ANTECEDENTES:

La colitis ulcerosa (CU) se caracteriza por ser una enfermedad crónica con remisiones y exacerbaciones. Aproximadamente el 15% de los pacientes presentan un cuadro grave que requiere hospitalización en algún momento de la enfermedad. Estos pacientes generalmente se tratan con corticosteroides por vía intravenosa con una tasa de respuesta del 60%. Los pacientes que no responden al tratamiento con esteroides generalmente necesitan la extirpación quirúrgica del intestino grueso (proctocolectomía o colectomía con un "pouch" anal). Este procedimiento quirúrgico básicamente cura al paciente de la enfermedad, pero se asocia con algunas complicaciones como la "pouchitis".

EXISTEN ALGUNOS TRATAMIENTOS ALTERNATIVOS PARA LA COLITIS ULCEROSA GRAVE:

las medicaciones inmunosupresoras (como la azatioprina) presentan un inicio de acción lento y, por lo tanto, son ineficaces. No se ha demostrado que los antibióticos sean efectivos y los tratamientos biológicos como infliximab, están todavía bajo investigación. La introducción de la ciclosporina A (CsA) para el uso en los pacientes con colitis ulcerosa (CU) grave, proporcionan una alternativa a los pacientes que anteriormente sólo tenían como opción el procedimiento quirúrgico. La ciclosporina actúa principalmente mediante la inhibición de la función de los linfocitos T, la cual es esencial para la propagación de la inflamación. A diferencia de otros agentes inmunosupresores, la CsA no suprime la actividad de otras células hematopoyéticas, no causa supresión de la médula ósea y posee un inicio de acción rápido. El objetivo de esta revisión es evaluar de forma sistemática la efectividad y seguridad de la CsA para la CU grave.

OBJETIVOS:

El objetivo de esta revisión era evaluar la efectividad de la ciclosporina A para los pacientes con colitis ulcerosa grave.

ESTRATEGIA DE BÚSQUEDA:

Búsquedas electrónicas en The Cochrane Library (Número 1, 2004), EMBASE (1980-2004), y MEDLINE (1966-2004); búsquedas manuales de las referencias de los estudios identificados; se estableció contacto con el primer autor de cada ensayo incluido.

CRITERIOS DE SELECCIÓN:

Ensayos clínicos aleatorios que comparaban la ciclosporina A con placebo o ninguna intervención para obtener y mantener la remisión de la colitis ulcerosa idiopática.

RECOPILACIÓN Y ANÁLISIS DE DATOS:

Dos revisores evaluaron de forma independiente la calidad de los ensayos y extrajeron los datos de los ensayos incluidos. Los riesgos relativos (RR) se calcularon con intervalos de confianza (IC) del 95%. Los revisores asumieron un análisis por intención de tratar (intention-to-treat analysis) para las medidas de resultado.

RESULTADOS PRINCIPALES:

