The Scleroderma Patient-Centered Intervention Network Cohort: baseline clinical features and comparison with other large scleroderma cohorts

The Scleroderma Patient-Centered Intervention Network Cohort: baseline clinical features and... 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. 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 remarkably 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. systemic sclerosis, scleroderma, systemic scleroderma, cohort Rheumatology key messages The web-based Scleroderma Patient-centered Intervention Network Cohort is designed to collect patient-reported 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 disease-specific psychosocial, educational, self-management and rehabilitation interventions that are important components of disease management and patient-centred care in more common diseases. In common chronic illnesses, evidence suggests that self-management strategies can positively impact disease-specific outcomes and quality of life [1, 2]. However, in the context of rare diseases 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, educational, 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 classified 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 complete questionnaires online in English or French. The SPIN sample is a convenience sample. The attending physician or nurse coordinator invites eligible patients, obtains informed consent and completes a medical data form that is submitted online to initiate patient registration. Cohort patients 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 between September 2004 and July 2013. Patients in the CSRG cohort are adults with a diagnosis of SSc confirmed by a rheumatologist (98% met the 2013 ACR/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 classification 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 (impossible). 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 measured 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 depressive 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 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 discomfort, and Subjective Dissatisfaction, reflecting dissatisfaction with various body parts. Higher scores indicate 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 variables; frequency and proportions for categorical variables]. SPIN Cohort characteristics were compared with the EUSTAR and CSRG cohorts, using published baseline data [6, 7]. Available data were extracted from the publications 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 outcome 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%). Table 1 Baseline SPIN demographic and clinical features and patient-reported core outcome measures Variable Combined (n = 1125) Diffuse (n = 460) Limited (n = 665) P-value (dcSSc vs lcSSc) Demographic variables     Age, mean (s.d.), in years 55.6 (12.1) 53.0 (12.2) n = 457 57.4 (11.7) n = 664 <0.001     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) n = 1125 25.3 (6.4) N = 460 26.0 (5.8) n = 665 0.053 Clinical variables     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) n = 1034 44.0 (13.0) n = 431 44.0 (13.7) n = 603 0.999     Time since first non-RP symptom, mean (s.d.) 11.6 (8.7) n = 1038 9.1 (7.2) n = 434 13.4 (9.3) n = 604 <0.001     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 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     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 Variable Combined (n = 1125) Diffuse (n = 460) Limited (n = 665) P-value (dcSSc vs lcSSc) Demographic variables     Age, mean (s.d.), in years 55.6 (12.1) 53.0 (12.2) n = 457 57.4 (11.7) n = 664 <0.001     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) n = 1125 25.3 (6.4) N = 460 26.0 (5.8) n = 665 0.053 Clinical variables     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) n = 1034 44.0 (13.0) n = 431 44.0 (13.7) n = 603 0.999     Time since first non-RP symptom, mean (s.d.) 11.6 (8.7) n = 1038 9.1 (7.2) n = 434 13.4 (9.3) n = 604 <0.001     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 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     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. Table 1 Baseline SPIN demographic and clinical features and patient-reported core outcome measures Variable Combined (n = 1125) Diffuse (n = 460) Limited (n = 665) P-value (dcSSc vs lcSSc) Demographic variables     Age, mean (s.d.), in years 55.6 (12.1) 53.0 (12.2) n = 457 57.4 (11.7) n = 664 <0.001     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) n = 1125 25.3 (6.4) N = 460 26.0 (5.8) n = 665 0.053 Clinical variables     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) n = 1034 44.0 (13.0) n = 431 44.0 (13.7) n = 603 0.999     Time since first non-RP symptom, mean (s.d.) 11.6 (8.7) n = 1038 9.1 (7.2) n = 434 13.4 (9.3) n = 604 <0.001     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 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     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 Variable Combined (n = 1125) Diffuse (n = 460) Limited (n = 665) P-value (dcSSc vs lcSSc) Demographic variables     Age, mean (s.d.), in years 55.6 (12.1) 53.0 (12.2) n = 457 57.4 (11.7) n = 664 <0.001     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) n = 1125 25.3 (6.4) N = 460 26.0 (5.8) n = 665 0.053 Clinical