Immunosenescence Phenotypes and Net Clinical Benefit of Advanced Therapies in Older Adults With Inflammatory Bowel Disease: A Prospective Multicenter Observational Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 300
- 主要终点
- Net Clinical Benefit at Week 52
研究概览
简要总结
The goal of this observational study is to learn whether signs of immune aging and frailty can help predict the balance of benefits and risks of advanced therapies in adults aged 60 years or older with inflammatory bowel disease (IBD) who are starting a new advanced therapy. Treatment will be chosen by the participant's usual clinical team and will not be assigned by the study.
The main questions it aims to answer are:
Are baseline immune-aging and frailty characteristics associated with net clinical benefit at 52 weeks, defined as steroid-free clinical remission without serious infection, treatment discontinuation because of adverse events, IBD-related hospitalization, or IBD-related surgery? Can a low-cost combination of clinical and laboratory markers help identify older adults with IBD who are more likely to have favorable or unfavorable outcomes after starting advanced therapy?
Participants will:
Continue the advanced therapy selected as part of their usual clinical care. Complete study assessments of frailty, nutritional status, disease activity, and other health factors.
Have routine and study-related blood tests, including measures related to immune aging such as CD4/CD8 ratio and interleukin-6 (IL-6).
Be followed at approximately baseline, weeks 6, 14, 26, and 52, with longer-term safety follow-up planned to week 104 when feasible.
Have information collected on remission, infections, hospitalizations, surgery, treatment continuation or change, and other health outcomes.
详细描述
Older adults with inflammatory bowel disease (IBD) represent a clinically heterogeneous population. Chronological age alone may not adequately reflect physiological reserve, immune competence, frailty, or vulnerability to treatment-related adverse outcomes. Immunosenescence, characterized by age-related changes in immune cell composition and chronic low-grade inflammation, may contribute to differences in both treatment effectiveness and safety among older adults receiving advanced therapies. However, prospective evidence linking clinically accessible markers of immune aging to treatment outcomes in IBD remains limited.
This prospective, multicenter observational cohort study will evaluate older adults with IBD who initiate a new advanced therapy as part of routine clinical care. Treatment selection and subsequent treatment modifications will remain entirely at the discretion of the treating clinicians and participants. The study will characterize participants using complementary domains including immune-aging markers, frailty, nutritional status, comorbidity and polypharmacy, inflammatory disease activity, and treatment exposure. Candidate immune-aging measures include the CD4/CD8 ratio, lymphocyte measures, interleukin-6, neutrophil-to-lymphocyte ratio, and other routinely available inflammatory and nutritional biomarkers.
The primary analytical objective is to determine whether baseline immunosenescence and frailty phenotypes are associated with the overall balance of effectiveness and safety after initiation of advanced therapy. The study will also assess whether these measures provide prognostic information beyond conventional clinical factors such as age, disease activity, comorbidity burden, and treatment type. Additional analyses will explore heterogeneity across different mechanisms of advanced therapy, relationships between immune aging, frailty, and nutritional status, and differences between elderly-onset IBD and IBD diagnosed earlier in life but treated during older age.
The study is intended to establish a clinically applicable framework for risk stratification in older adults with IBD and to provide prospective data for future studies of individualized treatment strategies based on biological aging and vulnerability rather than chronological age alone.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 60 years or older, regardless of sex. Confirmed diagnosis of Crohn disease, ulcerative colitis, or inflammatory bowel disease-unclassified based on standard clinical, endoscopic, imaging, histologic, and laboratory criteria.
- •Planning to initiate, or having initiated within the previous 4 weeks, a new advanced therapy, including vedolizumab, ustekinumab, an anti-TNF agent, a JAK inhibitor, an S1P receptor modulator, or another approved or clinically available advanced therapy.
- •Active IBD or a clear indication for treatment escalation at the time of advanced therapy initiation.
- •Availability of core baseline clinical and laboratory assessments required for the study.
- •Expected ability to complete at least 52 weeks of follow-up. Ability of the participant or legally authorized representative to understand the study and provide written informed consent.
排除标准
- •Uncertain diagnosis of IBD or another condition more likely to explain intestinal inflammation.
- •Active severe infection at enrollment, including sepsis, active tuberculosis, uncontrolled viral hepatitis, active cytomegalovirus colitis, or another serious opportunistic infection.
- •Clinically significant acute infection within 4 weeks before enrollment that may substantially affect baseline immune-aging measurements or short-term safety assessment.
- •Active malignancy or recent systemic treatment for malignancy, except for adequately treated low-risk cancers as judged by the investigator.
- •Severe immunodeficiency unrelated to IBD. Expected survival of less than 12 months or another severe end-stage condition likely to interfere with follow-up or interpretation of outcomes.
- •Inability to obtain core baseline variables within the predefined assessment window.
- •Continuous use of the same advanced therapy for more than 4 weeks before enrollment.
- •Participation in another interventional study that may substantially affect treatment effectiveness or safety assessment.
- •Any other condition that, in the investigator's judgment, would make participation inappropriate or compromise follow-up or data quality.
研究组 & 干预措施
Older Adults With IBD Initiating Advanced Therapy
Adults aged 60 years or older with Crohn disease, ulcerative colitis, or IBD-unclassified who are initiating a new advanced therapy as part of routine clinical care. Advanced therapies of interest include vedolizumab, ustekinumab, anti-TNF agents, JAK inhibitors, S1P receptor modulators, and other approved or clinically available advanced therapies. Treatment selection, dosing, optimization, switching, and discontinuation are determined by the treating clinician and are not assigned by the study. Participants will be followed prospectively to evaluate treatment effectiveness, safety, frailty, immunosenescence-related characteristics, and other clinical outcomes.
结局指标
主要结局
Net Clinical Benefit at Week 52
时间窗: 52 Weeks
Percentage of participants achieving net clinical benefit at Week 52. Net clinical benefit is defined as steroid-free clinical remission at Week 52 without any serious infection, discontinuation of the index advanced therapy due to an adverse event, IBD-related hospitalization, or IBD-related surgery during follow-up. Steroid-free clinical remission is defined as a partial Mayo score ≤2 with no individual subscore \>1 for ulcerative colitis, or a Harvey-Bradshaw Index ≤4 for Crohn disease, with no systemic corticosteroid use for at least 4 weeks before the Week 52 assessment. Participants with IBD-unclassified will be assessed according to the predominant UC- or CD-like clinical phenotype.
次要结局
- Steroid-Free Clinical Remission at Week 26(26 Weeks)
- Steroid-Free Clinical Remission at Week 52(52 weeks)
- Advanced Therapy Persistence at Week 52(52 weeks)
- Incidence of Serious Infection(From Baseline Through Week 52)
- Incidence of IBD-Related Hospitalization(From Baseline Through Week 52)
- Change From Baseline in Inflammatory Bowel Disease Frailty Score at Week 26(Baseline and Week 26)
- Change From Baseline in Inflammatory Bowel Disease Frailty Score at Week 52(Baseline and Week 52)
- Change From Baseline in Clinical Frailty Scale Score at Week 52(Baseline and Week 52)
研究者
Yun Qiu
Associate Professor of Gastroenterology
First Affiliated Hospital, Sun Yat-Sen University