ICI-Associated Colitis Linked to Persistent Morbidity After Therapy Discontinuation

New real-world findings suggest patients who develop immune checkpoint inhibitor (ICI)-associated colitis face substantial risks for rehospitalization, Intensive Care Unit (ICU) admission, and mortality even after discontinuing therapy, highlighting ongoing uncertainty surrounding long-term outcomes in this population.

Presented at Digestive Disease Week 2026, the retrospective analysis of > 17,000 patients found rehospitalization rates climbed from 25% at 30 days to 43% at 180 days following ICI discontinuation, while mortality increased from 7% to 23% over the same timeframe.

“Immune checkpoint inhibitor colitis is relatively new, so when we talk about long-term outcomes and unknowns, there’s a lot more we don’t know than we do know,” Miguel Regueiro, MD, Chief of Cleveland Clinic’s Digestive Disease Institute, said in an interview with HCPLive. “What we don’t know is how we should treat these patients… What happens to these patients after we stop the immune checkpoint inhibitor? What about hospitalization, surgery, or mortality? What are the long-term outcomes? Do they recur?”

Persistent Risks After ICI Therapy Cessation

Immune checkpoint inhibitors are increasingly used across malignancies including melanoma and lung cancer, but immune-mediated colitis remains among the more serious toxicities associated with treatment. Although corticosteroids and biologic therapies are commonly used to manage symptoms, limited data exist regarding long-term outcomes after therapy discontinuation.

To evaluate these outcomes, investigators used the TriNetX Research Network database, which includes data from more than 150 million patients. Adults aged ≥18 years treated with ICIs were identified, with immune-mediated colitis defined using ICD-10 K52 codes in combination with recurrent colitis encounters or steroid/biologic treatment exposure.

The final cohort included 17,353 adults with ICI-associated colitis (mean age 64.6 standard deviation [SD]: 12.4; 50.6% male). Investigators noted substantial baseline comorbidity burden, including ischemic heart disease (34.0%), diabetes (28.4%), and chronic kidney disease (23.3%).

Nearly all patients (96.0%) required corticosteroids, reflecting what investigators characterized as a clinically severe cohort.

Biologic Rescue Therapy Use Remained Low

Despite the severity of illness, use of biologic rescue therapy was uncommon. Investigators reported infliximab use in 0.8% of patients and vedolizumab use in 0.2%.

Current guidance from the Society for Immunotherapy of Cancer recommends escalation to infliximab or vedolizumab when corticosteroid therapy fails within 3-5 days or symptoms recur during steroid tapering. Prior literature has also suggested earlier biologic initiation may reduce hospitalizations, steroid taper failures, and symptom duration in immune-mediated colitis.2

“I think the take-home message from this study was that because rehospitalization, mortality, and ICU admission rates are so high, we need to be aggressive in treating these patients early,” Regueiro said. “A big takeaway is that using vedolizumab or infliximab in patients who are started on steroids for immune checkpoint inhibitor colitis should probably be done much earlier than we’re doing now.”

Rehospitalization remained frequent following discontinuation of ICI therapy:

• 25% at 30 days
• 36% at 90 days
• 43% at 180 days

Investigators also observed ICU utilization rates increasing from 6% at 30 days to 12% at 180 days. Mortality similarly rose over time, increasing from 7% to 23% across the same interval.

Although colectomy remained rare (<1%), investigators noted surgery was still required in a subset of patients with refractory disease.

Need for Long-Term Management Strategies

According to investigators, the findings suggest immune-mediated toxicities may persist beyond active ICI exposure and underscore the need for more standardized management strategies and multidisciplinary coordination between gastroenterology and oncology.

The study authors concluded that improved risk assessment and clearer guidance regarding ICI discontinuation may help improve long-term patient outcomes.

Editor’s Note: Regueiro reports relevant disclosures with AbbVie, Johnson and Johnson, and others.

References

1. Mannava A, Perez J, Sinh P, et al. Immune checkpoint inhibitor colitis: a US-based collaborative network propensity-matched cohort study of rehospitalization and outcomes after ICI therapy discontinuation. Presented at: Digestive Disease Week 2026; May 2026; San Diego, CA.

2. Puzanov I, Diab A, Abdallah K, et al. Society for Immunotherapy of Cancer clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2021;9(6):e002435.