variables     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) n = 1034 44.0 (13.0) n = 431 44.0 (13.7) n = 603 0.999     Time since first non-RP symptom, mean (s.d.) 11.6 (8.7) n = 1038 9.1 (7.2) n = 434 13.4 (9.3) n = 604 <0.001     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 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     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. Comparison of SPIN Cohort and CSRG A comparison of the SPIN and CSRG cohorts by subgroups 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. Abnormal nailfold capillaries, on the other hand, were more frequent in SPIN than in CSRG in both subsets, and there were no differences with respect to the presence of telangiectasia. Table 2 Comparison of the SPIN, CSRG and EUSTAR Cohorts by subgroups Variable SPIN CSRG SPIN vs CSRG EUSTAR SPIN vs EUSTAR Diffuse (n = 460) Limited (n = 665) Diffuse (n = 517) Limited (n = 873) P-value diffuse P-value limited Diffuse (n = 2838a) Limited (n = 4481a) P-value diffuse P-value limited Demographic variables     Age, mean (s.d.), in years 53.0 (12.2) n = 457 57.4 (11.7) n = 664 53.0 (11.7) 57.1 (12.3) 0.991 0.678 51.1 (13.7) n = 2787 56.6 (13.4) n = 4400 0.005 0.168     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) n = 460 26.0 (5.8) n = 665 N/A N/A N/A N/A 23.5 (4.2) n = 1731 24.6 (4.5) n = 2733 <0.001 <0.001 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) n = 431 44.0 (13.7) n = 603 44.0 (13.2) 45.5 (13.9) 0.968 0.036 44.2 (14.2) n = 2543 47.2 (14.1) n = 4015 0.749 <0.001 Time since first non-RP symptom, mean (s.d.) 9.1 (7.2) n = 434 13.4 (9.3) n = 604 9.0 (8.5) 11.5 (9.9) 0.821 <0.001 N/A N/A N/A N/A 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 Immunoassay (% positive) 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 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) n = 364 4.2 (4.2) n = 530 18.1 (10.3) 5.1 (4.2) <0.001 <0.001 N/A N/A N/A N/A mRSS median (IQR) 12 (13.5) 3 (3) N/A N/A N/A N/A 16 (14) 6 (6) b b Sclerodactyly(proximal to MCP) (% positive) 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 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     SLE (% positive) 2.4 (11/452) 3.8 (25/654) 3 (15) 3.8 (33) 0.653 0.966 N/A N/A N/A N/A     RA (% positive) 6.7 (30/451) 5.2 (34/652) 2.8 (14) 4.8 (41) 0.003 0.643 N/A N/A N/A N/A     Sjögren’s (% positive) 7.5 (33/441) 10.1 (64/634) 6.3 (32) 8.6 (74) 0.428 0.282 N/A N/A N/A N/A     Myositis (% positive) 8.5 (38/447) 4.0 (26/653) 5.3 (27) 3 (26) 0.043 0.285 N/A N/A N/A N/A Variable SPIN CSRG SPIN vs CSRG EUSTAR SPIN vs EUSTAR Diffuse (n = 460) Limited (n = 665) Diffuse (n = 517) Limited (n = 873) P-value diffuse P-value limited Diffuse (n = 2838a) Limited (n = 4481a) P-value diffuse P-value limited Demographic variables     Age, mean (s.d.), in years 53.0 (12.2) n = 457 57.4 (11.7) n = 664 53.0 (11.7) 57.1 (12.3) 0.991 0.678 51.1 (13.7) n = 2787 56.6 (13.4) n = 4400 0.005 0.168     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) n = 460 26.0 (5.8) n = 665 N/A N/A N/A N/A 23.5 (4.2) n = 1731 24.6 (4.5) n = 2733 <0.001 <0.001 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) n = 431 44.0 (13.7) n = 603 44.0 (13.2) 45.5 (13.9) 0.968 0.036 44.2 (14.2) n = 2543 47.2 (14.1) n = 4015 0.749 <0.001 Time since first non-RP symptom, mean (s.d.) 9.1 (7.2) n = 434 13.4 (9.3) n = 604 9.0 (8.5) 11.5 (9.9) 0.821 <0.001 N/A N/A N/A N/A 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 Immunoassay (% positive) 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 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) n = 364 4.2 (4.2) n = 530 18.1 (10.3) 5.1 (4.2) <0.001 <0.001 N/A N/A N/A N/A mRSS median (IQR) 12 (13.5) 3 (3) N/A N/A N/A N/A 16 (14) 6 (6) b b Sclerodactyly(proximal to MCP) (% positive) 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 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     SLE (% positive) 2.4 (11/452) 3.8 (25/654) 3 (15) 3.8 (33) 0.653 0.966 N/A N/A N/A N/A     RA (% positive) 6.7 (30/451) 5.2 (34/652) 2.8 (14) 4.8 (41) 0.003 0.643 N/A N/A N/A N/A     Sjögren’s (% positive) 7.5 (33/441) 10.1 (64/634) 6.3 (32) 8.6 (74) 0.428 0.282 N/A N/A N/A N/A     Myositis (% positive) 8.5 (38/447) 4.0 (26/653) 5.3 (27) 3 (26) 0.043 0.285 N/A N/A N/A N/A CSRG did not specify n when missing data were <10%. Calculations were based on total n when no % missing data was provided. a Missing 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. b Not possible to assess significance without EUSTAR raw data. IFA: Indirect immunofluorescence assay; mRSS: modified Rodnan skin score; CSRG: Canadian Scleroderma Research Group; EUSTAR: European Scleroderma Trials And Research; N/A: not applicable. Table 2 Comparison of the SPIN, CSRG and EUSTAR Cohorts by subgroups Variable SPIN CSRG SPIN vs CSRG EUSTAR SPIN vs EUSTAR Diffuse (n = 460) Limited (n = 665) Diffuse (n = 517) Limited (n = 873) P-value diffuse P-value limited Diffuse (n = 2838a) Limited (n = 4481a) P-value diffuse P-value limited Demographic variables     Age, mean (s.d.), in years 53.0 (12.2) n = 457 57.4 (11.7) n = 664 53.0 (11.7) 57.1 (12.3) 0.991 0.678 51.1 (13.7) n = 2787 56.6 (13.4) n = 4400 0.005 0.168     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) n = 460 26.0 (5.8) n = 665 N/A N/A N/A N/A 23.5 (4.2) n = 1731 24.6 (4.5) n = 2733 <0.001 <0.001 