From: Systematic review of outcome measures in pediatric eosinophilic esophagitis treatment trials
Study | Design | Intervention | Control | 1° Outcome(s) | 2° Outcome(s) | Outcome reporting | Outcome reporting bias | Conclusions |
---|---|---|---|---|---|---|---|---|
Konikoff [18] | Randomized, double blind, 2 arm | Swallowed fluticasone propionate (440 μg BID × 3 months) | Placebo | Histologic Remission (Peak Eo count ≤1 in all fields in proximal and distal esophagus at 3 months) | a. Presence of endoscopic furrowing | 1° Outcome: Yes | Some selective outcome reporting: Not all symptom data available for 2° outcome | Swallowed fluticasone effective in inducing histologic remission in EoE, with more pronounced effect in non-allergic and younger individuals, especially in proximal esophagus |
b. Reduction in epithelial hyperplasia | Post-hoc, histologic responsiveness also re-defined as higher peak Eo count; mean Eo count of <1 or <2; and % reduction of 90 or 95 % | Additional outcomes reported (Intervention responsiveness- allergic vs non-allergic subjects, age, height, weight; CD8+ T cell levels, esophageal mastocytosis, adverse events) | ||||||
c. Presence of symptoms | 2° Outcomes: a. Yes, b: Only vomiting reported | |||||||
Harms: adverse events reported | ||||||||
Schaefer [19] | Randomized, open label, 2 arm | Swallowed fluticasone (220 μg QID if 1–10 years, or 440 μg QID if 11–18 years) × 4 weeks with 8 week weaning protocol | Oral prednisone 1 mg/kg/dose BID (max 30 mg BID) × 4 weeks with 8 week weaning protocol | Improvement in “biopsy grade” by 1 or more after 4 weeks | Clinical response at 0, 4, 12, 18–24 weeks, based on presence or absence of presenting symptoms by patient report, and physician assessment. | 1° Outcome: yes | Additional outcomes reported (proportion of symptom free patients, relapse rate, time to relapse, systemic adverse effects) | Systemic and topical corticosteroids effective in achieving initial histologic and clinical improvement. Prednisone resulted in greater degree of histologic improvement, without evidence of associated clinical advantage over fluticasone for symptom resolution, relapse rates or time to relapse. Symptom relapse common to both groups upon therapy discontinuation |
2° Outcome: yes | ||||||||
Harms: adverse events reported | ||||||||
Dohil [20] | Randomized, double-blind, 2 arm | Oral viscous budesonide (<5ft: 1 mg; >5ft: 2 mg) + PPI | Placebo + PPI | Baseline and final peak esophageal Eo count/HPF: responders (0–6 Eo/HPF); partial responder (7–19 Eo/HPF); non-responders (≥20 Eo/HPF) | a. Endoscopic features (modified endoscopy tool) | 1° Outcome: yes | None evident | OVB improves symptoms and endoscopic and histologic features of pediatric EoE compared to PPI alone |
b. Symptom response (symptom scoring tool) | 2° Outcomes: yes | |||||||
c. Histologic features (histology scoring tool) | Harms: adverse events reported | |||||||
d.TGFβ1/TGFβ1 promoter genotype | ||||||||
Assa’ad [21] | Randomized, double blind, 3 arm | Mepolizumab 2.5 or 10 mg/kg at day 0, week 4 and 8 | Mepolizumab 0.55 mg/kg at day 0, week 4 and 8 | a. Proportion of “responders” (peak Eo <5/HPF at week 12), % partial responders: 5–19 Eo/HPF | a. Changes in peak & mean Eo counts | 1° Outcome: Yes | Post-hoc analysis of predictors of response for change in mean Eo counts. | IL5 involved in pathogenesis in EoE in children. mepolizumab reduces esophageal Eo inflammation in these patients |
b. Safety | b. Histopathologic findings | 2° Outcomes: Yes | Additional outcomes reported: changes in esophageal Eo density, changes in symptoms | |||||
