Clinical Characteristics, Treatment Patterns, and Outcomes of Hospitalized Patients With Refractory Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic relapsing inflammatory disorder of the gastrointestinal tract. Although biologic agents and small-molecule therapies have substantially expanded treatment options, a subset of patients still experience persistent inflammation, repeated treatment failure, cumulative bowel damage, and poor clinical outcomes. Refractory IBD represents a clinically important high-risk disease state characterized by complex disease phenotypes, advanced therapeutic exposure, and an increased risk of hospitalization and surgery. However, real-world evidence regarding the clinical characteristics, treatment patterns, and outcomes of refractory IBD in Asian populations remains limited.

This study is a multicenter retrospective observational cohort study conducted at three tertiary referral centers in China: Shanghai Tenth People's Hospital, the First Affiliated Hospital of Zhejiang University School of Medicine, and the Second Affiliated Hospital of Soochow University. Consecutive hospitalized patients with an established diagnosis of CD or UC between January 1, 2020 and December 31, 2024 will be retrospectively identified from electronic medical records. Hospitalized patients are selected because they represent a clinically relevant population with active inflammation, complicated disease behavior, and substantial treatment burden.

Eligible patients are those with a confirmed diagnosis of CD or UC based on clinical, endoscopic, radiologic, and histopathologic findings. Patients will be excluded if they participated in clinical trials or received investigational drugs, had concomitant malignancy, severe immunodeficiency, other systemic autoimmune diseases, or were diagnosed with IBD-unclassified. For patients with multiple admissions during the study period, the first eligible admission will be used for baseline characterization, while subsequent treatment and outcome information will be collected longitudinally from medical records.

Refractory IBD will be defined according to the International Organization for the Study of Inflammatory Bowel Diseases consensus criteria. Patients will be classified as having refractory IBD if they meet at least one of the following criteria: failure of at least two biologic or small-molecule therapies with different mechanisms of action; recurrence after at least two surgeries in adult patients with CD; complex perianal disease; or chronic antibiotic-refractory pouchitis. Psychological factors will not be included because they cannot be consistently assessed in this retrospective study.

Data will be extracted from electronic medical records, including demographic characteristics, disease type and duration, Montreal classification, intestinal complications, extraintestinal manifestations, history of perianal fistula surgery, prior intestinal surgery, laboratory indices, exposure to biologic or small-molecule therapies, treatment sequence, treatment duration, reasons for treatment discontinuation or switching, and use of advanced combination therapy. Advanced therapy will be defined as treatment with biologics or small-molecule agents, including anti-tumor necrosis factor agents, vedolizumab, ustekinumab, tofacitinib, and upadacitinib. A new treatment line will be defined as initiation of a new biologic or small-molecule agent, either after switching from a previous agent or as part of an advanced combination regimen.

The main objectives of this study are to characterize the clinical features of hospitalized patients with refractory IBD, identify clinical factors associated with refractory disease status, describe real-world treatment sequencing patterns, and evaluate clinical outcomes. The primary outcomes include clinical remission, endoscopic remission, and IBD-related surgery within one year after the most recent treatment adjustment. Clinical remission will be defined as a Crohn's Disease Activity Index score less than 150 in CD or a partial Mayo score of 1 or less in UC. Endoscopic remission will be defined as a Simple Endoscopic Score for Crohn's Disease of 2 or less or a Rutgeerts score of i1 or less in postoperative CD, and a Mayo endoscopic subscore of 1 or less in UC. IBD-related surgery will be defined as surgery performed for complications such as intestinal obstruction, perforation, massive gastrointestinal bleeding, or medically refractory disease. The secondary outcome is drug persistence, defined as the time from initiation of an advanced therapy to discontinuation or switching.

Descriptive statistics will be used to summarize baseline characteristics, treatment patterns, and outcomes. Continuous variables will be presented as mean with standard deviation or median with interquartile range, as appropriate. Categorical variables will be presented as frequencies and percentages. Between-group comparisons will be performed between refractory and non-refractory IBD patients. Logistic regression analyses will be used to identify clinical factors associated with refractory IBD, and separate analyses will be conducted for CD and UC where appropriate. Treatment sequences will be visualized using Sankey diagrams. Drug persistence across successive advanced therapy lines will be assessed using Kaplan-Meier analysis and compared using the log-rank test.

As this is a retrospective observational study using routinely collected, de-identified clinical data, no study intervention will be performed and no direct patient contact will be involved. Patient confidentiality will be strictly protected throughout the study. The study will be conducted in accordance with the Declaration of Helsinki and applicable institutional data protection regulations.