Medical management of Crohn's disease

The medical approach to Crohn's disease has been modified in recent years thanks to the introduction of new therapies, like biologics. Also, well-designed studies and systematic reviews have allowed better evaluation of the role of old drugs like steroids and immunosuppressors. This review aims to evaluate the recent evidence on the medical approach to Crohn's disease in the different settings of the disease.Randomized controlled trials and meta-analyses were included in the review. The research on all the studies discussed was based on the Cochrane Library, Medline and Embase, using the following medical subject headings: Crohn's disease, clinical trial, therapy, 5-aminosalicylic acid, ste…

Intraductal aspiration: a promising new tissue-sampling technique for the diagnosis of suspected malignant biliary strictures

Brushing is the most commonly used technique for biliary sampling at ERCP, despite its limited sensitivity. To evaluate intraductal aspiration (IDA) as a new combined endoscopic technique for cytodiagnosis, its cellular adequacy, diagnostic accuracy for cancer detection, feasibility, and safety. Prospective, observational study. Single tertiary referral center. IDA cellular adequacy, diagnostic accuracy for cancer detection, feasibility, and safety. From April 2009 to September 2010, 42 consecutive patients with suspected malignant biliary stricture underwent ERCP, with tissue sampling obtained with IDA. IDA included performance of standard brushing in all patients. After standard brushing,…

One-step endoscopic removal of a giant double esophageal fibrovascular polyp

Two-year effectiveness and safety of golimumab in ulcerative colitis: An IG-IBD study

Abstract Background Few data exist regarding the long‐term effectiveness of golimumab in ulcerative colitis. No data have been reported on real‐world continuous clinical response. Objective This study aimed to describe the long‐term outcomes in a large cohort of patients on golimumab who had ulcerative colitis. Methods Consecutive patients with active ulcerative colitis, started on golimumab, were enrolled and prospectively followed up. The primary end point was to evaluate the long‐term persistence on golimumab therapy. Results A total of 173 patients with ulcerative colitis were studied. Of these, 79.2% were steroid dependent, and 46.3% were naïve to anti‐tumour necrosis factor alpha agen…

γδ cells and tumor microenvironment: A helpful or a dangerous liason?

Abstract γδ T cells are a subset of T lymphocytes that have been implicated in immunosurveillance against infections and tumors. γδ T cells are endowed with antitumor activities, and hence several γδ T cell-based small-scale clinical trials have been conducted either by in vivo activation by intravenous administration of aminobiphosphonates or by adoptive transfer of in vitro expanded γδ T cells. Although both these strategies have yielded promising results, there are a number of limitations associated with each of them which, if overcome may help to further improve efficacy. One of the most important limits is the possible polarization of tumor-infiltrating γδ T cells toward different γδ T…

Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in post-operative Crohn's disease

Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in postoperative Crohn's disease. Renna S, Cammà C, Modesto I, Cabibbo G, Scimeca D, Civitavecchia G, Mocciaro F, Orlando A, Enea M, Cottone M. Dipartimento di Medicina, Pneumologia e Fisiologia della Nutrizione Umana, Università di Palermo, Palermo, Italy. BACKGROUNDS & AIMS: The benefit of therapy for prevention of postoperative recurrence of Crohn's 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 recurr…

Oral lichen planus after certolizumab pegol treatment in a patient with Crohn's disease

Dear Sir , Lichen planus (LP) is a relatively uncommon inflammatory dermatosis of the mucocutaneous surfaces that can present with a variety of clinical manifestations and, most commonly, affecting middle-aged adults. The disease course may be short or chronic, although most cases may resolve after 1 month to 7 years. The real prevalence of LP is unknown, but is estimated to be 1% in the USA.1 The pathogenesis of LP is not entirely understood. In general, activated T lymphocytes are recruited to the dermal–epidermal junction and induce apoptosis in basal keratinocytes. Both CD4+ and CD8+ T lymphocytes are found in the lichenoid infiltrate of LP, with a predominance of the latter cell type b…

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 obtaine…

MINIMIZING INFLIXIMAB TOXICITY IN THE TREATMENT OF INFLAMMATORY BOWEL DISEASE

Abstract 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 increas…

Cytomegalovirus disappearance after treatment for refractory ulcerative colitis in 2 patients treated with infliximab and 1 patient with leukapheresis

The role of CARD15 mutations and smoking in the course of Crohn's disease in a Mediterranean area.