3. Tolerability | c. Endoscopic findings | Harms: adverse events reported | ||||||
4. Pharmaco-kinetics | d. Blood Eo counts | |||||||
e. Frequency + severity of symptoms | ||||||||
Spergel [22] | Randomized, double blind, 4 arm | Reslizumab 1, 2 or 3 mg/kg infusions at 0, 4, 8 and 12 weeks | Placebo | a. Histologic: % change in peak esophageal Eo count | a. CHQ scores | 1° Outcome: yes | Certain data selectively described (e.g. positive trends in patient predominant symptom assessment (secondary outcome), but not actual values | Reslizumab significantly reduced intraepithelial esophageal Eo counts in children and adolescents with EoE. However, improvements in symptoms were observed in all treatment groups and were not associated with changes in esophageal Eo counts |
b. Symptoms: Physician global assessment score week 15 | b. Predominant symptom assessment scores | 2° Outcomes: yes | ||||||
c. Adverse events | Harms: adverse events reported | |||||||
Gupta [23] | Placebo-controlled, 4 am | Oral budesonide suspension: low-dose (0.35 mg if 2–9 years; 0.5 mg if 10–18 years), medium-dose (1.4 mg if 2–9 years; 2 mg if 10–18 years), high dose (2.8 mg if 2–9 years; 4 mg if 10–18 years) | Placebo | Compound histologic and symptom response to therapy | a. Percentage of subjects with histologic response (peak Eo ≤6/HPF) | Yes | None observed | Peak Eo counts significantly reduced throughout esophagus in pediatric patients with EoE given medium dose and high dose OBS. There was a large symptom response to placebo that was similar to symptom responses in the OBS groups. Symptom response did not distinguish OBS from placebo |
b. Clinical symptom response (≥50 % reduction in EoE clinical symptom score) | Harms/adverse events reported. | |||||||
c. Histologic remission (peak Eo ≤1/HPF at all levels) | ||||||||
d. Symptom resolution (EoE CSS 0) | ||||||||
Page [25] NCT01458418 (not yet recruiting) | Randomized, double-blind, 3 arm | Montelukast 10 or 5 mg/day | Placebo | Eo/HPF in the esophagus after 12 weeks of therapy. | Amount of MBP, tryptase and trichrome in esophageal specimens at 1–2 weeks | N/A | N/A | |
Di Nardo [26] NCT01846962 (recruiting) | Randomized, open-label, 3 arm | Swallowed budesonide 0.5 mg | N/A | Clinical severity score (frequency, intensity and interference on life quality) | Severity Score for endoscopy and histology | N/A | N/A | |
Swallowed fluticasone 0.5 mg | ||||||||
6-food ED + triggering foods per patients or parents | ||||||||
Teva Pharm [27] NCT00635089 (completed) | Open-label extension study for patients who completed Spergel study [22] | Reslizumab monthly | N/A | Safety | Profile of durability of response to treatment | Data not available | Data not available | |
McGuire Davis [28] NCT01821898 (recruiting) | Randomized, 4 arm | Group 1 (+FA): sham ED + PO budesonide (1–2 mg based on weight) | N/A | Eo/HPF after treatment | a. Quality of Life at 8 weeks (PedsQL) | N/A | N/A | |
Group 2 (+FA): ED + sham PO budenoside | b. Symptom score (validated tool “pediatric EoE symptom severity module”) | |||||||
Group 3 (−FA): 6-food ED | c. Exploratory proteomic and immune analysis | |||||||
Group 4 (-FA): PO budesonide (1–2 mg based on weight) | ||||||||
Heine [24] | Randomized, 2 arm | Group 1: oral PPI × 8–12 weeks + 4 food elimination diet | PPI alone | Histologic evidence of EoE expressed as #Eo/HPF | 1. Mechanistic investigations regarding regulation of inflammatory and remodeling changes (eotaxins, TSLP, fibrosis markers, other related effector molecules) | N/A | N/A | |
Group 2: PPI alone × 8–12 weeks | 2. Clinical response (symptom score) | |||||||
3. Endoscopic appearance (endoscopy score) |