Filling the "GAP" in Real-World Assessment of Psoriatic Arthritis Disease Activity: Performance Characteristics of a Global/Pain Composite Endpoint.

IF 2.9 3区医学 Q2 RHEUMATOLOGY Rheumatology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-07-02 DOI:10.1007/s40744-024-00690-1

William Tillett, Julie Birt, Aisha Vadhariya, Sarah Ross, Marcus Ngantcha, Khai Jing Ng

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Abstract

Introduction: Some retrospective data sources, such as electronic health records in the USA, report composite outcome measures not fully validated in psoriatic arthritis (PsA). However, they often contain global assessments, such as a Physician Global Assessment (PhGA) and Patient Global Assessment (PatGA), along with patient-reported pain scores, which individually are considered validated in PsA. This research described the performance characteristics of a 3-item global assessment and pain (GAP) composite endpoint using data from the ixekizumab phase 3 PsA clinical trial program.

Methods: Discrimination of GAP was assessed by comparing placebo to active treatment arms. The magnitude of treatment effect and responsiveness were compared to Disease Activity Index for PsA (DAPSA), clinical DAPSA, DAPSA28, and Psoriatic Arthritis Disease Activity Score (PASDAS) using effect size (ES) and standardized response mean (SRM), respectively. Construct validity was evaluated through correlation among the composite endpoints, and with other physician- and patient-reported outcomes. Change in GAP was compared in patients who reached low disease activity (LDA) levels based on DAPSA, cDAPSA, and PASDAS vs those who did not.

Results: GAP discriminated between active treatment and placebo with statistically significant separation as early as week 1. The largest ES/SRM was seen with GAP (2.29/1.74) and PASDAS (2.47/1.68). GAP had the strongest correlation with PASDAS (0.81-0.92) and showed moderate correlations with patient-assessed physical function, low correlations with physician-assessed skin and nail psoriasis, and low to moderate correlation with physician-assessed enthesitis. A significantly greater improvement in GAP was seen in the groups achieving LDA states compared to those not (p < 0.001).

Conclusion: The GAP composite, an abbreviated endpoint comprising measures common in electronic health records, has promising performance characteristics and could be used to address important clinical questions regarding outcomes and impact of PsA in existing datasets. CLINTRIALS.

Gov identifier: NCT01695239; NCT02349295.

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填补银屑病关节炎疾病活动性真实世界评估的 "空白"：全球/疼痛综合终点的性能特征。

导言：一些回顾性数据源（如美国的电子健康记录）报告的综合结果指标尚未在银屑病关节炎（PsA）中得到充分验证。然而，这些数据通常包含全局评估，如医生全局评估（PhGA）和患者全局评估（PatGA），以及患者报告的疼痛评分，这些单独的评估被认为在 PsA 中得到了验证。本研究利用ixekizumab 3期PsA临床试验项目的数据，描述了3项全局评估和疼痛（GAP）复合终点的性能特征：方法：通过比较安慰剂治疗组和活性治疗组来评估GAP的区分度。分别使用效应大小（ES）和标准化反应平均值（SRM）将治疗效果和反应性与PsA疾病活动指数（DAPSA）、临床DAPSA、DAPSA28和银屑病关节炎疾病活动评分（PASDAS）进行比较。通过综合终点之间的相关性以及与其他医生和患者报告的结果之间的相关性，对结构有效性进行了评估。比较了根据 DAPSA、cDAPSA 和 PASDAS 达到低疾病活动性（LDA）水平的患者与未达到低疾病活动性水平的患者的 GAP 变化：早在第一周，GAP 就对积极治疗和安慰剂产生了显著的统计学区分。GAP（2.29/1.74）和 PASDAS（2.47/1.68）的 ES/SRM 最大。GAP 与 PASDAS 的相关性最强（0.81-0.92），与患者评估的身体功能呈中等相关性，与医生评估的皮肤和指甲银屑病相关性较低，与医生评估的关节炎呈低至中等相关性。与未达到 LDA 状态的组别相比，达到 LDA 状态的组别在 GAP 方面的改善幅度明显更大（p 结论：GAP 综合指标，简称为 "GAP 综合指标"：GAP 综合指标是一种缩写终点，由电子健康记录中常见的测量指标组成，具有良好的性能特征，可用于解决现有数据集中有关 PsA 结果和影响的重要临床问题。CLINTRIALS.Gov标识符：NCT01695239；NCT02349295。

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来源期刊

Rheumatology and Therapy RHEUMATOLOGY-

CiteScore

6.00

自引率

5.30%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Rheumatology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of rheumatologic therapies. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. Areas of focus include, but are not limited to, rheumatoid arthritis, gout, gouty arthritis, psoriatic arthritis, osteoarthritis, juvenile idiopathic/rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis, Pompe’s disease, inflammatory joint conditions, musculoskeletal conditions, systemic sclerosis, and fibromyalgia. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial protocols, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Rheumatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Ethics and Disclosures The journal is a member of the Committee on Publication Ethics (COPE) and subscribes to its principles on how to deal with acts of misconduct thereby committing to investigate allegations of misconduct in order to ensure the integrity of research. Content in this journal is peer-reviewed (Single-blind). For more information on our publishing ethics policies, please see here: https://www.springer.com/gp/editorial-policies Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid and efficient communication of the latest research and reviews, allowing the advancement of rheumatologic therapies. 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Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. For examples of digital features please visit: https://springerhealthcare.com/expertise/publishing-digital-features/ Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Authors should disclose details of preprint posting during the submission process or at any other point during consideration in the journal. 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At least two extensive reviews are required to make the editorial decision. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor, and authors are welcome to make rebuttals against individual reviewer comments if appropriate. Considering the time and effort required for a detailed peer review we reward our regular reviewers with the opportunity to publish without publication fees (pending peer review) for every three reviews completed per calendar year. Copyright Rheumatology and Therapy is published under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0. Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €5,250/$6,000/£4,300. The journal will consider fee discounts and waivers for developing countries and this is decided on a case-by-case basis. Open Access All articles published by Rheumatology and Therapy are published open access. Contact For more information about the journal, including pre-submission enquiries, please contact charlotte.maddocks@springernature.com.