The Role of Medications in the Management of Eosinophilic Esophagitis (EoE): A Review of Current Treatment Options

Dr. Mary Sherlock MB BCh BAO, PhD, FRCPC, Dr. Vishal Avinashi MD, MPH, FRCPC, Dr. Jennifer Griffin MD, BSc Med, FRCPC

Written by: Dr. Mary Sherlock MB BCh BAO, PhD, FRCPC, Dr. Vishal Avinashi MD, MPH, FRCPC, Dr. Jennifer Griffin MD, BSc Med, FRCPC

Updated: May 21st, 2024

Several medications that have been found to be effective in treating patients with eosinophilic esophagitis (EoE). Treatments are aimed at reducing esophageal inflammation, hoping to reduce the risk of fibrosis (scar tissue) and strictures (narrowing) forming in the esophagus.

Patients and their families should discuss the medication options with their health care professional to help decide which medication is best for them. The process may require some trial and error and evaluation including repeat endoscopies. Dietary therapies are also effective in treating EoE. This article will only review medical therapies. It is important to note that several of these medications are used ‘off-label’. Also, while these therapies help control the condition, if stopped, the inflammation will come back.

This article was written by Dr. Mary Sherlock MB BCh BAO, PhD, FRCPC, Dr. Vishal Avinashi MD, MPH, FRCPC, Dr. Jennifer Griffin MD, BSc Med, FRCPC.

Proton Pump Inhibitor (PPI) Therapy

For many patients, proton pump inhibitor (PPI) therapy will be the first medication prescribed for the treatment of their eosinophilic esophagitis (EoE). These medications, which are very effective acid blockers, have been used for decades to treat gastro-esophageal reflux disease. While historically, these prescription antacids were used to distinguish reflux disease from EoE, as time went on, it was discovered that these medications work in a way that is beyond blocking acid and may block the recruitment of eosinophils. In a proportion (as many as half) of patients with eosinophilic esophagitis, these medications improve the eosinophilic inflammation in the esophagus. Patients tend to have a better response with higher doses and often the medications will be prescribed to be taken twice per day.

Several different brands and formulations are available including tablets, capsules, dissolving tablets, powdered sachets, or even compounded liquids. The formulation options should be discussed with your doctor as some patients with EoE have difficulty swallowing pills. In addition, there is a large variation in cost.  It is recommended to take the medication about 30 minutes prior to eating. Some patients will be able to reduce the medication down to once per day and may also still have benefit from lower doses; however, your doctor will aim to assess how well the medication is working with an endoscopy and biopsies prior to making changes to the dose.

Mechanism of action of PPI Therapy

While these medications are very effective at supressing stomach (gastric) acid production, this is not thought to be their main mode of action in EoE. In a normal esophagus we expect to find no eosinophils. PPIs appear to work in EoE by directly blocking or interacting with proteins that are responsible for attracting eosinophils into the tissue.

Potential side-effects of PPI Therapy

Long-term, there is some research (mostly at a population health level) suggesting that they may have a negative impact on bone density, although this has not been consistently demonstrated. For the most part, these medications are very well tolerated, easy to take, and have minimal side-effects.

Availability and Price of PPI Therapy

These are available in almost any pharmacy, and if the dose comes in a standard pill form, they are not expensive.

Swallowed Topical Corticosteroids

Swallowed topical corticosteroids act on the surface of the esophageal lining and are very effective at settling down the inflammation seen in EoE. These medications are similar or even borrowed from asthma treatment, but they are administered differently when treating EoE with the idea of delivering the medication directly to the esophagus. The two main types of corticosteroids used for EoE treatment are fluticasone and budesonide. It is important to note that these are not the same as systemic steroids and as a result have a much safer side effect profile.

Fluticasone is administered via a metered dose inhaler (MDI/asthma puffer), but instead if inhaling the medication, as in asthma treatment, the medication is sprayed in the mouth and swallowed. The standard puffer is orange and should not be used with a spacer or aerochamber.  A standard adult dose is two puffs swallowed twice per day. However different puffers contain differing amounts of fluticasone in each puff and your doctor will decide which dose is best for you. Young children will require a lower dose. Each puff should be swallowed separately. It is important not to eat or drink for at least 30 minutes after the dose. This will maximise the time that the medication is in contact with the esophageal lining. Rinsing out the mouth 30 minutes after the dose will help to reduce the risk of oral thrush (a Candida/yeast infection). Other versions of fluticasone are available such as diskus but these are not appropriate for delivering the medication to the esophagus. With the Metered Dose Inhaler, it is important to count the number of doses or puffs administered as even after the active medication is finished (typically 120 doses per canister), it will seem like product is coming out, but the active medication is no longer being delivered.

Budesonide is administered by opening a budesonide nebule (typically used in an asthma nebuliser) and mixing the liquid content with sucralose (an artificial sweetener) to make a thicker liquid slurry which is then swallowed. Some patients will mix the budesonide with honey, maple syrup or applesauce as they have a thick consistency.  Remember, honey cannot be used in children under 1 year of age because of the risk of Botulism. A third version may be available if a compounding pharmacy mixes budesonide with a commercial thickener to make a viscous liquid. This often has to be kept in the fridge and has a shorter shelf life. 

