PT - JOURNAL ARTICLE AU - Samantha Wratten AU - Linda Abetz-Webb AU - Ethan Arenson AU - Pip Griffiths AU - Simon Bowman AU - Wolfgang Hueber AU - Briana Ndife AU - Daniel Kuessner AU - Pushpendra Goswami TI - Development and testing of an alternative responder definition for EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) AID - 10.1136/rmdopen-2022-002721 DP - 2023 Mar 01 TA - RMD Open PG - e002721 VI - 9 IP - 1 4099 - http://rmdopen.bmj.com/content/9/1/e002721.short 4100 - http://rmdopen.bmj.com/content/9/1/e002721.full SO - RMD Open2023 Mar 01; 9 AB - Objectives Dryness, fatigue and joint/muscle pain are typically assessed in Sjögren’s trials using European Alliance of Associations for Rheumatology Sjögren’s Syndrome Patient Reported Index (ESSPRI). A Patient Acceptable Symptom State of <5 and a Minimal Clinically Important Improvement (MCII)/responder definition (RD) of ≥1 point or 15% on ESSPRI have previously been defined. This study explored alternative RDs to better discriminate between active treatment and placebo in trials.Methods 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 Sjögren’s. 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.Results Patients were predominantly female (>90%), white (90%), with mean age of 50 years. Receiver operating characteristic estimates supported an MCII threshold of 1.5–1.6 in the phase II data, whereas correlation-weighted mean change estimates supported a low/minimal symptom severity threshold of ≥2. A low/minimal symptom severity of ≤3 showed the greatest sensitivity/specificity balance. Analyses in the pooled data supported these thresholds (MCII: 1.5–2.1; low/minimal symptom severity: 2.7–3.7). Unblinded analyses confirmed the revised RD reduced placebo rates.Conclusions Completing a trial with an improvement of ≥1.5 points compared with baseline and an ESSPRI score of ≤3 points is a relevant RD for moderate-to-severe systemic Sjögren’s and reduces placebo rates.All data relevant to the study are included in the article or uploaded as supplemental information.