was highest in SPIN and remarkably 17

lower in EUSTAR (21.1% vs 2.4%), in line with the higher prevalence of SSc renal crisis 18

(4.5% vs 2.1%) in SPIN. 19

Conclusions: Although there are some differences, the SPIN Cohort is broadly 20

comparable to other large prevalent SSc cohorts, increasing confidence that insights 21

gained from the SPIN Cohort should be generalizable, although it should be noted that all 22

three cohorts include primarily White participants. 23

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1

Key words: Systemic Sclerosis, Scleroderma, Systemic Scleroderma, Cohort 2

3

Key messages: 4

* The web-based Scleroderma Patient-centered Intervention Network Cohort is designed 5

to collect patient-reported outcomes among scleroderma patients. 6

7

* Characteristics for the Scleroderma Patient-centered Intervention Network Cohort were 8

generally comparable to other large scleroderma cohorts. 9

10

* Insights gained from the Scleroderma Patient-centered Intervention Network Cohort 11

should be broadly generalizable. 12

13

14

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Patients living with rare diseases often lack access to disease-specific 1

psychosocial, educational, self-management, and rehabilitation interventions that are 2

important components of disease management and patient-centered care in more common 3

diseases. In common chronic illnesses, evidence suggests that self-management strategies 4

can positively impact disease-specific outcomes and quality of life [1,2]. However, in the 5

context of rare diseases like systemic sclerosis (SSc, or scleroderma), there is a lack of 6

evidence to support disease-specific interventions. To address this problem, the 7

Scleroderma Patient-centered Intervention Network (SPIN) was formed in 2011 as an 8

international collaboration to develop and test self-management, educational, 9

psychosocial, and rehabilitation interventions for patients living with SSc [3]. 10

Recognizing that rare diseases present a major barrier to conducting adequately 11

powered trials, SPIN utilizes the cohort multiple randomized controlled trial (cmRCT) 12

design [4]. In this design, a cohort of patients is followed longitudinally and consented to 13

participate in trials of online interventions. Upon enrollment, physicians provide basic 14

medical data, and patients complete a core set of patient-reported outcome measures 15

every three months [3]. 16

The objectives of this study were to summarize baseline demographic and clinical 17

characteristics of participants in the SPIN Cohort and to compare these baseline data to 18

two other large SSc cohorts with similar published data, the Canadian Scleroderma 19

Research Group (CSRG) Registry and the European Scleroderma Trials and Research 20

(EUSTAR) group cohort, in order to determine similarities or differences among these 21

cohorts which could affect the generalizability of SPIN findings. 22

23

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METHODS 1

SPIN Cohort 2

This study includes baseline data of patients enrolled in the SPIN Cohort who 3

completed study questionnaires from April 2014 through October 2016. Patients included 4

in the study were enrolled at 32 centers in Canada, the USA, the UK, and France. Eligible 5

patients must be classified by a SPIN physician as having SSc according to the 2013 6

ACR/EULAR classification criteria [5]; be at least 18 years of age; and be able to provide 7

consent and complete questionnaires online in English or French. The SPIN sample is a 8

convenience sample. The attending physician or nurse coordinator invites eligible 9

patients, obtains informed consent, and completes a medical data form that is submitted 10

online to initiate patient registration. Cohort patients complete patient-reported outcome 11

measures online upon enrollment and subsequently every 3 months. The SPIN Cohort 12

study was approved by the Research Ethics Committee of the Jewish General Hospital, 13

Montreal, Canada and by the Institutional Review Boards of participating centers [3]. 14

This approval covered the present study and no additional ethical approval was required. 15

16

17

Comparison Cohorts: CSRG and EUSTAR 18

A detailed description of inclusion and exclusion criteria and recruitment 19

procedures for in the CSRG and EUSTAR cohorts can be found elsewhere [6,7]. 20

In short, patients in the CSRG cohort were enrolled between September 2004 and 21

July 2013. Patients in the CSRG cohort are adults with a diagnosis of SSc confirmed by a 22

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rheumatologist (98% met the 2013 ACR/EULAR classification criteria) who completed 1

measures in English or French. 2

Patients in EUSTAR were enrolled between June 2004 and June 2011 from 174 3

(mainly European) centres. EUSTAR is a multinational, prospective and open SSc 4

cohort. A minimal essential dataset was completed for all consecutive consenting patients 5

classified according to the 1980 ACR criteria [6,8]. 6

Measures 7

Sociodemographic and Medical Data. For the SPIN Cohort, patients provided 8

demographic data. SPIN physicians completed a medical data form including all items of 9

the 2013 ACR/EULAR SSc classification criteria [5], as well as variables that were 10

deemed to be important by SPIN rheumatologists (see Appendix A). 11

Cochin Hand Function scale (CHFS). The 18-item CHFS [9] measures the ability 12

to perform daily hand-related activities. Items are scored on a scale from 0 (yes, without 13

difficulty) to 5 (impossible). Total scores range from 0 to 90, and higher scores indicate 14

more hand disability. The CHFS has been validated in SSc [10]. 15

Health Assessment Questionnaire - Disability Index (HAQ-DI). Functional 16

disability was measured using the HAQ-DI [11]. Items are rated on a 4-point scale, 17

ranging from 0 (without any difficulty) to 3 (unable to do). The total score is the mean of 18

the highest scores for each of the 8 categories with higher scores indicating greater 19

functional disability. The HAQ-DI has been validated in SSc [11]. Numerical rating 20

scales measured SSc-related functional disability due to Raynaud’s phenomenon, finger 21

ulcers, breathing problems, gastrointestinal problems, pain, and overall SSc, anchored 22

between 0 (did not limit activities) to 10 (very severe limitation). 23

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Patient Health Questionnaire-8 (PHQ-8). Symptoms of depression were 1

measured using the 8-item PHQ [12]. Items are rated on a 4-point scale, ranging from 0 2

