Methotrexate for Inflammatory Bowel Diseases - New Developments

Methotrexate (MTX) is an established therapy for patients with steroid dependent Crohn’s disease (CD). MTX is also frequently used in combination with anti-TNF agents to suppress anti-drug antibody formation. It has been suggested in the past that MTX lacks any clinical effectiveness in patients with ulcerative colitis (UC), however newer data at least partially contradict this assumption. The following review will discuss recent data for the use of MTX in CD, UC and in combination with anti-TNF agents

Cytomegalovirus viral load in the colon and risk of colectomy in hospitalized patients with inflammatory bowel diseases

To the Editor: We read with interest the article of Lee et al1 describing the risk factors for adverse outcomes in hospitalized patients with ulcerative colitis (UC) with concurrent cytomegalovirus (CMV) colitis. CMV reactivation and resolution can be spontaneous in patients with UC regardless of antiviral therapy; however, inconsistencies between CMV detection methods of various studies and criteria for defining CMV positivity may be leading to these disparate findings.2,3 In the study by Lee et al, CMV colitis was defined by the presence of 1 or more inclusion bodies on hematoxylin and eosin staining or CMV immunohistochemistry on colonic biopsies. The most accurate approach for detection of clinically significant CMV infection has not been firmly established and guidelines differ in their recommendations.3,4 A recent study using quantitative colonic PCR in consecutive patients with UC undergoing endoscopy in the setting of a moderate to severe flare demonstrated a correlation between higher viral load and resistance to immunosuppressive therapy with significant differences found when using a cutoff viral load of .250 per milligram tissue.

Methotrexate: Underused and Ignored?

For greater than a decade, methotrexate has been known to be an effective therapeutic agent in the treatment of steroid dependent active Crohn's disease. However, international data on medication utilization suggest that this drug is rarely used in clinical practice for an indication of Crohn's disease. This review investigates the potential reasons for the underuse of methotrexate in patients with inflammatory bowel diseases

Prevalence of a Gluten-free Diet and Improvement of Clinical Symptoms in Patients with Inflammatory Bowel Diseases:

Background—Maintaining a gluten free diet (GFD) without an underlying diagnosis of celiac disease has enjoyed widespread acceptance in the USA. Methods—We performed a cross-sectional study utilizing a GFD questionnaire in 1647 patients with inflammatory bowel diseases (IBD) participating in the CCFA Partners longitudinal, Internet-based cohort. Results—A diagnosis of celiac disease (CD) and non-celiac gluten sensitivity (NCGS) were reported by 10 (0.6%) and 81 (4.9%) respondents, respectively. Three hundred fourteen (19.1%) participants reported having previously tried a GFD and 135 (8.2%) reported current use of GFD. Overall 65.6% of all patients, who attempted a GFD described an improvement of their GI-symptoms and 38.3% reported fewer or less severe IBD flares. In patients currently attempting a GFD, excellent adherence was associated with significant improvement of fatigue (p<0.03). Conclusion—In this large group of patients with IBD, a substantial number had attempted a GFD, of whom the majority had some form of improvement in GI-symptoms. Testing a GFD in clinical practice in patients with significant intestinal symptoms, which are not solely explained by the degree of intestinal inflammation, has the potential to be a safe and highly efficient therapeutic approach. Further prospective studies into mechanisms of gluten sensitivity in IBD are warranted

Use of Biologics in Pouchitis: A Systematic Review

Data about the effectiveness of biologics, including anti-TNF therapy and anti-integrin strategies, in antibiotic refractory pouchitis or Crohn’s disease-associated pouch complications are sparse. We performed a systematic review of the literature in Medline and Web of Science. All English language publications and meeting abstracts describing patients with pouchitis treated with anti-TNF or anti-integrin therapies were included. We identified a total of 17 papers and 2 abstracts, most of these retrospective case series, including a total of 192 patients treated either with infliximab (IFX; n=140) or adalimumab (ADA; n=52). No reports were found for anti-integrin therapies or other anti-TNF agents such as certolizumab pegol or golimumab. Due to the heterogeneity of the studies, small numbers of patients, differing co-treatments and subjective outcome definitions, the exact efficacy of these biologic therapies cannot be assessed in a combined fashion. Overall IFX appears to have good clinical effectiveness in selected patients achieving up to 80% short and around 50% long-term response, whereas the few data available for ADA are not sufficient to draw valid conclusions. Larger prospectively collected multi-center data with clearly defined inclusion criteria and outcomes are necessary to better define the clinical value of anti-TNF therapy in patients with antibiotic refractory pouchitis or Crohn’s-like complications of the pouch

Modulation of the Intestinal Microbiota Alters Colitis-Associated Colorectal Cancer Susceptibility

It is well established that the intestinal microbiota plays a key role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) collectively referred to as inflammatory bowel disease (IBD). Epidemiological studies have provided strong evidence that IBD patients bear increased risk for the development of colorectal cancer (CRC). However, the impact of the microbiota on the development of colitis-associated cancer (CAC) remains largely unknown. In this study, we established a new model of CAC using azoxymethane (AOM)-exposed, conventionalized-Il10−/− mice and have explored the contribution of the host intestinal microbiota and MyD88 signaling to the development of CAC. We show that 8/13 (62%) of AOM-Il10−/− mice developed colon tumors compared to only 3/15 (20%) of AOM- wild-type (WT) mice. Conventionalized AOM-Il10−/− mice developed spontaneous colitis and colorectal carcinomas while AOM-WT mice were colitis-free and developed only rare adenomas. Importantly, tumor multiplicity directly correlated with the presence of colitis. Il10−/− mice mono-associated with the mildly colitogenic bacterium Bacteroides vulgatus displayed significantly reduced colitis and colorectal tumor multiplicity compared to Il10−/− mice. Germ-free AOM-treated Il10−/− mice showed normal colon histology and were devoid of tumors. Il10−/−; Myd88−/− mice treated with AOM displayed reduced expression of Il12p40 and Tnfα mRNA and showed no signs of tumor development. We present the first direct demonstration that manipulation of the intestinal microbiota alters the development of CAC. The TLR/MyD88 pathway is essential for microbiota-induced development of CAC. Unlike findings obtained using the AOM/DSS model, we demonstrate that the severity of chronic colitis directly correlates to colorectal tumor development and that bacterial-induced inflammation drives progression from adenoma to invasive carcinoma

Impact of capsule endoscopy on management of inflammatory bowel disease: A single tertiary care center experience:

Capsule endoscopy (CE) is performed to assess inflammatory bowel disease (IBD). We aimed to define results of CE in subtypes of IBD and to determine whether CE results in management changes

Narcotic use for inflammatory bowel disease and risk factors during hospitalization:

Growing evidence demonstrates adverse effects of narcotics in inflammatory bowel disease (IBD). We sought to study the relationship between narcotic use, objective measures of disease activity and other associated factors in hospitalized patients with IBD

Evaluation of a Non-invasive Method to Detect Cytomegalovirus (CMV)-DNA in Stool Samples of Patients with Inflammatory Bowel Disease (IBD): A Pilot Study

A severe flare of colitis in patients with IBD treated with immunosuppressive therapy may be complicated by an underlying CMV infection. The aim of this pilot study was to investigate the diagnostic efficacy of quantitative polymerase chain reaction (PCR) to detect CMV DNA in stool samples of IBD patients