Heterogeneity in Clinical, Endoscopic, and Histologic Outcome Measures and Placebo Response Rates in Clinical Trials of Eosinophilic Esophagitis: A Systematic Review

Christopher Ma, Bram D. van Rhijn, Vipul Jairath, Tran M. Nguyen, Claire E. Parker, Seema S. Aceves, Glenn T. Furuta, Sandeep Gupta, David A. Katzka, Ekaterina Safroneeva, Alain M. Schoepfer, Alex Straumann, Jonathan M. Spergel, Rish K. Pai, Brian G. Feagan, Ikuo Hirano, Evan S. Dellon, Albert J. Bredenoord

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Agents are being developed for treatment of eosinophilic esophagitis (EoE). However, it is not clear what outcome measures would best determine the efficacy and safety of these agents in clinical trials. We performed a systematic review of outcomes used in randomized placebo-controlled trials of EoE and we estimate the placebo response and rates of remission. Methods: We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the EU Clinical Trials Register from inception through February 20, 2018 for randomized controlled trials of pharmacologic therapies for EoE. Efficacy outcome definitions, measurement tools, and the proportion of patients responding to placebo were collected and stratified by based on histologic, endoscopic, and patient-reported outcomes. Results: We analyzed data from 22 placebo-controlled trials, comprising 1112 patients with EoE. Ten additional active registered trials were identified. Most published trials evaluated topical corticosteroid therapy (13/22, 59.1%). Histologic outcomes measuring eosinophil density and patient-reported outcomes were reported in 21/22 published trials (95.5%). No consistently applied definitions of histologic or patient-reported response or remission were identified. Endoscopic outcomes were described in 60% (12/20) of published trials. The EoE Endoscopic Reference Score is the most commonly applied tool for describing changes in endoscopic appearance. The median histologic response to placebo was 3.7% (range, 0%–31.6%) and the median rate of remission in patients given placebo was 0.0% (range, 0%–11.0%). The median patient-reported response to placebo was 14.4% (range, 8.6%–77.8%) and rate of remission in patients given placebo was 26.2% (range, 13.2%–35.7%). Conclusions: In a systematic review of the literature, we found that no standardized definitions of histologic, endoscopic, or patient-reported outcomes are used to determine whether pharmacologic agents produce a response or remission in patients with EoE. A core outcome set is needed to reduce heterogeneity in outcome reporting and facilitate trial interpretation and comparison of results from trials.

Original languageEnglish (US)
JournalClinical Gastroenterology and Hepatology
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Eosinophilic Esophagitis
Placebos
Outcome Assessment (Health Care)
Clinical Trials
Randomized Controlled Trials
Eosinophils
MEDLINE
Adrenal Cortex Hormones
Therapeutics
Safety

Keywords

  • Drug
  • Endoscopy
  • Esophagus
  • Histology
  • Inflammation
  • Patient-Reported Outcomes
  • Placebo

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Heterogeneity in Clinical, Endoscopic, and Histologic Outcome Measures and Placebo Response Rates in Clinical Trials of Eosinophilic Esophagitis : A Systematic Review. / Ma, Christopher; van Rhijn, Bram D.; Jairath, Vipul; Nguyen, Tran M.; Parker, Claire E.; Aceves, Seema S.; Furuta, Glenn T.; Gupta, Sandeep; Katzka, David A.; Safroneeva, Ekaterina; Schoepfer, Alain M.; Straumann, Alex; Spergel, Jonathan M.; Pai, Rish K.; Feagan, Brian G.; Hirano, Ikuo; Dellon, Evan S.; Bredenoord, Albert J.

In: Clinical Gastroenterology and Hepatology, 01.01.2018.

