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Abstract

Background:

Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and -13 signaling, is approved for the treatment of eosinophilic esophagitis (EoE) based on phase III clinical trials. However, real-world data on dupilumab use for EoE are lacking.

Objectives:

To assess the characteristics, treatment patterns, and outcomes among patients with EoE aged 12 years or older who receive treatment with dupilumab for EoE as prescribed under the US prescribing information.

Design:

This study protocol describes a phase IV, prospective, observational, multicenter patient registry, EDESIA, which will enroll approximately 300 patients aged 12 years or older who initiate dupilumab treatment as part of routine care across approximately 50 sites in the USA.

Methods and analysis:

Baseline data collection will include demographics, disease characteristics, medical history, and prior/concomitant therapies. Data will be collected at baseline (day 1 of treatment) and at follow-up visits through 36 months. Key primary outcomes assessed will include details of food elimination diet, history of food impaction and esophageal dilation, histologic and endoscopic findings, and patient-reported outcomes. Adverse events will be monitored throughout the study.

Ethics:

The EDESIA registry will be conducted in accordance with the Declaration of Helsinki, the International Council for Harmonization guidelines for Good Clinical Practice, and applicable regulatory requirements. The local institutional review board at each study center will approve the study. Written informed consent will be obtained from all patients and/or a parent/legal guardian.

Discussion:

EDESIA will address the safety and tolerability of long-term weekly dupilumab treatment in patients with EoE, and inform future treatment guidelines.

Trial registration:

A US registry of EoE adolescent and adult patients treated with DUPIXENT® as standard of care (EDESIA), NCT06693531 (https://www.clinicaltrials.gov/study/NCT06693531).

Plain language summary

A study protocol of the baseline characteristics, treatment patterns, and long-term outcomes in patients with eosinophilic esophagitis initiating dupilumab in routine clinical practice

Eosinophilic esophagitis (EoE) is a long-term inflammatory disease of the esophagus (the tube that carries food and liquids from your mouth to your stomach). EoE is becoming more common, affecting more people worldwide. Dupilumab, a type of medication called a biologic, was the first of its kind to be approved for the treatment of EoE. Based on results from two clinical trials, dupilumab is now approved in the USA and Europe for people with EoE aged 1 year or older, weighing at least 15 kg. Dupilumab has been shown to improve signs and symptoms of EoE in clinical trial settings. “Real-world” studies show how effective and safe a treatment is for patients in real-life situations outside of controlled clinical trials. The EDESIA patient registry will be the first large-scale, US-based, real-world study for patients with EoE. EDESIA will aim to recruit approximately 300 patients with EoE, across 50 clinics in the USA. Patients with EoE, aged 12 years or older, who are being treated with dupilumab will be invited to participate in the study. After starting dupilumab, patients will attend a check-in at month 3, month 6, and every 6 months thereafter, up to 36 months (3 years). Questionnaires completed by the patient and clinician-collected assessments will be carried out at each check-in. Procedures such as an endoscopy (a camera inserted into the esophagus) will be conducted, if required, as part of the patient’s standard care. Data collected throughout the study will be analyzed to assess the patient characteristics, treatment patterns, side effects, and outcomes. EDESIA will provide the largest US-specific, real-word data for the treatment of EoE with dupilumab to date. The data will build upon existing knowledge of the safety and effectiveness of dupilumab by providing new data on how dupilumab is prescribed and its effectiveness for the treatment of EoE in real-life situations.

Keywords

dupilumab eosinophilic esophagitis phase IV real-world data registry

Introduction

Eosinophilic esophagitis (EoE) is a chronic, progressive disease of the esophagus, characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation driven by type 2 inflammation.^1
–5 The clinical manifestations of EoE, including dysphagia, vomiting, abdominal pain, and food impaction, can significantly impact the quality of life of patients and their caregivers.^4,6
–8 Consistent with the increasing incidence and prevalence of EoE, the condition is now frequently encountered in clinical practice.^{1
–3,9
–11} Clinical guidelines for the treatment of EoE recommend empiric food elimination diet, pharmacologic and mechanical interventions, including proton pump inhibitors (PPIs), swallowed topical corticosteroids (STCs), biologics, and esophageal dilation.^2,12

Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and -13, is approved for the treatment of eight diseases marked by type 2 inflammation.^13
–15 In the EU and USA, dupilumab is approved for the treatment of patients with EoE aged 1 year and older, weighing at least 15 kg, based on results from two phase III studies: LIBERTY EoE TREET and EoE KIDS.^13,14 These studies assessed the safety and efficacy of dupilumab in patients aged 12 years or older and 1–11 years, respectively, for up to 52 weeks.^16,17 The safety profile for dupilumab in these studies was consistent with its known safety profile in other conditions.^16,17 Based on results from LIBERTY EoE TREET, which demonstrated that weekly dupilumab in adolescent and adult patients significantly improved histologic, symptomatic, and endoscopic outcomes versus placebo after 24 weeks of treatment, dupilumab was the first biologic to be approved for EoE. Dupilumab’s place in the EoE treatment algorithm is still being established²; however, current guidelines recommend that dupilumab should be used in patients with EoE who are non-responsive to PPI, STC, or food elimination therapy and/or considered in patients with severe atopic comorbidities.^2,18 Guidelines also suggest that dupilumab can be used as step-up therapy in difficult-to-treat patients, patients with severe disease, or those refractory or intolerant to current therapy.^2,18 Despite the evidence of effective EoE treatment with dupilumab in clinical trials, there are limited data assessing the use of dupilumab in patients with EoE in a real-world setting.

Existing studies that assess the treatment of EoE with dupilumab in real-world practice are limited by their population size, duration, and/or retrospective design.^19
–22 The phase IV, US-based patient registry EDESIA (NCT06693531) will address these limitations by providing long-term, prospective data on the use of dupilumab for the treatment of EoE in a large cohort in real-world clinical practice. Consistent with the European Medicines Agency guidelines on registry-based studies, specific research questions to assess patient characteristics, treatment patterns, outcomes, and safety using data collected during the EDESIA patient registry will be specified in forthcoming study protocols and/or statistical analysis plans.²³ Here we present the study design of the EDESIA patient registry.

Methods and analysis

Study design and patients

EDESIA is a phase IV, prospective, observational, multicenter patient registry that will be conducted in the USA. The primary objective is to assess the characteristics, treatment patterns, and outcomes among patients with EoE aged 12 years or older who receive treatment with dupilumab for EoE as part of their routine clinical care and prescribed under the US prescribing information.¹² The secondary objective is to generate long-term, real-world safety data of dupilumab in this patient population. The study will consist of a screening period of up to 12 weeks, followed by a 3-year assessment period (Figure 1). A protocol amendment is currently in progress for the inclusion of patients with EoE aged 1–11 years.

Figure 1.

EDESIA study design.

The target enrollment is approximately 300 patients with EoE. Enrollment will take place at approximately 50 participating sites in the USA, the selection of which will attempt to capture a geographically broad and diverse sample of patients, including community and specialist practice settings, as well as rural, urban, and military locations. Full inclusion and exclusion criteria are shown in Table 1.

Table 1.

Inclusion and exclusion criteria.

Inclusion criteria	Exclusion criteria
• Patients aged ⩾12 years at the baseline assessment • Initiating dupilumab treatment for EoE according to the US FDA-approved prescribing information^a • Willing and able to comply with the required registry procedures and assessments • Able to understand and complete registry-related questionnaires • Provide written, informed consent	• Contraindication to dupilumab per the US FDA-approved prescribing information • Treatment with dupilumab within 6 months prior to the screening assessment • Any condition that, in the opinion of the investigator, may interfere with the patient’s ability to participate in the registry • Participation in an ongoing interventional study within 6 months of the baseline assessment • Once enrolled in the registry, participation is allowed in other ongoing studies (at the discretion of the registry investigator)

Inclusion criteria

Exclusion criteria

• Patients aged ⩾12 years at the baseline assessment
• Initiating dupilumab treatment for EoE according to the US FDA-approved prescribing information^a
• Willing and able to comply with the required registry procedures and assessments
• Able to understand and complete registry-related questionnaires
• Provide written, informed consent

• Contraindication to dupilumab per the US FDA-approved prescribing information
• Treatment with dupilumab within 6 months prior to the screening assessment
• Any condition that, in the opinion of the investigator, may interfere with the patient’s ability to participate in the registry
• Participation in an ongoing interventional study within 6 months of the baseline assessment
• Once enrolled in the registry, participation is allowed in other ongoing studies (at the discretion of the registry investigator)

For the treatment of adult and pediatric patients aged ⩾1 year, weighing ⩾15 kg, with EoE.

