Estudio primario

No clasificado

Infliximab for acute, not steroid-refractory ulcerative colitis: a randomized pilot study.

Año 2004
Autores Ochsenkühn T , Sackmann M , Göke B
Revista European journal of gastroenterology & hepatology
Enlaces Pubmed , DOI

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OBJECTIVE:

Therapeutic alternatives for patients with acute ulcerative colitis in whom steroids would usually be contraindicated are rare. The antibody to tumor necrosis factor alpha, infliximab, has shown to be effective in the treatment of steroid-refractory ulcerative colitis in pilot studies. We therefore evaluated whether infliximab can achieve remission in patients with acute ulcerative pancolitis who were not steroid-refractory.

METHODS AND DESIGN:

Patients were eligible if they had acute disease with a modified Truelove and Witts activity score of more than 10 for at least 2 weeks and if they were currently not receiving immunomodulators or more than 10 mg/day prednisolone. Patients were randomly assigned to receive either three intravenous infusions of infliximab at 5 mg/kg (group A) or high-dose prednisolone (1.5 mg/kg body weight) daily for 2 weeks, followed by 1 mg/kg for 1 week, followed by a weekly reduction of 5 mg (group B). Therapy success was defined as clinical response in terms of a decrease of more than 5 points from the baseline score and to less than 10 points total after 3 weeks as well as after 13 weeks.

RESULTS:

Thirteen patients (seven women, six men) were randomized (six for group A and seven for group B). The median baseline activity scores were 13.5 (12-18) in group A and 14.0 (11-18) in group B. Five of six patients in group A and six of seven patients in group B showed therapy success after 3 weeks as well as after 13 weeks.

CONCLUSIONS:

Infliximab could be effective in the treatment of acute moderate or severe ulcerative colitis. The obtained data call for larger controlled trials.

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Estudio primario

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Genetics of ulcerative colitis.

Año 2011
Autores Thompson AI , Lees CW
Revista Inflammatory bowel diseases
Enlaces Pubmed , DOI
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Ulcerative colitis (UC) and Crohn's disease (CD) are related polygenic inflammatory bowel diseases (IBDs), with distinct and overlapping susceptibility loci. Recently, hypothesis-free genome-wide association (GWA) studies have revolutionized the field of complex disease genetics. Substantial advances have been achieved in defining the genetic architecture of IBD. To date, over 60 published IBD susceptibility loci have been discovered and replicated, of which approximately a third are associated with both UC and CD, although 21 are specific to UC and 23 to CD. In CD, the breakthrough identification of NOD2 as a susceptibility gene was followed by a rapid phase of gene discovery from GWA studies between 2006 and 2008. Progress in UC was slower; however, by initially testing hits for CD in UC, and later scanning larger UC cohorts, significant new loci for UC have been discovered, with exciting novel insights into disease pathogenesis. Notably, genes implicated in mucosal barrier function (ECM1, CDH1, HNF4α, and laminin B1) confer risk of UC; furthermore, E-cadherin is the first genetic correlation between colorectal cancer and UC. Impaired IL10 signaling has reemerged as a key pathway in intestinal inflammation, and is perhaps the most amenable to therapeutic intervention in UC. Collaborative international efforts with large meta-analyses of GWA studies and replication will yield many new UC genes. Furthermore, a large effort is required to characterize the loci found. Fine-mapping, deep resequencing, and functional studies will be critical to translating these gene discoveries into pathogenic insights, and ultimately into clinical insights and novel therapeutics.

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Revisión sistemática

No clasificado

Transdermal nicotine for induction of remission in ulcerative colitis

Año 2004
Revista Cochrane Database of Systematic Reviews
Enlaces Pubmed , DOI
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BACKGROUND:

Ulcerative colitis is largely a disease of nonsmokers. Intermittent smokers often experience improvement in their symptoms while smoking. Nonsmokers with ulcerative colitis who begin smoking may go into remission. Randomized controlled trials were developed to test the efficacy of transdermal nicotine for the induction of remission in ulcerative colitis.

OBJECTIVES:

(1) To determine the efficacy of transdermal nicotine for induction of remission in ulcerative colitis. (2) To assess adverse events associated with transdermal nicotine therapy for ulcerative colitis

SEARCH METHODS:

The MEDLINE (via PubMed) and EMBASE databases were searched using the search criteria "ulcerative colitis" and "transdermal nicotine" or "nicotine" to identify relevant papers published between 1970 and June 2008. Manual searches of reference lists from potentially relevant papers were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. The Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were also searched.