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) n = 431 44.0 (13.7) n = 603 44.0 (13.2) 45.5 (13.9) 0.968 0.036 44.2 (14.2) n = 2543 47.2 (14.1) n = 4015 0.749 <0.001 Time since first non-RP symptom, mean (s.d.) 9.1 (7.2) n = 434 13.4 (9.3) n = 604 9.0 (8.5) 11.5 (9.9) 0.821 <0.001 N/A N/A N/A N/A 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 Immunoassay (% positive) 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 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) n = 364 4.2 (4.2) n = 530 18.1 (10.3) 5.1 (4.2) <0.001 <0.001 N/A N/A N/A N/A mRSS median (IQR) 12 (13.5) 3 (3) N/A N/A N/A N/A 16 (14) 6 (6) b b Sclerodactyly(proximal to MCP) (% positive) 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 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     SLE (% positive) 2.4 (11/452) 3.8 (25/654) 3 (15) 3.8 (33) 0.653 0.966 N/A N/A N/A N/A     RA (% positive) 6.7 (30/451) 5.2 (34/652) 2.8 (14) 4.8 (41) 0.003 0.643 N/A N/A N/A N/A     Sjögren’s (% positive) 7.5 (33/441) 10.1 (64/634) 6.3 (32) 8.6 (74) 0.428 0.282 N/A N/A N/A N/A     Myositis (% positive) 8.5 (38/447) 4.0 (26/653) 5.3 (27) 3 (26) 0.043 0.285 N/A N/A N/A N/A Variable SPIN CSRG SPIN vs CSRG EUSTAR SPIN vs EUSTAR Diffuse (n = 460) Limited (n = 665) Diffuse (n = 517) Limited (n = 873) P-value diffuse P-value limited Diffuse (n = 2838a) Limited (n = 4481a) P-value diffuse P-value limited Demographic variables     Age, mean (s.d.), in years 53.0 (12.2) n = 457 57.4 (11.7) n = 664 53.0 (11.7) 57.1 (12.3) 0.991 0.678 51.1 (13.7) n = 2787 56.6 (13.4) n = 4400 0.005 0.168     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) n = 460 26.0 (5.8) n = 665 N/A N/A N/A N/A 23.5 (4.2) n = 1731 24.6 (4.5) n = 2733 <0.001 <0.001 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) n = 431 44.0 (13.7) n = 603 44.0 (13.2) 45.5 (13.9) 0.968 0.036 44.2 (14.2) n = 2543 47.2 (14.1) n = 4015 0.749 <0.001 Time since first non-RP symptom, mean (s.d.) 9.1 (7.2) n = 434 13.4 (9.3) n = 604 9.0 (8.5) 11.5 (9.9) 0.821 <0.001 N/A N/A N/A N/A 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 Immunoassay (% positive) 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 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) n = 364 4.2 (4.2) n = 530 18.1 (10.3) 5.1 (4.2) <0.001 <0.001 N/A N/A N/A N/A mRSS median (IQR) 12 (13.5) 3 (3) N/A N/A N/A N/A 16 (14) 6 (6) b b Sclerodactyly(proximal to MCP) (% positive) 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 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     SLE (% positive) 2.4 (11/452) 3.8 (25/654) 3 (15) 3.8 (33) 0.653 0.966 N/A N/A N/A N/A     RA (% positive) 6.7 (30/451) 5.2 (34/652) 2.8 (14) 4.8 (41) 0.003 0.643 N/A N/A N/A N/A     Sjögren’s (% positive) 7.5 (33/441) 10.1 (64/634) 6.3 (32) 8.6 (74) 0.428 0.282 N/A N/A N/A N/A     Myositis (% positive) 8.5 (38/447) 4.0 (26/653) 5.3 (27) 3 (26) 0.043 0.285 N/A N/A N/A N/A CSRG did not specify n when missing data were <10%. Calculations were based on total n when no % missing data was provided. a Missing 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. b Not possible to assess significance without EUSTAR raw data. IFA: Indirect immunofluorescence assay; mRSS: modified Rodnan skin score; CSRG: Canadian Scleroderma Research Group; EUSTAR: European Scleroderma Trials And Research; N/A: not applicable. In regard to other organ involvement, there was a higher occurrence of oesophageal involvement in SPIN compared with in CSRG. Among dcSSc patients, SPIN patients experienced more interstitial lung disease compared with CSRG patients. The frequency of pulmonary arterial hypertension and SSc renal crisis were similar between 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 subsets, 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 capillaries, 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 hypertension (PAH) could not be made, due to methodological differences in the measurement of these variables. Discussion 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 collection 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 conduct 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 methodology. 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 definitions” 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 perspective. Future studies should assess the complex interplay of clinical characteristics and their impact on quality of life. The present study has limitations that should be considered in interpreting results. First, as both the SPIN Cohort and the CSRG Registry enrol patients from Canada, there is potential overlap between the participants in both cohorts. Overall, 26% of SPIN Cohort participants were enrolled from Candian centres, indicating the maximum possible overlap between SPIN and the CSRG. As published summary data were used to compare the cohorts, data were not available to identify the exact overlap between the cohorts. Second, the timeframe of enrolment differed somewhat between the 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 for CSRG and EUSTAR, we compared SPIN Cohort data with the most comprehensive published data on these cohorts [9, 10]. Additional analyses comparing geographical 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, and patients at these centres may differ from those in other settings. Finally, SSc patients in the SPIN Cohort complete questionnaires online, and participants may differ from patients without internet access, for instance, in terms of education, coping or ability for self-advocacy. Overall, there are many similarities between the SPIN Cohort and the other large recently reported SSc cohorts. Therefore, data emerging from the SPIN Cohort should be generalizable to the broader population of SSc patients, although it should be noted that all three cohorts include primarily White participants. Acknowledgements SPIN is funded by the Canadian Institutes of Health Research (CIHR; PI = Thombs, TR3-119192; PI = Thombs, PJT-148504; PIs = Thombs, Mouthon, Poiraudeau, PJT-149073) and the Arthritis Society (SOG-16-380, PI = Thombs). In addition, SPIN has received institutional 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 supported by an Investigator Salary Award from the Arthritis Society. SPIN Investigators: Alexandra Albert, Université Laval, Québec, QC, Canada; Guylaine Arsenault, Sherbrooke University, Sherbrooke, QC, Canada; Lyne Bissonette, Sherbrooke University, Sherbrooke, QC, Canada; Isabelle Boutron, Université Paris Descartes, and Assistance Publique-Hôpitaux de Paris, Paris, France; 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; 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 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. References 1 Foster G , Taylor S , Eldridge S , Ramsay J , Griffiths CJ. Self-management education programmes by lay leaders for people with chronic conditions . Cochrane Database Syst Rev 2007 ; 4 : CD005108 . 2 Lorig KR , Sobel DS , Ritter PL , Laurent D , Hobbs M. Effect of a self-management program on patients with chronic disease . Eff Clin Pract 2001 ; 4 : 256 – 62 . Google Scholar PubMed 3 Kwakkenbos L , Jewett LR , Baron M 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 . Google Scholar CrossRef Search ADS PubMed 4 Relton C , Torgerson D , O’Cathain A , Nicholl J. Rethinking pragmatic randomized controlled trials: introducing the “cohort multiple randomised controlled trial” design . BMJ 2010 ; 340 : c1066 . Google Scholar CrossRef Search ADS PubMed 5 van den Hoogen F , Khanna D , Fransen J et al. . 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism collaborative initiative . Arthritis Rheumatol 2013 ; 65 : 2737 – 47 . Google Scholar CrossRef Search ADS 6 Meier FM , Frommer KW , Dinser R et al. . Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database . Ann Rheum Dis 2012 ; 71 : 1355 – 60 . Google Scholar CrossRef Search ADS PubMed 7 Diab S , Dostrovsky N , Hudson M et al. . Systemic sclerosis sine scleroderma: a multicenter study of 1417 subjects . J Rheumatol 2014 ; 41 : 2179 – 85 . Google Scholar CrossRef Search ADS PubMed 8 Walker UA , Tyndall A , Czirják L et al. . Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database . Ann Rheum Dis 2007 ; 66 : 754 – 63 . Google Scholar CrossRef Search ADS PubMed 9 Duruöz MT , Poiraudeau S , Fermanian J et al. . Development and validation of a rheumatoid hand functional disability scale that assesses functional handicap . J Rheumatol 1996 ; 23 : 1167 – 72 . Google Scholar PubMed 10 Rannou F , Poiraudeau S , Berezne A et al. . Assessing disability and quality of life in systemic sclerosis: construct validities of the Cochin Hand Function Scale, Health Assessment Questionnaire (HAQ), Systemic Sclerosis HAQ, and Medical Outcomes Study 36-Item Short Form Health Survey . Arthritis Rheumatol 2007 ; 57 : 94 – 102 . Google Scholar CrossRef Search ADS 11 Poole JL , Steen VD. The use of the Health Assessment Questionnaire (HAQ) to determine physical disability in systemic sclerosis . Arthritis Care Res 1991 ; 4 : 27 – 31 . Google Scholar CrossRef Search ADS PubMed 12 Kroenke K , Strine TW , Spitzer RL et al. . The PHQ-8 as a measure of current depression in the general population . J Affect Disord 2009 ; 114 : 163 – 73 . Google Scholar CrossRef Search ADS PubMed 13 Razykov I , Hudson M , Baron M , Thombs BD. The utility of the PHQ-9 to assess suicide risk in patients with systemic sclerosis . Arthritis Care Res 2013 ; 65 : 753 – 8 . Google Scholar CrossRef Search ADS 14 Milette K , Hudson M , Baron M , Thombs BD ; Canadian Scleroderma Research Group . Comparison of the PHQ-9 and CES-D depression scales in systemic sclerosis: internal consistency reliability, convergent validity and clinical correlates . Rheumatology 2010 ; 49 : 789 – 96 . Google Scholar CrossRef Search ADS PubMed 15 The NIH Patient-Reported Outcomes Measurement Information System. http://www.healthmeasures.net/explore-measurement-systems/promis (2 December 2016, date last accessed). 16 Kwakkenbos L , Thombs BD , Khanna D et al. . Performance of the patient-reported outcomes measurement information system-29 in scleroderma: a Scleroderma Patient-centered Intervention Network Cohort study . Rheumatology 2017 ; 56 : 1302 – 11 . Google Scholar CrossRef Search ADS PubMed 17 Lawrence JW , Heinberg LJ , Roca RP et al. . Development and validation of the Satisfaction With Appearance Scale: assessing body image among burn-injured patients . Psychol Assess 1998 ; 10 : 64 – 70 . Google Scholar CrossRef Search ADS 18 Mills SD , Fox RS , Merz EL et al. . Evaluation of the Satisfaction with Appearance Scale and its short form in systemic sclerosis: analysis from the UCLA Scleroderma Quality of Life study . Rheumatology 2015 ; 42 : 1624 – 30 . Google Scholar CrossRef Search ADS 19 Ritter PL , Lorig K. The English and Spanish Self-Efficacy to Manage Chronic Disease Scale measures were validated using multiple studies . J Clin Epidemiol 2014 ; 67 : 1265 – 73 . Google Scholar CrossRef Search ADS PubMed 20 Riehm KE , Kwakkenbos L , Carrier ME et al. . Validation of the Self-Efficacy for Managing Chronic Disease (SEMCD) Scale: a Scleroderma Patient-centered Intervention Network (SPIN) Cohort Study . Arthritis Care Res 2016 ; 68 : 1195 – 200 . Google Scholar CrossRef Search ADS © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. 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Abstract

