BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-mediated eosinophilic inflammatory disease isolated to the esophagus. As a clinicopathologic disorder, a diagnosis of EoE requires a constellation of clinical symptoms of esophageal dysfunction and histologic findings (at least 15 eosinophils/high-powered microscope field (eos/hpf)). Current guidelines no longer require the failure of response to proton pump inhibitor medications to establish a diagnosis of EoE, but continue to suggest the exclusion of other etiologies of esophageal eosinophilia. The treatment goals for EoE are improvement in clinical symptoms, resolution of esophageal eosinophilia and other histologic abnormalities, endoscopic improvement, improved quality of life, improved esophageal function, minimized adverse effects of treatment, and prevention of disease progression and subsequent complications. Currently, there is no cure for EoE, making long-term treatment necessary. Standard treatment modalities include dietary modifications, esophageal dilation, and pharmacologic therapy. Effective pharmacologic therapies include corticosteroids, rapidly emerging biological therapies, and proton pump inhibitor medications.
OBJECTIVES: To evaluate the efficacy and safety of medical interventions for people with eosinophilic esophagitis.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP to 3 March 2023.
SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing any medical intervention or food elimination diet for the treatment of eosinophilic esophagitis, either alone or in combination, to any other intervention (including placebo).
DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected studies and conducted data extraction and risk of bias assessment. We expressed outcomes as a risk ratio (RR) and as the mean or standardized mean difference (MD/SMD) with 95% confidence interval (CI). We assessed the certainty of the evidence using GRADE. Our primary outcomes were: clinical, histological, and endoscopic improvement, and withdrawals due to adverse events. Secondary outcomes were: serious and total adverse events, and quality of life.
MAIN RESULTS: We included 41 RCTs with 3253 participants. Eleven studies included pediatric patients while the rest recruited both children and adults. Four studies were in patients with inactive disease while the rest were in patients with active disease. We identified 19 intervention comparisons. In this abstract we present the results of the primary outcomes for the two main comparisons: corticosteroids versus placebo and biologics versus placebo, based on the prespecified outcomes defined of the primary studies. Fourteen studies compared corticosteroids to placebo for induction of remission and the risk of bias for these studies was mostly low. Corticosteroids may lead to slightly better clinical improvement (20% higher), measured dichotomously (risk ratio (RR) 1.74, 95% CI 1.08 to 2.80; 6 studies, 583 participants; number needed to treat for an additional beneficial outcome (NNTB) = 4; low certainty), and may lead to slightly better clinical improvement, measured continuously (standard mean difference (SMD) 0.51, 95% CI 0.17 to 0.85; 5 studies, 475 participants; low certainty). Corticosteroids lead to a large histological improvement (63% higher), measured dichotomously (RR 11.94, 95% CI 6.56 to 21.75; 12 studies, 978 participants; NNTB = 3; high certainty), and may lead to histological improvement, measured continuously (SMD 1.42, 95% CI 1.02 to 1.82; 5 studies, 449 participants; low certainty). Corticosteroids may lead to little to no endoscopic improvement, measured dichotomously (RR 2.60, 95% CI 0.82 to 8.19; 5 studies, 596 participants; low certainty), and may lead to endoscopic improvement, measured continuously (SMD 1.33, 95% CI 0.59 to 2.08; 5 studies, 596 participants; low certainty). Corticosteroids may lead to slightly fewer withdrawals due to adverse events (RR 0.64, 95% CI 0.43 to 0.96; 14 studies, 1032 participants; low certainty). Nine studies compared biologics to placebo for induction of remission. Biologics may result in little to no difference in clinical improvement, measured dichotomously (RR 1.14, 95% CI 0.85 to 1.52; 5 studies, 410 participants; low certainty), and may result in better clinical improvement, measured continuously (SMD 0.50, 95% CI 0.22 to 0.78; 7 studies, 387 participants; moderate certainty). Biologics result in better histological improvement (55% higher), measured dichotomously (RR 6.73, 95% CI 2.58 to 17.52; 8 studies, 925 participants; NNTB = 2; moderate certainty). We could not draw conclusions for this outcome when measured continuously (SMD 1.01, 95% CI 0.36 to 1.66; 6 studies, 370 participants; very low certainty). Biologics may result in little to no difference in endoscopic improvement, measured dichotomously (effect not estimable, low certainty). We cannot draw conclusions for this outcome when measured continuously (SMD 2.79, 95% CI 0.36 to 5.22; 1 study, 11 participants; very low certainty). There may be no difference in withdrawals due to adverse events (RR 1.55, 95% CI 0.88 to 2.74; 8 studies, 792 participants; low certainty).
