This article systematically reviews and updates the 2024 American Gastroenterological Association (AGA) clinical guidelines by evaluating efficacy differences of various biologics in patients with moderate-to-severe ulcerative colitis (UC) through network meta-analysis (NMA), providing important reference for treatment strategies.
Literature Overview
The article, titled 'Comparative Efficacy of Advanced Therapies for Management of Moderate-to-Severe Ulcerative Colitis: 2024 AGA Evidence Synthesis,' published in the journal 'Gastroenterology,' reviews and summarizes current advanced therapies for treating moderate-to-severe ulcerative colitis (UC) and compares their efficacy in inducing and maintaining clinical remission using network meta-analysis. This study includes multiple biologics and small molecule drugs, and stratifies the analysis based on the efficacy in biologic-naïve and biologic-experienced patients, providing data support for clinical treatment pathways.
Background Knowledge
Ulcerative colitis is a chronic inflammatory bowel disease affecting approximately 1.5 million people in the United States. Traditional treatment options for patients with moderate-to-severe UC have been increasingly replaced by biologics and targeted small molecule drugs, including TNF-α antagonists, integrin inhibitors, S1P receptor modulators, IL-12/23 and IL-23 antagonists, and JAK inhibitors. However, due to the lack of head-to-head trials, most studies rely on indirect comparisons using NMA methods. The 2024 AGA guideline update incorporates the latest phase III clinical trial data, including efficacy evidence for mirikizumab, guselkumab, risankizumab, and etrasimod. This study uses NMA to evaluate the positioning of different treatments in naïve and experienced populations, highlighting the relevance of efficacy differences to clinical practice.
Research Methods and Experiments
The research team systematically searched multiple databases (Ovid MEDLINE, Ovid EMBASE, Cochrane Database of Systematic Reviews) up to November 21, 2023, following the PRISMA-NMA extension statement. Inclusion criteria were: RCT studies, adult patients with moderate-to-severe UC, comparing different advanced therapies or placebo, with primary endpoints of clinical remission and endoscopic improvement. A frequentist NMA approach (R package netmeta) was used, and the certainty of evidence was assessed using the GRADE system. Trials that did not stratify results by biologic exposure, drugs not approved by the FDA (e.g., etrolizumab), and pediatric studies were excluded.
Key Conclusions and Perspectives
Research Significance and Prospects
This study provides key data support for the 2024 AGA clinical guideline update, helping to optimize treatment pathways for patients with moderate-to-severe UC. Future research directions include evaluating the long-term safety of different therapies, particularly whether JAK inhibitors carry higher risks of thrombosis or cardiovascular events. Additionally, the study emphasizes the impact of prior biologic exposure on subsequent treatment selection, suggesting that clinical decision-making should consider patients’ treatment history.
Conclusion
Through an updated network meta-analysis, this study systematically evaluated efficacy differences among various advanced therapies for moderate-to-severe ulcerative colitis and, in conjunction with the 2024 AGA guidelines, provided treatment positioning recommendations for biologic-naïve and biologic-experienced patients. The study found that risankizumab and ozanimod performed best in biologic-naïve patients, whereas upadacitinib demonstrated the highest efficacy in regions where it is approved as first-line therapy and in biologic-experienced patients. It also highlights that current efficacy assessments largely rely on indirect data and that efficacy differences among drugs are significant depending on prior treatment exposure. Future research should focus on balancing efficacy and safety and optimizing clinical outcomes through personalized treatment pathways.
