title: Outcome measures for primary Sjögren's syndrome: a comprehensive review.
abstract: Lymphocytic infiltration of different exocrine and non-exocrine epithelia is the pathological hallmark of primary Sjögren's syndrome, whereas involvement of salivary and lachrymal glands with the clinical counterpart of dry eye and dry mouth are the predominant features of the disease, together with fatigue and musculoskeletal pain. In addition, systemic manifestations, like arthritis, skin vasculitis, peripheral neuropathy, glomerulonephritis, may also be present in a consistent number of patients. As result, clinical features in SS can be divided into two facets: the benign subjective but disabling manifestations such as dryness, pain and fatigue, and the systemic manifestations. In the past decades, great efforts have been made to develop valid tools for the assessment of these both facets. Disease specific questionnaires such as Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptom Inventory (SSI) have been proposed for evaluation of patients' symptoms, whereas different composite indexes have been suggested for the assessment of systemic disease activity. After that, an international project supported by EULAR, emerged to develop consensus disease activity indexes: the EULAR Sjögren's Syndrome Patients Reported Index (ESSPRI), and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), a systemic activity index to assess systemic manifestations. Both EULAR indexes have been developed in an international collaboration to be consensual. Both indices have now been validated in a large independent international cohort. They both have been shown to be feasible, valid and reliable instruments. Also, we have found that these two scores did not correlate, suggesting that these two indexes assess two different disease components that poorly overlap, but were complementary. The sensitivity to change of both scores has been assessed, they are both able to detect change, however, ESSDAI score, like other systemic score, is more sensitive to change than ESSPRI and other patient scores. Current work is ongoing to define disease activity levels and clinically important changes for defining significant clinical improvement with the systemic score ESSDAI, and ESSPRI. We hope that this increased knowledge on the way to assess patients with primary SS, along with the emergence of new targeted therapy, will put a great input in the improvement of conduction of clinical trials in pSS.
authors.affiliation: Assistance Publique-Hopitaux de Paris, Hôpital Bicêtre, Department of Rheumatology, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France; Université Paris-Sud 11, INSERM U1012, Le Kremlin Bicêtre, France; Center of Clinical Epidemiology, Hôpital Hôtel Dieu, Paris, France; INSERM U738, Université Paris-René Descartes, Paris, France. Electronic address: raphaele.se@gmail.com.
authors.forename: Raphaèle
authors.initials: R
authors.lastname: Seror
authors.affiliation: Department of Rheumatology, Skane University Hospital Malmö, Lund University, Sweden.
authors.forename: Elke
authors.initials: E
authors.lastname: Theander
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Hendrika
authors.initials: H
authors.lastname: Bootsma
authors.affiliation: Rheumatology Department, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Bowman
authors.affiliation: Department of Pathophysiology, School of Medicine, University of Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Tzioufas
authors.affiliation: Rheumatology, Centre National de Référence des Maladies Auto-Immunes Rares, INSERM UMRS_1109, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg University Hospital, Université de Strasbourg, Strasbourg, France.
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.affiliation: Laboratory of Autoimmune Diseases "Josep Font", IDIBAPS, ICMiD, Hospital Clinic, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Ramos-Casals
authors.affiliation: Rheumatology Department, Charité, University Hospital, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
authors.affiliation: Center of Clinical Epidemiology, Hôpital Hôtel Dieu, Paris, France; INSERM U738, Université Paris-René Descartes, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
authors.affiliation: Assistance Publique-Hopitaux de Paris, Hôpital Bicêtre, Department of Rheumatology, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France; Université Paris-Sud 11, INSERM U1012, Le Kremlin Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Sections of Rheumatology, Instituto San Giuseppe, Como and Casa di Cura di Lecco, Lecco, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Vitali
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D017063:Outcome Assessment, Health Care; D015203:Reproducibility of Results; D057566:Self Report; D012720:Severity of Illness Index; D012859:Sjogren's Syndrome / Q000175:diagnosis* / Q000628:therapy*
keywords: Clinical trial; ESSDAI; ESSPRI; Outcome measure; Sjogren's syndrome