Erika Angelucci

European evidence based consensus on the diagnosis and management of Crohn’s disease: special situations

This third section of the European Crohn’s and Colitis Organisation (ECCO) Consensus on the management of Crohn’s disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn’s disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn’s disease.

Advanced Age Is an Independent Risk Factor for Severe Infections and Mortality in Patients Given Anti–Tumor Necrosis Factor Therapy for Inflammatory Bowel Disease

BACKGROUND & AIMS Few data are available on effects of biologic therapies in patients more than 65 years old with inflammatory bowel disease (IBD). We evaluated the risk and benefits of therapy with tumor necrosis factor (TNF) inhibitors in these patients. METHODS We collected data from patients with IBD treated with infliximab (n = 2475) and adalimumab (n = 604) from 2000 to 2009 at 16 tertiary centers. Ninety-five patients (3%) were more than 65 years old (52 men; 37 with ulcerative colitis and 58 with Crohns disease; 78 treated with infliximab and 17 with adalimumab). The control group comprised 190 patients 65 years old or younger who were treated with both biologics and 190 patients older than 65 years who were treated with other drugs. The primary end points were severe infection, cancer, or death. RESULTS Among patients more than 65 years old who received infliximab and adalimumab, 11% developed severe infections, 3% developed neoplasms, and 10% died. No variable was associated with severe infection or death. Among control patients more than 65 years old, 0.5% developed severe infections, 2% developed cancer, and 2% died. Among control patients less than 65 years old, 2.6% developed severe infections, none developed tumors, and 1% died. CONCLUSIONS Patients older than 65 years treated with TNF inhibitors for IBD have a high rate of severe infections and mortality compared with younger patients or patients of the same age that did not receive these therapeutics. The effects of anti-TNF agents in older patients with IBD should be more thoroughly investigated, because these patients have higher mortality related to hospitalization than younger patients.

Infliximab and newly diagnosed neoplasia in Crohn’s disease: a multicentre matched pair study

Background and aims: The widespread use of anti-tumour necrosis factor α antibody (Infliximab) in Crohn’s disease (CD) raises concerns about a possible cancer risk in the long term. In a matched pair study, we assessed whether Infliximab is associated with an increased risk of neoplasia. Methods: In a multicentre matched pair study, 404 CD patients treated with Infliximab (CD-IFX) were matched with 404 CD patients who had never received Infliximab (CD-C). Cases and controls were matched for sex, age (±5 years), site of CD, age at diagnosis (±5 years), immunosuppressant use, and follow up. New diagnoses of neoplasia from April 1999 to October 2004 were recorded. Results: Among the 404 CD-IFX, neoplasia was diagnosed in nine patients (2.22%) while among the 404 CD-C, seven patients developed neoplasia (1.73%) (odds ratio 1.33 (95% confidence interval 0.46–3.84); p = 0.40). The survival curve adjusted for patient year of follow up showed no differences between CD-IFX and CD-C (p = 0.90; log rank test). In the CD-IFX group, there was one cholangiocarcinoma, three breast cancers, one skin cancer, one leukaemia, one laryngeal cancer, and two anal carcinomas. Among the 7/404 (1.73%) CD-C, there were three intestinal adenocarcinomas (two caecum, one rectum), one basalioma, one spinalioma, one non-Hodgkin’s lymphoma, and one breast cancer. Age at diagnosis of neoplasia did not differ between groups (CD-IFX v CD-C: median 50 (range 40–70 years) v 45 (27–72); p = 0.50). Conclusion: In our multicentre matched pair study, the frequency of a new diagnosis of neoplasia in CD patients treated with Infliximab was comparable with CD patients who had never received Infliximab.

