系统性红斑狼疮患者长期疗效建模

IF 4.6 2区 医学 Q1 RHEUMATOLOGY
Z. Touma , S. Kayaniyil , A. Parackal , D. Bonilla , J. Su , A. Johnston , J. Gahn , E.D. Hille , R. Ohsfeldt , S. Chandran
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引用次数: 0

摘要

背景系统性红斑狼疮(SLE)的新疗法旨在提高耐受性,并在标准治疗(SoC)的基础上控制疾病活动。标准疗法通常包括每日使用糖皮质激素(GC),长期使用有可能造成器官损伤。方法设计了广义线性和参数加速失败时间生存模型(GLM)和参数加速失败时间生存模型(AFT),以确定系统性红斑狼疮患者治疗第一年后的疾病活动、复发率、糖皮质激素使用、器官损伤和死亡率的预测因素。该模型是通过对1997年至2020年间收集的多伦多狼疮队列(TLC)研究数据进行纵向回顾分析而建立的。通过双变量回归和多变量回归选择具有临床和统计学意义的相关变量,以找到最适合的模型。研究结果在1255名受试者中,89%为女性,65%为白种人。平均随访时间为 10-5 年。首次就诊时,51%的患者有中重度疾病活动(SLEDAI-2 K评分≥6)。在确诊后的几年中,平均器官损伤评分逐渐增加。组群的中位生存期为研究开始后的 35 年。在 GLM 模型中,SLEDAI-2 K 年平均值和 GC 平均剂量是预测 SLEDAI-2 K、GC 使用/剂量和复发(任何/速度)变化的关键。这些全面、纵向的预测模型表明,在以中重度系统性红斑狼疮为主的患者群体中,疾病活动和 GC 使用量是器官损伤和死亡率的重要预测因素。这加深了人们对系统性红斑狼疮自然病史的了解,并强调了对减少疾病活动和使用 GC 的新治疗方法的需求,以改善系统性红斑狼疮的长期预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Modelling long-term outcomes for patients with systemic lupus erythematosus

Background

New treatments for systemic lupus erythematosus (SLE) aim to improve tolerability and disease activity control over standard of care (SoC) treatment. SoC typically includes daily glucocorticoid (GC) which carries a risk of organ damage over time. This study sought to develop natural history models to identify predictors of long-term outcomes with current SoC SLE treatment.

Methods

Generalized linear and parametric accelerated failure time survival models (GLM) and parametric accelerated failure time (AFT) survival models were designed to identify predictors of disease activity, flare rate, GC use, organ damage, and mortality beyond the first year of treatment in patients with SLE. Models were run using a longitudinal retrospective analysis of prospectively collected Toronto Lupus Cohort (TLC) study data, collected between 1997 and 2020. Covariates of clinical and statistical significance were selected by bivariate- then multi-variate regression to find the model of best fit.

Findings

Of the 1255 subjects included, 89 % were female 89 % and 65 % Caucasian. Mean follow-up was 10·5 years. At first visit, 51 % of patients had moderate-to-severe disease activity (SLEDAI-2 K score ≥ 6). Mean organ damage scores gradually increased over the years following diagnosis. Median survival of the cohort was ∼35 years from study entry. In the GLM models, SLEDAI-2 K yearly average, and average GC dose were key for predicting change in SLEDAI-2 K, GC use/ dose, and flare (any/rate). Together, adjusted mean SLEDAI-2 K and GC dose were shown to be predictors of mortality and damage in at least 9 of 12 organ systems considered.

Interpretation

These comprehensive, longitudinal, predictive models show that disease activity and GC use are significant predictors of organ damage and mortality in a patient population with predominantly moderate to severe SLE. This deepens understanding of SLE natural history and underscores the need for new treatment approaches that reduce disease activity and GC use with an aim to improve long-term SLE outcomes.

Funding

This study was funded by AstraZeneca.

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来源期刊
CiteScore
9.20
自引率
4.00%
发文量
176
审稿时长
46 days
期刊介绍: Seminars in Arthritis and Rheumatism provides access to the highest-quality clinical, therapeutic and translational research about arthritis, rheumatology and musculoskeletal disorders that affect the joints and connective tissue. Each bimonthly issue includes articles giving you the latest diagnostic criteria, consensus statements, systematic reviews and meta-analyses as well as clinical and translational research studies. Read this journal for the latest groundbreaking research and to gain insights from scientists and clinicians on the management and treatment of musculoskeletal and autoimmune rheumatologic diseases. The journal is of interest to rheumatologists, orthopedic surgeons, internal medicine physicians, immunologists and specialists in bone and mineral metabolism.
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