BACKGROUND: Collagenous colitis is a cause of chronic diarrhea. This updated review was performed to identify therapies for collagenous colitis that have been assessed in randomized controlled trials (RCTs).
OBJECTIVES: The primary objective was to assess the benefits and harms of treatments for collagenous colitis.
SEARCH METHODS: We searched CENTRAL, the Cochrane IBD Group Specialized Register, MEDLINE and EMBASE from inception to 7 November 2016.
SELECTION CRITERIA: We included RCTs comparing a therapy with placebo or active comparator for the treatment of active or quiescent collagenous colitis.
DATA COLLECTION AND ANALYSIS: Data were independently extracted by two authors. The primary outcome was clinical response or maintenance of response as defined by the included studies. Secondary outcome measures included histological response, quality of life and the occurrence of adverse events. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The Cochrane risk of bias tool was used to assess bias. The overall quality of the evidence was assessed using the GRADE criteria.
MAIN RESULTS: Twelve RCTs (476 participants) were included. These studies assessed bismuth subsalicylate, Boswellia serrata extract, mesalamine, cholestyramine, probiotics, prednisolone and budesonide therapy. Four studies were low risk of bias. One study assessing mesalamine and cholestyramine was judged to be high risk of bias due to no blinding. The other studies had an unclear risk of bias for random sequence generation (five studies) allocation concealment (six studies), blinding (one study), incomplete outcome data (one study) and selective outcome reporting (one study). Clinical response occurred in 100% (4/4) of patients who received bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks) compared to 0% (0/5) of patients who received placebo (1 study; 9 participants; RR 10.80, 95% CI 0.75 to 155.93; GRADE = very low). Clinical response occurred in 44% (7/16) of patients who received Boswellia serrata extract (three 400 mg/day capsules for 8 weeks) compared to 27% (4/15) of patients who received placebo (1 study; 31 participants; RR 1.64, 95% CI 0.60 to 4.49; GRADE = low). Clinical response occurred in 80% (24/30) of budesonide patients compared to 44% (11/25) of mesalamine patients (1 study; 55 participants; RR 1.82, 95% CI 1.13 to 2.93; GRADE = low). Histological response was observed in 87% (26/30) of budesonide patients compared to 44% (11/25) of mesalamine patients (1 study, 55 participants; RR 1.97, 95% CI 1.24 to 3.13; GRADE = low). There was no difference between the two treatments with respect to adverse events (RR 0.69, 95% CI 0.43 to 1.10; GRADE = low), withdrawals due to adverse events (RR 0.09, 95% CI 0.01 to 1.65; GRADE = low) and serious adverse events (RR 0.12, 95% CI 0.01 to 2.21; GRADE = low). Clinical response occurred in 44% (11/25) of mesalamine patients (3 g/day) compared to 59% (22/37) of placebo patients (1 study; 62 participants; RR 0.74, 95% CI 0.44 to 1.24; GRADE = low). Histological response was observed in 44% (11/25) and 51% (19/37) of patients receiving mesalamine and placebo, respectively (1 study; 62 participants; RR 0.86, 95% CI 0.50 to 1.47; GRADE = low). There was no difference between the two treatments with respect to adverse events (RR 1.26, 95% CI 0.84 to 1.88; GRADE = low), withdrawals due to adverse events (RR 5.92, 95% CI 0.70 to 49.90; GRADE = low) and serious adverse events (RR 4.44, 95% CI 0.49 to 40.29; GRADE = low). Clinical response occurred in 63% (5/8) of prednisolone (50 mg/day for 2 weeks) patients compared to 0% (0/3) of placebo patients (1 study, 11 participants; RR 4.89, 95% CI 0.35 to 68.83; GRADE = very low). Clinical response occurred in 29% (6/21) of patients who received probiotics (2 capsules containing 0.5 x 10(10) CFU each of L. acidophilus LA-5 and B. animalis subsp. lactis strain BB-12 twice daily for 12 weeks) compared to 13% (1/8) of placebo patients (1 study, 29 participants, RR 2.29, 95% CI 0.32 to 16.13; GRADE = very low). Clinical response occurred in 73% (8/11) of patients who received mesalamine (800 mg three times daily) compared to 100% (12/12) of patients who received mesalamine + cholestyramine (4 g daily) (1 study, 23 participants; RR 0.74, 95% CI 0.50 to 1.08; GRADE = very low). Clinical response occurred in 81% (38/47) of patients who received budesonide (9 mg daily in a tapering schedule for 6 to 8 weeks) compared to 17% (8/47) of placebo patients (3 studies; 94 participants; RR 4.56, 95% CI 2.43 to 8.55; GRADE = low). Histological response was higher in budesonide participants (72%, 34/47) compared to placebo (17%, 8/47) (RR 4.15, 95% CI 2.25 to 7.66; GRADE = low). Clinical response was maintained in 68% (57/84) of budesonide patients compared to 20% (18/88) of placebo patients (3 studies, 172 participants, RR 3.30 95% CI 2.13 to 5.09; GRADE = low). Histological response was maintained in 48% (19/40) of budesonide patients compared to 15% (6/40) of placebo patients (2 studies; 80 participants; RR 3.17, 95% CI 1.44 to 6.95; GRADE = very low). No difference was found between budesonide and placebo for adverse events (5 studies; 290 participants; RR 1.18, o95% CI 0.92 to 1.51; GRADE = low), withdrawals due to adverse events (5 studies, 290 participants; RR 0.97, 95% CI 0.43 to 2.17; GRADE = very low) or serious adverse events (4 studies, 175 participants; RR 1.11, 95% CI 0.15 to 8.01; GRADE = very low). Adverse effects reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, excessive sweating and headache. Adverse effects reported in the mesalamine studies included nausea and skin rash. Adverse effects in the prednisolone study included abdominal pain, headache, sleep disturbance, mood change and weight gain.