Se identificaron sólo dos ensayos controlados aleatorios que cumplieron con los criterios de inclusión Estos ensayos no se pudieron combinar para el análisis ya que presentaban grandes diferencias en el diseño y las poblaciones de pacientes. En el primer ensayo, a 11 pacientes se les administró ciclosporina por vía intravenosa (4 mg/kg) y nueve pacientes recibieron placebo. Dos de los 11 pacientes en el grupo de tratamiento no respondieron al tratamiento comparado con nueve de los nueve pacientes del grupo placebo (RR: 0,18; IC del 95%: 0,05 a 0,64) Sin embargo, a 3/11 y a 4/9, eventualmente, se les realizó una colectomía en los grupos de tratamiento y de placebo, respectivamente y el seguimiento fue inferior a un mes. En el segundo ensayo, 15 pacientes se trataron con ciclosporina por vía intravenosa y 15 con metilprednisolona por vía intravenosa. Cinco de 15 pacientes en el grupo de ciclosporina no respondieron al tratamiento, comparado con siete de 15 pacientes en el grupo de metilprednisolona (RR: 0,71; IC del 95%: 0,29 a 1,75). Luego de un año, siete de los nueve pacientes que respondieron en el grupo con ciclosporina todavía se encontraban en remisión, comparado con cuatro de ocho pacientes en el grupo de esteroides (p > 0,05) y la tasa de colectomía fue similar en ambos grupos. El tiempo medio para responder en el grupo de ciclosporina en los dos ensayos fue corto (siete días y 5,2 días). Estos resultados deben interpretarse con cuidado dado el número pequeño de ensayos y pacientes que se evaluaron con fines comparativos y el seguimiento limitado (algunas semanas en un ensayo y un año aproximadamente en el otro). La evaluación precisa acerca de la aparición de eventos adversos fue difícil ya que los ensayos describieron reacciones adversas diferentes, que cesaron luego de la interrupción de la ciclosporina. En los ensayos revisados no se encontraron pruebas de que la ciclosporina haya sido más efectiva que el tratamiento estándar para prevenir la colectomía, pero este efecto no se puede excluir dado el pequeño tamaño de la muestra de este resultado. Otras limitaciones de la presente investigación incluyen el escaso número de datos sobre la calidad de vida, costos y resultados a largo plazo del tratamiento de ciclosporina.

CONCLUSIONES DE LOS AUTORES:

Existen pruebas limitadas de que la ciclosporina sea más efectiva que el tratamiento estándar solo para la colitis ulcerosa grave. La respuesta relativamente rápida permite al uso a corto plazo de la ciclosporina, lo cual es potencialmente atractivo, pero el beneficio a largo plazo es incierto, al hacerse evidentes eventos adversos como la nefrotoxicidad inducida por ciclosporina. Se necesita investigación adicional sobre la calidad de vida, los costos y resultados a largo plazo para el tratamiento con ciclosporina en la colitis ulcerosa grave.

OBJECTIVE:

To assess the safety and feasibility of laparoscopic surgery for patients with ulcerative colitis.

METHODS:

A search of published studies in English between January 1992 and September 2005 was obtained, using the MEDLINE and PubMed databases and the Cochrane Central Register of Controlled Trials. Two independent assessors reviewed the studies using a standardized protocol. Where raw data, means and standard deviations were available, meta-analysis was performed using the Forest plot review. Studies where medians and ranges were presented were separately analysed.

RESULTS:

The duration of surgery for laparoscopic and open procedures were similar (weighted mean difference 62.92 min, P = 0.19). Patients were able to tolerate oral intake significantly earlier, with a weighted mean difference of 1.39 days (P = 0.002), but recovery of bowel function was similar (weighted mean difference 0.73 days, P = 0.36). The length of hospital stay was shorter for patients who had undergone laparoscopic surgery, with a weighted mean difference of 2.64 days (P = 0.003). The complication rate was higher in open colectomy, compared to laparoscopic colectomy (67.6%vs 39.7%, P = 0.005). For restorative proctocolectomy, complication rates were comparable between the laparoscopic and open groups (P = 0.25).

CONCLUSIONS:

The time taken to perform laparoscopic surgery is similar to open surgery. Patients are able to tolerate oral intake earlier, and have a shorter hospitalization. Laparoscopic colectomy was safer compared to the open procedure, but both were equally safe for patients who had restorative proctocolectomy. Thus, laparoscopic surgery for ulcerative colitis is both safe and feasible.

OBJECTIVE:

To evaluate the efficacy and safety of extended-release mesalamine granules in the maintenance of remission in ulcerative colitis (UC).

DATA SOURCES:

Literature was obtained through searches of MEDLINE (1990-June 2012) using the terms mesalamine granules, ulcerative colitis, Apriso, and Salofalk. Bibliographies from retrieved articles were searched for additional citations.