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. 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 remarkably 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. systemic sclerosis, scleroderma, systemic scleroderma, cohort Rheumatology key messages The web-based Scleroderma Patient-centered Intervention Network Cohort is designed to collect patient-reported 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 disease-specific psychosocial, educational, self-management and rehabilitation interventions that are important components of disease management and patient-centred care in more common diseases. In common chronic illnesses, evidence suggests that self-management strategies can positively impact disease-specific outcomes and quality of life [1, 2]. However, in the context of rare diseases 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, educational, 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 classified 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 complete questionnaires online in English or French. The SPIN sample is a convenience sample. The attending physician or nurse coordinator invites eligible patients, obtains informed consent and completes a medical data form that is submitted online to initiate patient registration. Cohort patients 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 between September 2004 and July 2013. Patients in the CSRG cohort are adults with a diagnosis of SSc confirmed by a rheumatologist (98% met the 2013 ACR/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 classification 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 (impossible). 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 measured 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 depressive 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 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 discomfort, and Subjective Dissatisfaction, reflecting dissatisfaction with various body parts. Higher scores indicate 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 variables; frequency and proportions for categorical variables]. SPIN Cohort characteristics were compared with the EUSTAR and CSRG cohorts, using published baseline data [6, 7]. Available data were extracted from the publications 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 outcome 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%). Table 1 Baseline SPIN demographic and clinical features and patient-reported core outcome measures Variable Combined (n = 1125) Diffuse (n = 460) Limited (n = 665) P-value (dcSSc vs lcSSc) Demographic variables     Age, mean (s.d.), in years 55.6 (12.1) 53.0 (12.2) n = 457 57.4 (11.7) n = 664 <0.001     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) n = 1125 25.3 (6.4) N = 460 26.0 (5.8) n = 665 0.053 Clinical variables     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) n = 1034 44.0 (13.0) n = 431 44.0 (13.7) n = 603 0.999     Time since first non-RP symptom, mean (s.d.) 11.6 (8.7) n = 1038 9.1 (7.2) n = 434 13.4 (9.3) n = 604 <0.001     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 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     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 Variable Combined (n = 1125) Diffuse (n = 460) Limited (n = 665) P-value (dcSSc vs lcSSc) Demographic variables     Age, mean (s.d.), in years 55.6 (12.1) 53.0 (12.2) n = 457 57.4 (11.7) n = 664 <0.001     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) n = 1125 25.3 (6.4) N = 460 26.0 (5.8) n = 665 0.053 Clinical variables     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) n = 1034 44.0 (13.0) n = 431 44.0 (13.7) n = 603 0.999     Time since first non-RP symptom, mean (s.d.) 11.6 (8.7) n = 1038 9.1 (7.2) n = 434 13.4 (9.3) n = 604 <0.001     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 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     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. Table 1 Baseline SPIN demographic and clinical features and patient-reported core outcome measures Variable Combined (n = 1125) Diffuse (n = 460) Limited (n = 665) P-value (dcSSc vs lcSSc) Demographic variables     Age, mean (s.d.), in years 55.6 (12.1) 53.0 (12.2) n = 457 57.4 (11.7) n = 664 <0.001     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) n = 1125 25.3 (6.4) N = 460 26.0 (5.8) n = 665 0.053 Clinical variables     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) n = 1034 44.0 (13.0) n = 431 44.0 (13.7) n = 603 0.999     Time since first non-RP symptom, mean (s.d.) 11.6 (8.7) n = 1038 9.1 (7.2) n = 434 13.4 (9.3) n = 604 <0.001     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 