The Food and Drug Administration (FDA) has approved Dupixent (dupilumab) for eosinophilic esophagitis (EoE) in individuals aged 12 and above, the first approved therapy for this condition.
EoE, characterized by chronic inflammation and the
presence of eosinophils in the esophagus, commonly manifests in symptoms such
as swallowing difficulties and food impaction.
Researchers reported that Dupixent, a monoclonal
antibody designed to target the inflammatory process, demonstrated
effectiveness and safety in clinical trials, marking a significant breakthrough
in EoE treatment.
In May 2022, the U.S. Food
and Drug Administration
EoE is characterized by the presence of eosinophils, a
specific type of white blood cell, in the esophageal tissue.
In adults and adolescents with EoE, common symptoms
include difficulty swallowing, eating challenges, and food getting stuck in the
esophagus.
Dupixent is a monoclonal
antibody designed to inhibit a part of the inflammatory pathway.
Dr. Brooks Cash, a professor and chief of the
division of Gastroenterology, Hepatology, and Nutrition at UTHealth Houston,
told Medical News Today that “there are multiple different types of
immune reactions that the body uses to protect itself depending on the target (for
example viruses, parasites, bacteria, allergens).”
“In the case of EoE the
type of immune response is called a type 2 immune response, which is the type
of immune response directed toward allergens,” he explained.
“Other examples of this
type of immune response include asthma, hives, allergic rhinitis, and certain
food allergies,” Cash added.
“In the case of EoE, when
the body is exposed to certain allergens, an immune cascade occurs that results
in trafficking and accumulation of specific immune cells called eosinophils in
the esophagus,” Cash pointed out.
“These cells contain
molecules such as histamine that are released when the cells are activated and
release of these molecules can cause additional inflammation, swelling, and
edema and eventually an increase in connective tissue in the wall of the
esophagus,” he added.
“This final process is
known as fibrosis. The inflammation and fibrosis that occurs with EoE can cause
symptoms of dysphagia, or food getting stuck in the esophagus,” Cash said.
This can lead to food
impaction, especially with foods such as meats which may require removal with
upper endoscopy and are considered emergencies due to the risk of esophageal
rupture. EoE can affect adults as well as children and may be accompanied by
other allergic symptoms such as hives and allergic rhinitis.-Dr. Brooks Cash
Cash noted that “while the most common cause of
dysphagia is complications from gastroesophageal reflux disease (aka GERD), EoE
is an important cause of dysphagia to consider in patients with dysphagia,
especially if they do not suffer from chronic GERD symptoms or heartburn or
regurgitation.”
The efficacy
and safety of Dupixent for EoE were evaluated in a randomized, controlled,
double-blind clinical trial, conducted at multiple centers.
In the study, researchers
conducted two separate 24-week treatment periods, Part A and Part B. In Part A,
participants were given either a placebo or a 300-milligram dose of Dupixent
weekly. In Part B, participants were given a 300-milligram dose of Dupixent
weekly, a 300-milligram does of Dupixent every two weeks, or a placebo once
weekly.
Researchers measured the
reduction in eosinophil levels in the esophagus (throat) at week 24, which is
determined by looking at tissue samples under a microscope, and the change in a
questionnaire called the Dysphagia Symptom Questionnaire (DSQ)
score from the beginning to the end of the 24 weeks.
The DSQ helps assess how
difficult it is for people to swallow, with higher scores indicating more
severe symptoms.
In Part A, 60% of the
participants who received Dupixent achieved the desired reduction in eosinophil
levels, compared to only 5% of those who got a placebo.
Participants in Part A who
received Dupixent also reported an average improvement of 22 points in their
DSQ score, while those on placebo reported a 10-point improvement.
In Part B, target
eosinophil reduction was achieved in 59% of participants on weekly Dupixent and
60% of participants on Dupixent every two weeks, compared to just 6% of those
on placebo.
Participants in Part B who
received Dupixent weekly reported an average improvement of 24 points in their
DSQ score, while those receiving it every two seeks and those on placebo
reported a 14-point improvement.
Overall, researchers said,
these results suggest that Dupixent can be effective in reducing symptoms and
improving swallowing difficulties in patients with EoE.
Challenges for
healthcare providers when treating EoE
Cash
highlighted that the main challenge when treating EoE is raising awareness,
gaining access to diagnostic tests and finding effective therapies for EoE.
Diagnosis requires upper
endoscopy and biopsies. Initial treatments include food elimination diets, acid
suppression meds and swallowed steroids, although none are FDA-approved and not
universally effective.
Dupixent is therefore a
promising option, but its role, cost, and insurance coverage are still
uncertain, which can be a limitation, especially for uninsured people.
Dr. Zeeshan Afzal, a health content advisor at
Welzo who was not involved in the research, told Medical News Today that
“diagnosing EoE can be challenging as its symptoms can overlap with other
esophageal disorders. It often requires multiple tests, including endoscopy
with biopsy, to confirm the diagnosis.”
“Managing EoE typically
involves dietary modifications and medication to control symptoms and
inflammation,” Afzal explained.
“Before the approval of
Dupixent, there were limited treatment options for EoE. Patients might have had
to rely on corticosteroids or dietary restrictions, which may not provide
long-term relief,” he added.
This new
medication is a great advance in the care of patients with EoE and it’s
exciting to see medications directed toward the pathophysiologic basis for a
condition come to market based on good clinical research showing clinical
improvement in symptoms as well as the inflammatory changes in the esophagus.-Dr.
Brooks Cash
However, “we still need to determine where this
medication fits, right now it is generally used in patients who did not have a
complete or durable response to other therapies,” Cash pointed out.
“We also need to determine
how long patients should be treated with this medication and when and how we
should consider decreasing or stopping this medication in patients who respond,”
he added.
Afzal noted that the new
medication will allow people with EoE to experience symptom relief, “making it
easier to eat and swallow.”
This can lead to an
improved quality of life for those living with the condition.
However, “access to
Dupixent may be a concern for some patients due to its cost, but the approval
may prompt discussions around insurance coverage and affordability.”
In conclusion, Afzal said
that “healthcare providers will need to educate patients about the benefits,
risks and proper use of Dupixent, as well as monitor them for potential side
effects.”
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