(not at all) to 3 (nearly every day). A total score is obtained by summing item scores, 3

with higher scores indicating more depressive symptoms. The PHQ-8 performs 4

equivalently to the PHQ-9 [13], which is a validated measure of depressive symptoms in 5

patients with SSc [14]. 6

Patient-Reported Outcomes Measurement Information System-29 (PROMIS-7

29v2). The 29-item PROMIS-29 version 2.0 [15] measures 8 domains of health status 8

over the past 7 days. Items are scored on a 5-point scale, except for the item measuring 9

pain intensity, which uses an 11-point rating scale. Higher scores represent more of the 10

domain being measured (i.e., better physical function and ability to participate in social 11

roles and activities; higher levels of anxiety, depression, fatigue, sleep disturbance, pain 12

interference, and pain intensity). Summed raw scores for each domain are converted into 13

T-scores standardized from the general US population (mean = 50, standard deviation 14

[SD] = 10). The PROMIS-29v2 has been validated in patients with SSc [16]. 15

Satisfaction With Appearance (SWAP) Scale. Body image concerns due to 16

changes in appearance from SSc were assessed with the 14-item SWAP [17,18]. Items 17

are scored on a 7-point scale ranging from 1 (strongly disagree) to 7 (strongly agree). 18

The SWAP has two subscales, Perceived Social Impact, reflecting social discomfort, and 19

Subjective Dissatisfaction, reflecting dissatisfaction with various body parts. Higher 20

scores indicate greater body image dissatisfaction. 21

Self-Efficacy to Manage Chronic Disease Scale (SEMCD). The 6-item SEMCD 22

Scale measures confidence in one’s ability to manage disease symptoms as well as to 23

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reduce the need for medical care and reliance on medications [19]. Items are rated on a 1

10-point rating scale ranging from 1 (not confident at all) to 10 (totally confident). The 2

score for the scale is the mean of all items, with higher scores reflecting greater self-3

efficacy. The SEMCD scale has been validated in patients with SSc [20]. 4

Statistical Analyses 5

Descriptive statistics were used to summarize SPIN Cohort characteristics (means 6

and SDs for continuous variables, frequency and proportions for categorical variables). 7

SPIN Cohort characteristics were compared to the EUSTAR and CSRG cohorts using 8

published baseline data [6,7]. Available data were extracted from the publications and, 9

where possible, compared with the SPIN Cohort. Continuous variables were compared 10

using a t-test, and categorical variables were compared using a chi-square or Fisher exact 11

test. Statistical significance was set at p < 0.05. The analyses were performed with the 12

statistical software Stata version 14.2. 13

RESULTS 14

Characteristics of the SPIN Cohort 15

Baseline demographic, clinical, and patient-reported outcome data of the 1125 16

SPIN Cohort patients included in the analyses are presented in Table 1. There were 460 17

(41%) participants classified as dcSSc. Mean age was 55.6 years (SD=12.1), and most 18

patients were female (87%) and White (82%). 19

Comparison of SPIN Cohort and CSRG 20

A comparison of the SPIN and CSRG cohorts by subgroups is presented in Table 21

2. Scl70 antibodies were more frequent in both subsets in SPIN compared to CSRG. Skin 22

involvement, sclerodactyly and ulcers were more frequent in CSRG than SPIN in both 23

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subsets, and there were more pitting scars in the lsSSc group. Abnormal nailfold 1

capillaries, on the other hand, were more frequent in SPIN than CSRG in both subsets, 2

and there were no differences with respect to the presence of telangiectasia. 3

In regard to other organ involvement, there was a higher occurrence of 4

esophageal involvement in SPIN compared to CSRG. Among dcSSc patients, SPIN 5

patients experienced more interstitial lung disease compared to CSRG patients. The 6

frequency of pulmonary arterial hypertension and SSc renal crisis were similar between 7

the cohorts. 8

Comparison of SPIN Cohort and EUSTAR 9

A comparison of baseline features between the SPIN and EUSTAR cohorts is 10

presented in Table 2. Among both subsets, the frequency of Scl 70 antibody was lower in 11

SPIN compared to EUSTAR (dcSSc 32% vs 60%; lcSSc 19% vs 23%). RNA 12

polymerase3 was higher in the SPIN subset than in EUSTAR (dcSSc: 41% vs 5%, lcSSc: 13

5% vs 1%), however, there was a high proportion of missing data in EUSTAR. There was 14

a higher frequency of pitting scars in the SPIN dcSSc subset compared to EUSTAR, and 15

distal pulp ulcers were more frequent in both subsets of SPIN. Abnormal nailfold 16

capillaries, on the other hand, were less frequent in SPIN than EUSTAR. Esophageal 17

involvement was more frequent in SPIN compared to EUSTAR. A direct comparison of 18