EoE, eosinophilic esophagitis; FDA, Food and Drug Administration.

Treatment

Dupilumab will be prescribed by each local medical provider per their usual clinical practice. Patients can be prescribed other medications and treatments for EoE, and for any comorbidities, as per local standards of care. There are no protocol requirements regarding treatment discontinuation; if treatment with dupilumab is discontinued or interrupted, patients will be encouraged to remain in the registry and continue assessments. Patients who discontinue from the registry before the final assessment at month 36 will be asked to complete an early termination assessment.

Assessments and analysis

A full schedule of assessments is shown in Table 2. Screening will include collection of informed consent and assessment of eligibility based on the inclusion/exclusion criteria. Patients who do not initiate treatment within 12 weeks of screening will be considered screening failures. Data collected at baseline (day 1 of dupilumab treatment) will include standard demographic characteristics; EoE characteristics (including endoscopic/histologic findings, history of esophageal dilation, food impaction, and dietary eliminations for any medical reasons including EoE); full medical history (including type 2 inflammatory comorbidities and relevant family history); EoE medication history during the previous year; non-EoE medication history during the previous 3 months; type of health insurance coverage; and prior dupilumab exposure history. Screening and baseline assessments may be combined, provided that all required procedures and assessments are completed before dupilumab treatment is initiated.

Table 2.

Schedule of events.

Registry period	Screening^a	BL and dosing^a	Assessment timepoints (in person or remote)
Registry day (visit window, days)	Day -84 to day 1	BL day 1	M3 (±4 W)	M6 (±4 W)	M12 (±8 W)	M18 (±8 W)	M24 (±8 W)	M30 (±8 W)	M36 (±8 W)	Unscheduled assessment	Early termination assessment
Check-in visit number	V1	V2	V3	V4	V5	V6	V7	V8	V9
Screening/baseline
Inclusion/exclusion criteria	X	X
Informed consent	X
Physician information		X
Insurance confirmation		X
Socio-demographics		X
Family history		X
General medical history	X	X
Endoscopic/histologic history	X	X
Type 2 inflammatory comorbidity medical history		X
Dupilumab initiation/injection		X
Investigator-collected assessments
Dietary elimination for EoE		X	X	X	X	X	X	X	X	X	X
EGD			X	X	X	X	X	X	X	X	X
Histology			X	X	X	X	X	X	X	X	X
Impaction/dilation history		X	X	X	X	X	X	X	X	X	X
Non-EoE medications	X	X	X	X	X	X	X	X	X	X	X
EoE medications	X	X	X	X	X	X	X	X	X	X	X
Dupilumab treatment			X	X	X	X	X	X	X	X	X
Adverse events	X	X	X	X	X	X	X	X	X	X	X
Patient-reported assessments
EoE-IQ^b,24		X	X	X	X	X	X	X	X		X
EoE-SQ^b,25		X	X	X	X	X	X	X	X		X
EEsAI^b,26		X	X	X	X	X	X	X	X		X
EoE Dysphagia Severity Likert Scale^b,27		X	X	X	X	X	X	X	X		X
PGIS^b,28		X	X	X	X	X	X	X	X		X
PGIC^b,28			X	X	X	X	X	X	X		X

Screening and baseline assessments may be combined, provided that all required procedures and assessments are completed before dupilumab treatment is initiated/injected. When screening and baseline assessments are combined, procedures and assessments that are common to both assessments need to be performed only once and recorded for the baseline assessment.

Patient-reported outcomes will be completed by the patient via a mobile application on a compatible personal device or device provided as part of the study during in-person and remote check-ins.

BL, baseline; EEsAI, EoE Symptom Activity Index; EGD, esophagogastroduodenoscopy; EoE, eosinophilic esophagitis; EoE-IQ, EoE-Impact Questionnaire; EoE-SQ, EoE-Symptom Questionnaire; M, month; PGIC, Patient Global Impression of Change; PGIS, Patient Global Impression of Severity; V, visit; W, weeks.

