Introduction

Long-term maintenance treatment efficacy, safety and tolerability in eosinophilic esophagitis (EoE) is still partially understood. The aim of this study was to evaluate long-term outcomes of maintenance treatment for EoE with various drugs and dose regimens in real-world observational studies and randomized controlled trials (RCTs).

Aims & Methods

Systematic search was performed on Pubmed-MEDLINE, Embase and Cochrane Central Register of Controlled Trials from inception to October 2023. Studies reporting histologic success of maintenance therapy for EoE patients > 48 weeks, following 8-12 weeks of induction therapy with the same drug were included. Primary outcome was pooled histologic success (defined as < 15 eosinophils/HPF) at the end of follow-up for both study designs. Risk Difference (RD) or Odds Ratio (ORs) for histological success of maintenance therapy versus placebo (PBO) (for RCTs) and versus induction (for both study designs), pooled drug-related adverse events (AEs), endoscopic and clinical success rates were assessed as secondary outcomes. Random effects model metanalyses were performed. A-priori sub-group analyses were performed to address substantial inter-study heterogeneity (measured with I² statistic).

Results

From 3,916 full articles, 23 articles matched inclusion criteria (17 observational studies and 6 RCTs), 7 with pediatric patients only. Overall, 1,923 patients (M 70.1%; mean age 29.8±12.6 years). Mean follow-up time was 78.4 weeks. Budesonide (either oro-dispersible or viscous suspension) was administered in 7 studies (including 2 RCTs), PPI in 6 studies (all observational, 4 pediatric), Fluticasone in 5 studies (including 1 RCT with 4 cohorts), Dupilumab in 2 RCTs and Cendakimab in 1 RTC. Pooled rate of long-term histologic success for RCTs was 83% (95% CI, 77%-89%; I² 73.1%), while for observational studies attested at 53% (95% CI, 42%-65%; I² 93.5%) at a median follow-up of 97.8 weeks. Maintenance therapy in RCTs showed a RD of -0.71 (95% CI; -0.92-0.50; p<0.01; I² 88.9%) versus PBO, while a RD of -0.06 (95% CI; -0.11-0.01; p<0.016; I² 23.1%) compared with induction. Observational studies showed a non-significant (p=0.38) Odds Ratio (OR) of 1.37 (95% CI, 0.66-2.85; I² 81.3%) of losing histologic success during therapy de-escalation. Pooled clinical success among RCTs attested at 61% (95% CI, 51%-75%; I² 71.3%), comparable with observational studies (60% [95% CI, 42%-77%; I² 97.3%]). Biological therapy (either Dupilumab or Cendakimab at various regimens) ranked first for pooled histologic success rate among RCTs with 79% (95% CI; 71%-87%; I² 54.9%). In observational studies, PPI with histologic success of 64% (95% CI, 50%-78%; I² 88.7%) and clinical success of 79% (95% CI; 66%-93%; I² 85.2%) ranked first. Pooled rate of AEs among RCTs attested at 34% (95% CI; 22%-45%; I² 93.2%), with a pooled candidiasis infection rate of 6% (95% CI; 2%-10%; I² 61.9%), comparable with pooled AEs among observational studies (5% [95% CI, 2%-7%; I² 66.7%]). Pooled therapy discontinuation rate was 0.14 (95% CI, 0.073-0.210, I² 94.49%) in real-world data.

Conclusion

This is the first meta-analysis on efficacy and safety of long-term maintenance treatment (median 78 weeks) for EoE. All treatments showed good efficacy in maintaining long-term histological remission without clear disadvantage in de-escalating therapy during maintenance in real-word data. Biological therapies resulted the most effective in RCTs, while PPIs in observational studies. Low adverse events rates and low therapy discontinuation rates confirm long-term treatment is well tolerated.

References

1. Nistel M, Andrews R, Furuta GT, Atkins D. Elimination Diet or Swallowed Topical Steroid Treatment of Pediatric Eosinophilic Esophagitis: Five-Year Outcomes. J Allergy Clin Immunol Pract. 2023 Aug;11(8):2516-2523.e2. doi: 10.1016/j.jaip.2023.05.036. Epub 2023 May 30. PMID: 37263351; PMCID: PMC10525024.

Disclosure

ES has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapa-gos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Uni-farco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestlè, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Takeda, Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici.
Danese has served as a speaker, consultant and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Fer-ring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor.