From the Journals

Solid therapeutic hierarchy for eosinophilic esophagitis still unclear



Most available drugs for eosinophilic esophagitis (EoE) demonstrate greater efficacy than placebo, but data are too heterogenous to determine a reliable therapeutic hierarchy, shows a meta-analysis published in Gut.

Among agents available outside of clinical trials, the corticosteroid budesonide had the broadest evidence base for efficacy, while EoE-specific topical steroids typically outperformed adapted asthma formulations, wrote authors who were led by Edoardo Savarino, MD, PhD, of the department of surgery, oncology and gastroenterology at the University of Padua, Italy.

The AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters published clinical practice guidelines for eosinophilic esophagitis in 2020. The group issued 12 recommendations with only 1, the topical use of glucocorticosteroids over no treatment, being a “strong recommendation.” Both the AGA/JTF guidelines and guidelines issued May 23, 2022 , by the British Society of Gastroenterology and British Society of Pediatric Gastroenterology, Hepatology and Nutrition, recommend the use of proton pump inhibitors (PPIs) and topical glucocorticosteroids in certain cases. Neither set of guidelines addresses the use of dupilumab, which was approved in the United States on May 20, 2022, for adults and pediatric patients 12 years and older, and in January of this year by the European Commission for the same condition.

The current study is a meta-analysis that compared data from 1,813 subjects with active EoE who participated in 15 randomized controlled trials. All drugs tested in EoE were included, each compared against one another and placebo. Efficacy was characterized by induction of histological remission, symptomatic response, and endoscopic response. Topical steroids formulated for EoE were evaluated separately from off-label topical steroids for asthma.

This approach yielded a litany of efficacy findings.

Of note, budesonide orally disintegrating tablets ranked first for histological remission defined by no more than 15 eosinophils/high-powered field (HPF), while lirentelimab was best at achieving the lesser used histological remission threshold of 6 eosinophils/HPF. On the same topic of inducing histological remission, EoE-specific steroid formulations, along with dupilumab, showed greater efficacy than off-label topical steroids.

The investigators also highlighted that budesonide suspension and tablets were significantly better than placebo in terms of failure to achieve symptom improvement and failure to achieve endoscopic improvement according to EoE Endoscopic Reference Score.

Collectively, the analysis showed that most available drugs are significantly more effective than placebo for treating EoE, yet differences in study designs and population characteristics stand in the way of a clear road map to treatment selection.

“In summary, this network meta-analysis supports the efficacy of most available drugs over placebo for the treatment of EoE. All EoE-specific steroid formulations and dupilumab ranked higher than off-label topical steroids for the induction of histological remission in active EoE, and most EoE-specific steroid formulations and dupilumab ranked higher than esomeprazole, despite having comparable safety,” the authors wrote. “These results prompt further research to better understand the mechanisms underlying symptom generation in EoE, to target their cause and achieve better outcomes.”

Joy Weiling Chang, MD, Michigan Medicine Michigan Medicine

Dr. Joy Weiling Chang

Joy Weiling Chang, MD, a gastroenterologist and assistant professor of medicine at the University of Michigan Medicine, Ann Arbor, offered a similar perspective.

“This study tells us that we still need more data to establish this clear hierarchy of medication treatments,” she said in an interview.

Still, Dr. Chang added, these findings are applicable to clinical practice. Because most EoE drugs demonstrate significant efficacy over placebo, and the best starting option remains unclear, then shared decision-making should focus on patient preferences, she said in an interview.

“As clinicians, we need to be working with our patients to consider which strategies work best for their lifestyles,” Dr. Chang said.

The investigators disclosed relationships with AbbVie, Biogen, Sanofi, and others. Dr. Chang reported consulting fees for Sanofi-Regeneron, the maker of Dupixent.

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