Giuseppe Civitavecchia

Meta-Analysis of the Placebo Rates of Clinical Relapse and Severe Endoscopic Recurrence in Postoperative Crohn's Disease

BACKGROUNDS & AIMS The benefit of therapy for prevention of postoperative recurrence of Crohns disease (CD) is limited. Clinical relapse and severe endoscopic recurrence are the main outcomes in the evaluation of trials on prevention of recurrence. The aim of this meta-analysis was to focus on knowledge of the placebo rates of relapse and recurrence in postoperative CD and to identify factors influencing these rates. METHODS We performed a meta-analysis of placebo-controlled, randomized clinical trials, evaluating therapies for postoperative maintenance of CD identified on MEDLINE from 1990 to 2006. Primary outcomes were clinical relapse and severe endoscopic recurrence. RESULTS The pooled estimate of the placebo relapse rate was 23.7% (95% confidence interval [CI], 13-35; range 0-78). There was a statistically significant heterogeneity among studies (P < .0001). Heterogeneity in clinical relapse was present even if the trials were stratified according to the time of outcome. The pooled estimate of the severe endoscopic recurrence rate was 50.2% (95% CI, 28-73; range, 30-79). There was significant heterogeneity among the studies (P = .00038). This heterogeneity was less apparent in studies carried out within 12 months. The logistic analysis identified only duration of follow-up as a variable associated with different placebo relapse rates. No variable was identified as a predictor of a placebo endoscopic recurrence rate. CONCLUSIONS There is significant heterogeneity among placebo rates in postoperative CD. No single design variable was identified that explained the heterogeneity in placebo outcomes for clinical or endoscopic recurrence.

Clinical course of ulcerative colitis

AIM To provide a review of studies on prognosis in ulcerative colitis by reviewing the relevant population-based cohort studies. On the basis of incidence and population studies, ulcerative colitis has a favourable clinical course, with good quality of life, a chronic course characterized by at least one relapse, and a surgery rate of 30% after 10 years from diagnosis. Patients affected by severe ulcerative colitis have a higher risk of colectomy, and some clinical variables may predict the diseases clinical course. Most patients respond to steroids and only a low percentage become dependent, or non-responders to steroids. Patients who have a long-lasting ulcerative colitis (>10 years) or are affected by an extensive disease have an increased risk of developing colorectal cancer, while those treated with immunosuppressants for long period of time may have an increased risk of developing lymphomas. Data on mortality in ulcerative colitis patients are not homogeneous, but if a real risk exists it is in patients with extensive or severe disease. The evidence that patients with severe ulcerative colitis are often non-smokers may explain why in one study the mortality rate was lower.

The Role of CARD15 Mutations and Smoking in the Course of Crohn's Disease in a Mediterranean Area

AIM:To evaluate the role of CARD15 mutations and smoking in the main events of Crohns disease (CD).PATIENTS AND METHODS:A total of 182 patients with CD were included in a prospective study in order to evaluate the role of CARD15 mutations and smoking in the main outcomes of disease course: first operation and surgical recurrence. The following variables were evaluated in a univariable and multivariable analysis: age, sex, site of disease, pattern, smoking habit, extraintestinal manifestations, duration of disease, and CARD15 mutation. The Kaplan–Meier method for survival curves and Cox model for multivariable analysis were, respectively, used.RESULTS:A total of 110 patients were operated on and 32 were reoperated on. The 7-yr cumulative free rate of surgery was 42% (95% CI 34–51%). At multivariate analysis only stricturing and penetrating pattern were predictors of surgery (HR 1.7, 95% CI 1–2.8; HR 3.2, CI 1.8–5.5, respectively). The 7-yr cumulative free rate of reoperation was 75% (95% CI 0.52–0.88). At multivariable analysis in the model with any CARD15 mutation, only smoking habit at diagnosis (HR 3.6, 95% CI 1.4–9.1) was predictive of surgical recurrence. When single mutations were considered in the model smoking (HR 4.2, 95% CI 1.8–10.1) and L1007fs mutation (HR 2.9, 95% CI 1.1–7.3) were predictive of reoperation.CONCLUSIONS:In CD, smoking predicts recurrence after surgery. The role of CARD15 mutations in the clinical course of CD remains undefined.

