Development and testing of an alternative responder definition for EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI).
Author
Wratten, SamanthaAbetz-Webb, Linda
Arenson, Ethan
Griffiths, Pip
Bowman, Simon
Hueber, Wolfgang
Ndife, Briana
Kuessner, Daniel
Goswami, Pushpendra
Publication date
2023-03-17
Metadata
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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.Citation
Wratten S, Abetz-Webb L, Arenson E, Griffiths P, Bowman S, Hueber W, Ndife B, Kuessner D, Goswami P. Development and testing of an alternative responder definition for EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI). RMD Open. 2023 Mar;9(1):e002721. doi: 10.1136/rmdopen-2022-00272Type
ArticlePMID
36931685Journal
RMD OpenPublisher
BMJ Publishing Groupae974a485f413a2113503eed53cd6c53
10.1136/rmdopen-2022-002721