Supplemental data. Guillemette Thomas (MD), 1 Julien Mancini (MD, PhD), 2 Noémie Jourde-Chiche (MD, PhD), 3

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1 Supplemental data Mortality associated with systemic lupus erythematosus between 2000 and 2009 in France assessed by multiple cause-of-death analysis: the MORTALUP Study Guillemette Thomas (MD), 1 Julien Mancini (MD, PhD), 2 Noémie Jourde-Chiche (MD, PhD), 3 Gabrielle Sarlon (MD, PhD), 4 Zahir Amoura (MD, PhD), 5 Jean-Robert Harlé (MD), 1 Eric Jougla (MD), 6 Laurent Chiche (MD, PhD) 1 1

2 Standardized Mortality Rates/10 6 people 12,0 10,0 8,0 6,0 4,0 2,0 0, French Regions Figure S1: Age-standardized mortality rates (per million) for the period stratified by region. Numbers in axis correspond to each region code ( The number 97 corresponds to French Overseas Territories (FOT) and includes Guadeloupe (1), Martinique (2), French Guiana (3), La Réunion (4), and Mayotte (6). 2

3 Figure S2: Proportions of the various types of cancers reported as underlying causes of death (UCD) when systemic lupus erythematosus (SLE) was the non-underlying cause of death (NUCD). 3

4 Studies Location Period Design Jacobsen Moss United Kingdom Denmark Retrospective Retrospective Cervera 3,4, Europe * Prospective Bjornadal 6 Suede Retrospective 2004 National registry Chun South Korea Retrospective Bertnasky USA, Canada, Europe, Korea Prospective Mok Hong Kong, China Retrospective Urowitz 10,11,12 Canada Retrospective 2008 Hersh USA (CA) Retrospective Kang Korea Retrospective Mok 15,16, Voss Hong Kong, China Retrospective Denmark Retrospective SLE Patients Death/total: (%) 122/513: (23.8) 41/300: (13.7) 68/1000: (6.8) 2314/4737: (49) 10/466: # (2.1) 1255/9547: (13) Gender ratio F/M Mortality Table S1: Most recent SLE-related mortality studies (selection includes studies with a post-1990 period). CVD: Cardiovascular diseases; SMR: Standardized mortality ratio. *United Kingdom, Spain, Italy, Poland, Turkey, Belgium, Norway; $ SMR was 7.9 in 2000 and decreased to 2.17 in 2006; $$ SMR was 2.3 depending on how lost of follow-up patients were considered; # Excluding males and patients with <4 ACR criteria; ** Only for 36/72 patients. Age at death SMR Loss of life expectancy (-) or survival y: 91% 10y: 76% 15y: 64% (16-87) 5y: 82% Causes (%) SLE (29%); CVD (26%); Infection (21%); Cancer (7%) SLE (27%); Cancer (20%); Infections (17%); CVD (17%); Renal (15%) ±15: - 10y: 92% SLE (26.5%); CVD (26.5%); Infection (18-81) (25%); Cancer (5.9%) CVD (42%); SLE (21%); Cancer (12%) SLE (80%); Infection (10%) CVD (25%); SLE (23%); Cancer (9%); Infection (5%) 30/442: (6.8) ± $ - Infection (60%); CVD (10%); Renal (7%) 211/1241: (17) 72/957 (7.5) 59/1010: (5.8) 514/5243: (9.8) 38/215 (17.7) $$ y (21-100) 52 38±11-5y: 97.8% 10y: y: 90.1% - 52± y: 92% 10y: 83% ( ) SLE (53%); CVD (33%); Infection (19.7%); Cancer (11%)** 2.2 5y:98.6% 10y:93.6% 15y:86.5% Infection (37.3%); SLE (22%); CVD (5%); Cancer (1.7%) Infection (22%); SLE (21%); CVD*(16.4%); Cancer (12%) CVD (32%); Respiratory system (16%); Cancer (13%) 4