Minimizing infliximab toxicity in the treatment of inflammatory bowel disease

BACKGROUND Infliximab is a widely used biological agent for the treatment of inflammatory bowel disease, and has a favorable risk/benefit ratio. AIM It is useful to know that patients treated with infliximab are exposed to developing adverse events that could be reduced with a prudent and a rational clinical approach and by optimizing the treatment protocol. METHODS PubMed (including Epub) was searched in October 2006 and again in March 2007. RESULTS The high immunogenic potential of infliximab determines the antibodies that inhibit the effect of infliximab and the appearance of subsequent acute and delayed infusion reactions. Infliximab has an immunomodulatory effect, thus increasing the risk of serious and latent infections. Screening for tuberculosis, HBV, opportunistic or latent infections, heart failure, and haematological, neurological and hepatological disorders must be performed before infliximab therapy. There is no definitive evidence that infliximab increases the risk of neoplasia. Mortality in infliximab-treated patients does not appear increased compared to the controls. CONCLUSIONS Infliximab safety is similar to that of conventional immunomodulators and patients treated had similar rates of mortality, neoplasm and lymphoma as patients not treated with infliximab. Patients treated with infliximab have an increased risk of serious infections but it is not related to infliximab therapy.

Familial mediterranean fever gene (MEVF) mutations in Crohn's disease in a Mediterranean area

To the Editor: Familial Mediterranean fever (FMF) is an inflammatory disorder characterized by an uncontrolled immune response. The disease is prevalent in the Mediterranean area and the MEVF gene, responsible for FMF, has been localized on chromosome 16p13 and encodes for pyrin, which has been implicated in the regulation of neutrophil activity. Recently, Fidder et al evaluated the association of MEVF mutations with CD and did not find a significant association with CD susceptibility but suggested that carrying of MEVF mutations may have an impact on the clinical manifestation of CD. In Sicily, where there is an high incidence of Crohn’s disease and the frequency of CARD15/NOD2 mutations (L1007finsC, R702W and G908R) in CD patients is 30%, the MEVF gene could play a role in our geographic area as a modifier gene. For this reason, we decided to carry out a preliminary study of the allele frequency of MEVF mutations (E148Q, V726A, M680I, M694V, M694I, K695R) in a consecutive cohort of 84 CD patients (37 women, 47 men, mean age 30 years) in whom CARD15/ NOD2 mutations were previously studied and in 72 healthy controls. The clinical characteristics (pattern and site) and the allele frequency mutations are shown in Table 1. Thirty-one of 84 patients with CD were positive for CARD15/NOD2 mutations (allele frequency in CD patients, 22.3%; allele frequency in controls, 7.0%), and only 3 (CARD15/NOD2 negative) were heterozygote for at least 1 mutation of the MEVF gene (2 patients carrying M694V and 1 patient carrying M608I; allele frequency, 1.7%), whereas mutations were not present in 72 controls. The MEVF mutation seems not to play a role in our geographic area because a prevalence of 4% in CD is very low compared with that in other Mediterranean areas, in which a 13% prevalence of MEVF mutations has been observed. The low frequency of MEVF mutations in Sicily seems to exclude any relevant role of this gene in the phenotype of CD in our area. However, it is our aim to increase the sample in order to verify this conclusion.

W1113 Efficacy and Safety of Endoscopic Balloon Dilation of Symptomatic Intestinal Crohn's Disease Strictures

Aim: To evaluate prospectively the clinical efficacy and safety of endoscopic hydrostatic balloon dilation in a consecutive cohort of symptomatic intestinal Crohn’s disease strictures. Methods: Between September 2003 and December 2008 we performed endoscopic balloon dilations in 37 Crohn’s disease patients with 39 intestinal symptomatic strictures (4 naive and 35 postoperative). Dilations were performed using a Rigiflex through-the-scope balloon. Clinical success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation, following technical success. Actuarial curves of clinical, endoscopic (redilation) and surgical recurrence were obtained by Kaplan–Meier method. Demographic and disease variables were related to the main outcomes. Results: After a mean follow-up of 26.3 months (range, 2–61 months), the long-term global benefit rate was 89% (33/37). The 1–2–3 years cumulative symptom-free rates were respectively: 76%, 55% and 46%. Four patients were operated upon. Technical success predicts a lower rate of surgery. There were no complications related to the endoscopic procedures. Conclusions: Endoscopic balloon dilation of symptomatic Crohn’s disease strictures may achieve clinical benefit in many patients and is a valid alternative to surgery in the management of the disease. Dilation may be repeated in recurrent intestinal obstructions and appears safe without morbidity.