Clinical, histological and safety outcomes with long-term maintenance therapies for eosinophilic esophagitis: A systematic review and meta-analysis

Alberto Barchi; Luca Massimino; Francesco Vito Mandarino; Mona-Rita Yacoub; Luca Albarello; Edoardo Vincenzo Savarino; Federica Ungaro; Silvio Danese; Sandro Passaretti; Albert J Bredenoord; Edoardo Vespa

doi:10.1016/j.cgh.2024.11.007

Clinical, histological and safety outcomes with long-term maintenance therapies for eosinophilic esophagitis: A systematic review and meta-analysis

Clin Gastroenterol Hepatol. 2024 Dec 13:S1542-3565(24)01069-3. doi: 10.1016/j.cgh.2024.11.007. Online ahead of print.

Affiliations

¹ Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele; Department of Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam, the Netherlands. Electronic address: barchi.alberto@hsr.it.
² Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele.
³ Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁴ Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁵ Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy.
⁶ Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele; Università Vita-Salute San Raffaele, Faculty of Medicine, Milan, Italy.
⁷ Department of Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam, the Netherlands.

PMID: 39675404
DOI: 10.1016/j.cgh.2024.11.007

Abstract

Background and aim: Our aim was to evaluate outcomes of maintenance treatments for EoE among observational studies (OSs) and randomized controlled trials (RCTs).

Materials and methods: Studies reporting histological success of maintenance therapy ≥ 48 weeks were included. Primary outcome was histological success rate (defined as <15/<6 eos/HPF). Risk Ratios (RR) for histological success of maintenance therapy versus 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, histological < 15 eos/HPF rates were 86% (95%CI, 71%-96%) for corticosteroids and 79% (95%CI, 69%-87%) for biologics. Dupilumab alone accounted for 82% (95%CI, 72%-89%) while small molecules yielded 28%. Biologics showed higher <6 eos/HPF rates compared to 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 histological remission over therapy discontinuation. In OSs, proton pump inhibitors showed 64% (95%CI, 43%-83%) histological and 80% (95%CI, 53%-97%) clinical success, while corticosteroids achieved 49% (95%CI, 30%-68%) and 51% (95%CI, 18%-83%) rates, respectively. Therapy de-escalation was not associated with histological 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 histological 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.

Keywords: EoE; Maintenance treatments; biologics; corticosteroids; long-term; maintenance; meta-analysis.

Publication types

Review