{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T18:40:04Z","timestamp":1781030404330,"version":"3.54.1"},"reference-count":55,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2023,2,27]]},"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Dryness, fatigue and joint\/muscle pain are typically assessed in Sj\u00f6gren\u2019s trials using European Alliance of Associations for Rheumatology Sj\u00f6gren\u2019s Syndrome Patient Reported Index (ESSPRI). A Patient Acceptable Symptom State of &lt;5\u2009and a Minimal Clinically Important Improvement (MCII)\/responder definition (RD) of \u22651 point or 15% on ESSPRI have previously been defined. This study explored alternative RDs to better discriminate between active treatment and placebo in trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Anchor-based and distribution-based methods were used to derive RD thresholds in blinded phase IIb trial data (N=190) and confirm these in blinded data pooled from three early phase II trials (N=126). The populations consisted of individuals with moderate-to-severe systemic primary Sj\u00f6gren\u2019s. Anchors were prioritised by ESSPRI correlations and used in similar conditions. Triangulated estimates were discussed with experts (N=3). The revised RD was compared with the original using unblinded data to assess placebo and treatment responder rates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Patients were predominantly female (&gt;90%), white (90%), with mean age of 50 years. Receiver operating characteristic estimates supported an MCII threshold of 1.5\u20131.6 in the phase II data, whereas correlation-weighted mean change estimates supported a low\/minimal symptom severity threshold of \u22652. A low\/minimal symptom severity of \u22643 showed the greatest sensitivity\/specificity balance. Analyses in the pooled data supported these thresholds (MCII: 1.5\u20132.1; low\/minimal symptom severity: 2.7\u20133.7). Unblinded analyses confirmed the revised RD reduced placebo rates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Completing a trial with an improvement of \u22651.5 points compared with baseline and an ESSPRI score of \u22643 points is a relevant RD for moderate-to-severe systemic Sj\u00f6gren\u2019s and reduces placebo rates.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2022-002721","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T11:20:19Z","timestamp":1679052019000},"page":"e002721","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Development and testing of an alternative responder definition for EULAR Sj\u00f6gren\u2019s Syndrome Patient Reported Index (ESSPRI)"],"prefix":"10.1136","volume":"9","clinical-trial-number":[{"clinical-trial-number":"nct02962895","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02149420","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02291029","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02775916","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Samantha","family":"Wratten","sequence":"first","affiliation":[{"name":"Patient-Centered Outcomes, Adelphi Values, Bollington, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Abetz-Webb","sequence":"additional","affiliation":[{"name":"Patient-Centered Outcomes, Adelphi Values, Bollington, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Arenson","sequence":"additional","affiliation":[{"name":"Patient-Centered Outcomes, Adelphi Values, Bollington, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pip","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Patient-Centered Outcomes, Adelphi Values, Bollington, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Bowman","sequence":"additional","affiliation":[{"name":"Rheumatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hueber","sequence":"additional","affiliation":[{"name":"Department of Immunology, Novartis Pharma, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana","family":"Ndife","sequence":"additional","affiliation":[{"name":"Department of Oncology, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kuessner","sequence":"additional","affiliation":[{"name":"Department of Immunology, Novartis Pharma, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pushpendra","family":"Goswami","sequence":"additional","affiliation":[{"name":"Department of Immunology, Novartis Pharma, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"2025090312235600000_9.1.e002721.1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.143743"},{"key":"2025090312235600000_9.1.e002721.2","doi-asserted-by":"crossref","DOI":"10.1002\/brb3.586","article-title":"Cognition, depression, fatigue, and quality of life in primary sj\u00f6gren\u2019s syndrome: correlations","volume":"6","author":"Ko\u00e7er","year":"2016","journal-title":"Brain Behav"},{"key":"2025090312235600000_9.1.e002721.3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0210466","article-title":"Personality, depression and anxiety in primary sjogren\u2019s syndrome - 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