Research output: Contribution to journalArticle

Ma, C, van Rhijn, BD, Jairath, V, Nguyen, TM, Parker, CE, Aceves, SS, Furuta, GT, Gupta, S, Katzka, DA, Safroneeva, E, Schoepfer, AM, Straumann, A, Spergel, JM, Pai, RK, Feagan, BG, Hirano, I, Dellon, ES & Bredenoord, AJ 2018, 'Heterogeneity in Clinical, Endoscopic, and Histologic Outcome Measures and Placebo Response Rates in Clinical Trials of Eosinophilic Esophagitis: A Systematic Review', Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/j.cgh.2018.06.005
Ma, Christopher ; van Rhijn, Bram D. ; Jairath, Vipul ; Nguyen, Tran M. ; Parker, Claire E. ; Aceves, Seema S. ; Furuta, Glenn T. ; Gupta, Sandeep ; Katzka, David A. ; Safroneeva, Ekaterina ; Schoepfer, Alain M. ; Straumann, Alex ; Spergel, Jonathan M. ; Pai, Rish K. ; Feagan, Brian G. ; Hirano, Ikuo ; Dellon, Evan S. ; Bredenoord, Albert J. / Heterogeneity in Clinical, Endoscopic, and Histologic Outcome Measures and Placebo Response Rates in Clinical Trials of Eosinophilic Esophagitis : A Systematic Review. In: Clinical Gastroenterology and Hepatology. 2018.
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abstract = "Background & Aims: Agents are being developed for treatment of eosinophilic esophagitis (EoE). However, it is not clear what outcome measures would best determine the efficacy and safety of these agents in clinical trials. We performed a systematic review of outcomes used in randomized placebo-controlled trials of EoE and we estimate the placebo response and rates of remission. Methods: We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the EU Clinical Trials Register from inception through February 20, 2018 for randomized controlled trials of pharmacologic therapies for EoE. Efficacy outcome definitions, measurement tools, and the proportion of patients responding to placebo were collected and stratified by based on histologic, endoscopic, and patient-reported outcomes. Results: We analyzed data from 22 placebo-controlled trials, comprising 1112 patients with EoE. Ten additional active registered trials were identified. Most published trials evaluated topical corticosteroid therapy (13/22, 59.1{\%}). Histologic outcomes measuring eosinophil density and patient-reported outcomes were reported in 21/22 published trials (95.5{\%}). No consistently applied definitions of histologic or patient-reported response or remission were identified. Endoscopic outcomes were described in 60{\%} (12/20) of published trials. The EoE Endoscopic Reference Score is the most commonly applied tool for describing changes in endoscopic appearance. The median histologic response to placebo was 3.7{\%} (range, 0{\%}–31.6{\%}) and the median rate of remission in patients given placebo was 0.0{\%} (range, 0{\%}–11.0{\%}). The median patient-reported response to placebo was 14.4{\%} (range, 8.6{\%}–77.8{\%}) and rate of remission in patients given placebo was 26.2{\%} (range, 13.2{\%}–35.7{\%}). Conclusions: In a systematic review of the literature, we found that no standardized definitions of histologic, endoscopic, or patient-reported outcomes are used to determine whether pharmacologic agents produce a response or remission in patients with EoE. A core outcome set is needed to reduce heterogeneity in outcome reporting and facilitate trial interpretation and comparison of results from trials.",
keywords = "Drug, Endoscopy, Esophagus, Histology, Inflammation, Patient-Reported Outcomes, Placebo",
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T1 - Heterogeneity in Clinical, Endoscopic, and Histologic Outcome Measures and Placebo Response Rates in Clinical Trials of Eosinophilic Esophagitis

T2 - A Systematic Review

AU - Ma, Christopher

AU - van Rhijn, Bram D.

AU - Jairath, Vipul

AU - Nguyen, Tran M.

AU - Parker, Claire E.

AU - Aceves, Seema S.

AU - Furuta, Glenn T.

AU - Gupta, Sandeep

AU - Katzka, David A.

AU - Safroneeva, Ekaterina

AU - Schoepfer, Alain M.

AU - Straumann, Alex

AU - Spergel, Jonathan M.