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     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 Variable Combined (n = 1125) Diffuse (n = 460) Limited (n = 665) P-value (dcSSc vs lcSSc) Demographic variables     Age, mean (s.d.), in years 55.6 (12.1) 53.0 (12.2) n = 457 57.4 (11.7) n = 664 <0.001     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) n = 1125 25.3 (6.4) N = 460 26.0 (5.8) n = 665 0.053 Clinical variables     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) n = 1034 44.0 (13.0) n = 431 44.0 (13.7) n = 603 0.999     Time since first non-RP symptom, mean (s.d.) 11.6 (8.7) n = 1038 9.1 (7.2) n = 434 13.4 (9.3) n = 604 <0.001     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 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     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. Comparison of SPIN Cohort and CSRG A comparison of the SPIN and CSRG cohorts by subgroups 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. Abnormal nailfold capillaries, on the other hand, were more frequent in SPIN than in CSRG in both subsets, and there were no differences with respect to the presence of telangiectasia. Table 2 Comparison of the SPIN, CSRG and EUSTAR Cohorts by subgroups Variable SPIN CSRG SPIN vs CSRG EUSTAR SPIN vs EUSTAR Diffuse (n = 460) Limited (n = 665) Diffuse (n = 517) Limited (n = 873) P-value diffuse P-value limited Diffuse (n = 2838a) Limited (n = 4481a) P-value diffuse P-value limited Demographic variables     Age, mean (s.d.), in years 53.0 (12.2) n = 457 57.4 (11.7) n = 664 53.0 (11.7) 57.1 (12.3) 0.991 0.678 51.1 (13.7) n = 2787 56.6 (13.4) n = 4400 0.005 0.168     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) n = 460 26.0 (5.8) n = 665 N/A N/A N/A N/A 23.5 (4.2) n = 1731 24.6 (4.5) n = 2733 <0.001 <0.001 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) n = 431 44.0 (13.7) n = 603 44.0 (13.2) 45.5 (13.9) 0.968 0.036 44.2 (14.2) n = 2543 47.2 (14.1) n = 4015 0.749 <0.001 Time since first non-RP symptom, mean (s.d.) 9.1 (7.2) n = 434 13.4 (9.3) n = 604 9.0 (8.5) 11.5 (9.9) 0.821 <0.001 N/A N/A N/A N/A 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 Immunoassay (% positive) 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 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) n = 364 4.2 (4.2) n = 530 18.1 (10.3) 5.1 (4.2) <0.001 <0.001 N/A N/A N/A N/A mRSS median (IQR) 12 (13.5) 3 (3) N/A N/A N/A N/A 16 (14) 6 (6) b b Sclerodactyly(proximal to MCP) (% positive) 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 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     SLE (% positive) 2.4 (11/452) 3.8 (25/654) 3 (15) 3.8 (33) 0.653 0.966 N/A N/A N/A N/A     RA (% positive) 6.7 (30/451) 5.2 (34/652) 2.8 (14) 4.8 (41) 0.003 0.643 N/A N/A N/A N/A     Sjögren’s (% positive) 7.5 (33/441) 10.1 (64/634) 6.3 (32) 8.6 (74) 0.428 0.282 N/A N/A N/A N/A     Myositis (% positive) 8.5 (38/447) 4.0 (26/653) 5.3 (27) 3 (26) 0.043 0.285 N/A N/A N/A N/A Variable SPIN CSRG SPIN vs CSRG EUSTAR SPIN vs EUSTAR Diffuse (n = 460) Limited (n = 665) Diffuse (n = 517) Limited (n = 873) P-value diffuse P-value limited Diffuse (n = 2838a) Limited (n = 4481a) P-value diffuse P-value limited Demographic variables     Age, mean (s.d.), in years 53.0 (12.2) n = 457 57.4 (11.7) n = 664 53.0 (11.7) 57.1 (12.3) 0.991 0.678 51.1 (13.7) n = 2787 56.6 (13.4) n = 4400 0.005 0.168     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) n = 460 26.0 (5.8) n = 665 N/A N/A N/A N/A 23.5 (4.2) n = 1731 24.6 (4.5) n = 2733 <0.001 <0.001 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) n = 431 44.0 (13.7) n = 603 44.0 (13.2) 45.5 (13.9) 0.968 0.036 44.2 (14.2) n = 2543 47.2 (14.1) n = 4015 0.749 <0.001 Time since first non-RP symptom, mean (s.d.) 9.1 (7.2) n = 434 13.4 (9.3) n = 604 9.0 (8.5) 11.5 (9.9) 0.821 <0.001 N/A N/A N/A N/A 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 Immunoassay (% positive) 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 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) n = 364 4.2 (4.2) n = 530 18.1 (10.3) 5.1 (4.2) <0.001 <0.001 N/A N/A N/A N/A mRSS median (IQR) 12 (13.5) 3 (3) N/A N/A N/A N/A 16 (14) 6 (6) b b Sclerodactyly(proximal to MCP) (% positive) 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 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     SLE (% positive) 2.4 (11/452) 3.8 (25/654) 3 (15) 3.8 (33) 0.653 0.966 N/A N/A N/A N/A     RA (% positive) 6.7 (30/451) 5.2 (34/652) 2.8 (14) 4.8 (41) 0.003 0.643 N/A N/A N/A N/A     Sjögren’s (% positive) 7.5 (33/441) 10.1 (64/634) 6.3 (32) 8.6 (74) 0.428 0.282 N/A N/A N/A N/A     Myositis (% positive) 8.5 (38/447) 4.0 (26/653) 5.3 (27) 3 (26) 0.043 0.285 N/A N/A N/A N/A CSRG did not specify n when missing data were <10%. Calculations were based on total n when no % missing data was provided. a Missing 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. b Not possible to assess significance without EUSTAR raw data. IFA: Indirect immunofluorescence assay; mRSS: modified Rodnan skin score; CSRG: Canadian Scleroderma Research Group; EUSTAR: European Scleroderma Trials And Research; N/A: not applicable. Table 2 Comparison of the SPIN, CSRG and EUSTAR Cohorts by subgroups Variable SPIN CSRG SPIN vs CSRG EUSTAR SPIN vs EUSTAR Diffuse (n = 460) Limited (n = 665) Diffuse (n = 517) Limited (n = 873) P-value diffuse P-value limited Diffuse (n = 2838a) Limited (n = 4481a) P-value diffuse P-value limited Demographic variables     Age, mean (s.d.), in years 53.0 (12.2) n = 457 57.4 (11.7) n = 664 53.0 (11.7) 57.1 (12.3) 0.991 0.678 51.1 (13.7) n = 2787 56.6 (13.4) n = 4400 0.005 0.168     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) n = 460 26.0 (5.8) n = 665 N/A N/A N/A N/A 23.5 (4.2) n = 1731 24.6 (4.5) n = 2733 <0.001 <0.001 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) n = 431 44.0 (13.7) n = 603 44.0 (13.2) 45.5 (13.9) 0.968 0.036 44.2 (14.2) n = 2543 47.2 (14.1) n = 4015 0.749 <0.001 Time since first non-RP symptom, mean (s.d.) 9.1 (7.2) n = 434 13.4 (9.3) n = 604 9.0 (8.5) 11.5 (9.9) 0.821 <0.001 N/A N/A N/A N/A 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 Immunoassay (% positive) 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 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) n = 364 4.2 (4.2) n = 530 18.1 (10.3) 5.1 (4.2) <0.001 <0.001 N/A N/A N/A N/A mRSS median (IQR) 12 (13.5) 3 (3) N/A N/A N/A N/A 16 (14) 6 (6) b b Sclerodactyly(proximal to MCP) (% positive) 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 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     SLE (% positive) 2.4 (11/452) 3.8 (25/654) 3 (15) 3.8 (33) 0.653 0.966 N/A N/A N/A N/A     RA (% positive) 6.7 (30/451) 5.2 (34/652) 2.8 (14) 4.8 (41) 0.003 0.643 N/A N/A N/A N/A     Sjögren’s (% positive) 7.5 (33/441) 10.1 (64/634) 6.3 (32) 8.6 (74) 0.428 0.282 N/A N/A N/A N/A     Myositis (% positive) 8.5 (38/447) 4.0 (26/653) 5.3 (27) 3 (26) 0.043 0.285 N/A N/A N/A N/A Variable SPIN CSRG SPIN vs CSRG EUSTAR SPIN vs EUSTAR Diffuse (n = 460) Limited (n = 665) Diffuse (n = 517) Limited (n = 873) P-value diffuse P-value limited Diffuse (n = 2838a) Limited (n = 4481a) P-value diffuse P-value limited Demographic variables     Age, mean (s.d.), in years 53.0 (12.2) n = 457 57.4 (11.7) n = 664 53.0 (11.7) 57.1 (12.3) 0.991 0.678 51.1 (13.7) n = 2787 56.6 (13.4) n = 4400 0.005 0.168     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) n = 460 26.0 (5.8) n = 665 N/A N/A N/A N/A 23.5 (4.2) n = 1731 24.6 (4.5) n = 2733 <0.001 <0.001 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) n = 431 44.0 (13.7) n = 603 44.0 (13.2) 45.5 (13.9) 0.968 0.036 44.2 (14.2) n = 2543 47.2 (14.1) n = 4015 0.749 <0.001 Time since first non-RP symptom, mean (s.d.) 9.1 (7.2) n = 434 13.4 (9.3) n = 604 9.0 (8.5) 11.5 (9.9) 0.821 <0.001 N/A N/A N/A N/A 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 Immunoassay (% positive) 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 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) n = 364 4.2 (4.2) n = 530 18.1 (10.3) 5.1 (4.2) <0.001 <0.001 N/A N/A N/A N/A mRSS median (IQR) 12 (13.5) 3 (3) N/A N/A N/A N/A 16 (14) 6 (6) b b Sclerodactyly(proximal to MCP) (% positive) 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 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     SLE (% positive) 2.4 (11/452) 3.8 (25/654) 3 (15) 3.8 (33) 0.653 0.966 N/A N/A N/A N/A     RA (% positive) 6.7 (30/451) 5.2 (34/652) 2.8 (14) 4.8 (41) 0.003 0.643 N/A N/A N/A N/A     Sjögren’s (% positive) 7.5 (33/441) 10.1 (64/634) 6.3 (32) 8.6 (74) 0.428 0.282 N/A N/A N/A N/A     Myositis (% positive) 8.5 (38/447) 4.0 (26/653) 5.3 (27) 3 (26) 0.043 0.285 N/A N/A N/A N/A CSRG did not specify n when missing data were <10%. Calculations were based on total n when no % missing data was provided. a Missing 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. b Not possible to assess significance without EUSTAR raw data. IFA: Indirect immunofluorescence assay; mRSS: modified Rodnan skin score; CSRG: Canadian Scleroderma Research Group; EUSTAR: European Scleroderma Trials And Research; N/A: not applicable. In regard to other organ involvement, there was a higher occurrence of oesophageal involvement in SPIN compared with in CSRG. Among dcSSc patients, SPIN patients experienced more interstitial lung disease compared with CSRG patients. The frequency of pulmonary arterial hypertension and SSc renal crisis were similar between 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 subsets, 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 capillaries, 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 hypertension (PAH) could not be made, due to methodological differences in the measurement of these variables. Discussion 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 collection 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 conduct 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 methodology. 