AUTHORS' CONCLUSIONS: Corticosteroids (as compared to placebo) may lead to clinical symptom improvement when reported both as dichotomous and continuous outcomes, from the primary study definitions. Corticosteroids lead to a large increase in histological improvement (dichotomous outcome) and may increase histological improvement (continuous outcome) when compared to placebo. Corticosteroids may or may not increase endoscopic improvement (depending on whether the outcome is measured dichotomously or continuously). Withdrawals due to adverse events (dichotomous outcome) may occur less frequently when corticosteroids are compared to placebo. Biologics (as compared to placebo) may not lead to clinical symptom improvement when reported as a dichotomous outcome and may lead to an increase in clinical symptom improvement (as a continuous outcome), from the primary study definitions. Biologics lead to a large increase in histological improvement when reported as a dichotomous outcome, but this is uncertain when reported as a continuous outcome, as compared to placebo. Biologics may not increase endoscopic improvement (dichotomous outcome), but this is uncertain when measured as a continuous outcome. Withdrawals due to adverse events as a dichotomous outcome may occur as frequently when biologics are compared to placebo.
Antecedentes: Los cursos largos de corticosteroides orales se usan comúnmente en niños en el manejo de condiciones crónicas. Se sabe que se producen varias reacciones adversas a los medicamentos (ADR) con su uso. Esta revisión sistemática tuvo como objetivo identificar las ADR más comunes y graves y determinar sus niveles de riesgo relativo. Se realizó una búsqueda bibliográfica de Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Biblioteca Cochrane y PubMed sin restricciones de lenguaje para identificar estudios en los que se administraron corticosteroides orales a pacientes de 28 días a 18 años de edad por lo menos 15 Días de tratamiento. Cada base de datos se realizó una búsqueda desde sus fechas más tempranas hasta enero de 2016. Todos los estudios que proporcionaron información clara sobre ADRs fueron incluidos. RESULTADOS: Cien y un estudios que incluyeron 33 estudios prospectivos de cohortes; 21 ensayos controlados aleatorios; 21 series de casos y 26 informes de casos cumplieron los criterios de inclusión. Éstos involucraron a 6817 niños y reportaron 4321 ADRs. Los tres ADR experimentados por el mayor número de pacientes fueron el aumento de peso, el retraso del crecimiento y características de Cushingoid con las tasas de incidencia respectivas de 21,1%, 18,1% y 19,4% de los pacientes evaluados para estas ADR. 21,5% de los pacientes medidos mostraron disminución de la densidad ósea y 0,8% de los pacientes mostraron osteoporosis. La supresión bioquímica del eje HPA se detectó en 269 de 487 pacientes en los que se midió. La infección fue la ADR más grave, con veintiuna muertes. El varicela zóster fue la infección más frecuente (9 muertes). CONCLUSIONES: El aumento de peso, el retraso del crecimiento y las características de Cushingoid fueron las ADR más frecuentes observadas cuando se administraron corticosteroides orales a largo plazo a los niños. La mayor susceptibilidad a la infección fue la ADR más grave.
