To Treat or Not to Treat Asymptomatic Patients with Eosinophilic Esophagitis – The Debate Continues

Should individuals who become symptom-free after induction therapy for eosinophilic esophagitis (EoE) continue life-long treatment? This year’s Digestive Disease Week meeting provided an arena for a “gloves-off” debate in which experts in the treatment of EoE addressed both sides of the argument.

EoE is a chronic inflammatory disease that requires long-term management. However, the adequate maintenance strategy for patients who achieve clinical, endoscopic, and histological remission after treatment of active EoE remains a topic of debate.

“You must continue to treat or the esophagus will become concrete,” was the maxim under which Eric Low, MD, MPH, framed his argument. Low, a gastroenterology fellow at the University of California, San Diego, made a case for continuing maintenance therapy in asymptomatic patients. “EoE spontaneous resolution is uncommon, typically [reported at] about 3% in the literature,” he said. “This is a percentage that I would not gamble on, and I don’t think many of you would.”

Low cited studies that reviewed the natural history of EoE, in which clinical and endoscopic remission rates in both children and adults with EoE hovered around 3% after an average follow-up period of 3 to 7 years. Studies from the past decade also showed that disease activity recurs when treatments are stopped in approximately 80% of the cases. There is evidence that long-term therapy is necessary to maintain remission, Low said, citing results from a 48-week maintenance trial in which 75% of patients treated long-term with budesonide 1.0 mg twice daily maintained clinical and histological remission compared with only 4% of patients in the placebo group (Straumann A et al. Gastroenterology 2020;159:1672-1685.e5).

Long-term maintenance therapy has clinical as well as biological implications, as it can reduce the risk of food impaction and esophageal dilation and improve esophageal remodeling. Even in patients who are asymptomatic, symptoms may not correlate with endoscopic and histologic activity, Low cautioned. Studies have shown that physicians cannot rely on a lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE (Safroneeva E et al. Gastroenterology 2016;150:581-590.e4). “Once an effective therapy is achieved, disease remission should be maintained using the same option at the minimum effective dose or dietary restriction level,” Low concluded. Providers should continue to monitor symptoms and consider periodic endoscopy and biopsy on a case-by-case basis.

“Do benefits of long-term therapy outweigh risks?” asked Joan Chen, MD, MS, Clinical Associate Professor of Internal Medicine at the University of Michigan, in Ann Arbor, MI. Chen presented the other side of the argument, noting that the recommendation to continue therapy for EoE after remission is based on low-quality evidence. “Long-term studies evaluating the efficacy of maintenance medical and dietary therapies are listed under knowledge gaps,” Chen argued. “Meanwhile, concerns over the long-term use of medications should certainly make us think twice about recommending their indefinite use in patients. Long-term proton pump inhibitor use has been associated with a litany of conditions, including cardiovascular events, kidney dysfunction, bone issues, infectious complications, and dementia.”

Chronic use of topical corticosteroids (TCS) can also prove problematic, as these agents have been associated with oral, pharyngeal, and esophageal candidiasis and adverse effects on bone health when used long-term. Adrenal insufficiency has also been reported in children with EoE who were treated long-term with TCS, and the rates are likely higher than reported because very few gastroenterologists screen for adrenal insufficiency, the speaker said.

“We tend to recommend dietary therapy as the most natural way to treat EoE long term, but even a food elimination diet is not without risks,” Chen continued. “Growth impairment has been reported in children with food avoidance. Obesity can also occur with inappropriate substitutions. On an emotional level, diet therapy can also cause significant anxiety, stress, and can limit social interactions.”

Patients, especially younger ones, tend to have poor adherence to long-term dietary restrictions and worry about the adverse effects of pharmacotherapies. “At the end of the day, when you ask EoE patients what they care most about in terms of outcome, it’s not inflammation or fibrosis, it’s symptoms and quality of life, and that is [true] for short-term or long-term therapy,” Chen said. “If the disease is not causing symptoms, and given that EoE maintenance therapies are not yet optimized, is it still important to treat [those patients]? In this population, to choose a therapy that is not worse than the disease is very difficult.”

There is benefit in delaying the start of a life-long treatment, especially since fibrostenotic complications develop over years to decades, and may not occur in every patient with EoE. Moreover, EoE does not carry the risk of potential severe complications that are associated with Crohn’s disease, such as major bleeding, infections, malignancy.

The speakers agreed that, rather than rushing to consider lifelong therapy in every case, the optimal approach is a shared decision-making process that includes patients in the discussion. “Instead of rushing to put every EoE patient on lifelong therapy, I think we should focus our efforts on figuring out which patient should be on long-term therapy and which can be managed by watchful waiting,” Chen added.