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 definitions” 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 perspective. Future studies should assess the complex interplay of clinical characteristics and their impact on quality of life. The present study has limitations that should be considered in interpreting results. First, as both the SPIN Cohort and the CSRG Registry enrol patients from Canada, there is potential overlap between the participants in both cohorts. Overall, 26% of SPIN Cohort participants were enrolled from Candian centres, indicating the maximum possible overlap between SPIN and the CSRG. As published summary data were used to compare the cohorts, data were not available to identify the exact overlap between the cohorts. Second, the timeframe of enrolment differed somewhat between the 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 for CSRG and EUSTAR, we compared SPIN Cohort data with the most comprehensive published data on these cohorts [9, 10]. Additional analyses comparing geographical 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, and patients at these centres may differ from those in other settings. Finally, SSc patients in the SPIN Cohort complete questionnaires online, and participants may differ from patients without internet access, for instance, in terms of education, coping or ability for self-advocacy. Overall, there are many similarities between the SPIN Cohort and the other large recently reported SSc cohorts. Therefore, data emerging from the SPIN Cohort should be generalizable to the broader population of SSc patients, although it should be noted that all three cohorts include primarily White participants. Acknowledgements SPIN is funded by the Canadian Institutes of Health Research (CIHR; PI = Thombs, TR3-119192; PI = Thombs, PJT-148504; PIs = Thombs, Mouthon, Poiraudeau, PJT-149073) and the Arthritis Society (SOG-16-380, PI = Thombs). In addition, SPIN has received institutional 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 supported by an Investigator Salary Award from the Arthritis Society. SPIN Investigators: Alexandra Albert, Université Laval, Québec, QC, Canada; Guylaine Arsenault, Sherbrooke University, Sherbrooke, QC, Canada; Lyne Bissonette, Sherbrooke University, Sherbrooke, QC, Canada; Isabelle Boutron, Université Paris Descartes, and Assistance Publique-Hôpitaux de Paris, Paris, France; 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; 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 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. References 1 Foster G , Taylor S , Eldridge S , Ramsay J , Griffiths CJ. Self-management education programmes by lay leaders for people with chronic conditions . Cochrane Database Syst Rev 2007 ; 4 : CD005108 . 2 Lorig KR , Sobel DS , Ritter PL , Laurent D , Hobbs M. Effect of a self-management program on patients with chronic disease . Eff Clin Pract 2001 ; 4 : 256 – 62 . Google Scholar PubMed 3 Kwakkenbos L , Jewett LR , Baron M et al. . 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Assessing disability and quality of life in systemic sclerosis: construct validities of the Cochin Hand Function Scale, Health Assessment Questionnaire (HAQ), Systemic Sclerosis HAQ, and Medical Outcomes Study 36-Item Short Form Health Survey . Arthritis Rheumatol 2007 ; 57 : 94 – 102 . Google Scholar CrossRef Search ADS 11 Poole JL , Steen VD. The use of the Health Assessment Questionnaire (HAQ) to determine physical disability in systemic sclerosis . Arthritis Care Res 1991 ; 4 : 27 – 31 . Google Scholar CrossRef Search ADS PubMed 12 Kroenke K , Strine TW , Spitzer RL et al. . The PHQ-8 as a measure of current depression in the general population . J Affect Disord 2009 ; 114 : 163 – 73 . Google Scholar CrossRef Search ADS PubMed 13 Razykov I , Hudson M , Baron M , Thombs BD. The utility of the PHQ-9 to assess suicide risk in patients with systemic sclerosis . Arthritis Care Res 2013 ; 65 : 753 – 8 . Google Scholar CrossRef Search ADS 14 Milette K , Hudson M , Baron M , Thombs BD ; Canadian Scleroderma Research Group . Comparison of the PHQ-9 and CES-D depression scales in systemic sclerosis: internal consistency reliability, convergent validity and clinical correlates . Rheumatology 2010 ; 49 : 789 – 96 . Google Scholar CrossRef Search ADS PubMed 15 The NIH Patient-Reported Outcomes Measurement Information System. http://www.healthmeasures.net/explore-measurement-systems/promis (2 December 2016, date last accessed). 16 Kwakkenbos L , Thombs BD , Khanna D et al. . Performance of the patient-reported outcomes measurement information system-29 in scleroderma: a Scleroderma Patient-centered Intervention Network Cohort study . Rheumatology 2017 ; 56 : 1302 – 11 . Google Scholar CrossRef Search ADS PubMed 17 Lawrence JW , Heinberg LJ , Roca RP et al. . Development and validation of the Satisfaction With Appearance Scale: assessing body image among burn-injured patients . Psychol Assess 1998 ; 10 : 64 – 70 . Google Scholar CrossRef Search ADS 18 Mills SD , Fox RS , Merz EL et al. . Evaluation of the Satisfaction with Appearance Scale and its short form in systemic sclerosis: analysis from the UCLA Scleroderma Quality of Life study . Rheumatology 2015 ; 42 : 1624 – 30 . Google Scholar CrossRef Search ADS 19 Ritter PL , Lorig K. The English and Spanish Self-Efficacy to Manage Chronic Disease Scale measures were validated using multiple studies . J Clin Epidemiol 2014 ; 67 : 1265 – 73 . Google Scholar CrossRef Search ADS PubMed 20 Riehm KE , Kwakkenbos L , Carrier ME et al. . Validation of the Self-Efficacy for Managing Chronic Disease (SEMCD) Scale: a Scleroderma Patient-centered Intervention Network (SPIN) Cohort Study . Arthritis Care Res 2016 ; 68 : 1195 – 200 . Google Scholar CrossRef Search ADS © 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 This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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RheumatologyOxford University Press

Published: Jun 2, 2018

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