STUDY SELECTION AND DATA EXTRACTION:

All English-language articles reporting on use of extended-release mesalamine granules in humans identified through the search were evaluated and included.

DATA SYNTHESIS:

The preferred initial treatment for induction and maintenance of remission in mild to moderate UC is agents from the 5-aminosalicylate class (balsalazide, mesalamine, olsalazine, sulfasalazine). Mesalamine granules are available as an encapsulated product in the US and as a nonencapsulated formulation in Europe. Data evaluating encapsulated mesalamine granules for induction of remission are lacking; however, the European mesalamine granule formulation has been evaluated for induction of remission. Patients receiving mesalamine granules for induction achieved clinical and endoscopic remission more frequently than those receiving placebo. Two pivotal, randomized, double-blind, placebo-controlled, multicenter studies have evaluated encapsulated mesalamine granules for maintenance in 562 adults in remission from UC. In both studies, the proportion of patients who remained relapse-free at 6 months was higher for those receiving encapsulated mesalamine granules than placebo. Mesalamine granules are well tolerated, with headache, nausea, and upper respiratory infections being the most frequently reported adverse effects.

CONCLUSIONS:

Current evidence supports the use of extended-release mesalamine granules for maintenance of remission in mild to moderate UC. Further studies are necessary to examine the ideal dose and regimen of encapsulated mesalamine granules for induction of remission in UC.

BACKGROUND:

Corticosteroids are first-line therapy for induction of remission in ulcerative colitis. Although corticosteroids may improve symptoms, they have significant adverse effects. Steroids which act topically, with less systemic side-effects may be more desirable. Budesonide is a topically acting corticosteroid with extensive first pass hepatic metabolism. There are currently three formulations of budesonide: two standard formulations including a controlled-ileal release capsule and a pH-dependent capsule both designed to release the drug in the distal small intestine and right colon; and the newer Budesonide-MMX® capsule designed to release the drug throughout the entire colon.

OBJECTIVES:

The primary objective was to evaluate the efficacy and safety of oral budesonide for the induction of remission in ulcerative colitis.

SEARCH METHODS:

We searched MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD Group Specialised Register from inception to April 2015. We also searched reference lists of articles, conference proceedings and ClinicalTrials.gov.

SELECTION CRITERIA:

Randomised controlled trials comparing oral budesonide to placebo or another active therapy for induction of remission in ulcerative colitis were considered eligible. There were no exclusions based on patient age or the type, dose, duration or formulation of budesonide therapy.

DATA COLLECTION AND ANALYSIS:

Two independent investigators reviewed studies for eligibility, extracted data and assessed study quality. Methodological quality was assessed using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome was induction of remission (as defined by the primary studies) at week eight. Secondary outcomes included clinical, endoscopic and histologic improvement, adverse events and early withdrawal. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome and the mean difference (MD) and corresponding 95% CI for each continuous outcome. Data were analysed on an intention-to-treat basis.

MAIN RESULTS:

