NCT07167251

Management of Immune Checkpoint Inhibition-related Hepatitis Using Low-dose Corticosteroids

Management of Immune Checkpoint Inhibition-related Hepatitis Using Low-dose Corticosteroids - A Prospective Registry-based, Cohort Study

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 63 (estimated)
• Sponsor: University Hospital, Basel, Switzerland · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study evaluates the effectiveness of low-dose corticosteroids in managing grade 2-3 immune-related hepatitis in cancer patients treated with immune checkpoint inhibitors. It aims to determine whether of 0.5-1miligram per kilogram bodyweight prednisolone is sufficient to manage immune-related hepatitis without the need for dose escalation or additional immunosuppressive therapy.

Detailed description

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but are associated with immune-related adverse events (irAEs), including immune-related hepatitis, a potentially serious complication that affects up to 30% of patients undergoing ICI combination therapy. Current management guidelines recommend corticosteroids as the first-line treatment for moderate to severe irAEs. However, high doses of corticosteroids are associated with increased risks of infections, metabolic and psychiatric side effects, and potentially impaired anti-tumor efficacy. Retrospective data suggest that lower doses may be equally effective while reducing toxicity and preserving treatment efficacy. This prospective, registry-based cohort study aims to evaluate the clinical performance and outcomes of low-dose corticosteroid treatment for managing grade 2 or 3 IR-hepatitis. The hypothesis is that a corticosteroid "test dose" approach (0.5-1 mg/kg prednisolone) followed by early evaluation of clinical response can identify patients who benefit from reduced immunosuppression, thus minimizing side effects without compromising the effectiveness of ICI therapy. Patients will be recruited from participating oncology centers where standardized management of IR-hepatitis has been implemented. Eligible participants are adult cancer patients who develop grade 2 or 3 IR-hepatitis during ICI therapy, excluding those with prior high-dose corticosteroid use, concurrent neurological or cardiac irAEs requiring high-dose corticosteroids, or underlying chronic liver diseases. The primary endpoint is resolution of IR-hepatitis (defined as return to baseline or grade 1 liver function tests) within 8 weeks without corticosteroid dose escalation, additional immunosuppressive therapy, and with tapering to ≤10 mg/day prednisolone. Secondary endpoints include the proportion of patients requiring dose escalation, time to hepatitis resolution, cumulative corticosteroid exposure, relapse rates, occurrence of additional irAEs, progression-free survival (PFS), overall survival (OS), and identification of predictors of steroid-refractory hepatitis. Patients will be followed for six months after the onset of IR-hepatitis. Follow-up assessments will align with standard clinical care, with no additional study-specific visits. Liver function tests, immunotherapy status, corticosteroid and immunosuppressive use, and occurrence of new irAEs will be recorded. A liver biopsy is recommended in refractory or ambiguous cases. Data will be collected via the REDCap system, ensuring standardized electronic data capture. The study is powered to detect a successful resolution rate of at least 80% in patients with grade 3 IR-hepatitis treated with low-dose corticosteroids, assuming a null hypothesis threshold of 65%. Descriptive and exploratory statistical methods will be used to analyze the data, including Kaplan-Meier estimates for time-to-event outcomes and logistic regression for exploratory subgroup analyses. This study addresses a critical gap in prospective evidence on the management of IR-hepatitis. By evaluating the efficacy and safety of a pragmatic, low-cost, low-toxicity intervention, it may inform future guidelines and serve as a foundation for a randomized non-inferiority trial. The study's design allows for real-world applicability while ensuring scientific rigor through harmonized protocols and data collection.

Conditions

• Immune Related Adverse Events
• Immune-Mediated Hepatitis
• Cancer

Interventions

Type	Name	Description
DRUG	Low-dose corticosteroids for immune-related hepatitis grade 3	Prednisolone 0.5-1 mg/kg orally for grade 3 IR-hepatitis; adjusted based on liver function; treatment per local standard of care.
DRUG	Low-dose corticosteroids for immune-related hepatitis grade 2	Hold immunotherapy and reassess liver function at the treating physician's discretion. If liver function tests persistently worsen or continue to rise, consider administering prednisolone at 0.5 mg/kg body weight

Timeline

• Start date: 2025-08-25
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2025-09-11
• Last updated: 2025-09-11

Locations

2 sites across 2 countries: Switzerland, United Kingdom