Comprehensive assessment beyond eosinophils in eosinophilic esophagitis: an updated network meta-analysis

The rapid development of therapies for eosinophilic esophagitis (EoE), particularly involving biologics and small molecules, has prompted questions about their roles within current treatment algorithms. We aimed to examine the relative efficacy of novel biologics, small molecules and topical steroids by evaluating clinical, endoscopic, and histological improvements.

We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and major conference databases for articles published from inception to Jul 1, 2024. Randomized controlled trials (RCTs) evaluating the clinical, endoscopic and histological efficacy of novel biologics, small molecules or topical steroids as induction therapies for patients with EoE were included. A network meta-analysis (NMA) was performed to obtain effect size-risk ratio (RR), mean difference (MD), standardized mean difference (SMD)-with 95% confidence interval (CI) for different outcomes. The surface under the cumulative ranking (SUCRA) was estimated to present the relative ranking of treatment. The primary outcome was the induction of symptomatic improvement. The secondary outcomes were endoscopic improvement and histological remission. Higher SUCRA curve rankings indicate a greater probability of superior treatment efficacy. The review was registered in PROSPERO (CRD420251155393).

Our search strategy identified 409 records, of which 18 trials (total n = 2,506 patients) were eligible for inclusion. From 12 trials that assessed the induction of clinical improvement, Dupilumab 300 mg weekly (qw) ranked first (SMD -0.57, 95%CI [-0.79, -0.35]), while Dupilumab 300mg every 2 weeks (q2w) ranked relatively low. From 12 randomized controlled trials evaluating endoscopic improvement, Dupilumab 300 mg qw (MD -2.10, 95%CI [-2.49,-1.90]) and 300 mg q2w (MD -1.87, 95%CI [-2.25, -1.48])ranked second and fourth, respectively. In 17 RCTs assessing the induction of histological remission, Budesonide orally disintegrating tablet (BODT) ranked highest(RR 30.77, 95%CI [6.63, 294.95]), whereas Dupilumab (qw/q2w) showed moderate effectiveness.

This study suggests that Dupilumab 300mg qw might be the best performing agent for induction of clinical improvement (the primary endpoint) and BODT might be the most efficacious agents for histological and endoscopic improvement (the secondary endpoint). This could provide evidence for clinical therapy strategy for EoE patients.