AU - Pai, Rish K.

AU - Feagan, Brian G.

AU - Hirano, Ikuo

AU - Dellon, Evan S.

AU - Bredenoord, Albert J.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background & Aims: Agents are being developed for treatment of eosinophilic esophagitis (EoE). However, it is not clear what outcome measures would best determine the efficacy and safety of these agents in clinical trials. We performed a systematic review of outcomes used in randomized placebo-controlled trials of EoE and we estimate the placebo response and rates of remission. Methods: We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the EU Clinical Trials Register from inception through February 20, 2018 for randomized controlled trials of pharmacologic therapies for EoE. Efficacy outcome definitions, measurement tools, and the proportion of patients responding to placebo were collected and stratified by based on histologic, endoscopic, and patient-reported outcomes. Results: We analyzed data from 22 placebo-controlled trials, comprising 1112 patients with EoE. Ten additional active registered trials were identified. Most published trials evaluated topical corticosteroid therapy (13/22, 59.1%). Histologic outcomes measuring eosinophil density and patient-reported outcomes were reported in 21/22 published trials (95.5%). No consistently applied definitions of histologic or patient-reported response or remission were identified. Endoscopic outcomes were described in 60% (12/20) of published trials. The EoE Endoscopic Reference Score is the most commonly applied tool for describing changes in endoscopic appearance. The median histologic response to placebo was 3.7% (range, 0%–31.6%) and the median rate of remission in patients given placebo was 0.0% (range, 0%–11.0%). The median patient-reported response to placebo was 14.4% (range, 8.6%–77.8%) and rate of remission in patients given placebo was 26.2% (range, 13.2%–35.7%). Conclusions: In a systematic review of the literature, we found that no standardized definitions of histologic, endoscopic, or patient-reported outcomes are used to determine whether pharmacologic agents produce a response or remission in patients with EoE. A core outcome set is needed to reduce heterogeneity in outcome reporting and facilitate trial interpretation and comparison of results from trials.

AB - Background & Aims: Agents are being developed for treatment of eosinophilic esophagitis (EoE). However, it is not clear what outcome measures would best determine the efficacy and safety of these agents in clinical trials. We performed a systematic review of outcomes used in randomized placebo-controlled trials of EoE and we estimate the placebo response and rates of remission. Methods: We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the EU Clinical Trials Register from inception through February 20, 2018 for randomized controlled trials of pharmacologic therapies for EoE. Efficacy outcome definitions, measurement tools, and the proportion of patients responding to placebo were collected and stratified by based on histologic, endoscopic, and patient-reported outcomes. Results: We analyzed data from 22 placebo-controlled trials, comprising 1112 patients with EoE. Ten additional active registered trials were identified. Most published trials evaluated topical corticosteroid therapy (13/22, 59.1%). Histologic outcomes measuring eosinophil density and patient-reported outcomes were reported in 21/22 published trials (95.5%). No consistently applied definitions of histologic or patient-reported response or remission were identified. Endoscopic outcomes were described in 60% (12/20) of published trials. The EoE Endoscopic Reference Score is the most commonly applied tool for describing changes in endoscopic appearance. The median histologic response to placebo was 3.7% (range, 0%–31.6%) and the median rate of remission in patients given placebo was 0.0% (range, 0%–11.0%). The median patient-reported response to placebo was 14.4% (range, 8.6%–77.8%) and rate of remission in patients given placebo was 26.2% (range, 13.2%–35.7%). Conclusions: In a systematic review of the literature, we found that no standardized definitions of histologic, endoscopic, or patient-reported outcomes are used to determine whether pharmacologic agents produce a response or remission in patients with EoE. A core outcome set is needed to reduce heterogeneity in outcome reporting and facilitate trial interpretation and comparison of results from trials.

KW - Drug

KW - Endoscopy

KW - Esophagus

KW - Histology

KW - Inflammation

KW - Patient-Reported Outcomes

KW - Placebo

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