SELECTION CRITERIA:

We included only randomized controlled trials in which patients with active mild to moderate ulcerative colitis were randomly allocated to receive transdermal nicotine (15 to 25 mg/day) or a placebo or another treatment (corticosteroids or mesalamine).

DATA COLLECTION AND ANALYSIS:

Data extraction and assessment of the methodological quality of each trial were independently performed by each author. Any disagreement among reviewers was resolved by consensus. The primary outcome measure was the number of patients achieving clinical or sigmoidoscopic remission as defined by the primary studies (e.g. no symptoms of ulcerative colitis), and expressed as a percentage of the patients randomized (intention to treat analysis). Secondary outcomes included clinical response, adverse events and withdrawal because of adverse events.

MAIN RESULTS:

Nine studies were identified, five of which met the inclusion criteria. A meta-analysis of two trials in which 71 patients were randomized to nicotine and 70 to placebo showed a statistically significant benefit for nicotine treatment. After four to six weeks of treatment 19 of 71 patients treated with transdermal nicotine were in clinical remission compared to 9 of 70 treated with placebo (OR=2.56, 95% CI 1.02-6.45). In the same group of patients improvement or remission was noted in 29 of the 71 patients assigned to nicotine compared to 14 of 70 patients assigned to placebo (OR=2.72, 95% CI 1.28 - 5.81). For patients with left sided colitis the odds ratio was 2.31 (95% CI 1.05-5.10). When transdermal nicotine was compared to standard medical therapy no significant benefit for nicotine was observed. After four to six weeks of standard therapy (oral prednisone or mesalamine), 34 of 63 patients were in clinical or sigmoidoscopic remission compared to 33 of 66 patients treated with transdermal nicotine (OR=0.77, 95% CI 0.37-1.60). A meta-analysis of all five studies which included 137 patients treated with transdermal nicotine and 133 patients treated with a placebo or standard therapy demonstrated no statistically significant benefit of nicotine therapy (OR=1.23; 95% CI 0.71-2.14). Patients treated with transdermal nicotine were significantly more likely to withdrawal due to adverse events than patients treated with placebo or standard medical therapy (OR=5.82, 95% CI, 1.66 - 20.47) and were significantly more likely to suffer from an adverse event than patients treated with placebo or standard medical therapy (OR=3.54, 95% CI, 2.07 - 6.08).

AUTHORS' CONCLUSIONS:

The results of this review provide evidence that transdermal nicotine is superior to placebo for the induction of remission in patient's with ulcerative colitis. The review did not identify any significant advantage for transdermal nicotine therapy compared to standard medical therapy. Adverse events associated with transdermal nicotine are significant and limit its use in some patients.

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Revisión sistemática

No clasificado

Vedolizumab for induction and maintenance of remission in ulcerative colitis

Año 2014
Revista Cochrane Database of Systematic Reviews
Enlaces Pubmed , DOI
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BACKGROUND:

Cellular adhesion molecules play an important role in the pathogenesis of ulcerative colitis, making selective blockade of these molecules a promising therapeutic strategy. Vedolizumab, a recombinant humanized IgG1 monoclonal antibody, inhibits adhesion and migration of leukocytes into the gastrointestinal tract by binding the alpha4beta7 integrin. Animal studies have suggested that vedolizumab may be a useful therapy for ulcerative colitis. This updated systematic review summarizes the current evidence on the use of vedolizumab for induction and maintenance of remission in ulcerative colitis.

OBJECTIVES:

The primary objectives were to determine the efficacy and safety of vedolizumab used for induction and maintenance of remission in ulcerative colitis.

SEARCH METHODS:

A computer-assisted search for relevant studies (inception to 15 June 2014) was performed using PubMed, MEDLINE, EMBASE and CENTRAL. References from published articles and conference proceedings were searched to identify additional citations.

SELECTION CRITERIA:

Randomized controlled trials comparing vedolizumab to placebo or a control therapy for induction or maintenance of remission in ulcerative colitis were included.