ILD and PAH could not be made due to methodological differences in the measurement 19

of these variables. 20

21

DISCUSSION 22

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The results of our study suggest that the SPIN Cohort has many similarities with 1

the EUSTAR and CSRG cohorts. Methodological differences in the definition of organ-2

specific involvement, as well as differences in data collection and the underlying 3

rationale for establishing the cohort could explain some of the dissimilarities that were 4

identified. The purpose of the SPIN project is to conduct rigorous trials on interventions 5

to improve health-related quality of life and disability. Clinical data were collected to 6

confirm the diagnosis of SSc and to provide a disease profile in terms of presence or 7

absence of organ involvement at the time of enrollment. Both the CSRG and the 8

EUSTAR cohorts, on the other hand, were developed specifically to follow disease 9

progression over time. 10

With respect to organ involvement and antibody profiles it is uncertain whether 11

the differences between cohorts are clinically significant or due to differences in 12

methodology. For instance, for the definition of PAH, EUSTAR used the 2009 European 13

Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines, while CSRG 14

used echocardiographic measure of PASP of >45 mm Hg, and SPIN used the criterion 15

“according to standard definitions” without specific testing criteria. 16

Since the purpose of this study was to compare SPIN Cohort characteristics with 17

other SSc cohorts, we reported only the presence of clinical variables. Of note, the mere 18

presence of a manifestation does not equate clinical impact or symptom burden from a 19

patients’ perspective. Future studies should assess the complex interplay of clinical 20

characteristics and their impact on quality of life. 21

The present study has limitations that should be considered in interpreting results. 22

First, as both the SPIN Cohort and the CSRG Registry enroll patients from Canada, there 23

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Baseline Features of the SPIN Cohort

16

is potential overlap between participants in both cohorts. Overall, 26% of SPIN Cohort 1

participants were enrolled from Candian centres, indicating the maximum possible 2

overlap between SPIN and the CSRG. As published summary data were used to compare 3

the cohorts, data were not available to identify the exact overlap between the cohorts. 4

Second, the timeframe of enrolment was somewhat different between the three cohorts. 5

Third, the definitions of medical variables were somewhat different between the cohorts, 6

limiting the comparisons that can be made. Although additional measures of disease 7

variables may have been available for CSRG and EUSTAR, we compared SPIN Cohort 8

data with the most comprehensive published data on these cohorts [9,10]. Additional 9

analyses comparing geographical regions in more detail may be of interest, but were 10

beyond the scope of the present paper. Fourth, the SPIN Cohort constitutes a convenience 11

sample of SSc patients receiving treatment at a SPIN recruiting center, and patients at 12

these centers may differ from those in other settings. Finally, SSc patients in the SPIN 13

Cohort complete questionnaires online, and participants may differ from patients without 14

internet access, for instance, in terms of education, coping or ability for self-advocacy. 15

Overall, there are many similarities between the SPIN Cohort and the other large 16

recently reported SSc cohorts. Therefore, data emerging from the SPIN Cohort should be 17

generalizable to the broader population of SSc patients, although it should be noted that 18

all three cohorts include primarily White participants. 19

20

21

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Baseline Features of the SPIN Cohort

17

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Scleroderma Patient-centered Intervention Network (SPIN) Cohort: protocol for a 9

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psychosocial and rehabilitation interventions in a rare disease context. BMJ Open 11

2013;3:e003563. 12

4. Relton C, Torgerson D, O'Cathain A, Nicholl J. Rethinking pragmatic randomized 13

controlled trials: introducing the "cohort multiple randomised controlled trial" 14

design. BMJ 2010;340:c1066. 15

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Arthritis Rheumatol 2013;65:2737-47. 19

6. Meier FM, Frommer KW, Dinser R, Walker UA, Czirjak L, Denton CP et al. 20

Update on the profile of the EUSTAR cohort: an analysis of the EULAR 21

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Baseline Features of the SPIN Cohort

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Rheumatol 2014;41:2179-85. 3

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et al. Clinical risk assessment of organ manifestations in systemic sclerosis: a 5

report from the EULAR Scleroderma Trials And Research group database. Ann 6

Rheum Dis 2007;66:754-63. 7

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10. Rannou F, Poiraudeau S, Berezne A, Baubet T, Le-guern V, Cabane J, et al. 11

Assessing disability and quality of life in systemic sclerosis: construct validities 12

of the Cochin Hand Function Scale, Health Assessment Questionnaire (HAQ), 13

Systemic Sclerosis HAQ, and Medical Outcomes Study 36-Item Short Form 14

Health Survey. Arthritis Rheumatol 2007;57:94-102. 15

11. Poole JL, Steen VD. The use of the Health Assessment Questionnaire (HAQ) to 16

determine physical disability in systemic sclerosis. Arthritis Care Res 1991;4:27-17

31. 18

12. Kroenke K, Strine TW, Spitzer RL, Williams JBW, Berry JT, Mokdad AH. The 19

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13. Razykov I, Hudson M, Baron M, Thombs BD. The utility of the PHQ-9 to assess 22

suicide risk in patients with systemic sclerosis. Arthritis Care Res 2013;65:753-8. 23

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14. Milette K, Hudson M, Baron M, Thombs BD, Canadian Scleroderma Research 1

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sclerosis: internal consistency reliability, convergent validity and clinical 3

correlates. Rheumatology (Oxford) 2010;49:789-96. 4

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[http://www.healthmeasures.net/explore-measurement-systems/promis]. Accessed 6

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18. Mills SD, Fox RS, Merz EL, Clements PJ, Kafaja S, Malcarne VL, et al. 15

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Baseline Features of the SPIN Cohort

