Mortality in systemic sclerosis: an international meta-analysis of individual patient data.
OBJECTIVE
Studies on mortality associated with systemic sclerosis have been limited by small sample sizes. We aimed to obtain large-scale evidence on survival outcomes and predictors for this disease.


METHODS
We performed a meta-analysis of individual patient data from cohorts recruited from seven medical centers in the United States, Europe, and Japan, using standardized definitions for disease subtype and organ system involvement. The primary outcome was all-cause mortality. Standardized mortality ratios and predictors of mortality were estimated. The main analysis was based only on patients enrolled at each center within 6 months of diagnosis (incident cases).


RESULTS
Among 1645 incident cases, 578 deaths occurred over 11,521 person-years of follow-up. Standardized mortality ratios varied by cohort (1.5 to 7.2). In multivariate analyses that adjusted for age and sex, renal (hazard ratio [HR] = 1.9; 95% confidence interval [CI]: 1.4 to 2.5), cardiac (HR = 2.8; 95% CI: 2.1 to 3.8), and pulmonary (HR = 1.6; 95% CI: 1.3 to 2.2) involvement, and anti-topoisomerase I antibodies (HR = 1.3; 95% CI: 1.0 to 1.6), increased mortality risk. Renal, cardiac, and pulmonary involvement tended to occur together (P <0.001). For patients without adverse predictors for 3 years after enrollment, the subsequent risk of death was not significantly different from that for the general population in three cohorts, but was significantly increased in three cohorts that comprised mostly referred patients. Analyses that included all cases in each center (n = 3311; total follow-up: 19,990 person-years) yielded largely similar results.


CONCLUSIONS
Systemic sclerosis confers a high mortality risk, but there is considerable heterogeneity across settings. Internal organ involvement and anti-topoisomerase I antibodies are important determinants of mortality.
Ioannidis
John P A
JP
Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece. jioannid@cc.uoi.gr
Vlachoyiannopoulos
Panayiotis G
PG
Haidich
Anna-Bettina
AB
Medsger
Thomas A
TA
Lucas
Mary
M
Michet
Clement J
CJ
Kuwana
Masataka
M
Yasuoka
Hidekata
H
van den Hoogen
Frank
F
Te Boome
Liane
L
van Laar
Jacob M
JM
Verbeet
Nicolette L
NL
Matucci-Cerinic
Marco
M
Georgountzos
Athanasios
A
Moutsopoulos
Haralampos M
HM
D000328:Adult; D004264:DNA Topoisomerases, Type I / Q000276:immunology; D016208:Databases, Factual; D004935:Esophageal Diseases / Q000401:mortality; D005060:Europe / Q000453:epidemiology; D005260:Female; D006331:Heart Diseases / Q000401:mortality; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007674:Kidney Diseases / Q000401:mortality; D008171:Lung Diseases / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000208:ethnology / Q000401:mortality*; D015996:Survival Rate; D014481:United States / Q000453:epidemiology
D004264:DNA Topoisomerases, Type I