Rheumatology 2018;57:1623–1631

RHEUMATOLOGY doi:10.1093/rheumatology/key139
Advance Access publication 2 June 2018

Concise report
The Scleroderma Patient-Centered Intervention
Network Cohort: baseline clinical features and
comparison with other large scleroderma cohorts
Dane H. Dougherty1, Linda Kwakkenbos2,3,4, Marie-Eve Carrier3, Gloria Salazar1,
Shervin Assassi1, Murray Baron3,5, Susan J. Bartlett5,6,7, Daniel E. Furst8,9,10,

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Karen Gottesman11, Frank van den Hoogen12,13, Vanessa L. Malcarne14,15,
y
Luc Mouthon16,17, Warren R. Nielson18,19, Serge Poiraudeau16,20,21, ,
Maureen Sauvé22,23, Gilles Boire24, Alessandra Bruns24, Lorinda Chung25,
Christopher Denton26, James V. Dunne27,28, Paul Fortin29, Tracy Frech30,
Anna Gill27, Jessica Gordon31, Ariane L. Herrick32, Monique Hinchcliff33,
Marie Hudson5,34, Sindhu R. Johnson35,36, Niall Jones37, Suzanne Kafaja8,
Maggie Larché38, Joanne Manning39, Janet Pope40, Robert Spiera31,
Virginia Steen41, Evelyn Sutton42, Carter Thorne43, Pearce Wilcox28,29,
Brett D. Thombs2,3,5,44-47 and Maureen D. Mayes1; for the SPIN Investigators

Abstract
Objectives. The Scleroderma Patient-centered Intervention Network (SPIN) Cohort is a web-based cohort designed to
collect patient-reported outcomes at regular intervals as a framework for conducting trials of psychosocial, educational,
self-management and rehabilitation interventions for patients with SSc. The aim of this study was to present baseline
demographic, medical and patient-reported outcome data of the SPIN Cohort and to compare it with other large SSc
cohorts.

1
Department of Internal Medicine, Division of Rheumatology,
University of Texas McGovern Medical School, Houston, TX, USA,
2
Department of Psychiatry, McGill University, 3Lady Davis Institute for
Medical Research, Jewish General Hospital, Montreal, QC, Canada,
4
Behavioural Science Institute, Clinical Psychology, Radboud
University, Nijmegen, the Netherlands, 5Department of Medicine,
McGill University, Montreal, QC, Canada, 6Division of Rheumatology,
Johns Hopkins School of Medicine, Baltimore, MD, USA, 7McGill
University Health Center, Montréal, QC, Canada, 8Division of
Rheumatology, Geffen School of Medicine, University of California,
Los Angeles, Los Angeles, CA, USA, 9Medicine, University of
Washington, Seattle, WA, USA, 10Medicine, University of Florence,
Florence, Italy, 11Scleroderma Foundation, Danvers, MA, USA,
12
Department of Rheumatology, Radboud University Medical Center,
13
Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The
Netherlands, 14Department of Psychology, San Diego State University,
15
San Diego Joint Doctoral Program in Clinical Psychology, San Diego
State University/University of California, San Diego, CA, USA,
16
Médecine interne, Université Paris Descartes, Assistance Publique-
Hôpitaux de Paris, 17Service de Médecine Interne, Centre de
Référence Maladies Systémiques Autoimmunes Rares, vascularites
nécrosantes et sclérodermie systémique, Hôpital Cochin, Paris,
France, 18Beryl & Richard Ivey Rheumatology Day Programs, St
Joseph’s Health Care, 19Lawson Health Research Institute, London,
ON, Canada, 20Service de Médecine Physique et Réadaptation,
Hôpital Cochin, 21IFR Handicap INSERM, Paris, France,
22
Scleroderma Society of Ontario, Hamilton, 23Scleroderma Society of
Canada, Ottawa, ON, 24Département de médecine, Sherbrooke
University, Sherbrooke, QC, Canada, 25Medicine – Med/Immunology &
Rheumatology, Stanford University, Stanford, CA, USA, 26Department
of Rheumatology, Royal Free London Hospital, London, UK,
CLINICAL
SCIENCE
27
Rheumatology, St Paul’s Hospital, 28Department of Medicine,
University of British Columbia, Vancouver, BC, 29Département de
médecine, Université Laval, Québec, QC, Canada, 30Internal Medicine,
University of Utah, Salt Lake City, UT, 31Department of Rheumatology,
Hospital for Special Surgery, New York City, NY, USA, 32Division of
Musculoskeletal & Dermatological Sciences, University of Manchester,
Salford Royal NHS Foundation Trust, Manchester, UK, 33Feinberg
School of Medicine, Northwestern University, Chicago, IL, USA,
34
Center for Clinical Epidemiology and Community Studies, Jewish
General Hospital, Montréal, QC, 35Toronto Scleroderma Program,
Mount Sinai Hospital, Toronto Western Hospital, 36University of
Toronto, Toronto, ON, 37Division of Rheumatology, University of
Alberta, Edmonton, AB, 38Faculty of Health Sciences, McMaster
University, Hamilton, ON, Canada, 39Clinical and Research Vascular
Laboratories, Salford Royal NHS Foundation Trust, Salford, UK,
40
Bone & Joint Institute, University of Western Ontario, London, ON,
Canada, 41Department of Medicine, Georgetown University,
Washington, DC, USA, 42Division of Rheumatology, Dalhousie
University, Halifax, NS, 43Southlake Regional Health Centre,
Newmarket, ON, 44Department of Epidemiology, Biostatistics, and
Occupational Health, 45Department of Educational and Counselling
Psychology, 46Department of Psychology and 47School of Nursing,
McGill University, Montréal, QC, Canada
Submitted 7 July 2017; revised version accepted 20 April 2018
y
Deceased
Correspondence to: Linda Kwakkenbos, Jewish General Hospital,
4333 Côte-Sainte-Catherine Road, Montréal, Québec H3T 1E4,
Canada.
E-mail: kwakkenbosl@gmail.com

! The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com
Dane H. Dougherty et al.