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Table 1. Baseline SPIN Demographic and Clinical Features and Patient-reported Core

Outcome Measures

Combined

(n=1125)

Diffuse

(n=460)

Limited

(n=665)

p value

(dcSSc vs

lcSSc)

Demographic variables

Age in years, mean (SD) 55.6 (12.1) 53.0 (12.2)

n=457

57.4 (11.7)

n=664

p<0.001

Gender (% female) 87.3

(982/1125)

85.9 (395/460) 88.3 (587/665) p=0.235

Race (% White) 82.0

(922/1124)

75.4 (346/459) 86.6 (576/665) p<0.001

Body Mass Index, mean

(SD)

25.7 (6.0)

n=1125

25.3 (6.4)

n=460

26.0 (5.8)

n=665

p=0.053

Clinical Variables

Raynaud's phenomenon (%

positive)

98.5

(1101/1118)

97.8 (447/457) 98.9 (654/661) p=0.129

Age at first non-Raynaud’s

phenomenon, mean (SD)

44.0 (13.4)

n=1034

44.0 (13.0)

n=431

44.0 (13.7)

n=603

p=0.999

Time since first non-

Raynaud’s phenomenon

symptom, mean (SD)

11.6 (8.7)

n=1038

9.1 (7.2)

n=434

13.4 (9.3)

n=604

p<0.001

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Time since diagnosis,

mean (SD)

9.7 (8) 8.3 (7.0) 10.8 (8.4) p<0.001

<3 years since onset first

non-Raynaud’s

phenomenon, (%)

13.1

(147/1125)

18.3 (84/460) 9.5 (63/665) p<0.001

SSc-related Autoantibodies

Antinuclear antibody

(ANA) by IFA (%

positive)

92.9

(953/1026)

91.1 (388/426) 94.2 (565/600) p=0.058

ANA >1:160 (% positive) 92.1

(832/903)

89.8 (334/372) 93.8 (498/531) p=0.028

Nucleolar pattern (%

positive)

20.0

(225/1125)

24.3 (112/460) 17.0 (113/665) p=0.002

Centromere by IIF pattern

or Immunoassay (%

positive)

32.8

(276/841)

9.3 (32/344) 49.1 (244/497) p<0.001

Scl 70 (% positive) 24.8

(236/951)

32.0 (131/409) 19.4 (105/542) p<0.001

RNA Polymerase III (%

positive)

21.1

(115/545)

41.0 (100/244) 5 (15/301) p<0.001

Skin Involvement

mRSS median (IQR) 5 (9) 12 (13.5) 3 (3) p<0.001

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mRSS mean (SD) 7.9 (8.4) 13.3 (10) 4.2 (4.2) p<0.001

Puffy fingers (% positive) 61.5

(659/1071)

61.1 (267/437) 61.8 (392/634) p=0.809

Sclerodactyly

(proximal to MCP) (%

positive)

85.7

(955/1114)

89.1 (407/457) 83.4 (548/657) p=0.008

Digital tip pitting/scar (%

positive)

42.1

(463/1101)

50.4 (226/448) 36.3 (237/653) p<0.001

Distal pulp ulcers (%

positive)

35.9

(397/1107)

39.1 (176/450) 33.6 (221/657) p=0.062

Ulcer anywhere (%

positive)

17.7

(191/1082)

26.5 (116/438) 11.6 (75/644) p<0.001

Telangiectasias (any) (%

positive)

73.0

(805/1102)

68.0 (304/447) 76.5 (501/655) p=0.002

Teleangiectasias (face) (%

positive)

81.4

(516/634)

81.1 (189/233) 81.5 (327/401) p=0.893

Abnormal nailfold

Capillaries (% positive)

83.3

(779/935)

85.1 (326/383) 82.1 (453/552) p=0.218

Abnormal pigment (any)

(% positive)

32.9

(344/1047)

51.3 (219/427) 20.2 (125/620) p<0.001

Abnormal facial pigment

(% positive)

52.9

(171/323)

60.4 (116/192) 42.0 (55/131) p=0.001

Organ Involvement

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Musculoskeletal

Tendon friction rubs (%

positive)

24.6

(248/1008)

41.2 (167/405) 13.4 (81/603) p<0.001

Joint contractures small

(% positive)

25.5

(270/1059)

41.4 (180/435) 14.4 (90/624) p<0.001

Joint contracture large

(% positive)

12.7

(133/1046)

21.7 (93/429) 6.5 (40/617) p<0.001

Gastrointestinal

Involvement

Esophageal (% positive) 86.9

(971/1118)

88.5 (406/459) 85.7 (565/659) p=0.186

Stomach (% positive) 30.6

(334/1092)

37.7 (168/446) 25.7 (166/646) p<0.001

Intestinal (% positive) 39.5

(435/1100)

43.4 (195/449) 36.9 (240/651) p=0.029

Pulmonary Involvement

Interstitial Lung Disease

(% positive)

36.2

(398/1099)

48.5 (219/452) 27.7 (179/647) p<0.001

Pulmonary Arterial

Hypertension (%

positive)

10.4

(107/1029)

7.5 (31/414)

12.4 (76/615) p=0.012

History of SSc Renal

Crisis (% positive)

4.7

(53/1116)

9.2 (42/457) 1.7 (11/659) p<0.001

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Overlapping

Autoimmune Disease

Systemic Lupus

Erythematosus (%

positive)

3.3

(36/1106)