OBJETIVO: La esofagitis eosinofílica (EoE) se asocia con una morbilidad significativa en niños. Las estrategias para optimizar sus resultados son, por lo tanto, esenciales. Nuestro objetivo fue revisar las estrategias para el manejo médico de EoE en niños. MÉTODOS: Se realizó una revisión sistemática (SR) de ensayos controlados aleatorios (ECA) de intervenciones médicas en niños con EoE, utilizando la metodología Cochrane. Las bases de datos incluidas PubMed, EMBASE, CINAHL, Cochrane Central Library y Google scholar fueron investigadas hasta marzo de 2016. Los resultados primarios incluyeron histológicos (conteo de eosinófilos máximo) y remisión sintomática. Los resultados secundarios fueron la mejoría en los parámetros endoscópicos y otros parámetros histológicos y los efectos adversos. Resultados Se incluyó un total de 5 ECA (N = 448) con riesgo de sesgo bajo o poco claro. Las intervenciones incluyeron esteroides orales tópicos, esteroides entéricos tragados y agente anti-IL5. La agrupación de datos de todos los ensayos no fue posible debido a la heterogeneidad significativa en las intervenciones. El metanálisis de los datos (N = 141) de tres ECA (Budesonida viscosa oral: 2, Fluticasona: 1) mostró una remisión histológica significativa en la intervención frente a los participantes del grupo de control [RR: 10,32 (intervalo de confianza del 95%: 3,04, 35,03) ; P = 0.0002], Nivel de evidencia - bajo. En comparación con el agente anti-IL5, los ensayos que evaluaron los esteroides informaron altas tasas de remisión clínica. La remisión clínica no se correlacionó con la mejoría histológica en ningún ensayo. Con excepción de los corticosteroides sistémicos, no hubo efectos adversos significativos relacionados con otras intervenciones. CONCLUSIÓN: Existe poca evidencia de baja calidad sobre los efectos de diversas intervenciones en niños con EoE. Los efectos beneficiosos de los esteroides tragados deben ser confirmados en grandes ECA bien diseñados.
AIM: La esofagitis eosinofílica (EOE) es un trastorno del esófago caracterizado por endoscópica distintivo y características histológicas. El tratamiento óptimo para EOE no se ha definido. Una revisión sistemática y meta-análisis se llevaron a cabo para aclarar la ventaja de la terapia de esteroides para EOE.
MÉTODOS: PubMed, EMBASE, Medline, ISI Wed de la Ciencia y la Base de Datos Cochrane de Revisiones Sistemáticas Se realizaron búsquedas para obtener ensayos controlados aleatorios pertinentes (ECA) con la comparación de los esteroides y terapia no-esteroides, y los juicios retrospectivos y prospectivos sobre la terapia de esteroides EOE hasta marzo de 2013. RevMan 5.2 se utilizó para el análisis.
RESULTADOS: Seis ECA cumplieron los criterios de inclusión para el metanálisis, con 193 sujetos incluidos; Y otros 2 ECA, 3 prospectivo y 5 ensayos retrospectivos cumplen los criterios de revisión sistemática. Meta-análisis mostró esteroides tópicos disminuyeron significativamente la media y eosinófilos esofágicos pico (FOE) contar en comparación con la terapia no esteroideos (MDmean = -23,41, 95% CImean -42.08~ -4,73, P = 0,01 y MDpeak = -51,27, 95 % CIpeak -78.62~ -23,92; p = 0,0002). El deceso de eos media fue más pronunciada en el grupo de adultos y cuando los esteroides en comparación con el grupo placebo (P = 0,02 y P = 0,002, respectivamente). Y la disminución del recuento de pico eos mantuvo independiente significativo de la edad del paciente, tipo de esteroides (p <0,05). Hubo 14 ensayos que muestran la eficacia de los esteroides en la disminución de recuento eos, 10 ensayos muestran una mejoría de los síntomas, y 5 ensayos muestran una mejoría endoscópica. Sólo se reportaron efectos adversos leves de esteroides tópicos.
CONCLUSIONES: Los esteroides fueron eficaces en la disminución de la media y / o recuento pico eos para EOE. Su valor de la mejora de los síntomas y los cambios endoscópicos aún no se determinó debido a la falta de criterios unificados.
