Pharmacological Interventions for Eosinophilic Esophagitis
Background Eosinophilic oesophagitis (EoE) is a growing cause of dysphagia. Current therapies include dietary manipulation, steroids and biological drugs.
Aim To perform a systematic review and summarise the effect of different medical interventions on EoE.
Methods Two reviewers searched Pubmed and Embase for studies on treatment for EoE. We included randomised controlled trials (RCT) limited to pharmacological interventions. Two reviewers selected studies. Meta-analysis was done using random effects model to estimate odds ratio (OR). Heterogeneity was determined by Cochran's Q statistic and I.
Results Seventeen references met our inclusion criteria. Eleven RCTs involving 455 participants were included in the meta-analysis. 325 participants were evaluated for symptomatic improvement and 330 were evaluated for histological remission. Symptomatic improvement with topical steroids (7 studies, 250 participants) compared to the control group (placebo or PPI) was noted (OR: 3.03, 95% confidence interval, CI: 1.57–5.87). Histological remission was also noted in nine studies involving 330 participants (OR: 13.66, 95% CI: 2.65–70.34) comparing topical steroids to a control (placebo or PPI). There was no difference between anti-IL-5 drugs and placebo in terms of symptomatic improvement (OR: 0.69, 95% CI: 0.34–1.42).
Conclusions Topical steroids induce significant symptomatic and histological remission, and should be considered as a first line treatment. Anti-IL-5 therapy has a minor effect on eosinophilic oesophagitis. Future research in eosinophilic oesophagitis should standardise methodology according to published guidelines to improve quality and allow direct comparison between therapies.
Eosinophilic oesophagitis (EoE) is defined by the presence of significant eosinophilia in the squamous epithelium of the oesophagus leading to oesophageal symptoms not attributable to another cause. The most recent American College of Gastroenterology (ACG) guideline on EoE proposed diagnostic criteria which requires both clinical and pathological findings. EoE is diagnosed when the patient has symptoms related to oesophageal dysfunction with an eosinophil-predominant inflammation on oesophageal biopsy characteristically consisting of a peak value of ≥15 eosinophils per high-power field (eos/hpf). Mucosal eosinophilia is isolated to the oesophagus and persists after a proton-pump inhibitor (PPI) trial and secondary causes of oesophageal eosinophilia have been excluded. There should be 2–4 biopsies taken from both proximal and distal oesophagus along with biopsies from the antrum and duodenum to rule out secondary causes such as eosinophilic gastroenteritis. Treatment with PPI should be given for 2 months to rule out proton-pump inhibitor responsive oesophageal eosinophilia (PPI-REE), which is a different entity from EoE. The endpoints of treatment in EoE are improvement in symptoms and resolution of oesophageal tissue eosinophilia. Recently, Dellon, Gonsalves, Hirano et al. reviewed and updated prior EoE guidelines, where they incorporated the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). A prior Cochrane review on nonsurgical interventions for EoE in February, 2009 showed only a handful of randomised clinical trials (RCTs) and had limited capacity to compare the benefits and harms of medical interventions. Given that EoE is a disease on the rise and in the light of newer guidelines, we aimed to systematically evaluate and summarise the effect of medical therapy on EoE from randomised control trials (RCT) that included a comparison group. This review is not intended to study dietary modifications on EoE, which was recently reviewed by Arias et al. They found that elemental, 6-food elimination and allergy test result-directed food elimination diets were effective in producing histological remission in patients with EoE.
Abstract and Introduction
Abstract
Background Eosinophilic oesophagitis (EoE) is a growing cause of dysphagia. Current therapies include dietary manipulation, steroids and biological drugs.
Aim To perform a systematic review and summarise the effect of different medical interventions on EoE.
Methods Two reviewers searched Pubmed and Embase for studies on treatment for EoE. We included randomised controlled trials (RCT) limited to pharmacological interventions. Two reviewers selected studies. Meta-analysis was done using random effects model to estimate odds ratio (OR). Heterogeneity was determined by Cochran's Q statistic and I.
Results Seventeen references met our inclusion criteria. Eleven RCTs involving 455 participants were included in the meta-analysis. 325 participants were evaluated for symptomatic improvement and 330 were evaluated for histological remission. Symptomatic improvement with topical steroids (7 studies, 250 participants) compared to the control group (placebo or PPI) was noted (OR: 3.03, 95% confidence interval, CI: 1.57–5.87). Histological remission was also noted in nine studies involving 330 participants (OR: 13.66, 95% CI: 2.65–70.34) comparing topical steroids to a control (placebo or PPI). There was no difference between anti-IL-5 drugs and placebo in terms of symptomatic improvement (OR: 0.69, 95% CI: 0.34–1.42).
Conclusions Topical steroids induce significant symptomatic and histological remission, and should be considered as a first line treatment. Anti-IL-5 therapy has a minor effect on eosinophilic oesophagitis. Future research in eosinophilic oesophagitis should standardise methodology according to published guidelines to improve quality and allow direct comparison between therapies.
Introduction
Eosinophilic oesophagitis (EoE) is defined by the presence of significant eosinophilia in the squamous epithelium of the oesophagus leading to oesophageal symptoms not attributable to another cause. The most recent American College of Gastroenterology (ACG) guideline on EoE proposed diagnostic criteria which requires both clinical and pathological findings. EoE is diagnosed when the patient has symptoms related to oesophageal dysfunction with an eosinophil-predominant inflammation on oesophageal biopsy characteristically consisting of a peak value of ≥15 eosinophils per high-power field (eos/hpf). Mucosal eosinophilia is isolated to the oesophagus and persists after a proton-pump inhibitor (PPI) trial and secondary causes of oesophageal eosinophilia have been excluded. There should be 2–4 biopsies taken from both proximal and distal oesophagus along with biopsies from the antrum and duodenum to rule out secondary causes such as eosinophilic gastroenteritis. Treatment with PPI should be given for 2 months to rule out proton-pump inhibitor responsive oesophageal eosinophilia (PPI-REE), which is a different entity from EoE. The endpoints of treatment in EoE are improvement in symptoms and resolution of oesophageal tissue eosinophilia. Recently, Dellon, Gonsalves, Hirano et al. reviewed and updated prior EoE guidelines, where they incorporated the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). A prior Cochrane review on nonsurgical interventions for EoE in February, 2009 showed only a handful of randomised clinical trials (RCTs) and had limited capacity to compare the benefits and harms of medical interventions. Given that EoE is a disease on the rise and in the light of newer guidelines, we aimed to systematically evaluate and summarise the effect of medical therapy on EoE from randomised control trials (RCT) that included a comparison group. This review is not intended to study dietary modifications on EoE, which was recently reviewed by Arias et al. They found that elemental, 6-food elimination and allergy test result-directed food elimination diets were effective in producing histological remission in patients with EoE.
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