5 Pathology condition Systemic lupus erythematosus Infectious diseases Pneumonia Certain infectious and parasitic diseases* Cardiovascular diseases Ischemic heart diseases Cerebrovascular diseases Heart failure Hypertensive disease Arrhythmia/conduction disorders ** Pulmonary embolism/venous thrombosis *** Pericarditis / Endocarditis Atherosclerosis/arteritis Valve diseases **** Others Neoplasms Malignant neoplasm# Malignant neoplasms of lymphoid, hematopoietic and related tissue Diseases of the respiratory system ## Renal diseases ### Corresponding codes from ICD-10 L93-M32 L93.1, L93.2, M32.1, M32.8 or M32.9 J06-J189, J20-J22 A00-B99 I00 I99 I120-I259 I60-I698 I50-I50.9 I10, I11.9 I44-I45.9, I47-I49.9 I26.0-I26.9, I80-I82.9 I30-I33.9, I38, I39 I70-I70.9, I777.6-I77.9 I05-I08.9, I34-I37.9 I00-I159, I26-I528, I70-I99 C00-D099 C00-C809, C97-C97, D00-D099 C81-C96 J00-J051, J30-J998 N00-N19 Table S2: International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes. Terms are those from ICD-10 ( For practical reasons, the following corresponding terms have been used in this paper: *Other infections. # Solid malignant neoplasms (exclusion of malignant neoplasms of lymphoid-hematopoietic and related tissue, benign neoplasms and neoplasms of uncertain or unknown behavior). Hematologic malignancies. ## Respiratory diseases (exclusion of pneumonia). List of conditions corresponding to some ICD-10 codes: **Includes atrioventricular and left bundle-branch block, other conduction disorders, paroxysmal tachycardia, atrial fibrillation and flutter, other cardiac arrhythmias. ***Includes phlebitis and thrombophlebitis, portal-vein thrombosis, other venous embolisms and thromboses. ****Includes rheumatic mitral-valve diseases, rheumatic aortic-valve diseases, rheumatic tricuspid-valve diseases, multiple-valve diseases, non-rheumatic mitral-valve disorders, nonrheumatic aortic-valve disorders, non-rheumatic tricuspid-valve disorders, pulmonary-valve disorders. ### Includes glomerular diseases, renal tubulo-interstitial diseases, renal failure. 5

6 Deaths of SLE patients: n (%) FOT:* n = 116 France:** n = 1477 Age <40 y 35 (30.2) 161 (10.9) y 47 (40.5) 385 (26.1) y 27 (23.3) 572 (38.7) 80 y 7 (6.0) 359 (24.3) Gender Male 21 (18.1) 334 (22.6) Female 95 (81.9) 1143 (77.4) SLE as the UCD 50 (43.1) 587 (39.7) SLE as a NUCD 66 (56.9) 890 (60.3) Infectious diseases 6 (5.2) 92 (6.2) Cardiovascular diseases 20 (17.2) 321 (21.7) Neoplasms 6 (5.2) 127 (8.6) Respiratory diseases 2 (1.7) 32 (2.2) Renal diseases 2 (1.7) 27 (1.8) Others 30 (25.9) 291 (19.7) Table S3: Comparison of the distribution of deaths by gender and age and of underlying causes of death related to systemic lupus erythematosus (SLE) between French overseas territories (FOT) and regions in France for the period. * FOT (French overseas territories) include Guadeloupe (1), Martinique (2), French Guiana (3), La Réunion (4) and Mayotte (6). ** French regions except regions corresponding to FOT. 6