Methods. Descriptive statistics were used to summarize SPIN Cohort characteristics; these were compared with
published data of the European Scleroderma Trials and Research (EUSTAR) and Canadian Scleroderma Research
Group (CSRG) cohorts.
Results. Demographic, organ involvement and antibody profile data for SPIN (N = 1125) were generally comparable with
that of the EUSTAR (N = 7319) and CSRG (N = 1390) cohorts. There was a high proportion of women and White patients in
all cohorts, though relative proportions differed. Scl70 antibody frequency was highest in EUSTAR, somewhat lower in
SPIN, and lowest in CSRG, consistent with the higher proportion of interstitial lung disease among dcSSc patients in
SPIN compared with in CSRG (48.5 vs 40.3%). RNA polymerase III antibody frequency was highest in SPIN and remark-
ably lower in EUSTAR (21.1 vs 2.4%), in line with the higher prevalence of SSc renal crisis (4.5 vs 2.1%) in SPIN.
Conclusion. Although there are some differences, the SPIN Cohort is broadly comparable with other large prevalent
SSc cohorts, increasing confidence that insights gained from the SPIN Cohort should be generalizable, although it should
be noted that all three cohorts include primarily White participants.

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Key words: systemic sclerosis, scleroderma, systemic scleroderma, cohort

Rheumatology key messages

. The web-based Scleroderma Patient-centered Intervention Network Cohort is designed to collect patient-re-
ported outcomes among scleroderma patients.
. Characteristics for the Scleroderma Patient-centered Intervention Network Cohort were generally comparable
with those of other large scleroderma cohorts.
. Insights gained from the Scleroderma Patient-centered Intervention Network Cohort should be broadly
generalizable.

Introduction
Patients living with rare diseases often lack access to dis-
ease-specific psychosocial, educational, self-manage-
ment and rehabilitation interventions that are important
components of disease management and patient-centred
care in more common diseases. In common chronic ill-
nesses, evidence suggests that self-management strate-
gies can positively impact disease-specific outcomes and
quality of life [1, 2]. However, in the context of rare dis-
eases like SSc or scleroderma, there is a lack of evidence
to support disease-specific interventions. To address this
problem, the Scleroderma Patient-centered Intervention
Network (SPIN) was formed in 2011 as an international
collaboration to develop and test self-management, edu-
cational, psychosocial and rehabilitation interventions for
patients living with SSc [3].
Recognizing that rare diseases present a major barrier
to conducting adequately powered trials, SPIN utilizes the
cohort multiple randomized controlled trial (cmRCT)
design [4]. In this design, a cohort of patients is followed
longitudinally and consented to participate in trials of
online interventions. Upon enrolment, physicians provide
basic medical data, and patients complete a core set of
patient-reported outcome measures every 3 months [3].
The objectives of this study were to summarize baseline
demographic and clinical characteristics of participants in
the SPIN Cohort and to compare these baseline data with
that of two other large SSc cohorts with similar published
data, the Canadian Scleroderma Research Group (CSRG)
Registry and the European Scleroderma Trials and
Research (EUSTAR) group cohort, in order to determine
similarities or differences between these cohorts that
could affect the generalizability of SPIN findings.
Methods
SPIN Cohort
This study includes baseline data of patients enrolled in
the SPIN Cohort who completed study questionnaires
from April 2014 through October 2016. Patients included
in the study were enrolled at 32 centres in Canada, the
USA, the UK and France. Eligible patients must be clas-
sified by a SPIN physician as having SSc according to the
2013 ACR/EULAR classification criteria [5]; be at least
18 years of age; and be able to provide consent and com-
plete questionnaires online in English or French. The SPIN
sample is a convenience sample. The attending physician
or nurse coordinator invites eligible patients, obtains in-
formed consent and completes a medical data form that is
submitted online to initiate patient registration. Cohort pa-
tients complete patient-reported outcome measures
online upon enrolment and subsequently every 3 months.
The SPIN Cohort study was approved by the Research
Ethics Committee of the Jewish General Hospital,
Montreal, Canada and by the Institutional Review
Boards of participating centres [3]. This approval covered
the present study and no additional ethical approval was
required.
Comparison cohorts: CSRG and EUSTAR
A detailed description of inclusion and exclusion criteria
and recruitment procedures for the CSRG and EUSTAR
cohorts can be found elsewhere [6, 7].
In short, patients in the CSRG cohort were enrolled be-
tween September 2004 and July 2013. Patients in the
CSRG cohort are adults with a diagnosis of SSc con-
firmed by a rheumatologist (98% met the 2013 ACR/

