Anas Zaher ¹, Maria Julia Moura Nascimento Santos ², Hassan Elsaygh ³, Stephen J Peterson ¹, Carolina Colli Cruz ², Anusha Shirwaikar Thomas ², Yinghong Wang ²

Expert Opin Drug Saf. 2025 Apr 21:1-10. doi: 10.1080/14740338.2025.2496431. Online ahead of print.

Introduction: This review discusses the epidemiology, pathophysiology, and factors associated with refractory immune-mediated diarrhea and colitis (r-IMDC), emphasizing tailored treatment strategies.

Areas covered: The current literature on r-IMDC was reviewed using PubMed (2015-2025), focusing on clinical trials, meta-analyses, and case reports relevant to its management.

Expert opinion: Effectively managing r-IMDC is crucial for balancing toxicities and antitumor response. Available second and third-line management options for r-IMDC cases must be carefully evaluated. Future perspectives include development of standardized protocols beyond second-line therapies and predictive biomarkers to enable personalized treatment.

• ICIs are essential in cancer therapy but often cause IMDC, with up to 41% of patients developing steroid-refractory cases.
• Current guideline-recommended second-line therapies, such as infliximab and vedolizumab, fail in 11% of IMDC cases, underscoring the need for third-line interventions.
• Emerging therapies, including Janus kinase inhibitors, fecal microbiota transplantation, and interleukin-targeting agents, show promise for r-IMDC management. Also gma, IVIG.
• Personalized management strategies, incorporating gut microbiota modulation and targeted immune suppression, could improve outcomes in refractory colitis.
• Effective management of r-IMDC is critical for reducing prolonged immunosuppression, minimizing cancer treatment interruptions, and improving patient quality of life.

Elena Céspedes Martínez, Virginia Robles Alonso, Claudia Herrera-De Guise, Luis Mayorga, Francesc Casellas, María Roca-Herrera, Natalia Borruel, Rev Esp Enferm Dig 2023;115(10):567-573

Introduction: immune checkpoint inhibitors (ICI) are increasingly used to treat several types of cancer. These drugs lead to a wide range of toxicities. Immune-related gastrointestinal adverse events are common and potentially severe. In this manuscript, we recount the real clinical experience in a tertiary center. Methods: a retrospective and observational study was conducted in adult patients under ICI treatment. Included patients had been referred to the Gastrointestinal Service of Hospital Universitario Vall d’Hebron for evaluation of severe toxicities, from January 2017 to January 2020, for whom the clinical, epidemiological and evolutive data were collected. Results: a total of 18 patients were included. Fifty-five percent received anti-programmed cell death protein 1 (PD-1)/anti-programmed death-ligand 1 (anti PD-L1), 11 % received anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) and 33 % received both treatments. The toxicities were manifested as enterocolitis, microscopic colitis and gastritis. Upper gastrointestinal endoscopy was performed in seven patients; all were proved to have histological changes on duodenum biopsies. Treatment was stopped in all patients and steroids were initiated. Sixty-six per cent achieved clinical remission with steroids. Five patients received anti-TNF treatment (infliximab). Only one of the five had responded. Two anti-TNF refractory patients received ustekinumab, with an appropriate clinical response. One patient received apheresis granulocyte as concomitant treatment. A patient with a steroid-dependent course started vedolizumab. Three patients had other immune-related adverse events. Conclusion: gastrointestinal immune-related adverse events are acquiring a higher profile in daily practice and gastroenterologists play an even greater role in the management of these patients.

Severe and refractory gastrointestinal toxicity due to immune checkpoint inhibitors: clinical experience in a tertiary referral hospital – PubMed (nih.gov)

REED – Revista Española de Enfermedades Digestivas