A dissolvable tablet form of budesonide called Jorveza (R) is available and is the first approved therapy by Health Canada for patients with EoE who are over 18 years of age.  This is a tablet which does not need to be mixed with any liquid. It is placed on the tongue and dissolves itself when in contact with saliva. When swallowed, it coats the lining of the esophagus. 

For all swallowed topical corticosteroids, it is important not to eat or drink for at least 30 minutes after the dose. This will maximise the time that the medication is in contact with the esophageal lining. Rinsing out the mouth 30 minutes after the dose will help to reduce the risk of oral thrush (a Candida/yeast infection).

Mechanism of action of Topical Corticosteroids

Swallowed topical steroids work like other steroids, in that their main action is to improve inflammation. However, the steroids used in EoE act locally on the surface lining of the esophagus rather than having an effect throughout the body.

Potential side-effects of Topical Corticosteroids

Swallowed topical corticosteroids are rapidly broken down by the liver and so they do not typically cause the side effects that are seen with other steroids like prednisone, which are considered systemic, as they have effects around the body.

The most common side-effect is oral candidiasis (yeast infection in the mouth), which can be treated with an oral anti-fungal medication. Some studies have shown that early-morning cortisol level is lower in patients who are taking long-term swallowed steroid therapy, however, for the majority of patients, this does not appear to have any significant clinical consequence. If your doctor is concerned about a low cortisol level, they may consider an ACTH stimulation test to check the function of your adrenal glands. For children, your doctor will monitor your child’s growth while on steroid therapy, however the studies in the medical literature do not seem to show a negative impact on long-term growth with these medications in EoE patients. However, patients may be on additional forms of steroid therapy to treat other allergic conditions (such as skin, nose, lungs), and monitoring for potential side-effects of this treatment is important.

Availability and Price: Fluticasone is available in nearly all pharmacies as it is widely used.  Budesonide is less available and has been subject to supply issues at different times.  Jorveza (R) is stocked by the pharmacies and is certainly available but is slightly more expensive than other swallowed topical corticosteroids and more often covered by third party insurance compared to provincial formulary plans.

Biologic Therapy

Dupilumab is the newest medication which has been approved for treatment of EoE in Canada in 2023, for patients over the age of 12 years and who weigh more than 40 kg. The standard dose is 300 mg administered as an injection just under the skin every week.  In the United States, it is now approved for infants as young as 1 year who also weigh at least 15 kg. Dupilumab has been used for several years in the management of other conditions such as asthma and eczema, though the dosing may be different to the doses used in EoE.

Mechanism of action of Biologic Therapy

It works by interacting with proteins (called interleukin 4 and interleukin 13) that are heavily involved in the EoE inflammatory pathway, and as a result they reduce the eosinophilic inflammation in the esophagus.

It is available as a pre-filled syringe or as a pen.

Potential side-effects of Biologic Therapy

The medication is well tolerated. The most common side-effect is pain or discomfort at the injection site. Other described side-effects including irritation of the eye (conjunctivitis) and eye lid, upper respiratory tract infection and inflammation. Other rarer side-effects are described in the product monograph.

Availability and Price of Biologic Therapy

The medication is very expensive and in Canada, at present, is covered by some private insurance but not the provincial formularies. Certain provinces, may have eligibility / coverage for this medication for other indications such as severe eczema or asthma and will benefit the EoE if they co-exist.

Maintenance Therapy

It is also important to remember that these medications are not effective as instant relief for symptoms and need to be used for many weeks before benefit can be seen, hence why consistent use of the medication is necessary. Like other allergic disorders, the inflammation seen in EoE typically returns if treatment is stopped. Because of this, most gastroenterologists will recommend that the patient remains on treatment. Your gastroenterologist will likely try to reduce the dose of your medication to the lowest effective dose to help minimise potential adverse effects of long-term therapy and reduce unnecessary medication use. However, it is important to ensure that the new dose is still effective at keeping the inflammation under control. Symptoms alone are not sufficient to monitor the inflammation and the only way to monitor the inflammation in EoE is with an endoscopy and biopsies.

Footnote regarding side-effects:

Most common side-effects of the medications above are discussed in this article. Discussion of rarer events and other potential side-effects can be discussed with your provider and will be listed on the product monograph (patient information leaflet/documentation).

Useful Readings:

Lucendo AJ, Arias A, Molina-Infante J. Efficacy of Proton Pump Inhibitor Drugs for Inducing Clinical and Histologic Remission in Patients with Symptomatic Esophageal Eosinophilia: A systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2016;14(1):13-22 e1.

Dellon ES, Rothenberg ME, Collins MH, Hirano I, Chehade M, Bredenoord AJ et al. Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis. N Engl J Med. 2022;387(25):2317-30

Dellon ES, Woosley JT, Arrington A, McGee SJ, Covington J, Moist SE, et al. Efficacy of Budesonide vs Fluticasone for Initial Treatment of Eosinophilic Esophagitis in a Randomized Controlled Trial. Gastroenterology. 2019;157(1):65-73 e5.

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