2.4 (11/452) 3.8 (25/654) p=0.201

Rheumatoid Arthritis

(% positive)

5.8

(64/1103)

6.7 (30/451) 5.2 (34/652) p=0.316

Sjogren's (% positive) 9.0

(97/1075)

7.5 (33/441) 10.1 (64/634) p=0.142

Myositis (% positive) 5.8

(64/1100)

8.50 (38/447)

8.5

4.0 (26/653) p=0.002

Primary Biliary

Cirrhosis (% positive)

1.4

(15/1096)

0.90 (4/449)

0.9

1.7 (11/647) p=0.257

Autoimmune

Thyroiditis (% positive)

6.1

(66/1079)

6.1 (27/441) 6.1 (39/638) p=0.995

Patient-reported outcomes

CHFS, mean (SD) 13.7 (16.1) 19.2 (18.3) 9.8 (13.0) p<0.001

HAQ-DI, mean (SD) 0.8 (0.7) 1.0 (0.7) 0.6 (0.6) p<0.001

Numeric Rating Scales

Raynaud’s phenomenon,

mean (SD)

2.9 (2.9) 3.2 (3.1) 2.7 (2.8) p=0.005

Finger ulcers, mean (SD) 1.5 (2.7) 2.0 (3.0) 1.2 (2.4) p<0.001

Breathing problems, mean 2.2 (2.7) 2.3 (2.8) 2.0 (2.6) p=0.063

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(SD)

Gastrointestinal problems,

mean (SD)

2.5 (2.9) 2.5 (3.0) 2.5 (2.9) p=0.711

Pain, mean (SD) 3.3 (2.9) 3.7 (3.0) 3.1 (2.8) p<0.001

Overall SSc, mean (SD) 3.8 (0.2) 4.3 (0.1) 3.5 (0.1) p<0.001

PHQ-8, mean (SD) 6.1 (5.3) 6.4 (5.5) 5.80 (5.1) p=0.044

PROMIS-29

Physical

Function, mean (SD)

43.0 (9.0) 41.4 (8.9) 44.1 (8.8) p<0.001

Anxiety, mean (SD) 51.5 (9.9) 52.6 (9.8) 50.7 (9.9) p=0.001

Depression, mean (SD) 50.9 (9.3) 51.8 (9.5) 50.2 (9.1) p=0.006

Fatigue, mean (SD) 55.3 (11.1) 56.0 (11.0) 54.8 (11.2) p=0.079

Sleep disturbance, mean

(SD)

52.3 (8.8) 52.8 (8.8) 52.0 (8.8) p=0.113

Social roles, mean (SD) 48.0 (9.9) 46.7 (9.9) 48.9 (9.8) p<0.001

Pain interference, mean

(SD)

55.5 (9.7) 56.6 (9.9) 54.8 (9.5) p=0.003

SEMCD, mean (SD) 6.4 (2.3) 6.2 (2.3) 6.6 (2.3) p=0.112

SWAP

Social Impact, mean (SD) 9.3 (9.5) 11.6 (10.0) 7.7 (8.7) p<0.001

Dissatisfaction, mean (SD) 21.7 (12.9) 23.6 (12.3) 20.3 (13.2) p<0.001

ANA = antinuclear antibody; IFA = Indirect immunofluorescence assay; IIF = indirect

immunofluorescence; mRSS = modified Rodnan skin score; CHFS = Cochin Hand Function

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Scale; HAQ-DI = Health Assessment Questionnaire – Disability Index; PHQ-8 = Patient Health

Questionnaire-8; PROMIS-29 = Patient-Reported Outcomes Measurement Information System –

29; SEMCD = Self-Efficacy to Manage Chronic Disease scale; SWAP = Satisfaction With

Appearance Scale

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Table 1. Baseline SPIN Demographic and Clinical Features and Patient-reported Core

Outcome Measures

Combined

(n=1125)

Diffuse

(n=460)

Limited

(n=665)

p value (dcSSc

vs lcSSc)

Demographic variables

Age in years, mean

(SD)

55.6 (12.1) 53.0 (12.2)

n=457

57.4 (11.7)

n=664

p<0.001

Gender (% female) 87.3

(982/1125)

85.9 (395/460) 88.3 (587/665) p=0.235

Race (% White) 82.0

(922/1124)

75.4 (346/459) 86.6 (576/665) p<0.001

Body Mass Index,

mean (SD)

25.7 (6.0)

n=1125

25.3 (6.4)

n=460

26.0 (5.8)

n=665

p=0.053

Clinical Variables

Raynaud's

phenomenon (%

positive)

98.5

(1101/1118)

97.8 (447/457) 98.9 (654/661) p=0.129

Age at first non-

Raynaud’s

phenomenon, mean

(SD)

44.0 (13.4)

n=1034

44.0 (13.0)

n=431

44.0 (13.7)

n=603

p=0.999

Time since first non- 11.6 (8.7) 9.1 (7.2) 13.4 (9.3) p<0.001

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Raynaud’s

phenomenon

symptom, mean (SD)

n=1038 n=434 n=604

Time since diagnosis,

mean (SD)

9.7 (8) 8.3 (7.0) 10.8 (8.4) p<0.001

<3 years since onset

first non-Raynaud’s

phenomenon, (%)

13.1

(147/1125)

18.3 (84/460) 9.5 (63/665) p<0.001

SSc-related

Autoantibodies

Antinuclear antibody

(ANA) by IFA (%

positive)

