Z. Touma , S. Kayaniyil , A. Parackal , D. Bonilla , J. Su , A. Johnston , J. Gahn , E.D. Hille , R. Ohsfeldt , S. Chandran
{"title":"系统性红斑狼疮患者长期疗效建模","authors":"Z. Touma , S. Kayaniyil , A. Parackal , D. Bonilla , J. Su , A. Johnston , J. Gahn , E.D. Hille , R. Ohsfeldt , S. Chandran","doi":"10.1016/j.semarthrit.2024.152507","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Findings</h3><p>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.</p></div><div><h3>Interpretation</h3><p>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.</p></div><div><h3>Funding</h3><p>This study was funded by AstraZeneca.</p></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0049017224001471/pdfft?md5=ad77581972ce52f3f9a657deb50dc9f7&pid=1-s2.0-S0049017224001471-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Modelling long-term outcomes for patients with systemic lupus erythematosus\",\"authors\":\"Z. Touma , S. Kayaniyil , A. Parackal , D. Bonilla , J. Su , A. Johnston , J. Gahn , E.D. Hille , R. Ohsfeldt , S. Chandran\",\"doi\":\"10.1016/j.semarthrit.2024.152507\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Findings</h3><p>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.</p></div><div><h3>Interpretation</h3><p>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.</p></div><div><h3>Funding</h3><p>This study was funded by AstraZeneca.</p></div>\",\"PeriodicalId\":21715,\"journal\":{\"name\":\"Seminars in arthritis and rheumatism\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-07-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0049017224001471/pdfft?md5=ad77581972ce52f3f9a657deb50dc9f7&pid=1-s2.0-S0049017224001471-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Seminars in arthritis and rheumatism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0049017224001471\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Seminars in arthritis and rheumatism","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0049017224001471","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
