Predicting Short- and Long-term Risk of Serious Infections in Older Patients with Inflammatory Bowel Diseases

预测老年炎症性肠病患者严重感染的短期和长期风险

• 批准号: 10445054
• 负责人: Siddharth Singh
• 金额: $ 9.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10445054
• 关键词: Accounting; Adrenal Cortex Hormones; Aftercare; Antibiotics; Area Under Curve; Biological Products; Cessation of life; Characteristics; Chronic; Clinical; Clinical Treatment; Clinical Trials; Combined Modality Therapy; Data; Denmark; Disease; Elderly; Equilibrium; Evidence based treatment; Evolution; Goals; Health Care Costs; Hospitalization; Immune; Immunomodulators; Incidence; Infection; Inflammatory Bowel Diseases; Intravenous; Knowledge; Mission; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Opioid; Outcome; Participant; Patient risk; Patients; Population; Prediction of Response to Therapy; Predisposition; Prevalence; Principal Investigator; Provider; Public Health; Relative Risks; Research; Risk; Risk Estimate; Safety; Steroids; Testing; Therapeutic immunosuppression; Time; Treatment Effectiveness; Treatment Efficacy; United States National Institutes of Health; Weighing patient; aging population; base; clinical decision support; cohort; comparative effectiveness; comparative safety; disability; disorder control; disorder risk; evidence base; frailty; high risk; human old age (65+); individualized medicine; ineffective therapies; innovation; mortality; multiple chronic conditions; older patient; optimal treatments; patient population; personalized predictions; personalized risk prediction; point of care; resilience; risk prediction model; risk selection; risk stratification; support tools; treatment effect; treatment risk; treatment strategy

PROJECT SUMMARY/ABSTRACT Despite rising incidence, prevalence and healthcare costs of inflammatory bowel diseases (IBD) in older adults, there continues to be paucity of evidence-based treatment guidance for management of these understudied and susceptible patients. The long-term goal is to inform evidence-based, risk-congruent treatment approach for older patients with IBD, balancing patients’ dynamic risk of disease- vs. treatment- related complications with specific treatment’s efficacy vs. safety. The overall objectives in this application are to accurately predict the short- and long-term risk of serious infections with immunosuppressive therapy in older patients with IBD, based on pre-treatment baseline clinical characteristics and time-varying treatment effect. The central hypothesis is that pre-treatment clinical characteristics can accurately predict short-term risk of serious infections in older patients with starting immunosuppressive therapy; this risk evolves over time, on therapy, and can be accurately predicted by accounting for time-varying impact of treatment effectiveness. By controlling disease effectively and decreasing the need for corticosteroids and/or opiates, an effective, yet potent immunosuppressive therapy will be associated with lower risk of serious infections over time. The rationale for this project is that accurate individualized risk prediction for treatment-related complications in older adults with IBD on immunosuppressive therapy will provide patients and providers knowledge to tailor therapy based on patients’ predicted risk of disease- and treatment complications. The central hypothesis will be tested by pursuing two specific aims: 1) develop and validate a model that accurately predicts the short- term risk of serious infections in older patients with IBD starting immunosuppressive therapy; and 2) develop and validate a model that accurately predicts the long-term risk of serious infections in older patients with IBD while on immunosuppressive therapy. Under the first aim, the applicant will develop and validate a risk prediction model to accurately identify patients at high- vs. low-risk of serious infections in the short-term (within 6 months of treatment initiation) based on pre-treatment baseline patient-, disease- and treatment characteristics. For the second aim, a separate risk prediction model will be developed and validated to accurately predict long-term (6 to 24 months after treatment initiation) risk of serious infections, accounting for time-varying treatment effect, in older patients from the same cohort who have been on immunosuppressive therapy for 6 months. The context for this proposal will be the comprehensive, longitudinal Danish nationwide register of all older patients with IBD in Denmark. The research proposed in this application is innovative, in the applicant’s opinion, because it incorporates time-varying treatment effect, in addition to patients’ intrinsic susceptibility to infections, in predicting the dynamic risk of serious infections with immunosuppressive therapy in older patients with IBD. The proposed research is significant because it is expected to fill a key evidence gap in individualized prediction of treatment-related complications in a susceptible patient population.

