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About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.
“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”
The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.
Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.
With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.
The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.
The authors reported no funding sources and had no disclosures.
Proton pump inhibitor–responsive esophageal eosinophilia (PPI-REE) is a condition in which patients have symptoms of esophageal dysfunction (often dysphagia or heartburn), biopsies with at least 15 eosinophils per high-power field (eos/hpf), and symptomatic and histologic resolution after a PPI trial, typically at twice-daily dosing. Currently, PPI-REE and eosinophilic esophagitis (EoE) overlap substantially, but in the most recent guidelines, they are still considered to be distinct entities. PPI-REE was first reported almost 10 years ago, and since then multiple prospective and retrospective studies in both children and adults have further characterized it. The study by Dr. Lucendo and colleagues, a comprehensive and rigorously conducted systematic review and meta-analysis of 33 studies accounting for 619 patients, found that just over 50% of patients with esophageal eosinophilia had histologic remission (less than 15 eos/hpf) and just over 60% had symptomatic improvement after PPI use. Moreover, similar responses were seen whether or not there was pathologic acid exposure on pH testing.
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| Dr. Evan S. Dellon |
While there was heterogeneity between studies on meta-analysis, there are several important messages from this study. First, PPI-REE is commonly seen in patients with esophageal eosinophilia, and is not always simply due to reflux. Second, PPIs have a potent antieosinophil effect in these patients. Interestingly, novel acid-independent mechanisms for this anti-inflammatory action recently have been described in other studies. Third, a PPI trial remains important prior to confirming the diagnosis of EoE, and PPIs should be considered the first-line treatment when esophageal eosinophilia is identified. However, it bears emphasizing that all esophageal eosinophilia is not due to EoE. If a patient responds to the PPI trial, there is no clear need to move toward topical steroid or dietary elimination therapy specifically for EoE, and starting multiple antieosinophil treatments concomitantly precludes determining which is most effective. In the future, understanding which patients with esophageal eosinophilia will most benefit from a PPI trial will be important, as we are currently unable to predict this from clinical, endoscopic, and histologic factors. Future studies and guidelines will also need to address whether EoE and PPI-REE are distinct diseases or manifestations of the same underlying process.
Dr. Evan S. Dellon, MPH, is associate professor of medicine and epidemiology at the Center for Esophageal Diseases and Swallowing, division of gastroenterology and hepatology, University of North Carolina School of Medicine at Chapel Hill. He has received research funding from Meritage, Miraca, Receptos, and Regeneron and consulted for Aptalis, Banner, Novartis, Receptos, Regeneron, and Roche.
Proton pump inhibitor–responsive esophageal eosinophilia (PPI-REE) is a condition in which patients have symptoms of esophageal dysfunction (often dysphagia or heartburn), biopsies with at least 15 eosinophils per high-power field (eos/hpf), and symptomatic and histologic resolution after a PPI trial, typically at twice-daily dosing. Currently, PPI-REE and eosinophilic esophagitis (EoE) overlap substantially, but in the most recent guidelines, they are still considered to be distinct entities. PPI-REE was first reported almost 10 years ago, and since then multiple prospective and retrospective studies in both children and adults have further characterized it. The study by Dr. Lucendo and colleagues, a comprehensive and rigorously conducted systematic review and meta-analysis of 33 studies accounting for 619 patients, found that just over 50% of patients with esophageal eosinophilia had histologic remission (less than 15 eos/hpf) and just over 60% had symptomatic improvement after PPI use. Moreover, similar responses were seen whether or not there was pathologic acid exposure on pH testing.
|
| Dr. Evan S. Dellon |
While there was heterogeneity between studies on meta-analysis, there are several important messages from this study. First, PPI-REE is commonly seen in patients with esophageal eosinophilia, and is not always simply due to reflux. Second, PPIs have a potent antieosinophil effect in these patients. Interestingly, novel acid-independent mechanisms for this anti-inflammatory action recently have been described in other studies. Third, a PPI trial remains important prior to confirming the diagnosis of EoE, and PPIs should be considered the first-line treatment when esophageal eosinophilia is identified. However, it bears emphasizing that all esophageal eosinophilia is not due to EoE. If a patient responds to the PPI trial, there is no clear need to move toward topical steroid or dietary elimination therapy specifically for EoE, and starting multiple antieosinophil treatments concomitantly precludes determining which is most effective. In the future, understanding which patients with esophageal eosinophilia will most benefit from a PPI trial will be important, as we are currently unable to predict this from clinical, endoscopic, and histologic factors. Future studies and guidelines will also need to address whether EoE and PPI-REE are distinct diseases or manifestations of the same underlying process.