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EULAR classification criteria) who completed measures in
English or French.
Patients in EUSTAR were enrolled between June 2004
and June 2011 from 174 (mainly European) centres.
EUSTAR is a multinational, prospective and open SSc
cohort. A minimal essential dataset was completed for
all consecutive consenting patients classified according
to the 1980 ACR criteria [6, 8].
Measures
Sociodemographic and medical data
For the SPIN Cohort, patients provided demographic
data. SPIN physicians completed a medical data form
including all items of the 2013 ACR/EULAR SSc classifi-
cation criteria [5], as well as variables that were deemed to
be important by SPIN rheumatologists (see SPIN cohort
medical variables in the supplementary data, available at
Rheumatology online).
Cochin Hand Function Scale
The 18-item Cochin Hand Function scale [9] measures the
ability to perform daily hand-related activities. Items are
scored on a scale from 0 (yes, without difficulty) to 5 (im-
possible). Total scores range from 0 to 90, and higher
scores indicate more hand disability. The Cochin Hand
Function scale has been validated in SSc [10].
HAQ—Disability Index
Functional disability was measured using the
HAQ—Disability Index (HAQ-DI) [11]. Items are rated on
a 4-point scale, ranging from 0 (without any difficulty) to
3 (unable to do). The total score is the mean of the highest
scores for each of the eight categories, with higher scores
indicating greater functional disability. The HAQ-DI has
been validated in SSc [11]. Numerical rating scales mea-
sured SSc-related functional disability due to RP, finger
ulcers, breathing problems, gastrointestinal problems,
pain and overall SSc, anchored between 0 (did not limit
activities) to 10 (very severe limitation).
Patient Health Questionnaire-8
Symptoms of depression were measured using the
Patient Health Questionnaire-8 (PHQ-8) [12]. Items are
rated on a 4-point scale, ranging from 0 (not at all) to
3 (nearly every day). A total score is obtained by summing
item scores, with higher scores indicating more depres-
sive symptoms. The PHQ-8 performs equivalently to the
PHQ-9 [13], which is a validated measure of depressive
symptoms in patients with SSc [14].
Patient-Reported Outcomes Measurement Information
System-29
The Patient-Reported Outcomes Measurement
Information System-29 (PROMIS-29v2) [15] measures
eight domains of health status over the past 7 days.
Items are scored on a 5-point scale, except for the item
measuring pain intensity, which uses an 11-point rating
scale. Higher scores represent more of the domain
being measured (i.e. better physical function and ability
to participate in social roles and activities; higher levels
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Baseline features of the SPIN Cohort
of anxiety, depression, fatigue, sleep disturbance, pain
interference and pain intensity). Summed raw scores for
each domain are converted into t-scores standardized
from the general US population [mean (S.D.) = 50 (10)]. The
PROMIS-29v2 has been validated in patients with SSc [16].
Satisfaction With Appearance Scale
Body image concerns due to changes in appearance from
SSc were assessed with the 14-item Satisfaction
With Appearance Scale [17, 18]. Items are scored on a
7-point scale ranging from 1 (strongly disagree) to
7 (strongly agree). The Satisfaction With Appearance has
two subscales, Perceived Social Impact, reflecting social
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discomfort, and Subjective Dissatisfaction, reflecting dis-
satisfaction with various body parts. Higher scores indi-
cate greater body image dissatisfaction.
Self-Efficacy to Manage Chronic Disease Scale
The 6-item Self-Efficacy to Manage Chronic Disease Scale
measures confidence in one’s ability to manage disease
symptoms as well as to reduce the need for medical
care and reliance on medications [19]. Items are rated
on a 10-point rating scale ranging from 1 (not confident
at all) to 10 (totally confident). The score for the scale is the
mean of all items, with higher scores reflecting greater
self-efficacy. The Self-Efficacy to Manage Chronic
Disease scale has been validated in patients with SSc [20].
Statistical analyses
Descriptive statistics were used to summarize SPIN
Cohort characteristics [means (S.D.) for continuous vari-
ables; frequency and proportions for categorical vari-
ables]. SPIN Cohort characteristics were compared with
the EUSTAR and CSRG cohorts, using published baseline
data [6, 7]. Available data were extracted from the publi-
cations and, where possible, compared with the SPIN
Cohort. Continuous variables were compared using a
t test, and categorical variables were compared using a
Chi-square or Fisher exact test. Statistical significance
was set at P < 0.05. The analyses were performed with
the statistical software Stata version 14.2.
Results
Characteristics of the SPIN Cohort
Baseline demographic, clinical and patient-reported out-
come data of the 1125 SPIN Cohort patients included in
the analyses are presented in Table 1. There were 460
(41%) participants classified as dcSSc. Mean (S.D.) age
was 55.6 years (12.1), and most patients were female
(87%) and White (82%).
Comparison of SPIN Cohort and CSRG
A comparison of the SPIN and CSRG cohorts by sub-
groups is presented in Table 2. Scl70 antibodies were
more frequent in both subsets in SPIN compared with
CSRG. Skin involvement, sclerodactyly and ulcers were
more frequent in CSRG than in SPIN in both subsets,
and there were more pitting scars in the lsSSc group.
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Dane H. Dougherty et al.

