Acute severe ulcerative colitis trials: the past, the present and the future

Area of Science:

• Gastroenterology
• Clinical Pharmacology
• Medical Research Methodology

Background:

• Acute severe ulcerative colitis (ASUC) presents significant colectomy and mortality risks.
• Cortisone trials in 1955 established first-line therapy and early clinical trial endpoints for ASUC.
• Limited drug development progress for ASUC since infliximab and ciclosporin trials in the late 1990s/early 2000s.

Purpose of the Study:

• To systematically review all interventional randomized controlled trials (RCTs) for hospitalized severe ulcerative colitis (UC) patients.
• To provide an overview of ASUC treatment efficacy from historical to current therapies.
• To assess the evolution of ASUC clinical trial characteristics and identify future challenges and opportunities.

Main Methods:

• Systematic review of interventional randomized controlled trials (RCTs) in hospitalized severe UC patients.
• Analysis of treatment efficacy across different therapeutic eras.
• Evaluation of changes in study populations, eligibility criteria, and study designs over time.

Main Results:

• Historical cortisone trials established foundational treatment and endpoints.
• Trials in the 1990s/2000s demonstrated infliximab and ciclosporin efficacy.
• Recent progress in novel ASUC drug development has been limited, despite ongoing RCTs.

Conclusions:

• The review highlights the historical impact and subsequent stagnation in ASUC drug development.
• Understanding the evolution of trial designs is crucial for future research.
• Overcoming challenges in clinical trial programs is essential to deliver novel ASUC therapies.