Six studies (1808 participants) were included. Four studies compared budesonide-MMX® with placebo, one small pilot study looked at clinical remission at week four, and was subsequently followed by three large, studies that assessed combined clinical and endoscopic remission at week eight. Although two placebo-controlled studies had mesalamine and Entocort (standard budesonide) treatment arms, these studies were not sufficiently powered to compare Budesonide-MMX® with these active comparators. One small study compared standard budesonide with prednisolone and one study compared standard budesonide to mesalamine. Four studies were rated as low risk of bias and two studies had an unclear risk of bias. A pooled analysis of three studies (900 participants) showed that budesonide-MMX® 9 mg was significantly superior to placebo for inducing remission (combined clinical and endoscopic remission) at 8 weeks. Fifteen per cent (71/462) of budesonide-MMX® 9 mg patients achieved remission compared to 7% (30/438) of placebo patients (RR 2.25, 95% CI 1.50 to 3.39). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was moderate due to sparse data (101 events). A subgroup analysis by concurrent mesalamine use suggests higher efficacy in the 442 patients who were not considered to be mesalamine-refractory (RR 2.89, 95% CI 1.59 to 5.25). A subgroup analysis by disease location suggests budesonide is most effective in patients with left-sided disease (RR 2.98, 95% CI 1.56 to 5.67; 289 patients). A small pilot study reported no statistically significant difference in endoscopic remission between budesonide and prednisolone (RR 0.75, 95% CI 0.23 to 2.42; 72 patients). GRADE indicated that the overall quality of the evidence supporting this outcome was very low due to unclear risk of bias and very sparse data (10 events). Standard oral budesonide was significantly less likely to induce clinical remission than oral mesalamine after 8 weeks of therapy (RR 0.72, 95% CI 0.57 to 0.91; 1 study, 343 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was moderate due to sparse data (161 events). Another study found no difference in remission rates between budesonide-MMX® 9 mg and mesalamine (RR 1.48, 95% CI 0.81 to 2.71; 247 patients). GRADE indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (37 events). One study found no difference in remission rates between budesonide-MMX® 9 mg and standard budesonide 9 mg (RR 1.38, 95% CI 0.72 to 2.65; 212 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (32 events). Suppression of plasma cortisol was more common in prednisolone-treated patients (RR 0.02, 95% CI 0.0 to 0.33). While budesonide does appear to suppress morning cortisol to some extent, mean morning cortisol values remained within the normal range in 2 large studies (n = 899) and there was no difference in glucocorticoid-related side-effects across different treatment groups. Further, study withdrawal due to adverse events was not more common in budesonide compared with placebo treated patients (RR 0.85, 95% CI 0.53 to 1.38). Common adverse events included worsening ulcerative colitis, headache, pyrexia, insomnia, back pain, nausea, abdominal pain, diarrhoea, flatulence and nasopharyngitis.

AUTHORS' CONCLUSIONS:

Moderate quality evidence to supports the use of oral budesonide-MMX® at a 9 mg daily dose for induction of remission in active ulcerative colitis, particularly in patients with left-sided colitis. Budesonide-MMX® 9 mg daily is effective for induction of remission in the presence or absence of concurrent 5-ASA therapy. Further, budesonide-MMX® appears to be safe, and does not lead to significant impairment of adrenocorticoid function compared to placebo. Moderate quality evidence from a single study suggests that mesalamine may be superior to standard budesonide for the treatment of active ulcerative colitis. Low quality evidence from one study found no difference in remission rates between budesonide MMX® and mesalamine. Very low quality evidence from one small study showed no difference in endoscopic remission rates between standard budesonide and prednisolone. Low quality evidence from one study showed no difference in remission rates between budesonide-MMX® and standard budesonide. Adequately powered studies are needed to allow conclusions regarding the comparative efficacy and safety of budesonide versus prednisolone, budesonide-MMX® versus standard budesonide and budesonide versus mesalamine.

BACKGROUND:

For patients with acute colitis, the decision when and how to operate is difficult in most cases. It was the aim of this systematic review to analyze early mortality and morbidity of colectomy for severe acute colitis in order to identify opportunities to improve perioperative treatment and outcome.

METHODS:

A systematic review of the available literature in the Medline and PubMed databases from 1975 to 2007 was performed. All articles were assessed methodologically; the articles of poor methodological quality were excluded. Articles on laparoscopic colectomy for acute colitis were analyzed separately.

RESULTS:

In total, 29 studies met the criteria for the systematic review, describing a total of 2,714 patients, 1,257 of whom were operated on in an acute setting, i.e., urgent or emergency colectomy. Reported in-hospital mortality was 8.0%; the 30-day mortality was 5.2%. Morbidity was 50.8%. The majority of complications were of infectious and thromboembolic nature. Over the last three decades, there was a shift in indications from toxic megacolon, from 71.1% in 1975-1984 to 21.6% in 1995-2005, to severe acute colitis not responding to conservative treatment, from 16.5% in 1975-1984 to 58.1% in 1995-2007. Mortality decreased from 10.0% to 1.8%. Morbidity remained high, exceeding 40% in the last decade. Mortality after laparoscopic surgery was 0.6%. Complication rate varies from 16-37%.

