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.