In:
RMD Open, BMJ, Vol. 9, No. 1 ( 2023-03), p. e002721-
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
2056-5933
DOI:
10.1136/rmdopen-2022-002721
Sprache:
Englisch
Verlag:
BMJ
Publikationsdatum:
2023
ZDB Id:
2812592-7