ANTECEDENTES: La esofagitis eosinofílica (EOE) es una causa creciente de disfagia. Las terapias actuales incluyen la manipulación de la dieta, los esteroides y las drogas biológicas.
Objetivo: realizar una revisión sistemática y resumir el efecto de diferentes intervenciones médicas en EOE.
MÉTODOS: Dos revisores buscaron Pubmed y Embase para los estudios sobre el tratamiento para la EE. Se incluyeron ensayos controlados aleatorios (ECA) se limitan a las intervenciones farmacológicas. Dos revisores seleccionaron los estudios. El metanálisis se realizó utilizando el modelo de efectos aleatorios para calcular odds ratio (OR). La heterogeneidad se determina por Q estadística de Cochran y yo (2).
RESULTADOS: Diecisiete referencias cumplieron los criterios de inclusión. Once ECA con 455 participantes fueron incluidos en el meta-análisis. 325 participantes fueron evaluados para la mejoría sintomática y 330 fueron evaluados para la remisión histológica. Se observó una mejoría sintomática con esteroides tópicos (7 estudios, 250 participantes) en comparación con el grupo control (placebo o PPI) (OR: 3,03; intervalo de confianza del 95%, IC: 1,57 a 5,87). Remisión histológica También se observó en nueve estudios con 330 participantes (OR: 13,66 CI, 95%: 2,65 a 70,34) que compararon los esteroides tópicos a un control (placebo o PPI). No hubo diferencias entre los anti-IL-5 drogas y el placebo en cuanto a la mejoría sintomática (OR: 0,69 IC del 95%: 0,34 a 1,42).
CONCLUSIÓN: Los esteroides tópicos inducir la remisión sintomática e histológica significativa, y debe ser considerada como un tratamiento de primera línea. Anti-IL-5 terapia tiene un efecto menor en la esofagitis eosinofílica. La investigación futura en la esofagitis eosinofílica debe estandarizar la metodología de acuerdo con las directrices publicadas para mejorar la calidad y permitir la comparación directa entre las terapias.
Eosinophilic esophagitis (EoE) is a chronic antigen-mediated eosinophilic inflammatory disease isolated to the esophagus. As a clinicopathologic disorder, a diagnosis of EoE requires a constellation of clinical symptoms of esophageal dysfunction and histologic findings (at least 15 eosinophils/high-powered microscope field (eos/hpf)). Current guidelines no longer require the failure of response to proton pump inhibitor medications to establish a diagnosis of EoE, but continue to suggest the exclusion of other etiologies of esophageal eosinophilia. The treatment goals for EoE are improvement in clinical symptoms, resolution of esophageal eosinophilia and other histologic abnormalities, endoscopic improvement, improved quality of life, improved esophageal function, minimized adverse effects of treatment, and prevention of disease progression and subsequent complications. Currently, there is no cure for EoE, making long-term treatment necessary. Standard treatment modalities include dietary modifications, esophageal dilation, and pharmacologic therapy. Effective pharmacologic therapies include corticosteroids, rapidly emerging biological therapies, and proton pump inhibitor medications.
OBJECTIVES:
To evaluate the efficacy and safety of medical interventions for people with eosinophilic esophagitis.
SEARCH METHODS:
We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP to 3 March 2023.
SELECTION CRITERIA:
Randomized controlled trials (RCTs) comparing any medical intervention or food elimination diet for the treatment of eosinophilic esophagitis, either alone or in combination, to any other intervention (including placebo).
DATA COLLECTION AND ANALYSIS:
Pairs of review authors independently selected studies and conducted data extraction and risk of bias assessment. We expressed outcomes as a risk ratio (RR) and as the mean or standardized mean difference (MD/SMD) with 95% confidence interval (CI). We assessed the certainty of the evidence using GRADE. Our primary outcomes were: clinical, histological, and endoscopic improvement, and withdrawals due to adverse events. Secondary outcomes were: serious and total adverse events, and quality of life.