After initiating treatment, patients will undergo periodic assessments (“check-ins”) at month 3 (±4 weeks), month 6 (±4 weeks), and every 6 months (±8 weeks) thereafter until month 36 (Figure 1). Since this is a registry, scheduled visits are not mandated, but sites are encouraged to check in with registry participants according to the schedule for registry data collection. These check-ins can take place either as part of an in-person clinic assessment or remotely (e.g., via telephone). Any other EoE-related visits (defined at the discretion of the study investigator) between these intervals will also be recorded at the next scheduled check-in.

At each check-in, a specifically developed case report form will assess study outcomes, including details of dietary elimination, changes in dupilumab dosing or frequency, and all concomitant treatments for EoE. The case report form will also assess if there has been any food impaction and/or any interval endoscopy since the previous check-in. Follow-up timeframes are not intended to dictate care, such as endoscopy frequency; rather, they were created to provide a framework for the study sites to collect data in a systematic fashion and ensure patient-reported outcome collections from patients. Recent guidelines recommend endoscopy to assess treatment response 8–12 weeks after initiating a new therapy for EoE.² Based on clinical trial findings, appropriate endoscopy timing for dupilumab may range between 12 and 24 weeks after initiation.^16,17 If an endoscopy is performed at the discretion of the treating healthcare professional, results will be collected and the presence of structuring and/or fibrosis will be recorded, with or without formal EoE Endoscopic Reference Score and Index of Severity for Eosinophilic Esophagitis scores. If histologic assessment is available, the number of eosinophils per high-power field (eos/hpf) in the proximal, mid, and distal esophagus will be recorded via local reads. If the exact eosinophil counts or biopsy location(s) in the esophagus are unavailable or incomplete, the highest eosinophil count will be documented as “yes” or “no” using a threshold of ⩾15 eos/hpf. To further assess inflammation and fibrosis via histology, the presence of eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis will be recorded, if available. Patients will also be asked to complete several patient-reported outcomes electronically at baseline and at each check-in timeframe, including outcomes assessing the impact of EoE on quality of life (EoE-Impact Questionnaire),²⁴ the frequency and severity of EoE symptoms (EoE-Symptom Questionnaire,²⁵ EoE Symptom Activity Index,²⁶ and EoE Dysphagia Severity Likert Scale),²⁷ and the overall status (Patient Global Impression of Severity) and change in their condition (Patient Global Impression of Change).²⁸ Patient-reported outcomes will be completed by the patient via a mobile application on a compatible personal device or device provided as part of the study during in-person and remote check-ins. Further details of investigator and patient assessments are shown in Table 3.

Table 3.

Study outcomes.

Assessment	Description
Investigator-collected assessments
Dietary elimination for EoE	At baseline, full details of food avoidance (including reason) and any prescribed dietary elimination will be recorded, including which foods have been eliminated (dairy, wheat, eggs, soy, peanut/tree nut, or finned fish/shellfish). Use of enteral tube feeding and/or elemental diet will also be documented. During the registry, patients will be asked at each check-in whether any foods have been introduced since the last assessment and if an endoscopy was conducted to document the response.
EGD	If EGD is performed, EREFS^29,30 will be documented. iSEE score³¹ will also be documented if available.
Histology	If endoscopy is performed and histology is available (per standard of care at each center), eos/hpf in proximal/mid/distal esophagus will be recorded. If exact eosinophil counts or location(s) biopsied in the esophagus are not available or incomplete, ⩾15 eos/hpf or highest eos/hpf recorded will be documented as “yes” or “no.” Eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis will be recorded, if available.
History of esophageal food impaction and dilation	If performed as part of standard of care, esophageal food impaction and/or dilation history in the previous year (including ER, urgent care, and hospitalization visits) will be recorded. If the patient was dilated, the dilation size achieved from pre-dilation baseline will be recorded. Images and any occurrence of perforation will be recorded.
Non-EoE medications	All non-EoE medications received within 3 months of baseline and at any time during the study will be recorded.
EoE medications	All EoE medications received within 1 year of baseline and at any time during the study will be recorded.
Dupilumab treatment	Dupilumab dosing regimen, as well as any change in dupilumab treatment and the reason for change, will be recorded at baseline and throughout the study.
Patient-reported outcomes
EoE-IQ²⁴	A disease-specific measure of health-related quality of life in patients with EoE developed by the sponsor. It measures the impact of EoE on emotional, social, work/school, and sleep aspects of a patient’s quality of life.
EoE-SQ²⁵	A questionnaire measuring the frequency and severity of symptoms other than dysphagia and pain with swallowing that was developed by the sponsor. It assesses chest pain, stomach pain, burning feeling in chest, food or liquid coming back up into throat, and vomiting during the past 7 days.
EEsAI²⁶	A multimodular index in development at University Hospital Inselspital (Berne, Switzerland), part of the international EEsAI study group. The questionnaire used in this registry will assess the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (i.e., heartburn, acid regurgitation, and chest pain).
EoE Dysphagia Severity Likert Scale²⁷	Single-item outcome that assesses the severity of dysphagia over the past 30 days.
PGIS²⁸	Single-item outcome that assesses the patient’s impression of the overall severity of their EoE during the past week.
PGIC²⁸	Single-item outcome that assesses the patient’s impression of the overall change (improvement or worsening) in their EoE during the past week.