CONCLUSION:

Colectomy for acute colitis is complicated by considerable morbidity. The incidence of adverse outcome has substantially decreased over the last three decades, but further improvements are still required. The retrospective nature of the included studies allows for a considerable degree of selection bias that limits robust and clinically sound conclusions about both conventional and laparoscopic surgery.

Background: Low-dose methotrexate is a widely used and efficacious therapy in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. Prospective randomized controlled trials have demonstrated the efficacy of parenteral methotrexate in Crohn's disease (CD). We performed a systematic review of the efficacy of methotrexate in ulcerative colitis (UC) and discuss the results in the context of the known pharmacokinetics and adverse events of methotrexate therapy in inflammatory bowel diseases and other inflammatory conditions. Materials and Methods: We performed a systematic review of the literature in Medline, Embase, and Web of Science. All publications describing patients with UC treated with methotrexate were included. Results: We identified 12 studies or retrospective case series and 5 meeting abstracts that met the inclusion criteria. Only 1 study reported a prospective randomized placebo-controlled trial using methotrexate at a dose of 12.5 mg orally with no significant clinical benefit. However, the majority of uncontrolled retrospective analyses suggest a clinical response to methotrexate therapy in a range of 30%-80% when the drug is applied by parenteral route in doses between 20-25 mg. Conclusions: The only randomized controlled trial of methotrexate in UC employed oral dosing and doses lower than those shown to be effective in CD and did not demonstrate efficacy, whereas uncontrolled, retrospective studies using doses and routes of administration similar to those employed in CD suggest benefit. Well-designed, prospective, placebo-controlled trials of methotrexate in UC are needed. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

Ulcerative colitis (UC) is increasingly recognized as a disease affecting the elderly. Approximately 10%-30% of the UC population is over the age of 60 years. Additionally, younger patients with UC are aging and thus comprise a second group of elderly IBD patients. To date, there have been no clinical trials that have evaluated treatment efficacy of UC in the elderly population. The aim of our study was to conduct a systematic review of all randomized controlled trials (RCTs) addressing treatment outcome in UC; we also sought to identify the elderly population, defined as age 60 years or older, represented in these studies, to see if pooled data would lead to meaningful conclusions regarding treatment efficacy and safety profile in the elderly. A search of the MEDLINE database via PubMed and the EMBASE database via Scopus was performed to identify all RCTs evaluating medical therapy for UC in humans, published within the English language through September 2012. Studies were grouped into three categories: biological agent (BA) therapy; immunosuppressant (IS) therapy; and 5-aminosalicylic acid (5-ASA) therapy. To estimate the number of elderly patients in each study, mean age plus 1 and 2 standard deviations (SD) was calculated to find the closest approximation to age 60. Of 876 studies, 112 RCTs were included in the final analysis-20 studies for BA, 20 for IS, and 72 for 5-ASA agents. While nearly all studies reported either a mean or median age, only 38% additionally reported the SD and age range. The mean composite age was 39.2 years for the BA studies, 38.5 years for the IS studies, and 42.8 years for the 5-ASA studies, consistent with a young middle-aged patient. We estimated that no more than 16% of patients per study would have qualified as elderly, and in most cases a much smaller percentage (,8%). Additionally, there were no BA or IS RCTs that reported results by age subgroup analysis. Four studies in the 5-ASA group report age-specific analyses and showed no difference in treatment efficacy by age. None of the 112 RCTs reported age sub-analyses of safety, tolerability, adverse events, or withdrawal rates. There is insufficient evidence to evaluate efficacy of treatment and adverse events from treatment for UC in the elderly. With the rising number of elderly patients with UC, there is a need for more clinical trials that specifically address UC treatment in this unique population. © the author(s), publisher and licensee Libertas Academica Ltd.