Dr. Evan S. Dellon, MPH, is associate professor of medicine and epidemiology at the Center for Esophageal Diseases and Swallowing, division of gastroenterology and hepatology, University of North Carolina School of Medicine at Chapel Hill. He has received research funding from Meritage, Miraca, Receptos, and Regeneron and consulted for Aptalis, Banner, Novartis, Receptos, Regeneron, and Roche.
Proton pump inhibitor–responsive esophageal eosinophilia (PPI-REE) is a condition in which patients have symptoms of esophageal dysfunction (often dysphagia or heartburn), biopsies with at least 15 eosinophils per high-power field (eos/hpf), and symptomatic and histologic resolution after a PPI trial, typically at twice-daily dosing. Currently, PPI-REE and eosinophilic esophagitis (EoE) overlap substantially, but in the most recent guidelines, they are still considered to be distinct entities. PPI-REE was first reported almost 10 years ago, and since then multiple prospective and retrospective studies in both children and adults have further characterized it. The study by Dr. Lucendo and colleagues, a comprehensive and rigorously conducted systematic review and meta-analysis of 33 studies accounting for 619 patients, found that just over 50% of patients with esophageal eosinophilia had histologic remission (less than 15 eos/hpf) and just over 60% had symptomatic improvement after PPI use. Moreover, similar responses were seen whether or not there was pathologic acid exposure on pH testing.
|
| Dr. Evan S. Dellon |
While there was heterogeneity between studies on meta-analysis, there are several important messages from this study. First, PPI-REE is commonly seen in patients with esophageal eosinophilia, and is not always simply due to reflux. Second, PPIs have a potent antieosinophil effect in these patients. Interestingly, novel acid-independent mechanisms for this anti-inflammatory action recently have been described in other studies. Third, a PPI trial remains important prior to confirming the diagnosis of EoE, and PPIs should be considered the first-line treatment when esophageal eosinophilia is identified. However, it bears emphasizing that all esophageal eosinophilia is not due to EoE. If a patient responds to the PPI trial, there is no clear need to move toward topical steroid or dietary elimination therapy specifically for EoE, and starting multiple antieosinophil treatments concomitantly precludes determining which is most effective. In the future, understanding which patients with esophageal eosinophilia will most benefit from a PPI trial will be important, as we are currently unable to predict this from clinical, endoscopic, and histologic factors. Future studies and guidelines will also need to address whether EoE and PPI-REE are distinct diseases or manifestations of the same underlying process.
Dr. Evan S. Dellon, MPH, is associate professor of medicine and epidemiology at the Center for Esophageal Diseases and Swallowing, division of gastroenterology and hepatology, University of North Carolina School of Medicine at Chapel Hill. He has received research funding from Meritage, Miraca, Receptos, and Regeneron and consulted for Aptalis, Banner, Novartis, Receptos, Regeneron, and Roche.
About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.
“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”
The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.
Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.
With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.
The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.
The authors reported no funding sources and had no disclosures.
About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.
“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”
The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.
Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.
With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.
The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.
The authors reported no funding sources and had no disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Proton pump inhibitors should be considered in the first-line treatment of esophageal eosinophilia.
Major finding: Half of patients achieved clinical and histologic remission after a trial of PPIs.
Data source: Meta-analysis of 33 studies of 619 patients with symptomatic esophageal eosinophilia indicative of eosinophilic esophagitis.
Disclosures: The authors reported no funding sources and had no disclosures.