EEsAI, EoE Symptom Activity Index; EGD, esophagogastroduodenoscopy; EoE, eosinophilic esophagitis; EoE-IQ, EoE-Impact Questionnaire; EoE-SQ, EoE-Symptom Questionnaire; eos/hpf, eosinophils per high-power field; ER, emergency room; EREFS, EoE Endoscopic Reference Score; iSEE, Index of Severity for Eosinophilic Esophagitis; PGIC, Patient Global Impression of Change; PGIS, Patient Global Impression of Severity.

As per a preliminary analytical plan, the primary objective of EDESIA will be explored through descriptive summaries of patient and disease characteristics, type 2 atopic comorbidities, prior and concomitant treatments for EoE, food impactions and dilations, dupilumab dosing and frequency, EoE symptoms, endoscopic and histologic features, diet, and patient-reported outcomes. The secondary objective of EDESIA will be explored through a descriptive summary of adverse events (AEs) reported in the study.

In line with internal processes and procedures, and applicable regulatory requirements, safety will be reviewed internally throughout the registry. AEs, including those attributed to dupilumab or concomitant treatments/procedures, will be collected. AEs and medical history will be coded using the Medical Dictionary for Regulatory Activities. Each AE will be evaluated by the study site investigator as mild, moderate, or severe, and as treatment-related or non-treatment-related.

The number of participants enrolled in the registry, data quality, and high-level patient characteristics will be assessed throughout. Research questions concerning patient characteristics, treatment patterns, outcomes, and safety using registry data will be specified in forthcoming registry-based studies.

Statistics

As this is a registry, no formal statistical power or sample size calculation is needed. The sample size of approximately 300 patients was therefore chosen empirically, based on expert opinion on the number needed to generate impactful data, previous experience with non-interventional studies, the operational capabilities of enrollment within the target window, and the typical range of other EoE registries. Due to operational and budgetary constraints and limitations, the study sample size is not large enough to power sensitivity or subgroup analyses. For binary outcomes, using the normal approximation, a sample size of 300 patients will yield a 95% confidence interval (CI) width of 0.113, corresponding to a 95% CI of (0.44, 0.56) for the estimated proportion. For continuous outcomes with mean (μ) and standard deviation (σ), a sample size of 300 will produce a 95% CI width of 0.226 times σ, corresponding to a 95% CI of (μ – 0.113 σ, μ + 0.113 σ).

Continuous variables will be summarized using descriptive statistics (number of patients, mean, median, standard deviation, minimum, and maximum) or their respective geometric alternatives when appropriate. Summaries for categorical (discrete or dichotomous) variables will include the number and/or percentage of participants in a particular category. The percentage will be suppressed when the count is zero to draw attention to the non-zero counts. A row labeled “Missing” will be included in count tabulations, where specified on the shells, to account for dropouts and missing values. Population counts (either number of patients or number of timepoints at the assessment) will be used as the denominator in the calculation of percentages unless otherwise specified. Statistical Analysis Systems (v9.4; SAS Institute Inc., Cary, NC, USA) will be used for data analysis.