OBJECTIVE:

To evaluate evidence for probiotic efficacy for maintaining remission of ulcerative colitis (UC) in adults.

DATA SOURCES:

A MEDLINE search (1948-November 2009) was conducted using ulcerative colitis and probiotics as terms for identifying pertinent studies. Search limits included English language and humans. Additional information was obtained from bibliographies.

STUDY SELECTION AND DATA EXTRACTION:

Prospective trials published in English and conducted in adults were included. Two open-label and 3 double-blind randomized trials evaluated probiotic efficacy for maintaining remission of UC. Clinical and surrogate markers for maintaining remission of UC were assessed.

DATA SYNTHESIS:

A relationship between immune response and gastrointestinal microbials appears to be involved in the mechanism of UC. Trial results comparing the probiotic Escherichia coli Nissle 1917 to mesalazine have reported equivalent rates of UC relapse. Treatment with Lactobacillus rhamnosus GG strain alone or in combination with mesalazine resulted in a nonsignificant odds ratio decrease for relapse and a significant increase in time to relapse compared to treatment with mesalazine alone. Additionally, bifidobacteria- fermented milk-supplemented patients had significant reductions in UC exacerbations when compared to nonsupplemented patients. Probiotics were well tolerated, with adverse event rates similar between treatments.

CONCLUSIONS:

Studies evaluating probiotics for maintaining remission of UC are limited by trial design and use of different probiotics with variable bacterial contents. Thus, questions remain regarding optimal probiotic, dosing, specific patient populations, and placement in therapy. To answer these questions, large, randomized, controlled trials need to be conducted before probiotics can be routinely recommended for maintaining remission of UC.

PURPOSE:

The placebo response rate in randomized controlled trials (RCTs) in ulcerative colitis (UC) varies from 0 to 76%. The aims of this study were to quantify the pooled placebo response rate and identify the factors affecting it.

METHODS:

We performed a meta-analysis of 110 RCTs carried out between 1955 and 2005 and published in English. Regression analysis was used to identify factors significantly modifying placebo response.

RESULTS:

The pooled placebo remission rate was 23% (95%CI: 18.4-28%) and the pooled placebo improvement rate was 32.1% (95%CI: 28.1-36.3%). Multivariate analysis showed that the country where the study was performed (P = 0.025 for placebo remission and P = 0.0083 for placebo response rates) significantly influenced the placebo remission and response rates.

CONCLUSION:

Placebo remission and response rates in RCTs of UC are highly variable and are significantly influenced by the country in which the RCT is performed.

Unplanned readmission (UR) is considered to be an index of quality surgical care. We examined whether any perioperative factor was associated with UR after colectomy for ulcerative colitis (UC) or indeterminate colitis (IC). Patients undergoing a two-stage or three-stage ileal pouch-anal anastomosis were included. Patient, disease, and surgical factors were collected. UR occurring within 30 days of hospital discharge was assessed. The 202 study patients had a median age of 38 years. Median body mass index was 22. There were 130 (64%) UC patients and 72 (36%) IC patients. Indications for surgery were medically refractory disease (n = 176, 87%) and dysplasia/cancer (n = 26, 13%). Preoperative medical therapy included steroids alone in 25 patients and steroids combined with other immunomodulators in 151 patients. A two-stage and three-stage ileal pouch-anal anastomosis was used in 146 (72%) and 56 (28%) patients, respectively. Median white blood cell count before discharge was 8600 cells/mm3. Median length of stay after surgery was 7 days. Complications before discharge were observed in 28 patients (14%). Thirty-eight patients (19%) had a UR. No preoperative or surgical factor was associated with UR. Although UR occurs frequently (19%) after colectomy for UC or IC, it cannot be predicted.