Benefit-risk profiling of advanced therapies in moderate-to-severe ulcerative colitis: a clustered network meta-analysis
5 affiliations
- 1Hubei University of Chinese Medicine
- 2Shanghai University of Traditional Chinese Medicine
- 3Department of Anorectal Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine
- 4Hubei Shizhen Laboratory
- 5Hubei Key Laboratory of theory and application research of liver and kidney in traditional Chinese medicine
Abstract
Background and Aims: The therapeutic landscape for moderate-to-severe ulcerative colitis (UC) has expanded with the introduction of oral small molecules and recently approved biologics. However, the scarcity of head-to-head trials necessitates indirect comparisons to clarify their relative positioning. We aimed to determine the comparative efficacy and tolerability hierarchy of approved and emerging advanced therapies, incorporating the most contemporary evidence.
Methods: We retrieved randomized controlled trials (RCTs) from major databases up to November 2025. Efficacy outcomes included clinical remission and endoscopic improvement; tolerability was evaluated via discontinuations due to adverse events. We employed Bayesian network meta-analysis and bivariate clustered ranking to visualize efficacy-tolerability profiles, stratifying by prior biologic exposure.
Results: A total of 32 RCTs were included. In the induction phase, Upadacitinib, Ustekinumab, and Risankizumab co-occupied the “most favorable” quadrant, combining high efficacy with superior tolerability. In the maintenance phase, Upadacitinib 30 mg demonstrated the highest-ranking probability for efficacy, while IL-23 antagonists (Guselkumab, Mirikizumab) and low-dose Upadacitinib exhibited a highly favorable efficacy-tolerability profile. Notably, in biologic-exposed patients, Upadacitinib demonstrated the highest relative efficacy among evaluated therapies, whereas Guselkumab emerged as a highly effective biologic alternative based on current estimates.
Conclusion: Based on current network estimates, Upadacitinib is suggested among the most efficacious options for achieving clinical and endoscopic endpoints, particularly in refractory disease, while IL-23 antagonists present highly favorable tolerability profiles for maintenance without compromising efficacy. These findings support a tailored approach to drug selection, aligning patient-specific profiles of inflammatory burden with current evidence-based safety thresholds.
Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261292029 , identifier CRD420261292029.
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BibTeX
@article{zhang2026benefitrisk,
title = {{Benefit-risk profiling of advanced therapies in moderate-to-severe ulcerative colitis: a clustered network meta-analysis}},
author = {Xinyuan Zhang and Hao Qian and Lijuan Yang and Hao Wang and Guangjun Sun and Aizhen Lin},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1961820},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1961820/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Benefit-risk profiling of advanced therapies in moderate-to-severe ulcerative colitis: a clustered network meta-analysis
AU - Xinyuan Zhang
AU - Hao Qian
AU - Lijuan Yang
AU - Hao Wang
AU - Guangjun Sun
AU - Aizhen Lin
PY - 2026
DA - 2026/10/14
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1961820
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1961820/full
AB - Background and Aims: The therapeutic landscape for moderate-to-severe ulcerative colitis (UC) has expanded with the introduction of oral small molecules and recently approved biologics. However, the scarcity of head-to-head trials necessitates indirect comparisons to clarify their relative positioning. We aimed to determine the comparative efficacy and tolerability hierarchy of approved and emerging advanced therapies, incorporating the most contemporary evidence. Methods: We retrieved randomized controlled trials (RCTs) from major databases up to November 2025. Efficacy outcomes included clinical remission and endoscopic improvement; tolerability was evaluated via discontinuations due to adverse events. We employed Bayesian network meta-analysis and bivariate clustered ranking to visualize efficacy-tolerability profiles, stratifying by prior biologic exposure. Results: A total of 32 RCTs were included. In the induction phase, Upadacitinib, Ustekinumab, and Risankizumab co-occupied the “most favorable” quadrant, combining high efficacy with superior tolerability. In the maintenance phase, Upadacitinib 30 mg demonstrated the highest-ranking probability for efficacy, while IL-23 antagonists (Guselkumab, Mirikizumab) and low-dose Upadacitinib exhibited a highly favorable efficacy-tolerability profile. Notably, in biologic-exposed patients, Upadacitinib demonstrated the highest relative efficacy among evaluated therapies, whereas Guselkumab emerged as a highly effective biologic alternative based on current estimates. Conclusion: Based on current network estimates, Upadacitinib is suggested among the most efficacious options for achieving clinical and endoscopic endpoints, particularly in refractory disease, while IL-23 antagonists present highly favorable tolerability profiles for maintenance without compromising efficacy. These findings support a tailored approach to drug selection, aligning patient-specific profiles of inflammatory burden with current evidence-based safety thresholds. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261292029 , identifier CRD420261292029.
SN - 1663-9812
ER -