Immune Aging and Advanced Therapy Outcomes in Older Adults With IBD

N/ANot Yet RecruitingNCT07828886

First Affiliated Hospital, Sun Yat-Sen University300 enrolled

Overview

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.

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.

Eligibility

Sex: ALLMin age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: Age 60 years or older. Confirmed diagnosis of Crohn disease, ulcerative colitis, or inflammatory bowel disease-unclassified. Planned initiation of a new advanced therapy, or initiation of the new advanced therapy within 4 weeks before enrollment. Active inflammatory bowel disease or another clinically documented indication for treatment escalation. Availability of the core baseline clinical and laboratory data required for the study. Expected ability to complete at least 52 weeks of follow-up. Ability to provide written informed consent, or consent provided by a legally authorized representative when applicable. Exclusion Criteria: Uncertain diagnosis of inflammatory bowel disease or an alternative diagnosis that may mimic inflammatory bowel disease. Active severe infection at enrollment, including sepsis, active tuberculosis, uncontrolled viral hepatitis, cytomegalovirus disease, or another serious opportunistic infection. Significant acute infection within 4 weeks before enrollment that, in the investigator's judgment, could substantially affect baseline immune-aging measurements or treatment safety assessment. Active malignancy or recent systemic anticancer treatment, except for adequately treated low-risk malignancies as permitted by the study protocol. Severe non-IBD-related immunodeficiency. End-stage disease or another condition associated with an expected life expectancy of less than 12 months. Inability to obtain the core baseline variables required for the primary analyses. Treatment with the same index advanced therapy for more than 4 weeks before enrollment. Participation in an interventional clinical trial that could interfere with the study assessments or outcomes. Any other condition that, in the investigator's judgment, would make participation inappropriate or prevent adequate follow-up.

Outcomes

Primary Outcomes

Net Clinical Benefit at Week 52

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.

Time frame: 52 Weeks

Secondary Outcomes

Steroid-Free Clinical Remission at Week 26

Percentage of participants achieving steroid-free clinical remission at Week 26. 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 assessment.

Time frame: 26 Weeks

Steroid-Free Clinical Remission at Week 52

Percentage of participants achieving steroid-free clinical remission at Week 52, using the same disease-specific definitions as for the Week 26 assessment.

Time frame: 52 weeks

Advanced Therapy Persistence at Week 52

Percentage of participants who remain on the advanced therapy initiated at baseline at Week 52 without permanent discontinuation because of lack of effectiveness, adverse events, or patient preference. Dose escalation, interval shortening, or re-induction will not be considered treatment discontinuation.

Time frame: 52 weeks

Incidence of Serious Infection

Percentage of participants experiencing at least one serious infection, defined as an infection requiring hospitalization, intravenous antimicrobial treatment, being life-threatening, resulting in interruption of advanced therapy, or otherwise meeting criteria for a serious adverse event.

Time frame: From Baseline Through Week 52

Incidence of IBD-Related Hospitalization

Percentage of participants experiencing at least one IBD-related hospitalization during follow-up, including hospitalization related to active IBD, disease complications, infection, intestinal obstruction, bleeding, malnutrition, treatment-related adverse events, or preparation for IBD-related surgery.

Time frame: From Baseline Through Week 52

Change From Baseline in Inflammatory Bowel Disease Frailty Score at Week 26

The Inflammatory Bowel Disease (IBD) Frailty Score is a 28-item IBD-specific frailty assessment. Each item is scored 0 or 1, yielding a total score ranging from 0 to 28. Higher scores indicate greater frailty burden and therefore a worse outcome. A total score of ≥4 has been used to classify participants as frail. Change from baseline will be calculated as the Week 26 score minus the baseline score; negative values indicate improvement and positive values indicate worsening.

Time frame: Baseline and Week 26

Change From Baseline in Inflammatory Bowel Disease Frailty Score at Week 52

The Inflammatory Bowel Disease (IBD) Frailty Score is a 28-item IBD-specific frailty assessment. Each item is scored 0 or 1, yielding a total score ranging from 0 to 28. Higher scores indicate greater frailty burden and therefore a worse outcome. A total score of ≥4 has been used to classify participants as frail. Change from baseline will be calculated as the Week 52 score minus the baseline score; negative values indicate improvement and positive values indicate worsening.

Time frame: Baseline and Week 52

Change From Baseline in Clinical Frailty Scale Score at Week 52

The Clinical Frailty Scale is a clinician-rated global frailty measure ranging from 1 to 9, where 1 represents very fit and 9 represents terminally ill. Higher scores indicate greater frailty and therefore a worse outcome. Change from baseline will be calculated as the Week 52 score minus the baseline score; negative values indicate improvement and positive values indicate worsening.