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

Background: The long‐term risk of neoplasia in Crohns 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, follow‐up (±5 years), immunosuppressant use, and CD duration (±5 years). From 1999 to 2008 the frequency and characteristics of neoplasia were compared between CD‐IFX and CD‐C. Results: In 2008, 591 patients (304 CD‐IFX, 287 CD‐C) were in follow‐up. Matched couples included 442 patients: 221 CD‐IFX and 221 CD‐C (median follow‐up, months: 72, range 48–114 versus 75, range 44–114). From 1999 to 2008 the frequency of neoplasia among the 591 patients did not differ between CD‐IFX (12/304; 3.94%) and CD‐C (12/287; 4.19%; P = 0.95). A comparable frequency of neoplasia was also observed between the 221 matched couples (CD‐IFX: 8/221; 3.61% versus CD‐C: 9/221; 4.07%; P = 1). No specific histotype of cancer appeared associated with infliximab use. Conclusions: The frequency of neoplasia was comparable in an adult population of CD patients treated or not with infliximab, matched for clinical variables and followed up for a median of 6 years. (Inflamm Bowel Dis 2011)

Internet use among inflammatory bowel disease patients : an Italian multicenter survey

Background The internet has been increasingly used as a resource for accessing health-related information. A recent US survey found that approximately half of inflammatory bowel disease (IBD) patients in an IBD clinic use the internet to gather IBD-specific information. Aim The aim of this study was to evaluate the use of the internet among Italian IBD patients. Methods The study was performed in seven Italian IBD referral centers by using a 28-item anonymous questionnaire. Results In all, 495 questionnaires were returned for analysis, in which 305 of 495 patients (61.6%) indicated that they are able to access the internet. A large proportion used the internet to gather health-related information (180 of 305, 59.1%) and IBD-related information (226 of 305, 74.2%). The use of the internet increased significantly with level of education (P<0.0001) and household income (P<0.0001). In addition, the use of the internet to gather IBD-related information increased significantly with the increase of disease activity and severity. Conclusion Approximately half of the patients in Italian IBD referral centers used the internet to gather IBD-related information. This use positively correlated with disease activity and severity. The great majority of patients indicated that it was very important for IBD referral centers to have their own IBD-dedicated website.

Medical therapy for Crohn's disease : Top-down or step-up?

The emergency of effective biological therapy in the treatment of Crohn’s disease (CD) has led to a clinical debate about ‘step-up versus top-down strategy’. Step-up refers to the classic therapeutic approach, namely progressive intensification of treatment as disease severity increases. Top-down refers to the early introduction, in all CD patients, of intensive therapies, including biological agents and immunosuppressive drugs, with the aim of avoiding complications and improving quality of life, starting from the assumption that these drugs may interfere with the natural history of the disease. Very recently the Belgian IBD research group together with the Gut Club of North Holland designed ‘the Step Up versus Top Down Trial’. Combination of infliximab with immunosuppressives at onset was better than the current standard approach in terms of both induction and maintenance of remission. However, several observations still limit the use of infliximab as first-line treatment in adult CD patients. In particular, the epidemiological observation that over 50% of CD patients have a mild disease over time and will never require aggressive therapies is against the indiscriminate use of top-down strategy. Lack of markers able to identify high-risk patients, discussions about long-term safety and the high costs of infliximab are further factors supporting a more careful approach to the management of CD.

Clinical course of Crohn’s disease first diagnosed at surgery for acute abdomen

BACKGROUND The severity of clinical activity of Crohns disease is high during the first year after diagnosis and decreases thereafter. Approximately 50% of patients require steroids and immunosuppressants and 75% need surgery during their lifetime. The clinical course of patients with Crohns disease first diagnosed at surgery has never been investigated. AIM To assess the clinical course of Crohns disease first diagnosed at surgery for acute abdomen and to evaluate the need for medical and surgical treatment in this subset of patients. PATIENTS AND METHODS Hospital clinical records of 490 consecutive Crohns disease patients were reviewed. Patients were classified according to the Vienna criteria. Sex, extraintestinal manifestations, family history of inflammatory bowel diseases, appendectomy, smoking habit and medical/surgical treatments performed during the follow-up period were assessed. STATISTICAL ANALYSIS Kaplan-Meier survival method and Cox proportional hazards regression model. RESULTS Of the 490 Crohns disease patients, 115 had diagnosis of Crohns disease at surgery for acute abdomen (Group A) and 375 by conventional clinical, radiological, endoscopic and histologic criteria (Group B). Patients in Group A showed a low risk of further surgery (Log Rank test p<0.001) and a longer time interval between diagnosis and first operation compared to Group B (10.8 years vs. 5.8 years, p<0.01, respectively). Furthermore, patients in Group A used less steroids and immunosuppressants (OR 0.3, p<0.0001; OR 0.6, p<0.004, respectively). CONCLUSIONS Crohns disease patients first diagnosed at surgery for acute abdomen showed a low risk for reintervention and less use of steroids and immunosuppressants during follow-up than those not operated upon at diagnosis. Early surgery may represent a valid approach in the initial management of patients with Crohns disease, at least in the subset of patients with ileal and complicated disease.

