银屑病关节炎临床试验的综合指标：英国多中心研究中疼痛和疲劳改善情况的测试

Composite Measures for Clinical Trials in Psoriatic Arthritis: Testing Pain and Fatigue Modifications in a UK Multicenter Study.

作者信息

Tillett William, FitzGerald Oliver, Coates Laura C, Packham Jon, Jadon Deepak R, Massarotti Marco, Brook Mel, Lane Suzanne, Creamer Paul, Antony Anna, Korendowych Eleanor, Rambojun Adwaye, McHugh Neil J, Helliwell Philip S

机构信息

As part of the supplement series GRAPPA 2020, this report was reviewed internally and approved by the Guest Editors for integrity, accuracy, and consistency with scientific and ethical standards. This report is independent research funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research (Early detection to improve outcome in patients with undiagnosed PsA [PROMPT], RP-PG-1212-20007). The views expressed are those of the authors and are not necessarily those of the NIHR or the Department of Health and Social Care. W. Tillett, BSc, MBChB, PhD, FRCP, N.J. McHugh, MBChB, MD, FRCP, FRCPath, Department of Pharmacy and Pharmacology, University of Bath, and Royal National Hospital for Rheumatic Diseases, Bath, UK; O. FitzGerald, MD, FRCPI, FRCP, Conway Institute for Biomolecular Research, University College Dublin, Dublin, Ireland; L.C. Coates, MBChB, PhD, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; J. Packham, DM, FRCP, Haywood Rheumatology Centre, Stoke-on-Trent, UK; D.R. Jadon, MBBCh, MRCP, PhD, University of Cambridge, Cambridge, UK; M. Massarotti, MD, Department of Rheumatology, University Hospitals Dorset NHS Foundation Trust, Christchurch, New Zealand; M. Brook, Patient Research Partner, Royal National Hospital for Rheumatic Diseases, Bath, UK; S. Lane, MBChB, MD, FRCP, Ipswich Hospital NHS Trust, Ipswich; P. Creamer, MBChB, North Bristol NHS Foundation Trust, Bristol, UK; A. Antony, MBBS, School of Clinical Sciences, Monash University, Australia;1E. Korendowych, PhD, MRCP, Royal National Hospital for Rheumatic Diseases, Bath, UK; A. Rambojun, PhD, Department of Pharmacy and Pharmacology, University of Bath, Bath, UK; P.S. Helliwell, MD, PhD, Professor of Clinical Rheumatology, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds, UK. SL has received sponsorship for the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology conferences in 2020, both from AbbVie, and in 2019 for the EULAR conference in Madrid from Celgene, but no commercial work for any organizations. All other authors declare no conflicts of interest. Address correspondence to Dr. W. Tillett, Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Coombe Park, Bath BA1 3NG, UK. Email:

出版信息

J Rheumatol. 2021 Mar 1. doi: 10.3899/jrheum.201674.

DOI:10.3899/jrheum.201674

PMID:33649073

Abstract

OBJECTIVE

To test the addition of pain and fatigue to the Composite Psoriatic Arthritis Disease Activity (CPDAI) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) Composite Exercise (GRACE) composite measures of psoriatic arthritis (PsA).

METHODS

Clinical and patient-reported outcome measures were assessed in patients with PsA at 3 consecutive follow-up visits over 6 months in a UK multicenter observational study. A pain visual analog scale and Functional Assessment of Chronic Illness Therapy Fatigue scale were added as modifications to the CPDAI and GRACE composite measures. Original and modified versions were tested against the PsA Disease Activity Score (PASDAS) and the Disease Activity Index for PsA (DAPSA). Discrimination between disease states and responsiveness were tested with -scores, standardized response means (SRMs), and effect sizes. Data were presented to members at the 2020 annual meeting who then voted on the GRAPPArecommended composite and treatment targets for clinical trials.

RESULTS

One hundred forty-one patients were recruited with a mean PsA disease duration of 6.1 years (range 0-41 yrs). The SRMs for the GRACE and modified GRACE (mGRACE) were 0.67 and 0.64, respectively, and 0.54 and 0.46, respectively, for the CPDAI and modified CPDAI (mCPDAI). The -scores for the GRACE and mGRACE were unchanged at 7.8 for both, and 6.8 and 7.0 for the CPDAI and mCPDAI, respectively. The PASDAS demonstrated the best responsiveness (SRM 0.84) and discrimination (-scores 8.3). Most members (82%) agreed the composites should not be modified and 77% voted for the PASDAS as the GRAPPA-recommended composite for clinical trials, with 90% minimal disease activity (MDA) as the target.

CONCLUSION

Modifying the CPDAI and GRACE with the addition of pain and fatigue does not enhance responsiveness nor the measures' ability to detect disease status in terms of requiring treatment escalation. GRAPPA members voted for the PASDAS as the composite measure in clinical trials and MDA as the target.

摘要

目的

在银屑病关节炎（PsA）的综合银屑病关节炎疾病活动度（CPDAI）及银屑病和PsA研究与评估小组（GRAPPA）综合运动（GRACE）复合指标中加入疼痛和疲劳指标进行测试。

方法

在一项英国多中心观察性研究中，对PsA患者在6个月内连续3次随访时的临床和患者报告结局指标进行评估。将疼痛视觉模拟量表和慢性病治疗功能评估疲劳量表作为对CPDAI和GRACE复合指标的修改项加入其中。将原始版本和修改后的版本与PsA疾病活动评分（PASDAS）及PsA疾病活动指数（DAPSA）进行对比测试。采用z分数、标准化反应均值（SRM）和效应量对疾病状态之间的区分度和反应性进行测试。在2020年年会上向成员展示了数据，随后成员们对GRAPPA推荐的临床试验复合指标和治疗目标进行了投票。

结果

招募了141例患者，PsA疾病平均病程为6.1年（范围0 - 41年）。GRACE和改良GRACE（mGRACE）的SRM分别为0.67和0.64，CPDAI和改良CPDAI（mCPDAI）的SRM分别为0.54和0.46。GRACE和mGRACE的z分数均为7.8，无变化，CPDAI和mCPDAI的z分数分别为6.8和7.0。PASDAS表现出最佳的反应性（SRM为0.84）和区分度（z分数为8.3）。大多数成员（82%）同意不应修改复合指标，77%投票支持将PASDAS作为GRAPPA推荐的临床试验复合指标，以90%最小疾病活动度（MDA）作为目标。