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

项目总结/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， 成年人，仍然缺乏循证治疗指导，以管理这些 未被充分研究的易感患者长期目标是告知基于证据的、风险一致的 老年IBD患者的治疗方法，平衡患者的动态疾病风险与治疗， 与特定治疗的有效性和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 效果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中严重感染的风险;这种风险随着时间的推移而演变， 并且可以通过考虑治疗有效性的时变影响来准确预测。通过 有效地控制疾病和减少对皮质类固醇和/或阿片类药物的需要， 有效的免疫抑制治疗将与随着时间的推移严重感染的风险降低相关。的 该项目的基本原理是，准确的治疗相关并发症的个体化风险预测， 接受免疫抑制治疗的IBD老年人将为患者和提供者提供知识， 根据患者预测的疾病和治疗并发症风险进行治疗。核心假设将 通过追求两个具体目标进行测试：1）开发和验证一个模型，准确预测短期- 开始免疫抑制治疗的老年IBD患者中严重感染的长期风险;和2）发展 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。 同时进行免疫抑制治疗根据第一个目标，申请人将开发和验证风险 预测模型，可准确识别短期内严重感染的高风险与低风险患者 （治疗开始后6个月内）基于治疗前基线患者、疾病和治疗 特色对于第二个目标，将开发和验证单独的风险预测模型， 准确预测严重感染的长期（治疗开始后6至24个月）风险，占 在同一队列中接受免疫抑制剂治疗的老年患者中的时变治疗效果 治疗6个月。这一建议的背景是丹麦全国范围内的全面、纵向 在丹麦登记所有患有IBD的老年患者。本申请中提出的研究是创新的， 申请人的意见，因为它结合了随时间变化的治疗效果，除了患者的内在 感染易感性，在预测免疫抑制治疗严重感染的动态风险中 老年IBD患者这项拟议中的研究意义重大，因为它有望填补一个关键的证据空白 在易感患者人群中个体化预测治疗相关并发症。

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.