DATA COLLECTION AND ANALYSIS:

Two authors independently extracted data and assessed the risk of bias for each trial. The primary outcomes were failure to induce clinical remission and relapse. Secondary outcomes included failure to induce a clinical response, failure to induce endoscopic remission, failure to induce an endoscopic response, quality of life, adverse events, serious adverse events and withdrawal due to adverse events. We calculated the relative risk (RR) and 95% confidence intervals (CI) for each outcome. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria.

MAIN RESULTS:

Four studies (606 patients) were included. All of the studies were rated as having a low risk of bias. Pooled analyses revealed that vedolizumab was significantly superior to placebo for induction of remission, clinical response, and endoscopic remission and prevention of relapse. After 4 to 6 weeks of therapy 77% (293/382) of vedolizumab patients failed to enter clinical remission compared to 92% (205/224) of placebo patients (RR 0.86, 95% CI 0.80 to 0.91; 4 studies 606 patients). After 6 weeks of therapy 48% of vedolizumab patients failed to have a clinical response compared to 72% of placebo patients (RR 0.68, 95% CI 0.59 to 0.78; 3 studies 601 patients). After 4 to 6 weeks of therapy 68% of vedolizumab patients failed to enter endoscopic remission compared to 81% of placebo patients (RR 0.82, 95% CI 0.75 to 0.91; 3 studies, b583 patients). After 52 weeks of therapy, 54% of vedolizumab patients had a clinical relapse compared to 84% of placebo patients (RR 0.67, 95% CI 0.59 to 0.77; 1 study, 373 patients). One small study (28 patients) found no statistically significant difference in endoscopic response (RR 1.00, 95% CI 0.62 to 1.61). GRADE analyses indicated that the overall quality of the evidence for the primary outcomes was high for induction of remission and moderate for relapse (due to sparse data 246 events). There was no statistically significant difference between vedolizumab and placebo in terms of the risk of any adverse event (RR 0.99, 95% CI 0.93 to 1.07), or serious adverse events (RR 1.01, 95% CI 0.72 to 1.42). There was a statistically significant difference in withdrawals due to adverse events. Six per cent of vedolizumab patients withdrew due to an adverse event compared to 11% of placebo patients (RR 0.55, 95% CI 0.35 to 0.87; 2 studies, 941 patients). Adverse events commonly reported across the studies included: worsening ulcerative colitis, headache, nasopharyngitis, upper respiratory tract infection, nausea, and abdominal pain.

AUTHORS' CONCLUSIONS:

Moderate to high quality data from four studies shows that vedolizumab is superior to placebo for induction of clinical remission and response and endoscopic remission in patients with moderate to severely active ulcerative colitis and prevention of relapse in patients with quiescent ulcerative colitis. Moderate quality data from one study suggests that vedolizumab is superior to placebo for prevention of relapse in patients with quiescent ulcerative colitis. Adverse events appear to be similar to placebo. Future trials are needed to define the optimal dose, frequency of administration and long-term efficacy and safety of vedolizumab used for induction and maintenance therapy of ulcerative colitis. Vedolizumab should be compared to other currently approved therapies for ulcerative colitis in these trials.

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Revisión sistemática

No clasificado

Aceite de pescado para la inducción de remisión en la colitis ulcerosa

Traducción oficial
Año 2007
Revista Cochrane database of systematic reviews (Online)
Enlaces Pubmed , DOI
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ANTECEDENTES:

Los suplementos con aceite de pescado, que son ricos en ácidos grasos n-3, pueden reducir la inflamación, disminuir la necesidad de fármacos antiinflamatorios y promover el aumento de peso normal en los pacientes con colitis ulcerosa.

OBJETIVOS:

Esta revisión evalúa la eficacia del aceite de pescado para la inducción de remisión en la colitis ulcerosa con el uso de todos los ensayos controlados aleatorios disponibles.

ESTRATEGIA DE BÚSQUEDA:

Se realizaron búsquedas en el Registro Cochrane Central de Ensayos Controlados (CENTRAL), PUBMED, EMBASE, CINAHL, la base de datos de los ensayos en curso y las listas de referencias de todas las publicaciones de los ensayos incluidos o excluidos.

CRITERIOS DE SELECCIÓN:

Ensayos controlados aleatorios y cuasialeatorios en pacientes con colitis ulcerosa activa que fueron tratados con aceite de pescado.