TABLE 1 Baseline SPIN demographic and clinical features and patient-reported core outcome measures

P-value
Combined Diffuse Limited (dcSSc vs
Variable (n = 1125) (n = 460) (n = 665) lcSSc)

Demographic variables
Age, mean (S.D.), in years 55.6 (12.1) 53.0 (12.2) 57.4 (11.7) <0.001
n = 457 n = 664
Gender (% female) 87.3 (982/1125) 85.9 (395/460) 88.3 (587/665) 0.235
Race (% White) 82.0 (922/1124) 75.4 (346/459) 86.6 (576/665) <0.001
BMI, mean (S.D.) 25.7 (6.0) 25.3 (6.4) 26.0 (5.8) 0.053
n = 1125 N = 460 n = 665
Clinical variables

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RP (% positive) 98.5 (1101/1118) 97.8 (447/457) 98.9 (654/661) 0.129
Age at first non-RP, mean (S.D.) 44.0 (13.4) 44.0 (13.0) 44.0 (13.7) 0.999
n = 1034 n = 431 n = 603
Time since first non-RP symptom, mean (S.D.) 11.6 (8.7) 9.1 (7.2) 13.4 (9.3) <0.001
n = 1038 n = 434 n = 604
Time since diagnosis, mean (S.D.) 9.7 (8) 8.3 (7.0) 10.8 (8.4) <0.001
<3 years since onset first non-RP, (%) 13.1 (147/1125) 18.3 (84/460) 9.5 (63/665) <0.001
SSc-related autoantibodies
ANA by IFA (% positive) 92.9 (953/1026) 91.1 (388/426) 94.2 (565/600) 0.058
ANA >1: 160 (% positive) 92.1 (832/903) 89.8 (334/372) 93.8 (498/531) 0.028
Nucleolar pattern (% positive) 20.0 (225/1125) 24.3 (112/460) 17.0 (113/665) 0.002
Centromere by IIF pattern or Immunoassay (% positive) 32.8 (276/841) 9.3 (32/344) 49.1 (244/497) <0.001
Scl 70 (% positive) 24.8 (236/951) 32.0 (131/409) 19.4 (105/542) <0.001
RNA Polymerase III (% positive) 21.1 (115/545) 41.0 (100/244) 5 (15/301) <0.001
Skin involvement
mRSS median (IQR) 5 (9) 12 (13.5) 3 (3) <0.001
mRSS mean (S.D.) 7.9 (8.4) 13.3 (10) 4.2 (4.2) <0.001
Puffy fingers (% positive) 61.5 (659/1071) 61.1 (267/437) 61.8 (392/634) 0.809
Sclerodactyly (proximal to MCP) (% positive) 85.7 (955/1114) 89.1 (407/457) 83.4 (548/657) 0.008
Digital tip pitting/scar (% positive) 42.1 (463/1101) 50.4 (226/448) 36.3 (237/653) <0.001
Distal pulp ulcers (% positive) 35.9 (397/1107) 39.1 (176/450) 33.6 (221/657) 0.062
Ulcer anywhere (% positive) 17.7 (191/1082) 26.5 (116/438) 11.6 (75/644) <0.001
Telangiectasias (any) (% positive) 73.0 (805/1102) 68.0 (304/447) 76.5 (501/655) 0.002
Teleangiectasias (face) (% positive) 81.4 (516/634) 81.1 (189/233) 81.5 (327/401) 0.893
Abnormal nailfold capillaries (% positive) 83.3 (779/935) 85.1 (326/383) 82.1 (453/552) 0.218
Abnormal pigment (any) (% positive) 32.9 (344/1047) 51.3 (219/427) 20.2 (125/620) <0.001
Abnormal facial pigment (% positive) 52.9 (171/323) 60.4 (116/192) 42.0 (55/131) 0.001
Organ involvement
Musculoskeletal
Tendon friction rubs (% positive) 24.6 (248/1008) 41.2 (167/405) 13.4 (81/603) <0.001
Joint contractures small (% positive) 25.5 (270/1059) 41.4 (180/435) 14.4 (90/624) <0.001
Joint contracture large (% positive) 12.7 (133/1046) 21.7 (93/429) 6.5 (40/617) <0.001
Gastrointestinal involvement
Oesophageal (% positive) 86.9 (971/1118) 88.5 (406/459) 85.7 (565/659) 0.186
Stomach (% positive) 30.6 (334/1092) 37.7 (168/446) 25.7 (166/646) <0.001
Intestinal (% positive) 39.5 (435/1100) 43.4 (195/449) 36.9 (240/651) 0.029
Pulmonary involvement
ILD (% positive) 36.2 (398/1099) 48.5 (219/452) 27.7 (179/647) <0.001
Pulmonary arterial hypertension (% positive) 10.4 (107/1029) 7.5 (31/414) 12.4 (76/615) 0.012
History of SSc renal crisis (% positive) 4.7 (53/1116) 9.2 (42/457) 1.7 (11/659) <0.001
Overlapping autoimmune disease
SLE (% positive) 3.3 (36/1106) 2.4 (11/452) 3.8 (25/654) 0.201
RA (% positive) 5.8 (64/1103) 6.7 (30/451) 5.2 (34/652) 0.316
Sjögren’s (% positive) 9.0 (97/1075) 7.5 (33/441) 10.1 (64/634) 0.142
Myositis (% positive) 5.8 (64/1100) 8.50 (38/447)8.5 4.0 (26/653) 0.002
Primary biliary cirrhosis (% positive) 1.4 (15/1096) 0.90 (4/449)0.9 1.7 (11/647) 0.257
Autoimmune thyroiditis (% positive) 6.1 (66/1079) 6.1 (27/441) 6.1 (39/638) 0.995
Patient-reported outcomes
CHFS, mean (S.D.) 13.7 (16.1) 19.2 (18.3) 9.8 (13.0) <0.001
HAQ-DI, mean (S.D.) 0.8 (0.7) 1.0 (0.7) 0.6 (0.6) <0.001