AUTHORS' CONCLUSIONS: Low quality evidence suggests that budesonide may be effective for inducing and maintaining clinical and histological response in patients with collagenous colitis. We are uncertain about the benefits and harms of therapy with bismuth subsalicylate, Boswellia serrata extract, mesalamine with or without cholestramine, prednisolone and probiotics. These agents and other therapies require further study.
Objetivos: Realizar una revisión sistemática para determinar los tratamientos eficaces para los pacientes con colitis colágena y la colitis linfocítica, los dos subtipos de colitis microscópica.
MÉTODOS: documentos pertinentes fueron identificados a través del MEDLINE, PubMed, Cochrane Collaboration y bases de datos, búsquedas manuales de las referencias de los artículos identificados y artículos de revisión sobre colitis microscópica, así como búsquedas de resúmenes de los principales congresos de gastroenterología.
RESULTADOS: Todos los estudios que evalúan el tratamiento de la colitis microscópica tuvieron tamaños de muestra relativamente pequeños. Un total de 10 ensayos aleatorios que incluyeron a pacientes con colitis colágena. La budesonida se estudió para la inducción de la respuesta en tres ensayos y para el mantenimiento de la respuesta en dos ensayos. El odds-ratio combinado para inducir una respuesta clínica con budesonida fue 12,32 (intervalo de confianza 95%, IC 5.53-27.46), y para mantener la respuesta clínica fue de 8,82 (IC 95%: 3,19 a 24,37), con un número necesario a tratar (NNT) de 2 pacientes para cada resultado. Budesonida también induce y mantiene la respuesta histológica y fue bien tolerado. El subsalicilato de bismuto, prednisolona y mesalamina con o sin colestiramina puede ser eficaz, mientras que el extracto de Boswellia serrata y los probióticos eran ineficaces para el tratamiento de la colitis colágena. Tres ensayos clínicos aleatorizados incluyeron pacientes con colitis linfocítica. La budesonida se demostró en un estudio para ser eficaz para inducir una respuesta clínica (OR 9.00, IC 95% 1.98 a 40.93), con un NNT de tres pacientes. La budesonida también indujo la respuesta histológica y fue bien tolerado. El subsalicilato de bismuto y la mesalamina con o sin colestiramina puede ser eficaz para tratar la colitis linfocítica. No hay ensayos evaluaron el mantenimiento de la respuesta en pacientes con colitis linfocítica.
CONCLUSIONES: La budesonida es eficaz y bien tolerado para inducir y mantener la respuesta clínica e histológica en pacientes con colitis colágena, y para inducir una respuesta clínica e histológica en pacientes con colitis linfocítica. La determinación de la magnitud del beneficio está limitado por los pequeños tamaños de muestra de los estudios. La evidencia de otros agentes, incluyendo el subsalicilato de bismuto, la prednisolona, el extracto de B. serrata, los probióticos, y mesalamina con o sin colestiramina es más débil. No está claro que cualquiera de estos agentes de inducir o mantener la remisión real de la colitis colágena o linfocítica, en contraposición a la respuesta clínica o histológica.
Objetivos: Realizar una revisión sistemática para determinar los tratamientos eficaces para pacientes con colitis colagenosa clínicamente activa.
MÉTODOS: los artículos relevantes fueron identificados a través del MEDLINE, PubMed, Cochrane Collaboration y bases de datos, búsquedas manuales de las referencias de los artículos identificados y artículos de revisión sobre colitis colágena o microscópica, así como las búsquedas de los resúmenes de los principales congresos de gastroenterología.