RECOPILACIÓN Y ANÁLISIS DE DATOS:

Los revisores realizaron la selección de estudios, la evaluación de la calidad metodológica con diferentes enfoques: incluida la evaluación Cochrane de ocultación de la asignación y la puntuación de evaluación de calidad de Jadad. Los dos revisores usaron planillas específicas para extraer los datos de forma independiente. Se estableció contacto con los autores para obtener información adicional.

RESULTADOS PRINCIPALES:

Se incluyeron seis estudios. Tres fueron de diseño cruzado (crossover) y tres fueron de diseño paralelo. Los datos no se agruparon para el análisis debido a las diferencias en los resultados y la metodología de los estudios incluidos. Un estudio pequeño revela un beneficio positivo para la inducción de la remisión (RR 19,00; IC del 95%: 1,27 a 284,24). Algunos de los otros estudios incluidos revelan algunos beneficios positivos para los resultados secundarios. Sin embargo, estos resultados necesitan interpretarse con cuidado debido al reducido tamaño del estudio y la calidad deficiente del mismo.

CONCLUSIONES DE LOS AUTORES:

Los datos actuales no permiten una conclusión definitiva con respecto a la eficacia del aceite de pescado. No hay información adecuada para recomendar a la práctica clínica. Se necesita más investigación.

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Revisión sistemática

No clasificado

Systematic review: Infliximab therapy in ulcerative colitis

Año 2007
Revista Alimentary pharmacology & therapeutics
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Aim: To perform a systematic review and meta-analysis on the efficacy and tolerance of infliximab in ulcerative colitis. Methods: Selection of studies: evaluating efficacy of infliximab in ulcerative colitis. For the meta-analysis, randomized clinical trials comparing infliximab vs. placebo/steroids. Search strategy: electronic and manual. Study quality: independently assessed by two reviewers. Data synthesis: meta-analysis combining the odds ratios (OR). Results: Thirty-four studies (896 patients) evaluated infliximab therapy in UC, with heterogeneous results. Mean short-term (2.3 weeks) response and remission with infliximab was 68% (95% CI 65-71%) and 40% (36-44%). Mean long-term (8.9 months) response and remission was 53% (49-56%) and 39% (35-42%). Five randomized double-blind studies compared infliximab with placebo, the meta-analysis showing an advantage (P < 0.001) of infliximab in all endpoints (short-/long-term response/remission): ORs from 2.7 to 4.6, and number-needed-to-treat (NNT) from 3 to 5. Similar infliximab response was calculated independently of the indication (steroid-refractory/non-steroid- refractory) or the dose (5/10 mg/kg). Adverse effects were reported in 83% and 75% of the infliximab and placebo-treated patients (OR = 1.52; 95% CI 1.03-2.24; number-needed-to-harm (NNH) was 14). Conclusion: Infliximab is more effective than placebo, with an NNT from 3 to 5, for the treatment of moderate-to-severe UC, achieving clinical remission in 40% of the patients at approximately 9 months of follow-up. Further studies are necessary to confirm the long-term efficacy of infliximab in ulcerative colitis. © 2007 The Authors.

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Revisión sistemática

No clasificado

Meta-analysis: budesonide treatment for collagenous colitis.

Año 2004
Revista Alimentary pharmacology & therapeutics
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BACKGROUND:

Collagenous colitis is typified by chronic watery diarrhoea and characteristic histological alterations of the colonic mucosa without endoscopic abnormalities. Budesonide, a corticosteroid with high first-pass metabolism has been examined in collagenous colitis, but studies to date have had small numbers, and relatively low statistical power.

AIM:

A meta-analysis of existing published trials was undertaken to evaluate the treatment effect of budesonide in collagenous colitis.

METHODS:

All pertinent literature sources were searched for published reports in English of budesonide use in collagenous colitis. MEDLINE and EMBASE databases were reviewed, as well as bibliographies from published articles and available abstracts from relevant meetings. Literature that met prespecified criteria was selected for the meta-analysis.

RESULTS:

Three trials were included in the meta-analysis. Budesonide significantly decreased stool frequency (budesonide vs. placebo OR.: 20.1, 95% CI.: 7.0-57.5, P < 0.0001). In general, budesonide treatment was well-tolerated.