To evaluate the role of CARD15 mutations and smoking in the main events of Crohn's disease (CD).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.A total of 110 patients were operated on and 32 were reoperated on. The …

Characterization of γδ T cells in intestinal mucosa from patients with early onset or long standing inflammatory bowel disease and their correlation with clinical status

Abstract Background and Aims Inflammatory bowel disease [IBD] is a complex chronic inflammatory disease of the human gut with no clear aetiology. Traditionally, dysregulated adaptive immune responses play an important role even though accumulating evidence suggests a role also for innate immunity. Because of the well-known plasticity of γδ T cells, we investigated their percentage occurrence, phenotypic features and effector functions in the intestinal mucosa of early-onset and long-standing IBD patients, as compared to healthy subjects. Methods Fresh biopsies from 30 Crohn’s disease and ulcerative colitis patients were obtained and digested, and cells were analysed by flow cytometry. Resul…

Adalimumab Induction for Crohn’s Disease

A real life comparison of the effectiveness of adalimumab and golimumab in moderate-to-severe ulcerative colitis, supported by propensity score analysis

Abstract Background Adalimumab and golimumab are effective in the treatment of moderate to severe ulcerative colitis. Aims We reported the comparative effectiveness of adalimumab and golimumab in ulcerative colitis. Methods 118 patients treated with adalimumab and 79 treated with golimumab were included and evaluated at 8 weeks and at the end of follow up. Results Overall clinical benefit was 72.6% at 8 weeks and 58.9% at the end of follow up. Patients with longer disease duration and those treated with adalimumab had a better outcome. Clinical benefit was 78.8% in adalimumab patients and 63.3% in golimumab patients (p = 0.026) after 8 weeks; it was 66.9% in adalimumab patients and 46.8% in…

Efficacy and safety of endoscopic balloon dilation of symptomatic intestinal Crohn's disease strictures

Abstract 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 …

Persistence on Anti-Tumour Necrosis Factor Therapy in Older Patients with Inflammatory Bowel Disease Compared with Younger Patients: Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD)

BACKGROUND AND OBJECTIVE: Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). METHODS: We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls < 60 years of age at their first course of anti-TNF treatment. Data concerning persistence on therapy over the first year of treatment (primary objective) together …

Colorectal Cancer in Patients with Type 2 Diebetes Mellitus: Retrospective Analysis of 741 Cases

ABSTRACT Background Understanding the risk factors of colorectal cancer (CRC) is crucial to the development of effective strategies for its prevention. Type 2 diabetes mellitus (DM) is associated with increased CRC risk and epidemiological studies identified a correlation between these diseases. Aim: To evaluate prevalence of CRC in a cohort of Caucasian patients with type 2 DM and the association with other variables previously known to be related with increased CRC. Methods We retrospectively evaluated 741 DM 2 patients followed in our institution of southern Italy between 2000-2008 for the incidence of CRC. Patients were stratified based on gender, age, body mass index (BMI), alcohol and…

Successful induction of clinical response and remission with certolizumab pegol in Crohn's disease patients refractory or intolerant to infliximab: a real-life multicenter experience of compassionate use

Incidence of Crohn's disease and CARD15 mutation in a small township in Sicily.

Background: The incidence of Crohn's disease (CD) has been shown to be lower in Southern than in Northern Europe. Data on the frequency of the NOD2/CARD15 mutations for Mediterranean area are very scant. Aim: To determine the incidence of CD from 1979 to 2002 in a township in Sicily together with the allele frequency of NOD2/CARD15 mutations in patients, family members and controls, and to determine the allele frequency of these mutations in sporadic CD from other areas of Sicily in comparison with a control population. Methods: Casteltermini is a small town close to Agrigento (Sicily) with a population of 9,130 inhabitants. All the diagnoses of inflammatory bowel disease (IBD) made from 19…

Clinical course of ulcerative colitis

. Dig Liver Dis. 2008 Jul;40 Suppl 2:S247-52. Clinical course of ulcerative colitis. Cottone M, Scimeca D, Mocciaro F, Civitavecchia G, Perricone G, Orlando A. Department of Medicine, Pneumology and Nutrition Clinic, V. Cervello Hospital, University of Palermo, Palermo, Italy. 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 h…

Six year adalimumab efficacy in steroid-dependent Crohn's disease patients: A prospective single-center real life study.