Handling of missing or incomplete data

As EDESIA is an observational, real-world study, no imputation will be performed for patients who discontinue the study. These patients will be excluded from all analyses following their last completed visit, and the number of patients with available data at each visit will be reported.

Standardized imputation rules will be applied for missing or partial start and stop dates for medications (prior, concomitant, and post-treatment) and AEs. For medication start dates, missing day components will be imputed as the first day of the month, missing day and month components as January 1, and completely missing dates will not be imputed but will be treated as prior to the first dose of the study drug. If medication end dates are on or after the first study drug dose date and the start year and month match the first study drug dose date, the start date will be imputed as the first study drug dose date. Missing medication stop dates (day and/or month) will be imputed as the earliest of month-end, study completion, study discontinuation, or death; completely missing stop dates will be documented as ongoing. Comparable imputation rules will be applied to AE start and stop dates, with the additional criterion that AEs with missing start dates but end dates on or after the first dose will be classified as treatment-emergent AEs. Missing AE severity or study drug relationship assessments will not be imputed and will be queried for clarification.

Ethics and dissemination

This study will be conducted in accordance with the Declaration of Helsinki, the International Council for Harmonization guidelines for Good Clinical Practice, and any applicable regulatory requirements. The protocol and other relevant documents will be submitted for institutional review board review at each study site and must be approved before the study is initiated. The investigator or designee (if acceptable by local regulations) will obtain written informed consent from each patient (or assent with consent from the patient’s parent or legal guardian, per local requirements) before their participation in the registry. The local institutional review board or ethics committee at each study center will oversee trial conduct and documentation. Amendments to the protocol or informed consent form will require approval by the institutional review board, and if required by local legislation, regulatory authority approval will also be sought. Patients who reach the local age of majority during the registry will be reconsented at the next registry visit. Results will be published on public clinical trial registries according to applicable local guidelines and regulations. The results will also be disseminated at scientific congresses and in peer-reviewed journal publications.

Data obtained during the registry will be recorded on electronic Case Report Forms by trained site personnel, and the investigator will take appropriate measures to ensure that the anonymity of each patient is maintained. Each patient will be assigned a unique identifier by the study sponsor. Any patient records or datasets that are transferred to the sponsor will contain the identifier only; patient names or any other information that would make the patient identifiable will not be transferred. Patients will be informed that their personal registry-related data will be used by the sponsor in accordance with local data protection law. The level of disclosure will also be explained to the patient, who will be required to give consent/assent for their data to be used as described in the informed consent. A data management plan specifying all relevant aspects of data processing for the registry will be maintained and stored at the sponsor’s site.

An advisory board comprised of global EoE experts, including allergists and gastroenterologists, supported the review of the registry design and protocol. A steering committee will be convened to conduct a longitudinal review of the data and its interpretation and contribute to the strategy for its dissemination. The steering committee will also advise of any amendments required to the protocol.

Discussion

The efficacy and safety of dupilumab in patients with EoE have been assessed in two phase III trials: the LIBERTY EoE TREET study in adolescents and adults, and the EoE KIDS study in children.^16,17 A phase IV study (REMODEL) is currently ongoing, and has recruited 69 adult patients with EoE to assess the efficacy of dupilumab in reducing fibrostenotic changes in the esophagus.³² However, to date, few studies have assessed the outcomes of dupilumab treatment of EoE in routine clinical practice. Real-world studies are important because they typically include a patient population that is more representative of clinical practice, as opposed to clinical trials, which have strict inclusion and exclusion criteria, and in which some patient groups can be under-represented.^33,34 We therefore plan to conduct a phase IV observational patient registry that will provide data to assess the real-world use of dupilumab in patients with EoE aged 12 years or older. This will be the first large-scale prospective assessment of the real-world use of dupilumab for EoE.

