Development and testing of an alternative responder definition for EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI)
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 (MC...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-03-01
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| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/9/1/e002721.full |
| _version_ | 1797769267928629248 |
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| author | Simon Bowman Wolfgang Hueber Samantha Wratten Linda Abetz-Webb Ethan Arenson Pip Griffiths Briana Ndife Daniel Kuessner Pushpendra Goswami |
| author_facet | Simon Bowman Wolfgang Hueber Samantha Wratten Linda Abetz-Webb Ethan Arenson Pip Griffiths Briana Ndife Daniel Kuessner Pushpendra Goswami |
| author_sort | Simon Bowman |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T21:05:31Z |
| format | Article |
| id | doaj.art-ec6deec80b344146b3e256f90fec7ebe |
| institution | Directory Open Access Journal |
| issn | 2056-5933 |
| language | English |
| last_indexed | 2024-03-12T21:05:31Z |
| publishDate | 2023-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | RMD Open |
| spelling | doaj.art-ec6deec80b344146b3e256f90fec7ebe2023-07-30T13:30:07ZengBMJ Publishing GroupRMD Open2056-59332023-03-019110.1136/rmdopen-2022-002721Development and testing of an alternative responder definition for EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI)Simon Bowman0Wolfgang Hueber1Samantha Wratten2Linda Abetz-Webb3Ethan Arenson4Pip Griffiths5Briana Ndife6Daniel Kuessner7Pushpendra Goswami8Rheumatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKDepartment of Immunology, Novartis Pharma, Basel, SwitzerlandPatient-Centered Outcomes, Adelphi Values, Bollington, UKPatient-Centered Outcomes, Adelphi Values, Bollington, UKPatient-Centered Outcomes, Adelphi Values, Bollington, UKPatient-Centered Outcomes, Adelphi Values, Bollington, UKDepartment of Oncology, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USADepartment of Immunology, Novartis Pharma, Basel, SwitzerlandDepartment of Immunology, Novartis Pharma, Basel, SwitzerlandObjectives 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.https://rmdopen.bmj.com/content/9/1/e002721.full |
| spellingShingle | Simon Bowman Wolfgang Hueber Samantha Wratten Linda Abetz-Webb Ethan Arenson Pip Griffiths Briana Ndife Daniel Kuessner Pushpendra Goswami Development and testing of an alternative responder definition for EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) RMD Open |
| title | Development and testing of an alternative responder definition for EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) |
| title_full | Development and testing of an alternative responder definition for EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) |
| title_fullStr | Development and testing of an alternative responder definition for EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) |
| title_full_unstemmed | Development and testing of an alternative responder definition for EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) |
| title_short | Development and testing of an alternative responder definition for EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) |
| title_sort | development and testing of an alternative responder definition for eular sjogren s syndrome patient reported index esspri |
| url | https://rmdopen.bmj.com/content/9/1/e002721.full |
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