(continued)

1626 https://academic.oup.com/rheumatology
 Baseline features of the SPIN Cohort

TABLE 1 Continued

P-value
Combined Diffuse Limited (dcSSc vs
Variable (n = 1125) (n = 460) (n = 665) lcSSc)

Numeric Rating Scales

RP, mean (S.D.) 2.9 (2.9) 3.2 (3.1) 2.7 (2.8) 0.005
Finger ulcers, mean (S.D.) 1.5 (2.7) 2.0 (3.0) 1.2 (2.4) <0.001
Breathing problems, mean (S.D.) 2.2 (2.7) 2.3 (2.8) 2.0 (2.6) 0.063
Gastrointestinal problems, mean (S.D.) 2.5 (2.9) 2.5 (3.0) 2.5 (2.9) 0.711
Pain, mean (S.D.) 3.3 (2.9) 3.7 (3.0) 3.1 (2.8) <0.001
Overall SSc, mean (S.D.) 3.8 (0.2) 4.3 (0.1) 3.5 (0.1) <0.001
PHQ-8, mean (S.D.) 6.1 (5.3) 6.4 (5.5) 5.80 (5.1) 0.044
PROMIS-29
Physical Function, mean (S.D.) 43.0 (9.0) 41.4 (8.9) 44.1 (8.8) <0.001

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Anxiety, mean (S.D.) 51.5 (9.9) 52.6 (9.8) 50.7 (9.9) 0.001
Depression, mean (S.D.) 50.9 (9.3) 51.8 (9.5) 50.2 (9.1) 0.006
Fatigue, mean (S.D.) 55.3 (11.1) 56.0 (11.0) 54.8 (11.2) 0.079
Sleep disturbance, mean (S.D.) 52.3 (8.8) 52.8 (8.8) 52.0 (8.8) 0.113
Social roles, mean (S.D.) 48.0 (9.9) 46.7 (9.9) 48.9 (9.8) <0.001
Pain interference, mean (S.D.) 55.5 (9.7) 56.6 (9.9) 54.8 (9.5) 0.003
SEMCD, mean (S.D.) 6.4 (2.3) 6.2 (2.3) 6.6 (2.3) 0.112
SWAP
Social impact, mean (S.D.) 9.3 (9.5) 11.6 (10.0) 7.7 (8.7) <0.001
Dissatisfaction, mean (S.D.) 21.7 (12.9) 23.6 (12.3) 20.3 (13.2) <0.001

IFA: Indirect immunofluorescence assay; IIF: indirect immunofluorescence; ILD: interstitial lung disease mRSS: modified
Rodnan skin score; CHFS: Cochin Hand Function Scale; HAQ-DI: HAQ–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.

Abnormal nailfold capillaries, on the other hand, were Discussion

more frequent in SPIN than in CSRG in both subsets,
and there were no differences with respect to the pres-
ence of telangiectasia.
In regard to other organ involvement, there was a higher
occurrence of oesophageal involvement in SPIN com-
pared with in CSRG. Among dcSSc patients, SPIN
patients experienced more interstitial lung disease com-
pared with CSRG patients. The frequency of pulmonary
arterial hypertension and SSc renal crisis were similar be-
tween the cohorts.
Comparison of SPIN cohort and EUSTAR
A comparison of baseline features between the SPIN and
EUSTAR cohorts is presented in Table 2. For both sub-
sets, the frequency of the Scl 70 antibody was lower in
SPIN compared with in EUSTAR (dcSSc 32% vs 60%;
lcSSc 19% vs 23%). RNA polymerase 3 was higher in
the SPIN subset than in EUSTAR (dcSSc: 41 vs 5%,
lcSSc: 5 vs 1%), however, there was a high proportion
of missing data in EUSTAR. There was a higher frequency
of pitting scars in the SPIN dcSSc subset compared with
EUSTAR dcSSc subset, and distal pulp ulcers were more
frequent in both subsets of SPIN. Abnormal nailfold capil-
laries, on the other hand, were less frequent in SPIN than
in EUSTAR. Oesophageal involvement was more frequent
in SPIN compared with in EUSTAR. A direct comparison
of interstitial lung disease and pulmonary arterial hyper-
tension (PAH) could not be made, due to methodological
differences in the measurement of these variables.
The results of our study suggest that the SPIN Cohort has
many similarities with the EUSTAR and CSRG cohorts.
Methodological differences in the definition of organ-
specific involvement, as well as differences in data collec-
tion and the underlying rationale for establishing the
cohort could explain some of the dissimilarities that
were identified. The purpose of the SPIN project is to con-
duct rigorous trials on interventions to improve health-
related quality of life and disability. Clinical data were
collected to confirm the diagnosis of SSc and to provide
a disease profile in terms of presence or absence of organ
involvement at the time of enrolment. Both the CSRG and
the EUSTAR cohorts, on the other hand, were developed
specifically to follow disease progression over time.
With respect to organ involvement and antibody profiles
it is uncertain whether the differences between cohorts
are clinically significant or due to differences in method-
ology. For instance, for the definition of PAH, EUSTAR
used the 2009 European Society of Cardiology/
European Respiratory Society (ESC/ERS) guidelines,
while CSRG used echocardiographic measurement of
pulmonary artery systolic pressure of >45 mmHg, and
SPIN used the criterion ‘‘according to standard defin-
itions’’ without specific testing criteria.
Since the purpose of this study was to compare SPIN
Cohort characteristics with those of other SSc cohorts, we
reported only the presence of clinical variables. Of note,
the mere presence of a manifestation does not equate
clinical impact or symptom burden from a patient’s