92.9

(953/1026)

91.1 (388/426) 94.2 (565/600) p=0.058

ANA >1:160 (%

positive)

92.1 (832/903)

89.8 (334/372) 93.8 (498/531) p=0.028

Nucleolar pattern (%

positive)

20.0

(225/1125)

24.3 (112/460) 17.0 (113/665) p=0.002

Centromere by IIF

pattern

or Immunoassay (%

positive)

32.8 (276/841) 9.3 (32/344) 49.1 (244/497) p<0.001

Scl 70 (% positive) 24.8 (236/951) 32.0 (131/409) 19.4 (105/542) p<0.001

RNA Polymerase III 21.1 (115/545) 41.0 (100/244) 5 (15/301) p<0.001

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(% positive)

Skin Involvement

mRSS median (IQR)

mRSS mean (SD)

5 (9)

7.9 (8.4)

12 (13.5)

13.3 (10)

3 (3)

4.2 (4.2)

p<0.001

p<0.001

Puffy fingers (%

positive)

61.5

(659/1071)

61.1 (267/437) 61.8 (392/634) p=0.809

Sclerodactyly

(proximal to MCP) (%

positive)

85.7

(955/1114)

89.1 (407/457) 83.4 (548/657) p=0.008

Digital tip pitting/scar

(% positive)

42.1

(463/1101)

50.4 (226/448) 36.3 (237/653) p<0.001

Distal pulp ulcers (%

positive)

35.9

(397/1107)

39.1 (176/450) 33.6 (221/657) p=0.062

Ulcer anywhere (%

positive)

17.7

(191/1082)

26.5 (116/438) 11.6 (75/644) p<0.001

Telangiectasias (any)

(% positive)

73.0

(805/1102)

68.0 (304/447) 76.5 (501/655) p=0.002

Teleangiectasias (face)

(% positive)

81.4 (516/634) 81.1 (189/233) 81.5 (327/401) p=0.893

Abnormal nailfold

Capillaries (%

positive)

83.3 (779/935) 85.1 (326/383) 82.1 (453/552) p=0.218

Abnormal pigment 32.9 51.3 (219/427) 20.2 (125/620) p<0.001

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(any) (% positive) (344/1047)

Abnormal facial

pigment (% positive)

52.9 (171/323) 60.4 (116/192) 42.0 (55/131) p=0.001

Organ Involvement

Musculoskeletal

Tendon friction

rubs (% positive)

24.6

(248/1008)

41.2 (167/405) 13.4 (81/603) p<0.001

Joint contractures

small (% positive)

25.5

(270/1059)

41.4 (180/435) 14.4 (90/624) p<0.001

Joint contracture

large (% positive)

12.7

(133/1046)

21.7 (93/429) 6.5 (40/617) p<0.001

Gastrointestinal

Involvement

Esophageal (%

positive)

86.9

(971/1118)

88.5 (406/459) 85.7 (565/659) p=0.186

Stomach (%

positive)

30.6

(334/1092)

37.7 (168/446) 25.7 (166/646) p<0.001

Intestinal (%

positive)

39.5

(435/1100)

43.4 (195/449) 36.9 (240/651) p=0.029

Pulmonary

Involvement

Interstitial Lung

Disease (%

36.2

(398/1099)

48.5 (219/452) 27.7 (179/647) p<0.001

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positive)

Pulmonary Arterial

Hypertension (%

positive)

10.4

(107/1029)

7.5 (31/414)

12.4 (76/615) p=0.012

History of SSc

Renal Crisis (%

positive)

4.7 (53/1116) 9.2 (42/457) 1.7 (11/659) p<0.001

Overlapping

Autoimmune Disease

Systemic Lupus

Erythematosus (%

positive)

3.3 (36/1106) 2.4 (11/452) 3.8 (25/654) p=0.201

Rheumatoid

Arthritis (%

positive)

5.8 (64/1103) 6.7 (30/451) 5.2 (34/652) p=0.316

Sjogren's (%

positive)

9.0 (97/1075) 7.5 (33/441) 10.1 (64/634) p=0.142

Myositis (%

positive)

5.8 (64/1100) 8.50 (38/447)

8.5

4.0 (26/653) p=0.002

Primary Biliary

Cirrhosis (%

positive)

1.4 (15/1096) 0.90 (4/449)

0.9

1.7 (11/647) p=0.257

Autoimmune 6.1 (66/1079) 6.1 (27/441) 6.1 (39/638) p=0.995

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Thyroiditis (%

positive)

Patient-reported

outcomes

CHFS 13.7 (16.1) 19.2 (18.3) 9.8 (13.0) p<0.001

HAQ-DI 0.8 (0.7) 1.0 (0.7) 0.6 (0.6) p<0.001

Numeric Rating Scales

Raynaud’s

phenomenon

2.9 (2.9) 3.2 (3.1) 2.7 (2.8) p=0.005

Finger ulcers 1.5 (2.7) 2.0 (3.0) 1.2 (2.4) p<0.001

Breathing problems 2.2 (2.7) 2.3 (2.8) 2.0 (2.6) p=0.063

Gastrointestinal

problems

2.5 (2.9) 2.5 (3.0) 2.5 (2.9) p=0.711

Pain 3.3 (2.9) 3.7 (3.0) 3.1 (2.8) p<0.001

Overall SSc 3.8 (0.2) 4.3 (0.1) 3.5 (0.1) p<0.001

PHQ-8 6.1 (5.3) 6.4 (5.5) 5.80 (5.1) p=0.044

PROMIS-29

Physical

Function

43.0 (9.0) 41.4 (8.9) 44.1 (8.8) p<0.001

Anxiety 51.5 (9.9) 52.6 (9.8) 50.7 (9.9) p=0.001

Depression 50.9 (9.3) 51.8 (9.5) 50.2 (9.1) p=0.006

Fatigue 55.3 (11.1) 56.0 (11.0) 54.8 (11.2) p=0.079

Sleep disturbance 52.3 (8.8) 52.8 (8.8) 52.0 (8.8) p=0.113

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Social roles 48.0 (9.9) 46.7 (9.9) 48.9 (9.8) p<0.001