RESULTADOS: Cinco ensayos aleatorios que evaluaban los tratamientos para la colitis colágena se identificaron. Un ensayo estudió el subsalicilato de bismuto (nueve comprimidos de 262 mg al día durante 8 semanas) incluyeron 9 pacientes. Los pacientes que recibieron la preparación de bismuto eran más propensos a tener clínica (p = 0,003) e histológicos (p = 0,003) la mejora que los que recibieron placebo. En un ensayo que comparaba prednisolona (50 mg al día durante 2 semanas) con un placebo en 11 pacientes, una tendencia hacia la respuesta clínica en pacientes con prednisona se informó (p = 0,064). El efecto de la prednisolona en la mejora histológica no fue estudiado. Un total de 94 pacientes fueron incluidos en tres ensayos que estudiaron la budesonida (9 mg al día o en un programa de reducción durante 6-8 semanas). El odds ratio agrupado para la respuesta clínica al tratamiento con budesonida fue de 12,32 (IC 95%: 5.53-27.46). El NNT (número necesario de pacientes a tratar con budesonida para lograr una mejora de los pacientes) fue de 2 pacientes. Esta terapia fue bien tolerada. Hubo una mejora significativa con el tratamiento histológico en los tres ensayos que estudian la terapia con budesonida.
CONCLUSIONES: Existe una fuerte evidencia de que la budesonida es eficaz y bien tolerado para el tratamiento de la colitis colágena. La evidencia de los beneficios del subsalicilato de bismuto o prednisolona es más débil. No está claro que cualquiera de estos agentes producen remisión real, en oposición a la mejoría clínica e histológica de la enfermedad.
Antecedentes: la colitis colágena se caracteriza por diarrea acuosa crónica y alteraciones histológicas características de la mucosa del colon sin alteraciones endoscópicas. La budesonida, un corticosteroide con un alto metabolismo de primer paso ha sido examinado en la colitis colágena, pero los estudios realizados hasta la fecha han tenido un pequeño número, y el poder estadístico relativamente bajo.
AIM: Un meta-análisis de ensayos publicados existentes se llevó a cabo para evaluar el efecto del tratamiento con budesonida en la colitis colágena.
MÉTODOS: Todas las fuentes bibliográficas pertinentes en busca de informes publicados en Inglés de uso de budesonida en la colitis colágena. MEDLINE y EMBASE fueron revisados, así como las bibliografías de los artículos publicados y los resúmenes disponibles de congresos pertinentes. La literatura que se reunía los criterios predeterminados fue seleccionado para el meta-análisis.
Resultados: Se incluyeron tres ensayos en el meta-análisis. La budesonida redujo significativamente la frecuencia de deposiciones (budesonida frente a placebo OR: 20,1, IC 95%: 7,0-57,5, p <0,0001). En general, el tratamiento con budesonida fue bien tolerado.
CONCLUSIONES: La budesonida es clínicamente eficaz a corto plazo en la colitis colágena, y parece ser relativamente bien tolerada. Los médicos pueden considerar este fármaco como una opción razonable para los pacientes con este trastorno.
Collagenous colitis is a cause of chronic diarrhea. This updated review was performed to identify therapies for collagenous colitis that have been assessed in randomized controlled trials (RCTs).
OBJECTIVES:
The primary objective was to assess the benefits and harms of treatments for collagenous colitis.
SEARCH METHODS:
We searched CENTRAL, the Cochrane IBD Group Specialized Register, MEDLINE and EMBASE from inception to 7 November 2016.
SELECTION CRITERIA:
We included RCTs comparing a therapy with placebo or active comparator for the treatment of active or quiescent collagenous colitis.
DATA COLLECTION AND ANALYSIS:
Data were independently extracted by two authors. The primary outcome was clinical response or maintenance of response as defined by the included studies. Secondary outcome measures included histological response, quality of life and the occurrence of adverse events. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The Cochrane risk of bias tool was used to assess bias. The overall quality of the evidence was assessed using the GRADE criteria.