CONCLUSIONS:

Budesonide is clinically effective short-term in collagenous colitis, and seems to be relatively well-tolerated. Clinicians can consider this drug as a reasonable option for patients with this disorder.

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Revisión sistemática

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Vitamin D as a therapy for colitis: a systematic review.

Año 2012
Revista Journal of Crohn's & colitis
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BACKGROUND AND AIM:

The effect of vitamin D supplementation on immune disorders has been a topical research focus. The aim of this systematic review was to examine the current evidence of the effect of vitamin D supplementation as a therapy for colitis.

METHODS:

The following databases were searched: MEDLINE, Pubmed, Scopus, Web of Knowledge, Cinicaltrials.gov and the Cochrane Central Register of Controlled Trials using the terms 'inflammatory bowel disease' 'Crohn's disease' 'ulcerative colitis' 'colitis' [and] 'vitamin D'. Both human and animal studies published in English language were examined. The reference lists of included studies and review articles were manually searched for any relevant studies.

RESULTS:

Four studies were included in this systematic review. All reported an improvement in disease activity with vitamin D supplementation. The only high quality human study reported a non-significant reduction of relapse rate for Crohn's disease. No major adverse effects of vitamin D supplementation were reported.

CONCLUSIONS:

Although there is some evidence that supplemental vitamin D, as an adjunctive treatment, may help in controlling colitis, this evidence is not enough to justify using vitamin D in treating inflammatory bowel disease (IBD). Large high quality placebo-controlled randomised controlled trials are needed to explore a possible benefit of using vitamin D in treating IBD.

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Revisión sistemática

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Probiotics and remission of ulcerative colitis: a systematic review.

Año 2007
Autores Zigra PI , Maipa VE , Alamanos YP
Revista The Netherlands journal of medicine
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BACKGROUND:

Ulcerative colitis (UC) is an acute and inflammatory disease of the large bowel of unknown aetiology. The use of probiotics for this disease remains controversial. The objective of this systematic review was to identify studies based on randomised controlled trials comparing the effect of probiotics to the effect of anti-inflammatory drugs or placebo in the remission of UC.

METHODS:

We conducted a systematic review of clinical trials comparing the effect of probiotics to the effect of anti-inflammatory treatment or placebo in the remission of UC. PubMed, scienceDirect, Cochrane, Google scholar, metaRegister of Controlled Trials and National Institutes of Health were searched.

RESULTS:

Nine studies met the inclusion criteria. These studies present a significant heterogeneity concerning their methodology and their results. The improvement in UC remission and the frequency of adverse effects do not differ significantly between probiotic and control groups.

CONCLUSIONS:

There are a limited number of randomised trials published in the field of probiotics used for the remission of UC, and they present many methodological differences. The existing studies suggest a similar safety and efficacy of probiotics in comparison with anti-inflammatory drugs.

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Revisión sistemática

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Emerging treatments for ulcerative colitis: a systematic review.

Año 2017
Revista Scandinavian journal of gastroenterology
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OBJECTIVES:

Various investigational medicinal products have been developed for ulcerative colitis (UC). Our aim was to systematically evaluate novel pharmacological therapeutic agents for the treatment of UC.

MATERIAL AND METHODS:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed. A search of the medical literature was conducted in the MEDLINE database for original research papers published between 01 January 2010 and 31 October 2014.

RESULTS:

Twenty one studies, including 11,524 adults were analyzed. Thirteen different novel therapeutic drug options were identified. Vedolizumab and golimumab were superior to placebo as induction and maintenance therapy. Tofacitinib showed dose related efficacy for induction therapy. Etrolizumab showed higher clinical remission rates compared to placebo. Phosphatidylcholine led to an improved clinical activity index. HMPL-004 may become a mesalamine alternative for mild to moderate UC. PF00547,659 was well tolerated. Statins were not beneficial for acute exacerbations of UC. Abatacept, rituximab and visilizumab did not lead to improved outcomes compared to placebo. Higher concentration of BMS 936557 was associated with improved efficacy compared to placebo. Basiliximab did not enhance corticosteroid efficacy.

CONCLUSIONS:

Patients with UC might achieve clinical response or remission by utilizing some of these agents with a favorable side effect profile. Further studies are needed to evaluate their short- and long-term efficacy and safety.

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