Early versus delayed biologic therapy for immune checkpoint inhibitor–associated colitis: A propensity-matched real-world analysis.

e24204 Background: Immune checkpoint inhibitor (ICI)–associated colitis is a clinically significant immune-related adverse event that may require biologic therapy when refractory to corticosteroids. Although infliximab and vedolizumab are commonly used, the impact of timing of biologic initiation on clinical outcomes remains uncertain. We compared outcomes associated with early versus delayed biologic therapy in patients with ICI-associated colitis using a large real-world database. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Adult patients treated with ICIs (pembrolizumab, nivolumab, or ipilimumab) who subsequently developed colitis were identified. Patients were categorized based on timing of biologic initiation (infliximab or vedolizumab): early initiation (within 3 days of colitis diagnosis) versus delayed initiation (between days 3 and 14). Propensity score matching (1:1) was performed to balance demographics, malignancy type, comorbidities, corticosteroid exposure, and baseline laboratory parameters. Outcomes assessed over 12 months included all-cause mortality, hospitalization, immune checkpoint inhibitor reinitiation, colonic perforation, and long-term corticosteroid therapy. Time-to-event and risk-based analyses were performed. Results: After propensity matching, 588 patients were included in each cohort with well-balanced baseline characteristics. At 12 months, no statistically significant differences were observed between early and delayed biologic therapy in all-cause mortality (21.7% vs 23.7%; hazard ratio HR 0.90, 95% CI 0.71–1.15; p = 0.69) or hospitalization (46.0% vs 49.2%; HR 0.91, 95% CI 0.71–1.16; p = 0.78). Rates of immune checkpoint inhibitor reinitiation were similar between cohorts (33.0% vs 29.6%; HR 1.13, 95% CI 0.92–1.39; p = 0.66). The incidence of colonic perforation was low and comparable (2.2% vs 2.6%). There was no significant difference in the requirement for long-term corticosteroid therapy (26.3% vs 27.9%). Conclusions: In this study, the timing of biologic therapy initiation for immune checkpoint inhibitor–associated colitis was not associated with statistically significant differences in mortality, hospitalization, immune checkpoint inhibitor reinitiation, colonic perforation, or long-term corticosteroid therapy. Although early biologic initiation was associated with numerically favorable outcomes across several endpoints, the study may have been underpowered to detect modest but clinically meaningful differences between treatment strategies. As such, these findings should be interpreted as hypothesis-generating. Prospective, adequately powered studies are warranted to determine whether earlier biologic escalation confers a true clinical benefit and to better define optimal treatment sequencing in this population.