Abstract Background Adalimumab is effective in the treatment of Crohn's disease. We have already reported data on the efficacy of adalimumab in 110 steroid-dependent patients. At the end of the study 90 patients (64.5%) maintained clinical remission. Aims To assess efficacy and safety of adalimumab after 6 years in patients of the original cohort who responded to treatment. Methods The present study is an extension of the published paper on 90/110 patients. We report results on clinical remission and safety of 6 year maintenance therapy with adalimumab. Results Of the original cohort 90 patients completed the study, 17 were lost to follow-up and 3 died. At the end of follow-up (74.16 ± 10.3…

Colorectal cancer in patients with type 2 diabetes mellitus: a single-center experience

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC). The aim of the study is to evaluate the prevalence of CRC in a cohort of Caucasian patients with T2DM and the association with other variables previously known to be related with increased risk of CRC. We retrospectively evaluated the data of 741 consecutive Caucasian patients with T2DM who underwent colonoscopic screening in our tertiary referral center. A control cohort of 333 patients with thyroid disease was selected to evaluate the difference in the incidence of CRC. At a median follow-up of 132.5 months (range 33.3-175.7), 67 cases of cancer (prevalence 9%) occurred; among these, 14 cases …

Adalimumab in steroid-dependent Crohn's disease patients: prognostic factors for clinical benefit.

Background: Corticosteroids are effective in the treatment of Crohn's disease but some patients relapse during tapering or after discontinuation. We report data on efficacy and prognostic factors of response of adalimumab in steroid-dependent patients. Methods: In all, 110 steroid-dependent patients were treated with adalimumab (80/40 or 160/80 mg every other week followed by 40 mg every other week). Clinical remission was defined as steroid discontinuation without symptomatic recurrence and clinical response as the reduction or maintenance of the initial Crohn's Disease Activity Index (CDAI) value reducing steroid dosage but without its discontinuation at week 6 and at the end of follow-up…

Infliximab and ulcerative colitis

Expert Opin Biol Ther. 2006 Apr;6(4):401-8. Infliximab and ulcerative colitis. Cottone M, Mocciaro F, Modesto I. Università di Palermo, Istituto di Medicina Generale e Pneumologia, Via Trabucco 180, Palermo, Italy. dickens@tin.it Tumour necrosis factor (TNF)-alpha is an inflammatory cytokine that plays a main role in the inflammatory process underlying inflammatory bowel disease (IBD). Despite the fact that the cytokine profiles associated with ulcerative colitis (UC) and Crohn's disease (CD) are classically considered different (a Th2 pattern in UC and a Th1 pattern in CD), there are several evidences in vitro and in vivo that TNF-alpha has an important role in UC. For this reason, inflixi…

Improving patients' QoL: how the success of treatment can improve workability

A Propensity Score-matched Comparison of Infliximab and Adalimumab in Tumour Necrosis Factor-α Inhibitor-naïve and Non-naïve Patients with Crohn's Disease: Real-Life Data from the Sicilian Network for Inflammatory Bowel Disease

Background and aims There is an unmet need to better understand the effectiveness of different biologics in inflammatory bowel diseases. We aimed at performing a multicentre, real-life comparison of the effectiveness of infliximab [IFX] and adalimumab [ADA] in Crohn's disease [CD]. Methods Data of consecutive patients with CD treated with IFX and ADA from January 2013 to May 2017 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. We used propensity score-matching accounting for the main baseline characteristics in TNF-α inhibitor-naive and non-naive patients. Results A total of 632 patients [735 total treatments] were included. Among naive patients, a cli…

Analysis of colon-infiltrating γδ T cells in chronic inflammatory bowel disease and in colitis-associated cancer

