Objectives To determine the causes of death and risk factors in systemic sclerosis (SSc).
Methods Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation.
Results We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile.
Conclusion Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients’ survival.
- systemic sclerosis
- cardiovascular disease
- pulmonary fibrosis
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Handling editor Tore K Kvien
Contributors ME, CM and YA formulated the study hypotheses and contributed to its design and analysis of the data, literature search, composition of the tables and figures, and redaction of the first draft and subsequent iterations of the manuscript. ME, MB and CM performed the statistical analyses. JA, EH, ABG, GR, PA, BJ, SV, FC, SU, LC, MT, UML, PC, OD, FI, LPA, RH, RB, AG, ND, MJS, VR, CM, GS, UAW, NH, DM, VS, CDSM, CMM, DO, FI, PGV, BS, ER, SH, JHWD, TZ, MS, AV, EDL, SN, MC, LM, JH, CC, CAVM, KS, SR, LS, BA, VOS, MDS, SY, WASG, EC, JS, JVL, EL, PGDPL, KE, VC, JJAS, OKB, MMC and YA conceived and launched the EUSTAR database, collected data in their respective countries and offered critical comments regarding the manuscript. GR retrieved the death certificates of patients and of the general population and offered critical comments regarding the manuscript.
Funding This study was funded by the “Institut national de la santé et de la recherche médicale (INSERM)” (French National Health and Medical Research Institute).
Competing interests OD reports personal fees from 4D Science, grants and personal fees from Actelion, personal fees from Active Biotech, grants and personal fees from Bayer, personal fees from Biogen Idec, personal fees from BMS, grants and personal fees from Boehringer Ingelheim, personal fees from ChemomAb, personal fees from EpiPharm, personal fees from EspeRare Foundation, personal fees from Genentech/Roche, personal fees from GSK, personal fees from Inventiva, personal fees from Lilly, personal fees from Medac, personal fees from Mepha, personal fees from MedImmune, personal fees from Pharmacyclics, grants and personal fees from Pfizer, grants and personal fees from Sanofi, personal fees from Serodapharm, personal fees from Sinoxa, personal fees from AbbVie, personal fees from iQone Healthcare, outside the submitted work. In addition, OD has a patent mir-29 for the treatment of systemic sclerosis licensed. FI reports personal fees from AbbVie, personal fees from BMS, personal fees from MSD, personal fees from Novartis, outside the submitted work. JHWD reports personal fees from Actelion, grants and personal fees from Anamar, grants and personal fees from Bayer Pharma, grants and personal fees from Boehringer Ingelheim, grants from Celgene, personal fees from Galapagos, grants from GSK, grants and personal fees from Inventiva, personal fees from Pfizer, grants and personal fees from UCB, grants from Novartis, other from 4D Science, outside the submitted work. JvL reports personal fees from Pfizer, grants and personal fees from MSD, personal fees from Eli Lilly, personal fees from BMS, personal fees from Roche, outside the submitted work. Other coauthors have nothing to disclose.
Patient consent Obtained.
Ethics approval Local ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Data may be available from EUSTAR upon separate scientific request.