title: Development of the Sjögren's Syndrome Responder Index, a data-driven composite endpoint for assessing treatment efficacy.
abstract: OBJECTIVE
  To determine which outcome measures detected rituximab efficacy in the Tolerance and Efficacy of Rituximab in Sjögren's Disease (TEARS) trial and to create a composite endpoint for future trials in primary SS (pSS).
  
  
  METHODS
  Post hoc analysis of the multicentre randomized placebo-controlled double-blind TEARS trial. The results were validated using data from two other randomized controlled trials in pSS, assessing rituximab (single-centre trial in the Netherlands) and infliximab, respectively.
  
  
  RESULTS
  Five outcome measures were improved by rituximab in the TEARS trial: patient-assessed visual analogue scale scores for fatigue, oral dryness and ocular dryness, unstimulated whole salivary flow and ESR. We combined these measures into a composite endpoint, the SS Responder Index (SSRI), and we defined an SSRI-30 response as a ≥30% improvement in at least two of five outcome measures. In TEARS, the proportions of patients with an SSRI-30 response in the rituximab and placebo groups at 6, 16 and 24 weeks were 47% vs 21%, 50% vs 7% and 55% vs 20%, respectively (P < 0.01 for all comparisons). SSRI-30 response rates after 12 and 24 weeks in the single-centre rituximab trial were 68% (13/19) vs 40% (4/10) and 74% (14/19) vs 40% (4/10), respectively. No significant differences in SSRI-30 response rates were found between infliximab and placebo at any of the time points in the infliximab trial.
  
  
  CONCLUSIONS
  A core set of outcome measures used in combination suggests that rituximab could be effective and infliximab ineffective in pSS. The SSRI might prove useful as the primary outcome measure for future therapeutic trials in pSS.
authors.affiliation: Service de Rhumatologie, CHU de la Cavale Blanche, EA 2216, INSERM ESPRI, ERI29, Université de Brest, LabEx IGO, Brest.
authors.forename: Divi
authors.initials: D
authors.lastname: Cornec
authors.affiliation: Service de Rhumatologie, CHU de la Cavale Blanche, EA 2216, INSERM ESPRI, ERI29, Université de Brest, LabEx IGO, Brest.
authors.forename: Valérie
authors.initials: V
authors.lastname: Devauchelle-Pensec
authors.affiliation: Service de Rhumatologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, Le Kremlin Bicêtre.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Service de Rhumatologie, CHU de la Cavale Blanche, EA 2216, INSERM ESPRI, ERI29, Université de Brest, LabEx IGO, Brest.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Jousse-Joulin
authors.affiliation: Service de Rhumatologie, Hôtel-Dieu, CHU Nantes, Nantes.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Berthelot
authors.affiliation: Service de Rhumatologie, CHU, Hôpital Sud, Rennes.
authors.forename: Aleth
authors.initials: A
authors.lastname: Perdriger
authors.affiliation: Service de Rhumatologie, CH du Mans, Le Mans, Service de Médecine Interne, Hopital Cochin, Paris.
authors.forename: Xavier
authors.initials: X
authors.lastname: Puéchal
authors.affiliation: Service de Médecine Interne, Hopital Cochin, Paris.
authors.forename: Véronique
authors.initials: V
authors.lastname: Le Guern
authors.affiliation: Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg.
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.affiliation: Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg.
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.affiliation: Service de Médecine Interne, Hôpital de la Conception, Marseille, Département de Médecine Interne et Maladies Infectieuses, Hôpital Européen, Marseille.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chiche
authors.affiliation: Service de Médecine Interne, Claude Huriez Hospital, Université Lille Nord-de-France, Lille.
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: Service de Médecine Interne, Claude Huriez Hospital, Université Lille Nord-de-France, Lille.
authors.forename: Pierre Yves
authors.initials: PY
authors.lastname: Hatron
authors.affiliation: Service de Rhumatologie, CHRU de Rouen, Bois-Guillaume.
authors.forename: Vincent
authors.initials: V
authors.lastname: Goeb
authors.affiliation: Service de Rhumatologie, Hôpital Bichat, Paris.
authors.forename: Gilles
authors.initials: G
authors.lastname: Hayem
authors.affiliation: Service d'Immuno-Rhumatologie, CHU. Lapeyronie, Montpellier.
authors.forename: Jacques
authors.initials: J
authors.lastname: Morel
authors.affiliation: Service de Rhumatologie, CH J. Monod, Montivilliers.
authors.forename: Charles
authors.initials: C
authors.lastname: Zarnitsky
authors.affiliation: Service de Rhumatologie, Hôpital Gabriel Montpied, Clermont-Ferrand.
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Dubost
authors.affiliation: Service de Rhumatologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, Le Kremlin Bicêtre.
authors.forename: Raphaèle
authors.initials: R
authors.lastname: Seror
authors.affiliation: EA 2216, INSERM ESPRI, ERI29, Université de Brest, LabEx IGO, Brest, Odontologie, CHU Morvan, 29609 Brest, EA 2216, Université Bretagne Occidentale, Brest, France.
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Pers
authors.affiliation: Department of Oral and Maxillofacial Surgery.
authors.forename: Petra M
authors.initials: PM
authors.lastname: Meiners
authors.affiliation: Department of Oral and Maxillofacial Surgery.
authors.forename: Arjan
authors.initials: A
authors.lastname: Vissink
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands and.
authors.forename: Hendrika
authors.initials: H
authors.lastname: Bootsma
authors.affiliation: INSERM CIC 0502, CHU Brest, Brest, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nowak
authors.affiliation: Service de Rhumatologie, CHU de la Cavale Blanche, EA 2216, INSERM ESPRI, ERI29, Université de Brest, LabEx IGO, Brest, alain.saraux@chu-brest.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Saraux
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001799:Blood Sedimentation; D023381:Endpoint Determination / Q000379:methods*; D005221:Fatigue / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D000069285:Infliximab / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D017063:Outcome Assessment, Health Care / Q000379:methods*; D015203:Reproducibility of Results; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D012859:Sjogren's Syndrome / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D016896:Treatment Outcome; D014987:Xerostomia / Q000453:epidemiology
chemical_list: D018501:Antirheumatic Agents; D000069283:Rituximab; D000069285:Infliximab
keywords: efficacy; outcome measures; primary Sjögren’s syndrome; rituximab