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 TABLE 2 Comparison of the SPIN, CSRG and EUSTAR Cohorts by subgroups

1628
SPIN CSRG SPIN vs CSRG EUSTAR SPIN vs EUSTAR
Variable
Diffuse Limited Diffuse Limited P-value P-value Diffuse Limited P-value P-value
(n = 460) (n = 665) (n = 517) (n = 873) diffuse limited (n = 2838a) (n = 4481a) diffuse limited

Demographic variables
Dane H. Dougherty et al.

Age, mean (S.D.), in years 53.0 (12.2) 57.4 (11.7) 53.0 (11.7) 57.1 (12.3) 0.991 0.678 51.1 (13.7) 56.6 (13.4) 0.005 0.168
n = 457 n = 664 n = 2787 n = 4400
Gender (% female) 85.9 (395/460) 88.3 (587/665) 78.5 (406) 90.2 (787) 0.003 0.237 79.4 (2251/2835) 90.1 (4033/4477) 0.001 0.149
Race (% white) 75.4 (346/459) 86.6 (576/665) 82.6 (427) 91.4 (798) 0.006 0.003 84.5 (1149/1359) 92.1 (1977/2146) <0.001 <0.001
BMI, mean (S.D.) 25.3 (6.4) 26.0 (5.8) N/A N/A N/A N/A 23.5 (4.2) 24.6 (4.5) <0.001 <0.001
n = 460 n = 665 n = 1731 n = 2733
Clinical variables
RP (% positive) 97.8 (447/457) 98.9 (654/661) 96.3 (498) 97.5 (849) 0.173 0.020 96.1 (2703/2812) 96.6 (4290/4441) 0.074 0.001
Age at first non-RP, mean (S.D.) 44.0 (13.0) 44.0 (13.7) 44.0 (13.2) 45.5 (13.9) 0.968 0.036 44.2 (14.2) 47.2 (14.1) 0.749 <0.001
n = 431 n = 603 n = 2543 n = 4015
Time since first non-RP symptom, 9.1 (7.2) 13.4 (9.3) 9.0 (8.5) 11.5 (9.9) 0.821 <0.001 N/A N/A N/A N/A
mean (S.D.) n = 434 n = 604
SSc-related autoantibodies
ANA by IFA (% positive) 91.1 (388/426) 94.2 (565/600) 94.6 (489/517) 96.0 (838/873) 0.036 0.106 93.5 (2595/2776) 93.7 (4106/4382) 0.068 0.659
Centromere by IIF pattern or 9.3 (32/344) 49.1 (244/497) 12.1 (51/422) 47.5 (341/718) 0.218 0.583 7.2 (193/2679) 48.2 (2039/4230) 0.163 0.707
Immunoassay (% positive)
Scl 70 (% positive) 32 (131/409) 19.4 (105/542) 21.8 (92/422) 11.1 (80/718) <0.001 <0.001 59.8 (1607/2688) 23.2 (984/4244) <0.001 0.046
RNA polymerase III (% positive) 41.0 (100/244) 5.0 (15/301) 34.9 (107/307) 7.0 (34/488) 0.140 0.262
Skin involvement
mRSS, mean (S.D.) 13.3 (10.0) 4.2 (4.2) 18.1 (10.3) 5.1 (4.2) <0.001 <0.001 N/A N/A N/A N/A
n = 364 n = 530
b b
mRSS median (IQR) 12 (13.5) 3 (3) N/A N/A N/A N/A 16 (14) 6 (6)
Sclerodactyly(proximal to MCP) 89.1 (407/457) 83.4 (548/657) 96.3 (496) 91.7 (800) <0.001 <0.001 N/A N/A N/A N/A
(% positive)
Digital tip pitting/scar (% positive) 50.5 (226/448) 36.3 (237/653) 54.9 (282) 43.6 (380) 0.203 0.004 42.4 (1198/2827) 32.7 (1459/4463) 0.001 0.068
Distal pulp ulcers (% positive) 39.1 (176/450) 33.6 (221/657) 58.4 (302) 48.1 (420) <0.001 <0.001 20.1 (557/2773) 15.5 (679/4378) <0.001 <0.001
Telangiectasias (any) (% positive) 68.0 (304/447) 76.5 (501/655) 71.7 (352) 76.4 (654) 0.980 0.478 N/A N/A N/A N/A
Abnormal nailfoldcapillaries (% positive) 85.1 (326/383) 82.1 (453/552) 74.4 (384) 74.7 (651) <0.001 0.001 92.2 (1070/1161) 90.1 (1651/1833) <0.001 <0.001
Organ involvement
Gastrointestinal involvement
Oesophageal (% positive) 88.5 (406/459) 85.7 (565/659) 70.0 (319) 68.9 (557) <0.001 <0.001 69.5 (1966/2829) 66.4 (2966/4468) <0.001 <0.001
Pulmonary involvement
Interstitial lung disease (% positive) 48.5 (219/452) 27.7 (179/647) 40.3 (203) 25.4 (218) 0.004 0.237 N/A N/A N/A N/A
Pulmonary arterial hypertension (% positive) 7.5 (31/414) 12.4 (76/615) 10.5 (46) 11.1 (82) 0.438 0.068 22.1 (623/2821) 20.7 (922/4454) <0.001 <0.001
History of SSc renal crisis (% positive) 9.2 (42/457) 1.7 (11/659) 7.6 (39) 1.9 (16) 0.353 0.810 4 (113/2815) 1 (44/4445) <0.001 0.115
Overlapping autoimmune disease

