title: Systemic activity and mortality in primary Sjögren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients.
abstract: OBJECTIVE
  To score systemic activity at diagnosis and correlate baseline activity with survival in a large cohort of patients with primary Sjögren syndrome (SS).
  
  
  METHODS
  We include 1045 consecutive patients who fulfilled the 2002 classification criteria for primary SS. The clinical and immunological characteristics and level of activity (EULAR-SS Disease Activity Index (ESSDAI) scores) were assessed at diagnosis as predictors of death using Cox proportional hazards regression analysis adjusted for age at diagnosis. The risk of death was calculated at diagnosis according to four different predictive models.
  
  
  RESULTS
  After a mean follow-up of 117 months, 115 (11%) patients died. The adjusted standardised mortality ratio for the total cohort was 4.66 (95% CI 3.85 to 5.60), and survival rates at 5, 10, 20 and 30 years were 96%, 90%, 81% and 60%, respectively. The main baseline factors associated with overall mortality in the multivariate analysis were male gender, cryoglobulins and low C4 levels. Baseline activity in the constitutional, pulmonary and biological domains was associated with a higher risk of death. High activity in at least one ESSDAI domain (HR 2.14), a baseline ESSDAI score ≥14 (HR 1.85) and more than one laboratory predictive marker (lymphopenia, anti-La, monoclonal gammopathy, low C3, low C4 and/or cryoglobulins) (HR 2.82) were associated with overall mortality; these HRs increased threefold to 10-fold when the analysis was restricted to mortality associated with systemic disease.
  
  
  CONCLUSIONS
  Patients with primary SS, who present at diagnosis with high systemic activity (ESSDAI ≥14) and/or predictive immunological markers (especially those with more than one), are at higher risk of death.
authors.affiliation: Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), ICMiD, Hospital Clínic, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Brito-Zerón
authors.affiliation: Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), ICMiD, Hospital Clínic, Barcelona, Spain Primary Care Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Primary Care Centre Les Corts, CAPSE, Barcelona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Kostov
authors.affiliation: Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Solans
authors.affiliation: Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Fraile
authors.affiliation: Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Suárez-Cuervo
authors.affiliation: Department of Internal Medicine, Hospital Parc Taulí, Sabadell, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Casanovas
authors.affiliation: Department of Internal Medicine, Hospital Son Espases, Palma de Mallorca, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Rascón
authors.affiliation: Department of Internal Medicine, Hospital Joan XXIII, Tarragona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Qanneta
authors.affiliation: Department of Internal Medicine, Hospital do Meixoeiro, Vigo, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Pérez-Alvarez
authors.affiliation: Department of Internal Medicine, Hospital Infanta Sofía, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ripoll
authors.affiliation: Department of Internal Medicine, Hospital Infanta Leonor, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Akasbi
authors.affiliation: Department of Internal Medicine, Hospital Gregorio Marañón, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Pinilla
authors.affiliation: Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Bosch
authors.affiliation: Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Nava-Mateos
authors.affiliation: Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Díaz-López
authors.affiliation: Department of Internal Medicine, Hospital Parc Taulí, Sabadell, Spain.
authors.forename: M L
authors.initials: ML
authors.lastname: Morera-Morales
authors.affiliation: Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), ICMiD, Hospital Clínic, Barcelona, Spain.
authors.forename: H
authors.initials: H
authors.lastname: Gheitasi
authors.affiliation: Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), ICMiD, Hospital Clínic, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Retamozo
authors.affiliation: Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), ICMiD, Hospital Clínic, Barcelona, Spain.
authors.forename: M
authors.identifier: http://orcid.org/0000-0001-5709-6734
authors.initials: M
authors.lastname: Ramos-Casals
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D003450:Cryoglobulins / Q000032:analysis; D005060:Europe; D005260:Female; D006801:Humans; D008231:Lymphopenia / Q000097:blood; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000097:blood; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012720:Severity of Illness Index; D012859:Sjogren's Syndrome / Q000097:blood / Q000401:mortality*; D013997:Time Factors
chemical_list: D000974:Antibodies, Antinuclear; D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; D003450:Cryoglobulins
keywords: B cells; Disease Activity; Sjögren's Syndrome