EDESIA aims to assess patient characteristics, treatment patterns, and long-term safety data from patients treated for EoE with dupilumab in real-world clinical settings. Real-world studies can provide insights into patient adherence and how healthcare providers are using a treatment in clinical practice outside the confines of a clinical trial setting. For example, because EoE medication history during the previous year will be recorded at baseline, EDESIA may provide insights into treatment algorithms used by healthcare providers and how these align with current guidelines.² Additionally, data collected throughout the registry may highlight differences in practice, including the frequency/timing of endoscopies to monitor disease management. These data may also identify whether treatment approaches differ depending on patient or disease characteristics, such as disease phenotype. Based on safety data collected in multiple phase III clinical trials and long-term registry studies in EoE and other atopic diseases, dupilumab is generally well tolerated and has a favorable safety profile in children, adolescents, and adults.^{16,17,35
–37} However, EoE is the only indication for which weekly dosing of dupilumab is indicated (300 mg every week in patients weighing ⩾40 kg).^13,14 EDESIA will therefore provide important safety information regarding the use of weekly dupilumab dosing in a real-world population. In addition, the target enrollment of approximately 300 patients, and the 3-year observational period, may provide a more extensive characterization of dupilumab safety compared with the previous clinical trials in EoE.

Generally, registry studies, and therefore EDESIA, can be limited by poor clinician engagement,³⁸ and lack of active follow-up and data accuracy, completeness, and continuity.³⁹ An additional limitation of EDESIA is that histology and endoscopy techniques will not be standardized across sites. Furthermore, these assessments will not be mandatory at each visit and will be collected only if performed as part of routine care. Consequently, data collected for histologic and endoscopic outcomes may be limited, which could make it challenging to draw definitive conclusions from real-world evidence. In addition, the study will be performed only in the USA, so results may not be generalizable to European or other international care settings, where practice standards differ.^2,40,41 However, because US registry data are lacking, EDESIA will address an important research gap by generating US-specific data for the treatment of EoE with dupilumab in real-world practice.

In summary, the phase IV EDESIA patient registry will provide data to expand on prior randomized clinical trials by assessing patient characteristics, treatment patterns, and long-term safety data in patients aged 12 years or older receiving dupilumab for EoE in a real-world US clinical setting. Although EDESIA may have limitations inherent to real-world studies, results may help further inform the role of biologic therapy in the EoE treatment algorithm and explore the safety of weekly dupilumab dosing in a real-world setting.

Supplemental Material

sj-doc-1-tag-10.1177_17562848261443887 – Supplemental material for Baseline characteristics, treatment patterns, and long-term outcomes in patients with eosinophilic esophagitis initiating dupilumab in routine clinical practice: study protocol of a phase IV, prospective, observational, multicenter registry (EDESIA)

Supplemental material, sj-doc-1-tag-10.1177_17562848261443887 for Baseline characteristics, treatment patterns, and long-term outcomes in patients with eosinophilic esophagitis initiating dupilumab in routine clinical practice: study protocol of a phase IV, prospective, observational, multicenter registry (EDESIA) by Evan S. Dellon, Mirna Chehade, Emily C. McGowan, Elizabeth T. Jensen, John Leung, Devrim Eren, James T. Angello, Amr Radwan, Sandy R. Durrani and Sabina deMarchi in Therapeutic Advances in Gastroenterology

Footnotes

Acknowledgements

Medical writing/editorial support was provided by Emily Prior, MSc, of Adelphi Group, Bollington, UK, and was funded by Sanofi and Regeneron Pharmaceuticals Inc., according to the Good Publication Practice guidelines.

Declarations

ORCID iD

Evan S. Dellon

Supplemental material

Supplemental material for this article is available online.

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Baseline characteristics,treatment patterns,and long-term outcomes in patients with eosinophilic esophagitis initiating dupilumab in routine clinical practice: study protocol of a phase IV,prospective,observational,multicenter registry (EDESIA)

Abstract

Background:

Objectives:

Design:

Methods and analysis:

Ethics:

Discussion:

Trial registration:

Plain language summary

Keywords

Introduction

Methods and analysis

Study design and patients

Treatment

Assessments and analysis

Statistics

Handling of missing or incomplete data

Ethics and dissemination

Discussion

Supplemental Material

Footnotes

Acknowledgements

Declarations

ORCID iD

Supplemental material

References

Supplementary Material