项目概要/摘要 尽管老年人炎症性肠病 (IBD) 的发病率、患病率和医疗费用不断上升 对于成年人来说，仍然缺乏管理这些问题的循证治疗指南 长期目标是向未充分研究和易受影响的患者提供基于证据的、风险一致的信息。 老年 IBD 患者的治疗方法，平衡患者疾病与治疗的动态风险 与特定治疗的疗效与安全性相关的并发症 本申请的总体目标是 准确预测免疫抑制治疗中严重感染的短期和长期风险 老年 IBD 患者，基于治疗前基线临床特征和随时间变化的治疗 中心假设是治疗前的临床特征可以准确预测短期风险。 开始免疫抑制治疗的老年患者出现严重感染的风险随着时间的推移而变化； 治疗，并且可以通过考虑治疗效果随时间变化的影响来准确预测。 有效控制疾病并减少对皮质类固醇和/或阿片类药物的需求，这是一种有效但 随着时间的推移，有效的免疫抑制治疗将降低严重感染的风险。 该项目的基本原理是对治疗相关并发症进行准确的个体化风险预测 患有 IBD 的老年人接受免疫抑制治疗将为患者和提供者提供定制知识 基于患者预测的疾病风险和治疗并发症的治疗的中心假设将是。 通过追求两个具体目标进行测试：1）开发并验证一个模型，该模型可以准确预测短期 开始免疫抑制治疗的老年 IBD 患者出现严重感染的长期风险；2) 并验证一个模型，该模型可以准确预测老年 IBD 患者严重感染的长期风险 在接受免疫抑制治疗时，申请人将开发并验证风险。 预测模型可准确识别短期内严重感染高风险与低风险的患者 （治疗开始后 6 个月内）基于治疗前基线患者、疾病和治疗 对于第二个目标，将开发并验证单独的风险预测模型。 准确预测长期（治疗开始后 6 至 24 个月）严重感染的风险，考虑到 同一队列中接受免疫抑制治疗的老年患者的治疗效果随时间变化 该提案的背景将是丹麦全国范围内的综合纵向治疗。 丹麦所有老年 IBD 患者的登记 本申请中提出的研究是创新的。 申请人的意见，因为它除了考虑患者的内在因素外，还考虑了随时间变化的治疗效果 对感染的易感性，预测免疫抑制治疗严重感染的动态风险 这项研究对于老年 IBD 患者意义重大，因为它有望填补一个关键的证据空白。 对易感患者群体中治疗相关并发症的个体化预测。

项目成果

Frailty Is Independently Associated with Mortality and Readmission in Hospitalized Patients with Inflammatory Bowel Diseases.

• DOI: 10.1016/j.cgh.2020.08.010
• 发表时间: 2021-10
• 期刊: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
• 作者: Qian AS;Nguyen NH;Elia J;Ohno-Machado L;Sandborn WJ;Singh S
• 通讯作者: Singh S

Spatial Evolution of Histologic and Endoscopic Healing in the Left and Right Colon in Patients With Ulcerative Colitis.

• DOI: 10.1016/j.cgh.2021.02.007
• 发表时间: 2022-04
• 期刊: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

Systematic Review and Meta-Analysis: Risk of Hospitalization in Patients with Ulcerative Colitis and Crohn's Disease in Population-Based Cohort Studies.

• DOI: 10.1007/s10620-021-07200-1
• 发表时间: 2022-06
• 期刊: Digestive diseases and sciences
• 影响因子: 3.1
• 作者: Tsai L;Nguyen NH;Ma C;Prokop LJ;Sandborn WJ;Singh S
• 通讯作者: Singh S

HLA-DQA1∗05 Genotype and Immunogenicity to Tumor Necrosis Factor-α Antagonists: A Systematic Review and Meta-analysis.

HLA-DQA1-05 肿瘤坏死因子-α 拮抗剂的基因型和免疫原性：系统评价和荟萃分析。

• DOI: 10.1016/j.cgh.2023.03.044
• 发表时间: 2023
• 期刊: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
• 作者: Solitano,Virginia;Facciorusso,Antonio;McGovern,DermotPB;Nguyen,Tran;Colman,RubenJ;Zou,Lily;Boland,BrigidS;Syversen,SiljeW;Jørgensen,KristinKaasen;Ma,Christopher;Armuzzi,Alessandro;Wilson,Aze;Jairath,Vipul;Singh,Siddharth
• 通讯作者: Singh,Siddharth

Correlations Between Gastrointestinal Symptoms and Endoscopic-Histologic Disease Activity in Adults with Ulcerative Colitis.

成人溃疡性结肠炎胃肠道症状与内镜组织学疾病活动之间的相关性。

• DOI: 10.1007/s10620-023-07986-2
• 发表时间: 2023
• 期刊: Digestive diseases and sciences
• 影响因子: 3.1
• 作者: Tse,ChungSang;Nguyen,HangP;Singh,Siddharth;Dulai,ParambirS;Neill,Jennifer;Le,Helen;Valasek,Mark;Dervieux,Thierry;Collins,AngelinaE;Boland,BrigidSweeney
• 通讯作者: Boland,BrigidSweeney