7 Neoplasms O/E 95% CI p All 0.40 [ ] <0.001 Hematologic malignancies 1.08 [ ] 0.63 Digestive 0.39 [ ] <0.001 Esophagus 0.48 [ ] Stomach 0.22 [ ] Colon/Rectum/Anus 0.34 [ ] <0.001 Liver/Biliary tract 0.69 [ ] Pancreas 0.35 [ ] Gynecological 0.21 [ ] <0.001 Breast 0.22 [ ] <0.001 Ovary 0.13 [ ] <0.001 Uterus/Cervix 0.21 [ ] <0.001 Lung 0.50 [ ] <0.001 Melanoma 0.86 [ ] 1.00 Table S4: Age- and gender-adjusted observed/expected (O/E) ratios for neoplasm-related underlying causes of death when systemic lupus erythematosus (SLE) was the nonunderlying cause of death. Data are OR (95% CI) and the p-value. 7

8 Present study Souza D et al. Country France Brazil Regions Every French region including FOT Sao Paolo state Total population 65 M 40 M Data source CépiDc SEADE Study period Codes ICD-10 (since 2000) ICD-9 (<1996) then ICD-10 Total SLE-related Deaths SLE as the UCD, n (%) 637 (40) 3133 (65) SLE as a NUCD, n (%) 956 (60) 1682 (35) Number of diagnoses/death certificates, mean Gender ratio: F/M 3.5 (stable) 9 (stable) Age at death (y), mean (SD)* UCD: 61.3 (± 19.3) NUCD: 65 (±17.5) SLE as the UCD: * Cardiovascular diseases: 49.5 Proportions of NUCDs, % Heart failure: 20.2 Cerebrovascular diseases: 14.2 Hypertensive diseases: 8.1 Ischemic heart diseases: 6.9 SLE as the NUCD: * Proportion of UCDs, % (O/E#) UCD: 38.5 (±15.81) NUCD: 40.8 (±16.10) Infectious diseases: 65.2 Septicemia: 33.4 Pneumonia: 31.8 Infectious diseases: 24.5 Renal diseases: 26.5 Renal diseases: 23.2 Cardiovascular diseases: ~ 25 Hypertensive diseases: 10.6 Heart failure: 5 Cerebrovascular diseases: 4.5 Ischemic heart diseases: 3 Cardiovascular: 35.7 (1.58) Ischemic heart diseases: 9.6 (1.67) Cerebrovascular diseases: 7.5 (1.34) Neoplasms: 13.9 (0.40) Solid malignant neoplasms: 10.9 (0.34) Hematologic malignancies: 3 Infectious diseases: 10.3 (2.96) Pneumonia: 3.3 (2.29) Cardiovascular diseases: 29.2** Cerebrovascular diseases: 6.8 Ischemic heart diseases: 4.4 (0.66) Infectious diseases: 14 (##) Pneumonia: 4.6 Septicemia: 4.5 (5.3) Renal diseases: 8.2 (3.78) Renal diseases: 3 (3.29) Neoplasms: 5.9 (0.39) *** Table S5: Comparison of the results of the two available studies that used multiple cause-ofdeath analysis on SLE patients, the present study conducted in France, and the study conducted by Souza et al. in Brazil. SLE: systemic lupus erythematosus; UCD: underlying cause of death; NUCD: non-underlying cause of death; FOT: French overseas territories; ICD: International classification of diseases; SEADE: Fundaçao Sistema Esatadual de Analise de Dados. *Data correspond to the period for the Brazilian study. # O/E (Observed over expected number of deaths) ratio provided only when significant; ## O/E ratio not available. **O/E ratio was >1 for patients aged <50: cardiovascular (5.63), cerebrovascular diseases (4.22), and ischemic heart diseases (3.22). ***O/E ratios were <1 except for ovary cancer (2.2), leukemia (1.3), and NHL (1.1). 8

Table E1. Standardized Mortality Ratios for Total and Specific Causes of Death Parameter Radiologists Psychiatrists No. of Deaths

RSNA, 2016 10.1148/radiol.2016152472 Table E1. Standardized Mortality Ratios for Total and Specific Causes of Death Parameter Radiologists Psychiatrists No. of Deaths Observed/Expected No. of Deaths Observed/Expected