MAIN RESULTS:
We included 41 RCTs with 3253 participants. Eleven studies included pediatric patients while the rest recruited both children and adults. Four studies were in patients with inactive disease while the rest were in patients with active disease. We identified 19 intervention comparisons. In this abstract we present the results of the primary outcomes for the two main comparisons: corticosteroids versus placebo and biologics versus placebo, based on the prespecified outcomes defined of the primary studies. Fourteen studies compared corticosteroids to placebo for induction of remission and the risk of bias for these studies was mostly low. Corticosteroids may lead to slightly better clinical improvement (20% higher), measured dichotomously (risk ratio (RR) 1.74, 95% CI 1.08 to 2.80; 6 studies, 583 participants; number needed to treat for an additional beneficial outcome (NNTB) = 4; low certainty), and may lead to slightly better clinical improvement, measured continuously (standard mean difference (SMD) 0.51, 95% CI 0.17 to 0.85; 5 studies, 475 participants; low certainty). Corticosteroids lead to a large histological improvement (63% higher), measured dichotomously (RR 11.94, 95% CI 6.56 to 21.75; 12 studies, 978 participants; NNTB = 3; high certainty), and may lead to histological improvement, measured continuously (SMD 1.42, 95% CI 1.02 to 1.82; 5 studies, 449 participants; low certainty). Corticosteroids may lead to little to no endoscopic improvement, measured dichotomously (RR 2.60, 95% CI 0.82 to 8.19; 5 studies, 596 participants; low certainty), and may lead to endoscopic improvement, measured continuously (SMD 1.33, 95% CI 0.59 to 2.08; 5 studies, 596 participants; low certainty). Corticosteroids may lead to slightly fewer withdrawals due to adverse events (RR 0.64, 95% CI 0.43 to 0.96; 14 studies, 1032 participants; low certainty). Nine studies compared biologics to placebo for induction of remission. Biologics may result in little to no difference in clinical improvement, measured dichotomously (RR 1.14, 95% CI 0.85 to 1.52; 5 studies, 410 participants; low certainty), and may result in better clinical improvement, measured continuously (SMD 0.50, 95% CI 0.22 to 0.78; 7 studies, 387 participants; moderate certainty). Biologics result in better histological improvement (55% higher), measured dichotomously (RR 6.73, 95% CI 2.58 to 17.52; 8 studies, 925 participants; NNTB = 2; moderate certainty). We could not draw conclusions for this outcome when measured continuously (SMD 1.01, 95% CI 0.36 to 1.66; 6 studies, 370 participants; very low certainty). Biologics may result in little to no difference in endoscopic improvement, measured dichotomously (effect not estimable, low certainty). We cannot draw conclusions for this outcome when measured continuously (SMD 2.79, 95% CI 0.36 to 5.22; 1 study, 11 participants; very low certainty). There may be no difference in withdrawals due to adverse events (RR 1.55, 95% CI 0.88 to 2.74; 8 studies, 792 participants; low certainty).
AUTHORS' CONCLUSIONS:
Corticosteroids (as compared to placebo) may lead to clinical symptom improvement when reported both as dichotomous and continuous outcomes, from the primary study definitions. Corticosteroids lead to a large increase in histological improvement (dichotomous outcome) and may increase histological improvement (continuous outcome) when compared to placebo. Corticosteroids may or may not increase endoscopic improvement (depending on whether the outcome is measured dichotomously or continuously). Withdrawals due to adverse events (dichotomous outcome) may occur less frequently when corticosteroids are compared to placebo. Biologics (as compared to placebo) may not lead to clinical symptom improvement when reported as a dichotomous outcome and may lead to an increase in clinical symptom improvement (as a continuous outcome), from the primary study definitions. Biologics lead to a large increase in histological improvement when reported as a dichotomous outcome, but this is uncertain when reported as a continuous outcome, as compared to placebo. Biologics may not increase endoscopic improvement (dichotomous outcome), but this is uncertain when measured as a continuous outcome. Withdrawals due to adverse events as a dichotomous outcome may occur as frequently when biologics are compared to placebo.
