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.

Luca Pastorelli ¹, Theresa T Pizarro, Fabio Cominelli, Maurizio Vecchi Expert Opin Emerg Drugs. 2009 Sep;14(3):505-21. doi: 10.1517/14728210903146882.

Background: Ulcerative colitis (UC) is a chronic, relapsing inflammatory disorder of the colon for which the etiology is currently unknown. At present, strategies to treat UC are primarily targeted to control inflammation during active phases of disease as well as maintain remission during quiescence. As such, several unmet needs in the treatment of UC still remain. In recent years, basic research has led to the recognition of several key factors in the pathogenesis of UC, translating into the development of several novel therapeutic agents. Objective: The aim of this study is to review emerging therapies that may advance the treatment and improve the overall care of UC patients. Methods: An extensive literature search on published manuscripts and meeting proceedings has been performed to provide a comprehensive review of future drug therapies to treat UC. Results/conclusion: The translational application of new discoveries in the basic understanding of UC pathogenesis is continuing and critical for the development of novel treatment strategies. Design of novel biologic therapies to treat UC has the challenge of addressing potential safety issues, while more traditional drugs should be further developed to facilitate patient compliance to treat this chronic, debilitating disease.

https://pubmed.ncbi.nlm.nih.gov/19656075/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563345/