系统性红斑狼疮（BEAT-LUPUS）试验中 B 细胞耗竭治疗后贝利尤单抗的安全性和疗效：统计分析计划。

Safety and efficacy of belimumab after B cell depletion therapy in systemic LUPUS erythematosus (BEAT-LUPUS) trial: statistical analysis plan.

机构信息

Comprehensive Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK.

Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham, UK.

出版信息

Trials. 2020 Jul 16;21(1):652. doi: 10.1186/s13063-020-04391-2.

DOI:10.1186/s13063-020-04391-2

PMID:32677992

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7364494/

Abstract

BACKGROUND

There is limited evidence that rituximab, a B cell depletion therapy, is an effective treatment for systemic lupus erythematosus (SLE). Data on the mechanisms of B cell depletion in SLE indicate that the combination of rituximab and belimumab may be more effective than rituximab alone. The safety and efficacy of belimumab after B cell depletion therapy in systemic LUPUS erythematosus (BEAT-LUPUS) trial aims to determine whether belimumab is superior to placebo, when given 4-8 weeks after treatment with rituximab. This article describes the statistical analysis plan for this trial as an update to the published protocol. It is written prior to the end of patient follow-up, while the outcome of the trial is still unknown.

DESIGN AND METHODS

BEAT-LUPUS is a randomised, double-blind, phase II trial of 52 weeks of belimumab versus placebo, initiated 4-8 weeks after rituximab treatment. The primary outcome is anti-dsDNA antibodies at 52 weeks post randomisation. Secondary outcomes include lupus flares and damage, adverse events, doses of concomitant medications, quality of life, and clinical biomarkers. We describe the trial's clinical context, outcome measures, sample size calculation, and statistical modelling strategy, and the supportive analyses planned to evaluate for mediation of the treatment effect through changes in concomitant medication doses and bias from missing data.

DISCUSSION

The analysis will provide detailed information on the safety and effectiveness of belimumab. It will be implemented from July 2020 when patient follow-up and data collection is complete.

TRIAL REGISTRATION

ISRCTN: 47873003 . Registered on 28 November 2016. EudracT: 2015-005543-14 . Registered on 19 November 2018.

摘要

背景

有有限的证据表明，利妥昔单抗（一种 B 细胞耗竭疗法）是治疗系统性红斑狼疮（SLE）的有效方法。关于 SLE 中 B 细胞耗竭机制的数据表明，利妥昔单抗与贝利尤单抗联合使用可能比单独使用利妥昔单抗更有效。在系统性红斑狼疮（BEAT-LUPUS）试验中，评估利妥昔单抗治疗后 B 细胞耗竭治疗中贝利尤单抗的安全性和有效性，旨在确定在利妥昔单抗治疗后 4-8 周给予贝利尤单抗是否优于安慰剂。本文描述了该试验的统计分析计划，作为已发表方案的更新。这是在患者随访结束之前撰写的，而试验结果仍未知。

设计和方法

BEAT-LUPUS 是一项为期 52 周的随机、双盲、二期试验，比较利妥昔单抗治疗后 4-8 周开始的贝利尤单抗与安慰剂治疗。主要终点是随机分组后 52 周时的抗 dsDNA 抗体。次要终点包括狼疮发作和损伤、不良事件、伴随药物剂量、生活质量和临床生物标志物。我们描述了试验的临床背景、结局指标、样本量计算和统计建模策略，以及计划进行的支持性分析，以评估通过伴随药物剂量的变化和缺失数据的偏倚来介导治疗效果。