Abstract Inflammatory bowel disease (IBD) remains a global health problem with a significant percentage of patients progressing to chronic inflammation and colitis-associated cancer (CAC). Whether or not γδ T cells contribute to initiation and maintenance of inflammation in IBD and in the development of CAC is not known. We have evaluated the frequency, phenotype, and functions of γδ T cells among tissue-infiltrating lymphocytes in healthy donors and IBD and CAC patients. Results show that Vδ1 T cells are the dominant γδ T-cell population in healthy tissue, whereas Vδ2 T significantly abound in chronic IBD. Vδ2 T cells produce more IFN-γ, TNF-α, and IL-17 than Vδ1 T cells in chronic inflame…

Placebo Therapy in Crohn's disease

The knowledge of the outcome among patients receiving placebo is important for evaluating the response to therapy, for evaluating the natural history of a disease and for calculating the sample size for future clinical trials. In Crohn's disease placebo has been used in therapeutic trials in every relevant setting: active disease, prevention of relapse after induced medical remission and after surgery and fistulising disease. The analysis of the placebo response shows that in every setting there is a high heterogeneity demonstrating mainly that the selection of patients is not often homogeneous and that the outcome criteria used in the trials is not highly reliable. Better selection of pati…

Cancer in Crohn's Disease patients treated with infliximab: a long-term multicenter matched pair study

Background: The long-term risk of neoplasia in Crohn's disease (CD) patients treated with infliximab is undefined. The aim was to assess, in a multicenter, matched-pair study, whether infliximab use in CD is associated with an increased frequency of neoplasia in the long term. Methods: A multicenter, long-term, matched-pair study was conducted in 12 referral inflammatory bowel disease (IBD) centers. An initial cohort of 808 CD patients, including 404 infliximab-treated (CD-IFX) and 404 matched CD controls never treated with infliximab (CD-C) studied from 1999 to 2004, was followed up for an additional 4 years (2004–2008). Cases and controls were matched for: sex, age (±5 years), CD site, fo…

Blood-based prognostic biomarkers in Crohn’s Disease patients on biologics: a promising tool to predict endoscopic outcomes

There is a growing need for biomarkers to predict therapeutic outcome in Crohn's disease (CD).The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics.Patients with CD who started biologics were enrolled. Multivariate analysis was used to evaluate whether NLR, PLR, ELR and ENLR at baseline and at w12 could predict ER (Simple Endoscopic Score for Crohn's disease [SES-CD] ≤2 or SES-CD≤2 and Rutgeerts i0-i1) after 52 weeks of treatment. Area under the curve (AUC) was calcul…

Cyclosporine or infliximab as rescue therapy in severe refractory ulcerative colitis: Early and long-term data from a retrospective observational study

Introduction: About 30-40% of patients with acute severe ulcerative colitis (UC) fail to respond to intensive intravenous (iv) corticosteroid treatment. Iv cyclosporine and infliximab are an effective rescue therapy in steroid-refractory UC patients but up to now it is still unclear which is the best therapeutic choice. Methods: We reviewed our series of severe steroid-refractory colitis admitted consecutively since 1994 comparing two historical cohort treated with iv cyclosporine (2 mg/kg) or iv infliximab (5 mg/kg). The main outcome was the colectomy rate at 3 months, 12 months and at the end of the follow-up. Results: A total of 65 patients were included: 35 in the cyclosporine group and…

Early postoperative recurrence of severe crohnʼs disease, with colonic involvement and associated human cytomegalovirus infection, treated with oral valganciclovir and adalimumab

JC Virus, Helicobacter pylori, and Oesophageal Achalasia: Preliminary Results from a Retrospective Case-Control Study.

Blood-based prognostic biomarkers in Crohn’s Disease patients on biologics: a promising tool to predict endoscopic outcomes

There is a growing need for biomarkers to predict therapeutic outcome in Crohn’s disease (CD). The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics. Patients with CD who started biologics were enrolled. Multivariate analysis was used to evaluate whether NLR, PLR, ELR and ENLR at baseline and at w12 could predict ER (Simple Endoscopic Score for Crohn’s disease [SES-CD] ≤2 or SES-CD≤2 and Rutgeerts i0-i1) after 52 weeks of treatment. Area under the curve (AUC) was calc…