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.

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.

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.

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.

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.

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.

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.

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.