Pain interference 55.5 (9.7) 56.6 (9.9) 54.8 (9.5) p=0.003

SEMCD 6.4 (2.3) 6.2 (2.3) 6.6 (2.3) p=0.112

SWAP

Social Impact 9.3 (9.5) 11.6 (10.0) 7.7 (8.7) p<0.001

Dissatisfaction 21.7 (12.9) 23.6 (12.3) 20.3 (13.2) p<0.001

ANA = antinuclear antibody; IFA = Indirect immunofluorescence assay; IIF = indirect

immunofluorescence; mRSS = modified Rodnan skin score; CHFS = Cochin Hand Function

Scale; HAQ-DI = Health Assessment Questionnaire – Disability Index; PHQ-8 = Patient Health

Questionnaire-8; PROMIS-29 = Patient-Reported Outcomes Measurement Information System –

29; SEMCD = Self-Efficacy to Manage Chronic Disease scale; SWAP = Satisfaction With

Appearance Scale

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Appendix A: SPIN Cohort medical variables* 1. Local participant ID: [free entry by enrolling physician] 2. Date of visit: [dd/mm/yyyy] 3. Gender: [male/female] 4. Date of birth: [mm/yyyy] 5. Height (if exact height is not known, provide best approximate estimate): [entry in cm

or ft/inch] 6. Weight (if exact weight is not known, provide best approximate estimate): [entry in kg

or lb] 7. Raynaud’s Phenomenon Self-reported or reported by a physician, with at least a 2-

phase color change in finger(s) and often toe(s) consisting of pallor, cyanosis, and/or reactive hyperemia in response to cold exposure or emotion; usually one phase is pallor (at any time, now or in the past): [positive/negative/not available]

8. Date of onset of Raynaud’s (if exact date is not known, provide best approximate estimate. If month is unknown, please enter July (07)): [mm/yyyy; not available]

9. Date of onset of first non-Raynaud’s disease manifestation (if exact date is not known, provide best approximate estimate. If month is unknown, please enter July (07)): [mm/yyyy; not available]

10. Date of SSc diagnosis (if exact date is not known, provide best approximate estimate.

If month is unknown, please enter July (07)): [mm/yyyy; not available] 11. Disease Subset (Limited – skin sclerosis confined to the limbs distal to the elbows

and knees and/or face; Diffuse – skin sclerosis involving the limbs proximal to the elbows and knees and/or the chest and/or trunk, at any time;): [Limited/Diffuse/Sine/Not available]

*A preliminary version of the medical data form was previously published in: Kwakkenbos L, Jewett LR, Baron M, Bartlett SJ, Furst D, Gottesman K et al. The Scleroderma Patient-centered Intervention Network (SPIN) Cohort: protocol for a cohort multiple randomized controlled trial (cmRCT) design to support trials of psychosocial and rehabilitation interventions in a rare disease context. BMJ Open 2013;3:e003563.

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12. SSc-related autoantibodies - Anticentromere antibody or centromere pattern seen on antinuclear antibody testing, anti– topoisomerase I antibody (also known as anti–Scl-70 antibody), or anti–RNA polymerase III antibody. Positive according to local laboratory standards. a. - Antinuclear Antibody (ANA): [positive/negative/not done]

- If ANA positive, titre > 1:160: [yes/no/not available] - Pattern in ANA: [Nucleolar/Speckled/Homogeneous/Centromere/Not available]

b. Anti-centromere - By IIF or other antigen-based methods: [positive/negative/not done] c. Anti-topoisomerase I (also called Scl-70): [positive/negative/not done] d. Anti-RNA polymerase III: [positive/negative/not done]

13. Modified Rodnan Skin Score (MRSS, range 0-51): [score entry/not available]

14. Puffy fingers - Swollen digits; a diffuse, usually nonpitting increase in soft tissue mass of the digits extending beyond the normal confines of the joint capsule. Normal digits are tapered distally with the tissues following the contours of the digital bone and joint structures. Swelling of the digits obliterates these contours. Not due to other causes such as inflammatory dactylitis (at any time, now or in the past documented by physician): [positive/negative/not available]

15. Sclerodactyly - distal to the 4 metacarpophalangeal joints but proximal to the proximal interphalangeal joints (at any time, now or in the past documented by physician): [yes/no/not available]

16. Skin thickening of the fingers of both hands extending proximal to the metacarpophalangeal joints (Skin thickening or hardening not due to scarring after injury, trauma, etc. At any time, now or in the past documented by physician): [yes/no/not available]

17. Fingertip pitting scars - Digital pitting scars are depressed areas at digital tips as a

result of ischemia, rather than trauma or exogenous causes: [yes/no/not available]