MAIN RESULTS:
Twelve RCTs (476 participants) were included. These studies assessed bismuth subsalicylate, Boswellia serrata extract, mesalamine, cholestyramine, probiotics, prednisolone and budesonide therapy. Four studies were low risk of bias. One study assessing mesalamine and cholestyramine was judged to be high risk of bias due to no blinding. The other studies had an unclear risk of bias for random sequence generation (five studies) allocation concealment (six studies), blinding (one study), incomplete outcome data (one study) and selective outcome reporting (one study). Clinical response occurred in 100% (4/4) of patients who received bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks) compared to 0% (0/5) of patients who received placebo (1 study; 9 participants; RR 10.80, 95% CI 0.75 to 155.93; GRADE = very low). Clinical response occurred in 44% (7/16) of patients who received Boswellia serrata extract (three 400 mg/day capsules for 8 weeks) compared to 27% (4/15) of patients who received placebo (1 study; 31 participants; RR 1.64, 95% CI 0.60 to 4.49; GRADE = low). Clinical response occurred in 80% (24/30) of budesonide patients compared to 44% (11/25) of mesalamine patients (1 study; 55 participants; RR 1.82, 95% CI 1.13 to 2.93; GRADE = low). Histological response was observed in 87% (26/30) of budesonide patients compared to 44% (11/25) of mesalamine patients (1 study, 55 participants; RR 1.97, 95% CI 1.24 to 3.13; GRADE = low). There was no difference between the two treatments with respect to adverse events (RR 0.69, 95% CI 0.43 to 1.10; GRADE = low), withdrawals due to adverse events (RR 0.09, 95% CI 0.01 to 1.65; GRADE = low) and serious adverse events (RR 0.12, 95% CI 0.01 to 2.21; GRADE = low). Clinical response occurred in 44% (11/25) of mesalamine patients (3 g/day) compared to 59% (22/37) of placebo patients (1 study; 62 participants; RR 0.74, 95% CI 0.44 to 1.24; GRADE = low). Histological response was observed in 44% (11/25) and 51% (19/37) of patients receiving mesalamine and placebo, respectively (1 study; 62 participants; RR 0.86, 95% CI 0.50 to 1.47; GRADE = low). There was no difference between the two treatments with respect to adverse events (RR 1.26, 95% CI 0.84 to 1.88; GRADE = low), withdrawals due to adverse events (RR 5.92, 95% CI 0.70 to 49.90; GRADE = low) and serious adverse events (RR 4.44, 95% CI 0.49 to 40.29; GRADE = low). Clinical response occurred in 63% (5/8) of prednisolone (50 mg/day for 2 weeks) patients compared to 0% (0/3) of placebo patients (1 study, 11 participants; RR 4.89, 95% CI 0.35 to 68.83; GRADE = very low). Clinical response occurred in 29% (6/21) of patients who received probiotics (2 capsules containing 0.5 x 10(10) CFU each of L. acidophilus LA-5 and B. animalis subsp. lactis strain BB-12 twice daily for 12 weeks) compared to 13% (1/8) of placebo patients (1 study, 29 participants, RR 2.29, 95% CI 0.32 to 16.13; GRADE = very low). Clinical response occurred in 73% (8/11) of patients who received mesalamine (800 mg three times daily) compared to 100% (12/12) of patients who received mesalamine + cholestyramine (4 g daily) (1 study, 23 participants; RR 0.74, 95% CI 0.50 to 1.08; GRADE = very low). Clinical response occurred in 81% (38/47) of patients who received budesonide (9 mg daily in a tapering schedule for 6 to 8 weeks) compared to 17% (8/47) of placebo patients (3 studies; 94 participants; RR 4.56, 95% CI 2.43 to 8.55; GRADE = low). Histological response was higher in budesonide participants (72%, 34/47) compared to placebo (17%, 8/47) (RR 4.15, 95% CI 2.25 to 7.66; GRADE = low). Clinical response was maintained in 68% (57/84) of budesonide patients compared to 20% (18/88) of placebo patients (3 studies, 172 participants, RR 3.30 95% CI 2.13 to 5.09; GRADE = low). Histological response was maintained in 48% (19/40) of budesonide patients compared to 15% (6/40) of placebo patients (2 studies; 80 participants; RR 3.17, 95% CI 1.44 to 6.95; GRADE = very low). No difference was found between budesonide and placebo for adverse events (5 studies; 290 participants; RR 1.18, o95% CI 0.92 to 1.51; GRADE = low), withdrawals due to adverse events (5 studies, 290 participants; RR 0.97, 95% CI 0.43 to 2.17; GRADE = very low) or serious adverse events (4 studies, 175 participants; RR 1.11, 95% CI 0.15 to 8.01; GRADE = very low). Adverse effects reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, excessive sweating and headache. Adverse effects reported in the mesalamine studies included nausea and skin rash. Adverse effects in the prednisolone study included abdominal pain, headache, sleep disturbance, mood change and weight gain.
AUTHORS' CONCLUSIONS:
Low quality evidence suggests that budesonide may be effective for inducing and maintaining clinical and histological response in patients with collagenous colitis. We are uncertain about the benefits and harms of therapy with bismuth subsalicylate, Boswellia serrata extract, mesalamine with or without cholestramine, prednisolone and probiotics. These agents and other therapies require further study.
Pregunta de la revisión sistemática»Revisión sistemática de intervenciones
