Background & aims: Our aim was to evaluate the outcomes of maintenance treatments for eosinophilic esophagitis (EoE) among observational studies (OSs) and randomized controlled trials (RCTs). Materials and methods: Studies reporting histologic success of maintenance therapy ≥48 weeks were included. The primary outcome was histologic success rate (defined as <15/<6 eosinophils/high-power field). Risk ratios (RRs) for histologic success of maintenance therapy vs placebo or induction and drug safety were also assessed. Random effects meta-analyses with heterogeneity measured with I2 were performed. RCTs and OSs were analyzed separately. Results: In RCTs, histologic <15 eosinophils/high-power field rates were 86% (95% confidence interval [CI], 71%-96%) for corticosteroids and 79% (95% CI, 69%-87%) for biologics. Dupilumab alone accounted for 82% (95% CI, 72%-89%), whereas small molecules yielded 28%. Biologics showed higher <6 eosinophils/high-power field rates compared with corticosteroids (70% vs 59%). Clinical success was 58% (95% CI, 31%-83%) for corticosteroids and 59% (95% CI, 34%-82%) for biologics. Budesonide showed common-effect adjusted RR of 7.87 (95% CI, 4.19-14.77) of maintaining histologic remission over therapy discontinuation. In OSs, proton pump inhibitors showed 64% (95% CI, 43%-83%) histologic and 80% (95% CI, 53%-97%) clinical success, whereas corticosteroids achieved 49% (95% CI, 30%-68%) and 51% (95% CI, 18%-83%) rates, respectively. Therapy de-escalation was not associated with histologic relapse (RR, 1.04; 95% CI, 0.72-1.51). Long-term safety was confirmed with 3% (95% CI, 1%-6%) severe adverse events in RCTs and 5% (95% CI, 2%-9%) in OSs. Treatment withdrawal rates were low (10% for RCTs, 4% for OSs). Moderate to substantial heterogeneity was observed for most outcomes. Conclusions: Maintenance therapies prevent histologic relapse in the long term, without clear disadvantage of dose de-escalation from induction to maintenance phase. Low adverse events and withdrawal rates confirm long-term treatment is well-tolerated.
Clinical, Histologic, and Safety Outcomes With Long-term Maintenance Therapies for Eosinophilic Esophagitis: A Systematic Review and Meta-analysis
Savarino Edoardo;
2025
Abstract
Background & aims: Our aim was to evaluate the outcomes of maintenance treatments for eosinophilic esophagitis (EoE) among observational studies (OSs) and randomized controlled trials (RCTs). Materials and methods: Studies reporting histologic success of maintenance therapy ≥48 weeks were included. The primary outcome was histologic success rate (defined as <15/<6 eosinophils/high-power field). Risk ratios (RRs) for histologic success of maintenance therapy vs placebo or induction and drug safety were also assessed. Random effects meta-analyses with heterogeneity measured with I2 were performed. RCTs and OSs were analyzed separately. Results: In RCTs, histologic <15 eosinophils/high-power field rates were 86% (95% confidence interval [CI], 71%-96%) for corticosteroids and 79% (95% CI, 69%-87%) for biologics. Dupilumab alone accounted for 82% (95% CI, 72%-89%), whereas small molecules yielded 28%. Biologics showed higher <6 eosinophils/high-power field rates compared with corticosteroids (70% vs 59%). Clinical success was 58% (95% CI, 31%-83%) for corticosteroids and 59% (95% CI, 34%-82%) for biologics. Budesonide showed common-effect adjusted RR of 7.87 (95% CI, 4.19-14.77) of maintaining histologic remission over therapy discontinuation. In OSs, proton pump inhibitors showed 64% (95% CI, 43%-83%) histologic and 80% (95% CI, 53%-97%) clinical success, whereas corticosteroids achieved 49% (95% CI, 30%-68%) and 51% (95% CI, 18%-83%) rates, respectively. Therapy de-escalation was not associated with histologic relapse (RR, 1.04; 95% CI, 0.72-1.51). Long-term safety was confirmed with 3% (95% CI, 1%-6%) severe adverse events in RCTs and 5% (95% CI, 2%-9%) in OSs. Treatment withdrawal rates were low (10% for RCTs, 4% for OSs). Moderate to substantial heterogeneity was observed for most outcomes. Conclusions: Maintenance therapies prevent histologic relapse in the long term, without clear disadvantage of dose de-escalation from induction to maintenance phase. Low adverse events and withdrawal rates confirm long-term treatment is well-tolerated.
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