Early post-operative endoscopic recurrence in Crohn's disease patients: Data from an Italian Group for the study of inflammatory bowel disease (IG-IBD) study on a large prospective multicenter cohort

INTRODUCTION The incidence of endoscopic recurrence (ER) in Crohns disease following curative resection is up to 75% at 1 year. Endoscopy is the most sensitive method to detect the earliest mucosal changes and the severe ER at 1 year seems to predict a clinical relapse. METHODS The aim of this prospective study was to evaluate the incidence of early ER 6 months after curative resection. Secondary outcome was to evaluate the role of 5-aminosalicylic acid (5-ASA) in the prevention of ER at 6 months. A total of 170 patients were included in the study. They were carried-out from the evaluation of the appearance of ER during a trial performed to assess the role of azathioprine vs. 5-ASA as early treatment of severe ER. All the patients started 5-ASA treatment 2 weeks after surgery. RESULTS Six months after surgery ER was observed in 105 patients (62%). The endoscopic score was reported as severe in 78.1% of them (82 out of 105). At univariable analysis only ileo-colonic disease influenced the final outcome associating to a lower risk of severe ER (p=0.04; OR 0.52, 95% CI 0.277-0.974). CONCLUSION In this prospective Italian multicenter IG-IBD study a great proportion of ER occur within 6 months from ileo-colonic resection, with a significant rate of severe ER. Furthermore this study confirms the marginal role of 5-ASA in the prevention of ER. This suggests that post-surgical endoscopic evaluation should be performed at 6 months instead of 1 year to allow an adequate early treatment.

The long journey of salicylates in ulcerative colitis: The past and the future

The advent of salicylates in the treatment of ulcerative colitis started in 1938 with the discovery of Salazopyrin by Nanna Svartz. This drug offered for the first time a therapeutic chance to patients with ulcerative colitis. In this paper we describe the fascinating history of Salazopyrin and salicylates from the first serendipitous observations to the last randomized clinical trials. Attention was paid to the pharmacokinetics and the mechanism of action of 5-aminosalicylates and, in particular, to the issue of the mucosal concentrations of 5-aminosalicylates and its therapeutic efficacy. Moreover a look at the new oral mesalazine formulations that allow the homogenous distribution of 5-aminosalicylate through all the large bowel was taken. Lastly, the possible use of mesalazine in the prevention of colorectal cancer was reviewed.

Guillain-Barrè syndrome after treatment with human anti-tumor necrosis factorα (adalimumab) in a Crohn's disease patient: case report and literature review.

Anti-tumor necrosis factor alpha antibodies have been used with increasing frequency despite the number of reported adverse effects. Further new information is still emerging. Here we report the case of a 71-years-old patient affected by Crohns disease and HCV-positive who developed Guillain-Barrè syndrome after four injections of fully human anti-tumor necrosis factor alpha antibodies (adalimumab). Indication for the treatment was severe clinical recurrence of Crohns disease following intestinal resection. Guillain-Barrè syndrome was treated by intravenous immunoglobulins, and methylprednisolone and plasmapheresis were started with a progressive partial resolution of neurological symptoms. To date, Crohns disease was maintained in clinical remission with low dose steroid therapy.