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.
ANTECEDENTES Y OBJETIVOS: La incidencia de la colitis microscópica y la carga de la enfermedad están aumentando, pero no se limita la información sistemática sobre el uso de corticosteroides convencionales y budesonida en la colitis microscópica. Se realizó una revisión sistemática y meta-análisis sobre la eficacia a corto y largo plazo de los corticosteroides en el tratamiento de la colitis microscópica.
MÉTODOS: Se incluyeron ensayos controlados aleatorios que cumplieron con los criterios de selección predeterminados fueron incluidos. Los artículos fueron identificados a través de MEDLINE, EMBASE, el Registro Cochrane Central de Ensayos Controlados, los procedimientos de los principales congresos de gastroenterología, y listas de referencias de ensayos y artículos de revisión.
RESULTADOS: Ocho ensayos aleatorios fueron identificados. Un total de 248 pacientes fueron aleatorizados para recibir placebo versus corticosteroide. La intervención fue budesonida en 7 pruebas y prednisolona en un juicio. La budesonida es significativamente más eficaz que el placebo a corto plazo la respuesta clínica (riesgo relativo [RR], 3,07; intervalo de confianza del 95% [IC], 2,06-4,57) y largo plazo, la respuesta clínica (RR 3,22, IC 95%, 1,05 -9,89). La prednisolona no era superior al placebo a corto plazo la respuesta clínica (RR 2,00, IC 95%, 0,38-10,58). Mejoría histológica fue visto con budesonida a corto y largo plazo (RR 3,76, IC 95%, 2,00-7,06, y RR, 2,50, IC 95%, 1,25-4,98, respectivamente). Síntoma recaída se produjo en el 46% -80% de los pacientes dentro de los 6 meses de la interrupción del tratamiento. La retirada debido a efectos adversos fue del 4,4% de los pacientes, sin diferencias entre los grupos de estudio (p = 0,55).
Conclusiones: El tratamiento tanto a corto como a largo plazo con budesonida es eficaz y bien tolerado para la colitis microscópica. Sin embargo, la tasa de recaída síntoma vez budesonida se interrumpe es alta. Se necesitan más estudios para determinar la duración óptima del tratamiento, la dosis y el procedimiento de retirada.
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.
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
