EP133 - Impact of Biologic Therapy on Time to Surgery in Inflammatory Bowel Disease: A TriNetX Study

Purpose/Background: The introduction of biologic immunotherapy changed the treatment paradigm in the management of inflammatory Bowel Disease (IBD). However, their long-term impact on the incidence and time to major abdominal surgery in patients with IBD remains unclear. This study aimed to assess the incidence of and time to surgical intervention for patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) in those treated with or without biologic therapy (BT).

Methods/Interventions: Retrospective analysis was performed using the TriNetX database, a large international cohort of over 100 million patients. Our cohort included patients with a diagnosis of CD or UC in the years 1990-2025 confirmed by colonoscopy or surgery. Patients were stratified by IBD type and whether or not they received treatment with BT. Time periods were based on the year of FDA approval of biologics for the treatment of CD/UC. The primary outcome was surgery-free survival (SfS), defined as the time from initial diagnosis to first major IBD-related surgery, which were identified using CPT codes. Kaplan-Meier analysis and log-rank tests were used to assess time-to-event outcomes.

Results/Outcomes: 210,424 patients met inclusion criteria (CD: 88,233; UC: 122,191). A total of 17.3% of CD patients and 9.4% of UC patients underwent a major surgical intervention over the study period. The incidence of surgical intervention decreased over each major time period, while the proportion of both CD and UC patients on BT increased (Figure 1A).

The time to surgery in biologic-treated CD (bT-CD) patients was longer than in biologic-naïve CD (bn-CD) patients (12.8 months vs. 7.5 months, p< 0.001). Similarly, the time to surgery in biologic-treated UC (bT-UC) patients was longer than in biologic-naïve UC (bn-UC) patients (12.3 months vs. 8.6 months, p< 0.001). In both CD and UC, the overall incidence of ultimately requiring a major IBD-related surgery was higher in both the bT-CD group compared to bN-CD group (21.5% vs. 14.4%, p< 0.001), as well as the bT-UC group compared to the bN-UC group (11.0% vs. 9.1%, p< 0.001) (Figure 1B).

For CD patients, the 1-year SfS was higher in the bT-CD group compared to bN-CD group (88.8% vs. 83.5%; p< 0.001), whereas the difference in SfS was not seen at 10 years (79.0% vs. 79.4%; p=0.287). For UC patients, the 1-year SfS was higher in the bT-UC group compared to bN-UC group (92.6% vs. 91.8%; p< 0.001), whereas the SfS at 10 years was in fact higher in the bN-UC group compared to bT-UC group (87.0% vs. 89.1%, p< 0.001) (Figure 1C).

Overall, BT was associated with a reduced hazard for surgery in CD (age-adjusted HR 0.88; 95% CI 0.85-0.91), while interestingly, biologic-treated UC was more likely to progress to surgery over time (age-adjusted HR 1.22; 95% CI 1.15-1.28). Overall survival was significantly improved with BT in both CD and UC (p < 0.001) (Figure 1D).

Conclusion/Discussion: In this large cohort, BT for the treatment of IBD was associated with short-term reduction in need for surgical intervention, however, this difference was not seen in the long term. The long-term findings potentially reflect the fact that patients with more severe disease are at higher risk for need of surgical intervention and thus, may be preferentially selected for BT. While the landscape of IBD management is shifting with improved short-term surgery-free outcomes since the introduction of BT, surgery remains a mainstay in the treatment of CD and UC.

Figure 1. Treatment Paradigms and Surgery-Free/Overall Survival for Patients with IBD Stratified by Biologic Treatment Status
A) Prevalence of any major abdominal surgery and any biologic therapy among patients with Crohn's Disease (CD) and Ulcerative Colitis (UC), stratified by therapeutic eras. The x-axis labels include the total number of patients at risk in each stratum. B) Risk of major abdominal surgery among patients with CD and UC, stratified by therapeutic era after biologics introduced. Labels include total patients at risk (N) and percent of cases that underwent surgery in each era. C) Kaplan-Meier analysis of the time from definitive diagnosis to the first major abdominal surgery for patients with Crohn's Disease (CD) and Ulcerative Colitis (UC). Patients were stratified by treatment with biologic therapy ("Biologic-Treated") versus those who were not ("Biologic-Naive"). D) Kaplan-Meier analysis of overall survival from the date of definitive diagnosis for the same cohorts. P-values were determined by the log-rank test