Respule or metered-dose inhaler for eosinophilic esophagitis treatment? A dose-ranging, randomized clinical trial study on efficacy, safety, and relapse rate

Farhad Seif; Nastaran Amiri; Majid Khoshmirsafa; Saba Arshi; Mohammad Nabavi; Mohammad Hassan Bemanian; Sima Shokri; Azizollah Yousefi; Banafshe Rajabian; Fatemeh Mahjoob; Nikoo Emtiazi; Morteza Fallahpour; Farhad Seif; Nastaran Amiri; Majid Khoshmirsafa; Saba Arshi; Mohammad Nabavi; Mohammad Hassan Bemanian; Sima Shokri; Azizollah Yousefi; Banafshe Rajabian; Fatemeh Mahjoob; Nikoo Emtiazi; Morteza Fallahpour

doi:10.3934/Allergy.2024010

AIMS Allergy and Immunology

2024, Volume 8, Issue 3: 193-203. doi: 10.3934/Allergy.2024010

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Research article

Respule or metered-dose inhaler for eosinophilic esophagitis treatment? A dose-ranging, randomized clinical trial study on efficacy, safety, and relapse rate

1.
Department of Photodynamic, Medical Laser Research Center, Yara Institute, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran
2.
Department of Allergy and Clinical Immunology, Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
3.
Department of Immunology, Medical School, Iran University of Medical Sciences, Tehran, Iran
4.
Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
5.
Farvardin Pathology Laboratory, Tehran University of Medical Science, Tehran, Iran
6.
Department of Pathology, School of Medicine, Maternal, Fetal and Neonatal Research Center, Family Health Research Institute
7.
Department of Pathology Medicine, Rasool Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

Received: 06 June 2024 Revised: 26 September 2024 Accepted: 09 October 2024 Published: 15 October 2024

Background
Eosinophilic esophagitis (EoE) is a chronic allergen/immune-mediated disease known by eosinophil infiltration into the esophagus. Topical steroids are used for its treatment. We investigated the efficacy, side effects, and symptom relapse after discontinuation of two budesonide forms in EoE patients.
Methods
In this prospective, dose-ranging, randomized trial, 35 EoE patients under 18 years who received two budesonide forms were assigned to low-dose oral respule (17 patients) and swallowed metered-dose inhaler (MDI) (18 patients) groups. Both groups received low-dose budesonide for eight weeks. Doses were doubled after the first eight weeks if symptom remission was not achieved, but the previous dose was continued for the next eight weeks for the subjects with symptom relief. At the end of week 16, budesonide was discontinued in all patients. The following outcomes were assessed: The primary outcome was symptom relief, assessed by Pediatric EoE Symptom Scores (PEESS®v2.0). Secondary outcomes included safety, side effects, and histological changes, based on repeated endoscopy at weeks 0, 8, 16, and 32.
Results
Non-response to low-dose treatment in the first eight weeks was observed in 2 cases (13.3%, 95% CI: 2.6%–35.2%) in the respule group and 7 cases (50.0%, 95% CI: 22.7%–77.3%) in the MDI group, indicating a significant difference between the groups (p = 0.033). In the 16^th week, the treatment failure rate was 13.3% and 26.6% in the oral respule and swallowed MDI groups, respectively (p = 0.048). The therapeutic response during the 8^th week was significantly higher in oral respule group than swallowed MDI group (OR = 8.418, p = 0.046).
Conclusion
This study indicates that the oral respule formulation of budesonide is more effective than the swallowed MDI in alleviating symptoms of eosinophilic esophagitis (EoE) in children. The oral respule not only resulted in a higher rate of symptom relief but also exhibited a better safety profile, with fewer incidents of oral thrush and adrenal suppression.
- Eosinophilic esophagitis,
- EoE treatment,
- budesonide oral respule,
- swallowed topical corticosteroids
Citation: Farhad Seif, Nastaran Amiri, Majid Khoshmirsafa, Saba Arshi, Mohammad Nabavi, Mohammad Hassan Bemanian, Sima Shokri, Azizollah Yousefi, Banafshe Rajabian, Fatemeh Mahjoob, Nikoo Emtiazi, Morteza Fallahpour. Respule or metered-dose inhaler for eosinophilic esophagitis treatment? A dose-ranging, randomized clinical trial study on efficacy, safety, and relapse rate[J]. AIMS Allergy and Immunology, 2024, 8(3): 193-203. doi: 10.3934/Allergy.2024010

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Abstract

Background

Eosinophilic esophagitis (EoE) is a chronic allergen/immune-mediated disease known by eosinophil infiltration into the esophagus. Topical steroids are used for its treatment. We investigated the efficacy, side effects, and symptom relapse after discontinuation of two budesonide forms in EoE patients.

Methods

In this prospective, dose-ranging, randomized trial, 35 EoE patients under 18 years who received two budesonide forms were assigned to low-dose oral respule (17 patients) and swallowed metered-dose inhaler (MDI) (18 patients) groups. Both groups received low-dose budesonide for eight weeks. Doses were doubled after the first eight weeks if symptom remission was not achieved, but the previous dose was continued for the next eight weeks for the subjects with symptom relief. At the end of week 16, budesonide was discontinued in all patients. The following outcomes were assessed: The primary outcome was symptom relief, assessed by Pediatric EoE Symptom Scores (PEESS®v2.0). Secondary outcomes included safety, side effects, and histological changes, based on repeated endoscopy at weeks 0, 8, 16, and 32.

Results

Non-response to low-dose treatment in the first eight weeks was observed in 2 cases (13.3%, 95% CI: 2.6%–35.2%) in the respule group and 7 cases (50.0%, 95% CI: 22.7%–77.3%) in the MDI group, indicating a significant difference between the groups (p = 0.033). In the 16^th week, the treatment failure rate was 13.3% and 26.6% in the oral respule and swallowed MDI groups, respectively (p = 0.048). The therapeutic response during the 8^th week was significantly higher in oral respule group than swallowed MDI group (OR = 8.418, p = 0.046).

Conclusion

This study indicates that the oral respule formulation of budesonide is more effective than the swallowed MDI in alleviating symptoms of eosinophilic esophagitis (EoE) in children. The oral respule not only resulted in a higher rate of symptom relief but also exhibited a better safety profile, with fewer incidents of oral thrush and adrenal suppression.

Acknowledgments

We would like to thank all the staff of the Allergy Department and Clinical Research and Development Center of Rasool Akram Hospital (RCRDC) for their valuable help.

Conflict of interest

The authors declare no conflict of interest.

Author contributions

FS, MF, NA conceived the study, drafted the manuscript, and gathered the data; MKh, SA, MN, MHB, SSh, AY, BR, FM, NE conducted statistical analysis and interpretation of data. FS revised the final manuscript for important intellectual content. All authors read and approved the final manuscript.

Ethical considerations

This study was approved by the Ethics Committee of Iran University of Medical Sciences (IR.IUMS.FMD.REC.1398.371) and registered at IRCT (IRCTID: IRCT20191211045703N1). https://www.irct.ir/trial/44589

Availability of data and material

Please get in touch with the corresponding author for data requests.

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