COMPARATIVE EFFICACY OF ADVANCED THERAPIES FOR MODERATE-TO-SEVERE ULCERATIVE COLITIS: A NETWORK META-ANALYSIS OF PHASE III TRIALS
Author(s)
XinDi Wang, BS1, Renshuang Cheng, BS1, Fenghao Shi, MS2, Xin Guan, PhD1.
1China Pharmaceutical University, Nanjing, China, 2Everest Medicines, Shanghai, China.
1China Pharmaceutical University, Nanjing, China, 2Everest Medicines, Shanghai, China.
OBJECTIVES: To systematically update and compare the relative efficacy of advanced therapies for moderate-to-severe ulcerative colitis (UC), and evaluate the impact of re-randomized responder (RER) versus treat-through (TT) trial designs on comparative treatment estimates.
METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov for phase III randomised controlled trials (RCTs) of biologics or small molecules in moderate-to-severe UC from database inception through March 2026. Network meta-analyses were conducted separately for re-randomised (RER) and treat-through (TT) trials. A random-effects model was used. Primary outcomes were clinical remission; Secondary outcomes included clinical response, endoscopic improvement, steroid free remission, and mucosal healing. Effect sizes were expressed as risk ratios (RR) with 95% confidence intervals (CIs). Treatments were ranked by SUCRA values.
RESULTS: Twenty-four phase III RCTs involving 8,922 patients were included, comprising 5,595 patients from RER trials and 3,327 patients from TT trials. Etrasimod 2 mg/day consistently ranked highest for clinical remission across all four primary analyses. In RER analyses, etrasimod likewise achieved the highest ranking for clinical remission during both induction (RR = 4.67, 95% CI: 1.71-12.76) and maintenance (RR = 3.84, 95% CI: 1.52-9.71). In TT analyses, etrasimod demonstrated the greatest relative efficacy for clinical remission during induction (RR = 3.65, 95% CI: 1.29-10.29) and maintenance (RR = 4.82, 95% CI: 2.34-9.90). Treatment rankings differed for secondary outcomes, upadacitinib 30 mg/day ranked highest for clinical response and endoscopic improvement in RER maintenance analyses, infliximab 10 mg/kg in TT induction analyses, and vedolizumab for mucosal healing during TT maintenance.
CONCLUSIONS: Comparative efficacy differed across advanced therapies for moderate-to-severe UC, Etrasimod demonstrated consistently favorable efficacy for clinical remission across both induction and maintenance phases, whereas upadacitinib, infliximab, and vedolizumab showed advantages for selected outcomes. These findings highlight the importance of considering trial design when interpreting comparative efficacy estimates and support evidence-based treatment selection in UC.
METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov for phase III randomised controlled trials (RCTs) of biologics or small molecules in moderate-to-severe UC from database inception through March 2026. Network meta-analyses were conducted separately for re-randomised (RER) and treat-through (TT) trials. A random-effects model was used. Primary outcomes were clinical remission; Secondary outcomes included clinical response, endoscopic improvement, steroid free remission, and mucosal healing. Effect sizes were expressed as risk ratios (RR) with 95% confidence intervals (CIs). Treatments were ranked by SUCRA values.
RESULTS: Twenty-four phase III RCTs involving 8,922 patients were included, comprising 5,595 patients from RER trials and 3,327 patients from TT trials. Etrasimod 2 mg/day consistently ranked highest for clinical remission across all four primary analyses. In RER analyses, etrasimod likewise achieved the highest ranking for clinical remission during both induction (RR = 4.67, 95% CI: 1.71-12.76) and maintenance (RR = 3.84, 95% CI: 1.52-9.71). In TT analyses, etrasimod demonstrated the greatest relative efficacy for clinical remission during induction (RR = 3.65, 95% CI: 1.29-10.29) and maintenance (RR = 4.82, 95% CI: 2.34-9.90). Treatment rankings differed for secondary outcomes, upadacitinib 30 mg/day ranked highest for clinical response and endoscopic improvement in RER maintenance analyses, infliximab 10 mg/kg in TT induction analyses, and vedolizumab for mucosal healing during TT maintenance.
CONCLUSIONS: Comparative efficacy differed across advanced therapies for moderate-to-severe UC, Etrasimod demonstrated consistently favorable efficacy for clinical remission across both induction and maintenance phases, whereas upadacitinib, infliximab, and vedolizumab showed advantages for selected outcomes. These findings highlight the importance of considering trial design when interpreting comparative efficacy estimates and support evidence-based treatment selection in UC.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO106
Topic
Clinical Outcomes, Methodological & Statistical Research, Study Approaches
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Gastrointestinal Disorders