(continued)

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 Baseline features of the SPIN Cohort

CSRG did not specify n when missing data were <10%. Calculations were based on total n when no % missing data was provided. aMissing Data in EULAR was reported as a
percentage of combined data across subtypes. This table therefore makes the assumption of homogeneous missing data percentages across subtypes, used to calculate n for each
variable. bNot possible to assess significance without EUSTAR raw data. IFA: Indirect immunofluorescence assay; mRSS: modified Rodnan skin score; CSRG: Canadian Scleroderma
SPIN vs EUSTAR
perspective. Future studies should assess the complex

P-value P-value
diffuse limited

N/A
N/A
N/A
N/A
interplay of clinical characteristics and their impact on
quality of life.
The present study has limitations that should be con-

N/A
N/A
N/A
N/A
sidered in interpreting results. First, as both the SPIN
Cohort and the CSRG Registry enrol patients from
Canada, there is potential overlap between the partici-
(n = 4481a)

pants in both cohorts. Overall, 26% of SPIN Cohort par-

Limited

ticipants were enrolled from Candian centres, indicating

N/A
N/A
N/A
N/A
the maximum possible overlap between SPIN and the
CSRG. As published summary data were used to com-
EUSTAR

pare the cohorts, data were not available to identify the

exact overlap between the cohorts. Second, the time-

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(n = 2838a)

frame of enrolment differed somewhat between the

Diffuse

N/A
N/A
N/A
N/A

three cohorts. Third, the definitions of medical variables

also differed somewhat between the cohorts, limiting the
comparisons that can be made. Although additional
measures of disease variables may have been available
P-value P-value

0.966
0.643
0.282
0.285
diffuse limited
SPIN vs CSRG

for CSRG and EUSTAR, we compared SPIN Cohort data

with the most comprehensive published data on these
cohorts [9, 10]. Additional analyses comparing geograph-
0.653
0.003
0.428
0.043

ical regions in more detail may be of interest, but were

beyond the scope of the present paper. Fourth, the
SPIN Cohort constitutes a convenience sample of SSc
patients receiving treatment at a SPIN recruiting centre,
(n = 873)
Limited

and patients at these centres may differ from those in

(33)
(41)
(74)
(26)

other settings. Finally, SSc patients in the SPIN Cohort

3.8
4.8
8.6
3

complete questionnaires online, and participants may

CSRG

differ from patients without internet access, for instance,

Research Group; EUSTAR: European Scleroderma Trials And Research; N/A: not applicable.

in terms of education, coping or ability for self-advocacy.

(n = 517)
Diffuse

Overall, there are many similarities between the SPIN

(15)
(14)
(32)
(27)

Cohort and the other large recently reported SSc cohorts.

3
2.8
6.3
5.3

Therefore, data emerging from the SPIN Cohort should be

generalizable to the broader population of SSc patients,
3.8 (25/654)
5.2 (34/652)
(33/441) 10.1 (64/634)
4.0 (26/653)

although it should be noted that all three cohorts include

(n = 665)
Limited

primarily White participants.

SPIN

Acknowledgements
(11/452)
(30/451)

(38/447)
(n = 460)

SPIN is funded by the Canadian Institutes of

Diffuse

Health Research (CIHR; PI = Thombs, TR3-119192;

PI = Thombs, PJT-148504; PIs = Thombs, Mouthon,
2.4
6.7
7.5
8.5

Poiraudeau, PJT-149073) and the Arthritis Society (SOG-

16-380, PI = Thombs). In addition, SPIN has received in-
stitutional contributions from the Lady Davis Institute for
Medical Research of the Jewish General Hospital,
Montreal, QC, Canada and from McGill University,
Montreal, Canada. SPIN has also received support from
the Scleroderma Society of Ontario, Scleroderma Canada
and Sclérodermie Quebec. Dr L.K. was supported by a
CIHR Banting Postdoctoral Fellowship. Dr B.D.T. was
Sjögren’s (% positive)

supported by an Investigator Salary Award from the

Myositis (% positive)

