The growing potential of tofacitinib in immune checkpoint inhibitor-induced colitis: identifying remaining puzzle pieces

Abstract

Immunotherapy, a primary anti-neoplastic treatment, exploits the patient’s immune system to kill neoplastic cells by modulating immune checkpoints such as cytotoxic T-lymphocyte antigen 4 and programmed cell death 1. Despite an apparent anti-neoplastic efficacy, immunotherapeutic agents are often accompanied by multiorgan toxicity, including gastrointestinal ones. This particular class of immunotherapy-related adverse events, mainly represented by diarrhea and colitis, necessitates a nuanced treatment strategy. Current treatments are primarily based on standardized severity grading systems to guide and proportion therapeutic interventions, ranging from simple behavioral modifications or conventional molecules (such as anti-diarrheal) to advanced biological treatments. Tofacitinib, a pan-Janus kinase inhibitor, emerged as a potential option for managing immune-related (IR) colitis by targeting hyperactivated T cells within the colic microenvironment. However, evidence supporting the use of tofacitinib in IR colitis is primarily derived from case reports and small case series, lacking robust randomized clinical trial data. While preliminary findings demonstrate encouraging clinical control of IR colitis with tofacitinib, further research is warranted to elucidate its efficacy, safety, optimal dosage, and treatment duration. Although there are some worries about its effects on cancer response and safety, current evidence indicates that tofacitinib could be seen as a possible treatment choice if other therapies with more robust evidence profiles have not been successful.