18. Digital tip ulcers - Ulcers or scars distal to or at the proximal interphalangeal joint not thought to be due to trauma (at any time, now or in the past documented by physician) a. Digital pulp (volar), distal to distal interphalangeal joints (DIPs): [yes/no/not available] b. Anywhere else on the finger: [yes/no/not available]

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19. Telangiectasias - Telangiectasiae are visible macular dilated superficial blood vessels, which collapse upon pressure and fill slowly when pressure is released. Telangiectasiae in a scleroderma-like pattern are round and well demarcated and found on hands, lips, inside of the mouth, and/or are large mat-like telangiectasiae. Distinguishable from rapidly filling spider angiomas with central arteriole and from dilated superficial vessels (at any time, now or in the past documented by physician) a. Any [yes/no/not available] b. On the face [yes/no/not available]

20. Abnormal nailfold capillaries - Enlarged capillaries and/or capillary loss with or

without pericapillary hemorrhages at the nailfold. May also be seen on the cuticle (at any time, now or in the past documented by physician): [yes/no/not available] - Specify method of detection: [Naked eye/ Dermatoscope/ Opthalmoscope/ Widefield microscopy/ Videocapillaroscopy/ Other (specify)]

21. Abnormal skin pigmentation - Hyperpigmentation, often but not necessarily

containing areas of punctuate or patchy hypopigmentation or depigmentation (“pepper and salt”), thought to be related to SSc (at any time, now or in the past documented by physician) a. Any: [yes/no/not available] b. On the face: [yes/no/not available]

22. Tendon friction rubs- Palpable crepitus over flexor or extensor tendons,

particularly common over the wrists, fingers, knees and ankles [Never/ Currently, with or without past/In the past, but not currently/Not available]

23. Joint contractures - Limitation of range of motion of a joint secondary to tightening

around the joint a. Small joints - DIP, PIPs (proximal interphalangeal joints), MCPs and/or wrists:

[No/Mild (0-25%)/Moderate (25-50%)/Severe (>50%)/Not available] b. Large joints - Elbows, knees, hips, ankles: [No/Mild (0-25%)/Moderate (25-

50%)/Severe (>50%)/ Not available] 24. Gastrointestinal tract a. Esophageal - Dysphagia, heartburn and/or reflux, due to SSc (or requiring

medications to alleviate these symptoms) (at any time, now or in the past documented by physician) [yes/no/not available]

b. Stomach - Early satiety and/or vomiting, due to SSc (or requiring medications to

alleviate these symptoms) (at any time, now or in the past as reported by patient or documented by physician) [yes/no/not available]

c. Intestinal - Diarrhea, bloating and/or constipation, thought by the physician to be

due to SSc (or requiring medications to alleviate these symptoms)(at any time, now or in the past as reported by patient or documented by physician) [yes/no/not available]

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25. Interstitial lung disease - Pulmonary fibrosis seen on high-resolution computed

tomography or chest radiography, most pronounced in the basilar portions of the lungs, or occurrence of “Velcro” crackles on auscultation, not due to another cause such as congestive heart failure (at any time, now or in the past documented by physician): [yes/no/not available]

26. Pulmonary arterial hypertension (PAH) - Pulmonary arterial hypertension diagnosed by right-sided heart catheterization according to standard definitions (at any time, now or in the past documented by physician): [yes/no/not available]

27. History of scleroderma renal crisis [yes/no/not available] 28. Overlap syndrome (at any time, now or in the past) a. Systemic lupus erythematosus (by ACR classification criteria) [yes/no/not

available] b. Rheumatoid arthritis (by ACR/EULAR 2010 classification criteria) [yes/no/not

available] c. Sjogren’s syndrome (positive for at least two of three objective diagnostic tests:

1) anti-SS-A/B blood test. There are two scenarios: a) Positive serum levels of either the SSA and/or SSB antibody and/or b) positive serum levels of the rheumatoid factor antibody (RA) and elevated antinuclear antibody (ANA) titers; 2) ocular surface staining (measures the dissipation rate of a specialized dye that is applied to the tear film that bathes the surface of the eye; a score of three or more is considered to be positive); 3) salivary gland biopsy (one or more sites of inflammation per four millimeters squared area is considered positive) [yes/no/not available] d. Idiopathic inflammatory myositis - Either definite or probable polymyositis or dermatomyositis, according to the following criteria:

1. symmetric proximal muscle weakness

2. muscle biopsy evidence of myositis

3. MRI evidence of myositis

4. elevation in serum skeletal muscle enzymes

5. characteristic EMG pattern of myositis

6. typical rash of dermatomyositis (heliotrope rash or Gottron’s papules).

All of criteria 1-5 or any 3 of criteria 1-5 are required for definite or probable polymositis, respectively. Criteria 6 plus any 3 of criteria 1-5 or criteria 6 plus any 2 of criteria 1-5 are required for definite or probable dermatomyositis, respectively.

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The absence of other forms of myopathy, including inclusion body, metabolic, inherited or infectious forms, is also required to diagnose PM/DM. [yes/no/not available] e. Primary biliary cirrhosis (diagnosed by the presence of: persistent cholestatic indices, antimitochondrial antibodies, with no other clinical explanation with or without liver histology diagnostic of or compatible with PBC): [yes/no/not available] f. Autoimmune thyroid disease (with a diagnosis supported by clinical presentation and the presence of either thyroid peroxidase (TPO) or thyroglobulin (Tg) antibodies): [yes/no/not available]