Arthritis Society.
SLE (% positive)
RA (% positive)
TABLE 2 Continued

SPIN Investigators: Alexandra Albert, Université Laval,

Québec, QC, Canada; Guylaine Arsenault, Sherbrooke
University, Sherbrooke, QC, Canada; Lyne Bissonette,
Variable

Sherbrooke University, Sherbrooke, QC, Canada;

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

https://academic.oup.com/rheumatology 1629
Dane H. Dougherty et al.
Patricia Carreira, Servicio de Reumatologia del Hospital
12 de Octubre, Madrid, Spain; Angela Costa Maia,
University of Minho, Braga, Portugal; Pierre Dagenais,
Sherbrooke University, Sherbrooke, QC, Canada; Robyn
Domsic, University of Pittsburgh, Pittsburgh, PA, USA;
Ghassan El-Baalbaki, Université du Québec à Montréal,
Montréal, QC, Canada; Carolyn Ells, McGill University,
Montréal, QC, Canada; Cornelia van den Ende, Sint
Maartenskliniek, Nijmegen, The Netherlands; Kim
Fligelstone, Scleroderma Society, London, UK; Catherine
Fortune, Scleroderma Society of Ontario, Hamilton, ON,
Canada; Dominique Godard, Association des
Sclérodermiques de France, Sorel-Moussel, France;
Genevieve Gyger, Department of Medicine, McGill
University, Montreal, QC, Canada; Daphna Harel, New
York University, New York, NY, USA; Alena Ikic,
Université Laval, Québec, QC, Canada; Ann Impens,
Midwestern University, Downers Grove, IL, USA; Yeona
Jang, McGill University, Montréal, QC, Canada;
Artur Jose de B. Fernandes, Sherbrooke University,
Sherbrooke, QC, Canada; Ann Tyrell Kennedy,
Federation of European Scleroderma Associations,
Dublin, Ireland; Nader Khalidi, McMaster University,
Hamilton, ON, Canada; Benjamin Korman, Northwestern
University, Chicago, IL, USA; Catarina Leite, University of
Minho, Braga, Portugal; Patrick Liang, Sherbrooke
University, Sherbrooke, QC, Canada; Carlo Marra,
Memorial University, St John’s, NL, Canada; Ariel
Masetto, Sherbrooke University, Sherbrooke, QC,
Canada; Karen Nielsen, Scleroderma Society of Ontario,
Hamilton, ON, Canada; Alexandra Portales, Asociación
Española de Esclerodermia, Madrid, Spain; Robert
Riggs, Scleroderma Foundation, USA; David Robinson,
University of Manitoba, Winnipeg, MB, Canada; Tatiana
Sofia Rodriguez Reyna, Instituto Nacional de Ciencias
Médicas y Nutrición Salvador Zubirán, Mexico City,
Mexico; Sophie Roux, Sherbrooke University,
Sherbrooke, QC, Canada; Anne A. Schouffoer, Leiden
University Medical Center, Leiden, The Netherlands;
Doug Smith, University of Ottawa, Ottawa, ON, Canada;
Russell J. Steele, Jewish General Hospital and McGill
University, Montréal, QC, Canada; Maria E. Suarez-
Almazor, University of Texas MD Anderson Cancer
Center, Houston, TX, USA; John Varga, Northwestern
University, Chicago, IL, USA; Joep Welling, NVLE Dutch
patient organization for systemic autoimmune diseases,
Utrecht, The Netherlands; Fredrick Wigley, Division of
Rheumatology, Johns Hopkins School of Medicine,
Baltimore, MD, USA; Durhane Wong-Rieger, Canadian
Organization for Rare Disorders, Toronto, ON, Canada;
Julie Cumin, Jewish General Hospital; Vanessa C.
Delisle, Jewish General Hospital and McGill University,
Montréal, QC, Canada; Claire Fedoruk, Jewish General
Hospital, Montréal, QC, Canada; Rina S. Fox, San Diego
State University and University of California, San Diego,
San Diego, CA, USA; Shadi Gholizadeh, San Diego State
University and University of California, San Diego, San
Diego, CA, USA; Lisa R. Jewett, Jewish General
Hospital and McGill University, Montréal, QC, Canada;
1630
Brooke Levis, Jewish General Hospital and McGill
University, Montréal, QC, Canada; Sarah D. Mills, San
Diego State University and University of California, San
Diego, San Diego, CA, USA; Mia R. Pepin, Jewish
General Hospital, Montréal, QC, Canada; Jennifer
Persmann, Université du Québec à Montréal, Montréal,
QC, Canada; Kimberly Turner, Jewish General Hospital,
Montréal, QC, Canada.
Funding: No specific funding was received from any
bodies in the public, commercial or not-for-profit sectors
to carry out the work described in this manuscript.
Disclosure statement: D.E.F. has research support from
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AbbVie, Actelion, Amgen, BMS, Corbus, National
Institutes of Health, Novartis, Pfizer, and Roche/
Genentech, is a consultant to Abbvie, Actelion, Amgen,
BMS, Cytori, Novartis, Pfizer, and Roche/Genentech and
is on the speakers bureau for CMC Connect (McCnn
Health Company). The other authors have declared no
conflicts of interest.
Supplementary data
Supplementary data are available at Rheumatology online.
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